Simon Brooker

Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm

The three main soil-transmitted helminth infections, ascariasis, trichuriasis, and hookworm, are common clinical disorders in man. The gastrointestinal tract of a child living in poverty in a less developed country is likely to be parasitised with at least one, and in many cases all three soil-transmitted helminths, with resultant impairments in physical, intellectual, and cognitive development. The benzimidazole anthelmintics, mebendazole and albendazole, are commonly used to remove these infections. The use of these drugs is not limited to treatment of symptomatic soil-transmitted helminth infections, but also for large-scale prevention of morbidity in children living in endemic areas. As a result of data showing improvements in child health and education after deworming, and the burden of disease attributed to soil-transmitted helminths, the worldwide community is awakening to the importance of these infections. Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.

A world malaria map: Plasmodium falciparum endemicity in 2007

Background Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. Methods and Findings A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2–10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2−10 ≤ 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2−10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2−10 ≥ 40%) areas. High endemicity was widespread in the Africa+ region, where 0.35 billion people are at this level of risk. Most of the rest live at intermediate risk (0.20 billion), with a smaller number (0.11 billion) at low stable risk. Conclusions High levels of P. falciparum malaria endemicity are common in Africa. Uniformly low endemic levels are found in the Americas. Low endemicity is also widespread in CSE Asia, but pockets of intermediate and very rarely high transmission remain. There are therefore significant opportunities for malaria control in Africa and for malaria elimination elsewhere. This 2007 global P. falciparum malaria endemicity map is the first of a series with which it will be possible to monitor and evaluate the progress of this intervention process.

Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa

Health policy making in developing countries requires estimates of the (global) burden of disease. At present, most of the available data on schistosomiasis is limited to numbers of individuals harbouring the infection. We explored the relationship between the presence of schistosome infection and clinical morbidity, in order to estimate numbers of individuals with disease-specific morbidity for Schistosoma haematobium and Schistosoma mansoni infection in sub-Saharan Africa. We searched the literature for cross-sectional data from field studies reporting both schistosome infection and morbidity. This was used to derive a functional relationship between morbidity and infection. After standardisation for diagnostic method, the number of individuals with specific types of clinical morbidity or pathology was predicted. As only aggregated prevalences of infection were available for countries or areas, we adjusted for heterogeneity in infection levels within communities in those countries. In total, 70 million individuals out of 682 million (2000 estimate) in sub-Saharan Africa were estimated to experience haematuria in the last 2 weeks associated with S. haematobium infection, and 32 million dysuria. Ultrasound detected serious consequences of S. haematobium, major bladder wall pathology and major hydronephrosis, were predicted at 18 and 10 million, respectively. Infection with S. mansoni was estimated to cause diarrhoea in 0.78 million individuals, blood in stool in 4.4 million and hepatomegaly in 8.5 million. As the associations between prevalence of S. mansoni infection and prevalence of diarrhoea and blood in stool were not very clear, the resulting estimates may be underestimations. Using the very limited data available, we estimated the mortality rates due to non-functioning kidney (from S. haematobium) and haematemesis (from S. mansoni) at 150000 and 130000 per year. Given the overall high number of cases with schistosomiasis-related disease and associated death, we conclude that schistosomiasis remains an important public health problem in sub-Saharan Africa.

Global numbers of infection and disease burden of soil transmitted helminth infections in 2010

BackgroundQuantifying the burden of parasitic diseases in relation to other diseases and injuries requires reliable estimates of prevalence for each disease and an analytic framework within which to estimate attributable morbidity and mortality. Here we use data included in the Global Atlas of Helminth Infection to derive new global estimates of numbers infected with intestinal nematodes (soil-transmitted helminths, STH: Ascaris lumbricoides, Trichuris trichiura and the hookworms) and use disability-adjusted life years (DALYs) to estimate disease burden.MethodsPrevalence data for 6,091 locations in 118 countries were sourced and used to estimate age-stratified mean prevalence for sub-national administrative units via a combination of model-based geostatistics (for sub-Saharan Africa) and empirical approaches (for all other regions). Geographical variation in infection prevalence within these units was approximated using modelled logit-normal distributions, and numbers of individuals with infection intensities above given thresholds estimated for each species using negative binomial distributions and age-specific worm/egg burden thresholds. Finally, age-stratified prevalence estimates for each level of infection intensity were incorporated into the Global Burden of Disease Study 2010 analytic framework to estimate the global burden of morbidity and mortality associated with each STH infection.ResultsGlobally, an estimated 438.9 million people (95% Credible Interval (CI), 406.3 - 480.2 million) were infected with hookworm in 2010, 819.0 million (95% CI, 771.7 – 891.6 million) with A. lumbricoides and 464.6 million (95% CI, 429.6 – 508.0 million) with T. trichiura. Of the 4.98 million years lived with disability (YLDs) attributable to STH, 65% were attributable to hookworm, 22% to A. lumbricoides and the remaining 13% to T. trichiura. The vast majority of STH infections (67%) and YLDs (68%) occurred in Asia. When considering YLDs relative to total populations at risk however, the burden distribution varied more considerably within major global regions than between them.ConclusionImprovements in the cartography of helminth infection, combined with mathematical modelling approaches, have resulted in the most comprehensive contemporary estimates for the public health burden of STH. These numbers form an important benchmark upon which to evaluate future scale-up of major control efforts.

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases

The publication of the Global Burden of Disease Study 2010 (GBD 2010) and the accompanying collection of Lancet articles in December 2012 provided the most comprehensive attempt to quantify the burden of almost 300 diseases, injuries, and risk factors, including neglected tropical diseases (NTDs) [1]–[3]. The disability-adjusted life year (DALY), the metric used in the GBD 2010, is a tool which may be used to assess and compare the relative impact of a number of diseases locally and globally [4]–[6]. Table 1 lists the major NTDs as defined by the World Health Organization (WHO) [7] and their estimated DALYs [1]. With a few exceptions, most of the NTDs currently listed by the WHO [7] or those on the expanded list from PLOS Neglected Tropical Diseases [8] are disablers rather than killers, so the DALY estimates represent one of the few metrics available that could fully embrace the chronic effects of these infections. Table 1 Estimated DALYs (in millions) of the NTDs from the Global Burden of Disease Study 2010. Disease DALYs from GBD 2010 (numbers in parentheses indicate 95% confidence intervals) [1] NTDs 26.06 (20.30–35.12) Intestinal nematode infections 5.19 (2.98–8.81) Hookworm disease 3.23 (1.70–5.73) Ascariasis 1.32 (0.71–2.35) Trichuriasis 0.64 (0.35–1.06) Leishmaniasis 3.32 (2.18–4.90) Schistosomiasis 3.31 (1.70–6.26) Lymphatic filariasis 2.78 (1.8–4.00) Food-borne trematodiases 1.88 (0.70–4.84) Rabies 1.46 ((0.85–2.66) Dengue 0.83 (0.34–1.41) African trypanosomiasis 0.56 (0.08–1.77) Chagas disease 0.55 (0.27–1.05) Cysticercosis 0.50 (0.38–0.66) Onchocerciasis 0.49 (0.36–0.66) Trachoma 0.33 (0.24–0.44) Echinococcosis 0.14 (0.07–0.29) Yellow fever <0.001 Other NTDs * 4.72 (3.53–6.35) Open in a separate window * Relapsing fevers, typhus fever, spotted fever, Q fever, other rickettsioses, other mosquito-borne viral fevers, unspecified arthropod-borne viral fever, arenaviral haemorrhagic fever, toxoplasmosis, unspecified protozoal disease, taeniasis, diphyllobothriasis and sparganosis, other cestode infections, dracunculiasis, trichinellosis, strongyloidiasis, enterobiasis, and other helminthiases. Even DALYs, however, do not tell the complete story of the harmful effects from NTDs. Some of the specific and potential shortcomings of GBD 2010 have been highlighted elsewhere [9]. Furthermore, DALYs measure only direct health loss and, for example, do not consider the economic impact of the NTDs that results from detrimental effects on school attendance and child development, agriculture (especially from zoonotic NTDs), and overall economic productivity [10], [11]. Nor do DALYs account for direct costs of treatment, surveillance, and prevention measures. Yet, economic impact has emerged as an essential feature of the NTDs, which may trap people in a cycle of poverty and disease [10]–[12]. Additional aspects not considered by the DALY metrics are the important elements of social stigma for many of the NTDs and the spillover effects to family and community members [13], [14], loss of tourism [15], and health system overload (e.g., during dengue outbreaks). Ultimately NTD control and elimination efforts could produce social and economic benefits not necessarily reflected in the DALY metrics, especially among the most affected poor communities [11].

Global Epidemiology, Ecology and Control of Soil-Transmitted Helminth Infections

Soil-transmitted helminth (STH) infections are among the most prevalent of chronic human infections worldwide. Based on the demonstrable impact on child development, there is a global commitment to finance and implement control strategies with a focus on school-based chemotherapy programmes. The major obstacle to the implementation of cost-effective control is the lack of accurate descriptions of the geographical distribution of infection. In recent years, considerable progress has been made in the use of geographical information systems (GIS) and remote sensing (RS) to better understand helminth ecology and epidemiology, and to develop low-cost ways to identify target populations for treatment. This review explores how this information has been used practically to guide large-scale control programmes. The use of satellite-derived environmental data has yielded new insights into the ecology of infection at a geographical scale that has proven impossible to address using more traditional approaches, and has in turn allowed spatial distributions of infection prevalence to be predicted robustly by statistical approaches. GIS/RS have increasingly been used in the context of large-scale helminth control programmes, including not only STH infections but also those focusing on schistosomiasis, filariasis and onchocerciasis. The experience indicates that GIS/RS provides a cost-effective approach to designing and monitoring programmes at realistic scales. Importantly, the use of this approach has begun to transition from being a specialist approach of international vertical programmes to becoming a routine tool in developing public sector control programmes. GIS/RS is used here to describe the global distribution of STH infections and to estimate the number of infections in school-age children in sub-Saharan Africa (89.9 million) and the annual cost of providing a single anthelmintic treatment using a school-based approach (US

Human hookworm infection in the 21st century.

5.0-7.6 million). These are the first estimates at a continental scale to explicitly include the fine spatial distribution of infection prevalence and population, and suggest that traditional methods have overestimated the situation. The results suggest that continent-wide control of parasites is, from a financial perspective, an attainable goal.

Hookworm-Related Anaemia among Pregnant Women: A Systematic Review.

The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding of many aspects of this globally widespread parasite. This chapter reviews recent advances in our understanding in the biology, immunology, epidemiology, public health significance and control of hookworm, and to look forward to the study of this important parasite in the 21st century. Advances in molecular biology has lead to the identification of a variety of new molecules from hookworms, which have importance either in the molecular pathogenesis of hookworm infection or in the host-parasite relationship; some are also promising vaccine targets. At present, relatively little is known about the immune responses to hookworm infection, although it has recently been speculated that hookworm and other helminths may modulate specific immune responses to other pathogens and vaccines. Our epidemiological understanding of hookworm has improved through the development of mathematical models of transmission dynamics, which coupled with decades of field research across multiple epidemiological settings, have shown that certain population characteristics can now be recognised as common to the epidemiology, population biology and control of hookworm and other helminth species. Recent recognition of the subtle, but significant, impact of hookworm on health and education, together with the simplicity, safety, low cost and efficacy of chemotherapy has spurred international efforts to control the morbidity due to infection. Large-scale treatment programmes are currently underway, ideally supported by health education and integrated with the provision of improved water and sanitation. There are also on-going efforts to develop novel anthelmintic drugs and anti-hookworm vaccines.

Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya

Background and Objectives Hookworm infection is among the major causes of anaemia in poor communities, but its importance in causing maternal anaemia is poorly understood, and this has hampered effective lobbying for the inclusion of anthelmintic treatment in maternal health packages. We sought to review existing evidence on the role of hookworm as a risk factor for anaemia among pregnant women. We also estimate the number of hookworm infections in pregnant women in sub-Saharan Africa (SSA). Methods Structured searches using MEDLINE and EMBASE as well as manual searches of reference lists were conducted, and unpublished data were obtained by contacting authors. Papers were independently reviewed by two authors, and relevant data were extracted. We compared haemoglobin concentration (Hb) according to intensity of hookworm infection and calculated standardised mean differences and 95% confidence intervals. To estimate the number of pregnant women, we used population surfaces and a spatial model of hookworm prevalence. Findings One hundred and five reports were screened and 19 were eligible for inclusion: 13 cross-sectional studies, 2 randomised controlled trials, 2 non-randomised treatment trials and 2 observational studies. Comparing uninfected women and women lightly (1–1,999 eggs/gram [epg]) infected with hookworm, the standardised mean difference (SMD) was −0.24 (95% CI: −0.36 to −0.13). The SMD between women heavily (4000+ epg) infected and those lightly infected was −0.57 (95% CI: −0.87 to −0.26). All identified intervention studies showed a benefit of deworming for maternal or child health, but since a variety of outcomes measures were employed, quantitative evaluation was not possible. We estimate that 37.7 million women of reproductive age in SSA are infected with hookworm in 2005 and that approximately 6.9 million pregnant women are infected. Conclusions Evidence indicates that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women in poor countries. There are insufficient data to quantify the benefits of deworming, and further studies are warranted. Given that between a quarter and a third of pregnant women in SSA are infected with hookworm and at risk of preventable hookworm-related anaemia, efforts should be made to increase the coverage of anthelmintic treatment among pregnant women.

The potential of geographical information systems and remote sensing in the epidemiology and control of human helminth infections

The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May–July 2002. Household surveys of cases and age‐matched controls were conducted to collect information on household construction, exposure factors and socio‐economic status. Household geographical location and altitude were determined using a hand‐held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.