Evaluation of a Urine Pooling Strategy for the Rapid and Cost-Efficient Prevalence Classification of Schistosomiasis.

BACKGROUND: A key epidemiologic feature of schistosomiasis is its focal distribution, which has important implications for the spatial targeting of preventive chemotherapy programs. We evaluated the diagnostic accuracy of a urine pooling strategy using a point-of-care circulating cathodic antigen (POC-CCA) cassette test for detection of Schistosoma mansoni, and employed simulation modeling to test the classification accuracy and efficiency of this strategy in determining where preventive chemotherapy is needed in low-endemicity settings. METHODOLOGY: We performed a cross-sectional study involving 114 children aged 6-15 years in six neighborhoods in Azaguié Ahoua, south Côte d'Ivoire to characterize the sensitivity and specificity of the POC-CCA cassette test with urine samples that were tested individually and in pools of 4, 8, and 12. We used a Bayesian latent class model to estimate test characteristics for individual POC-CCA and quadruplicate Kato-Katz thick smears on stool samples. We then developed a microsimulation model and used lot quality assurance sampling to test the performance, number of tests, and total cost per school for each pooled testing strategy to predict the binary need for school-based preventive chemotherapy using a 10% prevalence threshold for treatment. PRINCIPAL FINDINGS: The sensitivity of the urine pooling strategy for S. mansoni diagnosis using pool sizes of 4, 8, and 12 was 85.9%, 79.5%, and 65.4%, respectively, when POC-CCA trace results were considered positive, and 61.5%, 47.4%, and 30.8% when POC-CCA trace results were considered negative. The modeled specificity ranged from 94.0-97.7% for the urine pooling strategies (when POC-CCA trace results were considered negative). The urine pooling strategy, regardless of the pool size, gave comparable and often superior classification performance to stool microscopy for the same number of tests. The urine pooling strategy with a pool size of 4 reduced the number of tests and total cost compared to classical stool microscopy. CONCLUSIONS/SIGNIFICANCE: This study introduces a method for rapid and efficient S. mansoni prevalence estimation through examining pooled urine samples with POC-CCA as an alternative to widely used stool microscopy.

Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study.

BACKGROUND: More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire. METHODS: We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted. FINDINGS: Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities. INTERPRETATION: Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment. FUNDING: Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund.

Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.

BACKGROUND: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. METHODS/DESIGN: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. DISCUSSION: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02105714 .

Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis.

BACKGROUND: Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries. METHODS: We did a systematic review to identify surveys including schistosomiasis prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African Journals Online, from inception to May 2, 2014, with no restriction of language, survey date, or study design. We used Bayesian geostatistical meta-analysis and rigorous variable selection to predict infection risk over a grid of 1 155 818 pixels at 5 × 5 km, on the basis of environmental and socioeconomic predictors and to calculate the number of doses of praziquantel needed for prevention of morbidity. FINDINGS: The literature search identified Schistosoma haematobium and Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique locations. Infection risk decreased from 2000 onwards, yet estimates suggest that 163 million (95% Bayesian credible interval [CrI] 155 million to 172 million; 18·5%, 17·6-19·5) of the sub-Saharan African population was infected in 2012. Mozambique had the highest prevalence of schistosomiasis in school-aged children (52·8%, 95% CrI 48·7-57·8). Low-risk countries (prevalence among school-aged children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and Rwanda. The numbers of doses of praziquantel needed per year were estimated to be 123 million (95% CrI 121 million to 125 million) for school-aged children and 247 million (239 million to 256 million) for the entire population. INTERPRETATION: Our results will inform policy makers about the number of treatments needed at different levels and will guide the spatial targeting of schistosomiasis control interventions. FUNDING: European Research Council, China Scholarship Council, UBS Optimus Foundation, and Swiss National Science Foundation.

Causes of death in the Taabo health and demographic surveillance system, Côte d'Ivoire, from 2009 to 2011.

BACKGROUND: Current vital statistics from governmental institutions in Côte d'Ivoire are incomplete. This problem is particularly notable for remote rural areas that have limited access to the health system. OBJECTIVE: To record all deaths from 2009 to 2011 and to identify the leading causes of death in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire. DESIGN: Deaths recorded in the first 3 years of operation of the Taabo HDSS were investigated by verbal autopsy (VA), using the InterVA-4 model. InterVA-4 is based on the World Health Organization 2012 VA tool in terms of input indicators and categories of causes of death. RESULTS: Overall, 948 deaths were recorded, of which 236 (24.9%) had incomplete VA data. Among the 712 deaths analyzed, communicable diseases represented the leading causes (58.9%), with most deaths attributed to malaria (n=129), acute respiratory tract infections (n=110), HIV/AIDS (n=80), and pulmonary tuberculosis (n=46). Non-communicable diseases accounted for 18.9% of the deaths and included mainly acute abdomen (n=38), unspecified cardiac diseases (n=15), and digestive neoplasms (n=13). Maternal and neonatal conditions accounted for 8.3% of deaths, primarily pneumonia (n=19) and birth asphyxia (n=16) in newborns. Among the 3.8% of deaths linked to trauma and injury, the main causes were assault (n=6), accidental drowning (n=4), contact with venomous plants/animals (n=4), and traffic-related accidents (n=4). No clear causes were determined in 10.0% of the analyzed deaths. CONCLUSIONS: Communicable diseases remain the predominant cause of death in rural Côte d'Ivoire. Based on these findings, measures are now being implemented in the Taabo HDSS. It will be interesting to monitor patterns of mortality and causes of death in the face of rapid demographic and epidemiological transitions in this part of West Africa.

Patients routinely report more symptoms to experienced field enumerators than physicians in rural Cote d'Ivoire.

Medical history-taking is among the most powerful diagnostic tools for healthcare professionals. However, its accuracy and reliability are underexplored areas. The present post-hoc study compares medical histories from 463 people in a rural part of Côte d'Ivoire. The medical histories of the same individuals were taken by physicians and experienced field enumerators who were blinded to the results of the others. Kappa (κ) statistics for 14 symptoms revealed only poor-to-moderate agreement between physicians and field enumerators (κ = 0.01-0.54). Participants reported consistently more symptoms to field enumerators than physicians. Only 33 (7.1%) participants gave no discordant statement at all. The average number of discordant statements per participant was 3.7. Poisson regression revealed no significant association between the number of discordant statements and participants' age, sex, educational attainment, occupation, or socioeconomic status. Operational research should further explore best practices to obtain reliable medical histories in resource-constrained settings.

A research agenda for helminth diseases of humans: towards control and elimination.

Human helminthiases are of considerable public health importance in sub-Saharan Africa, Asia, and Latin America. The acknowledgement of the disease burden due to helminth infections, the availability of donated or affordable drugs that are mostly safe and moderately efficacious, and the implementation of viable mass drug administration (MDA) interventions have prompted the establishment of various large-scale control and elimination programmes. These programmes have benefited from improved epidemiological mapping of the infections, better understanding of the scope and limitations of currently available diagnostics and of the relationship between infection and morbidity, feasibility of community-directed or school-based interventions, and advances in the design of monitoring and evaluation (M&E) protocols. Considerable success has been achieved in reducing morbidity or suppressing transmission in a number of settings, whilst challenges remain in many others. Some of the obstacles include the lack of diagnostic tools appropriate to the changing requirements of ongoing interventions and elimination settings; the reliance on a handful of drugs about which not enough is known regarding modes of action, modes of resistance, and optimal dosage singly or in combination; the difficulties in sustaining adequate coverage and compliance in prolonged and/or integrated programmes; an incomplete understanding of the social, behavioural, and environmental determinants of infection; and last, but not least, very little investment in research and development (R&D). The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to undertake a comprehensive review of recent advances in helminthiases research, identify research gaps, and rank priorities for an R&D agenda for the control and elimination of these infections. This review presents the processes undertaken to identify and rank ten top research priorities; discusses the implications of realising these priorities in terms of their potential for improving global health and achieving the Millennium Development Goals (MDGs); outlines salient research funding needs; and introduces the series of reviews that follow in this PLoS Neglected Tropical Diseases collection, "A Research Agenda for Helminth Diseases of Humans."

Effect of an armed conflict on relative socioeconomic position of rural households: case study from western Côte d'Ivoire.

BACKGROUND: Current conceptual frameworks on the interrelationship between armed conflict and poverty are based primarily on aggregated macro-level data and/or qualitative evidence and usually focus on adherents of warring factions. In contrast, there is a paucity of quantitative studies about the socioeconomic consequences of armed conflict at the micro-level, i.e., noncommitted local households and civilians. METHODS: We conducted a secondary analysis of data pertaining to risk factors for malaria and neglected tropical diseases. Standardized questionnaires were administered to 182 households in a rural part of western Côte d'Ivoire in August 2002 and again in early 2004. Between the two surveys, the area was subject to intensive fighting in the Ivorian civil war. Principal component analysis was applied at the two time points for constructing an asset-based wealth-index and categorizing the households in wealth quintiles. Based on quintile changes, the households were labeled as 'worse-off', 'even' or 'better-off'. Statistical analysis tested for significant associations between the socioeconomic fates of households and head of household characteristics, household composition, village characteristics and self-reported events associated with the armed conflict. Most-poor/least-poor ratios and concentration indices were calculated to assess equity changes in households' asset possession. RESULTS: Of 203 households initially included in the first survey, 21 were lost to follow-up. The population in the remaining 182 households shrunk from 1,749 to 1,625 persons due to migration and natural population changes. However, only weak socioeconomic dynamics were observed; every seventh household was defined as 'worse-off' or 'better-off' despite the war-time circumstances. Analysis of other reported demographic and economic characteristics did not clearly identify more or less resilient households, and only subtle equity shifts were noted.However, the results indicate significant changes in livelihood strategies with a significant return to agricultural production and a decrease in the diversity of socioeconomic activities. CONCLUSION: Situational constraints and methodological obstacles are inherent in conflict settings and hamper conflict-related socioeconomic research. Furthermore, sensitive methods to assess and meaningfully interpret longitudinal micro-level wealth data from low-income countries are lacking. Despite compelling evidence of socioeconomic dynamics triggered by armed conflicts at the macro-level, we could not identify similar effects at the micro-level. A deeper understanding of household profiles that are more resilient to armed conflict could help to better prevent and/or alleviate adverse conflict-related and increasingly civilian-borne socioeconomic effects.

Social and cultural aspects of 'malaria' and its control in central Côte d'Ivoire.

BACKGROUND: A sound local understanding of preventive measures and health-seeking behaviour is important for the effective control of malaria. The purpose of this study was to assess the knowledge, attitudes, practices and beliefs of 'malaria' and its control in two rural communities of central Côte d'Ivoire, and to examine associations between 'malaria' and the households' socioeconomic status. METHODS: A cross-sectional household survey was carried out, using a combination of qualitative and quantitative methods. People's socioeconomic status was estimated, employing a household asset-based approach. RESULTS: Malaria was identified as djèkouadjo, the local folk name of the disease. Although people were aware of malaria-related symptoms and their association with mosquitoes, folk perceptions were common. In terms of treatment, a wide array of modern and traditional remedies was employed, often in combination. Individuals with a sound knowledge of the causes and symptoms of malaria continued to use traditional treatments and only a few people sleep under bed nets, whereas folk beliefs did not necessarily translate into refusal of modern treatments. Perceived causes of malaria were linked to the household's socioeconomic status with wealthier individuals reporting mosquitoes more frequently than poorer households. Bed nets were more frequently used in wealthier social strata, whereas other protective measures--perceived to be cheaper--were more prominent among the poorest. CONCLUSION: Equitable access to resources at household, community and health system levels are essential in order to enable community members to prevent and treat malaria. There is a need for community-based approaches that match health care services with poor people's needs and resources.

Spatially-explicit risk profiling of Plasmodium falciparum infections at a small scale: a geostatistical modelling approach.

BACKGROUND: There is a renewed political will and financial support to eradicate malaria. Spatially-explicit risk profiling will play an important role in this endeavour. Patterns of Plasmodium falciparum infection prevalence were examined among schoolchildren in a highly malaria-endemic area. METHODS: A questionnaire was administered and finger prick blood samples collected from 3,962 children, aged six to 16 years, attending 55 schools in a rural part of western Côte d'Ivoire. Information was gathered from the questionnaire on children's socioeconomic status and the use of bed nets for the prevention of malaria. Blood samples were processed with standardized, quality-controlled methods for diagnosis of Plasmodium spp. infections. Environmental data were obtained from satellite images and digitized maps. Bayesian variogram models for spatially-explicit risk modelling of P. falciparum infection prevalence were employed, assuming for stationary and non-stationary spatial processes. FINDINGS: The overall prevalence of P. falciparum infection was 64.9%, ranging between 34.0% and 91.9% at the unit of the school. Risk factors for a P. falciparum infection included age, socioeconomic status, not sleeping under a bed net, distance to health care facilities and a number of environmental features (i.e. normalized difference vegetation index, rainfall and distance to rivers). After taking into account spatial correlation only age remained significant. Non-stationary models performed better than stationary models. CONCLUSION: Spatial risk profiling of P. falciparum prevalence data provides a useful tool for targeting malaria control intervention, and hence will play a role in the quest of local elimination and ultimate eradication of the disease.

Disparities in parasitic infections, perceived ill health and access to health care among poorer and less poor schoolchildren of rural Côte d'Ivoire.

Differences in the state of health between rural and urban populations living in Africa have been described, yet only few studies analysed inequities within poor rural communities. We investigated disparities in parasitic infections, perceived ill health and access to formal health services among more than 4000 schoolchildren from 57 primary schools in a rural area of western Côte d'Ivoire, as measured by their socioeconomic status. In a first step, we carried out a cross-sectional parasitological survey. Stool specimens and finger prick blood samples were collected and processed with standardized, quality-controlled methods, for diagnosis of Schistosoma mansoni, soil-transmitted helminths, intestinal protozoa and Plasmodium. Then, a questionnaire survey was carried out for the appraisal of self-reported morbidity indicators, as well as housing characteristics and household assets ownership. Mean travel distance from each village to the nearest health care delivery structure was provided by the regional health authorities. Poorer schoolchildren showed a significantly higher infection prevalence of hookworm than better-off children. However, higher infection prevalences of intestinal protozoa (i.e. Blastocystis hominis, Endolimax nana and Iodamoeba butschlii) were found with increasing socioeconomic status. Significant negative associations were observed between socioeconomic status and light infection intensities with hookworm and S. mansoni, as well as with several self-reported morbidity indicators. The poorest school-attending children lived significantly further away from formal health services than their richer counterparts. Our study provides evidence for inequities among schoolchildren's parasitic infection status, perceived ill health and access to health care in a large rural part of Côte d'Ivoire. These findings call for more equity-balanced parasitic disease control interventions, which in turn might be an important strategy for poverty alleviation.

Opportunities and limiting factors of intensive vegetable farming in malaria endemic Côte d'Ivoire.

Poverty reduction policies guide development strategies. In economies that depend heavily on agriculture, in the face of rapid population growth, innovative approaches are required to satisfy food needs, increase household welfare and alleviate poverty. Irrigated agriculture is an important strategy to enhance crop production, but it must be well tailored to specific socio-ecological settings, as otherwise, it might increase the burden of water-related parasitic diseases and delay economic advance. The purpose of this study is to assess and quantify the effect of ill health, particularly malaria, on the performance of farm activity, with an emphasis on drip-irrigated vegetable farming in rural Côte d'Ivoire. Vegetable yields and revenues were monitored among 12 farmers and linked with longitudinal medical and entomological surveys. Over the course of 10 months, farmers were classified as sick, on average, for 14-15 days, with malaria accounting for 8-9 days (58%), confirming that malaria is the most important disease in this setting. There was a large heterogeneity among farmers, with malaria-related work losses ranging between 0 and 26 days. Work absenteeism correlated with overall yields and revenues. During a single cabbage production cycle, those farmers who were prescribed sick because of malaria for more than 2 days (mean: 4.2 days) had 47% lower yields and 53% lower revenues than farmers who missed a maximum of 2 days (mean: 0.3 days). This is consequential in an intensive cropping system, where substitutes for qualified workers are not readily available. We conclude that mitigating the burden of malaria is an important step towards reducing the vulnerability of people engaged in intensive agricultural production. This calls for targeted interventions to facilitate agriculture-based rural development that might spur social and economic development and reduce inequities in sub-Saharan Africa.

Reduction in the prevalence and intensity of hookworm infections after praziquantel treatment for schistosomiasis infection.

Praziquantel exhibits activity against all major human schistosome parasites and has become the cornerstone for treatment and morbidity control of schistosomiasis. Praziquantel is also active against a wide range of trematodes, human and veterinary cestodes and displays cysticidal effects. To the best of our knowledge anthelminthic properties have never been documented. Here, we report a study among 96 schoolchildren from an area highly endemic for Schistosoma mansoni and hookworm infection, and place particular emphasis on the effect of praziquantel on the prevalence and intensity of hookworm infections. Stool specimens were screened over several consecutive days prior and 4 weeks after systematic administration of praziquantel. We found a significant reduction in the prevalence of hookworm infection from 75.0 to 40.6% (odds ratio (OR)=0.21; 95% confidence interval (CI): 0.11-0.40). Infection intensities, expressed by geometric mean egg counts of all children, were also reduced significantly from 10.7 to 2.0 eggs per gram stool (paired t-test=7.78, P<0.001). If these findings are confirmed in other epidemiological settings - following a similarly sensitive diagnostic approach - they might become of considerable relevance. In areas where both schistosome and hookworm coexist, and praziquantel is being recommended for schistosomiasis control, large-scale application of this drug might also reduce the burden of hookworms.