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In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis.

Strongyloidiasis is a disease caused by an infection with a soil-transmitted helminth that affects, according to largely varying estimates, between 30 million and 370 million people worldwide [1,2]. Not officially listed as a neglected tropical disease (NTD), strongyloidiasis stands out as particularly overlooked [3]. Indeed, there is a paucity of research and public health efforts pertaining to strongyloidiasis. Hence, clinical, diagnostic, epidemiologic, treatment, and control aspects are not adequately addressed to allow for an effective management of the disease, both in clinical medicine and in public health programs [4]. The manifold signs and symptoms caused by Strongyloides stercoralis infection, coupled with the helminth’s unique potential to cause lifelong, persistent infection, make strongyloidiasis relevant beyond tropical and subtropical geographic regions, where, however, most of the disease burden is concentrated. Indeed, strongyloidiasis is acquired through contact with contaminated soil, and the infection is, thus, primarily transmitted in areas with poor sanitation, inadequate access to clean water, and lack of hygiene. While the actual morbidity of chronically infected, immunocompetent individuals is subtle and difficult to appreciate [5], the particular importance of this parasitic worm is linked to its potential for maintaining lifelong autoinfections and causing a life-threatening hyperinfection syndrome in immunocompromised individuals [6]. Lack of point-of-care (POC) diagnostics and poor availability of, and access to, ivermectin (the current treatment of choice) are the two most significant bottlenecks that hinder effective management of the disease both in clinical and in public health settings. Examples of the management and importance of strongyloidiasis in two clinical contexts (in a tropical setting and a high-income country) and from a public health perspective are given in Boxes 1–3. Box 1. Individual Living in an Endemic Area with Diarrhea, Abdominal Pain, Pruritus, and Significant Dermatological Manifestations [10] A 43-year-old male farmer, living in the rural eastern part of Preah Vihear province, northern Cambodia, was diagnosed with a heavy Strongyloides stercoralis infection (924 and 478 larvae present in two Baermann examinations). Additionally, larvae and adult S. stercoralis were detected in Koga agar plate culture examinations of the stools. The patient was co-infected with hookworm and presented with abdominal pain, diarrhea, nausea, vomiting, fever, and a pronounced and persistent skin rash, which had been present with extensive itching for more than two years. The rash was observed on the back, chest, abdomen, and extremities and, due to frequent and intense scratching, showed signs of focal infection. Three weeks after treatment with a single oral dose of ivermectin (200 μg/kg) and a single oral dose of mebendazole, the patient’s rash had almost disappeared, and he was free of episodes of intensive itching.

Background\ud \ud Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.\ud \ud Methods and Findings\ud \ud The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.\ud \ud Conclusions \ud \ud Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.

Background\ud \ud Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention.\ud \ud Methodology/Principal Findings\ud \ud Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events.\ud \ud Conclusions/Significance\ud \ud Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs.

The symptomatology associated with human fascioliasis has been studied mostly in hospitalised subjects. Very little is known about clinical signs and symptoms associated with infections in human endemic zones, as well as on possible new ways of transmission which might be responsible for the increased number of human cases reported in recent years. This information is of great importance to facilitate diagnosis and plan effective control measures. With the objective to identify clinical signs, blood tests, household characteristics and hygienic habits associated with human fascioliasis, a cross-sectional case-control study was implemented among the rural population of three endemic foci in the Nile Delta, Egypt. Clinical history was collected from 53 cases of fascioliasis and the same number of individually matched controls. They received a complete clinical examination and a range of blood tests was performed on them. Information on socio-economic conditions, dietary and hygienic habits was also collected. The most important complaints, associated with the infection, were right abdominal pain (Odds Ratio 20, P = 0.005), epigastric burning (o.r. 16, P = 0.007) and nausea (o.r. 8, P = 0.05). Blood analyses reported a marked increase in blood eosinophils (o.r 1.3, P = 0.001) among cases. The presence of cows (o.r 3.2), buffaloes (o.r 3.0) and goats (o.r 2.6) in the household was closely associated with the infection together with the habit to bring those animals to the canal for bathing and/or drinking (o.r. 3.2). Among dietary habits investigated, eating raw seeds was more common in cases than controls (o.r. 9, P = 0.03) and emerged as a possible new way of infection.

OBJECTIVE: To evaluate the efficacy of and resistance to mebendazole (500 mg) and levamisole (40 or 80 mg), alone or in combination, for the treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections on Pemba Island - an area exposed to periodic school-based mebendazole treatment since 1994. METHODS: A randomized, placebo-controlled trial was carried out in 914 children enrolled from the first and fifth grades of primary schools. Stool samples collected at baseline and 21 days after treatment were examined by the Kato-Katz technique to assess the prevalence and intensity of helminth infection. FINDINGS: Efficacies of mebendazole and levamisole as single treatments against intestinal nematode infections were comparable with those in previous trials, but mebendazole treatment of hookworm infections gave significantly lower cure (7.6%) and egg reduction (52.1%) rates than reported in a study undertaken before the beginning of periodic chemotherapy (cure rate, 22.4%; egg reduction rate, 82.4%). Combined treatment with mebendazole and levamisole had a significantly higher efficacy against hookworm infections (cure rate, 26.1%; egg reduction rate, 88.7%) than either drug given alone. No difference in mebendazole efficacy was found in children who had been treated repeatedly compared with those who had not been treated previously. CONCLUSION: The overall efficacy of mebendazole against hookworm infections after periodic chemotherapy is reduced. The efficacy of benzimidazoles in chemotherapy-based control programmes should be monitored closely. Combined treatment with mebendazole and levamisole may be useful as a tool to delay the development of benzimidazole resistance.

Efficacy trials of antihelminthic therapies conducted in Africa have reported improvements in children's growth, but nutritional evaluations of large-scale deworming programs are lacking. We evaluated the first-year effect on growth of a school-based deworming program in Zanzibar, where growth retardation occurs in school children. Children in four primary schools were given thrice-yearly mebendazole (500 mg) and compared with children in four schools that received twice-yearly mebendazole and children in four non-program schools. Evaluation schools were randomly selected and allocated to control, twice-yearly or thrice-yearly deworming. Approximately 1000 children in each program group completed the 1-y follow-up. Children /=10 y old, overall program effects on height or weight gains were not significant. But in this age range, younger boys had significant improvements in height gain with thrice-yearly deworming, and children with higher heights-for-age had greater improvements in weight gain with deworming. We conclude that the deworming program improved the growth of school children, especially children who were younger and less stunted, but the improvements were small. More effective antihelminthic regimens or additional dietary or disease control interventions may be needed to substantially improve the growth of school children in areas such as Zanzibar.

Intestinal helminths, schistosomiasis and malaria have been recognized for decades to be major public health problems in Zanzibar, United Republic of Tanzania. During the evaluation of the impact of the Zanzibar Helminth Control Programme, baseline parasitological data on 3,605 schoolchildren were collected in Pemba Island. Prevalence of intestinal helminth infections was 72%, 94% and 96% for Ascaris lumbricoides, Trichuris tichiura and hookworm, respectively. Thirty one percent of children tested positive for haematuria, a reliable indicator of urinary schistosomiasis in the study area. Malaria parasites were found in 61% of children. Hookworm infections and haematuria were more prevalent in boys. Sixty seven percent of the children were infected with all three helminths, and 28% of children harbored double infections. No association was found between intestinal helminths and schistosomiasis or malaria. Children living in rural areas were more heavily infected with hookworms, schistosomiasis and malaria compared to children in towns. Results from this study provided relevant information for designing a Plan of Action for the integrated control of Filariasis, Intestinal Helminths, Malaria and Schistosomiasis in Zanzibar.

In many African populations, the prevalences of both iron deficiency and malarial infection exceed 50%. The control of iron deficiency anemia is of urgent public health importance, but assessment of iron status in these contexts has been controversial because of the effects of malarial disease on common iron status indicators. We assessed iron status in 3605 school children in Zanzibar by measuring hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin concentrations. Malaria parasitemia was quantified by counting against leukocytes. Iron deficiency was highly prevalent: 62.4% of hemoglobin concentrations were110 g/L, 59.7% of EP values were80 micromol/mol heme, and 41.5% of ferritin concentrations were12 microg/L. Prevalence of Plasmodium falciparum parasitemia was 60.6%, but1% of children had densities above 5000 parasites/microL blood. Neither hemoglobin nor EP concentration was associated with malaria parasite density, but prevalence of abnormal values increased byor = 25% with parasite density. Erythrocyte protoporphyrin and hemoglobin were strongly inversely related regardless of parasite density. The relationship of EP to hemoglobin was slightly attenuated when parasite density exceeded 1000 parasites/microL blood. Ferritin rose by 1.5 microg/L per 1000 parasites/microL for parasite densities1000 parasites/microL, but the relationship of ferritin to hemoglobin or EP was strong even when parasite densities exceeded this cutoff. The population prevalences of iron deficiency were not significantly biased by malarial infection. In this population of school children, iron status assessment using these indicators was not seriously influenced by malarial infection. We hypothesize that these indicators perform reliably in populations in which malarial infection is infrequently associated with disease; namely older children and adults in holoendemic environments.

Four indirect screening methods for the detection of Schistosoma haematobium morbidity are compared (history of haematuria, visual haematuria, and microhaematuria at the 1+ and 2+ positivity limit by reagent strips) in terms of their diagnostic performance under conditions of progressive decrease in prevalence of infection, intensity and risk of morbidity as a result of repeated schistosomiasis control programmes on Pemba Island, United Republic of Tanzania. The results show that the sensitivity of a history of haematuria was higher (71%) in children but lower in adults (40%), similar to the findings for visual haematuria in children (60%) and adults (40%) at baseline. However, visual haematuria had a higher specificity, positive predictive value, and efficiency than a history of haematuria in both children and adults. Microhaematuria at the 1+ positivity limit (by reagent strips) had the highest sensitivity of all the methods investigated, but the lowest specificity, positive predictive value, and efficiency. Quantitatively, the indirect methods tended to increase in specificity, negative predictive value, and efficiency during the course of the intervention programme. In contrast, positive predictive value tended to decrease, while the sensitivity remained fairly stable. Overall, these findings suggest that a history of haematuria and/or visual haematuria are appropriate methods for preliminary screening of communities to identify those at risk of morbidity. Thereafter, microhaematuria (1+ positivity limit) may be the more appropriate method for targeting intervention at the individual level.