Preparedness for Highly Pathogenic Avian Influenza Pandemic in Africa

Africa’s strategies for pandemic influenza must also strengthen overall public health capacity.

I n January 2006, chickens in Kano and Kaduna States in northern Nigeria exhibited diarrhea and respiratory distress and died within a few days. The National Veterinary Research Laboratory in Plateau State isolated infl uenza viruses from these dying chickens. A Food and Agriculture Organization laboratory in Rome confi rmed that the isolates were highly pathogenic infl uenza A subtype H5N1and genetically similar to infl uenza (H5N1) clade 2 viruses from China, Indonesia, Japan, South Korea, and other countries (1). Offi cial reports of the outbreak among poultry in Nigeria were disseminated on February 7, 2006, which initiated a wide range of bilateral and multilateral responses to the arrival of avian infl uenza in sub-Saharan Africa. Subsequently, the infl uenza viruses subtype H5N1 isolated in Nigeria were confi rmed as belonging to 3 distinct phylogenetic lineages, which suggested independent introduction into Nigeria through different sources (2).

Response to Infl uenza (H5N1) in Africa
After highly pathogenic infl uenza A virus subtype H5N1 was fi rst detected in Africa, plans were announced to implement strategies to eradicate the virus. Nigerian authorities formed a national steering committee led by the ministers of health, agriculture, and information. The committee focused on detection of affected farms, depopulation efforts on those farms and in surrounding areas, surveillance for human disease, and dissemination of messages to promote understanding and modifi cation of behaviors that encourage virus spread. Despite the endorsement of control strategies at the national and state levels, local resources were limited and the virus spread widely. By the end of February 2006, 4 Nigerian states and the Federal Capital Territory, all within central and northern parts of the country, had confi rmed infl uenza virus subtype H5N1 outbreaks in poultry, and presence of the virus was suspected in 9 other states. More than 770,000 birds had either died from illness or were culled. Bilateral donor agencies donated >$3 million, and the World Bank offered $50 million credit to add to several million dollars committed by the government of Nigeria. However, efforts to get human, material, and fi nancial resources rapidly to locally affected areas were inadequate, which stifl ed well-conceived national control efforts. By early June, 14 Nigerian states had confi rmed cases of infl uenza (H5N1) infection in birds, and several hundred thousand additional birds were reported dead, including chickens, geese, and ducks. Niger and Cameroon had also confi rmed infl uenza (H5N1) outbreaks near the Nigerian border.
Despite continued spread of H5N1 subtype among poultry, human cases of avian infl uenza were not identifi ed in Nigeria until January 2007, when 1 human case of infection with infl uenza virus subtype H5N1 was confi rmed in a woman. However, weaknesses in existing disease surveillance systems limited capacity to detect transmission of avian infl uenza to humans. To rule out avian infl uenza, as of May 2007, specimens from 301 patients have been tested in Nigeria.
That an epizootic of this magnitude in poultry would have negative economic and nutritional effects is not surprising. Nigeria's estimated 140-160 million poultry account for 10% of its gross domestic product and a substantial proportion of the protein ingested by its 132 million people (3). An assessment conducted by the United Nations Development Program showed that the greatest adverse effect was in impoverished areas like rural and semiurban Nigeria, affecting especially backyard and medium-scale farmers. Egg and chicken sales declined by >80% within 2 weeks after the announcement of the outbreak; 4 months later, sales were still <50% of baseline. Poultry feed sales also dropped by >80%; 80% of workers on affected farms and 45% on unaffected farms lost their jobs (4). The outbreak caused an immediate decline in chicken consumption, even in areas where the disease was not reported among poultry.
In March 2006, avian infl uenza outbreaks were reported among poultry in Egypt; these reports were followed by 38 laboratory-confi rmed cases and 15 human deaths. As of May 2007, infl uenza virus (H5N1) has been detected in fowl in 8 countries neighboring Nigeria and Egypt ( Figure). Outbreaks of avian infl uenza have continued in Nigeria; as of May 2007, 24 of 36 states had documented avian infl uenza in poultry. In many other countries in East and West Africa, bird die-offs were reported, but related disease (infl uenza A subtype H5N1) in humans has not been confi rmed. Whether the lack of reported human cases in sub-Saharan Africa, when compared with Egypt, is due to differences in surveillance systems or in animal handling practices that would promote transmission to humans is not clear.

Implications of Avian Infl uenza Emergence in Africa on Pandemic Preparedness
The next infl uenza pandemic, if it plays out like the 1918 pandemic, would likely cause more deaths proportionately in sub-Saharan Africa than anywhere else in the world (5). Poor nutritional status, high rates of concurrent diseases such as HIV/AIDS, and limited access to healthcare could contribute to high mortality rates (5). The devastating effect of pandemic infl uenza would likely exacerbate unaddressed public health problems and require immense humanitarian emergency assistance, which might not be feasible because of limited available global resources and restrictions on movement of persons worldwide.
Sub-Saharan Africa is uniquely characterized by vast geographic areas that are diffi cult to access; uneven socioeconomic development; nearly transcontinental limitations in epidemiologic, surveillance, and laboratory capacity; and profound infrastructure weaknesses relating to communications and health systems and capacity of government organizations to effectively focus limited resources.
An awareness of this situation has brought substantial pressure on nations in Africa to implement or strengthen detection and rapid response capacities. Animal health strategies have focused on improving surveillance in birds, enhancing laboratory capability to detect infl uenza A, including H5 strains, and supporting teams to do rapid depopulation. On the human side, an early warning system is needed for an emerging infl uenza pandemic, i.e., surveillance to detect clusters of infl uenza-like illness in healthcare facilities and communities and to rapidly confi rm them as infl uenza in the fi eld and at qualifi ed laboratories.
Effective preparedness and responses will require fresh, innovative thinking relevant to local circumstances, determination, political will, and national and international resources. The African Regional Offi ce (AFRO) of the World Health Organization (WHO) and its country offi ces have a clear mandate to address regional impending and ongoing health crises. Partners, including other United Nations agencies, development organizations, and allied nongovernment organizations, should line up with AFRO and national ministries of health and livestock to encourage and catalyze multisectoral government and nongovernment commitment and action.

Balancing Pandemic Infl uenza Concerns with Ongoing Health Priorities
The potential effects of pandemic infl uenza on human health and political stability in sub-Saharan Africa cannot be denied. Of paramount concern, however, is that this potential disaster emerges onto a backdrop of countries struggling to address epidemics of HIV, tuberculosis, and malaria; resurgence of paralytic poliomyelitis; and high childhood mortality rates due to pneumonia and diarrheal diseases. Many of the severe effects of these diseases could be prevented by use of proven public health tools (e.g., antiretroviral drugs; improved detection and treatment of tuberculosis; insecticide-treated bednets; vaccines against Streptococcus pneumoniae, Haemophilus infl uenzae type b, and rotavirus), but African countries lack the resources and infrastructure to take full advantage of these tools.
In fact, the frenetic global activity around avian infl uenza's potential threat to human health is diverting critical fi nancial and human resources and focus from the real ongoing, distressing effects of the major infectious disease syndromes. This diversion may be acceptable for a short time if the most pressing challenges for preparedness can be quickly and effectively addressed. However, for many months, ministries of health personnel in countries throughout Africa have been deeply immersed in pandemic preparedness and response planning; they have been pulled away from routine activities, and critical programs have been put on hold. In Nigeria, while senior health offi cials were struggling to maintain Global Fund resources for HIV and malaria, as well as to improve polio vaccination coverage and stop the export of polio to other nations, considerable immediate pressure was exerted to ramp up infl uenza surveillance, containment, and preparedness activities after the initial confi rmation of infl uenza virus (H5N1). Similarly, when avian infl uenza was confi rmed in poultry in Juba, Sudan, in September 2006, the newly formed Ministry of Health staff of the government of South Sudan had to balance already demanding commitments to battle HIV, tuberculosis, and an ongoing cholera epidemic with the need to prepare for potential infl uenza A virus (H5N1) infection of humans. The substantial effort required added more weight to a grossly overstressed public health system.
Tension between existing disease concerns and the potential threat of a pandemic raises several questions: whose concern is avian infl uenza; and what are appropriate, balanced responses, particularly in countries with severely limited public health resources and overwhelming health problems? A pandemic strain emerging in Africa is a global concern as much as an African concern. Without rapid detection systems and effective control measures, a highly transmittable strain would quickly spread globally.
Wealthier nations have recognized this and pledged nearly $2.5 billion to address the problem, although most is not specifi cally for use in Africa.
In addition, an infl ux of massive resources from more developed nations, if not well coordinated and balanced in scope, could distort the sense of priorities and damage other critical public health and agricultural programs. How then can a balance be achieved and result in appropriate enhancements to address the threat of pandemic infl uenza while keeping focus on the existing major health priorities facing Africa? One approach, detailed below, would be to use new resources in a way that is broadly applicable to building public health capacity in recipient nations.

Improving Pandemic Preparedness
The need and resources for rapid detection of potentially pandemic strains of infl uenza should be leveraged with support for surveillance (Table) for other epidemic-prone and vaccine-preventable diseases; parallel, vertical systems will ultimately not be sustainable in Africa. The drive for improved infl uenza surveillance can fuel the implementation of Integrated Disease Surveillance and Response (IDSR), promoted by WHO and its partners and endorsed in 1998 by 46 countries in the African region (6)(7)(8). IDSR includes surveillance for vaccine-preventable diseases and epidemic-prone diseases such as meningococcal disease, measles, cholera, typhoid, yellow fever, and viral hemorrhagic fever. If functioning well, IDSR should provide health offi cials with signals when disease incidence passes thresholds, suggesting an impending epidemic and the need to ramp up disease prevention activities like vaccination, safe water campaigns, or quarantine. Presently, however, IDSR is functional in a few countries, including Eritrea, Ghana, and Kenya. Strengthening IDSR throughout Africa would create an effective early warning system capable of detecting a pandemic strain of infl uenza or clusters of patients with severe acute respiratory illness, which could signal the beginning of person-to-person transmission. Early detection of a pandemic would facilitate the timely implementation of pharmaceutical and nonpharmaceutical containment measures. In addition, strengthening IDSR would have the dual benefi t of enhancing capacity for early detection of outbreaks of more conventional diseases and perhaps currently unrecognized threats.
For IDSR to effectively function as an early warning system for infl uenza and other communicable diseases, a number of steps should be taken. First, additional resources should be made available for fi eld training of national and local staff and subsequent site assessments. Second, this conventional public healthcare facility-based surveillance system should be expanded to cover private healthcare institutions and include community-level surveillance, through reporting by village chiefs, traditional healers, dispensaries, and primary schools. Finally, existing technology in Africa should be leveraged to make IDSR a user-friendly, more effi cient surveillance system. The widespread use of mobile telephones and extensive mobile phone networks throughout Africa could be extremely helpful for reporting unusual health occurrences through inexpensive, potentially automated, text messaging to an identifi ed, widely recognized, and toll-free number. Reports of disease clusters could then be immediately verifi ed and investigated by public health personnel (9). This tool could also be used for animal surveillance.

Intersectoral Communication and Collaboration
With similar urgency, enhanced veterinary surveillance and strong, functional networks of communication and collaboration between animal and human health experts would increase potential for prevention of transmission of infl uenza from animals to humans. Currently, linkages and communication mechanisms between health and veterinary offi cials are neither explicit nor functional. A major challenge in Nigeria's response to avian infl uenza (H5N1) was to ensure communication between Ministry of Health and Ministry of Agriculture staffs on the ground so that when poultry outbreaks occurred on farms, the Ministry of Health was alerted to look for human cases.

Laboratory Capacity
Resources for improving infrastructure to address threats of avian infl uenza must be channeled to improve local laboratory capacity and strengthen laboratory networks. WHO and AFRO have a critical role to promote, select, develop, train, and sustain laboratory capacity for diagnosis of infl uenza within regional reference laboratories and national infl uenza centers. AFRO has already designated several existing laboratories in Africa as regional reference laboratories for testing seasonal and avian infl uenza in humans. With enhanced surveillance, these laboratories should be able to rapidly confi rm or rule out infl uenza as the cause of a cluster of severe respiratory illness, which would allow for rapid epidemic responses. Already, laboratories in several countries in Africa have been upgraded, laboratorians have been trained, equipment (real-time and conventional PCR machines) and appropriate reagents (primers and probes) have been procured, and quality control mechanisms have been put in place so that PCR can be used in a timely manner to reliably document the pres-ence of highly pathogenic infl uenza A virus subtype H5N1. With additional reagents and training, these laboratories could have the capacity to rapidly detect causes for other outbreaks and assist with surveillance for routine and emerging diseases. As laboratory surveillance is initiated and strengthened, training, leveraging of equipment maintenance and service contracts, and resource sharing across animal and human facilities will be essential.

Epidemiologic Capacity
Being prepared for an infl uenza pandemic will require having a well-trained corps of epidemiologists. Field epidemiology training programs and Public Health Schools without Walls are in place in several countries in Africa; these programs are successfully training medical doctors (and laboratorians in the case of Kenya's Field Epidemiology and Laboratory Training Program) to become public health experts. To minimize out-migration, graduates should be rewarded through career advancement pathways within national public health systems.

Response and Containment
In a joint effort by WHO and the Centers for Disease Control and Prevention, rapid outbreak response teams are being trained in sub-Saharan African countries to recognize outbreaks, collect information and specimens, and implement quarantine measures, if indicated, while using and distributing personal protective equipment and antiviral drugs. Training rapid response teams in each country is a relatively new concept for Africa, but such teams in Asia have responded to dengue epidemics and, more recently, to avian infl uenza. If these teams are functional, they will strengthen responses in Africa to a wide array of epidemics, enabling timely implementation of interventions to prevent illness and death.
Should a major health disaster such as an infl uenza pandemic occur, essentially no capacity exists to appropriately address the healthcare crisis while continuing to deal with other routine health problems, which themselves can at times overwhelmingly stress healthcare systems. Preparation for a pandemic must strengthen hospital capacity to optimally and safely manage severely ill patients with potentially highly contagious illnesses. Although aiming for parity with hospitals in industrialized nations on quality standards for infection control is excessively ambitious, simple, practical approaches to implement basic infection control measures developed by WHO can be used (10).
Although data on the topic are limited, public awareness of avian infl uenza is minimal in Africa, specifi cally concerning the link between dying birds and human illness and the potential of catastrophic emergence of pandemic infl uenza. The United Nations Children's Fund has conducted participatory action research, which has shown that while community outreach campaigns will be needed across the continent, messages must be locally customized because of wide variations in literacy, awareness, experience, and beliefs (11). Recent efforts to strengthen information, education, and communication in Africa will improve societal mobilization for behavior modifi cation capacity, which can be called upon to address public health threats (12). Ultimately, by developing effective health communication measures, functional surveillance systems with strong epidemiologic and laboratory support, and capable multisectoral rapid response teams, it may be possible to curtail spread of a lethal pandemic strain and buy time to develop and deliver effective human-administered vaccines (13,14).

A Call for New Strategies
In Asia, the principal control approach has been depopulation of poultry in affected and nearby farms along with attempts to restrict movement of poultry and poultry products from affected areas. Even when aggressively pursued, these efforts were not always timely or comprehensive, and avian infl uenza became endemic among birds in many parts of Asia and has now spread to Europe and Africa. The diffuse spread of the virus in avian species and some transmission to humans and other mammals has provided numerous opportunities for a pandemic virus to appear; however, a strain easily transmittable from person to person has not yet emerged. Although this provides some comfort for now, a variety of ecologic and health factors could affect the emergence of a devastating pandemic strain.
The massive geographic spread of avian infl uenza in birds should cause a re-evaluation of bird depopulation as the principal strategy for control. Although depopulation appears to have worked when the virus was localized during 1997 in Hong Kong and 1.5 million birds were culled, widespread presence of the virus in migratory and domestic birds has severely limited the usefulness of this approach. In addition to direct costs, massive culling operations dramatically affect the economic and nutritional status of impoverished people. Compensation programs, critical to success of culling efforts, have not been implemented optimally in most countries where infl uenza virus (H5N1) epizootics have occurred. Without credible, adequate, and rapidly implemented compensation programs linked to depopulation efforts, farmers are not encouraged to report bird die-offs and may transport birds to unaffected areas, thereby spreading the virus (15). Furthermore, depopulation may counter evolutionary pressure. If the birds that survive local outbreaks are the fi ttest, killing them provides no evolutionary advantage to survival.
Vaccination of poultry may be a useful adjunct to depopulation in a defi ned area surrounding an affected farm (ring depopulation). Some available vaccines seem to pro-vide immunity to infection without substantially prolonging viral shedding (16)(17)(18)(19). If so, focusing vaccination programs on farms around affected areas may be a less costly, more socially acceptable, and more effective solution than mass culling, with or without compensation. Effective use of infl uenza vaccines in avian populations could theoretically reduce the risk for emergence of a pandemic strain by decreasing the numbers of circulating avian infl uenza strains that could mutate or reassort with other circulating infl uenza viruses (19). Additionally, use of emergency vaccination can be effective in conjunction with other measures at the time of poultry outbreaks (19). Ultimately, control measures will be implemented by agriculture and livestock ministries, which must address potentially confl icting commercial and public health interests.
Current vaccine supplies for poultry in risk areas may be insuffi cient. A clear avian vaccination strategy, articulated and implemented by international organizations, would encourage adequate production of effective vaccines for use in currently and prospectively affected areas. Analyses comparing costs and potential cost-effectiveness of depopulation and vaccination strategies (and strategies that use both approaches) would be helpful.

The Path Forward
Activities to address the threat of pandemic infl uenza should, whenever possible, build upon existing public health systems and enhance available health infrastructure rather than create new systems. In Vietnam, for instance, research organizations like Oxford University and The Wellcome Trust, and partners they support, were able to refocus their efforts onto avian infl uenza and provide substantial new knowledge relevant for protecting health (20,21). Likewise in Africa, many nongovernment and religious organizations can build on their existing networks and groundwork to assist governments with surveillance and risk-reduction efforts, as has been the case for initiatives to address HIV/AIDS, provide safe water, and eradicate poliomyelitis (22)(23)(24)(25)(26).
Identifying existing laboratory and disease-reporting mechanisms in individual countries is crucial so they can be augmented to achieve sustainable capacity for surveillance for infl uenza and other emerging diseases. National disease reporting systems-IDSR and polio surveillancemay provide entry points for such activity but will require strategic investments that in large part need to be defi ned in the context of national priorities and balanced with global needs. Early detection and improvement of the continent's preparedness for emerging diseases has been brought into focus by the recent adoption of a treaty by the World Health Assembly of new International Health Regulations (IHR [2005]), which now compels countries to have more effective surveillance and reporting systems to improve the ability for early detection of global disease threats (27). More specifi c to infl uenza, IHR (2005) compels countries to implement optimal communications, rapid risk assessment, and containment and response measures, should a pandemic strain emerge.
An old expression says, "You can't slide uphill." The diffi cult work associated with preparedness for pandemic infl uenza will help bring Africa closer to the top of the hill, making it possible to effi ciently respond to this and other threats and, when necessary, slide toward a benefi cial outcome.