Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study.

BACKGROUND: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19. METHODS: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up. FINDINGS: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19. INTERPRETATION: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission. FUNDING: European Research Council and WHO.

Comparison of platforms for testing antibodies to Chlamydia trachomatis antigens in the Democratic Republic of the Congo and Togo.

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis (Ct), is targeted for elimination as a public health problem. Serological testing for antibodies is promising for surveillance; determining useful thresholds will require collection of serological data from settings with different prevalence of the indicator trachomatous inflammation-follicular (TF). Dried blood spots were collected during trachoma mapping in two districts each of Togo and Democratic Republic of the Congo. Anti-Ct antibodies were detected by multiplex bead assay (MBA) and three different lateral flow assays (LFA) and seroprevalence and seroconversion rate (SCR) were determined. By most tests, the district with > 5% TF (the elimination threshold) had five-sixfold higher seroprevalence and tenfold higher SCR than districts with < 5% TF. The agreement between LFA and MBA was improved using a black latex developing reagent. These data show optimization of antibody tests against Ct to better differentiate districts above or below trachoma elimination thresholds.

Assessment of the usefulness of anti-Wb123 antibody for post-elimination surveillance of lymphatic filariasis.

BACKGROUND: The World Health Organization has targeted lymphatic filariasis (LF) for elimination as a public health problem and recommends, among other measures, post-elimination surveillance of LF. The identification of sensitive and specific surveillance tools is therefore a research priority. The Wuchereria bancrofti-specific antigen Wb123-based enzyme-linked immunosorbent assay (Wb123 ELISA) detects antibodies to the recombinant Wb123 antigen of W. bancrofti and may be useful as a surveillance tool for LF. Six years after stopping mass drug administration to eliminate LF and recording successful results on two post-treatment transmission assessment surveys, a study was conducted in Togo aimed at helping to identify the role of the Wb123 ELISA in post-validation surveillance of LF. METHODS: This was a cross-sectional study in eight previously LF-endemic districts and one non-endemic district in Togo. In each sub-district of these nine districts, two schools were selected and 15 children aged 6 to 9 years old at each school provided finger-stick blood for testing for antibodies to Wb123 using the Filaria Detect™ IgG4 ELISA kit® (InBios, International, Inc., Seattle, WA, USA). RESULTS: A total of 2654 children aged 6 to 9 years old were tested in 134 schools in the nine districts. Overall, 4.7% (126/2654) children tested positive for antibodies to the Wb123 antigen of W. bancrofti. The prevalence of Wb123 antibodies varied across the eight previously endemic LF districts, from 1.56 to 6.62%. The highest prevalence, 6.99%, was found in the non-endemic district, but this was not significantly different from the average of all the LF districts (4.49%, P = 0.062). CONCLUSIONS: The Wb123 ELISA was positive in 4.7% of Togolese school-age children who were almost certainly unexposed to LF. This apparent lack of specificity in the Togo context makes it difficult to establish a seroprevalence threshold that could serve to signal LF resurgence in the country, precluding the use of this test for post-validation surveillance in Togo. There remains a need to develop a useful and reliable test for post-elimination surveillance for LF in humans.

Impact of community-based integrated mass drug administration on schistosomiasis and soil-transmitted helminth prevalence in Togo.

BACKGROUND: Togo has conducted annual, integrated, community-based mass drug administration (MDA) for soil-transmitted helminths (STH) and schistosomiasis since 2010. Treatment frequency and target populations are determined by disease prevalence, as measured by baseline surveys in 2007 and 2009, and WHO guidelines. Reported programmatic treatment coverage has averaged over 94%. Togo conducted a cross-sectional survey in 2015 to assess the impact of four to five years of MDA on these diseases. METHODOLOGY/PRINCIPAL FINDINGS: In every sub-district in the country outside the capital, the same schools were visited as at baseline and a sample of fifteen children age 6 to 9 years old was drawn. Each child submitted urine and a stool sample. Urine samples were tested by dipstick for the presence of blood as a proxy measure of Schistosoma haematobium infection. Stool samples were analyzed by the Kato-Katz method for STH and Schistosoma mansoni. At baseline, 17,100 children were enrolled at 1,129 schools in 562 sub-districts; in 2015, 16,890 children were enrolled at the same schools. The overall prevalence of both STH and schistosomiasis declined significantly, from 31.5% to 11.6% for STH and from 23.5% to 5.0% for schistosomiasis (p<0.001 in both instances). Egg counts from both years were available only for hookworm and S. mansoni; intensity of infection decreased significantly for both infections from 2009 to 2015 (p<0.001 for both infections). In areas with high baseline prevalence, rebound of hookworm infection was noted in children who had not received albendazole in the past 6 months. CONCLUSIONS/SIGNIFICANCE: After four to five years of MDA in Togo, the prevalence and intensity of STH and schistosomiasis infection were significantly reduced compared to baseline. Data on STH indicate that stopping MDA in areas with high baseline prevalence may result in significant rebound of infection. Togo's findings may help refine treatment recommendations for these diseases.

The associations between water and sanitation and hookworm infection using cross-sectional data from Togo's national deworming program.

BACKGROUND: Sustainable control of soil-transmitted helminths requires a combination of chemotherapy treatment and environmental interventions, including access to safe drinking water, sufficient water for hygiene, use of clean sanitation facilities, and handwashing (WASH). We quantified associations between home-, school-, and community-level WASH characteristics and hookworm infection-both prevalence and eggs per gram of stool (intensity)-among Togolese school children in the context of community-based chemotherapy treatments administered in the country from 2010 through 2014. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from two surveys conducted by the Togo Ministry of Health: a school-based survey of students aged 6-9 years across Togo conducted in 2009 and a follow-up survey in 2015, after four to five years of preventive chemotherapy. Data were available for 16,473 students attending 1,129 schools in 2009 and for 16,890 students from 1,126 schools in 2015. Between surveys, children in study schools received 0 to 8 rounds of deworming chemotherapy treatments. Few WASH conditions (only unimproved drinking water) were found to be significantly associated with the presence or absence of hookworms in an individual; however, quantitative eggs per gram of feces was associated with availability of unimproved drinking water, availability of improved drinking water either on or off school grounds, having a handwashing station with water available, and access to a sex-separate non-private or private latrine. The association between school WASH conditions and hookworm infection or burden often depended on the 2009 prevalence of infection, as more WASH characteristics were found to be significant predictors of infection among schools with high underlying endemicity of hookworm. CONCLUSIONS/SIGNIFICANCE: Our findings emphasize the complex and often inconsistent or unpredictable relationship between WASH and hookworm. Specifically, we found that while preventive chemotherapy appeared to dramatically reduce hookworm infection, WASH was associated with infection intensity.

Pilot community-mobilization program reduces maternal and perinatal mortality and prevents obstetric fistula in Niger.

OBJECTIVE: To assess the impact of a pilot community-mobilization program on maternal and perinatal mortality and obstetric fistula in Niger. METHODS: In the program, village volunteers identify and evacuate women with protracted labor, provide education, and collect data on pregnancies, births, and deaths. These data were used to calculate the reduction in maternal mortality, perinatal mortality, and obstetric fistula in the program area from July 2008 to June 2011. RESULTS: The birth-related maternal mortality fell by 73.0% between years 1 and 3 (P<0.001), from 630 (95% confidence interval [CI] 448-861) to 170 (95% CI 85-305) deaths per 100 000 births. Early perinatal mortality fell by 61.5% (P<0.001), from 35 (95% CI 31-40) to 13 (95% CI 10-16) deaths per 1000 births. No deaths due to obstructed labor were reported after the lead-in period (February to June 2008). Seven cases of community-acquired fistula were reported between February 2008 and July 2009; from August 2009 to June 2011 (23 months; 12 254 births), no cases were recorded. CONCLUSION: Community mobilization helped to prevent obstetric fistula and birth-related deaths of women and infants in a large, remote, resource-poor area.

Comparison of anaemia and parasitaemia as indicators of malaria control in household and EPI-health facility surveys in Malawi.

BACKGROUND: The World Health Organization has recommended that anaemia be used as an additional indicator to monitor malaria burden at the community level as malaria interventions are nationally scaled up. To date, there are no published evaluations of this recommendation. METHODS: To evaluate this recommendation, a comparison of anaemia and parasitaemia among 6-30 month old children was made during two repeated cross-sectional household (HH) and health facility (HF) surveys in six districts across Malawi at baseline (2005) and in a follow-up survey (2008) after a scale up of malaria control interventions. RESULTS: HH net ownership did not increase between the years (50.5% vs. 49.8%), but insecticide treated net (ITN) ownership increased modestly from 41.5% (95% CI: 37.2%-45.8%) in 2005 to 45.3% (95% CI: 42.6%-48.0%) in 2008. ITN use by children 6-30 months old, who were living in HH with at least one net, increased from 73.6% (95% CI:68.2%-79.1%) to 80.0% (95% CI:75.9%-84.1%) over the three-year period. This modest increase in ITN use was associated with a decrease in moderate to severe anaemia (Hb <8 g/dl) from 18.4% (95% CI:14.9%-21.8%) in 2005 to 15.4% (13.2%-17.7%) in 2008, while parasitaemia, measured as positive-slide microscopy, decreased from 18.9% (95% CI:14.7%-23.2%) to 16.9% (95% CI:13.8%-20.0%), a relative reduction of 16% and 11%, respectively. In HF surveys, anaemia prevalence decreased from 18.3% (95% CI: 14.9%-21.7%) to 15.4% (95% CI: 12.7%-18.2%), while parasitaemia decreased from 30.6% (95% CI: 25.7%-35.5%) to 13.2% (95% CI: 10.6%-15.8%), a relative reduction of 15% and 57%, respectively. CONCLUSION: Increasing access to effective malaria prevention was associated with a reduced burden of malaria in young Malawian children. Anaemia measured at the HF level at time of routine vaccination may be a good surrogate indicator for its measurement at the HH level in evaluating national malaria control programmes.

Diagnosis of malaria: challenges for clinicians in endemic and non-endemic regions.

Malaria is a leading cause of morbidity and mortality worldwide. Prompt diagnosis and treatment are critical factors in reducing morbidity and mortality, as delayed treatment of malaria increases the risk of death. Microscopy has long been the standard of malaria diagnosis, but newer diagnostic tests now offer advantages in certain settings. Malaria diagnosis is complicated by the fact that acquired immunity to malaria can result in asymptomatic infections. In a symptomatic (febrile) patient, no existing malaria diagnostic test can distinguish malarial illness from parasitemia with concomitant fever of another cause. In this review we discuss the available malaria diagnostic tests, appropriate applications for each, and the challenges of malaria diagnosis in both endemic and non-endemic settings.

Using malarial retinopathy to improve the classification of children with cerebral malaria.

The mechanisms leading to death in cerebral malaria (CM) remain unclear. We compared clinical and laboratory data among children with CM, categorized by ocular fundus findings, to elucidate differences that suggest different underlying pathological processes. From 1999-2005, standard examinations, treatment and record keeping were used for children with a clinical diagnosis of CM. Children were divided into ocular subgroups: normal fundus (N), malarial retinopathy (R), or papilloedema alone (P) and appropriate statistical tests were used to compare clinical and laboratory findings among groups. Eight hundred and eighty children who had eye examinations within 6 h of admission were included in the analysis. The groups differed significantly in case-fatality rates: Group P, 44.4% (95% CI 25.3-63.2), Group R, 18.0% (95% CI 15.6-22.3) and Group N, 7.0% (95% CI 4.2-9.8). There were also significant differences among the groups in blood pressure, prevalence of deep breathing, haematocrit, parasite density, platelet concentration and, among survivors, hours taken to recover from coma. Differences among groups suggest that different underlying pathophysiological processes are operating in children with CM defined by existing criteria. Our proposed classification, by improving the specificity of diagnosis, would enhance consistency among different study sites and prove useful in future research studies.

Cost-effectiveness of on-site antenatal screening to prevent congenital syphilis in rural eastern Cape Province, Republic of South Africa.

OBJECTIVES: On-site screening and same-day treatment of maternal syphilis in underresourced settings can avert greater numbers of congenital syphilis cases, but health outcomes and associated costs must be evaluated jointly. METHODS: We used decision analysis to estimate the incremental cost-effectiveness of two on-site antenatal syphilis screening strategies to avert congenital infections-qualitative RPR (on-site RPR) and treponemal immunochromatographic strip assay (on-site ICS)-compared to the current practice (off-site RPR/TPHA). FINDINGS: With antenatal active syphilis prevalence of 6.3%, the incremental cost-effectiveness of on-site ICS in averting congenital infections was estimated to be USD104, averting 82% of cases expected in absence of a program. The incremental cost-effectiveness of off-site RPR/TPHA was USD82 but would avert only 55% of congenital syphilis cases. On-site RPR was dominated by the other screening strategies. CONCLUSIONS: In settings of high maternal syphilis prevalence, on-site antenatal screening with ICS is a cost-effective approach to reduce the incidence of congenital syphilis.

Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome.

BACKGROUND: Previous prospective studies of bacteremia in African children with severe malaria have mainly included children with cerebral malaria, and no study has examined the impact of human immunodeficiency virus (HIV) infection. We examined the prevalence and etiology of bacteremia and the impact of HIV infection on bacteremia in Malawian children with severe malaria, as well as the impact of bacteremia and HIV infection on outcome. METHODS: From 1996 until 2005, blood for culture was obtained on admission from all children admitted with severe malaria during the rainy season to the Paediatric Research Ward at the Queen Elizabeth Central Hospital in Blantyre, Malawi. HIV testing was performed prospectively from 2001 to 2005 and retrospectively for those admitted from 1996 to 2000. Multivariate regression analysis examined independent risk factors for bacteremia and death. RESULTS: Sixty-four (4.6%) of 1388 children with severe malaria had bacteremia; nontyphoidal Salmonellae (NTS) accounted for 58% of all bacteremias. The prevalence of any bacteremia and of NTS bacteremia was highest in children with severe malarial anemia (11.7% and 7.6%), compared with the prevalence in children with cerebral malaria and severe anemia (4.7% and 3.8%) and in those with cerebral malaria alone (3.0% and 0.9%). HIV infection status was determined in 1119 patients. HIV prevalence was 16% (and was highest in those with severe malaria anemia, at 20.4%), but HIV infection was not significantly associated with bacteremia. Neither bacteremia nor HIV infection was associated with death. CONCLUSIONS: Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic. However, antibiotic therapy should be used to treat NTS infection if bacteremia is suspected in children with severe malarial anemia.

On-site rapid antenatal syphilis screening with an immunochromatographic strip improves case detection and treatment in rural South African clinics.

OBJECTIVES: Congenital syphilis is a significant cause of adverse pregnancy outcomes. In South Africa, rural clinics perform antenatal screening offsite, but unreliable transport and poor client follow up impede effective treatment. We compared 3 syphilis screening strategies at rural clinics: on-site rapid plasma reagin (RPR), on-site treponemal immunochromatographic strip (ICS) test, and the standard practice offsite RPR with Treponema pallidum hemagglutination assay (RPR/TPHA). METHODS: Eight rural clinics performed the on-site RPR and ICS tests and provided immediate treatment. Results were compared with RPR/TPHA at a reference laboratory. Chart reviews at 8 standard practice clinics established diagnosis and treatment rates for offsite RPR/TPHA. FINDINGS: Seventy-nine (6.3%) of 1,250 women screened on-site had active syphilis according to the reference laboratory. The on-site ICS resulted in the highest percentage of pregnant women correctly diagnosed and treated for syphilis (89.4% ICS, 63.9% on-site RPR, 60.8% offsite RPR/TPHA). The on-site RPR had low sensitivity (71.4% for high-titer syphilis). The offsite approach suffered from poor client return rates. One percent of women screened with the ICS may have received penicillin unnecessarily. There were no adverse treatment outcomes. CONCLUSIONS: The on-site ICS test can reduce syphilis-related adverse outcomes of pregnancy through accurate diagnosis and immediate treatment of pregnant women with syphilis.