Experience of a global laboratory network in responding to infectious disease epidemics.

The challenge of emerging infections transcends national borders. Influenza A (H5N1), severe acute respiratory syndrome (SARS), and diseases that continue to re-emerge such as cholera, drug-resistant malaria, and dengue can expand rapidly from local to regional or global threats. We were pleased to see that Georgios Pappas and colleagues, in their global review of human brucellosis epidemiology, discussed serious problems in tracking and containing the disease, which apply to many emerging infections: lack of appropriate diagnostic capabilities in developing countries, cross-border disease spread from countries with high incidence, and emergence of new endemic foci because of socioeconomic and other changes.

Several of us have proposed a network of new, broad-based laboratories as a way to address such challenges for emerging infections of international importance. These laboratories would assist host countries in developing surveillance systems and responding to epidemics, strengthen global epidemic detection and response efforts of WHO in key regions, and form links with specialised institutions worldwide to support these activities.

We offered, as a model for the proposed network, US military overseas infectious disease research laboratories. Following World War 2, the US military and host countries established these laboratories to study infectious diseases of bilateral concern. Broad-based laboratory proficiencies and access to key populations facilitated important research (see, for example, 4, 5, 6, 7, 8). Currently, there are five such Department of Defense (DoD) Overseas Laboratories: Naval Medical Research Center Detachment (NMRCD; Lima, Peru), Naval Medical Research Unit-3 (NAMRU-3; Cairo, Egypt), US Army Medical Research Unit-Kenya (USAMRU-K; Nairobi), Armed Forces Research Institute of Medical Sciences (AFRIMS; Bangkok, Thailand), and Naval Medical Research Unit-2 (NAMRU-2; Jakarta, Indonesia).

In 1996, a Presidential directive instructed federal departments and agencies to strengthen US detection, response, and prevention for emerging infections. The DoD, in turn, codified the missions of emerging infection surveillance, outbreak response, and host country capacity building for these research-oriented laboratories. The DoD-Global Emerging Infections Surveillance and Response System (DoD-GEIS) was established to support and coordinate these activities at the Overseas Laboratories and in the Military Health System. The DoD-GEIS network of Overseas Laboratories currently maintains surveillance activities in more than 20 countries. These include a global influenza surveillance system and surveillance for malaria, dengue, diarrhoeal diseases, other febrile illnesses, and antimicrobial resistance. The Overseas Laboratories respond to outbreaks on invitation by host countries or WHO.

Between Oct 1, 2003 and Feb 28, 2006, the Overseas Laboratories responded to 66 outbreaks in 22 countries (table ; we provide country of occurrence only for selected outbreaks because of host country sensitivities). They provided laboratory and field support, laboratory support only, and field support only for 36, 26, and four responses, respectively, identifying the causal agent in 55 of 62 (89%) responses involving laboratory support. 62 responses targeted human outbreaks only. The four others included veterinary (with or without human) response.

Table

DoD-GEIS overseas outbreak responses, October, 2003, to February, 2006

Disease or agent		Number of outbreaks
Bartonellosis		1
Brucellosis		1
Chikungunya		10
Cholera		4
Crimean-Congo haemorrhagic fever		1
Cryptosporidium		1
Cyclospora		2
Dengue fever or haemorrhagic fever		10
Ebola haemorrhagic fever		1
Enterotoxigenic Escherichia Coli		2
Enterovirus meningitis		1
Hepatitis (viral)		4
Influenza		9
Japanese encephalitis		1
Leishmaniasis (cutaneous)		2
Leptospirosis		1
Marburg haemorrhagic fever		1
Plague (bubonic)		1
Q fever		1
Typhoid fever		2
Yellow fever		2
Unknown aetiology
	Febrile syndrome	2
	Gastrointestinal syndrome	3
	Respiratory syndrome	3
Total		66

Among human outbreaks, size ranged from fewer than ten cases (eg, Crimean-Congo haemorrhagic fever in Sudan) to thousands (eg, chikungunya in Kenya). Response to outbreaks involving animals included influenza A (H5N1) in Egypt, Iraq, Kazakhstan, and Turkey. Overall, the three most common diseases were chikungunya (ten outbreaks in Comoros, Indonesia, Kenya, and Somalia), dengue fever or dengue haemorrhagic fever (ten outbreaks in Eritrea, Indonesia, Peru, Sudan, and Yemen), and influenza (nine outbreaks in Cambodia, Egypt, Indonesia, Iraq, Kazakhstan, Kenya, Nepal, and Turkey). Laboratory testing did not identify the causal agent but excluded SARS in two outbreaks (in Iraq and Peru) where it was suspected initially because of patient travel history or clinical features.

Several outbreak responses helped to identify disease emergence or re-emergence. These include influenza A (H5N1) in Egypt, Indonesia, Iraq, Kazakhstan, and Turkey; a large outbreak of cutaneous leishmaniasis in a forested region of Ghana (an unusual focus, since the disease usually occurs in arid or semi-arid areas); outbreaks of chikungunya in Lamu and Mombasa, Kenya (the first confirmed outbreaks along the Kenyan coast); emergence of dengue haemorrhagic fever in Iquitos, Peru; re-emergence of dengue in Lima, Peru (after a 60-year absence); and isolation of a novel virus associated with a haemorrhagic fever outbreak in Bolivia (further viral characterisation is pending). Several outbreaks involved diseases recognised by the International Health Regulations as capable of rapid international spread. These include ebola and Marburg haemorrhagic fever in Sudan and Angola, respectively; cholera in Kenya; yellow fever in Peru and Sudan; and dengue and influenza A (H5N1) as described above.

The Overseas Laboratories collaborated with WHO or the US Centers for Disease Control and Prevention in 22 outbreak responses. Host country collaborations are integral to the success of the Overseas Laboratories. Host country Overseas Laboratory staff provide understanding of local language and culture, and maintain continuity since US personnel rotate every few years. Outbreak responses provide opportunities for training and technology transfer with Ministry of Health personnel, strengthening partnerships and readiness for future outbreaks.

The model presented here—broad-based laboratories with epidemiologic capabilities, links to wider networks, and strong host country collaborations—has proven useful in responding to outbreaks of epidemic, endemic, and emergent diseases. The DoD Overseas Laboratories also devote considerable resources to applied research (such as clinical trials of vaccines and drugs), development of host country surveillance systems, and training of host country and US military medical personnel, activities that facilitate outbreak response. We encourage government and public health leaders to consider establishing facilities similar to these in countries where the need is most critical.