Maria P. Rebollo

Preventive chemotherapy as a strategy for elimination of neglected tropical parasitic diseases: endgame challenges

Global efforts to address neglected tropical diseases (NTDs) were stimulated in January 2012 by the London declaration at which 22 partners, including the Bill & Melinda Gates Foundation, World Bank, World Health Organization (WHO) and major pharmaceutical companies committed to sustaining and expanding NTD programmes to eliminate or eradicate 11 NTDs by 2020 to achieve the goals outlined in the recently published WHO road map. Here, we present the current context of preventive chemotherapy for some NTDs, and discuss the problems faced by programmes as they consider the ‘endgame’, such as difficulties of access to populations in post-conflict settings, limited human and financial resources, and the need to expand access to clean water and improved sanitation for schistosomiasis and soil-transmitted helminthiasis. In the case of onchocerciasis and lymphatic filariasis, ivermectin treatment carries a significant risk owing to serious adverse effects in some patients co-infected with the tropical eye worm Loa loa filariasis. We discuss the challenges of managing complex partnerships, and maintain advocacy messages for the continued support for elimination of these preventable diseases.

Toward the elimination of lymphatic filariasis by 2020: treatment update and impact assessment for the endgame

Lymphatic filariasis (LF) is an important public health problem endemic in 73 countries, where it is a major cause of acute and chronic morbidity and a significant impediment to socioeconomic development. It is targeted for elimination by 2020, through preventive chemotherapy using albendazole in combination with either ivermectin or diethylcarbamazine citrate. Preventive chemotherapy enables the regular and coordinated administration of safe, single-dose medications delivered through mass drug administration (MDA). Many countries are now scaling down MDA activities after achieving 100% geographic coverage and instituting monitoring and evaluation procedures to establish the impact of several consecutive rounds of MDA and determine if transmission has been interrupted. At the same time, countries yet to initiate MDA for elimination of LF will adopt improved mapping and coverage assessment protocols to accelerate the efforts for achieving global elimination by 2020. This review provides an update on treatment for LF and describes the current global status of the elimination efforts, transmission control processes and strategies for measuring impact and continuing surveillance after MDA has ceased.

The global distribution and transmission limits of lymphatic filariasis: past and present

BackgroundLymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination by 2020 and to guide elimination efforts countries have, in recent years, conducted extensive mapping surveys. Documenting the past and present distribution of LF and its environmental limits is important for a number of reasons. Here, we present an initiative to develop a global atlas of LF and present a new global map of the limits of LF transmission.MethodsWe undertook a systematic search and assembly of prevalence data worldwide and used a suite of environmental and climatic data and boosted regression trees (BRT) modelling to map the transmission limits of LF.ResultsData were identified for 66 of the 72 countries currently endemic and for a further 17 countries where LF is no longer endemic. Our map highlights a restricted and highly heterogeneous distribution in sub-Saharan Africa, with transmission more widespread in West Africa compared to east, central and southern Africa where pockets of transmission occur. Contemporary transmission occurs across much of south and South-east Asia and the Pacific. Interestingly, the risk map reflects environmental conditions suitable for LF transmission across Central and South America, including the southern States of America, although active transmission is only known in a few isolated foci. In countries that have eliminated LF, our predictions of environmental suitability are consistent with historical distribution.ConclusionsThe global distribution of LF is highly heterogeneous and geographically targeted and sustained control will be required to achieve elimination. This first global map can help evaluate the progress of interventions and guide surveillance activities.

Epidemiology and Individual, Household and Geographical Risk Factors of Podoconiosis in Ethiopia: Results from the First Nationwide Mapping

Although podoconiosis is one of the major causes of tropical lymphoedema and is endemic in Ethiopia its epidemiology and risk factors are poorly understood. Individual-level data for 129,959 individuals from 1,315 communities in 659 woreda (districts) were collected for a nationwide integrated survey of lymphatic filariasis and podoconiosis. Blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests. A clinical algorithm was used to reach a diagnosis of podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Bayesian multilevel models were used to identify individual and environmental risk factors. Overall, 8,110 of 129,959 (6.2%, 95% confidence interval [CI] 6.1–6.4%) surveyed individuals were identified with lymphoedema of the lower limb, of whom 5,253 (4.0%, 95% CI 3.9–4.1%) were confirmed to be podoconiosis cases. In multivariable analysis, being female, older, unmarried, washing the feet less frequently than daily, and being semiskilled or unemployed were significantly associated with increased risk of podoconiosis. Attending formal education and living in a house with a covered floor were associated with decreased risk of podoconiosis. Podoconiosis exhibits marked geographical variation across Ethiopia, with variation in risk associated with variation in rainfall, enhanced vegetation index, and altitude.

Integrated mapping of lymphatic filariasis and podoconiosis: lessons learnt from Ethiopia

BackgroundThe World Health Organization (WHO), international donors and partners have emphasized the importance of integrated control of neglected tropical diseases (NTDs). Integrated mapping of NTDs is a first step for integrated planning of programmes, proper resource allocation and monitoring progress of control. Integrated mapping has several advantages over disease specific mapping by reducing costs and enabling co-endemic areas to be more precisely identified. We designed and conducted integrated mapping of lymphatic filariasis (LF) and podoconiosis in Ethiopia; here we present the methods, challenges and lessons learnt.MethodsIntegrated mapping of 1315 communities across Ethiopia was accomplished within three months. Within these communities, 129,959 individuals provided blood samples that were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). Wb123 antibody tests were used to further establish exposure to LF in areas where at least one ICT positive individual was detected. A clinical algorithm was used to reliably diagnose podoconiosis by excluding other potential causes of lymphoedema of the lower limb.ResultsA total of 8110 individuals with leg swelling were interviewed and underwent physical examination. Smartphones linked to a central database were used to collect data, which facilitated real-time data entry and reduced costs compared to traditional paper-based data collection approach; their inbuilt Geographic Positioning System (GPS) function enabled simultaneous capture of geographical coordinates. The integrated approach led to efficient use of resources and rapid mapping of an enormous geographical area and was well received by survey staff and collaborators. Mobile based technology can be used for such large scale studies in resource constrained settings such as Ethiopia, with minimal challenges.ConclusionsThis was the first integrated mapping of podoconiosis and LF globally. Integrated mapping of podoconiosis and LF is feasible and, if properly planned, can be quickly achieved at nationwide scale.

Elimination of Lymphatic Filariasis in The Gambia

Background The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission. Methodology/Principal Finding We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997–2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6–7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts. Conclusions We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF.

Shrinking the lymphatic filariasis map: update on diagnostic tools for mapping and transmission monitoring

Lymphatic filariasis (LF), which is highly endemic in 73 countries worldwide, is targeted for elimination by 2020. The strategy for achieving this goal is based on 4 sequential programmatic steps: mapping, Mass drug administration (MDA) implementation, post-MDA surveillance and verification of LF elimination. All 4 stages of the implementation process are dependent on the availability of user friendly and highly sensitive rapid diagnostic tools. By the end of 2012, 59 countries had completed mapping for LF and Eritrea was the only country yet to start the process. Rolling out new diagnostic tools to facilitate the mapping process will enable an accelerated shrinking of the LF map to zero endemic countries by 2020. When the Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, diagnostic tools for LF were limited to clinical examination, detection of microfilaria (MF) by microscopy in night blood samples and detection of antibodies to native-antigen preparations. There has been a significant improvement in the traditional LF diagnostic methods in recent years and some new tools are now available. This paper provides an update on the human diagnostic tests available for LF and their current applications as tools in mapping and transmission monitoring. The values of entomological indicators and parasite detection and speciation methods applied to vector populations are also discussed.

Mapping and Modelling the Geographical Distribution and Environmental Limits of Podoconiosis in Ethiopia

Background Ethiopia is assumed to have the highest burden of podoconiosis globally, but the geographical distribution and environmental limits and correlates are yet to be fully investigated. In this paper we use data from a nationwide survey to address these issues. Methodology Our analyses are based on data arising from the integrated mapping of podoconiosis and lymphatic filariasis (LF) conducted in 2013, supplemented by data from an earlier mapping of LF in western Ethiopia in 2008–2010. The integrated mapping used woreda (district) health offices’ reports of podoconiosis and LF to guide selection of survey sites. A suite of environmental and climatic data and boosted regression tree (BRT) modelling was used to investigate environmental limits and predict the probability of podoconiosis occurrence. Principal Findings Data were available for 141,238 individuals from 1,442 communities in 775 districts from all nine regional states and two city administrations of Ethiopia. In 41.9% of surveyed districts no cases of podoconiosis were identified, with all districts in Affar, Dire Dawa, Somali and Gambella regional states lacking the disease. The disease was most common, with lymphoedema positivity rate exceeding 5%, in the central highlands of Ethiopia, in Amhara, Oromia and Southern Nations, Nationalities and Peoples regional states. BRT modelling indicated that the probability of podoconiosis occurrence increased with increasing altitude, precipitation and silt fraction of soil and decreased with population density and clay content. Based on the BRT model, we estimate that in 2010, 34.9 (95% confidence interval [CI]: 20.2–51.7) million people (i.e. 43.8%; 95% CI: 25.3–64.8% of Ethiopia’s national population) lived in areas environmentally suitable for the occurrence of podoconiosis. Conclusions Podoconiosis is more widespread in Ethiopia than previously estimated, but occurs in distinct geographical regions that are tied to identifiable environmental factors. The resultant maps can be used to guide programme planning and implementation and estimate disease burden in Ethiopia. This work provides a framework with which the geographical limits of podoconiosis could be delineated at a continental scale.

Cessation of Mass Drug Administration for Lymphatic Filariasis in Zanzibar in 2006: Was Transmission Interrupted?

Background Lymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4–6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped. Methodology/Principal Findings In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded. Conclusions Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.

Modelling the distribution and transmission intensity of lymphatic filariasis in sub-Saharan Africa prior to scaling up interventions: integrated use of geostatistical and mathematical modelling

BackgroundLymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination. The ability to interrupt transmission is, partly, influenced by the underlying intensity of transmission and its geographical variation. This information can also help guide the design of targeted surveillance activities. The present study uses a combination of geostatistical and mathematical modelling to predict the prevalence and transmission intensity of LF prior to the implementation of large-scale control in sub-Saharan Africa.MethodsA systematic search of the literature was undertaken to identify surveys on the prevalence of Wuchereria bancrofti microfilaraemia (mf), based on blood smears, and on the prevalence of antigenaemia, based on the use of an immuno-chromatographic card test (ICT). Using a suite of environmental and demographic data, spatiotemporal multivariate models were fitted separately for mf prevalence and ICT-based prevalence within a Bayesian framework and used to make predictions for non-sampled areas. Maps of the dominant vector species of LF were also developed. The maps of predicted prevalence and vector distribution were linked to mathematical models of the transmission dynamics of LF to infer the intensity of transmission, quantified by the basic reproductive number (R0).ResultsThe literature search identified 1267 surveys that provide suitable data on the prevalence of mf and 2817 surveys that report the prevalence of antigenaemia. Distinct spatial predictions arose from the models for mf prevalence and ICT-based prevalence, with a wider geographical distribution when using ICT-based data. The vector distribution maps demonstrated the spatial variation of LF vector species. Mathematical modelling showed that the reproduction number (R0) estimates vary from 2.7 to 30, with large variations between and within regions.ConclusionsLF transmission is highly heterogeneous, and the developed maps can help guide intervention, monitoring and surveillance strategies as countries progress towards LF elimination.