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ARMED FORCES RESEARCH INSTITUTE OF MEDICAL SCIENCES

C. “Thailand RTA Antibiotic Resistance Gonorrhoeae Study (WRAIR#2039). Discarded
clinical swabs from patients suspected of having a sexually transmitted infection in 9 RTA
hospitals are being sent to PMK microbiology lab for isolate growth/identification and
AST testing

D. Successfully coordinated the GEIS program, with the most important result being the high
quality influenza data reported in every week report to AFHSB-GEIS and bi-weekly reports
to all stakeholders. EDS provided AFRIMS influenza surveillance activity presentation
for visitors, stakeholders, RTA collaborators, and infectious disease physician fellowships.
EDS cooperated in Respiratory Infection presentation at ASTMH Conference.

E. Executed Prospective RTA Sexually Transmitted Infections (STI) Study in 9 RTA
Hospitals. Continue to collect samples from 9 RTA hospitals throughout Thailand. During
this period, 95 discard swabs from 9 RTA hospitals throughout Thailand were collected;
58 isolates were identified as Neisseria gonorrhoeae and underwent AST testing. 132
isolates were shipped to the U.S. Department of Defense (DoD) GC resistance lab and
repository at the Uniformed Services University for further phenotypic, genotypic or
molecular analysis and characterization. RTA-AFRIMS team has visited current and new
sites for expanding this study. Poster title: “Surveillance of antibiotic resistance of
Neisseria gonorrhoeae in Thai Military hospitals” was presented at Asia Pacific Military
Health Exchange (APMHE) Conference in 2016.

F. Executed Mongolian Armed Forces (MAF) Respiratory Burden of Disease Study in 15
MAF Clinics, providing very valuable respiratory disease incidence and impact data,
which has helped the MAF Command support the establishment of routine respiratory
surveillance as part of their force health protection policy. WRAIR#2025, titled “Estimation
of the Burden of Disease of Influenza and Other Respiratory Pathogens Among Mongolian
Armed Forces” had been concluded in FY16. New non-human used protocol was submitted
in 2017 to continue providing very valuable support and collaboration with the Mongolia
Armed Force Command and Mongolia National Center for Communicable Diseases as a
part of their newly established force health protection policy.

Submitted the annual World Health Organization (WHO) progress report detailing the
progress made in the implementation of the agreed activities included in the WHO
Collaborating Centre’s (CC) workplan. As partners within the Southeast Asia region,
WHO gains access to top institutions worldwide and the institutional capacity to support
its work. Similarly, institutions designated as WHO CC gain increased visibility and
recognition by national authorities, and greater attention from the public for the health
issues on which they work. The centers also gain opportunities to work together (e.g.
sharing objectives, exchanging information, pooling resources and developing technical
cooperation), particularly at the international level; and opportunities to mobilize additional
and sometimes important resources from funding partners

G. Assisted in 2017 Balikatan Exercises and for Collection of Samples as Well as Geographic
Information System Recording for Samples.

H. Continued Assisting Department of Enteric Disease, AFRIMS with Geographic Information
System (GIS) for the “Prevalence of Antibodies to Infectious Diseases of Public Health
Importance Among Recruits in The Royal Thai Army” project.

Resource Management and Budget:

AFRIMS EDS manages and coordinates the roughly $7 Million GEIS budget for the institute and
implements projects valued at approximately $1 million. This is expected to continue into the
future.

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DEPARTMENT OF IMMUNOLOGY AND MEDICINE

Mission:

The mission of the Department of Immunology and Medicine is to conduct medical product
research, development, and disease surveillance to minimize the threat from malaria. The
Department also conducts disease surveillance studies to help identify patterns and incidence
rates of diseases of military importance in South East Asia.

Organization and Personnel:

Training and Education:

A. In-house Training

• AFRIMS staff in Cambodia (IMM) provided malaria diagnosis training course, given
monthly for 3 consecutive months to RCAF medical laboratory personnel to train
them on routine microscopy standards (approximately 50 RCAF personnel) and
malaria RDTs (100 RCAF each) to support an active epidemiology clinical trial and
RCAF malaria information system (MIS). On 13 October and 28 December 2016

• 2-Day Malaria Microscopy Training for family medicine resident, Phramongkutklao
Hospital, RTA, Bangkok and PGY2 resident, Department of Medicine, William
Beaumont Army Medical Center, Speaker: Field Section staff, sponsored by
Department of Immunology and Medicine. 3-4 April 2017

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• Malaria Microscopy Training for Medical Officer, Communicable Diseases Surveillance
at World Health Organization, Bangladesh, Speaker: Field Section staff, sponsored by
Department of Immunology and Medicine 13 June 2017

• Department of Immunology and Medicine, AFRIMS, hosted PharmD students from
College of Pharmacy, University of Florida on antimalarial drug development. All
staff in Department of Immunology and Medicine trained the student in microscopy
technique, in vitro culture laboratory, molecular biology techniques, pharmacology
and bioanalytical laboratory and clinical study conducted in the department. 19-22
June 2017

• AFRIMS staff (IMM) provided training on antimalarial drug resistance. This comprised
1-3 days training on new technical methods for parasite culture, drug sensitivity testing
and Good Laboratory Practice (GLP) guidelines in sentinel sites, Anlong Veng (AV)
District, Oddar Meanchey (OMC) province. Approximately 10-15 trainees participated
in the training (7-9 August, 31 August, 1 September, 20-23 September and 1 December
2016 and 10-11 January and 12 January 2017).

• AFRIMS staff in Cambodia (IMM) provided 2 separate malaria microscopy training
courses of 10 days for 4 RCAF and 2 PHD medical laboratory staff in AV, OMC
province before External Competency Assessment of Malaria Microscopists (ECAMM)
course. From 6-16 March 2017 and 21-30 April 2017

• AFRIMS staff in Cambodia (IMM) provided malaria diagnosis training course, given
monthly for 3 consecutive months to RCAF medical laboratory personnel to train
them on routine microscopy standards (approximately 50 RCAF personnel) and
malaria RDTs (100 RCAF each) to support an active epidemiology clinical trial and
RCAF malaria information system (MIS). 28 July 2017

• Department of Immunology and Medicine, AFRIMS, hosted PharmD student from
Faculty of Pharmacy, Srinakarinwirot University on antimalarial drug development.
All staff in Department of Immunology and Medicine trained the student in microscopy
technique, in vitro culture laboratory, molecular biology techniques, pharmacology and
bioanalytical laboratory and clinical study conducted in the department. 31 August-
8 September 2017

• In vitro culture laboratory, Department of Immunology and Medicine hosted NAMRU-6
and USAMRD-K for harmonized ring stage survival assay workshop. Bangkok,
Thailand 21-26 August 2017

• In vitro culture laboratory, Department of Immunology and Medicine hosted Cambodia
field team for HRP-II ELISA Assay training. 18-22 September 2017

B. Outside Training

• Pharmacology and Bioanalytical Laboratory staff attended “Xevo G2-XS Training
with MassLynx and Progenesis QI for Metabolomics” Waters Pacific Pte. Ltd.,
Singapore. 16-19 May 2017

Research and Development:

A. Malaria Drug Development

1) Preclinical Malaria Drug Development in Nonhuman Primates

The AFRIMS Department of Immunology and Medicine, Pharmacology Section,
conducts preclinical development studies of new drug candidates for the U.S. Military
Malaria Research Program (MMRP), the Military Infectious Diseases Research Program
(MIDRP), and for external collaborators engaged in malaria drug development. In
healthy rhesus monkeys, IMM investigates the pharmacokinetic/ pharmacodynamic
(PK/PD) properties of promising lead candidate molecules as potential new anti-malarial

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drugs. These compounds, ideally represent diverse chemical classes with novel
mechanisms of action, are selected based on available preclinical data.

Detailed PK models in healthy rhesus are developed and compared with ex vivo activity
in plasma from monkeys administered test compounds against human P. falciparum
blood stages to prioritize compounds for advanced preclinical development. In the
department, we analyze plasma samples via LC/ MS or LC/ MS-MS, when greater
analytical sensitivity is needed, to determine if the parent molecule and/ or a metabolite(s)
are responsible for antimalarial activity. Besides analyzing plasma, we are developing
dried blood spot methods that require only 15 µl of blood per time-point applied to
cellulose-based filter papers to analyze blood PK. These blood levels can serve as
markers of the intra-erythrocytic parasite’s exposure to the compound. Furthermore,
potential safety concerns identified previously in small animal models will be fully
explored using appropriate clinical and laboratory endpoints. The most promising
drug candidates are further evaluated in a rhesus P. cynomolgi efficacy model, using a
dosing regimen identified from the healthy rhesus model which is likely to be safe and
efficacious. The combined results attained in the PK/ PD rhesus model and the
subsequent efficacy studies are critical information necessary to support an FDA
investigational new drug (IND) application.

In 2017, the department entered into a collaboration with the Medicines for Malaria
Venture (MMV) and Department of Veterinary Medicine, AFRIMS on a project
investigating the pharmacology and malaria prophylactic and radical curative properties
of a new drug candidate, DDD498 (MMV121/MSC2576186B) in P. cynomolgi-infected
rhesus monkeys. DD498/ MMV121/ MSC2576186B is a blood-stage schizonticide
with the potential to be a component in a single dose cure and the compound has
activity in gametocyte, ookinete and liver infection assays suggesting a role beyond
the asexual blood stage. Department of Veterinary Medicine and the Department of
Immunology and Medicine conducted the rhesus portion of the study with two (2)
oral doses for radical curative effect and two (2) oral doses for causal prophylactic
effect. PKPD analysis was evaluated and reported as part of the publication entitle
“Antimalarial efficacy of MMV390048, and inhibitor of Plasmodium phosphatidylinositol
4-kinase”, Science Translational Medicine 2017 Apr; 9(387):eaad9735

In addition, the Department of Immunology and Medicine has worked with the
Experimental Therapeutics Branch, WRAIR, to support optimization of a new class of
anti-malarials containing a triazine core (compounds WR909486 and 911639). The
compounds are provided to AFRIMS IMM and Vet Med, and evaluated for efficacy
in the P. cynomolgi-infected rhesus monkey model. Dose selection was based on the
optimal dose determined from the healthy rhesus PK/PD model managed by AFRIMS
Vet Med. The 3 triazine lead candidates that AFRIMS evaluated are the subject of an
exploratory of Investigational New Drug (IND) that will allow micro-dose PK in
humans. The Experimental Therapeutics Branch also provided target compounds of
the pyrimidinylguanidine class (WR081844, 147759 and 911195) to be tested in P.
cynomolgi-infected rhesus monkey model. The PG compounds were tested for their
prophylactic and radical curative effects compared to Atovaquone/Proguanil as a
positive control. The results showed that WR911195 prevented clinical signs of malaria
from occurring with the observed parasitemia.

Finally, the follow-on experiment of TZ, PG and acridone compounds were evaluated
(WR910735, WR911639, WR911540, WR911195 and WR826893) for efficacy in
P. cynomolgi-infected rhesus monkey model to determine which members of these
lead drug series will advance to pre-clinical status for candidates profiling. The dose
selection for this study was optimized based on several experiments that were done in
mice and monkeys. The PKPD analysis is ongoing.

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2) Phase 3 Study with Tafenoquine for Single-Dose Radical Cure of vivax Malaria
(WR2134)

Since 2014, AFRIMS/IMM has continued work related to execution of clinical trial
WR2134/TAF112582 entitled “A study to evaluate the efficacy, safety and tolerability
of tafenoquine (TQ) in subjects with Plasmodium vivax in Cambodia as part of a multi-
centre trial (NCT01376167)”. Tafenoquine is an 8-amino quinolone being developed
by Glaxo Smith Kline Pharmaceutical Company. Study WR2134 is a phase 3 clinical
trial of TQ in combination with chloroquine, initiated 29 January 2015 as part of a
multi-centre, double-blind, double-dummy, parallel group, randomised, active control
study intended to support regulatory approval of TQ in the U.S. as well as vivax-
endemic regions around the world. The primary objective is to determine the efficacy
of tafenoquine as a radical cure for Plasmodium vivax (P. vivax) malaria, relative to a
chloroquine control. The secondary objective is to assess the safety, tolerability,
socioeconomic impact and population pharmacokinetics of tafenoquine when
administered to subjects with P. vivax malaria.

TQ is a synthetic analogue of primaquine, and has been shown to be well-tolerated in
the treatment and prevention of plasmodial infections in pre-clinical models and during
Phase 1, 2 and 3 clinical studies in >4,000 subjects. Of note, TQ possesses activity
against all stages of the Plasmodium life cycle, including the dormant P. vivax
hypnozoite. Part 1 of the current study (TAF112582) was completed late 2015 and an
efficacious and well tolerated TQ dose (300mg) was determined. Part 2 investigated
the selected TQ/CQ regimen and its safety and efficacy in the treatment and radical
cure of P. vivax malaria in patients from Cambodia, where nearly 50% of malaria
cases are due to P. vivax.

AFRIMS enrolled 38 volunteers by the end of 2015. Enrollment in Cambodia was
halted at 38 due to unavailability of the CQ but the Department continued the study
through completion of the 6 follow ups into early 2016. In December 2016,
GlaxoSmithKline informed AFRIMS/IMM that the study was fully enrolled based on
review of accrual at all study sites and the changes in required sample size to meet study
objectives that was approved by the FDA. Through 2017, IMM participated in the
data review and manuscript preparation with the sponsor, GSK. In 2017, the data form
our site and other participating recruitment sites, was presented by GSK at P. vivax
International Conference in Manaus, Brazil and ASTMH Conference in Baltimore,
U.S.A. The main manuscript on the efficacy of TQ was recently submitted to a
scientific journal and we anticipate publication of the findings in the early 2018.

B. Malaria Drug Resistance Surveillance

Artemisinin based combination therapies (ACTs) are the first line treatment for drug
resistant Plasmodium falciparum malaria. The current major global investment in ACTs
is threatened by emerging and spreading of resistance to artemisinins, as signaled by a
trend of increasing ACT treatment failures on the Thai-Cambodian border, which has
historically been an epicenter of drug resistant malaria. There are no effective alternatives
to artemisinins for the treatment of malaria either on the market or nearing the end of the
drug development process. Strategies for containing artemisinin resistance require the
ability to detect it rapidly and accurately, both in humans (in vivo) and in collected parasite
isolates (ex vivo). AFRIMS’ proven ability to monitor artemisinin resistance with a
consistent regionally applied method and standards for its ex vivo drug sensitivity testing
and in vivo efficacy trials is critical in this regard. Artesunate in combination with
mefloquine has been the first-line drug for uncomplicated falciparum malaria on the Thai
side of the border since 1995 and in Cambodia since 2000. Therapeutic efficacy monitoring
is regularly conducted by both the Thai and Cambodian malaria control programs. Both

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progressively increased parasite clearance times and unusually high failure rates with
artesunate-mefloquine have been reported recently on both sides of the border. Funding
for anti-malarial drug resistance work is sourced from DoD-GEIS, WHO, MMV and the
Bill and Melinda Gates Foundation.

1) Thailand

AFRIMS began working in collaboration with the Thai MOPH in Trat Province,
Thailand, to investigate why the artemisin-based treatment failures described by the
Thai National Malaria Program (Vijaykadja, 2006) were occurring. An integrated in
vivo-in vitro approach was adopted using existing protocols and found that the PCR-
corrected ACPR (cure rate) at 42 days for Trat in 2005 was 81%. The second Trat study,
(WRAIR#1327) started in September 2007 to compare the efficacy and tolerability of
artesunate and mefloquine given over 2 or 3 days for the treatment of uncomplicated
P. falciparum malaria, but due to the changed local epidemiology of malaria in Trat
and the malaria containment efforts in border districts in Trat, this site did not generate
a sufficient number of enrolled volunteers with P. falciparum malaria before the end
of the trial in 2012. In collaboration with our colleagues at the Royal Thai Army (RTA)
Medical Department, in 2013 we expanded our anti-malarial drug resistance work to
include malaria patients presenting to RTA facilities along Thailand’s other international
borders. This on-going trial, WRAIR#1917, entitled “Evaluation of Molecular Markers of
Antimalarial Drug Resistance and in Vitro Antimalarial Drug Sensitivity in P. falciparum
Malaria Parasites from Patients Presenting to Thai Military Health Facilities in
Thailand” involves active surveillance of malaria drug resistance in P. falciparum cases
occurring at sentinel sites of multidrug resistance emergence along the Thai-Cambodian
border. Emergence of artemisinin resistance, especially along the Thai-Cambodian
border, is currently the largest threat to malaria control.

Through 2017, IMM had enrolled 117 subjects and sample specimens are being analyzed
to determine in vitro drug sensitivity and presence/absence of K-13 molecular markers,
which are linked to artemisinin resistance. The results showed that all samples were
K-13 mutation (100%), including C580Y and R539T, why plasmepsin 2 copy number
which are correlated to piperaquine resistance were also presented in this area (78%),
but pfmdr 1 copy number which are linked to mefloquine resistance were found only a
few samples. They showed that the molecular markers of drug resistance to artemisinin
and piperaquine are presented in this area.

IMM also initiated a second malaria drug study in Thailand in 2013, and through
September 2017, the study remains open for data analysis. The clinical trial WR#2017
is a DoD GEIS effort involving close collaboration of 3 different DoD research labs in
Kenya, Peru, and Thailand. The main focus of the study is to investigate artemisinin
resistance trends in the 3 countries by examining the efficacy of artesunate-mefloquine
(AS-MQ) in uncomplicated P. falciparum malaria patients and studying key parasitological,
pharmacological, molecular drug resistance marker, and immunological endpoints.

AS-MQ is one of the five ACT combinations recommended for the treatment of
uncomplicated P. falciparum malaria, is commonly used in many malaria endemic
regions, and is a standard treatment regimen in all three study venues. This integrated
in vivo-in vitro therapeutic efficacy surveillance study was initiated at the AFRIMS’
malaria research center at the Kwai River Christian Hospital (KRCH) in Sangklaburi
Kanchanaburi, close to the Thai-Myanmar border, between 31 October 2013, and 7
October 2015, we enrolled 48 subjects 46 of whom were evaluable for parasite
clearance at 72h. Of these, 33 (72%) had K13 wild type (WT) genotypes while 13
subjects (28%) harbored K13 mutations at enrollment, including the C580Y mutation.
Over the course of the following months through September 2016, data analysis

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revealed that the median PC1/2 of the mutant K13 group was significantly longer than
the K13 WT group (4.91h 95% CI 4.4-6.5 vs. 3.3h, 95% CI 2.9-4.2, p = 0.0003), thus
meeting the WHO definition of ART-R ≥ 5 hrs. We also found polymorphisms in the
MAL genes associated with delayed parasite clearance in nine subjects, including a
single subject with both K13 and MAL 10 mutations. Despite this, 100% of subjects
achieved adequate clinical and parasitological response (ACPR) at 42 days. While
our data suggest that clinical effectiveness of the traditionally employed 3 day A+M
regimen has yet to be compromised, clinical ART-R is now confirmed in this area of
western Thailand based on a sequential monotherapy regimen.

In conclusion when analyzed the data from three continents: the characterization of
artemisinin resistance in a U.S. DoD Army-Navy multicenter trial in Peru, Kenya and
Thailand in patients with uncomplicated P. falciparum malaria, we found that: To our
knowledge, this is the first study of its kind assessing parasite clearance half-life in
South America, and the first multicenter study characterizing ART-R across these
continents. We demonstrate that ART-R is absent in the areas studied in Iquitos, Peru;
ART-R is similarly absent in Kisumu, Kenya. Parasite clearance half-life (both K13 WT
and MT) is significantly prolonged in Sangklaburi, Thailand compared either Peru or
Kenya or both sites combined. In Thailand, four of five subjects had WHO resistance-
validated K13 mutations (R561H and C580Y) and PC1/2 ≥ 5h, thus confirming the
presence of artemisinin resistance by WHO criteria. The median PC1/2 found in the
K13 mutant group was significantly longer than the K13 WT group and is consistent
with previously reported PC1/2s in western Thailand. Even K13 WT isolates from
Thailand were significantly longer than either Peru or Kenya, suggesting the presence
of non K13 mediated mechanisms of delayed parasite clearance and ART-R. Study
was conceived and executed before the development of the ring stage specific assay
(RSA) a phenotypic test of ART-R. The DoD collaborating sites are following up this
study focusing on refining and standardizing the RSA across the three continents to
facilitate generalizability of results.

2) Cambodia

Data from AFRIMS’ Artemisinin Resistance in Cambodia trial 1 (ARC1) study
conducted in Western Cambodia in 2006 resulted in significant contributions as these
were the first reports to identify P. falciparum isolates that are highly resistant to
artemisinins. In ARC1, some individual isolates were associated with greatly increased
parasite clearance times, treatment failures despite 7 days of artesunate monotherapy
(4 mg/kg), and very high inhibitory concentrations for artemisinins in vitro. Reports
from the Ministries of Public Health on both sides of the Thai-Cambodian borders
indicated increasing numbers of treatment failures with artemisinin-based combination
therapies and artemisinin resistance was later confirmed by others.

In 2009, the Department of Immunology and Medicine completed the Artemisinin
Resistance in Cambodia 2 trial (ARC2) with the aim to determine whether regimens
with increased doses of artesunate could overcome the problem of reduced drug
sensitivity to artemisinins and to determine if high-dose regimen was safe and well
tolerated. Increasing doses of artesunate monotherapy given for 7 days did not improve
clinical or parasitological outcomes in Cambodian patients with uncomplicated P.
falciparum malaria and underscored the importance of current containment strategies
and need for combination therapies.

In 2010, a new clinical trial site in Anlong Veng District of Cambodia in the northern
province of Oddor Meanchey was developed, and the first study to be conducted there
was a collaboration with the National Cambodian Malaria Program (CNM) and Royal
Cambodian Armed Forces (RCAF), WRAIR#1737 “An active malaria epidemiology

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cohort study with evaluation of a 2 day versus 3 day treatment regimen of DHA-
Piperaquine for patients with uncomplicated malaria". In the approximately 80 active
duty soldiers enrolled, it was found that there were no differences in 2-or 3-day DHA-
piperaquine efficacy for treatment of all-species of malaria (90-92%); however, while
treatment efficacy for P. vivax was high (91-96%), the P. falciparum cure rate was
only 75-83%. Both regimens appeared safe with mild and transient cardiac QTc
prolongations on the EKGs performed. In 2012, the department conducted a follow-on
study in collaboration with USAMMDA which was the first malaria chemoprophylaxis
study conducted in the RCAF (WRAIR#1849). This study aimed to determine if a 2-day
course of DHA-piperaquine taken monthly was safe and effective as a chemoprophylaxis
regimen in an area of multi-drug resistant falciparum and vivax malaria. Careful
cardiac monitoring was implemented in this study, and after 6 weeks, the study was
halted due to four volunteers meeting pre-specified halting criteria in regards to QTc
prolongations on EKGs taken during treatment. All volunteers remained asymptomatic
but given the potential risk of cardiac adverse events, the 2-day regimen of DHA-
piperaquine was abandoned. Additional plans for 2018 include re-assessment of the
EKGs from that study to determine if the effect of PIP on u-wave had an effect on the
observed QTc interval.

The next study to be conducted in Anlong Veng was a therapeutic efficacy study of
3 days of DHA-piperaquine with and without a 45 mg transmission blocking dose of
primaquine in collaboration with CNM (WRAIR#1877). During 2013, 107 volunteers
with falciparum malaria were enrolled. The results from the study demonstrated a
staggering loss of efficacy of DHA-piperaquine in this region (46%). The results were
presented to CNM and contributed to the eventual decision to change national first-line
therapy for malaria from DHA-piperaquine back to artesunate-mefloquine in 2014.
This study also demonstrated that volunteers with detectable gametocytes on smear
were more likely to transmit to mosquitoes than those with sub-microscopic gametocytes.
There are ongoing study investigations involving volunteers from WRAIR#1877.
Currently 40 out of the 107 volunteers have agreed to have genotyping of the CYP450
2D6 liver enzyme done. This enzyme is responsible for effective metabolism of
primaquine, a drug required for vivax cure. Starting in September 2017, 27 of the 40
volunteers participated in a healthy adult pharmacokinetic study of primaquine. Once the
results are available it will provide the first ever data about primaquine metabolism in
Cambodians.

From 2015 through 2016, AFRIMS Department of Immunology and Medicine has
focused on multidrug resistant (MDR) malaria in Cambodia by finding alternative
drug regimens and being involved in Regional Malaria Elimination (section E). The
trial, WRAIR#2115, entitled “Comparison of atovaquone-proguanil and artesunate
atovaquone-proguanil for the treatment of uncomplicated P. falciparum malaria in areas
of multidrug resistance in Cambodia” evaluated the efficacy and safety of artesunate
atovaquone-proguanil (ASAP) against treatment with atovaquone-proguanil, without
artesunate (AP). This was first time that AFRIMS and NAMRU-2 in Phnom Penh
conducted clinical trial together, and there were 205 out of the targeted 345 P. falciparum
patients enrolled to the study. The last volunteer was enrolled in the latter part of
2015 and clinical portion of the study was completed the same year. Through 2017,
AFRIMS and NAMRU-2 worked to combine all the data into a single database and
then initiated data analysis which remains on-going. Of the 205 study subjects, 94.1%
(193/205) were evaluable and completed 6 weeks follow up. There were 16 subjects
with recurrent P. falciparum (uncorrected PCR), 14 of these were confirmed
recrudescences. The preliminary outcomes have shown that most failures in Cambodia
lacked cytb mutations, which has been attributed as the main cause of treatment failures

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from AP in case reports. The efficacy between the arms was similar; however,
differences in post treatment gametocytes were observed between the study arm. Future
studies are planned to investigate these new findings, as they could have significant
implications on how AP is used in malaria endemic countries. AFRIMS/NAMRU2
have plans to conduct future studies of AP in combination with other antimalarials,
which may prevent the spread of drug resistance and provide stop-gap therapy for
multi-drug resistance malaria in the areas where all other ACTs have failed. 5 other
ACTs have shown inadequate efficacy in Cambodia and could not be recommended by
WHO for treatment of Pf; underscoring the importance of the studies with AP and how
it can be used for treatment in areas where few options remain. This study also resulted
in 6 presentations at international scientific meetings between 2016-2017, which
included an oral presentation at ASTMH in Baltimore, U.S.A. in 2017. MAJ Wojnarski,
who is AFRIMS principal investigator on the study, was invited by the WHO to present
the findings from this study to WHO Technical Expert Group on Drug Efficacy and
Response. This presentation resulted in new recommendations made by WHO and
their support of additional studies of AP in combination with ACTs. Manuscripts are
in preparation with publications are planned in 2018.

C. WRAIR#1576 - Survey for In Vitro and Molecular Markers of Antimalarial Drug
Resistance in Cambodia

In vitro drug sensitivity assays have been used as a tool to characterize the drug
susceptibility phenotype of clinical P. falciparum isolates and to screen new candidate
drugs in development. Variability in in vitro drug sensitivity testing throughout the malaria
research world makes comparison between different data sets, different labs, and different
time periods difficult. In order to develop a testable model system for generating IC50
values with patients’ specimens, we finalized the evaluation of dynamics of W2 standard
clones as a mechanism to establish a validated control.

In late 2015 to present, in vitro laboratory, received 2-year MIDRP funded entitled
“Immediate ex vivo activity testing of antimalarial drug candidates against fresh field
isolates in Cambodia and Thailand”. The aims of this study are to establish ex vivo
P.vivax drug susceptibility assays for routine use at AFRIMS field sites, to evaluate
ex vivo activity of Military Malaria Research Program (MMRP)’s drug candidates against
P. falciparum and P.vivax clinical isolates and to monitor the antimalarial drug resistance.
The half maximal inhibitory concentration (IC50) values for several drug candidates and
also their relative potential for developing cross resistance to current antimalarials is
continuing testing and preliminary result is being analysis.

The in vitro lab will continue antimalarial resistance surveillance using the standard IC50
assay, RSA, and molecular markers. The PPQ-resistant isolates with extremely high PPQ
IC50 collected from Cambodia in 2014 will be sent to the University of Maryland for whole
genome analysis to identify genetics responsible for PPQ resistance. To continue method
validation for RSA, LDH-ELISA and/or other methods for parasite growth measurement
will be tried and compared with microscopic readings, aiming to find a measurement
system with less variation of RSA results than microscopic reading. To continue method
validation for P. vivax drug susceptibility assay, flow cytometry and other novel methods,
new media or supplements that can increase P. vivax growth may be tried.

D. Vaccinology & Immunology Studies in Support of Malaria Vaccine Program and
Influenza Studies

1) Malaria Immunology and Vaccinology

Since 2014, the Immunology and Vaccinology Section explored local immunity which
is required for protection against localized infections such as influenza, TB and malaria.

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We have completed a study looking at tissue distribution of memory T, B and plasma
cells in rhesus monkeys following 2009 pandemic H1N1 infection. The results of this
work were published in the J. Immunology, 2015. We also investigated the role of
liver-resident memory T cells in protection against P. knowlesi liver stage parasites in
rhesus monkeys. We demonstrated that P. knowlesi chemoprophylaxis with sporozoites
immunization is able to elicit protection from subsequent sporozoite challenge in a
rhesus monkey model. Sporozoite-specific CD4+ and CD8+ memory T cells producing
IFN-γ was generated with a large proportion residing in the liver and bone marrow.
Sporozoite-specific memory T cells in the liver expressed CD69 and chemokine
receptors CCR5 and CXCR6, suggesting effector T cells resident in the liver sinusoids.
Our findings from the P. knowlesi rhesus model are likely to be relevant to human
malaria, and provide further insights into generating sporozoite-specific T cell responses
in the liver where protection is needed (manuscript was submitted for publication in
the fall of 2016). The results from this study will help to better design malaria vaccines
aiming to induce protective immune response in the liver.

In FY17, we received funding support from MIDRP to establish a relapsing P. cynomolgi
model in rhesus monkeys for vaccine study. The well-established sporozoite inoculation
dose for inducing relapse in P. cynomolgi rhesus model for antimalarial drug testing at
AFRIMS is 106 sporozoites via intravenous injection (IV). However, this dose of
sporozoite is likely much higher compared to what humans would encounter naturally,
and may not be the optimal dose to study vaccine efficacy in this animal model. We
conducted a dose ranging study and found that IV inoculation of 104 sporozoites
consistently induced primary infection and 2 relapses similar to 106 sporozoites. This
dose of sporozoites will be used to test 2 regimens of chemoprophylaxis with sporozoite
vaccine in 2018.

2) Influenza Surveillance

This DoD-GEIS-funded project allows for ongoing surveillance of Influenza-Like-
Illnesses (ILIs) and detection of influenza and highly pathogenic influenza among
vulnerable military and civilian populations in Cambodia. GEIS participates in the
collection and characterization of influenza viruses circulating within the human
population in Asia. Various AFRIMS departments collect respiratory specimens from
sites in Cambodia, Thailand, Nepal, the Philippines, Bhutan and U.S. Embassies in
Southeast Asia with plans on expansion to Cambodia and Vietnam, and definitive test
results are shared with the Ministries of Health and WHO Flu Net. These surveillance
data contribute towards the annual re-formulation of the influenza vaccine as well as
early detection of novel influenza strains or existing subtypes with pandemic potential
which can increase the lead time for implementation of control and prevention measures.

According to the data on influenza activity in Cambodia from January to December
2017, a total of 399 respiratory specimens were tested influence viruses in clinical
laboratories and 87 were positive for influenza. Among them, 85% were influenza A
viruses. Antigenic characterized, 49 were influenza A (H3N2) viruses and 25
influenza A 2009 H1N1 pandemic. The Influenza hospitalization surveillance in
Cambodia ILI patients were collected data from 4 clinical health centers in Anlong
Veng, Banteay Meanchey, Battambang and Pailin provinces. Influenza-like Illness
surveillance by months, influenza activities has been peak at 31% and 33% around
month of September and October, respectively. The 2009 H1N1 pandemic and
influenza A (H3N2) viruses has been found mild ILI in all months and evened has
not been detected ILI only in March and May.

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3) Zika virus (ZIKV) Research

While several efforts are focusing on development of vaccines to prevent ZIKV
infection, parallel development of other therapeutics for treatment must be explored.
Therapeutic immunoglobulin or intravenous immunoglobulin (IVIg) could be a
potential treatment option for ZIKV infection. We have evaluated three IVIg lots
prepared from healthy Thai blood donors by the Thai Red Cross and found that all
three lots were able to neutralize ZIKV infection in vitro with neutralizing activity
ranging from 300-600 PRNT50. This work was compared to three commercially
available IVIg therapies from Flebogamma, I.V., Globulin SN and Kiovig. The
commercial therapies did not result in neutralizing activity. A research proposal
(2016 PRMRP) has been submitted with the aim to develop high titer IVIg antibodies
as a ZIKV immunotherapy.

We began to examine the generation of memory T cells in a rhesus monkeys that have
been infected with ZIKV. We have found that ZIKV infection induced central
memory and effector memory T cell responses. We were able to identify T cells that
were specific to African-lineage ZIKV and also demonstrated high cross-reactivity
(80-90%) to Asian-lineage ZIKV but only 20-30% cross-reactivity to dengue virus
type 2. Second inoculation with Asian-lineage ZIKV did not enhance the magnitude
of T cell responses against either Asian or African-lineage ZIKV. T cell responses
were still detected after 239 days (about 8 months) after the last viral inoculation.

E. Regional Malaria Elimination Initiatives

Regional Malaria Elimination Initiatives by AFRIMS includes defining effective,
appropriate, implementable strategies for malaria elimination in military forces in
Cambodia as a model for mobile migrant populations. The study WR2211 supporting
this initiative was initiated in January 2016, funded by Bill and Melinda Gates Foundation
and Department of Defense (DoD).

As multidrug resistant (MDR) malaria outpaces the development of effective antimalarial
drugs, the focus of research has now also includes plans to elimination of MDR malaria
along the Thai-Cambodia border. In collaboration with the Royal Cambodian Armed
Forces, this project focuses on identifying ‘real world’ tools via a rigorous head-to-head
approach of various strategies in soldiers and nearby border populations. We compared
the effectiveness of monthly malaria prophylaxis with dihydroartemisinin-piperaquine and
combination of weekly primaquine versus a focused screening and treatment following
Cambodia’s national treatment guidelines. Secondary objectives evaluated the effectiveness
of permethrin-treated uniforms and compared commercially available rapid diagnostic
tests for both malaria and G6PD deficiency screening, versus laboratory reference standards.
A total of 1,050 soldiers stationed along the northern Thai-Cambodian border were enrolled,
all volunteers were screened for G6PD deficiency. The predominance of the subjects was
military (75.8%). The other volunteers included their family members. Prevalence of
malaria at screening by RT-PCR was 14.6%, consistent with the higher risk exposure along
the Thai-Cambodia borders. The results of the study are groundbreaking as we were able
to demonstrate a significant reduction of Pf malaria through follow up, nearly down to zero
cases at 6 month of follow, despite the high prevalence observed on enrollment. G6PD
prevalence was 15.2% and outcomes for Pv malaria were less pronounced, underscoring
the importance of needing new tools for eliminating P. vivax malaria. Insecticide treated
uniforms had an impact on malaria transmission in areas of high malaria burden. The
results from this study resulted in multiple presentations at international scientific meetings,
to include oral presentation at ASTMH in 2016 and more recently at P.vivax International
Conference, following an invitation by the conference sponsors. Data analysis is ongoing
and manuscripts are planned for 2017.

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F. DMAP (Defense Malaria Assistance Program)

At the beginning of FY17, the Defense Malaria Assistance Program (DMAP) received
FY16 RDT&E funds in advance of the start of planned program activity in FY18. In an
effort to understand the interface between military and civilian malaria control, prevention
and elimination efforts AFRIMS convened a meeting in Bangkok, Thailand on June 26-28,
2017 to build upon existing regional momentum for civilian-military cooperation. The
objectives for this meeting were: 1) To review existing military and civilian national
malaria collaboration; identify and prioritize key areas of mutual military-civilian interest;
2) Discuss and plan concrete military-civilian coordination to help achieve national
elimination goals; and 3) Identify the necessary advocacy and political support to implement
military and civilian collaboration. Participants included Ministry of Health (MoH) and
Ministry of Defense (MoD) medical officials from six countries: Cambodia, Indonesia, Lao
PDR, Myanmar (Burma), Thailand, and Vietnam. Also in attendance were representatives
from the WHO, Global Fund for the Fight Against AIDS, Malaria and Tuberculosis, the
U.S. President’s Malaria Initiative, the University of California, San Francisco, the
Australian and U.S. Defense Departments, and the Asian Pacific Leaders Malaria Alliance
(APLMA).

This meeting aimed to define the ministries’ respective roles and strengths, and develop
an actionable collaboration roadmap. To ensure political and organizational commitment
for enhanced military-civilian cooperation, all countries agreed that key areas of mutual
military-civilian interest must be predicated on signature of a formal letter of collaboration
between the respective Ministries in each country, backed by the highest-level political
engagement of the MoDs. In addition, to ensure complementarity and efficiency, it was
agreed DMAP would benefit from working closely with the APLMA and the World Health
Organization to leverage political support and establish linkages with the Regional Steering
Committee of the Regional Artemisinin Initiative of the Global Fund (RSC-RAI2E).
Coordination of each of these malaria stakeholders–along technical, resourcing and
advocacy lines–will both optimize high quality and technically impactful implementation
while making best use of available resources.

In addition to keynote addresses, panel discussions, and country-level presentations, the
meeting included three facilitated country-level breakout sessions on malaria prevention,
diagnosis and treatment; case reporting and response; and advocacy, resources and
management. During the breakout sessions, representatives of the MoH and MoD within
each country worked together to identify priority areas for military-civilian collaboration
and define specific collaborative activities they aim to implement in the next 18 months.

G. Biological Clock Control of Malaria Infection

As part of the Biochronicity Program sponsored by Defense Advanced Research Program
Agency (DARPA), Department of Biology at Duke University obtained a grant to study
the biological clock of the malaria parasite. This group has been developing experimental,
mathematical, statistical, and computational tools to infer the structure of the interconnected
networks that comprise the cell cycle and circadian clocks, and to learn their function.
Analyses can be conducted to assess the numerous transcriptional markers of both the
hosts and the parasites, and to see if there is commonality, rhythmicity, or links between
the host’s and parasites’ responses either in a diurnal/circadian or other types of clock
control mechanisms. If there is a pattern, or potential cause-and-effect association, this
information could result in discovery of potential targets or methods for vaccine or drug
development for prevention or transmission interruption of malaria.

A clinical trial was planned and executed by AFRIMS Department of Immunology and
Medicine in collaboration with Duke University at a new AFRIMS study site in Ubon
Ratchathani, in the northeastern part of Thailand. The study included two parts. The first

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had a “limit-of-detection” objective, enrolling 10 patients with P. vivax infection at either
low, medium or high levels of parasitemia. A one-time blood draw was performed and the
sample sent to Duke to provide information on the parasitemia level necessary to have to
conduct robust analyses. The second part of the study enrolled 10 patients with P. vivax
infection to provide one blood sample which would then be cultured in the Ubon lab for
48 hours, and parasite samples aliquoted every three hours to send to Duke University to
see if biological clock mechanisms can be elucidated. All volunteers were enrolled in
September-October 2016, and all samples sent to the collaborators at Duke University
who are now conducting the assays.

H. Public Health Response

Starting in the summer of 2017 Thailand experienced an apparent malaria outbreak along
its Cambodia border in Sisaket province. Sisaket is one of Thailand’s northeastern
provinces, bordering Oddar Meancheay and Preah Vihear of Cambodia. No clear cause
has been identified for the marked increase in cases, which included 5 deaths.

The Department of Disease Control (DDC) at the Ministry of Public Health (MoPH),
Thailand formally requested assistance from AFRIMS, in order to respond effectively to
the outbreak. AFRIMS began field support in July 2017 under a public health exemption
granted by the WRAIR IRB. AFRIMS personnel initiated efforts to assist MOPH to
diagnosis and treatment activities, ensure close follow up and investigation of malaria
cases, and investigate the role of drug resistance in malaria outbreak. In September 2017,
AFRIMS received IRB approval to conduct a rapid drug efficacy study in Sisaket. AFRIMS
provided didactic and practical instruction on malaria diagnosis and treatment and on the
1-3-7 formula to MoPH personnel deployed as part of the outbreak responses. AFRIMS
microscopists, accompanied by MoPH personnel will collect blood to perform microscopy
and Rapid Diagnostic Test (RDT) to establish laboratory evidence of malaria parasites
and provide this information to MoPH personnel. Secondly, AFRIMS assisted MoPH
evaluate need to refine or develop new training aids and/or SOPs.

I. Overview of Research Projects

1) WR 2349 “Pilot Clinical Evaluation of the FilmArray Infectious Disease (ID) Fever
Panel.” Objective of this study is to provide an initial evaluation of the clinical
relevance of the FilmArray ID Fever Panel by testing archived specimens with
previously determine results for the following pathogens; Leptospirosis, Chikungunya,
Dengue and Malaria. Status as of September 2017: approved all IRBs and specimens
are on testing procedures.

2) WR 2466 “Clinical Evaluation of the FilmArray Global Fever (GF) Panel”. Status as
of September 2017: WRAIR IRB review.

3) WR 2261 “Biological Clock Control of Malaria Infection” status: approved all IRBs
and study site is set up. Study initiated in 19 September 2016 and completed enrollment
in November 2016 for Part A and Part B. Specimen is on analysis through 2017.

4) WR 2211 “Defining Effective, Appropriate, Implementable Strategies for Malaria
Elimination in Military Forces in Cambodia as a Model for Mobile Migrant Populations”,
status: approved all IRBs and set up sentinel sites. Study initiated in 13 January 2016,
fully enrolled with 1,050 volunteers by 25 February, 2016, completed data collection
in August 2016. Data analysis is ongoing through 2017.

5) WR 2134 “An IND Study to Evaluate the Efficacy, Safety and Tolerability of
Tafenoquine (TQ) in Subjects with Plasmodium vivax in Cambodia as part of a
Multicentre Trial”, status: WR2134 completed enrollment. Study initiated in 27
January 2015 at Anlong Veng site. There was 38 subjects enrolled to the study and
completed 6 month follow up in January 2016. The results of the study contributed to

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the FDA application, for the indication of radical cure for Pv, which is currently filed
and under review by the FDA.
6) WR 2115 “Therapeutic Efficacy of Atovaquone-Proguanil and Artesunate-Atovaquone-
Proguanil for the Treatment of Uncomplicated P. falciparum Malaria in Areas of
Multidrug Resistance in Cambodia”, status: The trial completed collection of data in
December 2015. There were 205 volunteers with P. falciparum enrolled to the study
and 94.1% (193/205) were evaluable at 6 weeks follow up. The data analysis is ongoing.
Manuscripts are in preparation.
7) WR1525 - Evaluation of in Vitro Cross-Reactivity with Avian Influenza H5N1 Virus
in Healthy Volunteers Vaccinated with a Prime Boost Regimen of Seasonal Influenza
Vaccine. Status: Completed in 2012. Manuscript published in Am J Trop Med Hyg,
2014, 90:149.
8) WR1630 - Human Influenza Sentinel Surveillance in Cambodia. Status: Ongoing at
3 sentinel sites–over 800 ILI-specimens collected since 2010- more than 30% of total
specimens were influenza positive and genomes obtained for spatial molecular analysis.
Status: Protocol amendment is continued processing. Data analysis is ongoing by
Department of Virology. Manuscript in preparation.

Resource Management and Budget:

AFRIMS Department of Immunology and Medicine manages and coordinates the roughly $800k
GEIS budget for projects related to malaria, influenza, and diarrheal disease surveillance. This is
expected to continue into the future.

Awards:

• MAJ Wojnarski received travel award to attend P.vivax International Conference in
Manaus, Brazil. He was the lead AFRIMS investigator on the Pilot Malaria Elimination
Study and presented the latest data from that study at the meeting, with the focus on P.
vivax and vector control.

• MAJ Wojnarski was a recipient of the best poster award at JITMM Internatinal Conference
both in 2016 and 2017.

Core Accomplishments and Capabilities:

The Department of Immunology and Medicine (IMM) maintains a variety of classical and state-of-
the-art capabilities, employing and integrating the latest technologies, to execute a multi-faceted
clinical and preclinical research program focused on malaria. IMM maintains a mobile epidemiology
team that conducts clinical work in remote field locations in malaria endemic areas, including
field sample collection and processing, screening, reference microscopy, assessment of rapid
diagnostics for various tropical infectious diseases, with a staff well-versed in performing clinical
trials to GCP and ICH standards. The Department routinely conducts malaria drug susceptibility
profiling of fresh clinical Plasmodium falciparum and P. vivax isolates from malaria patients using
antibody- and microscopy-based methods to help interpret efficacy outcomes, detect cases of drug
resistant infections, and actively track geographical and temporal drug resistance trends in Thailand
and Cambodia. The Department maintains routine cultures of reference P. falciparum clones and
emergent drug resistant isolates which are cloned for molecular and phenotypic characterization.
State-of-the art molecular methodologies are available for the study of the efficacy of vaccine and
drug candidates, to include advanced molecular biology methods such as sequencing, SNP analysis,
and real-time PCR. Technologies for detecting and monitoring safety signals in clinical trials
include high resolution melting real-time PCR detection of glucose-6-phosphate dehydrogenase

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(G6PD) deficiency mutations and electrocardiogram monitoring of patients administered test drugs.
Cellular immunology techniques are available, such as flow cytometry and sorting technologies,
ELISPOT, and molecular methods. The preclinical research teams are all trained in laboratory
animal research and regulations, current AALAAC requirements, and laboratory animal test and
observation methods. Our staff has experience in FDA-regulated studies and in-house expertise
in clinical pharmacology, drug-drug interactions, and with a dedicated pharmacology section that
conducts PK/PD studies for human clinical trials and multiple pharmacokinetic studies of anti-
malarial lead compounds in hon-human primates. Pharmacology assays include HPLC, LC-MS,
and LC-MS/MS analyses of in vivo levels of drugs and drug candidates evaluated in nonhuman
primates and in clinical trials, as well as a unique malaria bioassay to measure the ex vivo anti-
malarial bioactivity of preclinical and clinical plasma samples to ascertain correlations between
pharmacokinetics and pharmacodynamics of antimalarial evaluation.

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DEPARTMENT OF RETROVIROLOGY

Mission:

The mission of the Department of Retrovirology is to support the mission of the Military HIV
Research Program (MHRP) to protect the U.S. Military from HIV and improve global health by
conducting research to develop an HIV vaccine, reduce new infections and find a cure.

Organization and Personnel:

The Department of Retrovirology consists of 81 total personnel, including 3 active duty U.S. Army
officers (1 Medical Corps and 2 Medical Service Corps), 5 Foreign Service Nationals, and 73
contract personnel.

Statistical Data:

Various output measures speak to the productivity of the Department. One of those is the number
of clinical studies that are supported. At the end of FY2017, the Department supported 11 active
human clinical trials, 5 under U.S. FDA investigational new drug (IND) status. In addition, the
Department continues to support numerous human clinical trials that are no longer active in the
clinical phase but are still open for laboratory analysis, and is preparing for 4 new clinical trials.
Gearing up for such studies takes a tremendous amount of work in every case.

The clinical and research laboratories were extremely busy, conducting 26 discrete assays, with a
total of 99,233 samples analyzed (a 27% increase compared to FY2016), in addition to all required
specimen processing, shipment, and handling. Finally, the non-human primate laboratory performed

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19 different processes, including 7,871 samples that were analyzed to support exploratory
scientific analyses.

Healthcare Delivery:

The Department does not provide healthcare delivery per se, but it does support clinical research
conducted under current good clinical practice. The Department assures the safety and well-
being of all clinical research volunteers, and that research is conducted following all applicable
international, national, and local ethical practices. In addition, the Department provides high-
quality research and clinical laboratory services for volunteers enrolled in clinical studies. In
order to meet the required quality laboratory standards, the Department’s clinical laboratory
continues to be accredited by the College of American Pathologists, and possesses a Clinical
Laboratory Improvement Program (CLIP) high complexity registration.

Training and Education:

Extensive training and education activities occur every year. In FY 2017, the following took
place:

A. In-House Training Programs Provided by/to the Department

• CITI Program Training on “Biomedical Research Support Staff”, Online Training
• CITI Program Training (Human Subject Protection and Good Clinical Practice) for

investigators, Online Training
• DoD Information Assurance Awareness, Online Training
• “AFRIMS Emergency Response Exercise- HVRC LN2 incident” by AFRIMS safety

team at Retro-HVRC, AFRIMS. 18 November 2016
• RV348B Sensitivity training by SWING for protocol team and ECHO, at AFRIMS.

22-23 December 2016
• Bacteriophage Cocktails as an Alternative Therapy Against MDR Bacterial Wound

Infections by LTC Stuart Tyner. 11 January 2017
• Basic Life Support Renewal Class follow AHA Guideline by Dr. Somchai Sriplienchan

and Ms. Yinglak Fuangmarayat, AFRIMS. 17 January 2017
• Radiation Safety Self-Training. 18 January 2017
• RV348B Protocol Training in Bangkok by USAMMDA and Retrovirology Department,

AFRIMS (COG, IT and Laboratory staff). 23 January 2017
• Delta Vision Elite Training by Dr. Sunisa Poonpipatgul. 25 January 2017
• AFRIMS Protocol Review Process and Local Requirement by Ms. Bussara

Sukpanichnant, AFRIMS. 2 February 2017
• Primary Hazard Training by Ms. Yinglak Fuangmarayat. 2 February 2017
• The Humane Care and Use of Laboratory Animals by Dr. Rawiwan Im-erbsin.

2 February 2017
• Animal Biosafety Level-3 (ABSL-3) Hazard Training by Dr. Rawiwan Im-erbsin.

3 February 2017
• Occupational Health & Safety Program, and Communication by Ms. Yinglak

Fuangmarayat/Ms. Amorn Upakaew. 3 February 2017
• Animal Biosafety Level-3 (ABSL-3) Hazard Training by LTC Christine A. Ege.

22 February 2017
• Occupational Health & Safety Program, and Communication, LTC Donald C.

Johnston. 22 February 2017
• The Human Care and Use of Laboratory Animals by LTC Christine A. Ege.

23 February 2017

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• Fourth Year Med Student Discovers He Doesn’t Know Everything by ENS Yusof
Becker, MC, AFRIMS. 23 February 2017

• Good Pipette Practices and Preventive Maintenance of Pipette According to ISO8655
by Ms. T.J. Yang from Mettler Toledo-Rainin company, at Retrovirology Department,
AFRIMS. 27 February 2017

• GPP Overview Calibration Routine Operation, by Mettler Toledo-Rainin Company,
AFRIMS. 27 February 2017

• Arbinger Leadership Training, by Cameron Cozzens, Director of The Arbinger
Institute, AFRIMS. 10-11 and 13-14 March 2017

• Seminar on RNA Scope Technology by Dr. Nina Nguyen, AFRIMS. 20 March 2017.
• The MiSeq Refresher by Mr. Kian Chew Lim and Tan Yue Ying, AFRIMS. 31 March

2017
• Mucosal Inflammation, Gut Homing, and the Risk of HIV Transmission by Dr. Lyle

McKinnon, Department of Medical Microbiology, University of Manitoba, Winnipeg,
Canada, at Retrovirology Department. 1 May 2017
• Predictive Resource Staffing Model (PRSM) Mr. Eric Jackson (Teleconference with
slides). 11 May 2017
• “SCBA (self-contained breathing apparatus)” by AFRIMS Senior Biosafety Specialist
for AFRIMS emergency response team including key personnel at HVRC. Retro-HVRC
Conference Room, AFRIMS. 25 May 2017
• Characterization of Enteric Pathogens Causing Diarrheal Illness in Kenya CPT Stacey
Bateman, AFRIMS. 22 June 2017
• RV417, HIVA004 protocol training by Quintile for COG and involved Laboratory
staff, at HVRC AFRIMS. 24 August 2017
• Primary Hazard Training (Guidelines for Prevention of Herpesvirus Simian (B Virus)
infection in Monkey Handlers, Self-training. 21 August 2017
• BSC/IBC Committee Training by MAJ Damon W. Ellison. 30 August 2017

B. Outside Training

• 5th Thailand Laboratory Accreditation Forum 2016 “Lower Risk with Heartfelt
Quality Lab” by Thailand Medical Technology Council, Impact Forum, Muang
Thong Thani, Nontaburi, Thailand. 30 October-1 November 2016

• 19th Bangkok International Symposium on HIV Medicine, Queen Sirikit National
Convention Center, Bangkok, Thailand. January 2017

• Quality Control Planning in Clinical Laboratory by Bio-Rad Thailand, Bangkok,
Thailand. 27 February 2017

• ACC (Euramet cg-18) & GWP Executive Seminar by Mr. Santi Jitniyom, Technical
Manager LabTec, Mettler Toledo (Thailand) Ltd., Bangkok, Thailand. 2 March 2017

• HIV Vaccines, Keystone Symposia, Colorado U.S.A. 26-30 March 2017
• Hands-on training on Equipment Management by Benjapar Vesamavibool for

Microbiology & Hematology Department at MH175, Ho Chi Minh City, Vietnam.
29 March 2017
• HIV AIDS Seminar, Muangthongthani, Nontaburi. March 2017
• HIV Vaccine: The Ultimate Game-Changer, Faculty of Tropical Medicine, Mahidol
University. 18 May 2017
• RV348M Protocol Training in Nakhon Ratchasima by MOPH, BIOPHICS, and
Department of Retrovirology, AFRIMS (COG, IT and Laboratory staff). 17-18 July
2017
• RV348M Protocol Training in Ratchaburi by MOPH, BIOPHICS and Department of
Retrovirology, AFRIMS (COG, IT and Laboratory staff). 31 July-1 August 2017

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• The Current State of Research in Rabies by Dr. Henry Wilde, an infectious disease
doctor at the Thai Red Cross Institute and Chulalongkorn University. 18 August 2017

• Enabling and Managing Office 365, by The Enterprise Resources Training Co., Ltd.
Bangkok. 21-25 August 2017

• Presentation topic” Equipment Preventive Maintenance” by LTC Kirsten Smith and
“PM program, plan and PM implementing at Department of Retrovirology, AFRIMS”
by Benjapar Vesamavibool, Equipment and Process Management Workshop, Hanoi,
Vietnam. 5-7 September 2017

• Thailand Lab International 2017, BITEC, Bangkok, Thailand. 6-8 September 2017.
• Hands-on training on Equipment Management by Benjapar Vesamavibool for Blood

Transfusion Service Department, MH103 and Diagnostic Department, MH354,
Hanoi, Vietnam. 13-14 September 2017
• Coaching for Performance & Powerful Feedback training for ECHO and COG, at
ECHO, Pattaya Chonburi. 18-19 September 2017

C. Military

• All required annual military training

Research and Development:

The Department conducted numerous activities in four major areas, in concert with the Military
HIV Research Program: Preventive HIV vaccine trials, acute HIV infection trials, non-human
primate studies, and laboratory quality assurance support for the President’s Emergency Plan for
AIDS Relief.

Resource Management and Budget:

The Department operates on a $12M annual budget. The largest proportion of funds comes from
the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of
Health, and the U.S. Army. Minor contributors include the State Department via the President’s
Emergency Plan for AIDS Relief.
Information Management:

The Department supports specialized information systems to manage clinical trial visits (CAST),
and to manage specimens (Freezerworks). Both of these systems are extremely important to
efficient operation of research activities.

Modernization:

Building on the FY 2015 expansion of the liquid nitrogen storage capacity for the HIV Vaccine
Research Center of Excellence specimen repository, a broader initiative was initiated by the
Department to expand this more secure and economic storage solution to AFRIMS as a whole.
This initiative will ultimately result in replacement of outdated and less efficient cold specimen
storage equipment in Retrovirology and will also provide new storage capacity for precious
clinical trial specimens to other AFRIMS Science Departments.

Health and Environment:

Department personnel are fully integrated into the occupational health programs administered by
USAMD-AFRIMS. These include prevention and management of occupational exposures to
bloodborne pathogens, as well as a latent tuberculosis management program.

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DEPARTMENT OF VETERINARY MEDICINE

Mission:

The mission of the Department of Veterinary Medicine is to protect military personnel and their
families against tropical disease threats through pre-clinical product development of new
prophylactic and therapeutic drugs and new or improved vaccines.
To fulfill this mission, the Department of Veterinary Medicine (DVM) conducts bio-medical
research in animal models and zoonotic disease surveillance, provides veterinary expertise and
research animals that are free of confounding diseases to intra- and extra-mural collaborators, and
ensures that all animals receive humane, proper, and safe care and that the USAMD-AFRIMS'
Animal Care and Use Program complies with appropriate laws, regulations and guidelines.

Organization and Personnel:

The department has three branches: 1) Program Management, 2) Pathology, and 3) Research and
Laboratory Animal Medicine (RLAM). The Department Chief directly supervises the Program
Management and RLAM branches and provides administrative oversight to the Pathology Branch.
The RLAM branch provides administration of animal resources, animal health and surveillance,
veterinary care, research and protocol support, personnel training, and lab animal conduct. The
RLAM is divided into four sections: Nonhuman Primate, Small Animal, Support, and Veterinary
Care. The department currently consists of 3 military, 9 FSN, and 35 Cooperative Agreement
personnel.

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Statistical Data:

A. Malaria Research

Two experiments for the ongoing efficacy model for drug development and therapeutics
in the nonhuman primate (Macaca mulatta) was conducted in 2017. This model provides
a mechanism to identify effective new drugs for the enhanced prevention and treatment of
malaria infections. The experiments conducted were for WRAIR-ET. For the WRAIR-ET
study, 2 naïve monkeys were used for control and 14 naïve monkeys were utilized as the
experimental monkeys. The monkeys on both studies were used for prophylaxis and
radical curative treatment, and substituted triazines, pyrimidinylguanidine and substituted
acridone as antimalarial compounds, were administered.

B. Research Support

1) Active Research: The DVM provided research support to five departments at the
USAMD-AFRIMS for 19 active animal use protocols studying disease mechanisms of,
and developing therapeutics and vaccines for, tropical disease threats in Southeast Asia.

2) Breeding Colony: The DVM maintains breeding colonies of rhesus monkeys and
rodents to support the USAMD-AFRIMS research needs. Thirty-four (34) baby
rhesus macaques were born in the colony. 4,631 ICR mice (Mus musculus) were
produced and 1,887 mice were used for active protocols. Thirty six (36) ICR mice
were used for one protocol to maintain mosquito and sand fly colonies.

3) Clinical Laboratory Support: The veterinary clinical laboratory is an integral part of
the research support efforts for malaria drug development, malaria vaccine testing,
drug-drug interaction investigation, dengue anti-viral drug development, diarrhea
model development, Scrub typhus model development, and SHIV model development.
The clinical laboratory performed nearly 4,097 malaria parasite counts, 587 doses of
test compounds, 2,339 complete blood counts, 14,141 serum chemistries, and 3,086
tissue sections.

C. Publications

The DVM has directly contributed to 144 published scientific articles dating back to 1966.

Veterinary Services:

Departmental goals:

• Continue to use and improve animal models of malaria in nonhuman primates. This
effort will include not only the relapsing malaria model for Plasmodium cynomolgi but
also a model of severe cerebral malaria (Plasmodium coatneyi) and the fifth human
malaria Plasmodium knowlesi.

• Develop new animal models of human disease, including a natural challenge Rhesus
scrub typhus model in collaboration with Mahidol-Oxford Research Unit, Naval Medical
Research Center, and Louisiana State University

• Rhesus dengue vaccine models for two large long-term immunity studies.
• Maintain GLP capabilities for preclinical studies.
• Continue to develop partnerships for testing vaccines and therapeutics against dengue

fever in the rhesus macaque model.
• Continue to develop animal models of human disease, including a Rhesus simian-human

immunosuppressive virus (SHIV) model in collaboration with the Military HIV Research
Program (MHRP).
• Develop the training program in rhesus monkeys for blood collection techniques utilizing
positive reinforcement and the training program in rhesus monkeys to utilize CANTAB

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apparatus for evaluating the cognitive/memory and motor (behavioral) changes in SHIV
infected rhesus monkeys. Provide expertise and assistance to support development of a
regional primate center and other research organizations in Thailand.

• Provide expertise, training and assistance to the Chulalongkorn University, Department of
Veterinary Pathology, through technician exchanges and direct training of faculty and
students.

• Continue to support the USAMD-AFRIMS research mission by providing veterinary
expertise and animal resources for product testing.

• Continue to maintain an exceptional animal care and use program and prepare for the
2018 AAALAC site visit.

Training and Education:

A. External Training of Departmental Personnel

• The 7th Asian Federation of Laboratory Animal Science Associations (AFLAS)
Congress. Singapore. 8-10 November 2016

• The 34th Annual Symposium on Nonhuman Primate Models for AIDS. New Orleans,
LA. 11-14 October 2016

• IACUC Training on Roles and Responsibilities, Problems and Obstacles and
Corrective Actions. National Research Council of Thailand. Bangkok, Thailand.
30-31 January 2017

• In house special training: Nonhuman primate Behavioral Management Training by
Dr. Hou-chun Chen at DVM, AFRIMS. February and June 2017

• Veterinarian at Establishment Unit Course. National Research Council of Thailand.
Bangkok, Thailand. 17 June-27 August 2017

• Veterinary Stability Operations. Athens, GA. 19-23 June 2017
• The 11th Thai Association for Laboratory Animal Science International Symposium

“Advanced IACUC Training and Current Issues in Laboratory Animal Research and
Precision Therapy”. Bangkok, Thailand. 20-23 June 2017

• Animal Use for Science Symposium. Bangkok, Thailand. 25-27 July 2017

• Frontier in Animal Models and Ethics. Bangkok, Thailand. 22-23 August 2017
• The 9th Tick-Borne Pathogen and 1st Asia Pacific Rickettsia Conference. Cairns,

Australia. 27-31 August 2017

• Development of Experimental Animals for Scientific Purposes for Specific Pathogens
Free (SPF) National Research Council of Thailand. Bangkok, Thailand. 27-28
September 2017

B. Training of Non-AFRIMS Personnel

• AALAS Certification Training/Testing: The DVM organizes and conducts weekly
American Association for Laboratory Animal Science (AALAS) certification training
and serves as an official testing site. Training was held for one and a half hours twice
weekly (8 times per month) for a total of 58 classes in 2017. All DVM personnel and
personnel from outside collaborating institutions who work with laboratory animals
are encouraged to participate in the AALAS certification course. The supervisors and
qualified technicians conducted the regular classroom training for staff seeking all
levels of AALAS certification. The AFRIMS’ English teacher set up a course called
“Essential English for AALAS ALAT Certificate Seekers,” which was held every week
on Wednesday from 1500-1700 (total of 32 classes). The 3 levels of certification (in
order, from most difficult to least difficult) are Laboratory Animal Technologist (LATG),
Laboratory Animal Technician (LAT), and Assistant Laboratory Animal Technician
(ALAT). AFRIMS-DVM serves as Thailand’s AALAS Certificate official testing site

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for institutes and agencies outside of AFRIMS; (i.e. Mahidol University, Chulalongkorn,
etc.). Department of Veterinary Medicine currently holds 31 certifications.
• AC, RLAM, provided the training to a summer student from Faculty of Veterinary
Medicine, Kasetsart University during 26 June-21 July 2017.
• The Chief, Department of Veterinary Medicine provided 6 hours of training in
laboratory animal care and responsibilities to 20 graduate students at the Faculty of
Science, Mahidol University during January 2017.

C. Pathology Training

• The Pathology Division has provided direct training to veterinary students and PhD
students at Chulalongkorn University as well as at several regional meetings on topics
of zoonotic disease pathology, histopathology description, and macroparasite
histopathology.

• The Pathology Division has provided the training to two summer students from
Faculty of Science, Kesetsart University during 1 June-21 July 2017.

• Additionally, the Veterinary Pathologist has led necropsy training in Lao PDR in
support of their National Animal Health Laboratory, providing both didactic and
hands-on practical training in a variety of areas deemed to be lacking in the Laos
public health infrastructure. The intent of the ongoing project is to train from “death
to diagnosis,” extending from the incident (field site, slaughter house, necropsy floor)
to the point of sample receipt and subsequent diagnosis by laboratory personnel.
Training was conducted at three provincial laboratories in Lao: Oudomxay, Xieng
Khuang, and Attapeu. At the completion of these training events, all provinces have
had personnel that received this training.

Research and Development:

The research protocols supported in FY17 included the following:

• Antimalarial Drug Efficacy Testing in the Rhesus Monkey (Macaca mulatta)/
Plasmodium cynomolgi Malaria Models: Two studies for prophylaxis treatment were
conducted in 2017 for WRAIR-ET. Substituted triazines, pyrimidinylguanidine and
substituted acridone compounds were tested. 33 monkeys were utilized for testing
antimalarial compounds.

• Care and Maintenance of Rhesus (Macaca mulatta) Monkeys and Management of
Breeding Colonies: Thirty-four baby rhesus monkeys were born this year. Our
production of rhesus in the USAMD-AFRIMS colony was slightly lower than the target
goal of 50 this year.

• Care and Maintenance of Laboratory Rodents and Rabbits, Maintenance of Rodent
Breeding Colonies and Quality Assurance/ Quality Surveillance Program: 4,631 ICR
mice (Mus musculus) were produced, and 1,887 ICR mice were used for four active
protocols. Mosquito and Sand Fly Feeding Using in Vitro and in Vivo Techniques with
Mice (Mus musculus) as a Blood Source: 36 culled mice were used to maintain mosquito
and sand fly colonies.

• Maintenance of the Leptotrombidium Larval Mite Colonies: Chigger Feeding on ICR
Mice (Mus musculus): 540 mice were used to maintain the chigger mite colony.

• Inoculation of Dengue Viruses in Suckling Mice: 1,251 mice were used to produce high
titers of dengue virus antigens.

• Production of Plasmodium cynomolgi-Infected Blood Products Utilizing a Rhesus Monkey
(Macaca mulatta) Malaria Model: 5 monkeys were employed for producing infective
P. cynomolgi blood products to be provided to research collaborators on a pre-determined

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schedule for in vitro or in vivo research efforts, which may include evaluation and
screening of novel antimalarial compounds or vaccine discovery efforts.

• Biosample Collection Procedures for Mice and Nonhuman Primates: 34 monkeys were
utilized this year to provide blood, blood products, or other biological samples (including
urine, cervical vaginal mucosal samples, semen and anal mucosal samples) from normal,
healthy animals, as needed to the investigators, veterinarians, and diagnostic laboratories
supported by AFRIMS and other DoD institutes.

• Experimental Dengue Virus Infection in Rhesus Macaque via Mosquito Bite: Total 9
monkeys were trained to allow voluntary blood sampling, and 6 monkeys were used this
year for Dengue virus Infection in via mosquito bite.

• Generation of Nonhuman Primate (NHP) ZIKA Virus (ZIKV) Serum IgM for Preparation
of a Diagnostic Assay for ZIKV Infection: One monkey was utilized this year for
rechallenging ZIKV.

• Evaluation of a Candidate Bivalent DENV Vaccine Antigen in Rhesus Macaques
(Macaca mulatta): 44 monkeys (experiment 1 and 2) were used this year. They were
immunized with recombinant dengue viruses, and challenged with dengue viruses on day
360.

• Efficacy of Combination Therapy with the HIV-Specific Broadly Neutralizing Monoclonal
Antibody 3BNC117 and HIV Latency Reversing Agent Romidepsin to Achieve Virologic
Remission in SHIV-Infected Rhesus Monkeys (Macaca mulatta) Who Initiated Antiretro-
viral Therapy during Acute Infection: 9 rhesus monkeys were utilized for SHIV challenge
and testing on the combination SHIV therapy.

• Induction of Protective Immunity Against Primary Infection and Relapse in a Relapsing
P. cynomolgi Rhesus Model by Chemoprophylaxis with Sporozoite (CPS) Immunization:
17 monkeys were used this year to assess the standard inoculation dose for inducing
relapse using the P. cynomolgi rhesus monkeys.

• Efficacy of Latency Reversing Agent TLR7 Agonist GS-986 and HIV-Specific Broadly
Neutralizing Antibodies N6-LS and PGT121 to Achieve Virologic Remission in SHIV-
Infected Rhesus Macaques (Macaca mulatta) that Initiated Antiretroviral Therapy During
Acute Infection: 16 rhesus monkeys were all successfully inoculated with SHIV and
subsequently all initiated on antiretroviral therapy for the treatment of acute SHIV
infection.

Resource Management and Budget:

A. Agreements:

1) MOUs: No active MOUs.

2) CTAs: No active CTAs.

3) CRADAs:

a. Mahidol-Oxford Research Unit, AFRIMS-Entomology and AFRIMS-DVM
engaged to perform work on scrub typhus development in rhesus monkeys.

b. GlaxoSmithKline, Belgium, AFRIMS-Virology and AFRIMS-DVM engaged to
perform work on novel anti-viral compounds for dengue fever virus using a
collaborative research and development agreement.

c. Novartis, AFRIMS-Entomology and AFRIMS-DVM engaged to produce
Plasmodium cynomolgi-infected blood products utilizing a rhesus monkey
(Macaca mulatta) malaria model.

d. Mahidol-Oxford Research Unit, SIgN Singapore, and AFRIMS-DVM engaged to
perform work on immunopathological study of scrub typhus in rhesus macaques
by intradermal inoculation of Orientia tsutsugamushi Karp and Gilliam strains.

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e. Oxford University and AFRIMS-DVM engaged to perform work on comparative
pathology of the rhesus macaque/Plasmodium coatneyi model of severe malaria.

f. Oxford University and AFRIMS-DVM engaged to perform work measuring the
effect of laboratory adaptation on the virulence of Orientia tsutsugamushi in ICR
mice (Mus musculus).

B. Budget:

Federal funding supports a portion of the animal research conducted at USAMD-AFRIMS.
Typically one third to one half of the annual budget for animal research comes directly
from a combination of Department of Defense funding sources, including general and
administrative (G&A) WRAIR funding sources and, the Military Infectious Disease
Research Program (MIDRP). Additional research funding is received from private sector
sources through Cooperative Research and Development Agreements (CRADAs).

The Department receives an annual allocation of funds to support the departmental
operating budgets. The majority of the allocated funding to maintain the animal colony is
derived from MIDRP and G&A. Based on the data from preceding years, the majority of
the allocated amount is used to support the departmental salaries and benefits. The
allocation amount tends to increase each year.

Budget changes will directly impact the operational expenses, resulting in rearrangement
of expense priority (operational items, must-have or should-have items) as well as new
facility planning or renovation of the existing facility which requires a long-term budget
forecast.

Operations:

A. Operational Success: Compliance with the Thai Animals for Scientific Purposes Act

The newly promulgated Thai law for animal use, known as the Animals for Scientific
Purposes (ASP) Act, B.E. 2558 (2015) required several changes to the animal care and use
program at USAMD-AFRIMS. First, all individuals using animals for scientific research
or persons breeding animals to be used for scientific research required the appropriate
license from the National Research Council of Thailand (NRCT). All personnel were able
to obtain the appropriate license in the required timeframe. Second, a semi-annual report
must be prepared and submitted through the Royal Thai Army component of AFRIMS to
the NRCT. Data reported includes the number of active protocols, number of animals used
or produced, personnel involve in animal-based research, etc.

The final and most difficult change to the care and use program involved IACUC oversight
of invertebrates. According to the ASP, “any other living organism scientifically recognized
to have pain sensation as prescribed in the Ministerial Regulation.” As a result of this
language, the USAMD-AFRIMS Department of Entomology’s insectary and all research
conducted on or using insects requires IACUC oversight, though the manner or level of
oversight is not specified in the ASP Act. The USAMD-AFRIMS IACUC developed a plan
whereby a sub-committee would conduct an initial review Department of Entomology
SOPs, current funded research protocols, and the animal facilities. After the initial review,
the Entomology review would be conducted as part of the semi-annual Facility Inspection
and Program Review. To date, IACUC oversight of the insects housed, produced, and
used at USAMD-AFRIMS has been minimally disruptive to the Entomology program but
has been beneficial in identifying several areas where both parties can improve.

B. Operational Risk: CITES

In addition to the protocol support and departmental goals of DVM, outlined previously,
for the several years we have been working through a complex issue related to both CITES

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and the Nagoya Protocol. In 2011, the Government of Thailand promulgated regulations to
implement the 1992 Convention on Biological Diversity and the 2011 Nagoya Protocol on
Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from
their Utilization to the Convention on Biological Diversity. These regulations were adopted
in Thailand as the National Conservation and Utilization of Biodiversity Commission's
Rules and Measures for Access to Biological Resources and Benefits Arising from Their
Utilization B.E. 2554 (2011). The intent of the regulations is to ensure the conservation
of biological diversity, the sustainable use of its components, and promote and safeguard
the fair and equitable sharing of the benefits arising from the utilization of local genetic
resources.

We have continued to encourage a good working relationship with DNP through
facilitation by the RTA.

Modernization:

The Department has evaluated equipment and processes in order to optimize and modernize the
facility. To improve the facility’s capability, the department acquired the following equipment:

• Two binocular mircoscopes were ordered to replace the old model. The new model
provides better resolution.

• Laboratory grade water purification system was ordered to replace the old system. This
water purification system is point-of-use deionization with high flow rate.

• Plan Apochromat 60x Oil objective len was ordered for florescent microscope. The
objective len is suitable for observing staining of small bacteria and virus particle.

• Two high performance laboratory refrigerators were installed to replace the kitchen
refrigerator. These refrigerators offer microprocessor control system, alarms, controllers,
and door locks ideal for research uses.

• Pneumatic Tube System was installed to improve the sample transportation time and
increase efficiency in the facility.

• Analytical balance will deliver the highest accuracy for the small minimal weight of drug
and other reagents.

• Biosafety cabinet has been ordered to replace the current machine. This system will protect
the animals to be free from pathogens, increase a high health standard, and improve the
working environment by reducing the airborne allergens.

• Cage wash renovation project has been initiated. Renovations are to occur September 2017-
March 2018.

• Two new autoclaves were ordered and replaced for sterilizing the surgical equipment, and
equipment or material that will be utilized with mice and monkeys in order to create a
pathogen-free housing environment.

• Surgical lights were ordered and installed for enhancing the quality surgical or necropsy
procedures.

• Flexible gastrointestinal endoscope unit was ordered for supporting research studies.
• Ice machine was ordered for supporting the nonhuman primate enrichment program.

Logistics:

New facilities maintenance contract has improved communication and service for work orders in
the Department of Veterinary Medicine. Timely and proper response to work order requests have
improved standards of care within the Department of Veterinary Medicine.

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Construction:
A. Significant Planned Construction Projects for FY17 and FY18
• Seek funding to renovate the ABSL-3 containment (ABSL-3)
• Upgrade AHU 1-4 (Wings A and B)
• Design and build cooling system for a NHP in wings C and D (Wings C, D).
• Renovate the biohazard waste storage (Pump house)
• Install a new fire suppression system (Building 5 and the vivarium)
• Renovate the clean cage storage to be able to keep all cages (BC1, M3)
• Replace the water storage tanks (Pump house)
• Construct dirty airlock for the vivarium loading dock (COR 9-west)
• Renovate roof, gutter, and stairway for the office loading dock (COR 10-west)
• Renovate the main plumbing system (Pump house)
• Install new water towers and new RO systems for the vivarium (M3)
• Renovate the clinic (C1)
• Install ventilation system for the clean airlock of the vivarium (M5)
• Upgrade roof gutters and downspout for the vivarium (Wing)
• Replace the chilled water system (Roof)
• Replace the epoxy floor in the cage wash area (B11, B12)
• Upgrade animal room doors (Wing C)
B. Ongoing Significant Construction Projects
• Install two new cage washers and renovate cage wash area (B12)
• Install a new specimen delivery system (COR 7, 110)
• Replace the defective bulk water heater (AB3)

Health and Environment:
All potential exposures, accident, injury/ illness, exposures to an infectious substance and unsafe
or unhealthful working conditions are reported to the immediate supervisors and the
Occupational Health and Safety Officer for evaluation in accordance with AFRIMS and DVM
SOPs. Diagnostics, therapeutics, and other medical treatments are provided to potentially
exposed employees as required.

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DEPARTMENT OF VIROLOGY

Mission:

The mission of the Department of Virology is to develop and evaluate biomedical products, and
collect epidemiologic data to protect the soldiers and citizens from viral infectious diseases.

Organization and Personnel:

Statistical Data:

Function Table 1: Workload Summary Workload Count
Function #1: Clinical trials Workload 46
and research execution
Research studies prepared and conducted 140
Function #2: Biological
sample and data Reports generated to stakeholders and 13
management regulators
60,000
Reports in medical literature
80
Samples received, processed, inventoried, 30
stored and monitored 94,500

Freezers maintained and monitored

Databases developed and maintained

Data entries into databases

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Function Workload Workload Count

Function #3: Research Research studies or experiments coordinated, 46

coordination and compliance monitored, or regulatory files maintained

Audits or reviews conducted or coordinated 20

Function #4: Public health Public health samples received, processed 4,300
30
testing, training and capacity and tested

building Public health consultations and assessments

Function #5: Serological Serological assays performed 12,100
laboratory support Cell cultures performed 17,119

Function #6: Molecular PCR/Sequencing assays performed 6,850
laboratory support Bioinformatics analyses performed 500

Healthcare Delivery:

During 2017, we continued our surveillance and response capabilities by accepting and testing
(by Polymerase Chain Reaction-PCR) biological specimens suspected of multiple respiratory
pathogens as requested.

Training and Education:

A. Support for Academics Pursuing Degrees

1) One Medical Research Technologist attending Microbiology (International Program)
in the Doctor of Philosophy (PhD) program at Faculty of Science, Mahidol University,
Thailand

2) One Medical Research Technologist attending Bioinformatics and Biology System in
the PhD program at the King Mongkut’s University of Technology Thonburi,
Thailand

3) One Data Analyst completed her Master of Science Program in Computer Science at
Mahidol University Computing Center, the Faculty of Information and Communication
Technology at Mahidol University, Thailand in 2017. She has been selected to pursue
a PhD program at the University of Florida.

B. Other Training Offered to External Personnel

1) Summer Training/Overseas Rotation, part of their academic program/rotations for a
few months
a. One medical student, Western Michigan University School of Medicine, U.S.A.
for an academic program
b. One medical student, SUNY Upstate Medical University, U.S.A. for a rotation
program
c. One medical student, University of Central Florida College of Medicine, U.S.A
for an academic program
d. One CPT, Walter Reed National Military Medical Center, U.S.A. for a rotation
program
e. One CPT, Eisenhower Army Medical Center, U.S.A for a rotation program

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2) Short Laboratory Visit
a. 100 3rd year medical cadets, Phramongkutklao College of Medicine, Thailand in
October 2016 and August 2017
b. One professor and 21 students, University of Wisconsin, U.S.A.
c. 20 teachers and students, Department of Biology, Faculty of Science, Suranaree
University of Technology, Thailand
d. One Japanese medical officer, Self-Defense Forces Central Hospital, Japan
e. 13 Thai infectious disease fellows, King Chulalongkorn Memorial Hospital /
Siriraj Hospital / Ramathibodi Hospital, Thailand
f. Several senior officers, Queen Sirikit Naval Hospital, Thailand

3) Specific Training
a. Six laboratory staff, Eijkman Institute for Molecular Biology, Indonesia for
database management, clinical research regulatory and laboratory training
b. Two laboratory staff, Royal Centre for Disease Control, Bhutan for cell/virus
culture training
c. One associate researcher, International Vaccine Institute, Republic of Korea for
dengue virus culture and plaque reduction neutralization test (PRNT) training

C. Training Given by the Department of Virology Outside of Thailand

1) The following personnel at Armed Forces of the Philippines Health Service
Command Victoriano Luna Medical Center (AFPHSC-VLMC) have been provided
background on AFRIMS/PAVRU collaborations, updates on current projects (e.g.
influenza, MDRO, MDR-TB, dengue), future research activities and orientation on
use of Quickvue influenza A and B test kit and respiratory specimen collection,
transport and management.
a. 20 postgraduate interns (PGIs) and one pre-resident from the Department of
Pediatrics
b. 14 PGIs from the Department of Pediatrics
c. Hospital infection control officers
d. 14 PGIs and one pre-resident from the Department of Pediatrics
e. Eight nurses from the Department of Internal Medicine-Infectious Diseases Ward
f. 24 PGIs from the Department of Pediatrics
g. New batch of first year medical residents and postgraduate interns (PGIs) from all
departments
h. 23 PGIs from the Department of Pediatrics

2) The five following presentations have been given at the International Training
Workshop on Laboratory Diagnosis for Dengue/Zika/Chikungunya in Taiwan.
a. Overview of mosquito-borne viral diseases.
b. Molecular diagnosis of arbovirus infection protocols and experiences.
c. Molecular diagnosis of mosquito-borne viral disease.
d. Serological diagnosis of arboviral infection: protocols and experiences sharing.
e. Serological diagnosis of mosquito-borne viral disease.

3) The laboratory staff at Royal Centre for Disease Control, Bhutan was trained on
influenza virus isolation in MDCK cells and Typing by HAI Training.

4) The three following presentations have been given at the Asia Pacific Military Health
Exchange "Future Challenges and Collaborations in Military Health" in Singapore.
a. Evidence for dengue virus antibody dependent enhancement of zika virus infection
of THP-1 cells via downregulation of RIG-I and IRF-I.
b. In vitro study of ivermectin inhibitory effects on zika virus infection.

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c. Other respiratory viral pathogens detection in influenza like illness (ILI) patients
using multiplex PCR systems during influenza surveillance in Nepal, Philippines,
and Thailand during 2012-2015.

Research and Development:

A. The Dengue Hemorrhagic Fever Project IV: Continued Prospective Observational
Studies of Children with Suspected Dengue

1) The study involves children who have been admitted with suspected dengue virus
infections to the Queen Sirikit National Institute for Child Health (QSNICH), Bangkok,
Thailand. The proposed research extends our past studies of dengue immunopatho-
genesis to more severely ill children, with the additional objectives of testing the
utility of new non-invasive continuous monitoring devices and identifying positive
and negative predictors of disease complications.

2) There are 256 enrollees in the study: Of 256 enrolled subjects, 5 were withdrawn, 19
were lost to follow-up and 232 have completed all study activities. All study activities
involving subject follow-up have been completed. The study plan is to continue
laboratory testing and data analysis per protocol.

B. Sentinel Human Surveillance for Influenza in Asia

1) This study collects respiratory samples in order to characterize influenza viruses
circulating within the human population at the respective host sites. This data is used to
provide influenza surveillance data to the U.S. CDC and WHO surveillance network
towards the annual re-formulation of the influenza vaccine. We also report the results
of the circulating influenza strains and other respiratory pathogens to the respective
host sites and countries.

2) During year 2017, 4,505 samples were collected from Bhutan, Nepal, Philippines and
Thailand. We have completed Real time PCR for 4,432 samples. Of these, 45.05%
were influenza positive.

3) Results of influenza PCR testing:

Flu PCR Result Number of Specimen Percent of Positive
Flu A/H3 307 6.93%
Flu A/H3 + pdm H1 1 0.02%
Flu A/pdm Flu A 1 0.02%
Flu A/pdm H1 29.40%
Flu B 1,303 8.64%
Flu B + Flu A/H3 383 0.02%
Flu B + Flu A/Un-Subtype 1 0.02%
Neg 1 54.94%
Total
2,435 100.00%
4,432

C. Collaborative Electronic Disease Surveillance Project in the Philippines

1) This study evaluates the ongoing SMS text-based fever surveillance system in Cebu
City, Philippines to detect early spikes in febrile illnesses within the Cebu City Health
Department (CCHD). Integrate the SMS fever surveillance system with laboratory-
based sentinel influenza surveillance to determine in real time if influenza is the cause
of detected spikes in febrile illnesses. Implement the SMS reporting system into other
public health initiatives by the CCHD.

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2) This study is complete and will be removed from the next annual report. It is
mentioned here only to make clear that this study has concluded.

D. Efficacy and Safety of a Novel Tetravalent Dengue Vaccine in Healthy Children
Aged 2 to 14 Years in Asia (CYD14), Kamphaeng Phet and Cebu Site Specific
Annexes

1) This study assesses the efficacy of CYD dengue vaccine after three vaccinations at 0,
6, and 12 months in preventing symptomatic virologically-confirmed dengue cases,
regardless of the severity, due to any of the four serotypes in children aged 2 to 14
years at the time of inclusion.

2) There are 2 study sites include Cebu, Philippines and Kamphaeng Phet, Thailand in
collaborative relationship between USAMRMC and Sanofi Pasteur in development of
CYD vaccine candidate.
a. Nine hundred thirty-four subjects in total were enrolled in the study in Cebu,
Philippines. Subject enrollment and follow-ups were completed.
b. Five hundred eighty-five subjects in total were enrolled in the study in
Kamphaeng Phet, Thailand. Subject enrollment and follow-ups were completed.

3) The tetravalent dengue vaccine manufactured by Sanofi Pasteur has been approved
for use in several countries such as Mexico, Brazil, the Philippines, El Salvador,
Paraguay, Costa Rica, Peru, Guatemala, Indonesia, Thailand and Singapore for the
prevention of dengue caused by all four dengue virus serotypes. New analysis of
long-term Dengvaxia® data was done and found differences in vaccine performance
based on prior dengue infection. In children >9 years old in CYD14 and 15, vaccine
efficacy (VE) was 65.6 against virologically confirmed disease (VCD) (52.5% in
seronegative subjects at baseline and 81.9% in seropositive subjects at baseline) and
80.8% against hospitalization for dengue. VE was 93.2% against severe dengue and
92.9% against DHF. However, in the youngest age group 2-5 year olds, there was a
statistically significant increase in hospitalization due to virologically confirmed
disease in those who received the vaccine and were seronegative at baseline compared
to the placebo group and those seropositive at baseline in this age group. Assessment
of the impact of this finding is ongoing.

E. Pathological and Immunological Events in Fatal Dengue Based on Autopsy
Evaluation

1) The goals of this study are to define the pathology associated with fatal dengue using
up-to-date histological techniques to analyze tissue samples obtained from fatal dengue
cases in both children and adults and to identify the cellular targets of dengue virus
in vivo and to identify molecular changes of the endothelium and serosal epithelium in
anatomical locations where plasma leakage occurs.

2) Four autopsy cases have been obtained from Vicente Sotto Memorial Medical Center:
No further enrollment in this study occurred during 2017. The study will remain open
for data analysis and potentially a new source of specimens, but the contract with
VSMMC will be terminated.

F. Prospective Cohort Study of Influenza and Dengue Infection in Children and
Adults, Cebu City, Philippines (CPC Study)

1) To prospectively monitor a cohort of subjects age greater than or equal to 6 months
old in Cebu City, Philippines, for evidence of influenza infection and dengue infection
including transmission dynamics among household contacts of cohort subjects with
influenza A infection, and to determine other etiologies of febrile illnesses.

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2) The initial purpose of this study plan has already been completed. Protocol was
amended to include the following study objectives:
a. To identify the age-specific incidence of dengue in a cohort population age greater
than or equal to 6 months old and to specifically distinguish dengue from related
arboviral infections by using a new serological assay
b. To use mathematical modeling to estimate the proportion of the population
infected by each pathogen each year.

3) 1,148 cohort and 50 household subjects were enrolled to the study. A total of 890
subjects completed their 24-month annual follow-up visits from 3 March 2014 to 28
May 2014. All study activities involving interactions with subjects were completed
since 31 May 2014. No subject enrolled to the study since then. The study is open
for laboratory testing and data analysis.

4) Preliminary results and findings of this study: A total of 622 acute and serial cohort
respiratory samples were collected and tested since the start of the study, 205 (33%)
were positive by flu RT-PCR testing with breakdown as follows: 90 (44%) Flu B; 49
(24%) Flu A/pdmH1; 53 (26%) Flu A/H3; and 13 (6%) Flu A/unsubtyped. Out of
423 acute blood samples from the cohort that were tested so far since the start of the
study, 26 (6.1%) were positive for DENV by PCR, 15 (3.5%) were DENV-I, 6 (1.4%)
DENV-2, 2 (0.5%) DENV-3 and 3 (0.7%) DENV-4. Three (0.7%) were positive by
ELISA only. Of the 29 acute Dengue illnesses, serological testing showed: 3 (10.3%)
acute primary dengue infections; 19 (65.5%) acute secondary dengue infections; 1
(3.4%) had no paired serum, hence there was no serological diagnosis. The remaining
6 (20.6%) were indeterminant. 23 (5.4%) were positive for Chikungunya by PCR.
Another 3 (0.7%) were positive by ELISA. One of 268 were positive for Zika RT-PCR.

G. Immunological Correlates of Clinical Outcomes in a Tetravalent Dengue Vaccine
Cohort - an Ancillary Study (Cebu City, Philippines) (NMC Study)

1) The overall purpose of this ancillary study is to identify immunologic correlates of
clinical outcomes in participants in the parent CYD vaccine efficacy trial.

2) There were 114 and 502 subjects enrolled into pre-vaccination and post-vaccination
group respectively. Six hundred and sixteen subjects in total were enrolled in the
study.

3) The scheduled study activities from V01 to V12 (enrollment to V05+60 months) were
completed for the pre-vaccination volunteers and from V06 to V12 for the post-
vaccination volunteers. The study was extended to continue the long term safety and
immunological follow-up of subjects.

4) Laboratory testing to define immunological correlates and additional dengue assays
are ongoing.

H. Sentinel Human Influenza Surveillance in Royal Thai Army Recruits

1) The purpose of this study is to identify influenza virus and other respiratory pathogens
causing disease in Royal Thai Army (RTA) enlisted personnel living in barracks, study
seasonal trends, determine the burden of influenza virus, to study transmission patters
of influenza, determine influenza seroconversion rates, and to measure the frequency,
duration and seasonal variation of person-to-person contact amount recruits in the
Royal Thai Army barracks setting. This can be used to develop models of disease
transmission and the possible impact of different transmission interventions.

2) The study enrolls new RTA recruits and follows them at routine intervals for up to
24 months, obtaining a small amount of blood at baseline and occasional respiratory
samples and additional respiratory samples during episodes of acute illness.

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Radiofrequency badges are on occasion worn in order to tract movement and
transmission dynamics. The data collected from this unique population will provide
useful information about overall impact and behavior of influenza virus infection in
this restricted environment.

3) The study recruitments were completed in May 2015. There are 2,083 subjected
enrolled into the study. The follow-up activities of all recruit class members that
remain resident on the camp grounds have been completed in December 2015. The
total of 4,861 blood samples was collected from subjects for the routine baseline, and
every six-month follow-up visits. The total of 2,095 respiratory samples was collected
for the baseline and acute respiratory. Since study started, 812 acute respiratory
illness specimens were collected from subjects. The study was closed in March 2017.

4) Only 2.4% of recruits had received influenza vaccine in the previous 12 months.
Influenza real-time PCR has been performed on 1165 specimens including scheduled
and acute respiratory samples with results as follows: 8 (0.7%) positive for Influenza
A/pdm(H1); 25 (2.1%) positive for Influenza A(H3); 1 (0.1%) positive for Influenza
A/Un-subtype; 17 (1.5%) positive for Influenza B and 1114 (95.6%) negative. Selected
sample were isolated on MDCK cells. Samples included PCR positive samples, PCR
negative samples, and discordant samples. Results were as follows: 1 (0.7%)
Influenza A(H3); 2 (1.4%) Influenza A; 1 (0.7%) Adenovirus; 1 (0.7%) B Brisbane and
9 (6.5%) B Massachusetts. The overall rate of influenza was 1.7 (95% CI: 1.0-2.6) per
100 person-months; influenza comprised 13.8% of URI cases. Influenza B was
responsible for 80% of clinical influenza cases. In the serology subset, the rate of
influenza infection was 3.4 per 100 person-months. Thirteen of 169 (8%) recruits
seroconverted over the 10-week training period. Seroconversion was most common
against influenza B/Massachusetts (n=7) and influenza A/H3 (n=3). Median baseline
titres were 1:80 (IQR: 1:40-1:160) for influenza B/Massachusetts, 1:40 (IQR: 1:20-1:80)
for influenza A/H3, 1:20 (IQR: 1:10-1:40) for influenza A/pdmH1N1, and 1:10 (IQR:
1:10-1:10) for influenza B/Brisbane.

5) Overall rates of URI and ILI were 25.1 and 15.8 per 100 person-months respectively.
Among URI samples, the most commonly identified viruses were rhinovirus (26.9%),
influenza B (11.0%) and coronavirus 229 (4.8%). H. influenzae type B and non-type B
were commonly found in the absence of other pathogens (12.4% and 8.3% respectively).
Colonization with H. influenzae type B at entry was high (84.0%). Increases in
colonization between start and end of follow-up were seen for H. influenzae non-type B
(31.9% to 78.8%) and S. pneumoniae (8.0% to 28.4%). Among URI cases, 26%
received antibiotics. Of these, over half had infections attributable to a viral infection.

I. Phase II, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and
Immunogenicity of the Recombinant Live-Attenuated Tetravalent Dengue Virus
Vaccine Admixtures TV003 and TV005 in Healthy Adults, Adolescents, and
Children in Thailand

1) The study evaluates the immunogenicity and safety of two admixtures of a live
attenuated partial chimeric dengue vaccine attenuated with direct mutagenesis
developed at the NIAID/NIH in the United States.

2) 339 subjects were screened in the study. 294 all age de-escalation subjects in total
were enrolled in the study. The enrollment was completed on 8 November 2015.
a. Adult Cohort: 100 volunteers were screened and 84 adult subjects were enrolled
and randomized to receive either 2 doses of TV003/ placebo or TV005 followed
by placebo. The DSMB identified no safety concerns and recommended the study
continue enrollment. The adult cohort subjects have completed all study activities
visit 1-19.

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b. Adolescent Cohort: 80 volunteers were screened and 70 adolescent subjects were
enrolled to receive either TV005 or Placebo following the sponsor’s recommendation
to proceed with the second phase (Step B) of the study. The subject have completed
study activities visit 1-18.

c. Children Cohort: 79 volunteers were screened and 70 children were enrolled into
the study. The subjects have completed study activities visit 1-18.

d. Young Children: 80 volunteers were screened and 70 young children were enrolled
to the study. 67 subjects were completed study activities visit 1-18. One subject
has been withdrawn from the study because the subject cannot comply with study
procedures. Two subjects were lost to follow-up at Year-2 follow-up visit (visit 18).

3) Three subjects met elimination criteria as follows:
a. Subject received a licensed vaccine (Tetanus vaccine) during the period starting
from 30 days before each dose of vaccine/placebo.
b. Subject received blood components during the study period due to an elective
surgery of hemangioma at the occipital area. These subjects continue to be
evaluated for safety purposes at the scheduled visit.
c. Subject use of non-registered product (drug or vaccine) other than the study
vaccine (placebo)

There were 24 Serious Adverse Events (SAEs) since study initiation. These SAEs
were not related to the study product or study procedures.

4) Detection of suspected dengue and febrile illness case is ongoing. Of the 23 acute
febrile illness cases with 27 episodes, RT-PCR testing showed 4 positive dengue
infections in this report period. One subject had DENV-3 infection and three subjects
had DENV-4 infection.

J. Laboratory Analysis of Febrile and Vector-Borne Illnesses and Respiratory
Pathogen Surveillance in Southern Thailand

1) The objectives of this study are to support a preliminary surveillance study of
hospitalized patients and outpatients to identify and characterize Arbovirus species of
medical importance, testing of clinical laboratory and point-of-care diagnostic kits and
to identify and characterize the respiratory infections causing influenza-like illness
(ILI) in Southern Thailand. Specific Arboviruses include Dengue, Chikungunya,
Japanese Encephalitis, Zika virus. Other organisms include Leptospirosis, Scrub
typhus and Q fever in Southern Thailand.

2) As of October 2017, 2,335 subjects have been enrolled and 1,810 specimens shipped to
AFRIMS. We have identified the following PCR positive results: Dengue (374 PCR
positive/1,630 tested), Chikungunya (3 PCR positive/1,339 tested), Japanese encephalitis
(JE) (0/891 tested), Zika (3 PCR positive/898 tested), Ross River Virus (RRV) (0/357
tested), West Nile (WN) (0/335 tested), Leptospirosis (1/71 tested), Coxiella burnetii
IS1111 spacer region (0/99 tested) and Orientia (77/259 tested). Seroconversion of
acute and convalescent paired serum was determined and analyzed by DenJE IgM/IgG
ELISA (1,152 acute and 1,178 convalescent specimens tested), Den1234JE Chik HAI
(1,127 acute and 1,243 convalescent tested), Zika HAI (156 acute and 267 convalescent
tested). Approximately, 97% of the population tested displayed prior exposure to
dengue, JE, Chikungunya or other flaviviruses. Virus Isolation is on-going and to
date we have successfully isolated the following viruses Dengue (110), Chik (2), and
Zika (2). Sequencing of the isolates is also progressing and a subset of DENV 1, 2, 3,
4 and Chikungunya have been sequenced to date. Specimens from 206 subjects
(801-1,058) were used in collaboration with InBios to tests their NS1 ELISA.

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3) As of October 2017, 1,200 VTM samples have been collected and were shipped to
AFRIMS from subjects presenting with ILI like symptoms who were enrolled in the
study. Influenza PCR was performed on 505 samples thus far showing 92 Flu A
positive and 200 Flu B positive results so far.

K. Familial Force of Infection: Dengue in Households in Kamphaeng Phet, Thailand
(KFCS)

1) The general purpose is to determine the incidence of DENV infection in a prospective
cohort of family units containing family members of all ages.

2) Enrollment and annual follow up status: as of September 2017, 516 of the targeted
500 family units (including replacement), or approximately 3,300 individuals, have
been enrolled into the study (see attached flowchart). 516 of the enrolled pregnant
women have delivered, with successful collection of cord blood specimens, and their
families have entered active surveillance. 48 of the 516 family units (420 enrollees)
were withdrawn from the study due to failure to collect cord blood, fetal or neonatal
death, or moving outside of Kamphaeng Phet. A total of 468 families, with 2,880
participants, remain in the study.

368 family units comprising approximately 2,180 individuals (those enrolled between
September 2015 and June 2016) underwent the second annual follow-up blood
collection in spring of 2017.

A total of 1,394 routine specimens have undergone testing to identify seroconversion
to DENV by hemagglutination inhibition assay. 69 subclinical dengue infections were
detected as seroconversions by HAI (for an incidence of 4.9%). Seroconversions were
identified in individuals across all age ranges, with the highest rate observed in children
aged 1-5 years (11.4%). The next highest seroconversion rate was noted in children
aged 10-19 years (9.7%). Given that at least one DENV infection was detected in a
household, members of that household had a seroconversion rate of 33.9%. The
seroconversion rate in homes with an acute DENV illness was higher still at 38.2%.

Testing of enrollment and the first annual blood specimens from 73 family units:
82.4% of children aged 0-2 years had detectable DENV antibody by FlowNT50 in
their enrollment serum specimen, including testing of cord blood in newborns. This
dropped to 41% in children aged 3-5 and rose to 55% and 87% for children aged 6-10
and 11-15, respectively. By age 31, all individuals tested had multitypic DENV antibody
profiles in their enrollment serum.

3) Illness surveillance status: 151 acute febrile illness investigations have been performed.
11 of these illnesses were associated with DENV detection by PCR (8 were DENV-4
and 3 were DENV-2) and 9 household investigations within associated family units
were subsequently performed. An additional 9 febrile illnesses were attributed to DENV
following ELISA testing of acute and convalescent specimens (5- acute primary dengue
infection and 4 acute secondary dengue infection). The serological testing is pending
for specimens in September 2017.

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Flowchart demonstrating study activities and achievements as of September 2017

L. Prospective Observational Studies of Hospitalized Children and Adults with
Suspected Dengue (KDHF)
1) The general purposes are to characterize the clinical course of dengue in children and
adults, compare early and late clinical, host immunologic (e.g., DENV-specific immune
cells) and virologic (e.g., viral load) markers in children and adults with different
severities of dengue disease, determine if non-invasive monitoring parameters (e.g.,
muscle pH, muscle oxygen saturation and cardiac reserve index) can predict the
subsequent development/sla severity of shock and the clinical response to treatment and
evaluate the 1997 and 2009 World Health Organization (WHO) criteria in identifying
severe dengue in children and adults.
2) Enrollment status. As of September 2017, a total of 194 patients admitted to the
Kamphaeng Phet Hospital meeting study criteria were briefed and screened for
enrollment into the study. 84 subjects agreed to be enrolled into the study. 34 of the
enrolled subjects are adults and 50 are pediatric patients. 37 subjects are female and
47 are male. To date, 66 patients were diagnosed with an acute dengue infection based
on either a positive PCR result or serologic testing. Of this, subjects diagnosed with
acute dengue infection, 43 subjects tested positive by PCR testing. 8 were infected
with DENV-2 serotype, 2 were infected with DENV-3 serotype and 33 were infected
with DENV-4 serotype. 57 patients were diagnosed as having acute secondary dengue
infection via serologic testing. 15 of the enrolled patients tested negative for dengue
by both PCR and serologic testing.

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3) Classification according to the old (1997) WHO criteria vs the new (2009) WHO
criteria has been completed on 84 subjects. Using the 1997 WHO Classification
criteria, 15 subjects were classified as non-dengue, 40 were classified as dengue fever,
13 were classified as dengue hemorrhagic fever Grade I, 15 were classified as dengue
hemorrhagic fever Grade II and 1 was classified as dengue hemorrhagic fever Grade
III. Using the 2009 WHO Classification criteria 15 were classified as non-dengue, 30
were classified as dengue, 36 were classified as dengue with warning signs and 3 were
classified as severe dengue. There has been no DHF grade IV case according to 1997
WHO Classification. However, a number of adult dengue cases have clear evidence
of plasma leakage detected by serial ultrasonographic examinations.

4) Near Infrared Spectroscopy (NIRS) monitoring has been conducted on 44 enrollees
and will be analyzed as per study protocol. No patients to date have had measurement
of arterial waveform as was described in study protocol due to unanticipated delays in
delivery of the device needed to conduct this monitoring.

A preliminary analysis of the NIRS data suggests that the muscle oxygen levels are
lower in patients with DHF compared to patients with DF. The declining trend in
muscle oxygen levels was observed in cases without hypotension or shock and coincided
with the time of defervescence and plasma leakage. Interestingly, the baseline muscle
oxygen levels in older patients were lower than those of children and young adults
suggesting different status of tissue oxygenation in these age groups that may have
implications on dengue pathogenesis and clinical manifestations and severities.

Flowchart demonstrating study activities and results as of September 2017

M. Phase III, Double-Blind, Randomized, Placebo-Controlled Trial to Investigate the
Efficacy, Safety and Immunogenicity of a Tetravalent Dengue Vaccine (TDV)
Administered Subcutaneously in Health Children Aged 4 – 16 Years Old (DEN301)

1) This is a collaborative project between USAMRMC and Takeda Vaccines, Inc.

2) The trial includes three time periods (Parts 1, 2 and 3) for surveillance of febrile
illness with potential dengue etiology.

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a. Part 1: Active surveillance for the primary assessment of efficacy in all subjects.
During this time the subjects will be contacted at least weekly to ensure identification
of febrile illness that could potentially be due to dengue.

b. Part 2: Active surveillance for an additional six months for each subject following
the completion of Part 1. During this time the subjects will be contacted at least
weekly to ensure identification of febrile illness that could potentially be due to
dengue. Virologically-confirmed cases in Parts 1 and contribute towards the
secondary efficacy objectives.

c. Part 3: Modified active surveillance for the assessment of safety in all subjects
following the completion of Part 2 and lasting three years for each subject.

3) The study aims to evaluate the efficacy of 2 doses of TDV in preventing symptomatic
dengue fever of any severity and due to any of the 4 dengue virus serotypes in 4-16 year
old subjects.

4) 644 subjects were screened in the study. Initial study population assigned to the site
was 500. The sponsor increased the study population to 627. All 627 subjects were
enrolled in the study. The enrolment was completed on 29 March 2017. The subjects
were randomized to belong to either the standard group or to the subset group. The
subjects were further randomized to receive either 2 doses (90 days apart) of TDV or
placebo.

5) The standard group has 4 scheduled visits and the subset group has 9 scheduled visits,
as follows:

PARTS 1 AND 2 SUBJECTS START DATE ACTUAL END DATE
ACTIVE SURVEILLANCE

Visit 1 (Day 1/Month 0) Standard/Subset 9 Jan 2017 Completed on 29 Mar 2017

Visit 2(Day 30/Month 1) Standard/Subset 6 Feb 2017 Completed on 2 May 2017

Visit 3 (Day 90/Month 3) Standard/Subset 24 Mar 2017 Completed on 23 Jun 2017

Visit 4 (Day 120/Month 4) Standard/Subset 24 Apr 2017 Completed on 24 Jul 2017

Visit 5 (Day 270/Month 9) Subset 14 Sep 2017 Completed on 27 Nov 2017

Visit 6 (Day 450/Month 15) Subset 4 Mar 2018 Tentative completion date: 21 July 2018

Part 3: MODIFIED ACTIVE SURVEILLANCE

Visit 7 (Year 1) Subset 16 Aug 2019 Tentative completion date: 1 Feb 2020
15 Aug 2020 Tentative completion date: 31 Jan 2021
Visit 8 (Year 2) Subset 15 Aug 2021 Tentative completion date: 31 Jan 2022

Visit 9 (Year 3) Subset

6) As of 1 December 2017:
a. There were 10 Serious Adverse Events (SAEs) since study initiation. These SAEs
were not related to the study product or study procedures.
b. There were 430 acute illness visits and 418 convalescent visits.

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Resource Management and Budget:

TABLE 2: 3-year budget

Funding Sources FY2015 ($) FY2016 ($) FY2017 ($)

U.S. Army Medical Materiel Development Activity 441,032 614,004 825,985

Military Infectious Diseases Research Program 718,110 696,780 640,690

Armed Forces Health Surveillance Center-Global 1,785,910 2,178,906 2,249,591
Emerging Infections Surveillance and Response
System

National Institute of Health-University of Rhode Island 904,742 960,292 1,185,772

Defense Threat Reduction Agency 688,920 827,250 -

National Institute of Health-NIAID - 225,503 -

Naval Medical Research Center - --

Others 42,180 51,012 114,071

Total 4,580,894 5,553,747 5,016,109

Information Management:

Several servers were utilized to handle large information from the next generation sequencing
(NGS) by MiSeq (approximately 1 Terabytes generated during 2017). One Linux-based storage
server is served as a central storage for the generated data and the archives of the analysis results.
Two Linux operating stations with 2 Intel® Xeon® CPU E5-2687W/16 Cores/32 Threads and
1 Intel® Xeon® Processor E5 v3/12 Cores/24 Threads hosts verified pipelines for bioinformatics
data analysis, an in-house bioinformatics pipelines in one and Empowering the Development of
Genomics Expertise (EDGE) v2.0.0 in the other building. Two high performance Linux server
with 4 Intel® Xeon® CPU E7-4880 v2/ 60 Cores/ 120 Threads and 1 Intel® Xeon Phi™ Processor
7290/ 72 Cores/ 72 Threads were dedicated to the development of new analysis pipelines and
initiatives. The previous WRAIR developed program, the NGS Mapper, analyzes the data with
faster turn-around times was updated to a new version. A separate Windows-based server is setup
to handle tools only made available in Windows. All servers have Geneious software installed.
A Virtual Local Area Network (VLAN) has been setup to securely link all the servers with the
central storage.

A. Strength: Our current capacity is enough to manage the output information from the NGS
in 2017.

B. Shortcoming: The transfer rate among the servers is greatly limited despite their physical
proximity, and thus, affects the efficiency of the overall operation. In addition, the
information keeps growing; we also continuously require larger computational capacity
for storage and data analysis.

Operations:

Several respiratory specimens from U.S. service members participating in the 2017 Corbragold
training exercise involving the United States armed services, the Royal Thai Army and several
other participating nations. None were positive for influenza and no specimens uncovered any
novel pathogens.

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Modernization:

Two MiSeq have been used to assist the disease surveillance network and will be part of a wider
disease surveillance network. It is also utilized in the role of capacity building; in 2017, the
Department of Virology, AFRIMS, provided training and assisting on Next Generation Sequencing
techniques, MiSeq operation and primary bioinformatics analysis to laboratory personnel from
the Department of Immunology, Entomology, and Enterics. The achievements from the training
and assisting enhanced the effectiveness of NGS operation for viruses, bacteria, parasites, and
mosquito genome studies.

Construction/Renovation:

During the reporting period, the Department of Virology received funds sufficient to initiate
several renovation projects.

A. Vicente Soto Memorial Medical Center (VSMMC) elevator shaft renovation in new
VSMMC laboratory building. VCMMC awarded a contract to build a new four-storey
laboratory building on their campus in Cebu, Philippines. AFRIMS/Philippines-AFRIMS
Virology Research Unit (PAVRU), utilizing The Naval Facilities Engineering Command
(NAVFAC) contracting services, awarded a contract to complete a renovation to this
structure by installing an elevator shaft in 2014. The project on the ground has been
significantly delayed and continues to be delayed. The overall construction of the building
is more than 3 years behind schedule which affected the ability to complete the elevator
portion of the structure. Also electrical load of the building has been grossly underplanned
for despite the contractor having all necessary load estimates. Expectation at this stage is
that the overall building will be completed sometime during the Spring of 2018. After
completion of this project, the AFRIMS/PAVRU Cebu laboratory will occupy the fourth
floor of this laboratory in order to increase our ability to collaborate with VSMMC and
the local public health agencies. A second contract was awarded through NAVFAC to a
U.S. firm to complete detailed architectural and engineering plans for the actual renovation
of the fourth floor of the laboratory building that the AFRIMS/PAVRU laboratory will
occupy. This project is on hold however during late October of 2016 (post reporting
period for this report) the architectural and engineering representatives from NAVFAC
visited the site and took measurements. After receiving an upcoming “as built” building
design from the main contractor (expected in November 2016), NAVFAC can execute the
design portion of the 4th floor renovation.

B. Contract was awarded in Bangkok to complete the detailed architectural and engineering
drawings for a planned renovation to the second floor of the main research building on the
AFRIMS campus. This project will allow for better utilization of space and modernization
of our laboratory facility. During 2015, the floorplan was finalized and approved with
relocation of the staff in January of 2016. This project was largely completed just after
the reporting period for this annual report. Work on this project was completed and the
2nd floor fully occupied during 2017. Several modifications were required after occupation
and some issues related to the renovation continue to be addressed.

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คณะนกั เรยี นแพทย์ จากมหาวทิ ยาลยั แพทยท์ หารที่ 2 สาธารณรัฐประชาชนจีน ดูงานการวิจยั ทางการแพทย์ ณ กองวจิ ัย สวพท. 14 ตลุ าคม 2559
Medical cadets from Second Military Medical University (SMMU), Republic of China, visited Research Division, AFRIMS, 14 October 2016

การตรวจสขุ ภาพประจ�ำ ปี สวพท. 19 ตุลาคม 2559 ณ ห้องพินทโุ ยธนิ สวพท.
RTA - AFRIMS Annual Health Check Up, 19 October 2016 at Phintuyothin Auditorium, AFRIMS

การเก็บตวั อยา่ งจากหนู นาํ้ และดนิ จากแปลงนาสาธิตฯ 19 - 21 ตุลาคม 2559 และ 7 - 9 มิถนุ ายน 2560
ณ โรงเรยี นนายร้อยพระจุลจอมเกล้า จังหวดั นครนายก

Leptosirosis Surveillance as Royal Health Security for H.R.H.Princess Sirindhorn at CRMA Demonstration Rice Field before Harvesting season
19 - 21 October 2016 and 7 - 9 June 2017 at Chulachomklao Royal Military Academy, Nakhon Nayok Province

นพท.วพม. ชนั้ ปีที่ 3 ดงู านหอ้ งปฏิบัติการไวรัสวทิ ยา หนว่ ยวจิ ัยฝ่ายสหรัฐอเมริกา สวพท.
โดย ผอ.สวพท. ให้การต้อนรบั 20 ตลุ าคม 2559 ณ ห้องพนิ ทุโยธิน สวพท.

The third year of Medical Cadets from Phramongkutklao College of Medicine visited Virology Department of AFRIMS,
welcomed by AFRIMS Director General 20 October 2016 at Phintuyothin Auditorium, AFRIMS

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ผอ.สวพท. และคณะ ให้การต้อนรับ พลตรหี ญงิ บาร์บารา่ อาร์ ฮอลคอม ผู้บญั ชาการหน่วยวจิ ัยและยุทโธปกรณ์ทางการแพทย์ กองทัพบกสหรฐั อเมริกา
และคณะ ในการเยย่ี มชม สวพท. 20 ตลุ าคม 2559 ณ หอ้ งมิตรภาพ สวพท.

AFRIMS Director General and colleague welcomed MG Barbara R. Holcomb, Commanding General, USAMRMC and colleague to visit AFRIMS
20 October 2016 at Friendship Room, AFRIMS

การบรกิ ารตรวจสุขภาพประจำ�ปกี �ำ ลงั พลกองทัพบก ณ ที่ตัง้ หนว่ ยในเขตกทม.และปรมิ ณฑล ปงี บประมาณ 2560
Annual Health Check - up for Royal Thai Army Personnel at Army Installations in Bangkok and Its Perimeter, Fiscal Year 2017

โครงการหนว่ ยทหารสีขาว เพอื่ ปอ้ งกนั การแพร่ระบาดของยาเสพตดิ ในหน่วยทหาร ปีงบประมาณ 2560
“White Royal Thai Army Unit” To Prevent Narcotic Drug Abuse Problems in the Royal Thai Army Installations”, Fiscal Year 2017

การเกบ็ ตัวอย่างปสั สาวะจากทหาร ตามโครงการ “การเฝ้าตรวจสารเสพตดิ ให้โทษในทหาร” ปงี บประมาณ 2560
Collections of Urine Specimens from the Royal Thai Army Personnel in “Surveillance of Drug Abuse in Military”, Fiscal Year 2017

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การด�ำ เนินโครงการเฝ้าระวังโรคมาลาเรีย และโรคที่เป็นอุปสรรคการปฏบิ ัติการทางทหารตามแนวชายแดน ปีงบประมาณ 2560
Active Surveillance for Malaria and Diseases of Non-Battle Injury along Thai Borders, Fiscal Year 2017

การด�ำ เนินงานโครงการพัฒนาตน้ แบบการก�ำ จัดมาลาเรียแบบมสี ่วนรว่ ม ทหาร – พลเรอื น ในพนื้ ท่ปี ฏิบัตกิ ารทางทหารทีเ่ ปน็ พ้ืนทร่ี ะบาดของโรค
จงั หวดั ศรีสะเกษ ปีงบประมาณ 2560

Development of Military – Civilian Malaria Elimination Model in Military Areas of Operation, Srisakat Province, Fiscal Year 2017

การเก็บตวั อยา่ งนํ้าอุปโภค – บรโิ ภค และนํ้าเสยี – น้าํ ทง้ิ เพอ่ื นำ�มาวเิ คราะห์คณุ ภาพน้ําจากหนว่ ยทหารพน้ื ท่ีกองทพั ภาคท่ี 1
1 พฤศจกิ ายน – 20 ธนั วาคม 2559

Collections of Water Samples from Army Installations for Water Quality Analysis 1 November – 20 December 2016, at 1st Army Area

คณะผู้บรหิ าร พบ. และ ผอ.สวพท. เยย่ี มหน่วยงานวิจยั ทางการแพทย์ทหาร สหรัฐอเมริกา 30 ตลุ าคม – 9 พฤศจกิ ายน 2559
ณ กรงุ วอชงิ ตันดีซี เมอื งซานอนั โตนโิ อ มลรัฐเท็กซัส และเมืองฮอนโนลูลู มลรฐั ฮาวาย ประเทศสหรฐั อเมริกา

RTA – Medical Department Executive Officers and AFRIMS Director General visited US Military Medical Research Institutes
30 October – 9 November 2016, at Washington DC; San Antonio, Texas; and Honnolulu, Hawaii; USA

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สมเด็จพระเทพรัตนราชสุดาฯ สยามบรมราชกมุ ารี รับการถวายรายงานผลงานวจิ ยั ของ สวพท. โดย พ.อ.หญงิ ดร.จริยาณาฏ เกวี
และ พ.อ. ดร. วุฒกิ รณ์ รอดความทกุ ข์ 10 พฤศจิกายน 2559 ณ โรงเรยี นนายร้อยพระจลุ จอมเกลา้ จงั หวดั นครนายก

Princess Maha Chakri Sirindhorn visited AFRIMS research exhibition by COL Jariyanart Gaywee and COL Wuttikon Rodkvamtook,
10 November 2016 at Chulachomklao Royal Military Academy, Nakhon Nayok Province

สมาคมแมบ่ า้ นทหารบก ร่วมกับ กรมแพทยท์ หารบก โดย สถาบันวิจัยวิทยาศาสตรก์ ารแพทยท์ หาร จัดการอบรมให้ความรูเ้ ร่อื ง “ร้ทู ันโรคติดเชอื้ ไวรัสซกิ า”
17 พฤศจกิ ายน 2559 ณ วิทยาลัยแพทยศาสตร์พระมงกุฎเกลา้

Thai Army Wives Association and Royal Thai Army Medical Department by AFRIMS organized the meeting “To Know Zika Virus Disease”
17 November 2016 at Phramongkutklao College of Medicine

ผอ.สวพท. และคณะ ตรวจเยย่ี มโรงพยาบาลสนาม ศูนยป์ ฏิบตั ิการร่วมการแพทย์ และสาธารณสุข 24 พฤศจกิ ายน 2559 ณ ท้องสนามหลวง กรุงเทพฯ
AFRIMS Director General and colleague visited Field Hospital, Center of Medical and Public Health Opearation 24 November 2017
at Sanam Luang, Bangkok

ข้าราชการ สวพท. รบั รางวัลการประกวดผลงานวิจยั การประชุมวิชาการพระมงกุฎเกล้า ครงั้ ท่ี 44 24 พฤศจิกายน 2559 ณ โรงพยาบาลพระมงกฎุ เกล้า
RTA – AFRIMS personnel received Research Awards at the 44th Phramongkutklao Hospital Annual Academic Conference
24 November 2016 at Phramongkutklao Hospital

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ผอ.สวพท. และคณะ ให้การตอ้ นรับ ดร. แพทริเซยี เอฟ วอลค์ เกอร์ นายกสมาคมเวชศาสตรเ์ ขตรอ้ น และสขุ อนามยั สหรฐั อเมริกา และคณะ
ในการเยยี่ มชม สวพท. 8 ธันวาคม 2559 ณ หอ้ งมิตรภาพ สวพท.

AFRIMS Director General and colleague welcomed Dr. Patricia F. Walker, president of the American Society of Tropical Medicine and Hygiene
and colleague to visit AFRIMS 8 December 2016 at Friendship Room, AFRIMS

รองผูบ้ ัญชาการทหารบก มอบรางวัลเชดิ ชูเกียรติทหารแพทย์ ดา้ นงานวิจัย ประจำ�ปี 2560 ใหแ้ ก่ พ.อ. หญงิ ดร.จรยิ าณาฏ เกวี
และ พ.อ. ดร. วฒุ กิ รณ์ รอดความทกุ ข์ ขา้ ราชการ สวพท. ในวนั สถาปนากรมแพทยท์ หารบก ครบรอบปที ่ี 117 7 มกราคม 2560 ณ กรมแพทยท์ หารบก

RTA Deputy Commander in Chief presented “Outstanding Medical Core Personnel Awards, Research Branch in Fiscal Year 2017”
to COL Jariyanart Gaywee and COL Wuttikon Rodkvamtook in 117th RTA Medical Department Anniversary,
7 January 2017 at RTA Medical Department Headquarter

ชุดห้องปฏิบัตกิ ารเคลอ่ื นที่เร็ว สวพท. รว่ มสอบสวนการระบาดของโรคติดเช้อื ระบบทางเดินหายใจในนักเรียนทหารหลกั สูตรทหารเสือ
18 มกราคม 2561 ณ คา่ ยนวมนิ ทร์ทราชินี จังหวดั ชลบุรี

AFRIMS Laboratory Rapid Response Team investigated respiratory infection outbreak
18 January 2017 at Nawamindhachini Army Base, Chonburi Province

กรมแพทยท์ หารบก โดย สวพท. จดั การอบรมเชงิ ปฏบิ ตั กิ าร “การใช้รถหอ้ งปฏบิ ตั ิการทางการแพทย์เคล่อื นท่ี เพื่อการสอบสวนโรค”
1 กมุ ภาพนั ธ์ 2560 ณ สวพท.

AFRIMS on behalf on RTA Medical Department organized “Mobile Medical Laboratory for Outbreak Investigation Workshop”
1 February 2017 at AFRIMS

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สวพท. น�ำ เสนอผลงานวจิ ัย ในโครงการพัฒนางานวิจัย และสิง่ ประดษิ ฐ์ทางการทหารดา้ นการแพทย์ จัดโดยกรมแพทยท์ หารบก รว่ มกบั
โรงพยาบาลพระมงกุฎเกลา้ และ สวพท. 21 กุมภาพันธ์ 2560 ณ โรงพยาบาลพระมงกฎุ เกล้า

RTA – AFRIMS personnel presented Research and Innovation in “Research Development and Military Medical Inventions Project”
organized by RTA – Medical Department, Phramongkutklao Hospital and AFRIMS 21 February 2017 at Phramongkutklao Hospital

การประชุมใหญ่สามญั ประจ�ำ ปี 2560 มูลนธิ ทิ ่านผู้หญิง วริ ะยา ชวกุล เพ่อื การวจิ ัยวทิ ยาศาสตร์การแพทย์ทหาร
23 กุมภาพนั ธ์ 2560 ณ ห้องพนิ ทโุ ยธนิ สวพท.

Annual General Meeting of Thunpuying Viraya Javakul Foundation for Military Medical Research
23 February 2017 at Phintuyothin Auditorium, AFRIMS

พ.อ.หญิง ดร.จรยิ าณาฏ เกวี และ พ.อ. ดร. วุฒิกรณ์ รอดความทกุ ข์ รว่ มประชมุ และน�ำ เสนอผลงานในการประชมุ สัมมนาแพทย์ทหารนานาชาติ
สาธารณรัฐแหง่ สหภาพเมียนมาร์ (สมม.) ครงั้ ที่ 24 7 – 10 มนี าคม 2560 ณ กรงุ ยา่ งกงุ้ สาธารณรฐั แหง่ สหภาพเมยี นมาร์

Col Jariyanart Gaywee and Col Wuttikon Rodkvamtook presented research findings at the 24th Myanmar Military Medical Conference,
7 – 10 March 2017 in Yangon, Myanmar

สวพท.ท�ำ ดตี ามรอยพอ่ สานต่อโครงการ สตั วป์ ลอดโรค คนปลอดภัย จากโรคพษิ สนุ ัขบ้า
ตามปณิธาน ศ.ดร.สมเดจ็ พระเจา้ ลกู เธอ เจ้าฟา้ จุฬาภรณว์ ลยั ลักษณ์ อคั รราชกุมารี 8 มีนาคม 2560 ณ กรมพลาธกิ ารทหารบก
Rabies Vaccination Campaign by H.R.H.Princess Chulabhorn’s Rabies Eradication Program 8 March 2017 at RTA – Quartermaster Department

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ท่ีปรกึ ษาพิเศษ สวพท. ผอ.สวพท.และคณะผบู้ ริหาร ดูงานท่ี สถาบนั วจิ ัยวอลเตอร์รดี 19 – 25 มนี าคม 2560 ณ กรุงวอชงิ ตันดซี ี ประเทศสหรัฐอเมรกิ า
AFRIMS Special Advisor, AFRIMS Director General and Colleague visited Walter Reed Army Institute of Research
19 – 25 March 2017 at Washington DC, USA

พิธรี ับ – สง่ หน้าที่ ผอู้ ำ�นวยการสถาบนั วจิ ัยวทิ ยาศาสตร์การแพทย์ทหาร โดย พลตรี สรุ เดช จารจุ ินดา สง่ มอบหน้าทใี่ ห้ พลตรี พีระพล ปกป้อง
4 เมษายน 2560 ณ หอ้ งพินทุโยธิน สวพท.

AFRIMS Director General Change of Command Ceremony from Major General Suradet Jaruchinda to Major General Peerapol Pokpong
4 April 2017 at Phintuyothin Auditorium, AFRIMS

พล.ท. สายันต์ สวัสด์ิศรี ผู้อำ�นวยการ ศนู ย์อำ�นวยการแพทยพ์ ระมงกุฎเกล้า นำ�คณะนักวจิ ยั กองวจิ ยั สวพท. ไปประสานการดำ�เนนิ งานวจิ ัย
โดยมคี ณะนายทหาร กอ.รมน.ภาค 4 สว่ นหนา้ ให้การต้อนรบั 19 เมษายน 2560 ณ ค่ายสิรนิ ธร จังหวัดปตั ตานี

LT.GEN Sayan Sawatsri, Director General, Pramongkutklao Medical Center together with researchers from Research Division, AFRIMS
visited Internal Security Operation Command Region 4 19 April 2017 at Sirindhorn Fort, Pattani Province

ร.อ.หญิง มณรี ตั น์ สมศรี ประจ�ำ แผนกพยาธวิ ิทยา กองวิจัย ฝกึ ศกึ ษาดงู าน การตรวจวนิ ิจฉยั สายพันธเ์ุ ช้ือกอ่ โรคไข้ริคเค็ทเซียดว้ ยเทคนคิ อณูชวี โมเลกุล
1 - 30 เมษายน 2560 ณ ศนู ยว์ จิ ยั วทิ ยาศาสตร์การแพทยท์ หารเรอื มลรฐั แมรีแลนด์ สหรัฐอเมรกิ า

Capt. Maneerat Somsri, Pathology Section, Research Division, AFRIMS, as visiting scientist received training in molecular identification of
rickettsial species 1 - 30 April 2017 at Naval Medical Research Center, Maryland, USA

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ผอ.ศพม. และคณะ ตรวจเยี่ยม สวพท. 9 พฤษภาคม 2560
Director of Phramongkutklao Medical Center visited AFRIMS 9 May 2017

ข้าราชการ สวพท. รว่ มประชุม และน�ำ เสนอผลงานวิชาการ การประชุมแลกเปล่ยี นองค์ความรูด้ ้านสุขภาพทหารภาคพน้ื เอเซียแปซฟิ ิก
22 – 26 พฤษภาคม 2560 ณ ประเทศสงิ คโปร์

AFRIMS personnel participated in the Asia Pacific Military Health Exchange Conference 22 – 26 May 2017, Singapore

ผอ.สวพท. และคณะ ให้การตอ้ นรบั พ.อ.หญิง เด็บบารา แอล วิทเมอร์ ผู้บงั คบั การสถาบนั วิจัยวอลเตอรร์ ดี และคณะ ในการเย่ียมชม สถาบนั วจิ ัย
วิทยาศาสตร์การแพทย์ทหาร และ ศูนยแ์ พทย์ทหารอาเซียน 1 มถิ ุนายน 2560 ณ ห้องมิตรภาพ สวพท. และกรมแพทยท์ หารบก

AFRIMS Director General and colleague welcomed COL Debahra L. Whitmer, Commander of the Walter Reed Army Institute of Research and
colleague to visit AFRIMS and Asian Center of Military Medicine 1 June 2017 at Friendship Room, AFRIMS and RTA – Medical Department

วันสถาปนา สถาบนั วจิ ัยวทิ ยาศาสตรก์ ารแพทย์ทหาร ครบรอบปีที่ 56 6 มถิ ุนายน 2560
The 56th AFRIMS Anniversary, 6 June 2017

152 รายงานประจำ�ปี ๒๕๖๐

สถาบนั วิจัยวทิ ยาศาสตรก์ ารแพทยท์ หาร

ARMED FORCES RESEARCH INSTITUTE OF MEDICAL SCIENCES

สวพท. จัดการประชุมนานาชาติ “การเสรมิ สร้างความรว่ มมือระหว่างพลเรอื น และทหารเพื่อเร่งรัดก�ำ จัดโรคมาลาเรียในภูมิภาคเอเชยี ตะวนั ออกเฉียงใต้”
26 – 28 มิถุนายน 2560 ณ โรงแรมเดอะ สโุ กศล กรงุ เทพมหานคร

“Enhancing Civilian – Military Cooperation to Accelerate Malaria Elimination in Southern Asia” organized by AFRIMS
26 – 28 June 2017 at The Sukosol Hotel, Bangkok

ผอ.สวพท. และคณะ ตอ้ นรบั คณะผเู้ ขา้ รว่ มประชมุ นานาชาติ “การเสริมสรา้ งความรว่ มมอื ระหวา่ งพลเรือน และทหารเพอ่ื เร่งรัดก�ำ จดั โรคมาลาเรยี
ในภมู ภิ าคเอเชยี ตะวันออกเฉียงใต้” เพือ่ ศกึ ษาดูงานที่ สวพท. 28 มิถุนายน 2560 ณ หอ้ งพินทโุ ยธิน สวพท.

AFRIMS Director General and Colleague welcomed the Delegates from “Enhancing Civilian – Military Cooperation to Accelerate Malaria
Elimination in Southern Asia” to visit AFRIMS 28 June 2017 at Phintuyothin Auditorium, AFRIMS

โครงการสำ�รวจเชื้อเลปโตสไปรา และอตั ราการตดิ เชื้อเลปโตสไปราในสนุ ขั ทหาร และส่งิ แวดล้อมบริเวณพนื้ ท่ีปฏิบัตกิ ารทางทหาร
ณ ศนู ย์การสนุ ัขทหาร และกองพันสุนขั ทหาร กรมการสตั ว์ทหารบก 15 – 16 มิถุนายน 2560 ณ กรมการสตั ว์ทหารบก จังหวดั นครราชสีมา

“Seroprevalence Study for Leptospira spp. in Dogs at Army War Dogs Center and War Dog Battalion”
15 – 16 June 2017 at War Dog Battalion, Nakhorn Ratchasima Province

กองวจิ ัย สวพท. ด�ำ เนนิ งานโครงการศึกษาอตั ราความชกุ ของโรคตดิ เช้ือท่ีส�ำ คัญต่อการปฏบิ ัติการทางทหารของก�ำ ลงั พลทปี่ ฏิบตั ิงาน
ในสามจังหวัดชายแดนภาคใต้ ในพ้ืนที่ จงั หวัดยะลา ปัตตานี และนราธวิ าส 4 – 8 กรกฎาคม 2560

Activities of research entitled “Survey for Prevalence of Infectious Diseases of Military Importance among Military Personnel Deployed
to the Three Southern Provinces of Thailand”, Yala, Pattani and Narathiwas Provinces, 4 – 8 July 2017

ANNUAL REPORT 2017 153