Jean T. Coulibaly

Intestinal parasitic infections in schoolchildren in different settings of Côte d'Ivoire: effect of diagnostic approach and implications for control

BackgroundSocial-ecological systems govern parasitic infections in humans. Within the frame of assessing the accuracy of a rapid diagnostic test for Schistosoma mansoni in Côte d’Ivoire, three different endemicity settings had to be identified and schoolchildren’s intestinal parasitic infection profiles were characterized.MethodsIn September 2010, a rapid screening was conducted in 11 schools in the Azaguié district, south Côte d’Ivoire. In each school, 25 children were examined for S. mansoni and S. haematobium. Based on predefined schistosome endemicity levels, three settings were selected, where schoolchildren aged 8–12 years were asked to provide three stool and three urine samples for an in-depth appraisal of parasitic infections. Triplicate Kato-Katz thick smears were prepared from each stool sample for S. mansoni and soil-transmitted helminth diagnosis, whereas urine samples were subjected to a filtration method for S. haematobium diagnosis. Additionally, a formol-ether concentration method was used on one stool sample for the diagnosis of helminths and intestinal protozoa. Multivariable logistic regression models were employed to analyse associations between schoolchildren’s parasitic infections, age, sex and study setting.ResultsThe prevalences of S. mansoni and S. haematobium infections in the initial screening ranged from nil to 88% and from nil to 56%, respectively. The rapid screening in the three selected areas revealed prevalences of S. mansoni of 16%, 33% and 78%. Based on a more rigorous diagnostic approach, the respective prevalences increased to 33%, 53% and 92% S. haematobium prevalences were 0.8%, 4% and 65% (rapid screening results: 0.0%, 0.0% and 54%). Prevalence and intensity of Schistosoma spp., soil-transmitted helminths and intestinal protozoan infections showed setting-specific patterns. Infections with two or more species concurrently were most common in the rural setting (84%), followed by the peri-urban (28%) and urban setting (18%).ConclusionsMore sensitive diagnostic tools or rigorous sampling approaches are needed to select endemicity settings with high fidelity. The observed small-scale heterogeneity of helminths and intestinal protozoan infections has important implications for control.

A new rapid diagnostic test for detection of anti- Schistosoma mansoni and anti- Schistosoma haematobium antibodies

BackgroundParasitological methods are widely used for the diagnosis of schistosomiasis. However, they are insensitive, particularly in areas of low endemicity, and labour-intensive. Immunoassays based on detection of anti-schistosome antibodies have the merit of high sensitivity and recently a rapid diagnostic test (RDT), incorporating Schistosoma mansoni cercarial transformation fluid (SmCTF) for detection of anti-schistosome antibodies in blood has been developed. Here, we assessed the diagnostic performance of the SmCTF-RDT for S. mansoni and S. haematobium infections by comparing it with microscopy for egg detection.MethodsA cross-sectional survey was carried out in Azaguié, south Côte d’Ivoire. 118 pre-school-aged children submitted two stool and two urine samples, which were subjected to the Kato-Katz and urine filtration methods for the detection of S. mansoni and S. haematobium eggs, respectively. Urine was also subjected to a commercially available cassette test for S. mansoni, which detects circulating cathodic antigen. A finger-prick blood sample was used for the SmCTF-RDT for detection of anti-S. mansoni and anti-S. haematobium antibodies.ResultsThe prevalence of both anti-S. mansoni and anti-S. haematobium antibodies was more than three times higher than the prevalence of infection estimated by egg detection under a microscope. Using quadruplicate Kato-Katz as the reference standard for the diagnosis of S. mansoni infection, the sensitivity, negative predictive value (NPV), and positive predictive value (PPV) of the SmCTF-RDT was 75.0%, 84.2% and 22.5%, respectively. When two urine filtrations were considered as the reference standard for the diagnosis of S. haematobium infection, the sensitivity, NPV and PPV of SmCTF-RDT was 66.7%, 94.9% and 5.1%, respectively. The specificity of SmCTF-RDT, when using egg-detection as the reference standard, was estimated to be 34.4%. This low specificity may be a reflection of the relative insensitivity of the direct diagnostic approaches using microscopy.ConclusionsThe SmCTF-RDT is at least as sensitive as duplicate Kato-Katz and a single urine filtration for detection of S. mansoni and S. haematobium, respectively. Further investigations into the specificity of the test for anti-schistosome antibodies are necessary, but our results suggest that it may be a useful tool for mapping the prevalence of anti-schistosome antibodies in a given population pending intervention.

A call to strengthen the global strategy against schistosomiasis and soil-transmitted helminthiasis: the time is now

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 worlds 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

Dynamics of Schistosoma haematobium egg output and associated infection parameters following treatment with praziquantel in school-aged children

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.

Assessment of global guidelines for preventive chemotherapy against schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study

BackgroundPraziquantel is the drug of choice in preventive chemotherapy targeting schistosomiasis. Increasing large-scale administration of praziquantel requires monitoring of drug efficacy to detect early signs of development of resistance. Standard protocols for drug efficacy monitoring are necessary. Here, we determined the optimal time point for praziquantel efficacy assessment against Schistosoma haematobium and studied the dynamics of infection parameters following treatment.MethodsNinety school-aged children from south Côte d’Ivoire with a parasitologically confirmed S. haematobium infection were treated with a single oral dose of praziquantel (40 mg/kg) and followed up for 62 days post-treatment. Urine samples were collected on 23 schooldays during this period and were subjected to visual examination (macrohaematuria), urine filtration and microscopy (S. haematobium eggs) and reagent strip testing (microhaematuria, proteinuria and leukocyturia).ResultsObserved cure and egg reduction rates were highly dependent on the time point post-treatment. Egg reduction rates were high (>97%) in weeks 3–9 post-treatment. Cure rates were highest in weeks 6 (92.9%) and 9 (95.0%) post-treatment. The prevalence of infection-associated parameters decreased after treatment, reaching a minimum of 2.4% in weeks 5 (proteinuria) and 7 (leukocyturia) post-treatment, and 16.3% at the end of week 8 (microhaematuria). Macrohaematuria disappeared between weeks 3 and 6 post-treatment.ConclusionsFor monitoring praziquantel efficacy against S. haematobium, we recommend that the cure rate is assessed at week 6 post-treatment. The egg reduction rate can be evaluated earlier, from day 14 post-treatment onwards. Reagent strips are a useful additional tool for evaluating treatment outcomes in areas with high endemicity, preferably at weeks 5 and 6 post-treatment. The delayed decrease of microhaematuria confirms that lesions in the urinary tract persist longer than egg excretion post-treatment.

Effect of deworming on school-aged children’s physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic area of Côte d’Ivoire

BACKGROUND WHO guidelines recommend annual treatment for schistosomiasis or soil-transmitted helminthiasis when prevalence in school-aged children is at or above a threshold of 50% and 20%, respectively. Separate treatment guidelines are used for these two helminthiases, and integrated community-wide treatment is not recommended. We assessed the cost-effectiveness of changing prevalence thresholds and treatment guidelines under an integrated delivery framework. METHODS We developed a dynamic, age-structured transmission and cost-effectiveness model that simulates integrated preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis. We assessed a 5-year treatment programme with praziquantel (40 mg/kg per treatment) against schistosomiasis and albendazole (400 mg per treatment) against soil-transmitted helminthiasis at 75% coverage. We defined strategies as highly cost-effective if the incremental cost-effectiveness ratio was less than the World Bank classification for a low-income country (gross domestic product of US

Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Côte d’Ivoire

1045 per capita). We calculated the prevalence thresholds for cost-effective preventive chemotherapy of various strategies, and estimated treatment needs for sub-Saharan Africa. FINDINGS Annual preventive chemotherapy against schistosomiasis was highly cost-effective in treatment of school-aged children at a prevalence threshold of 5% (95% uncertainty interval [UI] 1·7-5·2; current guidelines recommend treatment at 50% prevalence) and for community-wide treatment at a prevalence of 15% (7·3-18·5; current recommendation is unclear, some community treatment recommended at 50% prevalence). Annual preventive chemotherapy against soil-transmitted helminthiasis was highly cost-effective in treatment of school-aged children at a prevalence of 20% (95% UI 5·4-30·5; current guidelines recommend treatment at 20% prevalence) and the entire community at 60% (35·3-85·1; no guidelines available). When both helminthiases were co-endemic, prevalence thresholds using integrated delivery were lower. Using this revised treatment framework, we estimated that treatment needs would be six times higher than WHO guidelines for praziquantel and two times higher for albendazole. An additional 21·3% (95% Bayesian credible interval 20·4-22·2) of the population changed from receiving non-integrated treatment under WHO guidelines to integrated treatment (both praziquantel and albendazole). Country-specific economic differences resulted in heterogeneity around these prevalence thresholds. INTERPRETATION Annual preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis are likely to be highly cost-effective at prevalences lower than WHO recommendations. These findings support substantial treatment scale-up, community-wide coverage, integrated treatment in co-endemic settings that yield substantial cost synergies, and country-specific treatment guidelines. FUNDING Doris Duke Charitable Foundation, Mount Sinai Hospital-University Health Network AMO Innovation Fund, and Stanford University Medical Scholars Programme.

Toward Measuring Schistosoma Response to Praziquantel Treatment with Appropriate Descriptors of Egg Excretion.

BackgroundMalaria and helminth infections are thought to negatively affect children’s nutritional status and to impair their physical and cognitive development. Yet, the current evidence-base is weak. The purpose of this study was to determine the effect of deworming against soil-transmitted helminthiasis and schistosomiasis on children’s physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic setting of Côte d’Ivoire.MethodsWe designed an intervention study with a 5-month follow-up among schoolchildren aged 5–14 years from Niablé, eastern Côte d’Ivoire. In late 2012, a baseline cross-sectional survey was conducted. Finger-prick blood, stool and urine samples were subjected to standardised, quality-controlled techniques for the diagnosis of Plasmodium spp., Schistosoma spp., soil-transmitted helminths and intestinal protozoa infections. Haemoglobin level was determined and anthropometric measurements were taken for appraisal of anaemia and nutritional status. Children underwent memory (digit span) and attention (code transmission) cognitive testing, and their physical fitness and strength were determined (20 m shuttle run, standing broad jump and grip strength test). All children were treated with albendazole (against soil-transmitted helminthiasis) and praziquantel (against schistosomiasis) after the baseline cross-sectional survey and again 2 months later. Five months after the initial deworming, the same battery of clinical, cognitive and physical fitness tests was performed on the same children.ResultsLower scores in strength tests were significantly associated with children with harbouring nutritional deficiencies. Surprisingly, boys infected with Schistosoma mansoni achieved longer jumping distances than their non-infected counterparts. Light-intensity infection with S. mansoni was associated with slightly better aerobic capacity. Deworming showed no effect on haemoglobin levels and anaemia, but children with moderate- to heavy-intensity Schistosoma infection at baseline gained weight more pronouncedly than non-infected children. Interestingly, children with soil-transmitted helminth or Schistosoma infection at baseline performed significantly better in the sustained attention test than their non-infected counterparts at the 5-month follow-up.ConclusionsThis study revealed conflicting results regarding clinical parameters and cognitive behaviour of children after two rounds of deworming. We speculate that potential beneficial effects of deworming are likely to be undermined in areas where malaria is co-endemic and nutritional deficiencies are widespread.

Sustaining control of schistosomiasis mansoni in moderate endemicity areas in western Côte d'Ivoire: a SCORE study protocol

Background Handheld light microscopy using compact optics and mobile phones may improve the quality of health care in resource-constrained settings by enabling access to prompt and accurate diagnosis. Methodology Laboratory technicians were trained to operate two handheld diagnostic devices (Newton Nm1 microscope and a clip-on version of the mobile phone-based CellScope). The accuracy of these devices was compared to conventional light microscopy for the diagnosis of Schistosoma haematobium, S. mansoni, and intestinal protozoa infection in a community-based survey in rural Côte d’Ivoire. One slide of 10 ml filtered urine and a single Kato-Katz thick smear from 226 individuals were subjected to the Newton Nm1 microscope and CellScope for detection of Schistosoma eggs and compared to conventional microscopy. Additionally, 121 sodium acetate-acetic acid-formalin (SAF)-fixed stool samples were examined by the Newton Nm1 microscope and compared to conventional microscopy for the diagnosis of intestinal protozoa. Principal Findings The prevalence of S. haematobium, S. mansoni, Giardia intestinalis, and Entamoeba histolytica/E. dispar, as determined by conventional microscopy, was 39.8%, 5.3%, 20.7%, and 4.9%, respectively. The Newton Nm1 microscope had diagnostic sensitivities for S. mansoni and S. haematobium infection of 91.7% (95% confidence interval (CI) 59.8–99.6%) and 81.1% (95% CI 71.2–88.3%), respectively, and specificities of 99.5% (95% CI 97.0–100%) and 97.1% (95% CI 92.2–99.1%), respectively. The CellScope demonstrated sensitivities for S. mansoni and S. haematobium of 50.0% (95% CI 25.4–74.6%) and 35.6% (95% CI 25.9–46.4%), respectively, and specificities of 99.5% (95% CI 97.0–100%) and 100% (95% CI 86.7–100%), respectively. For G. intestinalis and E. histolytica/E. dispar, the Newton Nm1 microscope had sensitivity of 84.0% (95% CI 63.1–94.7%) and 83.3% (95% CI 36.5–99.1%), respectively, and 100% specificity. Conclusions/Significance Handheld diagnostic devices can be employed in community-based surveys in resource-constrained settings after minimal training of laboratory technicians to diagnose intestinal parasites.

Experiences and Lessons from a Multicountry NIDIAG Study on Persistent Digestive Disorders in the Tropics.

Background The control of schistosomiasis emphasizes preventive chemotherapy with praziquantel, which aims at decreasing infection intensity and thus morbidity in individuals, as well as transmission in communities. Standardizing methods to assess treatment efficacy is important to compare trial outcomes across settings, and to monitor program effectiveness consistently. We compared customary methods and looked at possible complementary approaches in order to derive suggestions for standardizing outcome measures. Methodology/Principal Findings We analyzed data from 24 studies conducted at African, Asian, and Latin American sites, enrolling overall 4,740 individuals infected with Schistosoma mansoni, S. haematobium, or S. japonicum, and treated with praziquantel at doses of 40–80 mg/kg. We found that group-based arithmetic and geometric means can be used interchangeably to express egg reduction rates (ERR) only if treatment efficacy is high (>95%). For lower levels of efficacy, ERR estimates are higher with geometric than arithmetic means. Using the distribution of individual responses in egg excretion, 6.3%, 1.7% and 4.3% of the subjects treated for S. haematobium, S. japonicum and S. mansoni infection, respectively, had no reduction in their egg counts (ERR = 0). The 5th, 10th, and 25th centiles of the subjects treated for S. haematobium had individual ERRs of 0%, 49.3%, and 96.5%; the corresponding values for S. japonicum were 75%, 99%, and 99%; and for S. mansoni 18.2%, 65.3%, and 99.8%. Using a single rather than quadruplicate Kato-Katz thick smear excluded 19% of S. mansoni-infected individuals. Whilst the effect on estimating ERR was negligible by individual studies, ERR estimates by arithmetic means were 8% lower with a single measurement. Conclusions/Significance Arithmetic mean calculations of Schistosoma ERR are more sensitive and therefore more appropriate to monitor drug performance than geometric means. However, neither are satisfactory to identify poor responders. Group-based response estimated by arithmetic mean and the distribution of individual ERRs are correlated, but the latter appears to be more apt to detect the presence and to quantitate the magnitude of suboptimal responses to praziquantel.