Neglected Tropical Diseases among the Association of Southeast Asian Nations (ASEAN): Overview and Update

The ten member states of the Association of Southeast Asian Nations (ASEAN) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (NTDs). Almost 200 million people live in extreme poverty in ASEAN countries, mostly in the low or lower middle-income countries of Indonesia, the Philippines, Myanmar, Viet Nam, and Cambodia, and many of them are affected by at least one NTD. However, NTDs are prevalent even among upper middle-income ASEAN countries such as Malaysia and Thailand, especially among the indigenous populations. The three major intestinal helminth infections are the most common NTDs; each helminthiasis is associated with approximately 100 million infections in the region. In addition, more than 10 million people suffer from either liver or intestinal fluke infections, as well as schistosomiasis and lymphatic filariasis (LF). Intestinal protozoan infections are widespread, while leishmaniasis has emerged in Thailand, and zoonotic malaria (Plasmodium knowlesi infection) causes severe morbidity in Malaysia. Melioidosis has emerged as an important bacterial NTD, as have selected rickettsial infections, and leptospirosis. Leprosy, yaws, and trachoma are still endemic in focal areas. Almost 70 million cases of dengue fever occur annually in ASEAN countries, such that this arboviral infection is now one of the most common and economically important NTDs in the region. A number of other arboviral and zoonotic viral infections have also emerged, including Japanese encephalitis; tick-borne viral infections; Nipah virus, a zoonosis present in fruit bats; and enterovirus 71 infection. There are urgent needs to expand surveillance activities in ASEAN countries, as well as to ensure mass drug administration is provided to populations at risk for intestinal helminth and fluke infections, LF, trachoma, and yaws. An ASEAN Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation provides a policy framework for the development of new control and elimination tools. Together with prominent research institutions and universities, the World Health Organization (WHO), and its regional offices, these organizations could implement important public health improvements through NTD control and elimination in the coming decade.     

Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control

The neglected tropical diseases (NTDs) are highly endemic but patchily distributed among the 20 countries and almost 400 million people of the Middle East and North Africa (MENA) region, and disproportionately affect an estimated 65 million people living on less than US$2 per day. Egypt has the largest number of people living in poverty of any MENA nation, while Yemen has the highest prevalence of people living in poverty. These two nations stand out for having suffered the highest rates of many NTDs, including the soil-transmitted nematode infections, filarial infections, schistosomiasis, fascioliasis, leprosy, and trachoma, although they should be recognized for recent measures aimed at NTD control. Leishmaniasis, especially cutaneous leishmaniasis, is endemic in Syria, Iran, Iraq, Libya, Morocco, and elsewhere in the region. Both zoonotic (Leishmania major) and anthroponotic (Leishmania tropica) forms are endemic in MENA in rural arid regions and urban regions, respectively. Other endemic zoonotic NTDs include cystic echinococcosis, fascioliasis, and brucellosis. Dengue is endemic in Saudi Arabia, where Rift Valley fever and Alkhurma hemorrhagic fever have also emerged. Great strides have been made towards elimination of several endemic NTDs, including lymphatic filariasis in Egypt and Yemen; schistosomiasis in Iran, Morocco, and Oman; and trachoma in Morocco, Algeria, Iran, Libya, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates. A particularly noteworthy achievement is the long battle waged against schistosomiasis in Egypt, where prevalence has been brought down by regular praziquantel treatment. Conflict and human and animal migrations are key social determinants in preventing the control or elimination of NTDs in the MENA, while local political will, strengthened international and intersectoral cooperative efforts for surveillance, mass drug administration, and vaccination are essential for elimination.     

Diagnosing point-of-care diagnostics for neglected tropical diseases

Inadequate and nonintegrated diagnostics are the Achilles’ heel of global efforts to monitor, control, and eradicate neglected tropical diseases (NTDs). While treatment is often available, NTDs are endemic among marginalized populations, due to the unavailability or inadequacy of diagnostic tests that cause empirical misdiagnoses. The need of the hour is early diagnosis at the point-of-care (PoC) of NTD patients. Here, we review the status quo of PoC diagnostic tests and practices for all of the 24 NTDs identified in the World Health Organization’s (WHO) 2021–2030 roadmap, based on their different diagnostic requirements. We discuss the capabilities and shortcomings of current diagnostic tests, identify diagnostic needs, and formulate prerequisites of relevant PoC tests. Next to technical requirements, we stress the importance of availability and awareness programs for establishing PoC tests that fit endemic resource-limited settings. Better understanding of NTD diagnostics will pave the path for setting realistic goals for healthcare in areas with minimal resources, thereby alleviating the global healthcare burden.     

The contribution of mass drug administration to global health: past,present and future

Mass drug administration (MDA) is a means of delivering safe and inexpensive essential medicines based on the principles of preventive chemotherapy, where populations or sub-populations are offered treatment without individual diagnosis. High-coverage MDA in endemic areas aims to prevent and alleviate symptoms and morbidity on the one hand and can reduce transmission on the other, together improving global health. MDA is the recommended strategy of the World Health Organisation to control or eliminate several neglected tropical diseases (NTDs). More than 700 million people now receive these essential NTD medicines annually. The combined cost of integrated NTD MDA has been calculated to be in the order of $0.50 per person per year. Activities have recently been expanded due, in part, to the proposed attempt to eliminate certain NTDs in the coming two decades. More than 1.9 billion people need to receive MDA annually across several years if these targets are to be met. Such extensive coverage will require additional avenues of financial support, expanded monitoring and evaluation focusing on impact and drug efficacy, as well as new diagnostic tools and social science strategies to encourage adherence. MDA is a means to help reduce the burden of disease, and hence poverty, among the poorest sector of populations. It has already made significant improvements to global health and productivity and has the potential for further successes, particularly where incorporated into sanitation and education programmes. However logistical, financial and biological challenges remain.     

Reviewing Dengue: Still a Neglected Tropical Disease?

Dengue is currently listed as a “neglected tropical disease” (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003–2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.     

Scoping review of Neglected Tropical Disease Interventions and Health Promotion: A framework for successful NTD interventions as evidenced by the literature

BackgroundNeglected Tropical Diseases (NTDs) affect more than one billion people globally. A Public Library of Science (PLOS) journal dedicated to NTDs lists almost forty NTDs, while the WHO prioritises twenty NTDs. A person can be affected by more than one disease at the same time from a range of infectious and non-infectious agents. Many of these diseases are preventable, and could be eliminated with various public health, health promotion and medical interventions. This scoping review aims to determine the extent of the body of literature on NTD interventions and health promotion activities, and to provide an overview of their focus while providing recommendations for best practice going forward. This scoping review includes both the identification of relevant articles through the snowball method and an electronic database using key search terms. A two-phased screening process was used to assess the relevance of studies identified in the search–an initial screening review followed by data characterization using the Critical Appraisal Skills Program (CASP). Studies were eligible for inclusion if they broadly described the characteristics, methods, and approaches of (1) NTD interventions and/or (2) community health promotion.Principal findings90 articles met the CASP criteria partially or fully and then underwent a qualitative synthesis to be included in the review. 75 articles specifically focus on NTD interventions and approaches to their control, treatment, and elimination, while 15 focus specifically on health promotion and provide a grounding in health promotion theories and perspectives. 29 of the articles provided a global perspective to control, treatment, or elimination of NTDs through policy briefs or literature reviews. 19 of the articles focused on providing strategies for NTDs more generally while 12 addressed multiple NTDs or their interaction with other infectious diseases. Of the 20 NTDs categorized by the WHO and the expanded NTD list identified by PLOS NTDs, several NTDs did not appear in the database search on NTD interventions and health promotion, including yaws, fascioliasis, and chromoblastomycosis.ConclusionsBased on the literature we have identified the four core components of best practices including programmatic interventions, multi sectoral and multi-level interventions, adopting a social and ecological model and clearly defining ‘community.’ NTD interventions tend to centre on mass drug administration (MDA), particularly because NTDs were branded as such based on their being amenable to MDA. However, there remains a need for intervention approaches that also include multiple strategies that inform a larger multi-disease and multi-sectoral programme. Many NTD strategies include a focus on WASH and should also incorporate the social and ecological determinants of NTDs, suggesting a preventative and systems approach to health, not just a treatment-based approach. Developing strong communities and incorporating social rehabilitation at the sublocation level (e.g. hospital) could benefit several NTDs and infectious diseases through a multi-disease, multi-sectoral, and multi-lateral approach. Finally, it is important the ‘community’ is clearly defined in each intervention, and that community members are included in intervention activities and viewed as assets to interventions.     

Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk

BackgroundIn the past decade, research on neglected tropical diseases (NTDs) has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania.ConclusionsNTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national) levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease interventions.     

Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa

Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well-documented economic impacts. However, much less is known about the population-level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual-based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions.     

Eliminating onchocerciasis within the Meme River Basin of Cameroon: A social-ecological approach to understanding everyday realities and health systems

BackgroundOnchocerciasis affects some of the world’s most marginalized people, perpetuating poverty and inequalities. Mass Drug Administration (MDA) with Ivermectin has taken place within the Meme River basin region in Cameroon for over 15 years. Despite this, onchocerciasis is still prevalent in the region due to existing and emerging contextual challenges. Using a social-ecological approach we explore the everyday realities of communities, highlighting the challenges and potential solutions that could support Neglected Tropical Disease (NTD) programmes when transitioning from control to elimination of onchocerciasis in this highly endemic area and other similar communities.Methodology/Principal findingIn-depth interviews (71) with community members and Community Drug Distributors (CDDs) were conducted to understand current knowledge, attitudes, and behaviours in relation to transmission, prevention and treatment of onchocerciasis. Through application of the social-ecological model, four key themes were identified: 1. Contextual factors on health promotion interventions (Onchocerciasis history and understanding of the disease, prevention and mitigation strategies and MDA experience); 2. Social determinants (poverty and livelihoods, economic and social impacts on CDD volunteers and stigma); 3. Environmental determinants (exposure, housing, occupation and poverty); and 4. health seeking pathways and decision making for treatment (access, cost and preferable treatment routes).We discuss these core and cross cutting themes (gender differences and community participation/ownership) in relation to intersectoral collaboration, gender equity and health systems support, making recommendations for NTD programmes within the context of integrated and interdisciplinary approaches. These include the need for; intersectional and gender analysis at the local level, addressing environmental dimensions of onchocerciasis through integrated and regular health promotion, vector control strategies and access to safe water sources; reflection and action that embeds responses to social and economic barriers to MDA; integrated case detection and management that is responsive to onchocerciasis symptoms and related stigma and a fair and just support network for CDDs.Conclusion/SignificanceNTD programmes need to respond to diverse community circumstances and behaviours. Communities are not a homogeneous risk group and treating them in this way will delay elimination. A deeper understanding of individual needs and their capacity to seek prevention and treatment must be considered if onchocerciasis is to be eliminated and the remaining impacts managed.     

Does prenatal screening for 5,10-methylenetetrahydrofolate reductase (MTHFR) mutations in high-risk neural tube defect pregnancies make sense?

Despite the fact that neural tube defects (NTDs) are the most common congenital malformations of the central nervous system, investigators have yet to identify responsible gene(s). Research efforts have been productive in the identification of environmental factors, such as periconceptional folic acid supplementation, that modulate risk for the development of NTDs. Studies of the folic acid biosynthetic pathway led to the discovery of an association between elevated levels of homocysteine and NTD risk. Researchers subsequently identified single nucleotide polymorphisms in the gene coding for the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR). Association studies suggested it was a potential risk factor for NTDs, because the thermolabile form of the enzyme led to elevated homocysteine concentrations when folic acid intake is low. Numerous studies analyzing MTHFR variants have resulted in positive associations with increased NTD risk only in certain populations, suggesting that these variants are not large contributors to the etiology of NTDs. With our limited understanding of the genes involved in regulating NTD susceptibility, the paucity of data on how folic acid protects the developing embryo, as well as the observed decrease in birth prevalence of NTDs following folic acid supplementation and food fortification, it makes little sense for prospective parents to be tested for MTHFR variants, or for variants of other known folate pathway genes.     

Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review

BackgroundFolate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data.ConclusionsMany WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.     

Asymmetries of poverty: why global burden of disease valuations underestimate the burden of neglected tropical diseases

The disability-adjusted life year (DALY) initially appeared attractive as a health metric in the Global Burden of Disease (GBD) program, as it purports to be a comprehensive health assessment that encompassed premature mortality, morbidity, impairment, and disability. It was originally thought that the DALY would be useful in policy settings, reflecting normative valuations as a standardized unit of ill health. However, the design of the DALY and its use in policy estimates contain inherent flaws that result in systematic undervaluation of the importance of chronic diseases, such as many of the neglected tropical diseases (NTDs), in world health. The conceptual design of the DALY comes out of a perspective largely focused on the individual risk rather than the ecology of disease, thus failing to acknowledge the implications of context on the burden of disease for the poor. It is nonrepresentative of the impact of poverty on disability, which results in the significant underestimation of disability weights for chronic diseases such as the NTDs. Finally, the application of the DALY in policy estimates does not account for the nonlinear effects of poverty in the cost-utility analysis of disease control, effectively discounting the utility of comprehensively treating NTDs. The present DALY framework needs to be substantially revised if the GBD is to become a valid and useful system for determining health priorities.     

Public Awareness and Knowledge of Neglected Tropical Diseases (NTDs) Control Activities in Abuja,Nigeria

The need to engage the public in Neglected Tropical Diseases (NTDs) control activities has become imperative in the context of morbidity reduction through preventive chemotherapy and community participation. Therefore, a survey was conducted among the general public to assess their knowledge and awareness of NTDs control activities in Nigeria. A simple questionnaire was administered to the general public attending a job fair in Abuja, Nigeria. Of the 461 respondents, a significant proportion 337 (73.1%) have heard of NTD before, but only 291 (63.1%) have good knowledge about NTDs. However, among the specific NTDs, only the control of onchocerciasis (50.8%) was of average public awareness in Nigeria, while all the other NTDs control activities were significantly less known to the general public. 397 (87.1%) stated that government support for NTD control activities is poor and were willing to assist to advocate for NTDs control. This survey demonstrates that despite government''s numerous activities towards the control of NTDs in Nigeria, there is little sensitization of the general public. There is a need for policy changes that would raise the participation and involvement of the general public in NTDs control activities for sustainability.     

Canadian contributions to research on neglected tropical diseases

BackgroundThe World Health Organization’s (WHO) Neglected Tropical Disease (NTD) Road Map for 2021–2030 was recently endorsed by all member states at the World Health Assembly in November 2020. Although only 3 of the 20 NTDs are endemic in Canada (i.e., echinococcosis, rabies, and scabies), the Canadian research community has contributed to advancing the knowledge base of all 20 NTDs. Previous research comprehensively detailed Canadian research on 11 NTDs between 1950 and 2010 using a network analysis approach. The specific objective of the present analysis was to update the publication record over the last decade (2010–2019) to include all 20 NTDs.Materials and methodsA bibliometric analysis was conducted in Scopus and Web of Science databases (for English or French articles published between January 1, 2010 and December 31, 2019) using appropriate search terms for each of the 20 NTDs and where at least 1 of the authors had a Canadian institution address. A 21st search was added to include publications including multiple NTDs or a discussion of NTDs in general. Following assessment of inclusion and exclusion criteria, 2 reviewers independently screened all abstracts, with discordant observations rereviewed to arrive at an agreement. Duplicates were removed.ResultsA total of 1,790 publications were retrieved (1,738 with a disease–specific NTD focus and 52 with a general NTD focus, resulting in 1,659 unique publications), giving an average of over 160 articles per year. Over 80% were classified as full–length research articles. The top 3 journals in terms of frequency were PLOS Neglected Tropical Diseases, PLOS ONE, and the American Journal of Tropical Medicine and Hygiene. Authors’ institutions were from all Canadian provinces. While all 20 NTDs were addressed in these publications, the 5 most commonly studied were leishmaniasis, dengue fever and chikungunya, Chagas disease, soil–transmitted helminthiases, and rabies.ConclusionsCanadian researchers across the country have contributed to the evidence base of all 20 NTDs, publishing an average of over 160 publications per year between 2010 and 2019. As WHO NTD Road Map 2021–2030 rolls out globally, the Canadian research community, in collaboration with its partners and in solidarity with people living in vulnerable circumstances in endemic regions worldwide, is well positioned to meet future research challenges so that the goal of eliminating the disease burden attributable to NTDs can be achieved.     

Decline in the prevalence of neural tube defects following folic acid fortification and its cost-benefit in South Africa

BACKGROUND: In October 2003 South Africa embarked on a program of folic acid fortification of staple foods. We measured the change in prevalence of NTDs before and after fortification and assessed the cost benefit of this primary health care intervention. METHODS: Since the beginning of 2002 an ecological study was conducted among 12 public hospitals in four provinces of South Africa. NTDs as well as other birth defect rates were reported before and after fortification. Mortality data were also collected from two independent sources. RESULTS: This study shows a significant decline in the prevalence of NTDs following folic acid fortification in South Africa. A decline of 30.5% was observed, from 1.41 to 0.98 per 1,000 births (RR = 0.69; 95% CI: 0.49–0.98; p = .0379). The cost benefit ratio in averting NTDs was 46 to 1. Spina bifida showed a significant decline of 41.6% compared to 10.9% for anencephaly. Additionally, oro‐facial clefts showed no significant decline (5.7%). An independent perinatal mortality surveillance system also shows a significant decline (65.9%) in NTD perinatal deaths, and in NTD infant mortality (38.8%). CONCLUSIONS: The decrease in NTD rates postfortification is consistent with decreases observed in other countries that have fortified their food supplies. This is the first time this has been observed in a predominantly African population. The economic benefit flowing from the prevention of NTDs greatly exceeds the costs of implementing folic acid fortification. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Strengthening data collection for neglected tropical diseases: What data are needed for models to better inform tailored intervention programmes?

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.     

Eliminating the Neglected Tropical Diseases: Translational Science and New Technologies

Today, the World Health Organization recognizes 17 major parasitic and related infections as the neglected tropical diseases (NTDs). Despite recent gains in the understanding of the nature and prevalence of NTDs, as well as successes in recent scaled-up preventive chemotherapy strategies and other health interventions, the NTDs continue to rank among the world’s greatest global health problems. For virtually all of the NTDs (including those slated for elimination under the auspices of a 2012 London Declaration for NTDs and a 2013 World Health Assembly resolution [WHA 66.12]), additional control mechanisms and tools are needed, including new NTD drugs, vaccines, diagnostics, and vector control agents and strategies. Elimination will not be possible without these new tools. Here we summarize some of the key challenges in translational science to develop and introduce these new technologies in order to ensure success in global NTD elimination efforts.     

Interactions between Global Health Initiatives and Country Health Systems: The Case of a Neglected Tropical Diseases Control Program in Mali

Background

Recently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali''s health system where it was first implemented in 2007.

Methods and Findings

Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local health systems. The campaign budget barely financed institutional strengthening. Finally, though the initiative rested at least partially on national structures, pressures to absorb donated drugs and reach short-term coverage results contributed to distract energies away from other priorities, including overall health systems strengthening.

Conclusions

Our study indicates that positive synergies between disease specific interventions and nontargeted health services are more likely to occur in robust health services and systems. Disease-specific interventions implemented as parallel activities in fragile health services may further weaken their responsiveness to community needs, especially when several GHIs operate simultaneously. Health system strengthening will not result from the sum of selective global interventions but requires a comprehensive approach.