Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger.

BACKGROUND: Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. METHODS: We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. RESULTS: Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. CONCLUSIONS: Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).

Case-Fatality Rates and Sequelae Resulting from Neisseria meningitidis Serogroup C Epidemic, Niger, 2015.

We describe clinical symptoms, case-fatality rates, and prevalence of sequelae during an outbreak of Neisseria meningitidis serogroup C infection in a rural district of Niger. During home visits, we established that household contacts of reported case-patients were at higher risk for developing meningitis than the general population.

Rotavirus surveillance in urban and rural areas of Niger, April 2010-March 2012.

Knowledge of rotavirus epidemiology is necessary to make informed decisions about vaccine introduction and to evaluate vaccine impact. During April 2010-March 2012, rotavirus surveillance was conducted among 9,745 children <5 years of age in 14 hospitals/health centers in Niger, where rotavirus vaccine has not been introduced. Study participants had acute watery diarrhea and moderate to severe dehydration, and 20% of the children were enrolled in a nutrition program. Of the 9,745 children, 30.6% were rotavirus positive. Genotyping of a subset of positive samples showed a variety of genotypes during the first year, although G2P[4] predominated. G12 genotypes, including G12P[8], which has emerged as a predominant strain in western Africa, represented >80% of isolates during the second year. Hospitalization and death rates and severe dehydration among rotavirus case-patients did not differ during the 2 years. The emergence of G12P[8] warrants close attention to the characteristics of associated epidemics and possible prevention measures.

The dynamics of measles in sub-Saharan Africa.

Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur.

Health care seeking behavior for diarrhea in children under 5 in rural Niger: results of a cross-sectional survey.

BACKGROUND: Diarrhea remains the second leading cause of death in children under 5 years of age in sub-Saharan Africa. Health care seeking behavior for diarrhea varies by context and has important implications for developing appropriate care strategies and estimating burden of disease. The objective of this study was to determine the proportion of children under five with diarrhea who consulted at a health structure in order to identify the appropriate health care levels to set up surveillance of severe diarrheal diseases. METHODS: A cluster survey was done on 35 clusters of 21 children under 5 years of age in each of four districts of the Maradi Region, Niger. Caretakers were asked about diarrhea of the child during the recall period and their health seeking behavior in case of diarrhea. A weighted cluster analysis was conducted to determine the prevalence of diarrhea, as well as the proportion of consultations and types of health structures consulted. RESULTS: In total, the period prevalence of diarrhea and severe diarrhea between April 24th and May 21st 2009 were 36.8% (95% CI: 33.7 - 40.0) and 3.4% (95% CI: 2.2-4.6), respectively. Of those reporting an episode of diarrhea during the recall period, 70.4% (95% CI: 66.6-74.1) reported seeking care at a health structure. The main health structures visited were health centers, followed by health posts both for simple or severe diarrhea. Less than 10% of the children were brought to the hospital. The proportion of consultations was not associated with the level of education of the caretaker, but increased with the number of children in the household. CONCLUSIONS: The proportion of consultations for diarrhea cases in children under 5 years old was higher than those reported in previous surveys in Niger and elsewhere. Free health care for under 5 years old might have participated in this improvement. In this type of decentralized health systems, the WHO recommended hospital-based surveillance of severe diarrheal diseases would capture only a fraction of severe diarrhea. Lower levels of health structures should be considered to obtain informative data to ensure appropriate care and burden estimates.

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model.

BACKGROUND: Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. METHODS: We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. RESULTS: Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. CONCLUSIONS: The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child.

Rural-urban gradient in seasonal forcing of measles transmission in Niger.

Seasonally driven cycles of incidence have been consistently observed for a range of directly transmitted pathogens. Though frequently observed, the mechanism of seasonality for directly transmitted human pathogens is rarely well understood. Despite significant annual variation in magnitude, measles outbreaks in Niger consistently begin in the dry season and decline at the onset of the seasonal rains. We estimate the seasonal fluctuation in measles transmission rates for the 38 districts and urban centres of Niger, from 11 years of weekly incidence reports. We show that transmission rates are consistently in anti-phase to the rainfall patterns across the country. The strength of the seasonal forcing of transmission is not correlated with the latitudinal rainfall gradient, as would be expected if transmission rates were determined purely by environmental conditions. Rather, seasonal forcing is correlated with the population size, with larger seasonal fluctuation in more populous, urban areas. This pattern is consistent with seasonal variation in human density and contact rates due to agricultural cycles. The stronger seasonality in large cities drives deep inter-epidemic troughs and results in frequent local extinction of measles, which contrasts starkly to the conventional observation that large cities, by virtue of their size, act as reservoirs of measles.

Effectiveness of ready-to-use therapeutic food compared to a corn/soy-blend-based pre-mix for the treatment of childhood moderate acute malnutrition in Niger.

Standard nutritional treatment of moderate acute malnutrition (MAM) relies on fortified blended flours though their importance to treat this condition is a matter of discussion. With the newly introduced World Health Organization growth standards, more children at an early stage of malnutrition will be treated following the dietary protocols as for severe acute malnutrition, including ready-to-use therapeutic food (RUTF). We compared the effectiveness of RUTF and a corn/soy-blend (CSB)-based pre-mix for the treatment of MAM in the supplementary feeding programmes (SFPs) supported by Médecins Sans Frontières, located in the Zinder region (south of Niger). Children measuring 65 to <110 cm, newly admitted with MAM [weight-for-height (WHM%) between 70% and <80% of the NCHS median] were randomly allocated to receive either RUTF (Plumpy'Nut®, 1000 kcal day(-1)) or a CSB pre-mix (1231 kcal day(-1)). Other interventions were similar in both groups (e.g. weekly family ration and ration at discharge). Children were followed weekly up to recovery (WHM% ≥ 85% for 2 consecutive weeks). In total, 215 children were recruited in the RUTF group and 236 children in the CSB pre-mix group with an overall recovery rate of 79.1 and 64.4%, respectively (p < 0.001). There was no evidence for a difference between death, defaulter and non-responder rates. More transfers to the inpatient Therapeutic Feeding Centre (I-TFC) were observed in the CSB pre-mix group (19.1%) compared to the RUTF group (9.3%) (p = 0.003). The average weight gain up to discharge was 1.08 g kg(-1) day(-1) higher in the RUTF group [95% confidence interval: 0.46-1.70] and the length of stay was 2 weeks shorter in the RUTF group (p < 0.001). For the treatment of childhood MAM in Niger, RUTF resulted in a higher weight gain, a higher recovery rate, a shorter length of stay and a lower transfer rate to the I-TFC compared to a CSB pre-mix. This might have important implications on the efficacy and the quality of SFPs.

Investigating persistent measles dynamics in Niger and associations with rainfall.

Measles is a major cause of child mortality in sub-Saharan Africa. Current immunization strategies achieve low coverage in areas where transmission drivers differ substantially from those in high-income countries. A better understanding of measles transmission in areas with measles persistence will increase vaccination coverage and reduce ongoing transmission. We analysed weekly reported measles cases at the district level in Niger from 1995 to 2004 to identify underlying transmission mechanisms. We identified dominant periodicities and the associated spatial clustering patterns. We also investigated associations between reported measles cases and environmental drivers associated with human activities, particularly rainfall. The annual and 2-3-year periodicities dominated the reporting data spectrum. The annual periodicity was strong with contiguous spatial clustering, consistent with the latitudinal gradient of population density, and stable over time. The 2-3-year periodicities were weaker, unstable over time and had spatially fragmented clustering. The rainy season was associated with a lower risk of measles case reporting. The annual periodicity likely reflects seasonal agricultural labour migration, whereas the 2-3-year periodicity potentially results from multiple mechanisms such as reintroductions and vaccine coverage heterogeneity. Our findings suggest that improving vaccine coverage in seasonally mobile populations could reduce strong measles seasonality in Niger and across similar settings.

Effect of preventive supplementation with ready-to-use therapeutic food on the nutritional status, mortality, and morbidity of children aged 6 to 60 months in Niger: a cluster randomized trial.

CONTEXT: Ready-to-use therapeutic foods (RUTFs) are an important component of effective outpatient treatment of severe wasting. However, their effectiveness in the population-based prevention of moderate and severe wasting has not been evaluated. OBJECTIVE: To evaluate the effect of a 3-month distribution of RUTF on the nutritional status, mortality, and morbidity of children aged 6 to 60 months in Niger. DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized trial of 12 villages in Maradi, Niger. Six villages were randomized to intervention and 6 to no intervention. All children in the study villages aged 6 to 60 months were eligible for recruitment. INTERVENTION: Children with weight-for-height 80% or more of the National Center for Health Statistics reference median in the 6 intervention villages received a monthly distribution of 1 packet per day of RUTF (92 g [500 kcal/d]) from August to October 2006. Children in the 6 nonintervention villages received no preventive supplementation. Active surveillance for conditions requiring medical or nutritional treatment was conducted monthly in all 12 study villages from August 2006 to March 2007. MAIN OUTCOME MEASURES: Changes in weight-for-height z score (WHZ) according to the World Health Organization Child Growth Standards and incidence of wasting (WHZ <-2) over 8 months of follow-up. RESULTS: The number of children with height and weight measurements in August, October, December, and February was 3166, 3110, 2936, and 3026, respectively. The WHZ difference between the intervention and nonintervention groups was -0.10 z (95% confidence interval [CI], -0.23 to 0.03) at baseline and 0.12 z (95% CI, 0.02 to 0.21) after 8 months of follow-up. The adjusted effect of the intervention on WHZ from baseline to the end of follow-up was thus 0.22 z (95% CI, 0.13 to 0.30). The absolute rate of wasting and severe wasting, respectively, was 0.17 events per child-year (140 events/841 child-years) and 0.03 events per child-year (29 events/943 child-years) in the intervention villages, compared with 0.26 events per child-year (233 events/895 child-years) and 0.07 events per child-year (71 events/1029 child-years) in the nonintervention villages. The intervention thus resulted in a 36% (95% CI, 17% to 50%; P < .001) reduction in the incidence of wasting and a 58% (95% CI, 43% to 68%; P < .001) reduction in the incidence of severe wasting. There was no reduction in mortality, with a mortality rate of 0.007 deaths per child-year (7 deaths/986 child-years) in the intervention villages and 0.016 deaths per child-year (18 deaths/1099 child-years) in the nonintervention villages (adjusted hazard ratio, 0.51; 95% CI, 0.25 to 1.05). CONCLUSION: Short-term supplementation of nonmalnourished children with RUTF reduced the decline in WHZ and the incidence of wasting and severe wasting over 8 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00682708.

Ciprofloxacin for contacts of cases of meningococcal meningitis as an epidemic response: study protocol for a cluster-randomized trial.

BACKGROUND: Epidemics of meningococcal meningitis are common in the "African meningitis belt." Current response strategies include reactive vaccination campaigns, which are often organized too late to have maximal impact. A novel strain of Neisseria meningitidis serogroup C has been circulating in recent years, and vaccine supplies are limited. An evaluation of chemoprophylaxis with single-dose ciprofloxacin for household contacts of meningitis cases has therefore been recommended. METHODS/DESIGN: A three-arm cluster-randomized trial has been designed for implementation during a meningococcal meningitis epidemic in a health district in Niger in which at least two Health Zones (HZs) have met the weekly epidemic threshold. The primary outcome is the incidence (attack rate) of meningitis during the epidemic. Villages will be randomized in a 1:1:1 ratio to one of three different arms: standard care, household-level prophylaxis, or village-wide prophylaxis. After study launch, when a case of meningococcal meningitis is identified in an HZ, the first reported case from a village will trigger the inclusion and randomization of the village. Household-level prophylaxis with single-dose ciprofloxacin will be offered in the home to all household members within 24 hours of the notification of the case, and village-wide distributions will occur within 72 hours of the notification of the case. The sample size necessary to detect differences between each of the two intervention arms and the standard care arm will be set after 4 weeks of data collection, in order to quantify multiple variables that could be particular to a given area. The primary analysis will compare attack rates at the end of the epidemic in each of the three arms. A nested sub-study will assess the effects of ciprofloxacin prophylaxis on the prevalence of ciprofloxacin-resistant enterobacteriaceae. A total of 200 participants in the standard care arm and 200 in the village-wide prophylaxis arm will provide stool samples at days 0, 7, and 28 following their village's inclusion in the study. DISCUSSION: An innovative trial is proposed for implementation during an epidemic that will assess the impact of a novel strategy for meningitis outbreak response. In parallel, we will describe potential negative effects of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02724046 . Registered on 15 March 2016. Last updated on 13 June 2017.

Measuring populations to improve vaccination coverage.

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes.

The actual and potential costs of meningitis surveillance in the African meningitis belt: Results from Chad and Niger.

BACKGROUND: The introduction of serogroup A meningococcal conjugate vaccine in the African meningitis belt required strengthened surveillance to assess long-term vaccine impact. The costs of implementing this strengthening had not been assessed. METHODOLOGY: The ingredients approach was used to retrospectively determine bacterial meningitis surveillance costs in Chad and Niger in 2012. Resource use and unit cost data were collected through interviews with staff at health facilities, laboratories, government offices and international partners, and by reviewing financial reports. Sample costs were extrapolated to national level and costs of upgrading to desired standards were estimated. RESULTS: Case-based surveillance had been implemented in all 12 surveyed hospitals and 29 of 33 surveyed clinics in Niger, compared to six out of 21 clinics surveyed in Chad. Lumbar punctures were performed in 100% of hospitals and clinics in Niger, compared to 52% of the clinics in Chad. The total costs of meningitis surveillance were US$ 1,951,562 in Niger and US$ 338,056 in Chad, with costs per capita of US$ 0.12 and US$ 0.03, respectively. Laboratory investigation was the largest cost component per surveillance functions, comprising 51% of the total costs in Niger and 40% in Chad. Personnel resources comprised the biggest expense type: 37% of total costs in Niger and 26% in Chad. The estimated annual, incremental costs of upgrading current systems to desired standards were US$ 183,299 in Niger and US$ 605,912 in Chad, which are 9% and 143% of present costs, respectively. CONCLUSIONS: Niger's more robust meningitis surveillance system costs four times more per capita than the system in Chad. Since Chad spends less per capita, fewer activities are performed, which weakens detection and analysis of cases. Countries in the meningitis belt are diverse, and can use these results to assess local costs for adapting surveillance systems to monitor vaccine impact.

Predominance of CRF02-AG and CRF06-cpx in Niger, West Africa.

A total of 110 HIV-1-positive samples obtained in 1997 (n = 44) and 2000 (n = 66) were genetically characterized in the V3-V5 envelope region and the p24 gag region. The majority of the strains were CRF02-AG (54.3%) or CRF06-cpx (18.1%) in env and gag. More than 9% of the samples were recombinants between CRF02 and CRF06; 9 were CRF06 in env but CRF02 in gag, and for one sample the opposite was seen. Overall for 23 (20.9%) samples, the subtype designation was different between env and gag, and in 20 of these 23 samples a CRF was involved in the recombination event. No significant differences were seen between subtype distributions in 1997 and 2000, except that the proportion of recombinants increased from 13.6% in 1997 to 27.2% in 2000.

Emergence of complex and diverse CRF02-AG/CRF06-cpx recombinant HIV type 1 strains in Niger, West Africa.

On the basis of partial env and gag subtyping, we documented that the majority of HIV-1 strains circulating in Niger were CRF02-AG (54.3%) or CRF06-cpx (18.1%) and that 9% of the samples were possible recombinants between CRF02 and CRF06. To determine in more detail the precise structure of these viruses we sequenced the full-length genomes for three such strains (97NE-003, 00NE-036, and 00NE-095). From the bootscan and phylogenetic tree analysis it is evident that the new viruses are the result of recombination events between CRF02-AG and CRF06-cpx strains. Importantly, each virus had a different complex recombinant structure with multiple breakpoints, leading to viruses with complex mosaic patterns.

[Chlamydia pneumoniae and acute respiratory tract infections in breast-feeding infants: simultaneous mother-child serological study in Niamey (Niger)]. / Chlamydia pneumoniae et infections respiratoires aiguës chez l'enfant nourri au sein: étude sérologique simultanée mére-enfant à Niamey (Niger).

The age and the origin of Chlamydia pneumoniae primary infection in Sahelian areas are unknown. To evaluate the prevalence of C. pneumoniae antibodies, the authors studied the serological status of C. pneumoniae-, C. psittaci- and C. trachomatis-specific antibodies of 50 mother-child couples using the microimmunofluorescence technique. Children were 10 to 34 month-old (18,1 6,2, mean SD), breast-fed and hospitalized with acute respiratory tract infections in Niamey (republic of Niger). Specific C. pneumoniae IgG antibodies were present in 46/48 (95.8%) children, IgA in 32/48 (66.6%). In the mothers, specific C. pneumoniae IgG antibodies were present in 40/48 (83.3%), IgA in 31/48 (64.6%). The specific IgM antibodies were steadily absent in mothers and children. In the mother-child couples, 38/46 (79.2%) had specific C. pneumoniae IgG antibodies and 23/47 (48.9%) had IgA. The prevalence of specific C. pneumoniae IgG and IgA antibodies is very high in this population. These results point out that C. pneumoniae primary infection is very precocious in this paediatric population and is very different from American, Asian and European reports. A mother-child direct contamination during the first months of life in this breast-feeding pediatric population is discussed.

Safety and efficacy of praziquantel syrup (Epiquantel®) against Schistosoma haematobium and Schistosoma mansoni in preschool-aged children in Niger.

Given the characteristic age-prevalence curve of Schistosoma infection, preventive chemotherapy with praziquantel is primarily targeted at school-aged children, whilst, in highly endemic areas, other high-risk groups might be included for regular treatment. Nevertheless, schistosomiasis can affect children well before they reach school-age, but this population group is usually excluded from preventive chemotherapy. We assessed the safety and efficacy of praziquantel syrup (Epiquantel®) in preschool-aged children in three villages of Niger. Children aged ≤72 months provided multiple urine and stool samples that were microscopically examined using standard protocols. Schistosoma-positive children were treated with praziquantel syrup at a dose of 40 mg/kg after a meal of millet porridge. Children remained under medical supervision for 4h and adverse events were recorded. Additionally, a questionnaire was administrated to the mothers/guardians 24h post-treatment for further probing of adverse events. Treatment efficacy was evaluated 3 and 6 weeks post-treatment using multiple stool and urine samples. A third of the 243 treated children reported adverse events within 4h, whilst a further 6.2% reported adverse events upon probing 24h post-treatment. Abdominal pain, bloody diarrhoea and sleepiness were the most common adverse events, but these were transient and self-limiting. Praziquantel syrup showed moderate-to-high efficacy against Schistosoma haematobium with egg reduction rates of 69.4% and 71.2% 3 and 6 weeks post-treatment and cure rates of 85.7% (95% confidence interval (CI) 79.7-90.5%) and 94.9% (95% CI 90.5-97.6%), respectively. Considerably lower cure and egg reduction rates were observed against Schistosoma mansoni (e.g. cure rate at 6-week post-treatment follow-up was only 50.6% (95% CI 39.9-61.2%). Concluding, praziquantel syrup is well tolerated in preschool-aged children with moderate-to-high efficacy against S. haematobium, but considerably lower efficacy against S. mansoni in Niger. A larger study is warranted to investigate the observed differences in species-specific susceptibilities and to assess operational issues and community-effectiveness.

Efficacy and safety of two closely spaced doses of praziquantel against Schistosoma haematobium and S. mansoni and re-infection patterns in school-aged children in Niger.

The aim of this study was to assess the efficacy and safety of two closely spaced doses of praziquantel (PZQ) against Schistosoma haematobium and S. mansoni infection in school-aged children, and to characterise re-infection patterns over a 12-month period. The study was carried out in five villages in western Niger: Falmado, Seberi and Libore (single S. haematobium infection foci), and Diambala and Namarigoungou (mixed S. haematobium-S. mansoni infection foci). Parasitological examinations consisted of triplicate urine filtrations and triplicate Kato-Katz thick smears at each visit. Two 40mg/kg oral doses of PZQ were administered 3 weeks apart. Adverse events were monitored within 4h after dosing by the survey team and 24h after treatment using a questionnaire. Our final study cohort comprised 877 children who were infected with either S. haematobium, or S. mansoni, or both species concurrently and received both doses of PZQ. Follow-up visits were conducted 6 weeks, 6 months and 12 months after the first dose of PZQ. At baseline, the geometric mean (GM) infection intensity of S. haematobium ranged from 3.6 (Diambala) to 30.3eggs/10ml of urine (Falmado). The GM infection intensity of S. mansoni ranged from 86.7 (Diambala) to 151.4eggs/g of stool (Namarigoungou). Adverse events were reported by 33.0% and 1.5% of the children after the first and second doses of PZQ, respectively. We found cure rates (CRs) in S. haematobium-infected children 3 weeks after the second dose of PZQ ranging between 49.2% (Falmado) and 98.4% (Namarigoungou) and moderate-to-high egg reduction rates (ERRs) (71.4-100%). Regarding S. mansoni, only moderate CRs and ERRs were found (51.7-58.8% in Diambala, 55.2-60.2% in Namarigoungou). Twelve months post-treatment, prevalence rates approached pre-treatment levels, but infection intensities remained low. In conclusion, PZQ, given in two closely spaced doses, is efficacious against S. haematobium, but the low ERR observed against S. mansoni raises concern about mounting PZQ tolerance.

Removing the regional level from the Niger vaccine supply chain.

OBJECTIVE: Since many of the world's vaccine supply chains contain multiple levels, the question remains of whether removing a level could bring efficiencies. METHODS: We utilized HERMES to generate a detailed discrete-event simulation model of Niger's vaccine supply chain and compared the current four-tier (central, regional, district, and integrated health center levels) with a modified three-tier structure (removing the regional level). Different scenarios explored various accompanying shipping policies and frequencies. FINDINGS: Removing the regional level and implementing a collection-based shipping policy from the district stores increases vaccine availability from a mean of 70-100% when districts could collect vaccines at least weekly. Alternatively, implementing a delivery-based shipping policy from the central store monthly in three-route and eight-route scenarios only increases vaccine availability to 87%. Restricting central-to district vaccine shipments to a quarterly schedule for three-route and eight-route scenarios reduces vaccine availability to 49%. The collection-based shipping policy from district stores reduces supply chain logistics cost per dose administered from US$0.14 at baseline to US$0.13 after removing the regional level. CONCLUSION: Removing the regional level from Niger's vaccine supply chain can substantially improve vaccine availability as long as certain concomitant adjustments to shipping policies and frequencies are implemented.