History
ORIGINS ~ 1960s ~ 1970s ~ 1980s ~ 1990s ~ 2000s ~ 2010s
 
ORIGINS
The Armed Forces Research Institute of Medical Sciences started out, in 1959, as the Thailand Southeast Asia Treaty Organization Cholera Research Project in Bangkok. During the spring of 1958, a cholera epidemic, the first in almost 10 years, began near Dacca, East Pakistan, spread through Calcutta, India, and hit Bangkok and surrounding provinces. A similar cholera outbreak appeared to be underway in the spring of 1959. At the fifth annual meeting of the SEATO Council, in April 1959, the U.S. representative and ambassador to Thailand secured backing for a cooperative cholera research project under SEATO sponsorship. 

In the summer of 1959, a committee was established to develop an organizational plan and recommend a location for the CRP in South or Southeast Asia. By August 1959, the committee provided two suggestions for the location of the SEATO CRP: Dacca, East Pakistan, and Bangkok, Thailand. Although the committee was impressed by the professional qualifications and experience of Bangkok’s medical community, its laboratory resources, and the country’s relative political stability, Thailand was not the logical choice for location of the CRP, with cholera at most episodic and apparently receding that spring. Still, in line with military and foreign policy considerations, the committee recommended to the SEATO Council that Bangkok be the CRP’s temporary location. In response to a diplomatic note, the Thai minister of foreign affairs replied that the Thai Ministry of Public Health was authorized to cooperate with the United States in establishing the Thailand SEATO CRL. Operations commenced in late December. 

In Thailand, the SEATO CRL became the SEATO Medical Research Laboratory in January 1961 after an exchange of diplomatic letters in December 1960 between the US Department of State, the Royal Thai Ministry of Foreign Affairs, and SEATO headquarters. The SEATO MRL was then quickly restructured and augmented in mission, personnel, and resources. A comprehensive survey of medical research resources in Asia Pacific by the U.S. Army Medical Research and Development Command confirmed the strategic importance of the SEATO MRL. During and after the Vietnam conflict, the MRL conducted medical research on infectious diseases important to the soldier and public health. The MRL also provided research and reference laboratory support, teams, and medical experts to support the U.S. Army Medical Research Team from the Walter Reed Army Institute of Research in Vietnam during the war. The SEATO MRL became AFRIMS in 1977 and remains the largest U.S. Army overseas medical research laboratory.

1960s
The SEATO MRL included a Thai component, with a command chain from the Royal Thai Armed Forces Supreme Command, and a U.S. component, staffed from the U.S. Army Medical Research and Development Command.
 
The new MRL grew rapidly in both staffing and range of projects undertaken. While cholera remained a major focus, the MRL also conducted studies on a wide variety of tropical diseases. Joint efforts were initiated between the U.S. and Thai components to study a broad range of topics like antimicrobials, arboviruses, arthropods of medical importance and bladder stones. In parallel, staff developed laboratory methods and assay; for example, the report “Testing and evaluation of a holding medium for enteric bacteria” established the widely adopted Carey-Blair media for culture of enteric bacteria.
 
During the MRL’s initial decade, a number of seminal studies quickly established the laboratory’s reputation as a major force in tropical medical research. For example, a test for neutralizing antibodies to dengue in a pair of 1967 papers that have been cited in nearly 500 subsequent publications. Others include multidisciplinary field studies, tracking the epidemiology and ecology of infections like dengue, Japanese encephalitis, malaria and rickettsial diseases.

1970s
As the war in Vietnam continued into the 1970s, the SEATO MRL maintained support for the USAMRT–Vietnam in Saigon, focusing on diseases of military importance, including hepatitis, diarrheal diseases, Japanese encephalitis and malaria. The MRL was also involved in the drug screening program of troops in Vietnam and helped combat disease outbreaks among U.S. troops in the region.

Studies of patients with diarrhea led to the first isolation of Vibrio parahemolyticus in Thailand. Malaria drug studies for both treatment and prophylaxis were major efforts of the laboratory. Building on the malaria drug screening program at WRAIR, candidate drugs were evaluated in field studies. Most of this testing was done in collaboration with the Royal Thai Army in border areas.

During the 1970s, major political changes in Southeast Asia had an impact on the laboratory. As part of the drawdown of troops from the region after the Paris Peace Accords in 1973, American Service Members were also withdrawn from Thailand. Fortunately for the SEATO MRL, the Ministry of Foreign Affairs supported the continuation of its medical research and the continued presence of U.S. Army researchers at the MRL.

One consequence of the ending of the Vietnam War was the dissolution of SEATO in 1977. Letters of Agreement between the Thai and US governments preserved the MRL’s operation on the same basis as previously, still under the Royal Thai Army Supreme Command, but its name was changed to the Armed Forces Research Institute of Medical Sciences. The change took effect on 1 July 1977.

1980s
The decade began with significant AFRIMS assistance to the Khmer refugees who had flowed into Thailand in late 1979 and settled in camps just inside the Thai border. AFRIMS medical teams mobilized quickly and began providing assistance while the United Nations High Commissioner for Refugees built a medical and logistic support structure. Through subsequent years, AFRIMS clinicians and laboratories continued to provide diagnostic information for disease outbreaks in the camps, including cholera, murine typhus and enteritis necroticans, and the director of the American component became an advisor to the U.S. ambassador on refugee medical matters.

Malaria research teams showed that mefloquine, which had been introduced less than 10 years earlier, was losing efficacy against the falciparum parasites circulating on the Thai-Cambodian border. They also demonstrated that doxycycline, a familiar and approved drug, was effective for prophylaxis (it is still in use today). Research at the time also laid the groundwork for the first trial of a candidate malaria vaccine in Asia. 

AFRIMS entomologists studied the vector component of malaria. Scientists developed an assay that enabled easier and more reliable malaria field epidemiology. To increase understanding of individual infections, researchers from AFRIMS and Mahidol University established a controlled human challenge model using the bites of Plasmodium falciparum-infected mosquitoes. Such models have proven useful in the assessment of malaria candidate drugs and vaccines.

The studies of Japanese encephalitis begun in the 1970s continued. Assays were developed that allowed diagnosis of acute infections and differentiation of JE from dengue. A vaccine trial in 40,000 school children in Kamphaeng Phet proved the vaccine’s efficacy and safety and led to its incorporation into the childhood immunization program of Thailand and to vaccine licensure in the United States.

AFRIMS virologists also studied dengue. Diagnostics were developed that not only distinguished dengue from JE, but also primary from secondary infections. A study of Bangkok children with dengue added to evidence that second cases may be more serious than first cases. Entomologists studied the vector mosquito, Aedes aegypti, and found that its efficacy was temperature dependent. This finding helped explain the cyclic patterns of dengue transmission. 

Diarrheal diseases were another area in which laboratory advances were matched with extensive field work. Patterns of diarrhea occurring at high rates (>50%) were described in Peace Corps volunteers newly arrived in Thailand and in travelers in Nepal. DNA probes were developed in the laboratory for numerous pathogens and toxins, increasing both sensitivity and specificity of diagnoses. An example of cross-departmental collaboration was the creation by the diarrheal research team of a DNA probe against falciparum malaria, allowing diagnoses of malaria from dried blood spots collected in remote field sites.

1990s
In the 1990s, AFRIMS was involved in a collaborative field efficacy trials of the Smith-Kline Beecham hepatitis A vaccine in 1991, carried out in partnership with the Thai Ministry of Public Health, in 40,000 school children in Kamphaeng Phet Province. The trial showed that the vaccine was safe, immunogenic and protective, and it was a major factor in the US Food and Drug Administration’s approval of the vaccine. Researchers also evaluated two malaria vaccines. 

The 1990s also marked the start of a human immunodeficiency virus (HIV) research program at AFRIMS, leading to the screening for HIV of all Royal Thai Army recruits. WRAIR supported AFRIMS and the RTA Institute of Pathology in the establishment of a state-of-the-art HIV testing program to reduce the incidence of false-positive results. HIV-positive recruits were retained on active military duty and provided counseling and care.

WRAIR and AFRIMS’s RTA and U.S. components began to build human, laboratory and field capacity to evaluate candidate HIV vaccines. In the late 1990s a number of these candidate vaccines were assessed in clinical studies and one “prime-boost” combination was advanced to phase III testing, which was implemented in the next decade. To prepare for the phase III trial, cohort development studies were done in over 5,000 volunteers in three locations. 

The departments of Virology and Bacteriology both developed collaborations in Nepal. The former focused on hepatitis E infections, laying the foundation for a clinical trial of a promising candidate vaccine and the latter on travelers’ diarrhea. Because of similarities in vulnerability to diarrhea among Western travelers and military personnel, AFRIMS worked with Kathmandu travel clinics to show that infecting organisms varied with time abroad and duration of symptoms. The researchers showed that a protozoan parasite, Cyclospora, was a cause of diarrhea, and demonstrated how to treat it. Over time, these collaborative studies led to the establishment of the Walter Reed-AFRIMS Research Unit–Nepal (WARUN).

The U.S. AFRIMS component also supported the annual Cobra Gold joint training exercises, usually focusing on diagnosis and treatment of diarrheal diseases and determination of evolving levels of drug resistance in these infections.

During the 1990s, insightful observations by WRAIR and AFRIMS entomologists showed that falciparum malaria had returned as a public health threat in deforested areas recently replanted as orchards, creating a favorable environment for the breeding of vector mosquitoes. They also reported that the surface protein of Plasmodium falciparum sporozoites had two variants, allowing a new level of epidemiologic specificity. In 1999 the Veterinary Medicine Department became the first laboratory animal facility in Thailand to achieve international accreditation.

2000s
In 2003 a satellite unit in northern Thailand moved into its own building when the Department of Virology opened the Kamphaeng Phet–AFRIMS Virology Research Unit (KAVRU) on the grounds of the Kamphaeng Phet provincial hospital (AFRIMS’s relationship with the hospital had started in the 1980s with the Japanese encephalitis vaccine trial).

AFRIMS HIV research, begun in the 1990s, became the most successful and visible part of the mission after 2000. Based on a series of phase I/II vaccine trials and cohort studies of new HIV infections, the world’s largest HIV vaccine trial was started in 2003. This collaboration was led by the Thai Ministry of Public Health, with Mahidol University, the RTA Medical Department, the US Army Medical Research and Materiel Command and two vaccine manufacturers (Sanofi Pasteur and VaxGen). Results of the 16,000-person trial were released in 2009, revealing that the vaccine combination had provided moderate protection (31% efficacy) from HIV infection. This was the first HIV vaccine to show any protective benefit, and the study reinvigorated the demoralized discipline of HIV vaccinology.

Other important vaccine developments also occurred during the decade. A collaboration between the Walter Reed–AFRIMS Research Unit, Nepal, and the Nepalese Army in a 2,000-person efficacy trial found that a GlaxoSmithKline vaccine was very effective (95% efficacy) in protecting against hepatitis E viral infections. Phase I/II trials of dengue vaccines were carried out in a collaboration among AFRIMS, GSK and pediatricians at Phramongkutklao Army Hospital.

Malaria researchers conducted regulated clinical trials of two important drugs in the U.S. Army development portfolio: tafenoquine for treatment of relapsing malaria in collaboration with Mahidol University (2003) and intravenous artesunate for severe malaria at the Kwai River Christian Hospital (2007) in parallel with AFRIMS’s sister laboratory in Kenya—both now approved by the U.S. FDA. Toward the end of the decade, new collaborations in malaria prophylaxis and drug resistance were established in Cambodia. Resistance of falciparum malaria against artemisinin was described, raising concern that one of the few remaining effective antimalarial drugs may be lost. 

In 2005 AFRIMS was designated as a World Health Organization (WHO) collaborating center for “reference, training and investigation of emerging infectious diseases.” A prime example of a reemerging infectious disease was the outbreak of chikungunya virus infections in southern Thailand in 2008. SEATO MRL investigators had studied this virus in the 1960s and 1970s, but it had largely disappeared, while dengue continued to increase in prevalence. In the 2008 event, the chikungunya virus had mutated and was now easily transmitted by Aedes albopictus. The Department of Virology established molecular assays and provided diagnostic support to the RTA and the Ministry of Public Health as they responded to the outbreak. Surveillance for influenza virus increased in mid-decade as part of global efforts to prepare against a new pandemic. As the decade ended, a new pandemic form of influenza struck Thailand, and both components of AFRIMS were extensively involved in supporting military and civilian public health teams responding to this major challenge.
 

2010s
At the beginning of the decade, the Ministry of Public Health announced the outcomes of the RV144 Thai trial, a community-based HIV vaccine trial involving 16,000 participants. The RV144 trial demonstrated, for the first time, that a HIV vaccine could offer at least partial protection (31%) against HIV infection. AFRIMS, which coordinated the multiple Thai components of this collaborative seven-year effort, led the testing and preservation of the crucial clinical specimens. The Retrovirology research community then focused on building upon these results for the next decade. 

In 2011, AFRIMS continued its surveillance project on water quality with the aim of supporting all military units in preventing water-related diseases. Laboratory analysis was carried out on samples of natural water resources, drinking water, and wastewater collected from military units in various regions of Thailand.

In 2017, the Defense Malaria Assistance Program (DMAP) was established to support military-to-military operational research in mitigating the problem of malaria. With this new funding, anti-malaria initiatives were expanded in Bangladesh, Cambodia, Laos, as well as in Thailand with the Royal Thai Army and MoPH. Tafenoquine, approved by the US Food and Drug Administration (FDA) on July 20, 2018, for radical cure of Plasmodium vivax malaria, was based in part on data generated by AFRIMS's research and field clinical trials conducted over a 40-year period. Tafenoquine is metabolically stable and eliminated slowly, thus enabling its administration as a single dose for radical cure or as weekly chemoprophylaxis.

In 2017, AFRIMS, led by the Department of Virology research units in Thailand (KAVRU) and the Philippines (PAVRU), completed the clinical trials of Dengvaxia, the world's first licensed dengue vaccine for people aged 6 to 45 years. Dengvaxia is only administered to people who have had a positive test result indicating a previous infection with the dengue virus.