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GEIS at U.S. Army Medical Research Unit, Kenya

The U.S. Army Medical Research Unit, Kenya (USAMRU-K), was first established in 1969 as a temporary program put in place at the invitation of the Kenyan government to study trypanosomiasis. In 1973, USAMRU-K was made permanent through a cooperative agreement between the Walter Reed Army Institute of Research (WRAIR), Washington, D.C., and the Kenya Medical Research Institute (KEMRI), the Kenyan governmental agency responsible for all biomedical research in Kenya. Research focused on the immunobiology of trypanosomiasis and on the development of a potential vaccine until the early 1980s, when investigators began research on Rift Valley fever, malaria epidemiology, and clinical and field aspects of leishmaniasis. USAMRU-K operates as a WRAIR Special Foreign Activity and is unofficially known within Kenya as “The Walter Reed Project” (Gambel and Hibbs, 1996; GEIS, 2001f).

USAMRU-K has worked primarily as a research organization since its inception. Historically, USAMRU-K has been dedicated to and supported by applied medical research, and its charter and invitation to operate in Kenya are founded on its research mission. Approximately $500,000 was received from GEIS during fiscal year 2000 (USAMRU-K, 2000). In fiscal year 2001, GEIS is expected to supply USAMRU-K with approximately $460,000 (GEIS, 2000c). The majority of USAMRU-K’s budget, which amounted to $2.5 million in 2000, comes from the U.S. Military Infectious Diseases Research Program (MIDRP). Congressional appropriations for a human immunodeficiency virus (HIV) vaccine and prevention of HIV infection/AIDS, the Intra-Laboratory Innovative Research program of the U.S. Department of Defense (DoD), and various grants



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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review 6 GEIS at U.S. Army Medical Research Unit, Kenya The U.S. Army Medical Research Unit, Kenya (USAMRU-K), was first established in 1969 as a temporary program put in place at the invitation of the Kenyan government to study trypanosomiasis. In 1973, USAMRU-K was made permanent through a cooperative agreement between the Walter Reed Army Institute of Research (WRAIR), Washington, D.C., and the Kenya Medical Research Institute (KEMRI), the Kenyan governmental agency responsible for all biomedical research in Kenya. Research focused on the immunobiology of trypanosomiasis and on the development of a potential vaccine until the early 1980s, when investigators began research on Rift Valley fever, malaria epidemiology, and clinical and field aspects of leishmaniasis. USAMRU-K operates as a WRAIR Special Foreign Activity and is unofficially known within Kenya as “The Walter Reed Project” (Gambel and Hibbs, 1996; GEIS, 2001f). USAMRU-K has worked primarily as a research organization since its inception. Historically, USAMRU-K has been dedicated to and supported by applied medical research, and its charter and invitation to operate in Kenya are founded on its research mission. Approximately $500,000 was received from GEIS during fiscal year 2000 (USAMRU-K, 2000). In fiscal year 2001, GEIS is expected to supply USAMRU-K with approximately $460,000 (GEIS, 2000c). The majority of USAMRU-K’s budget, which amounted to $2.5 million in 2000, comes from the U.S. Military Infectious Diseases Research Program (MIDRP). Congressional appropriations for a human immunodeficiency virus (HIV) vaccine and prevention of HIV infection/AIDS, the Intra-Laboratory Innovative Research program of the U.S. Department of Defense (DoD), and various grants

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review and subsidies from commercial partners and granting agencies also support USAMRU-K. To date, the principal activities of USAMRU-K have included the following: Investigation of basic immune responses to the malaria parasite and HIV; testing of drugs against the malaria parasite and HIV and testing of antimalarial drugs and drug resistance; development and testing of simplified diagnostics for malaria, leishmaniasis, and dengue; epidemiology and control of vector-borne diseases; and epidemic response (e.g., Rift Valley fever and Marburg virus infection). A subcommittee of the Institute of Medicine (IOM) Committee to Review the Department of Defense Global Emerging Infections Surveillance and Response System visited USAMRU-K from October 16 to 20, 2000. The subcommittee consisted of committee members Kathleen Gensheimer, James Hospedales, and Guénaël Rodier. G.Rodier was recalled on October 17 to coordinate the World Health Organization (WHO) response to an epidemic of viral hemorrhagic fever in Uganda. A list of the people met and the itinerary followed can be found at the end of this chapter. LABORATORY In 1985, KEMRI took occupancy of new laboratory facilities in Nairobi, and USAMRU-K headquarters were moved into this new KEMRI space. Research teams from the U.S. Centers for Disease Control and Prevention (CDC) and the Japanese International Cooperation Agency (JICA) are also collocated on the KEMRI campus. In Nairobi, USAMRU-K headquarters are housed within the KEMRI Clinical Research Center, 1 of 10 KEMRI centers. In addition to a floor of laboratories and offices that house bacteriology, entomology, parasitology, and molecular biology activities at USAMRU-K headquarters in Nairobi, field operations are maintained at the western location of Kisian on Lake Victoria (for malaria studies) and at the high-elevation site of Kericho (for HIV studies). Smaller sites are maintained at Kisii in the highlands (for cerebral malaria), Baringo in the Rift Valley (for leishmaniasis), and Kilifi on the coast (for dengue). Limited virological capabilities are available within KEMRI through the KEMRI Center for Virus Research, a WHO Collaborating Center for Arbovirus and Viral Hemorrhagic Fever Reference and Research. This laboratory is not directly ad-

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review ministered by USAMRU-K, although Global Emerging Infections Surveillance and Response System (GEIS) resources are contributed to support it. The KEMRI Center for Virus Research also receives support, through a series of complex arrangements, from other agencies such as the CDC and the WHO. At the time of the subcommittee’s visit, the KEMRI Center for Virus Research did not possess the technology and reagents necessary to diagnose Ebola, Marburg, Lassa, or Crimean-Congo hemorrhagic fever.1 The U.S. Army Medical Research Institute of Infectious Diseases does not routinely provide USAMRU-K with reagents or supplies (Ludwig, 2001). Boundaries between those operations and facilities that are specific to KEMRI and those that belong to USAMRU-K are difficult to discern. Some laboratory space is occupied solely by USAMRU-K or by KEMRI, and other space (such as facilities for the detection and evaluation of enteric pathogens) is shared. In shared laboratories, USAMRU-K supplies many reagents, supplies, and equipment for common use. USAMRU-K facilities operate at a biosafety level 2 capacity, though biosafety level 3 capabilities are available through the KEMRI Center for Virus Research. Much of USAMRU-K’s work is conducted at field sites (USAMRU-K, 2000). Although the subcommittee did not visit the site, the field laboratory in Kisian (shared with the KEMRI Center for Vector Biology and Control Research) reportedly exceeded its operating capacity years ago. Several current field activities, such as global positioning system work and drug studies, have had to set up in hotel and rented quarters. Plans exist to build a new facility at this site. GEIS funds may be used to equip the facility. USAMRU-K operations are substantially affected by infrastructure limitations in the country. Basic functionalities that are generally taken for granted in developed countries, such as electrical power, can be in short supply because of frequent power outages and rationing. Two freezers (purchased with GEIS funds) for the storage of specimens for drug testing have yet to be plugged in because no outlets are available. Emergency power is undependable and inadequate. Communications within and outside of the country are likewise erratic, as even the most basic technological support, such as a telephone system, is not always available (USAMRU-K, 2000). Also, operations in Kenya take a relatively harsh toll on equipment. For instance, because of hazardous road conditions and theft, the effective lives of all motor vehicles in Kenya are less than 5 years. 1   Steps are being taken to make these reagents regularly available to KEMRI (Dunster, 2001; Ludwig, 2001).

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review Conclusions The location of USAMRU-K in Kenya, a country that is geographically diverse and rich in transmissible pathogens, offers exciting potential for the study of emerging infectious diseases in country as well as within the region. Kenya’s troubled infrastructure gives rise to operational challenges and, at the same time, heightens the need for GEIS efforts. To achieve program objectives, investment in improving national public health capacity is crucial. Continued investment in improving USAMRU-K’s laboratory capabilities is a part of this process. At all sites that the IOM subcommittee visited, USAMRU-K’s physical facilities range from marginally adequate to basic. In addition, lack of reagents such as those that would be necessary to enable capabilities for the diagnosis of viral hemorrhagic fevers limits USAMRU-K’s capacity to achieve its full potential as part of GEIS. STAFFING The U.S. Army authorizes USAMRU-K a contingent of nine professional and two administrative U.S. personnel. Despite adequate funding, only five Army officers and one GS-11 civilian were assigned to the unit at the time of the subcommittee’s visit. In addition to the U.S. staff, USAMRU-K employs about 120 Kenyan technical staff through a contractual agreement with KEMRI. Nonmilitary USAMRU-K personnel are actually contracted to KEMRI through annually renewable contracts. There is currently no doctoral-level Kenyan national on staff at USAMRU-K, although arrangements are in place to have a physician assigned to USAMRU-K from KEMRI’s Center for Clinical Research. This physician is to work in association with a preventive medicine officer to be posted at USAMRU-K later in 2001. This preventive medicine officer is to work full time on GEIS activities. The lack of a virologist among USAMRU-K staff assignees was noted. Although USAMRU-K can use the services of the KEMRI virologist, this individual is primarily responsible to KEMRI and other institutes of the Kenyan Ministry of Health (MoH). At the time of the site visit, this individual was heavily engaged with the MoH, attempting to provide public health-type advice regarding the establishment of a surveillance system for Ebola virus in Kenya, and was unavailable to provide virological support for ongoing activities or for diagnostic responses. Additional virological support could have made USAMRU-K a key player in the Ebola virus epidemic. The salaries of three technicians who work with the KEMRI virologist and most of the supplies used by the virologist in his work are paid for directly by USAMRU-K with GEIS funds.

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review As an aside, the efforts of USAMRU-K staff to learn Swahili are noteworthy, as such skills help to integrate projects and foster collaborative associations with the public health community in the host country. Conclusions A net loss of personnel, including the loss of three of four medical officers, during the 18 months leading up to the subcommittee’s site visit has made it difficult for USAMRU-K to achieve its objectives. This loss of personnel has interfered with GEIS implementation. The subcommittee recognizes that USAMRU-K is obligated to all agencies (chiefly MIDRP) and partners from which it accepts funds and that juggling such responsibilities presents a challenge to a laboratory that is understaffed, underscoring the need to recruit and retain competent staff. USAMRU-K is particularly deficient in staff who possess expertise in public health and epidemiology and who can be available on site to guide USAMRU-K as it moves beyond its traditional research-based mission to substantially and substantively support public health-focused activities as well. Although a U.S. Army physician-epidemiologist is scheduled to join USAMRU-K in September 2001, other staffing options also warrant consideration. Additional senior-level foreign service nationals could offer further public health and epidemiological expertise, as well as insight into the working of the country. The current lack of foreign service nationals among senior-level staff at USAMRU-K represents a missed opportunity for USAMRU-K and for GEIS. Given the scope of GEIS and the threat that viral infectious disease entities pose in Kenya and the region, the placement of another virologist within the KEMRI laboratory, funded by USAMRU-K, may also be worth considering for the purposes of expanding the scope of virological surveillance activities in country and providing USAMRU-K and GEIS with better access to virological support. GEIS at USAMRU-K would also benefit from a full-time, on-site manager, possessing applied epidemiology and public health expertise. Efforts to become integrated with the culture of the host country work well to enhance working relationships and help stimulate research and surveillance activities. The presence of native-born professionals, such as the senior research officer at the Center for Microbiology Research (KEMRI), actively working with GEIS significantly expands the scope of the in-country activities of USAMRU-K by providing cultural and linguistic links to government- and institution-based professionals within the country. Staff efforts to learn and communicate with collaborators in the local language similarly serve to enhance working relationships. The efforts of current U.S. military staff to learn Swahili are commendable.

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review TECHNOLOGY AND INFORMATION MANAGEMENT A range of information and communication technology resources are available within the KEMRI complex. Some have been recently acquired, in whole or in part, through GEIS. For example, a very-small-aperture-terminal (VSAT) system2 installed 6 months before the site visit has greatly improved access to the Internet, facilitating e-mail communication, medical literature searches, and the sharing of data from field sites. The VSAT system supports satellite communications for USAMRU-K and its partners: CDC, JICA, WHO, and the Oxford-Wellcome Foundation. This KEMRI system is linked to the Multilateral Initiative on Malaria Communications Network (MIMCom) network,3 which seeks to foster communication among malaria researchers in Africa (MIMCom, 2001) as part of a joint effort supported by the Fogarty Foundation and the National Library of Medicine of the U.S. National Institutes of Health (GEIS, 2000b). The director of KEMRI spoke highly of the value added by the VSAT system in a country where regular telephone communications are unreliable. He was also enthusiastic about the four computers recently purchased with GEIS funds and installed in KEMRI’s library. A newly hired systems administrator has contributed to the improvement of the information technology infrastructure and is planning to introduce a KEMRI website, Voice Over Internet Protocol (VOIP), and an intranet. A local area network exists and is being upgraded. However, an overall information plan—a comprehensive strategy for making use of technical resources to share information with and receive information from public health partners—does not exist. No regular surveillance bulletin or other means of routine distribution of GEIS project data is undertaken specifically by USAMRU-K, although KEMRI has plans to begin producing a quarterly newsletter that will provide updates on specimen numbers, diagnoses, epidemics, profiles of laboratory methods, staff profiles, and a forum for discussion. The commander of USAMRU-K acknowledged that the communication and sharing of information on disease patterns and trends with those who need to take action was an area in great need of improvement. Nor was it clear that information on emerging patterns and trends is shared with the GEIS Central Hub or other GEIS sites on a routine and timely basis. The commander of USAMRU-K expressed concern that guidance regarding dissemination of 2   A VSAT receives information from and transmits to information terminals that have been installed at dispersed sites and that are connected to a central hub by satellite with small-diameter (0.6- to 3.8-meter) antenna dishes (Spread Spectrum Scene Online, 2001). 3   In Nairobi, the communications infrastructure is supplied by USAMRU-K; in western Kenya, MIMCom and the National Library of Medicine supply this infrastructure.

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review GEIS surveillance data and planning for dissemination of GEIS surveillance data have been insufficient. USAMRU-K does not yet have a laboratory information system to facilitate laboratory management and surveillance needs. Conclusions The information technology environment at USAMRU-K is sufficient, despite infrastructure challenges in Kenya, to support the achievement of GEIS objectives. The VSAT system—and the communications support that it provides—represents a valuable investment by GEIS. GEIS at USAMRU-K would benefit from the development of an overall information plan, including the development of a laboratory information system, and the development of systematic means of communicating surveillance information to short- and long-term data users, including the MoH as well as other GEIS sites. SURVEILLANCE USAMRU-K conducted several surveillance-related activities before the introduction of GEIS, although it cannot be said that an applied public health surveillance program was in place. The GEIS focus on infectious disease surveillance and response was added in fiscal year 1997 to the existing USAMRU-K operating structure, historically dedicated to laboratory-based infectious disease research. A GEIS implementation plan for fiscal years 2000 through 2004 has been developed. The primary areas of USAMRU-K GEIS program focus are as follows: strengthening of the infrastructure for surveillance, surveillance for the agents of dysentery and associated antibiotic resistance, surveys of hantavirus and rickettsia in Kenya, surveillance for viral hemorrhagic fevers, and surveillance for drug resistance in malaria parasites. Infrastructure Strengthening The infrastructure for surveillance and communication in Kenya is poor. Information technology capabilities within the MoH appear to be very limited for effective disease surveillance and information sharing. MoH capabilities are heavily dependent on the resources of its collaborators. One of the first GEIS undertakings has been the installation of a VSAT

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review system dish and related communication technology at KEMRI (discussed in the section Technology and Information Management of this chapter). These efforts have increased the capacity for data management and information sharing. The installation of a backup generator at the KEMRI Virus Research Center has also contributed to strengthening of the infrastructure. Future plans include the expansion of the KEMRI communications network to connect all KEMRI investigators to the VSAT system and the contribution of funds to develop a laboratory with rooms dedicated to GEIS and geographic information system (GIS) work in Kisian. Other partners are also working to build the MoH’s capacity; for instance, the WHO-supported project on integrated disease surveillance that started in 2000 has provided four computers and training to 4 of 10 Kenyan health districts involved in the project. Surveillance for Agents of Dysentery In a collaboration between USAMRU-K and the African Medical and Research Foundation (AMREF) and KEMRI, surveillance for agents of dysentery has commenced at Magadi-Entasopia, a site in southern Kenya near the border with Tanzania. This effort focuses on the Masai people, who live in or migrate through the area and who live in close proximity to livestock. AMREF has provided the study site, supplied initial coordination and guidance to clinic staff, and is supposed to analyze stool samples for parasites. KEMRI and USAMRU-K are primarily responsible for bacteriological analysis, antimicrobial susceptibility testing, and molecular and toxin characterization of isolates. However, USAMRU-K has not received information regarding parasitic analyses from AMREF since March 2000, when the study began. This surveillance project has shown that the most common causes of dysentery are enterotoxigenic Escherichia coli and Shigella and that multiple drug resistance is common among these organisms. This project has also resulted in the description of the first cases of verotoxic Shigella flexneri, Shigella dysenteriae type 12, and E. coli O157:H7 in Africa. Future work is to include an enterhemorrhagic E. coli study in slaughterhouses, slum districts, and rotating sites in Kenya and Eastern Africa. Renewal of the contract with AMREF and the conduct of active and passive surveillance at a number of clinics in Kenya and Eastern Africa are also planned. USAMRU-K reportedly intends to expand its work with enteric pathogens throughout the region to make use of the extensive network of Médicins Sans Frontières (MSF; Doctors Without Borders), an international medical aid organization that operates in Kenya and other countries in the region.

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review Surveys of Hantavirus and Rickettsia Surveys of hantavirus and rickettsia have been conducted in collaboration with the WHO. Projects use the existing WHO Yellow Fever Surveillance Network. The hantavirus study is based in 24 mission and district hospitals in eight of the nine Kenyan provinces. Samples collected from patients with fever of unknown origin are tested. One of the study sites reported clinical presentations consistent with hantavirus infection, and serological evidence of infection was found in test sera. The study of rickettsial infection has just begun and is based on the collection of ticks from slaughterhouses and field sites around Kijabe Mission Hospital. It uses polymerase chain reaction techniques to provide evidence of infection. Tick bites of humans and livestock are a common occurrence, and several clinical cases suggestive of rickettsial infection were found. The patients responded to treatment with doxycycline. Future work on hantavirus is to include trapping and testing of rodents, expansion of the study to other locations, and analysis of possible arthropod vectors within the vector population. Future work on Rickettsia is to focus on suspected human cases by using serological surveys and on vector studies. Surveillance for Fevers of Unknown Origin and Viral Hemorrhagic Diseases Surveillance for fevers of unknown origin and viral hemorrhagic diseases is being undertaken in collaboration with the KEMRI Center for Virus Research and is based in the same 24 mission and district hospitals as the study of Rickettsia. The KEMRI virologist has been proactive in reactivating these sites for the purpose of limited surveillance for hemorrhagic fever, an effort that receives GEIS support. The subcommittee attended one of the sensitization sessions for this project at the Kijabe Mission Hospital in the Rift Valley. Future plans for work in this area include screening of specimens sent through the network for a range of possible causes of fever of unknown origin, including hantavirus and viral hemorrhagic fever. This work resulted in the discovery of endemic dengue transmission in coastal Kenya (GEIS, 2000b). Follow-up epidemiological investigations regarding dengue virus transmission are also intended to elucidate patterns of transmission and vector distribution. Surveillance for Drug Resistance in Malaria Parasites GEIS-funded studies for surveillance for drug resistance in malaria parasites have been conducted at Kericho and Kisumu, Nairobi, and Entasopia in west, central, and southern Kenya, respectively. Work involves comparison of the results of in vitro drug susceptibility testing with those of molecular biology-based analyses (polymerase chain reac-

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review tion) for markers of resistance. Initial study results have shown very high levels of chloroquine resistance among malaria parasites and a positive correlation of that resistance with molecular markers. Future work is to include a retrospective 10-year study of mutation patterns, the development of laboratory capabilities, the provision of reference testing, and the development of a malaria parasite resistance database for East Africa. Other Surveillance Activities and Plans USAMRU-K has provided research training for many DoD preventive medicine residents and other scientists and students over the years. USAMRU-K has supported at least one trainee as part of the GEIS Overseas Medical Research Laboratory Orientation Training Program. As part of GEIS implementation, USAMRU-K has also developed a plan to coordinate epidemiology and epidemic response training for Kenyan nationals using University of Nairobi staff (USAMRU-K, 2000). This plan has not yet been implemented. USAMRU-K is not involved in the development of a new epidemiology training course that is to be offered in Kenya under the direction of the GEIS Central Hub and AMREF (McCarthy, 2000). The GEIS Central Hub, however, did not actively seek USAMRU-K involvement in this activity. Plans also exist to develop methods that can be used to predict atypical patterns of transmission of important pathogens, especially those that are vector borne. Focus will be on identifying patterns resulting from environmental changes. This venture will be undertaken in partnership with the International Livestock Research Institute (ILRI), which, as noted above, has an impressive GIS capability. Conclusions USAMRU-K is well positioned to meet the goals and objectives of GEIS and can substantially contribute to a global infectious disease surveillance and response network. Current and planned surveillance activities are generally in line with the GEIS mission, but these activities could be expanded, resources permitting. Also, present USAMRU-K GEIS activities appear to represent a collection of individual projects rather than respective parts of a cohesive program. GEIS at USAMRU-K would benefit from better integration of the projects. Establishment of GEIS within the research framework of USAMRU-K (USAMRU-K research activities are funded primarily by MIDRP) can benefit both MIDRP and GEIS in a synergistic fashion: GEIS can benefit from the scientific and technical facilities, staff expertise, established research efforts, and working relationships already in existence. In return, GEIS can strengthen and build partnerships and can provide surveillance infor-

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review mation useful in guiding the development of future MIDRP-funded research projects that maximize benefits to the U.S. military, as well as to Kenya and the surrounding region. Finding a balance between these missions is important to the success of both and to the effective functioning of USAMRU-K. Expansion of key partnerships such as those with the MoH and the WHO can greatly increase the success of USAMRU-K GEIS activities. Provision of training in epidemiology, as planned, would also help to build the competences and capacities necessary to support emerging infectious disease surveillance in Kenya. These training activities seem supportive of the MoH plans and the WHO project, but USAMRU-K must be a leader in all GEIS efforts in the region—including but not limited to training. The Geographic Information System (GIS) activities being developed in collaboration with ILRI have much potential to enhance surveillance for emerging infectious diseases. However, as all surveillance data need to result in information for action, it is important to develop a plan for transmission of this information to the MoH in such a way that it will be useful for response at the national, district, and local levels. For instance, combining the human vector information with information from expanded veterinary epidemiological activities could enhance surveillance and response activities for emerging zoonotic diseases. Influenza is not considered a priority disease in Kenya, and to date, it has not been a part of GEIS efforts there. However, because influenza is one of the GEIS pillars and because influenza surveillance activities are lacking throughout much of Africa, it would be prudent to capture some information regarding currently circulating influenza viruses to enhance the global influenza surveillance effort. RESPONSE CAPACITY Epidemics of emerging infectious diseases with known and unknown origins occur regularly in Kenya and within Eastern Africa. The MoH is currently involved in pulling together resources to implement for Kenya a plan of action for the management of disease epidemics. The plan attempts to outline the resources required to respond to the priority diseases in the country. The MoH is seeking to establish rapid response teams to deal with crisis infectious disease situations. During the subcommittee site visit to USAMRU-K, an epidemic of Ebola virus was occurring in neighboring Uganda. USAMRU-K was only an observer of the response team assembled to deal with the crisis. Although the MoH spent a great deal of effort attempting to prevent importation of the virus into Kenya and dedicated epidemic response teams to border locations to create surveillance sites for the virus, the role of

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review USAMRU-K remained limited. Although Kenya is geographically situated in a region of Africa that has experienced repeated epidemics of viral hemorrhagic fever, and despite repeated requests to the international scientific community for the appropriate reagents for the diagnosis of Ebola, Lassa, and Marburg fevers, such reagents have not been regularly made available to the KEMRI Center for Virus Research, which USAMRU-K relies upon for virology diagnostic capabilities. In 1997–1998, during a Rift Valley fever epidemic in Kenya, USAMRU-K was reportedly active in epidemic response efforts. It was also reported that at the time of this epidemic, additional diagnostic tools and staff resources were available to USAMRU-K. Conclusions Emerging infectious disease response is one of the goals of GEIS outlined in the GEIS strategic plan (GEIS, 1998). One objective of GEIS is to “establish mechanisms and partnerships needed to ensure rapid and effective development and implementation of assessment, response, and prevention measures” (GEIS, 1998, p. 36). At present, USAMRU-K is not in a position to accomplish this objective. To optimize response capacity, USAMRU-K needs to work with the MoH and other partners to enhance the surveillance system within Kenya so that epidemics can be detected and reported to the MoH in a timely fashion. Without this capacity for surveillance, epidemics may never be detected or reported to the central government. Until USAMRU-K becomes fully integrated with other potential partners, USAMRU-K will remain on the sidelines as an observer rather than being called in as an active participant. USAMRU-K needs to be a fully staffed and equipped facility if it is to provide adequate support in an epidemic situation. USAMRU-K needs to have the technical, professional, and laboratory capacities required to provide assistance in response to requests from the MoH, the WHO, or other sub-Saharan African countries. Such requests may be for assistance with the identification of an etiological agent and its mode of transmission or assistance with the implementation of the preventive strategies needed to end the epidemic. If capabilities for the rapid diagnosis of infectious disease entities that pose a significant public health threat and sufficient applied epidemiological expertise are not consistently made available to USAMRU-K, the laboratory will not be in an optimal position to be a full partner in responding to disease entities that exist on its doorstep.

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review COLLABORATIONS KEMRI is a component of the MoH. Until recently, KEMRI operated under the direction of the Ministry of Education, Research, and Technology. KEMRI has 10 centers that report to a deputy director of research and development. As noted previously, USAMRU-K headquarters are physically located on the KEMRI campus in Nairobi, an arrangement that permits close collaborations with KEMRI scientists and other staff. USAMRU-K projects are integrated throughout KEMRI. For instance, USAMRU-K has collaborated with the Center for Microbiology Research on enteric disease and drug resistance studies. USAMRU-K and the Center for Virus Research have worked closely together to study such disease entities as arboviruses (the agent of yellow fever) and viral hemorrhagic fevers. Other collaborative projects have included work on dengue virus transmission, measles virus shedding in HIV-positive individuals, and a study of fevers of unknown origin. Since USAMRU-K moved into KEMRI space, KEMRI has administered all civilian personnel and has provided laboratory space, utilities, and vehicles as part of a renewable 3-year cooperative agreement. The arrangements for USAMRU-K collaborations with KEMRI centers are not governed by a cooperative agreement but are informally approved by the director of KEMRI. The potential for collaborative relationships with other areas of the MoH also exists. The current head of the Division of Communicable Diseases (not part of KEMRI) indicated an interest in working with USAMRU-K. She specifically indicated an interest in involving USAMRU-K in setting up and facilitating the disease epidemic management units within Kenya; preparing and responding to disease epidemics; developing an integrated disease surveillance pilot project in collaboration with the WHO; and planning, implementing, and evaluating malaria control activities, an MoH priority. The MoH is currently involved in pulling together resources to implement for Kenya a plan of action for the management of disease epidemics. The plan attempts to outline the resources and response needs for priority diseases in the country, including cholera, bacillary dysentery, plague, measles, yellow fever, meningococcal meningitis, viral hemorrhagic fever, poliomyelitis, guinea worm infection, neonatal tetanus, leprosy, HIV infection, tuberculosis, trypanosomiasis, onchocerciasis, and malaria. The plan calls for collaboration with other programs and partners in plan development and implementation. MoH staff advised the subcommittee that USAMRU-K participation in this effort would be welcome. The International Livestock Research Institute possesses an extensive laboratory and is actively engaged in the development of a GIS for Kenya and the African continent. It already uses remote sensing to model epidemics and the distribution of a variety of livestock diseases, a number of

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review which, like Rift Valley fever, trypanosomiasis, and babesiosis, also affect human populations. Many of the data for this work originate from a receiver operated by the Meteorological Department in Nairobi (part of Kenya’s Ministry of Natural Resources). This dish receives 1-kilometer-resolution surface temperature and vegetation data from a U.S. National Oceanic and Atmospheric Administration satellite. A team from the National Aeronautics and Space Administration’s Goddard Space Center and USAMRU-K recently replaced the receiver. AMREF, with which USAMRU-K has begun to collaborate, supports a network of more than 120 well-established health care sites in three East African countries and has in place good communication and specimen transport systems. A visit to AMREF headquarters in Nairobi revealed a laboratory of limited capacity with a focus on a medical care-emergency response mission. One of the objectives of AMREF is to support the establishment of a national laboratory program in Kenya. AMREF was established in 1957 with a mission to improve the health of disadvantaged people in Africa. AMREF programs address sexual health, child health, environmental health, health care policy and reform, and clinical services and responses. AMREF is perhaps best known for the latter activity, which is known popularly as “The Flying Doctors.” Collaborations with AMREF as part of GEIS include work at Entasopia (dysentery studies) and work in the shantytown of Kibera (urban malaria studies). USAMRU-K reports that it is beginning to work with MSF. Collaborations with MSF involve surveillance for enteric pathogens and antibiotic resistance at MSF clinic sites in Nairobi slums. USAMRU-K has informal ties to the CDC. Areas of collaboration include mutual support for the KEMRI Center for Virus Research (a WHO collaborating center), for which USAMRU-K supplies technicians who support the head of the center. The head of the center is in turn supported by the CDC. USAMRU-K also works with the CDC in support of the development of the LIFE Initiative, an AIDS education and prevention program. USAMRU-K also reports collaborations with the Oxford-Wellcome group on dengue surveillance at Kilifi, environmental change and high-land malaria at Kericho, and the molecular pathology of severe pediatric malaria. USAMRU-K also shares HIV-related information with USAID, although they are not active partners. Work with the WHO has focused primarily on support of surveillance for fevers of unknown origin by use of the WHO Yellow Fever Network (a network of sites that was active during the yellow fever epidemic of 1992–1993 in Kenya but that subsequently became inactive and that is now being redeveloped), support for the KEMRI Center for Virus Research, and support for studies of hantavirus and rickettsia. USAMRU-K is not participating directly in a WHO pilot project to develop an integrated disease surveillance network

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review in Kenya. Notably, USAMRU-K is not involved in managing the viral respiratory surveillance and acute febrile illness surveillance projects being conducted by the GEIS Central Hub in Uganda. Conclusions USAMRU-K faces many challenges in a country that is lacking in basic public health and communications infrastructures and that is rife with political difficulties. Nonetheless, its unique geographical location places it in a strategic position to monitor infectious diseases and to achieve GEIS goals. By strengthening and expanding existing partnerships and actively soliciting new partners and collaborators, many of which already support programs that share GEIS’s mission, the current USAMRU-K structure can be leveraged to overcome existing hurdles. Operations in Kenya are very dependent on partnerships, given the relative scarcity of scientific resources. USAMRU-K has a wide variety of existing and potential partners that can assist in accomplishing both research and surveillance objectives. The relationship between USAMRU-K and KEMRI is perhaps the best established. Integration of activities has facilitated collaboration with Kenyan and other visiting scientists. The research centers within KEMRI with which USAMRU-K works offer additional opportunities for collaboration and partnerships that can be used to achieve GEIS goals. The recent transfer of KEMRI to the MoH bodes well for the realization of both the research and the surveillance missions of USAMRU-K. USAMRU-K’s location within KEMRI is of benefit to USAMRU-K and offers the possibility for a variety of surveillance activities in support of GEIS goals. Indeed, some of this leveraging has already begun, particularly through work with the Center for Virus Research and the Center for Microbiology Research. Additional activities can be undertaken to help develop the surveillance infrastructure within Kenya. Of importance to the establishment of a Kenyan public health surveillance system is the direction of more effort to promote the relationship with the MoH. Integral to the provision of surveillance system support is a close working relationship with the central public health agency within the country. The director of the MoH’s Communicable Disease Division understands the deficiencies of the current disease reporting system and is eager to work to overcome the lack of infrastructure and to move forward to create an active surveillance system that has the potential to respond to disease epidemics. The epidemiological expertise possessed by the head of the Communicable Disease Control Center would serve GEIS efforts well, and a partnership seems to be worth pursuing. Additionally, providing the MoH with assistance in the development of an epidemic management plan is an activity germane

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review to GEIS and of great potential benefit to Kenya and other in-country partners. Many of the partnerships that are in place could be expanded. The GIS in development at the International Livestock Research Institute offers exciting potential for the mapping of emerging diseases, such as Rift Valley fever, in Kenya and the surrounding region. MSF and AMREF offer a network of health care facilities throughout the country and throughout Eastern Africa that could be used as a base where active surveillance of priority public health diseases for the country could be initiated or expanded. To the extent that the subcommittee was able to assess its structure, AMREF does not appear to have the capacity or the programmatic interest to conduct basic surveillance activities. AMREF is, however, anxious to obtain support for its ongoing efforts to establish basic diagnostic capabilities within the local clinics that it administers. The laboratory needs of AMREF and the surveillance needs of USAMRU-K may be able to be reconciled to achieve outcomes of benefit to both. The MSF focus on partnership and capacity building corresponds well with GEIS goals. To the extent that these heavily burdened agencies can reliably support USAMRU-K GEIS surveillance efforts, partnerships with both AMREF and MSF would seem to offer valuable opportunities worth actively pursuing. Insofar as the subcommittee was able to assess the association, it appears that the potential exists for stronger collaboration between USAMRU-K and the CDC for the purposes of emerging infectious disease surveillance. In Kenya, the CDC, like USAMRU-K, has traditionally been oriented to the performance of research rather than the performance of surveillance. However, the CDC is in the process of expanding its staff base in Kenya, and there is a move toward increased surveillance for emerging infectious diseases internationally (Dowell, 2001; Dowell et al., 2001). As such, the sharing of resources and expertise would seem to be in the interests of both partners. Although the subcommittee was not able to meet with representatives of USAID, the WHO, the Oxford-Wellcome group, or MSF to fully explore existing partnerships and to discuss opportunities for and constraints affecting expanded collaboration, it would appear that each of these organizations, whose missions focus on improving and enhancing public health and infectious disease surveillance throughout the world, represents a potentially valuable collaborator. As the committee site visit occurred during the early stages of the Ebola virus epidemic in the Gulu District of Uganda, it was particularly evident that close collaborations with and support of the WHO Collaborating Center for Arbovirus and Viral Hemorrhagic Fever Reference and Research and its associated Yellow Fever Surveillance Network are important to USAMRU-K, to Kenya, and throughout the region. Such part-

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review nerships present USAMRU-K with an opportunity to strengthen in-country and regional laboratory-based surveillance for viral hemorrhagic fevers and responses to epidemics of viral hemorrhagic fevers. Direct involvement in the WHO integrated disease surveillance project seems to offer the potential to advance GEIS surveillance objectives. The subcommittee notes, with alarm, the fragmentation of GEIS activities within the region, as evidenced by a lack of coordination and communication between the GEIS Central Hub and USAMRU-K regarding surveillance projects for viral respiratory diseases and acute febrile illnesses in Uganda and Kenya. Such a fragmented approach detracts from the development and presentation of a cohesive GEIS and is damaging to GEIS interests in the long term. RECOMMENDATIONS • GEIS activities at USAMRU-K are of critical importance to the program as a whole. The committee encourages the DoD to plan for GEIS activities at USAMRU-K on a long-term basis. USAMRU-K provides an important resource for both research and surveillance missions. Demand for, and support of, both missions should be balanced so that neither one is jeopardized. Recommendation: DoD commitment to GEIS at USAMRU-K should be long term. • Current GEIS surveillance activities also work to accomplish outcomes deemed important by the MoH. Recommendation: Current GEIS surveillance projects and activities should be continued as they represent activities in support of the GEIS mission. • The subcommittee recognizes that the GEIS pillar disease areas are important ones and that defining these targets helps to provide some standardization of GEIS activities across sites, but the pillar structure should be flexible enough to permit local infectious diseases that are of global concern to be addressed as high priorities through GEIS. This serves to take full advantage of the epidemiological setting of the facility, builds national health defenses in the host country, and can be of long-term benefit to the health of many populations, including U.S. military personnel and civilians. Recommendation: Consideration should be given to refining the focus of GEIS at USAMRU-K to better enable diseases outside of the pillar areas to be addressed. • Consideration needs to be given to expanding existing USAMRU-

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review K GEIS activities within sub-Saharan Africa, as applicable and as resources permit. Recommendation: Expansion of the reach of GEIS activities should be considered. • Reagents for the diagnosis of Ebola, Marburg, Crimean-Congo, and Lassa viral hemorrhagic fevers (and other infectious disease entities, as applicable) need to be made consistently and swiftly available to the KEMRI Center for Virus Research to support USAMRU-K surveillance for and response to regionally important pathogens. USAMRU-K relies upon KEMRI for its virology diagnostic capabilities. Without reagents, neither KEMRI nor USAMRU-K will be able to fully support responses to epidemics. Such resources are crucial to the work of GEIS at USAMRU-K and, more generally, to public health surveillance and emerging infectious disease response capacities in Kenya. Recommendation: USAMRU-K and the GEIS Central Hub should facilitate the acquisition of reagents for the diagnosis of Ebola, Marburg, Crimean-Congo, and Lassa hemorrhagic fevers (and other infectious disease entities, as applicable) to the extent possible. • In addition to reagents, USAMRU-K should have available means of safely, effectively, and rapidly diagnosing regionally important pathogens if it is to fulfill the goals of GEIS. This can be accomplished by improving USAMRU-K laboratory facilities and by forging closer ties with other DoD and non-DoD laboratories. Recommendation: Additional GEIS investment in improving USAMRU-K’s laboratory capacity is needed and should be pursued within program limits. • Effort needs to be made to correct staffing deficiencies and to return USAMRU-K to its authorized contingent of professionals. Recommendation: USAMRU-K should have a full-time GEIS program manager on site. The designated GEIS program manager should have training and expertise in applied epidemiology and public health. Recommendation: The assignment of a CDC epidemiologist to USAMRU-K, the assignment of a military public health physician with epidemiological experience, or the assignment of a civilian medical epidemiologist with public health experience should be pursued. To fully realize the GEIS surveillance mission, there should to be strong epidemiological input in USAMRU-K GEIS development and management.

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review Recommendation: USAMRU-K should explore the possibility of supplementing its military scientific staff with Kenyan nationals possessing comparable expertise to ensure continuity of projects, to expand expertise, and to foster collaborative relationships and project growth in important areas of public health surveillance. Recommendation: The availability of staff with virological expertise within USAMRU-K would assist in the achievement of GEIS’s goals and should be considered. • USAMRU-K needs to work more closely with partners such as the Kenyan MoH, the WHO, USAID, the CDC, and others to strengthen the national surveillance and response capacities for emerging infectious diseases. At the district level, this may include training and the provision of equipment and laboratory support. At the national level, this may include provision of equipment, communications support, and active participation in planning to address emerging infectious diseases. Recommendation: Collaborative relationships should continue to be forged and fostered to ensure that USAMRU-K is involved as a full partner in infectious disease surveillance and response activities. • Training local personnel in laboratory technology and providing an opportunity for DoD personnel and students to receive research training are important ways in which GEIS is and can increasingly be of benefit to Kenya and the DoD. Consolidating and coordinating USAMRU-K’s various training activities under the aegis of GEIS may make training activities more efficient, productive, and visible. The epidemiology training program that USAMRU-K has planned is an important step in these regards. Ultimately, however, a more broadly focused training program that takes full advantage of the expertise and opportunities available at USAMRU-K is desirable. GEIS objectives can be advanced by seeking partnerships with the CDC and other collaborators in training activities. All GEIS training programs in the region need to be part of a cohesive effort. Recommendation: DoD and Kenyan training needs should be assessed formally, and the development of a structured USAMRU-K-hosted training program should be considered. • Reporting of data on disease incidence is an essential component of a functioning surveillance system. This may take the form of monthly or quarterly reporting of data to the MoH for inclusion in the national or WHO regional surveillance bulletin. Routine reporting needs to be complemented by the development of channels that allow more rapid

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review feedback to the MoH in the event that an epidemic or some other important shift in trends related to a disease agent is detected. Recommendation: In consultation with the GEIS Central Hub and public health partners, USAMRU-K should develop and implement a system for the dissemination of public health data in a routine and timely manner to ensure public health action. • USAMRU-K GEIS projects need to work together instead of in isolation. All projects in Kenya and the region should operate in coordination with USAMRU-K GEIS activities. Linked projects make relatively efficient use of limited resources and will enhance GEIS visibility. Recommendation: Steps should be taken to link GEIS projects together as part of an integrated USAMRU-K GEIS effort. • Enhancement of communications infrastructure is an important need that GEIS can help meet. Support for enhancement of communications resources needs to be continued, and a comprehensive plan for improving internal and external networking should be developed. Recommendation: Expansion and refined application of communications technologies should be pursued by USAMRU-K with GEIS support. • Effort needs be directed to examine GIS output in conjunction with the results of human, vector, and animal studies so that surveillance for malaria and fevers of unknown origin can be enhanced. Recommendation: Effort should be directed to enhance the public health application of current GIS work (carried out in collaboration with the International Livestock Research Institute) so that such efforts can better result in information for action. • Partnerships benefit from knowledge of the native language by senior staff. Partnerships are of increased importance to USAMRU-K now that its research mission has been formally expanded to include GEIS activities, which necessitate increased interaction with partner agencies. Staff familiarity and comfort with the local language can also improve rates of retention of personnel as well as assist with cultural acclimation. Recommendation: Senior staff at USAMRU-K actively involved in GEIS projects should be conversant in the dominant language of the host country or should be encouraged to pursue, with the support of GEIS, language training, and should seek to become conversant to the extent possible.

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review PEOPLE MET AND INTERVIEWED USAMRU-K Staff Ronald Rosenberg, commander, USAMRU-K Raymond Dunton, Malaria Transmission Jon Davis, clinical laboratory officer, Enteric Pathogens Collaborators and Associates Lee Dunster, head, WHO Virus Reference Center, Center for Virological Research, KEMRI Bernard Ogutu, staff clinician, Center for Clinical Research, KEMRI Willie Kipkemboi Sang, senior research officer, Center for Microbiology Research, KEMRI Jane Mbui, research officer, Center for Clinical Research, KEMRI Joyce Onsongo, director, Division of Communicable Diseases, MoH Jane Y.Carter, head, Laboratory Programme, African Medical and Research Foundation Orgenes Lema, chief laboratory technologist, African Medical Research Foundation Brian D.Perry, veterinary epidemiologist, coordinator, Epidemiology & Disease Control, International Livestock Research Institute Russ Kruska, GIS analyst, International Livestock Research Institute Andrew G.Hill, consultant, general surgery; head, Department of Surgery; and director of medical electives, AIC Kijabe Hospital Kevin DeCock, director, CDC-Kenya Menique Wasunna, director, Center for Clinical Research, KEMRI ITINERARY Monday, October 16 0930 Tour of KEMRI 1100 Briefing (R.Rosenberg) 1200 Lunch 1400 Briefing (by L.Dunster in virology and by J.Davis and W.Sang in dysentery) Tuesday, October 17 0930 Ministry of Health: MoH-WHO pilot reportable disease network (J.Onsongo, MoH)

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Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review 1200 Lunch 1300 AMREF (J.Y.Carter and staff) 1500 Meet with Koech, director general, KEMRI Wednesday, October 18 1000 International Livestock Research Institute (B.D.Perry and R.Kruska, epidemiology and GIS) 1230 Lunch 1400 Kijabe Missionary Hospital (L.Dunster and Smith, Yellow Fever Network and rickettsia survey) Thursday, October 19 0900 Entasopia dysentery surveillance site (J.Davis, W.Sang, AMREF staff), whole day Friday, October 20   Depart Kenya