Azithromycin during Routine Well-Infant Visits to Prevent Death.

BACKGROUND: Mass distribution of azithromycin to children 1 to 59 months of age has been shown to reduce childhood all-cause mortality in some sub-Saharan African regions, with the largest reduction seen among infants younger than 12 months of age. Whether the administration of azithromycin at routine health care visits for infants would be effective in preventing death is unclear. METHODS: We conducted a randomized, placebo-controlled trial of a single dose of azithromycin (20 mg per kilogram of body weight) as compared with placebo, administered during infancy (5 to 12 weeks of age). The primary end point was death before 6 months of age. Infants were recruited at routine vaccination or other well-child visits in clinics and through community outreach in three regions of Burkina Faso. Vital status was assessed at 6 months of age. RESULTS: Of the 32,877 infants enrolled from September 2019 through October 2022, a total of 16,416 infants were randomly assigned to azithromycin and 16,461 to placebo. Eighty-two infants in the azithromycin group and 75 infants in the placebo group died before 6 months of age (hazard ratio, 1.09; 95% confidence interval [CI], 0.80 to 1.49; P = 0.58); the absolute difference in mortality was 0.04 percentage points (95% CI, -0.10 to 0.21). There was no evidence of an effect of azithromycin on mortality in any of the prespecified subgroups, including subgroups defined according to age, sex, and baseline weight, and no evidence of a difference between the two trial groups in the incidence of adverse events. CONCLUSIONS: In this trial conducted in Burkina Faso, we found that administration of azithromycin to infants through the existing health care system did not prevent death. (Funded by the Bill and Melinda Gates Foundation; CHAT ClinicalTrials.gov number, NCT03676764.).

Single-dose azithromycin for infant growth in Burkina Faso: Prespecified secondary anthropometric outcomes from a randomized controlled trial.

BACKGROUND: Antibiotic use during early infancy has been linked to childhood obesity in high-income countries. We evaluated whether a single oral dose of azithromycin administered during infant-well visits led to changes in infant growth outcomes at 6 months of age in a setting with a high prevalence of undernutrition in rural Burkina Faso. METHODS AND FINDINGS: Infants were enrolled from September 25, 2019, until October 22, 2022, in a randomized controlled trial designed to evaluate the efficacy of a single oral dose of azithromycin (20 mg/kg) compared to placebo when administered during well-child visits for prevention of infant mortality. The trial found no evidence of a difference in the primary endpoint. This paper presents prespecified secondary anthropometric endpoints including weight gain (g/day), height change (mm/day), weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC). Infants were eligible for the trial if they were between 5 and 12 weeks of age, able to orally feed, and their families were planning to remain in the study area for the duration of the study. Anthropometric measurements were collected at enrollment (5 to 12 weeks of age) and 6 months of age. Among 32,877 infants enrolled in the trial, 27,298 (83%) were followed and had valid anthropometric measurements at 6 months of age. We found no evidence of a difference in weight gain (mean difference 0.03 g/day, 95% confidence interval (CI) -0.12 to 0.18), height change (mean difference 0.004 mm/day, 95% CI -0.05 to 0.06), WAZ (mean difference -0.004 SD, 95% CI -0.03 to 0.02), WLZ (mean difference 0.001 SD, 95% CI -0.03 to 0.03), LAZ (mean difference -0.005 SD, 95% CI -0.03 to 0.02), or MUAC (mean difference 0.01 cm, 95% CI -0.01 to 0.04). The primary limitation of the trial was that measurements were only collected at enrollment and 6 months of age, precluding assessment of shorter-term or long-term changes in growth. CONCLUSIONS: Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03676764.

Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial.

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Effectiveness of Four Different Interventions Against Schistosoma haematobium in a Seasonal Transmission Setting of Côte d'Ivoire: A Cluster Randomized Trial.

BACKGROUND: Annual mass drug administration (MDA) using praziquantel is the cornerstone of schistosomiasis morbidity control but is not sufficient to interrupt transmission. We implemented a cluster-randomized trial to compare the effectiveness of 4 different intervention packages to interrupt transmission of Schistosoma haematobium in a seasonal transmission setting of Côte d'Ivoire. METHODS: Sixty-four localities with a S. haematobium prevalence in school children aged 13-14 years above 4% were randomly assigned to 1 of 4 intervention arms over a 3-year period: (1) the current standard strategy consisting of annual MDA before peak of transmission, (2) annual MDA after peak of transmission, (3) biannual MDA, and (4) standard MDA combined with snail control. The primary outcome was prevalence and intensity of S. haematobium infection in children aged 9-12 years 1 year after the final intervention, using urine filtration performed by experienced microscopists. RESULTS: By study end, we observed the lowest S. haematobium prevalence in the biannual MDA, compared to the standard treatment arm (0.6% vs 7.5%; odds ratio [OR] = 0.07, 95% confidence interval [CI] = .02 to .24). The prevalence in arms 2 and 4 was about 3.5%, which was not statistically significantly different from the standard strategy (both ORs 0.4, 95% CI = .1 to ~1.8). New cases of infection were still observed in all arms at study end. CONCLUSIONS: Biannual MDA was the only regimen that outperformed the standard treatment. All strategies resulted in decreased prevalence of infection; however, none of them was able to interrupt transmission of S. haematobium within a 3-year period. CLINICAL TRIALS REGISTRATION: ISRCTN10926858.

Malaria positivity following a single oral dose of azithromycin among children in Burkina Faso: a randomized controlled trial.

BACKGROUND: Azithromycin is a broad-spectrum antibiotic that has moderate antimalarial activity and has been shown to reduce all-cause mortality when biannually administered to children under five in high mortality settings in sub-Saharan Africa. One potential mechanism for this observed reduction in mortality is via a reduction in malaria transmission. METHODS: We evaluated whether a single oral dose of azithromycin reduces malaria positivity by rapid diagnostic test (RDT). We conducted an individually randomized placebo-controlled trial in Burkina Faso during the high malaria transmission season in August 2020. Children aged 8 days to 59 months old were randomized to a single oral dose of azithromycin (20 mg/kg) or matching placebo. At baseline and 14 days following treatment, we administered a rapid diagnostic test (RDT) to detect Plasmodium falciparum and measured tympanic temperature for all children. Caregiver-reported adverse events and clinic visits were recorded at the day 14 visit. RESULTS: We enrolled 449 children with 221 randomized to azithromycin and 228 to placebo. The median age was 32 months and 48% were female. A total of 8% of children had a positive RDT for malaria at baseline and 11% had a fever (tympanic temperature ≥ 37.5 °C). In the azithromycin arm, 8% of children had a positive RDT for malaria at 14 days compared to 7% in the placebo arm (P = 0.65). Fifteen percent of children in the azithromycin arm had a fever ≥ 37.5 °C compared to 21% in the placebo arm (P = 0.12). Caregivers of children in the azithromycin group had lower odds of reporting fever as an adverse event compared to children in the placebo group (OR 0.41, 95% CI 0.18-0.96, P = 0.04). Caregiver-reported clinic visits were uncommon, and there were no observed differences between arms (P = 0.32). CONCLUSIONS: We did not find evidence that a single oral dose of azithromycin reduced malaria positivity during the high transmission season. Caregiver-reported fever occurred less often in children receiving azithromycin compared to placebo, indicating that azithromycin may have some effect on non-malarial infections. Trial registration Clinicaltrials.gov NCT04315272, registered 19/03/2020.

Health systems' preparedness to provide post-abortion care: assessment of health facilities in Burkina Faso, Kenya and Nigeria.

BACKGROUND: In many parts of sub-Saharan Africa, access to abortion is legally restricted, which partly contributes to high incidence of unsafe abortion. This may result in unsafe abortion-related complications that demand long hospital stays, treatment and attendance by skilled health providers. There is however, limited knowledge on the capacity of public health facilities to deliver post-abortion care (PAC), and the spread of PAC services in these settings. We describe and discuss the preparedness and capacity of public health facilities to deliver complete and quality PAC services in Burkina Faso, Kenya and Nigeria. METHODS: A cross-sectional survey of primary, secondary and tertiary-level public health facilities was conducted between November 2018 and February 2019 in the three countries. Data on signal functions (including information on essential equipment and supplies, staffing and training among others) for measuring the ability of health facilities to provide post-abortion services were collected and analyzed. RESULTS: Across the three countries, fewer primary health facilities (ranging from 6.3-12.1% in Kenya and Burkina Faso) had the capacity to deliver on all components of basic PAC services. Approximately one-third (26-43%) of referral facilities across Burkina Faso, Kenya and Nigeria could provide comprehensive PAC services. Lack of trained staff, absence of necessary equipment and lack of PAC commodities and supplies were a main reason for inability to deliver specific PAC services (such as surgical procedures for abortion complications, blood transfusion and post-PAC contraceptive counselling). Further, the lack of capacity to refer acute PAC cases to higher-level facilities was identified as a key weakness in provision of post-abortion care services. CONCLUSIONS: Our findings reveal considerable gaps and weaknesses in the delivery of basic and comprehensive PAC within the three countries, linked to both the legal and policy contexts for abortion as well as broad health system challenges in the countries. There is a need for increased investments by governments to strengthen the capacity of primary, secondary and tertiary public health facilities to deliver quality PAC services, in order to increase access to PAC and avert preventable maternal mortalities.

Indication for Antibiotic Prescription Among Children Attending Primary Healthcare Services in Rural Burkina Faso.

Of 61 355 visits by children <5 years old to 48 government-run primary healthcare facilities in Nouna District, Burkina Faso, 30 975 had an antibiotic prescribed (58% for pneumonia diagnoses). A minority of prescriptions were for diagnoses not requiring antibiotics, including malaria, nonbloody diarrhea, and cough without pneumonia.

Effect of a single dose of oral azithromycin on malaria parasitaemia in children: a randomized controlled trial.

BACKGROUND: Azithromycin has recently been shown to reduce all-cause childhood mortality in sub-Saharan Africa. One potential mechanism of this effect is via the anti-malarial effect of azithromycin, which may help treat or prevent malaria infection. This study evaluated short- and longer-term effects of azithromycin on malaria outcomes in children. METHODS: Children aged 8 days to 59 months were randomized in a 1:1 fashion to a single oral dose of azithromycin (20 mg/kg) or matching placebo. Children were evaluated for malaria via thin and thick smear and rapid diagnostic test (for those with tympanic temperature ≥ 37.5 °C) at baseline and 14 days and 6 months after treatment. Malaria outcomes in children receiving azithromycin versus placebo were compared at each follow-up timepoint separately. RESULTS: Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. Children were a median of 26 months and 51% were female, and 17% were positive for malaria parasitaemia at baseline. There was no evidence of a difference in malaria parasitaemia at 14 days or 6 months after treatment. In the azithromycin arm, 20% of children were positive for parasitaemia at 14 days compared to 17% in the placebo arm (P = 0.43) and 7.6% vs. 5.6% in the azithromycin compared to placebo arms at 6 months (P = 0.47). CONCLUSIONS: Azithromycin did not affect malaria outcomes in this study, possibly due to the individually randomized nature of the trial. Trial registration This study is registered at clinicaltrials.gov (NCT03676751; registered 19 September 2018).

Single-dose azithromycin for child growth in Burkina Faso: a randomized controlled trial.

BACKGROUND: In lower resource settings, previous randomized controlled trials have demonstrated evidence of increased weight gain following antibiotic administration in children with acute illness. We conducted an individually randomized trial to assess whether single dose azithromycin treatment causes weight gain in a general population sample of children in Burkina Faso. METHODS: Children aged 8 days to 59 months were enrolled in November 2019 and followed through June 2020 in Nouna Town, Burkina Faso. Participants were randomly assigned to a single oral dose of azithromycin (20 mg/kg) or matching placebo. Anthropometric measurements were collected at baseline and 14 days and 6 months after enrollment. The primary anthropometric outcome was weight gain velocity in g/kg/day from baseline to 14 days and 6 months in separate linear regression models. RESULTS: Of 450 enrolled children, 230 were randomly assigned to azithromycin and 220 to placebo. Median age was 26 months (IQR 16 to 38 months) and 51% were female. At 14 days, children in the azithromycin arm gained a mean difference of 0.9 g/kg/day (95% CI 0.2 to 1.6 g/kg/day, P = 0.01) more than children in the placebo arm. There was no difference in weight gain velocity in children receiving azithromycin compared to placebo at 6 months (mean difference 0.04 g/kg/day, 95% CI - 0.05 to 0.13 g/kg/day, P = 0.46). There were no significant differences in other anthropometric outcomes. CONCLUSIONS: Transient increases in weight gain were observed after oral azithromycin treatment, which may provide short-term benefits. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT03676751 . Registered 19/09/2018.

Distance to primary care facilities and healthcare utilization for preschool children in rural northwestern Burkina Faso: results from a surveillance cohort.

BACKGROUND: Delays in care-seeking for childhood illness may lead to more severe outcomes. We evaluated whether community distance from a primary healthcare facility was associated with decreased healthcare utilization in a rural district of northwestern Burkina Faso. METHODS: We conducted passive surveillance of all government-run primary healthcare facilities in Nouna District, Burkina Faso from March 1 through May 31, 2020. All healthcare visits for children under 5 years of age were recorded on a standardized form for sick children. We recorded the age, sex, and community of residence of the child as well as any diagnoses and treatments administered. We calculated healthcare utilization per 100 child-months by linking the aggregate number of visits at the community level to the community's population of children under 5 months per a census that was conducted from August 2019 through February 2020. We calculated the distance between each community and its corresponding healthcare facility and assessed the relationship between distance and the rate of healthcare utilization. RESULTS: In 226 study communities, 12,676 primary healthcare visits were recorded over the three-month period. The median distance between the community and primary healthcare facility was 5.0 km (IQR 2.6 to 6.9 km), and median number of healthcare visits per 100 child-months at the community level was 6.7 (IQR 3.7 to 12.3). The rate of primary healthcare visits declined with increasing distance from clinic (Spearman's rho - 0.42, 95% CI - 0.54 to - 0.31, P < 0.0001). This relationship was similar for cause-specific clinic visits (including pneumonia, malaria, and diarrhea) and for antibiotic prescriptions. CONCLUSIONS: We documented a distance decay effect between community distance from a primary healthcare facility and the rate of healthcare visits for children under 5. Decreasing distance-related barriers, for example by increasing the number of facilities or targeting outreach to more distant communities, may improve healthcare utilization for young children in similar settings.

Prevalence and distribution of livestock schistosomiasis and fascioliasis in Côte d'Ivoire: results from a cross-sectional survey.

BACKGROUND: Schistosoma and Fasciola are zoonotic parasites of public health and veterinary importance. However, while the epidemiology of schistosomiasis in humans is well studied, little is known about fascioliasis and schistosomiasis in livestock in Côte d'Ivoire. This study aimed to determine the prevalence and the distribution of livestock schistosomiasis and fascioliasis across Côte d'Ivoire. In 2018, we conducted a cross-sectional survey in abattoirs and farms in 13 departments of Côte d'Ivoire. In abattoirs, the mesenteric veins and livers of slaughtered cattle, sheep and goats were examined for adult Schistosoma and Fasciola flukes. Faeces from live cattle, goats and sheep were collected and examined for Schistosoma and Fasciola eggs using a sedimentation technique. RESULTS: A total of 386 cattle, 174 goats and 151 sheep from abattoirs and 435 cattle, 22 goats and 176 sheep from farms were sampled. The observed prevalence of schistosomiasis was higher in slaughtered animals. Fascioliasis was more prevalent in farm animals. The prevalence of schistosomiasis in slaughtered cattle varied between 5.9% (95% confidence interval (CI): 0.7-19.7%) and 53.3% (95% CI: 37.9-68.3%) with the highest prevalence observed in Ouangolodougou in the North. Cattle from farms had a relatively low prevalence of schistosomiasis, with the highest prevalence found in Ouangolodougou (2.4%, 95% CI: 0.7-6.1%). The prevalence of fascioliasis varied considerably from one department to another, ranging from nil (95% CI: 0.0-18.5%) to 50.8% (95% CI: 43.4-58.2%), with the highest prevalence found in farm cattle in Dikodougou in the North. Sheep and goats had a lower prevalence of schistosomiasis and fascioliasis than cattle. In slaughtered animals, cattle aged 4 years and older were at highest risk for schistosomiasis (odds ratio (OR): 2.4; 95% CI: 1.0-5.6) and fascioliasis (OR: 2.1; 95% CI: 1.1-3.9). In farm animals, male cattle had higher odds of being infected with Schistosoma (OR: 4.3; 95% CI: 0.7-26.9) than females. CONCLUSIONS: Our study confirms that schistosomiasis and fascioliasis are endemic in livestock across Côte d'Ivoire. A strategic control programme should be considered, especially for cattle, including providing drinking water in troughs to reduce faecal contamination of water sources by cattle.

Association of riverine prawns and intermediate host snails and correlation with human schistosomiasis in two river systems in south-eastern Côte d'Ivoire.

The current emphasis of schistosomiasis control is placed on preventive chemotherapy using praziquantel. However, reinfection may occur rapidly in the absence of complementary interventions. Recent studies from Senegal suggest that predatory prawns might feed on intermediate host snails and thus impact on schistosomiasis transmission. We designed a study with four repeated cross-sectional surveys pertaining to prawns and snails, coupled with a single cross-sectional parasitological survey among humans. We assessed for potential associations between the presence/density of prawns and snails and correlation with Schistosoma infection in a composite sample of school-aged children and adults. The study was carried out between October 2015 and December 2016 in 24 villages located near the Agnéby and Mé coastal river systems in south-eastern Côte d'Ivoire. At each site, snails and prawns were collected, and in each village, 150 individuals were subjected to stool and urine examination for the diagnosis of Schistosoma mansoni and S. haematobium. We found peaks of relative abundance of intermediate host snails in the villages of the Agnéby River system, while predatory prawns were predominantly recorded in the Mé River system. A negative association was observed between intermediate host snail densities and riverine prawns; however, no pattern was found between this trend in the predator-prey relationship and the prevalence of human schistosomiasis.

Are schoolchildren less infected if they have good knowledge about parasitic worms? A case study from rural Côte d'Ivoire.

BACKGROUND: Parasitic worms (helminths) are common infections in low- and middle-income countries. For most helminth species, school-aged children are at highest risk of infection and morbidity, such as impaired cognitive and physical development. Preventive chemotherapy is the current mainstay for helminthiases control. Sanitation improvement and hygiene-related education are important complementary strategies, which act by altering children's behaviour. However, little is known about the effect of improved knowledge on the risk of helminth infection. The aim of this study was to assess the potential influence of knowledge that children acquired at home or in school, without any specific health education intervention, on helminth infections. METHODS: In May 2014, we conducted a cross-sectional survey in western Côte d'Ivoire. A total of 2498 children, aged 9-12 years, were subjected to three consecutive stool examinations using duplicate Kato-Katz thick smears to determine infections with soil-transmitted helminths and Schistosoma mansoni. Additionally, children were interviewed to assess their knowledge about helminth infections. Four knowledge scores were constructed by factor analysis; one, reflecting general knowledge about helminths and three manifesting helminth species-specific knowledge. The effect of general and specific knowledge on children's helminth infection status was determined using meta-analysis. RESULTS: Children who scored high in the hookworm-specific knowledge were less likely to be infected with hookworm but no association was found for the other helminth species. Moreover, greater general knowledge was not associated with lower odds of being infected with any helminth species. Most of the children interviewed believed that the effect of preventive chemotherapy is permanent, and hence, re-treatment is not necessary. CONCLUSIONS: Specific knowledge about different types of helminths might not suffice to induce behavioural change which in turn reduces infection and reinfection with helminths. Health education interventions should strive to strengthen the perception of risk and to clarify the true benefit of preventive chemotherapy.

Interrupting seasonal transmission of Schistosoma haematobium and control of soil-transmitted helminthiasis in northern and central Côte d'Ivoire: a SCORE study protocol.

BACKGROUND: To achieve a world free of schistosomiasis, the objective is to scale up control and elimination efforts in all endemic countries. Where interruption of transmission is considered feasible, countries are encouraged to implement a comprehensive intervention package, including preventive chemotherapy, information, education and communication (IEC), water, sanitation and hygiene (WASH), and snail control. In northern and central Côte d'Ivoire, transmission of Schistosoma haematobium is seasonal and elimination might be achieved. In a cluster-randomised trial, we will assess different treatment schemes to interrupt S. haematobium transmission and control soil-transmitted helminthiasis over a 3-year period. We will compare the impact of (i) arm A: annual mass drug administration (MDA) with praziquantel and albendazole before the peak schistosomiasis transmission season; (ii) arm B: annual MDA after the peak schistosomiasis transmission season; (iii) arm C: two yearly treatments before and after peak schistosomiasis transmission; and (iv) arm D: annual MDA before peak schistosomiasis transmission, coupled with chemical snail control using niclosamide. METHODS/DESIGN: The prevalence and intensity of S. haematobium and soil-transmitted helminth infections will be assessed using urine filtration and Kato-Katz thick smears, respectively, in six administrative regions in northern and central parts of Côte d'Ivoire. Once a year, urine and stool samples will be collected and examined from 50 children aged 5-8 years, 100 children aged 9-12 years and 50 adults aged 20-55 years in each of 60 selected villages. Changes in S. haematobium and soil-transmitted helminth prevalence and intensity will be assessed between years and stratified by intervention arm. In the 15 villages randomly assigned to intervention arm D, intermediate host snails will be collected three times per year, before niclosamide is applied to the selected freshwater bodies. The snail abundance and infection rates over time will allow drawing inference on the force of transmission. DISCUSSION: This cluster-randomised intervention trial will elucidate whether in an area with seasonal transmission, the four different treatment schemes can interrupt S. haematobium transmission and control soil-transmitted helminthiasis. Lessons learned will help to guide schistosomiasis control and elimination programmes elsewhere in Africa. TRIAL REGISTRATION: ISRCTN ISRCTN10926858 . Registered 21 December 2016. Retrospectively registered.

Epidemiology of malaria in the Taabo health and demographic surveillance system, south-central Côte d'Ivoire.

BACKGROUND: A deep understanding of the local epidemiology of malaria is essential for the design and implementation of setting-specific control and elimination efforts. In Côte d'Ivoire, new initiatives are underway to reduce the burden of malaria, which requires high-quality longitudinal data. The epidemiology of malaria was studied in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire and implications for control are discussed. METHODS: Two cross-sectional surveys were carried out in the rainy season of June/July in 2010 and 2011. Inhabitants of approximately 7% of randomly selected households in the Taabo HDSS were invited to participate. People were clinically examined, ear temperature was measured and spleen size determined. Finger-prick blood samples were collected and subjected to a rapid diagnostic test (RDT). Additionally, thick and thin blood films were prepared on microscope slides and diagnosed under a microscope for Plasmodium infection and parasitaemia. Haemoglobin (Hb) level was determined using a HemoCue device. RESULTS: A total of 1187 and 1264 people in 2010 and 2011, respectively, had complete data records. The prevalence of Plasmodium infection was 46.0% in 2010 and 56.6% in 2011, owing to a statistically significant difference (p < 0.05). Males showed a higher Plasmodium infection prevalence than females (49.6 and 62.8% versus 42.6 and 51.2%; respectively, in 2010 and 2011; both p < 0.05). The highest malaria prevalence was observed among infants and young children (aged ≤9 years). The risk of Plasmodium infection was significantly higher in villages compared to small hamlets and urban settings (p < 0.05). Fever, Hb level and splenomegaly were associated with parasitaemia. CONCLUSION: Malaria is highly endemic in the Taabo HDSS in south-central Côte d'Ivoire with considerable spatial heterogeneity of Plasmodium infection. There is a pressing need to scale-up control interventions against malaria.

Spatial and temporal variation of malaria entomological parameters at the onset of a hydro-agricultural development in central Côte d'Ivoire.

BACKGROUND: A deeper understanding of the ecology and small-scale heterogeneity of malaria transmission is essential for the design of effective prevention, control and elimination interventions. The spatial and temporal distribution of malaria vectors was investigated in five villages in close proximity to a hydro-agricultural system in Côte d'Ivoire over the course of construction and the early phase of irrigated rice farming. METHODS: The study was carried out in five villages (Raffierkro, N'Douakro, Ahougui, Kpokahankro, Koffikro) near Bouaké, central Côte d'Ivoire, between early 2007 and late 2009. In each village, mosquitoes were collected by human landing catches and identified morphologically at genus and species level, and entomological parameters were determined. Plasmodium infection was assessed by dissection and an enzyme-linked immunosorbent assay. RESULTS: A total of 19,404 mosquitoes belonging to the genus Anopheles were sampled during 328 human-night catches. Before the construction of the hydro-agricultural system, comparable densities of Anopheles gambiae were observed in all villages. In subsequent years, densities in Raffierkro and Ahougui were significantly higher than the other villages [Kruskal-Wallis (KW) test = 31.13, p < 0.001]. The density of Anopheles funestus in the five villages was comparable in the early stage of the project, while a high density was reported in Koffikro at the end (KW test = 11.91, p = 0.018). Transmission of Plasmodium falciparum is perennial in the study area. Over the course of the study, high entomological inoculation rates (EIRs) were found: 219-328 infectious bites per person per year with An. gambiae. For An. funestus considerably lower EIRs were observed (5.7-39.4). Changing patterns of An. gambiae were not correlated with malaria transmission. CONCLUSION: In this study setting, located in the bioclimatic transition zone of Côte d'Ivoire, rice cultivation was not observed to increase malaria transmission. The entomological parameters recorded until the onset of rice-growing activities in a hydro-agricultural system presented considerable heterogeneity both in space and time; a strong increase of Anopheles mosquitoes was observed in two of the five villages located in close proximity to the dam and irrigated rice fields. Malaria still is a main public health problem in all villages that require adequate control measures.

The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.

BACKGROUND: Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. METHODS: A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). RESULTS: After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 µg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). CONCLUSIONS: IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

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

BACKGROUND: Schistosomiasis is a parasitic disease that occurs in the tropics and subtropics. The mainstay of control is preventive chemotherapy with praziquantel. In Africa, an estimated 230 million people require preventive chemotherapy. In western Côte d'Ivoire, infections with Schistosoma mansoni are widespread. To provide an evidence-base for programme decisions about preventive chemotherapy to sustain control of schistosomiasis, a 5-year multi-country study with different treatment arms has been designed by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) and is currently being implemented in various African settings, including Côte d'Ivoire. METHODS/DESIGN: We report the study protocol, including ethics statement and insight from a large-scale eligibility survey carried out in four provinces in western Côte d'Ivoire. The study protocol has been approved by the ethics committees of Basel and Côte d'Ivoire. A total of 12,110 children, aged 13-14 years, from 264 villages were screened for S. mansoni using duplicate Kato-Katz thick smears from single stool samples. Among the schools with a S. mansoni prevalence of 10-24%, 75 schools were selected and randomly assigned to one of three treatment arms. In each school, three stool samples are being collected from 100 children aged 9-12 years annually and one stool sample from 100 first-year students at baseline and in the final year and subjected to duplicate Kato-Katz thick smears. Cost and coverage data for the different intervention arms, along with environmental, political and other characteristics that might impact on the infection prevalence and intensity will be recorded in each study year, using a pretested village inventory form. DISCUSSION: The study will document changes in S. mansoni infection prevalence and intensity according to different treatment schemes. Moreover, factors that determine the effectiveness of preventive chemotherapy will be identified. These factors will help to develop reasonable measures of force of transmission that can be used to make decisions about the most cost-effective means of lowering prevalence, intensity and transmission in a given setting. The gathered information and results will inform how to effectively sustain control of schistosomiasis at a low level in different social-ecological contexts. TRIAL REGISTRATION: ISRCTN99401114 (date assigned: 12 November 2014).

Dynamics of anemia in relation to parasitic infections, micronutrient status, and increasing age in South-Central Côte d'Ivoire.

BACKGROUND: Parasitic diseases (eg, malaria and helminthiases) exert enormous burdens on public health and social well-being. Moreover, parasitic infections are important causes of anemia in tropical Africa, exacerbated by lack of a diversified diet and inflammatory and genetic diseases. There is a paucity of longitudinal studies monitoring the dynamics of anemia in relation to the aforementioned parameters. METHODS: We designed a 14-month prospective longitudinal study in 3 cohorts (ie, infants aged 6-23 months, children aged 6-8 years, and women aged 15-25 years) in the Taabo health demographic surveillance system located in south-central Côte d'Ivoire. Parasitological, hematological, and micronutrient data were obtained from repeated cross-sectional surveys, utilizing standardized, quality-controlled methods. RESULTS: We found that young age, Plasmodium and Schistosoma infections, cellular iron deficiency, and stunting were significantly negatively associated with hemoglobin concentration. Moreover, iron status biomarkers (ie, ferritin and soluble transferrin receptor) were significantly associated with inflammatory parameters. CONCLUSIONS: Based on our results, effective prevention and control measures that target parasitic diseases and iron deficiency are needed. These measures might include the distribution of long-lasting insecticidal nets, intermittent preventive treatment for malaria, regular anthelmintic drug administration, and improved intake of bioavailable iron, coupled with health and nutritional education and improved hygiene, water, and sanitation.

Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial.

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.