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 .

Progress towards elimination of onchocerciasis transmission in Mali: A "pre-stop MDA" survey in 18 transmission zones.

BACKGROUND: Onchocerciasis control activities in Mali began in 1975 with vector larviciding carried out by the Onchocerciasis Control Programme (OCP), followed by the distribution of ivermectin from 1998 until the closure of the OCP in 2002. At that time, epidemiological evaluations, using skin snip microscopy and O-150 pool screening PCR in black flies, indicated that the disease had been largely controlled as a public health problem. Ivermectin distribution was nevertheless continued after 2002 in 34 of the 75 health districts in Mali as these were known to still be meso- or hyper-endemic for onchocerciasis. In addition, the onchocerciasis sites known to be hypo-endemic for onchocerciasis benefited from the distribution of ivermectin treatment as part of the mass drug administration (MDA) program for lymphatic filariasis. Various entomological and epidemiological evaluations have now indicated that Mali may have achieved successful interruption of onchocerciasis transmission. METHODS: A series of cross-sectional surveys to update vector breeding sites throughout the endemic areas, followed by a pre-stop ivermectin mass drug administration (Pre-stop MDA) survey, were undertaken in 2019-2020. Based on breeding site findings, historical epidemiological assessments, and vector collection site maps, 18 operational transmission zones (OTZ) were delineated within which a total of 104 first line villages were selected for evaluation. Dried blood spots (DBS) samples were collected from 10,400 children (5-9 years old) from these 104 first line villages and processed for the presence of OV16 antibody using a lab-based rapid diagnostic test. RESULTS: Within the 544 Simulium damnosum s.l. breeding sites visited in all five endemic onchocerciasis endemic regions of Mali 18.01% (98/544) were seen to be active with the presence of at least one stage of S. damnosum. The overall prevalence of OV16 positive children was 0.45% (47/10,400). However, two hotspots were identified: 2.60% (13/500) seroprevalence in the OTZ number 5 in Kayes Region and 1.40% (7/500) in the OTZ number 1 of Sikasso Region. CONCLUSION: These data show that onchocerciasis prevalence in the five endemic regions has declined to levels that indicate that Stop-MDA surveys should be now carried out in most of the OTZ except for one in the Kayes Region. This latter site will need additional ivermectin treatment before reevaluation, and an OTZ in the Sikasso Region requires revaluation before possibly reinitiating MDA.

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.

Measurement of tetanus antitoxin in oral fluid: a tool to conduct serosurveys.

BACKGROUND: Serosurveys that measure tetanus antitoxin can complement immunization coverage surveys to allow evaluation of immunization services in developing countries. Measurement of IgG tetanus antitoxin in oral fluid was investigated as a practical and noninvasive alternative to and correlate of serum antibodies. METHODS: Serum and oral fluid were collected from Malian infants, toddlers and adults (males without a history of tetanus vaccination). Specific IgG tetanus antitoxin was measured by enzyme-linked immunosorbent assay in serum (S-ELISA) and oral fluid (OF-ELISA). RESULTS: One hundred forty-two pairs of serum and oral fluid samples were collected from infants, 35 pairs from toddlers and 35 pairs from adults. IgG tetanus antitoxin titers measured by OF-ELISA were 100-fold lower than those measured by S-ELISA but they correlated strongly (r = 0.90, P < 0.001). All 35 toddlers who had received 2 or 3 doses of diphtheria-tetanus-pertussis (DTP) vaccine (100%) had serum tetanus antitoxin levels >or=0.15 IU/mL and 28 of 35 (80%) had oral fluid values >or=0.0015 IU/mL. Among adults lacking a history of tetanus immunization, only 6 of 35 (17.1%) had serum titers >or=0.15 IU/mL and 4 of 35 (11%) had oral fluid titers >or=0.0015 IU/mL in oral fluid. CONCLUSIONS: IgG tetanus antitoxin in oral fluid correlates well with levels in serum. OF-ELISA values >or=0.0015 IU/mL constitute protection against tetanus and in subjects >12 months of age imply multiple prior contacts with immunization services. IgG tetanus antitoxin measured by OF-ELISA provides a logistically practical alternative for performing seroprevalence surveys.

Quality of piped and stored water in households with children under five years of age enrolled in the Mali site of the Global Enteric Multi-Center Study (GEMS).

Water, sanitation, and hygiene information was collected during a matched case-control study of moderate and severe diarrhea (MSD) among 4,096 children < 5 years of age in Bamako, Mali. Primary use of piped water (conditional odds ratio [cOR] = 0.45; 0.34-0.62), continuous water access (cOR = 0.30; 0.20-0.43), fetching water daily (cOR = 0.77; 0.63-0.96), and breastfeeding (cOR = 0.65; 0.49-0.88) significantly reduced the likelihood of MSD. Fetching water in > 30 minutes (cOR = 2.56; 1.55-4.23) was associated with MSD. Piped tap water and courier-delivered water contained high (> 2 mg/L) concentrations of free residual chlorine and no detectable Escherichia coli. However, many households stored water overnight, resulting in inadequate free residual chlorine (< 0.2 mg/L) for preventing microbial contamination. Coliforms and E. coli were detected in 48% and 8% of stored household water samples, respectively. Although most of Bamako's population enjoys access to an improved water source, water quality is often compromised during household storage.