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 .

Superiority of 3 over 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine for the prevention of malaria during pregnancy in mali: a randomized controlled trial.

BACKGROUND: In 2003, Mali introduced intermittent preventive therapy in pregnancy (ITPp) with sulfadoxine-pyrimethamine (SP) for the control of malaria in pregnancy, consisting of 2 doses of SP given in the 2nd and 3rd trimester. This widely used regimen, although very effective, leaves many women unprotected from malaria during the last 4-to-8 weeks of gestation, which is a pivotal period for fetal weight gain. The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight (LBW). METHODS: We conducted a parallel-group, open-label, individually randomized controlled superiority trial involving 814 women of all gravidity, enrolled from April 2006 through March 2008. All women were seen at least 3 times and received either 2 (n = 401) or 3 (n = 413) doses of IPTp-SP. The primary endpoint measured was placental malaria, LBW, preterm births, and maternal anemia were secondary endpoints, and severe maternal skin reactions and neonatal jaundice were safety endpoints. RESULTS: Among the 96% of study subjects who were followed up until delivery, the prevalence of placental malaria was 2-fold lower in the 3-dose group (8.0%) than in the 2-dose group (16.7%); the adjusted prevalence ratio (APR) was 0.48 (95% confidence interval [CI], 0.32-0.71). LBW and preterm births were also reduced; the prevalence of LBW was 6.6% in the 3-dose group versus 13.3% in the 2-dose group (APR, 0.50; 95% CI, 0.32-0.79), and the prevalence of preterm births was 3.2% versus 8.9% (APR, 0.37; 95% CI, 0.19-0.71). No significant reductions in maternal anemia or differences in safety endpoints were observed. CONCLUSIONS: Adding a third dose of ITPp-SP halved the risk of placental malaria, LBW, and preterm births in all gravidae, compared with the standard 2-dose regimen, in this area of highly seasonal transmission with low levels of SP resistance. CLINICAL TRIALS REGISTRATION: ISRCTN 74189211.

Prevalence of Giardia intestinalis Infection in Schistosomiasis-Endemic Areas in South-Central Mali.

Intestinal parasite infections are frequent causes of diarrhea and malnutrition among children in the tropics. Transmission of helminths and intestinal protozoa is intimately connected with conditions of poverty, including inadequate sanitation and hygiene. Concurrent infections with several intestinal pathogens may lead to excess morbidity. Yet, there is a paucity of epidemiological data from Mali. In this study, stool samples from 56 individuals, aged 2-63 years, from Bamako and Niono, south-central Mali were examined for intestinal parasites using stool microscopy. Additionally, stool samples were subjected to a rapid diagnostic test (RDT) and polymerase chain reaction (PCR) for the detection of Cryptosporidium spp. and Giardia intestinalis. The predominant pathogens were Schistosoma mansoni and G. intestinalis with prevalences of 41% and 38%, respectively. Hymenolepis nana was detected in 4% of the participants, while no eggs of soil-transmitted helminths were found. Concurrent infections with G. intestinalis and S. mansoni were diagnosed in 16% of the participants. For the detection of G. intestinalis, PCR was more sensitive (100%) than RDT (62%) and microscopy (48%). As helminth-protozoa coinfections might have important implications for morbidity control programs, future studies should employ diagnostic tools beyond stool microscopy to accurately assess the co-endemicity of giardiasis and schistosomiasis.

The association between child Schistosoma spp. infections and morbidity in an irrigated rice region in Mali: A localized study.

BACKGROUND: Schistosomiasis is one of the neglected tropical diseases endemic to Mali. There has been insufficient investigation of the morbidity burden in highly endemic irrigated rice areas with the ongoing mass drug administration with praziquantel. In February 2005, a year after an initial mass drug administration in 2004, we performed the first cross-sectional survey of schistosomiasis in the Kokry-Bozo village in the Office du Niger rice irrigation region. In the fourteen years since this survey, there has been almost no research into schistosomiasis morbidity in Mali due to lack of funding. Therefore, the 2005 survey supplies near-baseline data for any future research into the treatment impacts in the area. METHODS: One hundred and ninety-four children aged 6-14 years from two schools were assessed for bladder pathology by ultrasound, and for anaemia and micro-haematuria by laboratory tests. Schistosoma eggs were examined microscopically in fresh stool and urine samples. Multivariate logistic regression analysis quantified the association of Schistosoma infections with anaemia, bladder pathology and micro-haematuria. Akaike's information criterion was used to test the assumption of linear effects of infection intensity classes and used to compare across models. RESULTS: The overall prevalence of schistosomiasis in 189 school children was 97%; 17% (33/189) had a single infection (S. mansoni,13%, or S. haematobium, 4%) and 80% (156/189) were co-infected with S. mansoni and S. haematobium. The overall prevalence of S. mansoni with light infection was 27% (53/194), moderate infection was 24% (47/194) and heavy infection was 42% (81/194). Of the 194 of children investigated for S. haematobium 59% (114/194) had light infection and 26% (50/194) had heavy infection. No hookworm eggs were detected. The level of abnormal bladder pathology was 18% (35/189) with the highest found in 10-14 year old children. The prevalence of anaemia was 91% (172/189) and was twice as likely to be associated (OR 2.0, 95% CI 1.1-3.9) with S. mansoni infections than in children without infection. As infection intensity with S. mansoni increased the risk of anaemia (OR 2.0, 95% CI 1.1-3.9) also increased. As infection intensity with S. haematobium increased bladder pathology (OR 2.4, 95%CI 1.3-4.5), haematuria (OR 6.7, 95%CI 3.3-13.6) and micro-haematuria increased (OR 2.4, 95%CI 1.3-4.5). CONCLUSION: Our research contributes an important micro-geographical assessment of the heavy burden of schistosomiasis and associated morbidity in children who live in the rice irrigation regions. Our literature review found that there has been very limited research conducted on the impact of the treatment to control morbidity in the ON. Therefore, there is a need to do a comparable, but more extensive, study to identify any changes in morbidity and to indicate current requirements for the control programme. Our results from 2005 called for routine integration of iron supplementation, food fortification and diet diversification into the deworming program.

Inflammation dynamics after praziquantel treatment of Schistosoma haematobium reflected by urinary eosinophil cationic protein.

Background: This cohort study assessed urinary eosinophil cationic protein (ECP) as an indicator for urinary tract morbidity and inflammation indication related to single-dose or dual-dose praziquantel (PZQ) treatment. Methods: Urinary ECP was measured at baseline, 24 h and 9 weeks after treatment (baseline 305, follow-up 204 participants, ages 2-40 years). Results: ECP was significantly associated with the intensity of infection at baseline (p<0.05). Levels at baseline were 8.31 times higher (p<0.01) in participants with bladder morbidity than in those without. There was no correlation with kidney morbidity and no significant effect of a repeated dose of PZQ 40 mg/kg. Baseline ECP and ECP after 9 weeks were associated with microhaematuria (geometric mean ratio at baseline 7.56 [95% confidence limit {CL} 2.34-24.45]; p<0.01) and macrohaematuria (geometric mean ratio at baseline 6.22 [95% CL 2.71-14.24]; p<0.001). Mean levels of ECP dropped significantly during the first follow-up period and far less so in the second follow-up period (mean ECP at baseline: 70.8 ng/mL; ECP at 24 h: 24.5 ng/mL; ECP at 9 weeks: 14.6 ng/mL). Conclusion: The urine ECP decrease happened immediately after treatment, reflecting the rapid action of PZQ on eggs in the bladder tissue. ECP in urine can be used as an indirect marker of the degree of local inflammatory reaction in the bladder and is not significantly affected by a repeated dose of PZQ.

Organomegaly in Mali before and after praziquantel treatment. A possible association with Schistosoma haematobium.

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from a highly endemic area in Mali. Mean intensity of infection at baseline (22.0 eggs per 10 ml) was reduced to 0.22 eggs per 10 ml 9 weeks after treatment (both treatments combined). Odds of persistent infection among those given dual-dose treatment was 41% of that in people given single dose (b = 0.41; p = 0.05; 95% CI 0.17-1.00), but after two years, 70.7% of the 157 participants, who completed the survey, were re-infected with no significant difference in prevalence and intensity of infection between treatment groups. Resolution of organomegaly occurred in all age groups after treatment. A novel association between Schistosoma haematobium infection and moderate portal vein enlargement was found in 35% (n: 55). Severe portal vein diameter enlargement was found in 3.2%. After two years, moderate hepatomegaly was present in 50.6%, moderate splenomegaly in 45.6% and moderate portal vein diameter enlargement in 19%. A subsequent dose of PZQ did not provide any additional long-term advantages.

Anemia and growth retardation associated with Schistosoma haematobium infection in Mali: a possible subtle impact of a neglected tropical disease.

Background: The aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali. Methods: Urine, feces and blood samples from 399 participants of both sexes (2-40 years of age) were analyzed and supplemented by anthropometric measurements. Results: S. haematobium prevalence was 79.8%, S. mansoni 13.2% and Plasmodium falciparum 80.2%. S. haematobium infection intensity as five categories was significantly associated with anemia; i.e., odds of having anemia in the highest and the next highest category was 3.25 (95% CL 1.61-6.55; p<0.01) and 2.45 (95% CL 1.28-4.70; p<0.01), respectively, of that in the three lower categories combined after adjusting for age group and gender and the interaction between the two factors. Anemia was most pronounced in the 2-5 year olds males (55.5%, n=98). P. falciparum infection was not significantly associated with anemia. Stunting (body mass index [BMI] for age z-score<-2.00) was observed in 2.6% (2/78) of the 2-5 years olds and in 7.7% (14/182) in the 6-19 years age group. Lower BMI-z-scores (as continuous variable) were associated with anemia (p<0.05) while high intensity of S. haematobium infection was not significant when adjusting for age group and anemia. Participants with malaria infection had lower z-scores (as continuous variables) of weight and height for age. Lower height for age z-scores were also associated with anemia. Conclusions: S. haematobium infection is likely to impact on child growth and possibly also anemia in all age groups and advocates for inclusion of whole populations into future control programes.

Mortality and Morbidity of Urban Road Traffic Crashes in Africa: Capture-Recapture Estimates in Bamako, Mali, 2012.

BACKGROUND: Low- and middle-income countries are currently facing the massive public health challenge of road traffic injuries. The lack of effective surveillance systems hinders proper assessment of epidemiologic status and intervention priorities. The objective of our study was to estimate the mortality and morbidity attributable to road crashes in Bamako, Mali using the capture-recapture method. METHODS: During the 1 January, 2012-31 April, 2012 period, we collected data on road traffic crashes from the road accident registers of the police forces of Bamako, Mali on the one hand, and from a register kept by health facilities in the same area. An automatic, then manual matching procedure was performed to find pairs of records related to the same crash victims. The number of victims and the number of fatalities were estimated by the capture-recapture method using the Chapman estimator. RESULTS: The health facility and the police registries included 3587 and 1432 records, respectively. The matching procedure identified 603 common records, 31 of which were fatalities. The annual incidence estimate for road victims was 1038 in 100 000 and the annual incidence estimate for road fatalities was 12 in 100 000. Victims from both sources were more likely to be male, in the 15-34 age group, and almost half of all injured road users and two in three fatalities were using motorized two-wheelers. One victim out of five was a pedestrian. CONCLUSION: Our estimates are in line with available literature data from low-income countries. While more cases were reported by health facilities than by police forces, we believe that an effective surveillance system should not be based solely on medical reports as much would be missing as regards the crash circumstances and characteristics.

Significantly reduced intensity of infection but persistent prevalence of schistosomiasis in a highly endemic region in Mali after repeated treatment.

BACKGROUND: Preventive chemotherapy against schistosomiasis has been implemented since 2005 in Mali, targeting school-age children and adults at high risk. A cross-sectional survey was conducted in 2010 to evaluate the impact of repeated treatment among school-age children in the highly-endemic region of Segou. METHODOLOGY/PRINCIPAL FINDINGS: The survey was conducted in six sentinel schools in three highly-endemic districts, and 640 school children aged 7-14 years were examined. Infections with Schistosoma haematobium and S. mansoni were diagnosed with the urine filtration and the Kato-Katz method respectively. Overall prevalence of S. haematobium infection was 61.7%, a significant reduction of 30% from the baseline in 2004 (p<0.01), while overall prevalence of S. mansoni infection was 12.7% which was not significantly different from the baseline. Overall mean intensity of S. haematobium and S. mansoni infection was 180.4 eggs/10 ml of urine and 88.2 epg in 2004 respectively. These were reduced to 33.2 eggs/10 ml of urine and 43.2 epg in 2010 respectively, a significant reduction of 81.6% and 51% (p<0.001). The proportion of heavy S. haematobium infections was reduced from 48.8% in 2004 to 13.8% in 2010, and the proportion of moderate and heavy S. mansoni infection was reduced from 15.6% in 2004 to 9.4% in 2010, both significantly (p<0.01). Mathematical modelling suggests that the observed results were in line with the expected changes. CONCLUSIONS/SIGNIFICANCE: Significant reduction in intensity of infection on both infections and modest but significant reduction in S. haematobium prevalence were achieved in highly-endemic Segou region after repeated chemotherapy. However, persistent prevalence of both infections and relatively high level of intensity of S. mansoni infection suggest that more intensified control measures be implemented in order to achieve the goal of schistosomiasis elimination. In addition, closer monitoring and evaluation activities are needed in the programme to monitor the drug tolerance and to adjust treatment focus.

Impact of Schistosoma haematobium infection on urinary tract pathology, nutritional status and anaemia in school-aged children in two different endemic areas of the Niger River Basin, Mali.

The aim of the present study was to contribute to define urinary schistosomiasis-related morbidity indicators and to understand the relationship between infection intensity and disease burden among school-aged children in different endemic areas of Mali. A cross sectional study was undertaken in two different endemic settings: Koulikoro district, along the river and Selingué dam area in the Niger River Basin in order to compare and describe morbidity related to Schistosoma haematobium infection. A total of 667 children aged 7-14 were enrolled in the study. Among these, 333 were from Koulikoro district (175 boys and 158 girls) and 334 from Selingué dam area (169 boys and 165 girls). The overall prevalence of S. haematobium in the two areas was 91.5%; Koulikoro (97.0%) and Selingué (85.9%) and this difference was significant after adjusting for age, sex and clustering within villages. Prevalence of heavy infection (≥ 50 eggs per 10 ml of urine), 57.6% in Koulikoro and 43.8% in Selingué, did not differ significantly after adjusting for age, sex and clustering within villages. The transmission of Schistosoma mansoni was mainly confined to Selingué dam area (12.5%) and was nearly absent in Koulikoro district (1.1%). Blood in urine was the most frequently reported clinical symptom, more common in Koulikoro (76.8%) than in Selingué (57.6%). In a multivariable logistic regression model adjusting for sex, age group, egg intensity category and clustering within villages, Selingué had higher prevalence of macro-haematuria, urinary tract pathology, upper urinary tract pathology and total pathology than Koulikoro, while micro-haematuria did not differ between the two areas. Morbidity measures increased to some extent with egg intensity category, especially micro-haematuria. The results obtained from this study are of importance for planning intervention as for monitoring and evaluation of control in different endemic settings in Mali.

Geostatistical model-based estimates of Schistosomiasis prevalence among individuals aged ≤ 20 years in West Africa.

BACKGROUND: Schistosomiasis is a water-based disease that is believed to affect over 200 million people with an estimated 97% of the infections concentrated in Africa. However, these statistics are largely based on population re-adjusted data originally published by Utroska and colleagues more than 20 years ago. Hence, these estimates are outdated due to large-scale preventive chemotherapy programs, improved sanitation, water resources development and management, among other reasons. For planning, coordination, and evaluation of control activities, it is essential to possess reliable schistosomiasis prevalence maps. METHODOLOGY: We analyzed survey data compiled on a newly established open-access global neglected tropical diseases database (i) to create smooth empirical prevalence maps for Schistosoma mansoni and S. haematobium for individuals aged ≤ 20 years in West Africa, including Cameroon, and (ii) to derive country-specific prevalence estimates. We used Bayesian geostatistical models based on environmental predictors to take into account potential clustering due to common spatially structured exposures. Prediction at unobserved locations was facilitated by joint kriging. PRINCIPAL FINDINGS: Our models revealed that 50.8 million individuals aged ≤ 20 years in West Africa are infected with either S. mansoni, or S. haematobium, or both species concurrently. The country prevalence estimates ranged between 0.5% (The Gambia) and 37.1% (Liberia) for S. mansoni, and between 17.6% (The Gambia) and 51.6% (Sierra Leone) for S. haematobium. We observed that the combined prevalence for both schistosome species is two-fold lower in Gambia than previously reported, while we found an almost two-fold higher estimate for Liberia (58.3%) than reported before (30.0%). Our predictions are likely to overestimate overall country prevalence, since modeling was based on children and adolescents up to the age of 20 years who are at highest risk of infection. CONCLUSION/SIGNIFICANCE: We present the first empirical estimates for S. mansoni and S. haematobium prevalence at high spatial resolution throughout West Africa. Our prediction maps allow prioritizing of interventions in a spatially explicit manner, and will be useful for monitoring and evaluation of schistosomiasis control programs.