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5
Naval Medical Research Unit 3 Egypt Avian and Pandemic Influenza Activities
U.S. Naval Medical Research Unit No. 3 (NAMRU-3) is a U.S. Navy research biosafety level 3 enhanced (BSL-3E) laboratory with extensive human and animal viral diagnostic capacity located in Cairo, Egypt. NAMRU-3 is one of the largest medical research laboratories in the North Africa-Middle East region and is also the regional influenza reference laboratory for the Eastern Mediterranean Regional Office (EMRO) of the World Health Organization (WHO) with close ties to the influenza laboratory at the U.S. Centers for Disease Control and Prevention (CDC) (DoD-GEIS, 2007a).
NAMRU-3 was formally established by the U.S. Secretary of the Navy in 1946 at the site of the former Typhus Commission in Cairo, Egypt (IOM, 2001; DoD-GEIS, 2007a). The early work at NAMRU-3 focused, in collaboration with the Egyptian Ministry of Health, on rickettsial diseases and febrile diseases (smallpox, meningitis, etc.) in patients admitted to the adjacent Abbasia Fever Hospital, Egypt’s largest fever hospital (DoD-GEIS, 2007a). In addition, NAMRU-3 has been heavily involved in avian and pandemic influenza surveillance. Though NAMRU-3 has historically been dedicated to a laboratory- and field-based infectious-disease research mission, influenza surveillance activities have been conducted at NAMRU-3 since the 1999 initiation of funding from the Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS) for seasonal influenza surveillance activities.
DoD-GEIS support for NAMRU-3 influenza surveillance and response projects totaled $4 million in fiscal year 2006. Using these funds, NAMRU-
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FIGURE 5-1 DoD’s regional presence in influenza surveillance (Africa), 2007.
SOURCE: DoD-GEIS, 2007b.
3 expanded a number of its activities, such as conducting training on influenza diagnosis, helping to build national influenza laboratory capacity in Egypt and the region (including Afghanistan, Jordan, Libya, and Ghana), and assisting with the WHO global influenza surveillance program through bilateral and trilateral influenza surveillance projects (see Figure 5-1). Limited migratory bird surveillance is also being conducted using DoD-GEIS funds. This surveillance has become more robust with the addition of avian influenza/pandemic influenza (AI/PI) funding from DoD-GEIS.
A site visit team of the Institute of Medicine (IOM) Committee for the Assessment of DoD-GEIS Influenza Surveillance and Response Programs visited NAMRU-3 from March 4-9, 2007.1 A list of the people with whom the site visit team met and the itinerary that was followed can be found at the end of this chapter.
1
Prior to the committee’s visit to NAMRU-3, the laboratory staff provided the committee with detailed background information on NAMRU-3 and the pandemic/avian influenza activities it was supporting. These materials are available from the IOM in the Public Access File.
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INFLUENZA IN EGYPT
The first confirmation of H5N1 in Egypt was made in February 2006 (WHO, 2007a). At that time, seven outbreaks of avian influenza (AI) virus subtype H5N1 were reported throughout seven governorates in Egypt (Cairo, Giza, Menia, Qina, Kalyubeya, Behera, and Dakahlia) (USDA, 2006). These outbreaks were diagnosed by the Animal Health Research Institute, Egypt’s national laboratory, and confirmed as H5N1 by NAMRU-3 (OIE, 2006). Reports of outbreaks continued to be received until December 2006 (WHO, 2007a).
In addition to the poultry outbreaks affecting both backyard and commercial poultry, Egypt has had 36 human cases of avian influenza infection, the highest number of bird flu cases among humans outside of Asia. Of these 36 cases, 15 have resulted in death (WHO, 2007b). Though avian influenza has been found in several areas of Africa, Egypt is one of only two African countries—the other being Nigeria—to have reported a human case of the infection (WHO, 2007a).
MANAGEMENT AND PLANNING
Generally, DoD-GEIS activities at NAMRU-3 are coordinated by the director of the Research Sciences Department and carried out by other research departments, including virology research, disease surveillance, enteric disease research, and vector biology research. DoD-GEIS AI/PI supplemental funding is managed primarily by the virology program head.
It is reportedly challenging to manage the large sums of money related to AI/PI activities, especially when the financing arrives late in the fiscal year, although in fiscal year 2006, when NAMRU-3 staff had to receive and obligate funds and then implement projects in a short period of time, they proved flexible enough to do so. In the future, additional personnel in both the finance and supply departments would potentially help to streamline the acquisition of equipment and reagents, but in 2006 the major delay was due to external circumstances. The purchase of high-dollar equipment or initiation of contracts must be routed through the Fleet and Industrial Supply Center (FISC). NAMRU-3 experienced up to a six-month delay when purchasing equipment since FISC did not award many contracts until September 2006 even though the purchase requests were submitted in April of that year.
Staffing
All of the research departments at NAMRU-3 have a variety of ongoing projects, only some of which are AI/PI-related. There are no dedicated
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DoD-GEIS personnel. However, the AI supplemental funding is being used to support 22 persons associated with 18 full-time equivalent (FTE) positions. These personnel include two virologists, three molecular biologists, two medical epidemiologists, four laboratory technologists, and two data clerks. The NAMRU-3 has supported a variety of employees with the supplemental funding, including a number of U.S. Government Service employees, non-personnel service contractors, and locally employed staff (Egyptian nationals). As the capacity of the laboratory increases, NAMRU-3 would like to hire additional laboratory technologists in the areas of viral isolation and molecular biology.
While there is still great need at the laboratory for expanded epidemiological expertise, with the increased personnel from CDC’s global disease detection and response program NAMRU-3 expects that these deficits will be covered. At the time of the IOM team’s site visit, it was still unclear what role the CDC staff would play at the laboratory, and a memorandum of understanding regarding the exact nature of tasks and activities that CDC will perform had not yet been written.
Given the importance of its geopolitical location in the Middle East, one of NAMRU-3’s greatest strengths is its reliance on Foreign Service Nationals to play key roles in the management and activities of the laboratory. NAMRU-3 has used this strength in expanding its avian/pandemic influenza programs and broadening its laboratory capacity, thus strengthening activities for the countries in the EMRO region.
Technology and Information Management
The technology capabilities of NAMRU-3 were found to be substantial and more than adequate to manage the current increase in activity resulting from additional AI funding. At the moment, NAMRU-3 relies on informal information-sharing methods to provide status reports to relevant government officials. While these methods do serve to strengthen personal relationships between NAMRU-3 staff and government officials, if human-to-human transmission occurs these informal channels will not be sufficient to provide timely and accurate information early in a pandemic. As more cases of avian influenza are identified in Egypt and the region, it will become increasingly important for key laboratory network hubs like NAMRU-3 to have formal systems in place to share information at the local, regional, and global levels in an accurate and timely way. Various sources of information, including findings from human surveillance, avian surveillance, and outbreak investigations, will have to be coordinated and shared with the relevant governments and with the international agencies involved in setting policy and implementing prevention and intervention efforts.
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One mechanism that NAMRU-3 is using to share relevant information in the country and the region is the production of a weekly bulletin on the influenza situation in the Middle East. While these bulletins are currently very useful, NAMRU-3—in conjunction with the host governments, EMRO, and WHO headquarters—will need to develop a real-time system if human-to-human transmission occurs.
Conclusions
The site visit team noted that the planning and implementation of specific projects being conducted by NAMRU-3 were well executed but the organizational strategy needed to guide the laboratory’s future influenza activities is lacking. NAMRU-3 staff were planning to hold a meeting regarding the laboratory’s organizational direction and how NAMRU-3 can best meet the needs of countries in the region.
RECOMMENDATION 5-1. NAMRU-3 should prepare a short-term (2-3 years) strategic plan that identifies its priorities (surveillance/research and implementation/service delivery) in the AI/PI program and indicates NAMRU-3’s role in the prepandemic stage.
The staffing is acceptable for the current activities, but NAMRU-3 may need to make staffing and equipment adjustments when it moves into the early pandemic phase. For example, staff members from other units may be cross-trained and deployed to assist with enhanced surveillance when their research activities are no longer a priority, due to the emergency.
NAMRU-3 staff members suggest that their method of information sharing—making telephone calls to pertinent local and international offices in order of priority—is adequate. It may not be adequate, however, in the case of an outbreak of pandemic influenza. The committee concluded that the development of the manual system as well as a web-based, password-protected reporting system would benefit NAMRU-3 and the host countries with which it works. Redundancy in reporting systems may also be useful. Radio, telephone, web and satellite communications are all vulnerable to breakdown due to overuse.
In a pandemic phase, all of the data being produced by NAMRU-3 would ideally be available on a protected website for partners like WHO and the Ministry of Health. Avian influenza data could be linked with the infectious disease database managed by the Ministry of Health. NAMRU-3 should develop an improved system of communication that enables all qualified partners to access information without reliance on individual phone or e-mail communication, such as a protected website or blast fax system.
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RECOMMENDATION 5-2. NAMRU-3 should develop and implement a comprehensive information-management system as soon as possible in order to prepare for the expanded needs that will be present during a potential pandemic and to improve routine information sharing in the EMRO region.
SURVEILLANCE
NAMRU-3 has greatly contributed to the avian influenza surveillance effort in Egypt and the Middle East. While most of its activities focusing on human influenza surveillance are related to building the capacity of national influenza centers, NAMRU-3 is participating in a targeted project for U.S. military personnel. In addition, NAMRU-3 is working with the Ministry of Environment in Egypt and its sister DoD laboratory, the U.S. Army Medical Research Unit- Kenya (USAMRU-K), to conduct surveillance of migratory birds.
Human Surveillance
Both independently and in its role as a WHO collaborating center, NAMRU-3 works to strengthen national laboratory capacity and also functions as a reference laboratory for countries across the region. In its effort to make best use of the supplemental funding for AI/PI influenza and strengthen the regional influenza network, NAMRU-3 has focused most of its funding for human influenza surveillance on providing support equipment and technical assistance to national influenza laboratories in places like Egypt, Afghanistan, Syria, Pakistan, Oman, Saudi Arabia, and Morocco (NAMRU-3, 2007b) (see Figure 5-2). Through these capacity-building activities, NAMRU-3 hopes to expand the regional surveillance network and establish a flow of influenza data and isolates from countries previously not represented in this network. Additional information is provided in the Capacity section below.
One primary benefit to the capacity-building efforts of NAMRU-3 is access to influenza samples and isolates from across the region. While NAMRU-3 is not collecting samples directly, researchers at NAMRU-3, working through partner governments’ laboratory systems and previously established seasonal influenza sites, are able to analyze samples from across the region and to provide that information to U.S. agencies like the CDC and to multilateral coordinators like the Food and Agricultural Organization (FAO) and WHO.
Between July 2006 and January 2007, NAMRU-3 received 2,470 samples from its seasonal influenza and H5 referencing activities, of which it processed 2006 (NAMRU-3, 2007c). These samples came from 11 coun-
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FIGURE 5-2 NAMRU-3 avian influenza assessment missions and outbreak support.
SOURCE: NAMRU-3, 2007b.
tries in the EMRO region plus Nigeria, with the majority of samples coming from NAMRU-3’s host country, Egypt. Fifty-one of the samples received were sent to NAMRU-3 for H5 reference testing by laboratories in Egypt, Iraq, Yemen, and Afghanistan; 22 of these samples were processed, resulting in four positive results for H5N1 (NAMRU-3, 2007c). All the samples positive for influenza H5N1 were from Egypt.
NAMRU-3 has also contributed to the development and implementation of an influenza-related surveillance project managed out of Doha, Qatar, looking at respiratory disease in active-duty U.S. military populations. A satellite laboratory allows for the collection of respiratory samples from troops on rest and recuperation from Afghanistan and Iraq. NAMRU-3 has also provided reference support to diagnose respiratory diseases among troops deployed in Iraq and at Camp Arifjan, Kuwait.
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Animal Surveillance
NAMRU-3 supports avian influenza surveillance in migratory birds in Ukraine, Egypt, and Kenya. NAMRU-3’s location in Egypt provides a unique opportunity to collect specimens and identify isolates from migratory birds traveling from Europe through the Egyptian flyways to sub-Saharan Africa. In addition, NAMRU-3 acts as a reference laboratory in the EMRO region for other suspected H5N1 animal cases.
In Egypt, NAMRU-3’s migratory bird surveillance is conducted in collaboration with the Ministry of Environment throughout the Nile Delta region, as this is a major location for stopover of migratory birds during their transit. Current environmental ministry collection sites are Port Said (Rasheed), El-Sharkeya, El-Manzala, Port Fouad, El-Fayoum, El-Arish, Sharm El-Sheik, Aswan, El-Minya, Alexandria, and Domietta. NAMRU-3 and the MoE have provided active surveillance of wild migratory birds since October 2003 in an effort to detect circulating influenza viruses. Specimens are collected using the appropriate personal protective equipment. Specimens such as tracheal swabs, cloacal swabs, tissue, serum, and so on are collected based on the method performed. As a result of these activities in Egypt, NAMRU-3 received and processed 490 wild bird samples in January 2007. Of these 48 (9.8 percent) tested positive for influenza A, 2 (0.3 percent) tested positive for H5, and none were found to be positive for H5N1 (NAMRU-3, 2007c).
NAMRU-3 has established similar surveillance activities in Kenya and Ukraine. As a result of NAMRU-3’s ongoing migratory bird surveillance activities in Ukraine, it was able to confirm an H5N1 highly pathogenic avian influenza outbreak among migratory birds in February 2006.
Through its animal H5 reference testing, NAMRU-3 was the first laboratory to diagnose and confirm influenza H5N1 infections in poultry in Afghanistan, Djibouti, Egypt, Iraq, Jordan, and Kazakhstan. Between July 2006 and January 2007, NAMRU-3 received 51 animal samples for H5 reference testing. Of the 46 which were processed by NAMRU-3, nine samples, most of which came from chickens and doves found dead, were found positive for influenza H5N1.
Conclusions
While NAMRU-3 is not conducting any human surveillance activities itself, the committee found that NAMRU-3 is an integral advisor to host country government in development of its surveillance programs and the associated laboratory capacity. As the regional surveillance network expands, the committee feels it would be beneficial to expand diagnostics to include
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emerging influenza pathogens beyond H5N1 as well as to integrate seasonal influenza and AI/PI programs as much as possible.
RECOMMENDATION 5-3. NAMRU-3 should assist the host country to develop the capacity to find emerging influenza pathogens beyond H5N1 and should integrate seasonal influenza and AI/PI programs as much as possible.
In terms of avian surveillance, the committee found that NAMRU-3 is working successfully with the Ministry of Environment to conduct influenza surveillance on wild bird populations in Egypt. However, NAMRU-3 does not conduct routine surveillance on domestic bird or poultry populations in Egypt. The Ministry of Agriculture reportedly does conduct surveillance at sites of previous H5N1 infection or sites of major poultry production, but little information on these activities was available.
RECOMMENDATION 5-4. NAMRU-3 should explore opportunities to support the Ministry of Agriculture in increasing surveillance of domestic birds kept in homes and back yards.
LABORATORY
NAMRU-3 headquarters in Cairo, Egypt, has extensive laboratory capacities, particularly in virology (DoD-GEIS, 2007a). The NAMRU-3 campus houses two BSL-3 laboratories. Using DoD-GEIS supplemental funding, NAMRU-3 has been able to increase the laboratory capacity at its headquarters, including equipment, reagents, BSL-3 space, reverse transcription polymerase chain reaction (RT-PCR) capability, and personnel (NAMRU-3, 2007b). NAMRU-3’s H5 surveillance sample testing is based mainly on RT-PCR methodology. NAMRU-3’s mobile laboratory response capability has been increased by the addition of four mobile RT-PCR devices, which have enhanced both its ability to address multiple outbreaks concurrently and to perform training at external sites. NAMRU-3 currently has the laboratory capability to do subtyping for influenza A, H5, H9 and N1 by RT-PCR; influenza A by ELISA; and H1, H16 and B by HI assays.
NAMRU-3 has also identified four satellite laboratories in Libya, Jordan, Ghana, and Afghanistan in which it plans to expand diagnostic capacity, both to strengthen this capacity closer to the bulk of U.S. troops in the region and to expand the regional surveillance network (NAMRU-3, 2007b). These NAMRU-3-established satellite laboratories will soon have the capacity for virus isolation and molecular identification of respiratory viruses. NAMRU-3 is working to increase the capacity of these laboratories
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though the acquisition of incubators, light cyclers, -80°C freezers, centrifuges, and other necessary supplies and equipment.
While NAMRU-3 is not leading any avian influenza surveillance activities, the NAMRU-3 laboratory is currently participating at various levels in the testing of samples and the isolation of virus from avian influenza surveillance systems across the EMRO region and beyond. The laboratory system used for influenza surveillance in the EMRO region is quite centralized. Laboratories located outside the capital cities have very limited capacity and thus are relegated solely to collecting specimens; some central labs are still working to develop the needed capability to process avian influenza samples. Because of NAMRU-3’s status as a WHO collaborating center, the laboratory has a different role from some other DoD-GEIS laboratories with regard to avian influenza surveillance. For example, in Egypt NAMRU-3 is currently acting as the Ministry of Health’s quality assurance mechanism. Possible AI samples are confirmed by NAMRU-3 after being sent to the central laboratory from identified fever and chest hospitals. In other countries, such as Libya, Jordan, Ghana, and Afghanistan, NAMRU-3 is still doing primary screening while these countries work to establish national laboratories with PCR capabilities. For suspected cases of AI in humans, NAMRU-3 turns around samples on the same day, while for seasonal flu virus isolation and subtyping the turnaround time is approximately 2 weeks. Results are reported to the Ministry of Health, WHO, NAMRU-3, and other influenza partners as appropriate (DoD-GEIS, the Naval Medical Research Center, CDC, and so on).
In Egypt, the Ministry of Agriculture processes all of the domestic and poultry specimens at its central laboratory in Cairo. Although the Ministry of Agriculture and the Ministry of Health have real-time RT-PCR capacity, the Ministry of Environment has NAMRU-3 do the primary screening of wild bird samples under an active surveillance program funded by DoD-GEIS because it does not have the needed PCR capabilities. NAMRU-3 reports to the Ministry of Environment on migratory bird surveillance specimens within 10 days of submission. NAMRU-3 also does the primary screening of wild bird samples for its other collaborative wild bird surveillance sites, including samples sent to Egypt from NAMRU-3’s sister laboratory, USAMRU-K.
Conclusions
NAMRU-3 facilities play an essential role in supporting influenza surveillance in Egypt and the region. Because of the laboratory’s unique position, NAMRU-3 has an opportunity to contribute to the knowledge of specific viral and bacterial agents in respiratory disease and should consider the purchase of multiplex diagnostic equipment in order to simplify quality
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control, increase automation, and expand the laboratory’s ability to detect a broad array of etiologic agents.
RECOMMENDATION 5-5. NAMRU-3 should explore the expansion of laboratory capacity to include multiplex diagnostic equipment for respiratory diseases.
At the current time NAMRU-3’s laboratory facilities are adequate for its influenza activities. However, as the number of avian influenza cases increases, changes will have to be made to the regular operations of the laboratory. In the days, weeks, or months before a pandemic takes over completely, laboratory testing that is rapid and accurate will help to diminish panic if it can rule out the pandemic strain where possible and rule in the pandemic strain where necessary. Planning out a move to a response mode in advance will be critical. The committee concluded that determining what equipment would be needed to increase laboratory output on a per-FTE basis—e.g. automated extraction, additional real-time PCR, and redundancy in sequencing devices if considered critical—will be central to NAMRU-3’s ability to handle an increase in samples. Instead of expanding laboratory staffing, automation might be increased to optimize the throughput and the speed of processing. For example, automated extraction devices, which have throughput similar to that of real-time PCR instruments, would increase the capacity of the laboratory without necessarily increasing the laboratory staff. In addition, while NAMRU-3’s research is valuable, justified, and leads to good information, a significant portion could be suspended in the case of a pandemic.
RECOMMENDATION 5-6. NAMRU-3 should develop a plan to expand its laboratory capacity in an early pandemic phase based on an assessment of how instrumentation and cross-training can be employed to optimize the laboratory and move from moderate throughput to high throughput with minimal staffing changes.
RESPONSE CAPACITY
NAMRU-3 has two primary response capacity functions. First, since it serves as a reference or quality control laboratory for many of the national central laboratories in the EMRO region, it has been called upon to provide surge capacity when the number of either human or animal samples exceeds the capacity of national laboratories. Second, NAMRU-3 has often been called on by WHO or national ministries of health to participate in outbreak-response teams (NAMRU-3, 2007b) (see Figure 5.2).
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ratory for animal-specimen processing and a separate facility for human specimens. NAMRU-3 has increased capacity for specimen processing by purchasing additional laboratory-based real-time PCR machines and adequate reagents and consumables to support any surge. NAMRU-3 has added technical staff to assist in both field and laboratory activities. In addition, four mobile RT-PCR machines were purchased to bolster outbreakresponse capacity. NAMRU-3 is reportedly now capable of responding to four simultaneous outbreaks by providing forward laboratory support with appropriate personal protective equipment, reagents, and consumables for a sustained period.
Building Capacity of Regional Laboratory System and Training
NAMRU-3 has spent a significant amount of funding and effort on consulting with, training, and equipping more than 20 laboratories in the U.S. Central Command (CENTCOM) and U.S. European Command (EUCOM) areas of responsibility (see Figure 5.2). This was done in order to achieve the laboratories’ capacity-building goal of creating a surveillance network that, with minimal continued support, can provide the necessary virological surveillance information for its own internal use while also contributing to the WHO-led global effort. To this end NAMRU-3 has expanded influenza surveillance expertise and diagnostic capacity throughout the region, including the countries of Azerbaijan, Djibouti, Egypt, Ghana, Iran, Iraq, Jordan, Kazakhstan, Kenya, Kyrgyzstan, Lebanon, Libya, Morocco, Nigeria, Oman, Pakistan, Saudi Arabia, Sudan, Syria, Ukraine, and Uzbekistan.
Capacity-building endeavors undertaken by NAMRU-3 generally incorporate a preliminary on-site assessment to determine the exact needs of the laboratory in terms of both infrastructure and expertise. NAMRU-3, WHO, FAO, various ministries of health, agriculture, and environment, DoD-GEIS headquarters, and other relevant partners determine how DoD-GEIS resources will be spent in the region. Capacity-building programs involving large-scale equipment placement take into account the geographic location of the laboratory, burden of disease, current political climate, location of deployed military forces, the location of NAMRU-3 assets, and other relevant factors. Capacity building involving training is prioritized and typically performed on a space-available basis. NAMRU-3 training will often be tailored to the laboratory capacity of the trainees’ home country in such a way that NAMRU-3 can immediately put it to use. The timing of training is coordinated with the delivery of anticipated laboratory equipment via external grants (e.g., from the World Bank). NAMRU-3 also provides limited supplies and reagents, thereby facilitating immediate diagnostic capacity in the trainees’ countries. Once NAMRU-3 has assisted in the establishment of the national influenza laboratories, oversight to en-
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sure quality will continue at each of these locations as they further develop their skills.
NAMRU-3 has continued to work in this way with the Egyptian Ministries of Health and Environment to expand its surveillance and laboratory capacities.
In addition to its work in Egypt, NAMRU-3 has used the fiscal year 2006 DoD-GEIS-AI supplemental funding to substantially expand laboratory capacity in four targeted satellite laboratories in Jordan, Libya, Ghana, and Afghanistan. Equipment and reagents were purchased and delivered to all of these countries to establish their first national influenza centers. These sites, each of which has been assessed and will continue to receive equipment, supplies, and training as deemed appropriate by NAMRU-3 staff and national and global partners, will be capable of performing extensive diagnostics on both avian and seasonal influenza.
NAMRU-3 has delivered to Kabul, Afghanistan, all the necessary equipment (including four 6-foot biological safety cabinets) to set up two complete laboratories (one for the Ministry of Health and one for the Ministry of Agriculture). NAMRU-3 sent one medical repair technician to Kabul to oversee equipment installation and to certify the biological safety cabinets. After the equipment was in place, NAMRU-3 sent a molecular biologist to Kabul to conduct training in the laboratory itself. Currently there is a NAMRU-3 staff member temporarily assigned to Afghanistan.
Jordan has agreed to enter into the Trilateral Agreement with NAMRU-3 and the WHO. Under this agreement, NAMRU-3 is now training approximately three veterinarians a month from Jordan in avian influenza diagnostics.
After being requested to conduct an assessment of public health laboratory capacity in Libya, NAMRU-3 identified the laboratory site within the Center for Infectious Disease in Tripoli and oversaw the purchase of equipment and reagents. Equipment is slated to be trucked to Tripoli in the very near future. In addition there are plans for a medical repair technician to accompany the equipment in order to certify the biological safety cabinets prior to initiation of work. This certification is a biosafety initiative that NAMRU-3 imposed on all of the collaborating sites. In preparation for the opening of this laboratory site, NAMRU-3 hosted four Ph.D. scientists from Libya for a two-week hands-on training course on avian influenza diagnostics. This marked the first time NAMRU-3 has had Libyans training side-by-side with U.S. and Egyptian scientists.
Building on relationships established through NAMRU-3’s detachment in Ghana, NAMRU-3 is supporting the establishment of a national influenza center in Accra, Ghana, located within the Noguchi Memorial Institute. All equipment and reagents have been purchased to outfit this site, and all of the previously used biological safety cabinets in its BSL-3 facility have been decontaminated and certified by NAMRU-3. All of the labora-
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tory staff has been trained on-site in Ghana in molecular diagnostics as well as in viral isolation and typing.
In addition to the work undertaken at these four satellite labs, NAMRU-3 provides as-needed capacity building, training, and technical assistance to many other laboratories in the region. For example, NAMRU-3 conducted a brief collaboration with a laboratory site in Tbilisi, Georgia, which now functions almost independently. NAMRU-3 also scheduled a two-week influenza-related training for a Ph.D.-level Djibouti scientist, followed by additional on-site training in Djibouti City.
After the initial intensive assistance from NAMRU-3, countries should value and support their own laboratories. NAMRU-3 should transition to a technical assistance role—following up, providing quality assurance, and adding capacity as necessary through activities such as training.
Conclusions
NAMRU-3 has developed a process of assessing the needs of national laboratories, assisting in the acquisition of necessary equipment and supplies, training relevant laboratory staff, and providing follow-up technical assistance and confirmatory services as needed. This process has the potential to create sustainability and to establish a high-quality regional early warning system. WHO acts as a quality-control entity, and NAMRU-3 will have to continue to coordinate its activities with WHO and EMRO representatives. As NAMRU-3 establishes appropriate national laboratories in various countries in the EMRO region, it will need to move to a role more focused on follow up, confirmation of results, advanced virology, and quality assurance.
RECOMMENDATION 5-7. In order to assure the quality and sustainability of the regional influenza surveillance system, NAMRU-3 should work to establish standards and foundation documents for each of the steps in its laboratory-establishment process as well as to provide technical assistance for a new regional quality-assurance entity including (1) the development of a solid plan of strengthening regional countries’ laboratory capacity with regard to avian influenza and maintaining this capacity through training, quality assurance, and proficiency testing; (2) continued collaboration with WHO to develop an external quality-assurance system for national central laboratories in the EMRO region; and (3) the use of NAMRU-3’s extensive experience in capacity building (training, supervision, and mentoring) to develop structured (yet adaptable to each context) laboratory assessment checklists, training guidelines, and monitoring tools.
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COLLABORATION AND COORDINATION
NAMRU-3 has many partners, including the Egyptian Ministries of Health, Environment, and Agriculture, governmental agencies of other countries in the EMRO region, other DoD departments, and a range of technical and financial partners such as the WHO and the CDC. NAMRU-3 is a WHO collaborating center for influenza. Information-sharing relationships between NAMRU-3 and its partners appear strong but seem to be informal, person-based, and circumstance-dependent.
Host Country Government
As a regional influenza reference laboratory, NAMRU-3 has the capacity to serve as a reference laboratory for all of the countries in the EMRO region, confirming influenza testing for ministries of health in the region. NAMRU-3 also extends assistance to the central Asian republics, West Africa, and countries such as Ukraine, Bulgaria, Macedonia, and Azerbaijan.
The Ministry of Health is the lead agent in Egypt’s influenza surveillance effort. NAMRU-3 staff work very closely with representatives from the Ministry of Health, expanding the national human surveillance system and sharing results of laboratory testing on possible avian influenza samples. In addition, NAMRU-3 staff members participate at all coordination meetings with the Egyptian High Committee. The close relationship between NAMRU-3 and the Ministry of Health has enabled NAMRU-3 to work strategically and efficiently in Egypt in support of the national avian influenza surveillance network.
In terms of other Egyptian national partners, NAMRU-3 and the Egyptian Ministry of Environment have a strong collaborative relationship focused on the surveillance of migratory birds and routinely share information between each other, as NAMRU-3 performs all diagnostic assays.
While NAMRU-3 has collaborated with the Ministry of Agriculture on surge capacity for animal samples (specifically during outbreak situations) and for molecular characterization, their relationship needs strengthening. The Ministry of Agriculture shares limited information with relevant partners. This has made it difficult to bridge the gaps in information between human and wild bird surveillance activities being conducted by the Ministries of Health and Environment and supported by NAMRU-3.
In other countries where NAMRU-3 has ongoing influenza-related activities, it works directly with the ministries of health. These collaborations are based on mutual benefit. The national governments’ commitment of personnel is instrumental in the timely collection and processing of influenza specimens. In turn, NAMRU-3’s reporting of results significantly
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reduces response time. These relations typically result in positive outcomes both in terms of the expansion of influenza surveillance at the national and global levels and in terms of the medical diplomacy of the U.S. government in general.
Multilateral Agencies
Because of NAMRU-3’s status as a WHO regional influenza reference laboratory, it works very closely with both EMRO and WHO headquarters in Geneva. This role was determined in collaboration with WHO and EMRO based on NAMRU-3’s technical expertise and facilities capacity. NAMRU-3 is expected to become a WHO H5 reference center in the near future, which will strengthen even further its WHO regional and headquarters partnerships. At the current time, NAMRU-3 provides personnel and support to WHO and EMRO for outbreak investigations in the region. At WHO headquarters in Geneva, NAMRU-3 is a member of the Global Outbreak Alert Response Network (GOARN). NAMRU-3 staff routinely participate in the WHO regional pandemic/avian influenza meetings of EURO, EMRO, and AFRO (WHO Regional Office for Africa). They also conducted a WHO avian influenza training course for approximately 200 clinicians, laboratorians, and public health officials in Kiev for the countries of Ukraine, Azerbaijan, Georgia, Belarus, and Uzbekistan. No financial resources are regularly committed by WHO to NAMRU-3 as a WHO collaborating center. Currently, NAMRU-3 is using GEIS AI supplemental funding to perform all regional specimen processing, diagnostics, and characterization.
NAMRU-3 coordinates its animal-surveillance activities with FAO to ensure an optimal use of funds. FAO funding has been well complemented because it provided for a logistical base for field surveillance while the DoD-GEIS funding provided the resources to support reference laboratories, as in the case of the laboratory in Kabul.
U.S. Government Agencies
NAMRU-3 activities in Cairo, Egypt, are directly linked with the U.S. Department of State and other U.S. government agencies. Monthly reports and weekly updates are available to other U.S. government partners, such as CDC, HHS, and the U.S. Agency for International Development (USAID), and assist in coordinating efforts. As a WHO collaborating center, NAMRU-3 collaborates with the CDC and routinely sends the CDC avian influenza specimens for further characterization. The CDC has committed its time to processing and relaying information back to both NAMRU-3 and WHO-Geneva.
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The upcoming assignment of CDC public health professionals to NAMRU-3 will strengthen its relationship with CDC as a key technical partner in Egypt. As of July 2007, NAMRU-3 was working with CDC to fill five positions at the laboratory including a senior epidemiologist to work as the director of the CDC International Emerging Infections Program (IEIP) in Cairo, an epidemiologist, a public health advisor, a Resident Advisor for the CDC Field Epidemiology Training Program, and a U.S. Public Health Service Captain to serve as influenza coordinator. NAMRU-3 staff expects that once the IEIP director is selected, administrative issues related to the organizational relationships will be determined collaboratively.
USAID is an additional collaborating partner of NAMRU-3 in a number of countries in which it conducts avian influenza activities. NAMRU-3 staff are routinely invited to USAID-sponsored meetings to provide input as regional experts. These meetings often lead to additional opportunities for avian influenza capacity building outside the regions in which NAMRU-3 is typically engaged. For Bulgaria and Macedonia, NAMRU-3 provided assistance with laboratory design, specimen-throughput consultation, and multiple training sessions, both at NAMRU-3 and in-country. Relations with USAID-Egypt seem to be less productive, though there are efforts under way to strengthen this collaboration.
Other DoD Entities
In terms of DoD in general, NAMRU-3’s strategic location enables it to support CENTCOM, EUCOM, and a future AFCOM (U.S. African Command) with diagnostic support, outbreak response capacity, and training. To date, NAMRU-3 has been able to contribute by providing specimen collection to a number of military preventive medicine units in Iraq, Kuwait, Qatar, and Djibouti. In addition, NAMRU-3 has responded to outbreaks in Azerbaijan, Iraq, Sudan, and Djibouti.
Other DoD entities, such as the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and other military laboratories operating overseas, are also essential partners with NAMRU-3. There are a number of ongoing project-specific collaborations between NAMRU-3 and other DoD entities related to avian influenza. All reporting on regional efforts is sent to a variety of DoD offices in the United States, including DoD-GEIS headquarters, NMRC, and the Naval Bureau of Medicine and Surgery. NAMRU-3 also collaborates with USAMRIID by providing influenza RNA to assist USAMRIID in its development of future diagnostics. NAMRU-3 has worked extensively with the Naval Health Research Center to assist with specimen provision for the development of an electrospray ionization mass spectrometry device for respiratory pathogen identification. NAMRU-3 works with the Air Force Institute for Operational Health to provide ac-
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curate surveillance data. Using the supplemental funding, NAMRU-3 has also expanded its wild bird surveillance via their collaboration with DoD personnel at the U.S. Army Medical Research Unit-Kenya.
While there are certainly fruitful collaborations taking place between NAMRU-3 and other DoD entities, it was not completely clear to the IOM site visit team how communication and coordination with the DoD-GEIS headquarters and other DoD-GEIS sites is realized.
Private Organizations
The virology program at NAMRU-3 works with Idaho Technology Incorporated (ITI) to validate primer/probe sets dedicated for the military-deployable mobile real-time PCR systems. These will eventually be used to further support NAMRU-3’s outbreak response. ITI provides limited supplies to conduct these validation studies, while DoD-GEIS AI supplemental funding covers labor costs and additional supplies. No cash resources are provided to NAMRU-3 by ITI.
Conclusions
NAMRU-3 has excellent long-term relationships with all of its partners in Egypt and the region. In particular, the AI/PI activities have increased the possibilities for capacity building with the Egyptian Ministry of Health in support of improved surveillance and response.
RECOMMENDATION 5-8. NAMRU-3 should continue to serve in a technical advisory role to the Egyptian Ministry of Health and carry out medical diplomacy by developing relationships with strategic partners while maintaining its role as an independent research agency with primary allegiances to the U.S. Navy.
NAMRU-3 has been actively engaged in host country collaborations and is heavily committed in terms of personnel and resources in Egypt and the wider region. However, NAMRU-3 leadership stated that targets of opportunity often drive its activities, and this creates problems when trying to develop longer-range plans for the organization.
RECOMMENDATION 5-9. NAMRU-3 should develop country- and region-specific 3-year strategies that focus on host sustainability as well as on the development, expansion, and maintenance of an influenza early warning system.
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The committee encourages NAMRU-3 to continue its complementary and integrated relationship with CDC. The committee concluded that the development of a memorandum of understanding that defines roles and responsibilities and the chain of command would facilitate this relationship and related influenza activities at NAMRU-3. In addition, increased bilateral information sharing with USAID, including more collaboration on complementary activities such as development of information, education, and communication materials for AI awareness, could benefit the influenza activities of both U.S. agencies. These efforts to improve its collaboration with USAID could be facilitated by the U.S. mission.
REFERENCES
DoD-GEIS (Department of Defense Global Emerging Infections System). 2007a. U.S. Naval Medical Research Unit No. 3. http://www.geis.fhp.osd.mil/GEIS/Training/namru-3.asp (accessed June 12, 2007).
DoD-GEIS. 2007b. Department of Defense influenza surveillance sites worldwide, 2007 (unpublished).
IOM (Institute of Medicine). 2001. Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A program review. Washington, DC: National Academy Press.
NAMRU-3. 2007a. Estimated laboratory surge capacity (unpublished).
NAMRU-3. 2007b. Viral and zoonotic disease research program. PowerPoint presentation presented during site visit March 4, 2007 Cairo, Egypt (unpublished).
NAMRU-3. 2007c. Regional surveillance for influenza and other respiratory viruses in the Middle East, central Asia, Africa, and Eastern Europe. PowerPoint presentation presented during site visit March 4, 2007 Cairo, Egypt (unpublished).
OIE (Organisation Mondiale de La Santé, World Organization for Animal Health). 2006. Avian influenza in Egypt follow-up report No. 1. http://www.oie.int/eng/info/hebdo/AIS_28.HTM#Sec7 (accessed June 12, 2007)
USDA (United States Department of Agriculture). 2006. Avian influenza, Egypt: Impact Worksheet. http://www.aphis.usda.gov/vs/ceah/cei/taf/iw_2006_files/foreign/hpaiegypt022306_files/hpaiegypt02232006bb.htm (accessed June 12, 2007).
WHO (World Health Organization). 2007a. H5N1 avian influenza: Timeline of major events. http://www.who.int/csr/disease/avian_influenza/Timeline_2007_03_20.pdf (accessed Sep-tember 5, 2007).
WHO. 2007b. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. http://www.who.int/csr/disease/avian_influenza/country/cases_table_2007_07_11/en/index.html (accessed September 5, 2007).
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LIST OF CONTACTS
DoD-GEIS NAMRU-3 Assessment: Egypt
Adam Armstrong, Head Enteric Diseases Research Program, U.S. Naval Medical Research Unit No. 3
CAPT Bruce Boynton, Commanding Officer, U.S. Naval Medical Research Unit No. 3
David Hoel, Vector Biology research Program, U.S. Naval Medical Research Unit No. 3
Edward Kilbane, Head Disease Surveillance Research Program, U.S. Naval Medical Research Unit No. 3
Moustafa Mansour, Director of Research Sciences, U.S. Naval Medical Research Unit No. 3
Marshall Monteville, Head Viral and Zoonotic Diseases Research Program, U.S. Naval Medical Research Unit No. 3
Guillermo Pimentel, Disease Surveillance Research Program, U.S. Naval Medical Research Unit No. 3
Maha Talaat, Disease Surveillance Research Program, U.S. Naval Medical Research Unit No. 3
Jeff Tjaden, Viral and Zoonotic Diseases Research Program, U.S. Naval Medical Research Unit No. 3
Sam Yingst, Viral and Zoonotic Diseases Research Program, U.S. Naval Medical Research Unit No. 3
Matt Weiner, Enteric Diseases Research Program, U.S. Naval Medical Research Unit No. 3
Nasr EL-Sayed, First Under Secretary for Preventive and Endemic Affairs, Egyptian Ministry of Health and Population
Holly Fluty-Dempsey, Chief Population and Health Division, United States Agency for International Development
Akmal Elerian, Population and Health Division, United States Agency for International Development
Tara Milani, Population and Health Division, United States Agency for International Development
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SCHEDULE OF EVENTS
DoD-GEIS NAMRU-3 Assessment
Cairo, Egypt
Participants: Mary J. R. Gilchrist
James Tibenderana
J. Alice Nixon
March 4-10, 2007
Sunday, March 4, 2007
0900-1000
Greeting and command brief
Dr. Moustafa Mansour
Lt. Stegall
1030-1030
Tour of NAMRU-3
Dr. Moustafa Mansour
1130-1130
Briefing on Enteric Diseases Research Program
Cdr. Adam Armstrong
1230-1230
Lunch
1400-1400
Briefing on Disease Surveillance Program
Capt. Edward Kilbane
1600-1600
Briefing on Viral and Zoonotic Diseases Research Program
Lt. Cdr. Marshall Monteville
1600-1630
Return to hotel
Monday, March 5, 2007
0700-0730
Depart NAMRU-3
0730-1430
Visit to Damietta, Port Said, and Manzallah Lake field sites for migratory bird sampling
1430-1700
Travel to Alexandria
Tuesday, March 6, 2007
1200-1200
Visit to Alexandria Fever Hospital
1400-1400
Visit to field sites in Alexandria
1730-1730
Return to Cairo
Wednesday, March 7, 2007
0900-1000
Overview of field visits
1000-1500
Field visits to MoH, WHO (EMRO), USAID, DCM
1500-
Return to hotel
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Thursday, March 8, 2007
0830-0900
Briefing with program heads
0900-1000
Overview of Vector Biology Research Program
Lt. Cdr. David Hoel
1000-1100
Out-briefing and open discussion
1600-
Return to hotel
Friday, March 9, 2007
0900-
Optional tour
Saturday, March 10, 2007
0900-
Departure
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