Arve Lee Willingham

A Research Agenda for Helminth Diseases of Humans: Diagnostics for Control and Elimination Programmes

Diagnostic tools appropriate for undertaking interventions to control helminth infections are key to their success. Many diagnostic tests for helminth infection have unsatisfactory performance characteristics and are not well suited for use in the parasite control programmes that are being increasingly implemented. Although the application of modern laboratory research techniques to improve diagnostics for helminth infection has resulted in some technical advances, uptake has not been uniform. Frequently, pilot or proof of concept studies of promising diagnostic technologies have not been followed by much needed product development, and in many settings diagnosis continues to rely on insensitive and unsatisfactory parasitological or serodiagnostic techniques. In contrast, PCR-based xenomonitoring of arthropod vectors, and use of parasite recombinant proteins as reagents for serodiagnostic tests, have resulted in critical advances in the control of specific helminth parasites. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR) was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, the diagnostic technologies relevant to control of helminth infections, either available or in development, are reviewed. Critical gaps are identified and opportunities to improve needed technologies are discussed.

World Health Organization Estimates of the Global and Regional Disease Burden of 11 Foodborne Parasitic Diseases, 2010: A Data Synthesis.

Background Foodborne diseases are globally important, resulting in considerable morbidity and mortality. Parasitic diseases often result in high burdens of disease in low and middle income countries and are frequently transmitted to humans via contaminated food. This study presents the first estimates of the global and regional human disease burden of 10 helminth diseases and toxoplasmosis that may be attributed to contaminated food. Methods and Findings Data were abstracted from 16 systematic reviews or similar studies published between 2010 and 2015; from 5 disease data bases accessed in 2015; and from 79 reports, 73 of which have been published since 2000, 4 published between 1995 and 2000 and 2 published in 1986 and 1981. These included reports from national surveillance systems, journal articles, and national estimates of foodborne diseases. These data were used to estimate the number of infections, sequelae, deaths, and Disability Adjusted Life Years (DALYs), by age and region for 2010. These parasitic diseases, resulted in 48.4 million cases (95% Uncertainty intervals [UI] of 43.4–79.0 million) and 59,724 (95% UI 48,017–83,616) deaths annually resulting in 8.78 million (95% UI 7.62–12.51 million) DALYs. We estimated that 48% (95% UI 38%-56%) of cases of these parasitic diseases were foodborne, resulting in 76% (95% UI 65%-81%) of the DALYs attributable to these diseases. Overall, foodborne parasitic disease, excluding enteric protozoa, caused an estimated 23.2 million (95% UI 18.2–38.1 million) cases and 45,927 (95% UI 34,763–59,933) deaths annually resulting in an estimated 6.64 million (95% UI 5.61–8.41 million) DALYs. Foodborne Ascaris infection (12.3 million cases, 95% UI 8.29–22.0 million) and foodborne toxoplasmosis (10.3 million cases, 95% UI 7.40–14.9 million) were the most common foodborne parasitic diseases. Human cysticercosis with 2.78 million DALYs (95% UI 2.14–3.61 million), foodborne trematodosis with 2.02 million DALYs (95% UI 1.65–2.48 million) and foodborne toxoplasmosis with 825,000 DALYs (95% UI 561,000–1.26 million) resulted in the highest burdens in terms of DALYs, mainly due to years lived with disability. Foodborne enteric protozoa, reported elsewhere, resulted in an additional 67.2 million illnesses or 492,000 DALYs. Major limitations of our study include often substantial data gaps that had to be filled by imputation and suffer from the uncertainties that surround such models. Due to resource limitations it was also not possible to consider all potentially foodborne parasites (for example Trypanosoma cruzi). Conclusions Parasites are frequently transmitted to humans through contaminated food. These estimates represent an important step forward in understanding the impact of foodborne diseases globally and regionally. The disease burden due to most foodborne parasites is highly focal and results in significant morbidity and mortality among vulnerable populations.

Zoonoses and marginalised infectious diseases of poverty: Where do we stand?

Despite growing awareness of the importance of controlling neglected tropical diseases as a contribution to poverty alleviation and achieving the Millennium Development Goals, there is a need to up-scale programmes to achieve wider public health benefits. This implementation deficit is attributable to several factors but one often overlooked is the specific difficulty in tackling diseases that involve both people and animals - the zoonoses. A Disease Reference Group on Zoonoses and Marginalised Infectious Diseases (DRG6) was convened by the Special Programme for Research and Training in Tropical Diseases (TDR), a programme executed by the World Health Organization and co-sponsored by UNICEF, UNDP, the World Bank and WHO. The key considerations included: (a) the general lack of reliable quantitative data on their public health burden; (b) the need to evaluate livestock production losses and their additional impacts on health and poverty; (c) the relevance of cross-sectoral issues essential to designing and implementing public health interventions for zoonotic diseases; and (d) identifying priority areas for research and interventions to harness resources most effectively. Beyond disease specific research issues, a set of common macro-priorities and interventions were identified which, if implemented through a more integrated approach by countries, would have a significant impact on human health of the most marginalised populations characteristically dependent on livestock.

A health-education intervention trial to reduce porcine cysticercosis in Mbulu District, Tanzania

We conducted a randomised community controlled trial to estimate the effectiveness of health and pig-management education intervention in reducing the incidence rate of porcine cysticercosis caused by Taenia solium in Mbulu District, northern Tanzania, between April 2002 and July 2004. We included a random sample of 827 pig-keeping households from 42 randomly selected villages in our 27-month study. We collected baseline data on the prevalence of porcine cysticercosis based on lingual examination of live pigs, and pig-management and sanitation knowledge and practices based on questionnaire interviews and observations. We allocated 21 of the villages to the health-education intervention, developed with community participation; we used stratified randomisation to balance the village-level baseline prevalence of porcine cysticercosis. From July 2003 to March 2004 following the intervention, we gave each participant household a sentinel piglet to raise (the timing was balanced between the intervention groups). Knowledge about the transmission and prevention of porcine cysticercosis was improved >42% in both groups when measured 10-12 months post-intervention. There was no improvement in observed practices in either group throughout the study period. However, the intervention had a significant reduction in the reported cases of household consumption of infected pork (a reduction by 20%). The intervention was associated with a considerable decrease in the incidence rate of porcine cysticercosis (incidence rate ratio 0.57) as measured by antigen-ELISA in sentinel pigs. Public education could lead to a reduction of the risk of infection in humans.

Prevalence and Risk Factors of Porcine Cysticercosis in Angónia District, Mozambique

Taenia solium is an important zoonosis in many developing countries. Cysticercosis poses a serious public health risk and incurs sizeable economic losses to pig production. Because data on the epidemiology of porcine cysticercosis in Mozambique are scarce, the present study was conducted to determine the prevalence and risk factors for porcine cysticercosis. A cross-sectional survey was carried out in 11 villages in Angónia district, Tete province in northwestern Mozambique. Between September and November, 2007, a total of 661 pigs were tested serologically and examined by tongue inspection. Serum samples were tested for the presence of circulating parasite antigen using a monoclonal antibody-based sandwich enzyme-linked immunosorbent assay (Ag-ELISA). In addition, a questionnaire survey to collect information on pig production, occurrence and transmission of porcine cysticercosis, risk factors and awareness of porcine cysticercosis was conducted in the selected households from which pigs were sampled. Two hundred thirty-one samples (34.9%) were found positive by the Ag-ELISA, while by tongue inspection on the same animals cysticerci were detected in 84 pigs (12.7%). Increasing age (OR = 1.63; 95% CI = 1.13–2.37) and free-range pig husbandry system (OR = 3.81; 95% CI = 2.08–7.06) were important risk factors for porcine cysticercosis in the district. The present findings indicate that porcine cysticercosis is endemic in the region, and that increasing pig age and pig husbandry practices contribute significantly to porcine cysticercosis transmission. Further epidemiological studies on the prevalence and transmission of porcine cysticercosis in rural communities in Mozambique are needed to enable collection of more baseline data and implementation of effective control strategies within the country.

Distribution and density of cysticerci of Taenia solium by muscle groups and organs in naturally infected local finished pigs in Tanzania

The distribution and density of cysticerci of Taenia solium among distinct carcass sites was determined in 24 naturally infected finished pigs from Mbulu district, Tanzania. The heart, tongue, internal and external masseters, triceps brachii, lungs, liver, kidneys, psoas, diaphragm and brain of each pig as well as the muscles from the forelimb, hind limb, abdomen, head and thorax from one half of each pig carcass were all designated as distinct carcass sites and sliced in such a way that all fully developed cysts could be revealed and enumerated (i.e. each slice was less than 0.5 cm thick). The carcasses harboured from 76 to 80,340 cysts in total. Carcass sites which harboured the highest proportion of cysts were those of the hind and forelimbs (mean: 27.7 and 24.5%, respectively, of the total cysts in the carcass), while lower proportions were found in the tongue, heart, triceps brachii, and diaphragm (7, 3.6, 2 and 2, respectively). Relative cyst density was calculated for the different carcass sites by dividing the mean proportion of the total weight of the tissue groups into the mean proportion of cysts located in that site. The cysticerci in the examined distinct carcass sites were found in the following order of relative density: psoas muscles (10.5), internal masseter (8.1), external masseter (7.1), triceps brachii (4.9), forelimb (4.0), head muscles (3.8), tongue (3.4), hind limb (3.2), diaphragm (2.4), heart (1.9), abdominal muscles (1.3), trunk muscles (1.1), brain (1.0) and oesophagus (0.3). The proportion of cysts expected to be found at the surfaces exposed by visual examination or incision at meat inspection was calculated using an indirect method, which incorporated the area revealed by incision and visual inspection of an organ and the proportion of cysts located in the particular organ. It was estimated that 10.6% of the cysts would be located at inspected sites if regulations were followed carefully.

The global burden of foodborne parasitic diseases: an update.

Foodborne diseases (FBDs) are a major cause of morbidity and mortality in the human population. Accurate information on the burden of FBDs is needed to inform policy makers and allocate appropriate resources for food safety control and intervention. Consequently, in 2006 the WHO launched an initiative to estimate the global burden of FBDs in terms of Disability Adjusted Life Years (DALYs). This review gives an update of the progress on evaluating the burden of foodborne parasitic diseases that has been generated by this study. Results to date indicate that parasitic diseases that can be transmitted through food make a substantial contribution to the global burden of disease.

Prevalence of Taenia solium cysticercosis in swine from a community-based study in 21 villages of the Eastern Cape Province, South Africa

The pork tapeworm, Taenia solium, causative organism of porcine cysticercosis and human neurocysticercosis is known to occur in areas of South Africa including Eastern Cape Province but, despite increasing reports of its occurrence throughout the subregion, the prevalence is yet to be clearly established. The parasite presents a potentially serious agricultural problem and public health risk in endemic areas. The human populations considered to be at highest risk of infection with this zoonotic helminth are people living in rural areas most of whom earn their livelihood wholly or partially through livestock rearing. Here we report on initial results of a community-based study of pigs owned by resource-poor, emerging pig producers from 21 villages in the Eastern Cape Province. Lingual examination (tongue palpation) in live pigs, two enzyme-linked immunosorbent assays (ELISAs), which detect parasite antigen (B158/B60 Ag-ELISA and HP10 Ag-ELISA) and an enzyme immunotransfer blot (EITB) assay, which detects antiparasite antibody, were used to verify endemicity and estimate apparent prevalence. In the absence of a gold standard true prevalence was obtained, using a Bayesian approach, with a model that uses both available data and prior information. Results indicate that the parasite is indeed present in the study villages and that true prevalence was 64.6%. The apparent prevalences as measured by each of the four tests were: 11.9% for lingual examination, 54.8% for B158/B60 Ag-ELISA, 40.6% for HP10 Ag-ELISA and 33.3% for EITB. This base-line knowledge of the prevalence of T. solium in pigs provides information essential to the design and monitoring of sustainable and appropriate interventions for cysticercosis prevention and control.

Prevalence and Risk Factors Associated with Human Taenia Solium Infections in Mbozi District, Mbeya Region, Tanzania

Background Taenia solium cysticercosis/taeniosis is emerging as a serious public health and economic problem in many developing countries. This study was conducted to determine prevalence and risk factors of human T. solium infections in Mbeya Region, Tanzania. Methods and Findings A cross-sectional survey was conducted in 13 villages of Mbozi district in 2009. Sera of 830 people (mean 37.9±11.3 years (SD); 43% females) were tested for circulating cysticerci antigen (Ag-ELISA) and antibody (Ab-ELISA). A subset of persons found seropositive by Ag-ELISA underwent computed tomography (CT) scan of the brain for evidence of neurocysticercosis. Stool samples from 820 of the same participants were tested for taeniosis by copro-antigens (copro-Ag-ELISA) and formol-ether concentration technique. Cases of T. solium taeniosis were confirmed serologically by EITB assay (rES38). A questionnaire was used for identification of risk factors. Active cysticercosis by positive Ag-ELISA was found in 139 (16.7%) persons while anti-cysticercal antibodies were detected in 376 (45.3%) persons by Ab-ELISA. Among 55 persons positive for Ag-ELISA undergoing CT scan, 30 (54.6%) were found to have structures in the brain suggestive of neurocysticercosis. Using faecal analysis, 43 (5.2%) stool samples tested positive for taeniosis by copro-Ag-ELISA while Taenia eggs were detected in 9 (1.1%) stool samples by routine coprology. Antibodies specifically against adult T. solium were detected in 34 copro-Ag-ELISA positive participants by EITB (rES38) indicating T. solium taeniosis prevalence of 4.1%. Increasing age and hand washing by dipping in contrast to using running water, were found associated with Ag-ELISA seropositivity by logistic regression. Gender (higher risk in females) and water source were risk factors associated with Ab-ELISA seropositivity. Reported symptoms of chronic severe headaches and history of epileptic seizures were found associated with positive Ag-ELISA (p≤0.05). Conclusion The present study indicates T. solium infection in humans is highly endemic in the southern highlands of Tanzania.

Taenia solium porcine cysticercosis: viability of cysticerci and persistency of antibodies and cysticercal antigens after treatment with oxfendazole.

The aim of this study was to assess the effect of treating Taenia solium infected pigs with oxfendazole (OFZ) on viability and clearance of cysticerci and the corresponding persistence of specific antibody isotypes (IgG(total), IgG1, IgG2 and IgA) and circulating cysticercal antigen (CCA). Antibody isotypes and CCA responses were measured by antibody-ELISA (Ab-ELISA) and antigen ELISA (Ag-ELISA), respectively. Correlations were made between antibodies, CCA and the total number of cysticerci enumerated at necropsy. Forty pigs with cysticercosis were randomly allocated into two groups: Treatment group (n=20) was treated with OFZ at 30 mg/kg orally while the treatment control group (n=20) was not treated. Five uninfected pigs served as negative controls. Pigs were killed at 1, 4, 8 and 26 weeks post-treatment (wkpt). Overall, the mean total cyst count in treated pigs was 2904+/-5397 (mean+/-S.D.) while in the controls it was 6235+/-6705. Mean cyst viability was 5+/-11% (mean+/-S.D.) and 97+/-4% in treated and control pigs, respectively. Results showed that OFZ killed muscular cysticerci over a period of 4 weeks but failed to kill cerebral cysticerci. Antibodies, CCA responses and clearance of dead cysts from the meat, depended on the cyst intensity of individual pigs at time of treatment since both antibody and CCA correlated with intensity of cysticerci at necropsy (r=0.441, P=0.005; r=0.654, P<0.001), respectively. IgG1 responses were the best indicator of treatment efficacy because they were predominant in both infected treated and control pigs and disappeared early after treatment. Both Ab/Ag-ELISA failed to detect cysts in the brain. Though dead cysticerci took some time (26 wkpt) to clear from the meat, treatment of porcine cysticercosis with OFZ should, in combination with other intervention measures be considered as an important, cost-effective measure in the control of taeniosis/cysticercosis.