The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study.

BACKGROUND: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. METHODS: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10. FINDINGS: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10. INTERPRETATION: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. FUNDING: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.

Enhanced effect of seasonal malaria chemoprevention when coupled with nutrients supplementation for preventing malaria in children under 5 years old in Burkina Faso: a randomized open label trial.

BACKGROUND: In rural African settings, most of the children under the coverage of Seasonal Malaria Chemoprevention (SMC) are also undernourished at the time of SMC delivery, justifying the need for packaging malarial and nutritional interventions. This study aimed at assessing the impact of SMC by coupling the intervention with nutrients supplementation for preventing malaria in children less than 5 years old in Burkina Faso. METHODS: A randomized trial was carried out between July 2020 and June 2021 in the health district of Nanoro, Burkina Faso. Children (n = 1059) under SMC coverage were randomly assigned to one of the three study arms SMC + Vitamin A (SMC-A, n = 353) or SMC + Vitamin A + Zinc (SMC-AZc, n = 353) or SMC + Vitamin A + PlumpyDoz(tm) (SMC-APd, n = 353)-a medium quantity-lipid-based nutrient supplement (MQ-LNS). Children were followed up for one year that included an active follow-up period of 6 months with scheduled monthly home visits followed by 6 months passive follow-up. At each visit, capillary blood sample was collected for malaria diagnosis by rapid diagnosis test (RDT). RESULTS: Adding nutritional supplements to SMC had an effect on the incidence of malaria. A reduction of 23% (adjusted IRR = 0.77 (95%CI 0.61-0.97) in the odds of having uncomplicated malaria in SMC-APd arm but not with SMC-AZc arm adjusted IRR = 0.82 (95%CI 0.65-1.04) compare to control arm was observed. A reduction of 52%, adjusted IRR = 0.48 (95%CI 0.23-0.98) in the odds of having severe malaria was observed in SMC-APd arm compared to control arm. Besides the effect on malaria, this combined strategy had an effect on all-cause morbidity. More specifically, a reduction of morbidity odds of 24%, adjusted IRR = 0.76 (95%CI 0.60-0.94) in SMC-APd arm compared to control arm was observed. Unlike clinical episodes, no effect of nutrient supplementation on cross sectional asymptomatic infections was observed. CONCLUSION: Adding nutritional supplements to SMC significantly increases the impact of this intervention for preventing children from malaria and other childhood infections. TRIAL REGISTRATION: NCT04238845.

Baseline malarial and nutritional profile of children under seasonal malaria chemoprevention coverage in the health district of Nanoro, Burkina Faso.

Seasonal Malaria chemoprevention (SMC) is one of the large-scale life-saving malaria interventions initially recommended for the Sahel subregion, including Burkina Faso and recently extended to other parts of Africa. Initially, SMC was restricted to children 3 to 59 months old, but an extension to older children in some locations was recently recommended. Further characterization of SMC population profile beyond age criterion is necessary for understanding factors that could negatively impact the effectiveness of the intervention and to define complementary measures that could enhance its impact. Children were assessed through a cross-sectional survey during the first month of the 2020 SMC campaign (July-August 2020) as part of the SMC-NUT project in the health district of Nanoro. Parameters such as body temperature, weight, height, mid-upper arm circumference (MUAC) were assessed. In addition, blood sample was collected for malaria diagnosis by rapid diagnostic tests (RDT) and microscopy, and for haemoglobin measurement. A total of 1059 children were enrolled. RDT positivity rate (RPR) was 22.2%, while microscopy positivity rate (MPR) was 10.4%, with parasitaemia levels ranging from 40 to 70480/µL. RPR and MPR increased as patient age increased. Wasting was observed in 7.25% of children under SMC coverage while the prevalence of stunting and underweight was 48.79% and 23.38%, respectively. As the age of the children increased, an improvement in their nutritional status was observed. Finally, undernourished children had higher parasite densities than children with adequate nutritional status. In the health district of Nanoro, children who received Seasonal Malaria Chemoprevention (SMC) were mostly undernourished during the period of SMC delivery, suggesting the need for combining the SMC with synergistic interventions against malnutrition to achieve best impact.

Malaria prevention knowledge, attitudes, and practices (KAP) among adolescents living in an area of persistent transmission in Senegal: Results from a cross-sectional study.

INTRODUCTION: While malaria morbidity has sharply declined in several areas in Senegal, it remains an important problem in the southern part of the country, particularly among adolescents. Understanding adolescents' knowledge, attitudes, prevention and care-seeking practices is important to inform more targeted interventions aimed at optimizing adolescents' uptake of malaria prevention and control measures. This study assessed malaria-related knowledge, attitudes, and practices (KAP) among adolescents living in a highly persistent transmission area in Senegal. METHODS: A community-based cross-sectional survey was conducted among 391 adolescents living in the Saraya health district. A multistage random sampling technique was used to select households. An electronic questionnaire developed on Open Data Kit (ODK), was used to collect data on socio-demographic characteristics, household assets, adolescents' knowledge of malaria, as well as their attitudes with regards to malaria prevention, and care-seeking behaviors. Bivariate and multivariate analyses were performed to assess factors associated with adolescents' KAP towards malaria. RESULTS: Nearly, one-third of the participants had good knowledge of malaria (34.4%) and good practice in regards to malaria preventive measures (32.8%) while 59.0% had a positive attitude and 73.8% had good care-seeking behavior regarding malaria. Multivariate analysis revealed that a primary (aOR = 5.43, p = 0.002) or secondary level of education (aOR = 10.41, p = 0.000) was associated with good knowledge of malaria transmission, signs, and prevention measures. Male individuals had lower knowledge compared to female ones (aOR = 0.40, p = 0.001). Individuals belonging to households from the highest wealth quintile were more likely to have a positive attitude towards malaria compared to those from households in the lowest wealth quintile (aOR = 3.49, p = 0.004). The odds of positive attitude towards malaria decreased among participants with koranic and primary education level, respectively (aOR = 0.14, p = 0.005) and (aOR = 0.24, p = 0.019). A positive attitude was 1.89 more likely to be (aOR = 1.89, p = 0.026) associated with good practice of prevention measures compared to adolescents who demonstrated negative attitudes. Individuals from households in the fourth (aOR = 0.42, p = 0.024), middle (aOR = 0.34, P = 0.005), and second (aOR = 0.42, p = 0.027) wealth quintiles were less likely to use malaria prevention measures compared to those from households in the highest wealth quintile. CONCLUSION: The study revealed that adolescents, generally have poor levels of malaria knowledge and low uptake of malaria prevention and control interventions. Targeted interventions for high-risk adolescents are needed, that focus on improving their knowledge of the disease and effective preventive measures, and on increasing their access to health care services and LLINs.

Could combined rapid diagnostic testing for malaria and c-reactive protein be helpful for the diagnosis and management of febrile illnesses in children under-5 years of age in rural Burkina Faso?

BACKGROUND: Febrile illnesses are among the most important reasons for medical consultation in sub-Saharan Africa and are frequently treated with antimicrobials due to the unavailability of appropriate diagnostic tools. This practice leads to antimicrobial resistance, with increasing mortality and morbidity as result. One of the few accessible diagnostic tools available in low resource settings is malaria rapid diagnostic tests (mRDTs) which contributed to reducing the over-prescription of anti-malarials, but cannot guide antibiotic prescriptions. To circumvent this problem, we explored whether combined testing with mRDT and c-reactive protein (CRP) could improve the diagnosis of febrile illnesses and subsequent prescription of antibiotics. METHODS: Clinical specimens (blood, stool and urine) collected from 396 febrile children (axillary temperature of ≥ 37.5 °C) were analyzed with rapid diagnostic tests (malaria and CRP) and microbiology culture to establish the possible cause of fever. Actual antimicrobial prescriptions given to the children were compared with those that could be given based on combined CRP-malaria testing. RESULTS: In total, 68.7% (272/396) of malaria cases were diagnosed by mRDT-Pf-HRP-2. CRP test was positive in 84.3% (334/396) of the children, but bacterial infections were confirmed in 12.4% (49/396) of them. A possible cause of fever could not be established in 20.5% (81/396) of cases. Based on the diagnostic practice in place, 265 of the children with a positive mRDT-Pf-HRP-2 received anti-malarial treatment. Furthermore, 89.5% (111/124) of negative mRDT results received antibiotic treatment and 37.1% (46/124) received antimalarial treatment. Of these 124 cases, 80 had positive CRP tests and 44 negative CRP tests. If the results of CRP testing are considered, 44 CRP/mRDT negative children would not get antibiotic treatment, resulting in a 35.5% reduction in antibiotic prescriptions. However, 2 cases with a bacterial infection would be denied appropriate treatment. CONCLUSION: Combining mRDT-PfHRP2 with CRP testing is particularly useful in children for whom both tests are negative as it results in a reduction of antibiotics prescriptions. However, there is a risk to miss potential severe bacterial infections and a close follow-up of these cases is strongly recommended.

Diagnostic Performance of Plasmodium falciparum Histidine-Rich Protein-2 Antigen-Specific Rapid Diagnostic Test in Children at the Peripheral Health Care Level in Nanoro (Burkina Faso).

(1) Background: Malaria control has strongly benefited from the implementation of rapid diagnostic tests (RDTs). The malaria RDTs used in Burkina Faso, as per the recommendation of the National Malaria Control Program, are based on the detection of histidine-rich protein-2 (PfHRP2) specific to Plasmodium falciparum, which is the principal plasmodial species causing malaria in Burkina Faso. However, there is increasing concern about the diagnostic performance of these RDTs in field situations, and so constant monitoring of their accuracy is warranted. (2) Methods: A prospective study was performed in the health district of Nanoro, where 391 febrile children under 5 years with an axillary temperature ≥37.5 °C presenting at participating health facilities were subjected to testing for malaria. The HRP2-based RDT and expert microscopy were used to determine the diagnostic performance of the former. Retrospectively, the correctness of the antimalaria prescriptions was reviewed. (3) Results: Taking expert malaria microscopy as the gold standard, the sensitivity of the employed RDT was 98.5% and the specificity 40.5%, with a moderate agreement between the RDT testing and microscopy. In total, 21.7% of cases received an inappropriate antimalarial treatment based on a retrospective assessment with expert microscopy results. (4) Conclusion: Malaria remains one of the principal causes of febrile illness in Burkina Faso. Testing with HRP2-based RDTs is inaccurate, in particular, due to the low specificity, which results in an over-prescription of antimalarials, with emerging antimalarial drug resistance as an important risk and many children not being treated for potential other causes of fever.

Impact and operational feasibility of adding malaria infection screening using an ultrasensitive RDT for placental and fetal outcomes in an area of high IPTP-SP coverage in Burkina Faso: the ASSER MALARIA pilot study protocol.

BACKGROUND: Malaria infection during pregnancy (MIP) is not only deleterious to the woman, but it also puts her fetus at increased risk of adverse outcomes, such as preterm delivery, low birth weight, and intrauterine growth retardation. Additionally, all-cause mortality during the first year of life in babies born to women with malaria during pregnancy is also increased. Many interventions such as IPTp-SP and long-lasting insecticidal nets have proven to be efficient at reducing malaria in pregnancy burden but adherence to recommended policies remains poor. In sub-Saharan Africa, malaria in pregnancy is often asymptomatic and many malaria infections may be missed due to the inadequate performance of the current rapid diagnostic test to detect low-level parasitemias. Therefore, additional strategies such as intermittent screening with ultrasensitive rapid diagnostic tests and treatment with an effective artemisinin-based combination therapy in addition to IPTp-SP could reduce placental malaria, peripheral malaria infection at delivery, and low birth weight. METHODS: This pilot 2-group randomized open trial with a nested qualitative social behavioral will be carried out in Nanoro district in which 340 pregnant women will be recruited. Pregnant women will be randomized into two groups and followed on a monthly basis until delivery. In the intervention group, monthly screening using ultrasensitive rapid diagnostic tests and treatment of those found to be infected with dihydroartemisinin-piperaquine will be performed. In addition, a reminder will be sent to increase the uptake of IPTp-SP doses per woman. During scheduled and unscheduled visits, malaria infection, hemoglobin level, and other clinical outcomes will be assessed and compared by the group. The primary feasibility outcome will evaluate the study site's capacity to enroll participants and the women's perception and acceptability of the intervention. The primary clinical outcome will be the prevalence of placental malaria at delivery. DISCUSSION: The present protocol aims to evaluate the feasibility on a large-scale and also to demonstrate the impact and the operational feasibility of additional screening with ultrasensitive rapid diagnostic tests and treatment with DHA-PQ on placental malaria, low birth weight, and peripheral malaria infection at delivery in a high-burden setting in Burkina Faso. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04147546 (14 October 2019).

Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial.

BACKGROUND: Malaria is a leading cause of morbidity and mortality worldwide. We previously reported the efficacy of the R21/Matrix-M malaria vaccine, which reached the WHO-specified goal of 75% or greater efficacy over 12 months in the target population of African children. Here, we report the safety, immunogenicity, and efficacy results at 12 months following administration of a booster vaccination. METHODS: This double-blind phase 1/2b randomised controlled trial was done in children aged 5-17 months in Nanoro, Burkina Faso. Eligible children were enrolled and randomly assigned (1:1:1) to receive three vaccinations of either 5 µg R21/25 µg Matrix-M, 5 µg R21/50 µg Matrix-M, or a control vaccine (the Rabivax-S rabies vaccine) before the malaria season, with a booster dose 12 months later. Children were eligible for inclusion if written informed consent could be provided by a parent or guardian. Exclusion criteria included any existing clinically significant comorbidity or receipt of other investigational products. A random allocation list was generated by an independent statistician by use of block randomisation with variable block sizes. A research assistant from the University of Oxford, independent of the trial team, prepared sealed envelopes using this list, which was then provided to the study pharmacists to assign participants. All vaccines were prepared by the study pharmacists by use of the same type of syringe, and the contents were covered with an opaque label. Vaccine safety, efficacy, and a potential correlate of efficacy with immunogenicity, measured as anti-NANP antibody titres, were evaluated over 1 year following the first booster vaccination. The population in which the efficacy analyses were done comprised all participants who received the primary series of vaccinations and a booster vaccination. Participants were excluded from the efficacy analysis if they withdrew from the trial within the first 2 weeks of receiving the booster vaccine. This trial is registered with ClinicalTrials.gov (NCT03896724), and is continuing for a further 2 years to assess both the potential value of additional booster vaccine doses and longer-term safety. FINDINGS: Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each child received the same vaccination for the booster as they received in the primary series of vaccinations; 132 participants received 5 µg R21 adjuvanted with 25 µg Matrix-M, 137 received 5 µg R21 adjuvanted with 50 µg Matrix-M, and 140 received the control vaccine. R21/Matrix-M had a favourable safety profile and was well tolerated. Vaccine efficacy remained high in the high adjuvant dose (50 µg) group, similar to previous findings at 1 year after the primary series of vaccinations. Following the booster vaccination, 67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant, 54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who received the rabies vaccine developed clinical malaria by 12 months. Vaccine efficacy was 71% (95% CI 60 to 78) in the low-dose adjuvant group and 80% (72 to 85) in the high-dose adjuvant group. In the high-dose adjuvant group, vaccine efficacy against multiple episodes of malaria was 78% (95% CI 71 to 83), and 2285 (95% CI 1911 to 2568) cases of malaria were averted per 1000 child-years at risk among vaccinated children in the second year of follow-up. Among these participants, at 28 days following their last R21/Matrix-M vaccination, titres of malaria-specific anti-NANP antibodies correlated positively with protection against malaria in both the first year of follow-up (Spearman's ρ -0·32 [95% CI -0·45 to -0·19]; p=0·0001) and second year of follow-up (-0·20 [-0·34 to -0·06]; p=0·02). INTERPRETATION: A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen maintained high efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine induced antibody concentrations that correlated with vaccine efficacy. The trial is ongoing to assess long-term follow-up of these participants and the value of further booster vaccinations. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2), Wellcome Trust, and NIHR Oxford Biomedical Research Centre. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Prospective observational study to evaluate the clinical and biological safety profile of pyronaridine-artesunate in a rural health district in Burkina Faso.

The assessment in real-life conditions of the safety and efficacy of new antimalarial drugs is of greatest interest. This study aimed to monitor and evaluate both clinical and biological safety of pyronaridine-artesunate (PA) in real-life conditions in Burkina Faso's health system. This was a single-arm, open-label study, where patients attending Nanoro health facilities with uncomplicated malaria were consented to be part of a cohort event monitoring (CEM). At inclusion (day-0), PA was administered orally once a day for 3 days. Patients spontaneous reported any clinical adverse events (AEs) occurring within 28 days following the treatment. Additionally, the study focused on AEs of special interest (AESI), namely clinical signs related to hepatotoxicity and increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). A nested subset of patients with blood sample collection at day-0 and day-7 were monitored to investigate the effect of PA on biochemistry parameters. From September 2017 to October 2018, 2786 patients were treated with PA. About 97.8% (2720/2786) of patients did not report any AE. The most commonly reported events were respiratory, thoracic, and mediastinal disorders (8.3 per 1000), infections and infestations (7.9 per 1000), and gastrointestinal disorders (7.2 per 1000). No clinical or biological hepatotoxicity event related to PA was reported during the follow-up. Changes in biochemistry parameters remained within laboratory reference ranges. The study showed that PA is a well-tolerated drug and should be considered as a good option by malaria control programs in countries where existing first-line antimalarial drugs are continuously threatened by the emergence of drug resistance.

Assessment of Recovery Time, Worsening, and Death among Inpatients and Outpatients with COVID-19, Treated with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso.

OBJECTIVES: Our study aimed to assess the statistical relationship between the use of chloroquine phosphate or hydroxychloroquine plus azithromycin (CQ/HCQ + AZ) and virological recovery, disease worsening, and death among out- and inpatients with COVID-19 in Burkina Faso. METHODS AND DESIGNS: This was a retrospective observational study that compared outcomes in terms of time to recovery, worsening, and death in patients who received CQ/HCQ + AZ and those who did not using a multivariable Cox or Poisson model before and after propensity matching. RESULTS: Of the 863 patients included in the study, about 50% (432/863) were home-based follow-up patients and 50% were inpatients. Of these, 83.3% (746/863) received at least 1 dose of CQ/HCQ + AZ and 13.7% (118/863) did not. There were no significant differences in associated time to recovery for patients receiving any CQ/HCQ + AZ (adjusted HR 1.44; 95% CI 0.76-2.71). Similarly, there was no significant association between CQ/HCQ + AZ use and worsening (adjusted IRR 0.80; 95% CI 0.50-1.50). However, compared with the untreated group, the treated group had a lower risk of death (adjusted HR 0.20; 95% CI 0.10-0.44). CONCLUSIONS: The study provided valuable additional information on the use of CQ/HCQ in patients with COVID-19 and did not show any harmful outcomes of CQ/HCQ + AZ treatment.

Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso: a protocol for a randomized open label trial.

BACKGROUND: Plasmodium falciparum malaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. METHODS: This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3-59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. CONCLUSION: The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention.

Safety of Chloroquine or Hydroxychloroquine Plus Azithromycin for the Treatment of COVID-19 Patients in Burkina Faso: An Observational Prospective Cohort Study.

INTRODUCTION: Though chloroquine derivatives are used in the treatment of coronavirus disease 2019 (COVID-19) in many countries worldwide, doubts remain about the safety and efficacy of these drugs, especially in African communities where published data are scarce. METHODS: We conducted an observational prospective cohort study from April 24 to September 03, 2020, in Burkina Faso to assess (as primary outcome) the clinical, biological, and cardiac (electrocardiographic) safety of chloroquine or hydroxychloroquine plus azithromycin administered to COVID-19 patients. The main secondary outcomes were all-cause mortality and median time of viral clearance. RESULTS: A total of 153 patients were enrolled and followed for 21 days. Among patients who took at least one dose of chloroquine or hydroxychloroquine (90.1% [138/153]), few clinical adverse events were reported and were mainly rash/pruritus, diarrhea, chest pain, and palpitations. No statistically significant increase in hepatic, renal, and hematological parameters or electrolyte disorders were reported. However, there was a significant increase in the QTc value without exceeding 500ms, especially in those who received chloroquine phosphate. Three adverse events of special interest classified as serious (known from chloroquine derivatives) were recorded namely pruritus, paresthesia, and drowsiness. One case of death occurred. The average onset of SARS-CoV-2 PCR negativity was estimated at 7.0 (95% CI: 5.0-10.0) days. CONCLUSION: Hydroxychloroquine appeared to be well tolerated in treated COVID-19 patients in Burkina Faso. In the absence of a robust methodological approach that could generate a high level of scientific evidence, our results could at least contribute to guide health decisions that should be made based on different sources of scientific evidence including those from our study.

[Polymorphisms in Plasmodium falciparum parasites and mutations in the resistance genes Pfcrt and Pfmdr1 in Nanoro area, Burkina Faso]. / Polymorphisme de Plasmodium falciparum et mutations des gènes de résistance Pfcrt et Pfmdr1 dans la zone de Nanoro, Burkina Faso.

INTRODUCTION: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso. METHODS: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP. RESULTS: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections. CONCLUSION: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs.

Pathogens associated with acute diarrhea, and comorbidity with malaria among children under five years old in rural Burkina Faso.

INTRODUCTION: acute diarrhea in children under five years is a public health problem in developing countries and particularly in malaria-endemic areas where both diseases co-exist. The present study examined the etiology of childhood diarrhea and its comorbidity with malaria in a rural area of Burkina Faso. METHODS: conventional culture techniques, direct stools examination, and viruses´ detection by rapid tests were performed on the fresh stools and microscopy was used to diagnose malaria. Some risk factors were also assessed. RESULTS: on a total of 191 samples collected, at least one pathogen was identified in 89 cases (46.6%). The proportions of pathogens found on the 89 positive stool samples were parasites 51.69% (46 cases), viruses 39.33% (35 cases), and bacteria 14.61% (13 cases), respectively. The relationship between malaria and infectious diarrhea was significant in viral and parasites causes (p=0.005 and 0.043 respectively). Fever, vomiting and abdominal pain were the major symptoms associated with diarrhea, with 71.51%, 31.72% and 23.66% respectively. The highest viral diarrhea prevalence was reported during the dry season (OR=5.29, 95% CI: 1.74 - 16.07, p=0.001) while parasite diarrhea was more encountered during the rainy season (OR=0.41, 95% CI: 0.33 - 0.87, p=0.011). CONCLUSION: Giardia spp and rotavirus were the leading cause of acute diarrhea in Nanoro, Burkina Faso with a predominance of rotavirus in children less than 2 years. Parasite and viral diarrhea were the most pathogens associated with malaria. However, the high rate of negative stool samples suggests the need to determine other enteric microorganisms.

Antibiotic susceptibility profile of bacterial isolates from febrile children under 5 years of age in Nanoro, Burkina Faso.

OBJECTIVES: Antibiotics efficacy is severely threatened due to emerging resistance worldwide, but there is a paucity of antibiotics efficacy data for the West African region in general. Therefore, this study aimed to determine the antibiotic susceptibility profile of bacterial isolated from febrile children under 5 years of age in Nanoro (Burkina Faso). METHODS: Blood, stool and urine samples were collected from 1099 febrile children attending peripheral health facilities and the referral hospital in Nanoro Health district. Bacterial isolates from these samples were assessed for their susceptibility against commonly used antibiotics by Kirby-Bauer method. RESULTS: In total, 141 bacterial isolates were recovered from 127 febrile children of which 65 from blood, 65 from stool and 11 from urine. Salmonella isolates were most frequently isolated and found to be highly resistant to ampicillin (70%; 56/80) and trimethoprim-sulphamethoxazole (65%; 52/80). Escherichia coli isolates showed a high resistance rate to trimethoprim-sulphamethoxazole (100%), ampicillin (100%), ciprofloxacin (71.4%; 10/14), amoxicillin-clavulanate (64.3%; 9/14), ceftriaxone (64.3%; 9/14) and gentamycin (50%; 7/14). Moreover, half of the E. coli isolates produced ß-lactamase suggesting multi-drug resistance against ß-lactam as well as non-ß-lactam antibiotics. Multi-drug resistance was observed in 54.6% (59/108) of the isolates, mainly Gram-negative bacteria. CONCLUSIONS: This study showed high resistance rates to common antibiotics used to treat bacterial infections in Nanoro. The work prompts the need to expand antibiotic resistance surveillance studies in Burkina Faso.

Assessment of a combined strategy of seasonal malaria chemoprevention and supplementation with vitamin A, zinc and Plumpy'Doz™ to prevent malaria and malnutrition in children under 5 years old in Burkina Faso: a randomized open-label trial (SMC-NUT).

BACKGROUND: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage. METHODS: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. DISCUSSION: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845.

Antibiotic Susceptibility of Staphylococcus aureus and Streptococcus pneumoniae Isolates from the Nasopharynx of Febrile Children under 5 Years in Nanoro, Burkina Faso.

(1) Background: nasopharynx colonization by resistant Staphylococcus aureus and Streptococcus pneumoniae can lead to serious diseases. Emerging resistance to antibiotics commonly used to treat infections due to these pathogens poses a serious threat to the health system. The present study aimed to determine the antibiotic susceptibility of S. aureus and S. pneumoniae isolates from the febrile children's nasopharynx under 5 years in Nanoro (Burkina Faso). (2) Methods: bacterial isolates were identified from nasopharyngeal swabs prospectively collected from 629 febrile children. Antibiotic susceptibility of S. aureus and S. pneumoniae isolates was assessed by Kirby-Bauer method and results were interpreted according to the Clinical and Laboratory Standard Institute guidelines. (3) Results: bacterial colonization was confirmed in 154 (24.5%) of children of whom 96.1% carried S. aureus, 3.2% had S. pneumoniae, and 0.6% carried both bacteria. S. aureus isolates showed alarming resistance to penicillin (96.0%) and S. pneumoniae was highly resistant to tetracycline (100%) and trimethoprim-sulfamethoxazole (83.3%), and moderately resistant to penicillin (50.0%). Furthermore, 4.0% of S. aureus identified were methicillin resistant. (4) Conclusion: this study showed concerning resistance rates to antibiotics to treat suspected bacterial respiratory tract infections. The work highlights the necessity to implement continuous antibiotic resistance surveillance.

Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density.

BACKGROUND: Multi-genotype malaria infections are frequent in endemic area, and people commonly harbour several genetically distinct Plasmodium falciparum variants. The influence of genetic multiplicity and whether some specific genetic variants are more or less likely to invest into gametocyte production is not clearly understood. This study explored host and parasite-related risk factors for gametocyte carriage, and the extent to which some specific P. falciparum genetic variants are associated with gametocyte carriage. METHODS: Gametocytes and asexual forms were detected by light microscopy on thick smears collected between 2010 and 2012 in Nanoro, Burkina Faso. Merozoite surface protein 1 and 2 were genotyped by nested PCR on clinical samples. Associations between gametocyte carriage and factors, including multiplicity of infection, parasite density, patient age, gender, haemoglobin (Hb) level, and body temperature were assessed. The relationship between the presence of a particular msp1 and msp2 genetic variants and gametocyte carriage was also explored. RESULTS: Of the 724 samples positive to P. falciparum and successfully genotyped, gametocytes were found in 48 samples (6.63%). There was no effect of patient gender, age and body temperature on gametocyte carriage. However, the probability of gametocyte carriage significantly increased with increasing values of multiplicity of infection (MOI). Furthermore, there was a negative association between parasite density and gametocyte carriage. MOI decreased with parasite density in gametocyte-negative patients, but increased in gametocyte carriers. The probability of gametocyte carriage decreased with Hb level. Finally, the genetic composition of the infection influenced gametocyte carriage. In particular, the presence of RO33 increased the odds of developing gametocytes by 2 while the other allelic families K1, MAD20, FC27, and 3D7 had no significant impact on the occurrence of gametocytes in infected patients. CONCLUSION: This study provides insight into potential factors influencing gametocyte production in symptomatic patients. The findings contribute to enhance understanding of risk factors associated with gametocyte carriage in humans. Trial registration NCT01232530.

Determinants of Plasmodium falciparum multiplicity of infection and genetic diversity in Burkina Faso.

BACKGROUND: Investigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso. METHODS: Blood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction. RESULTS: In the study area, infected people harboured an average of 2.732 (± 0.056) different parasite genotypes. A significant correlation between the monthly MOI and the monthly malaria incidence was observed, suggesting that MOI could be a good predictor of transmission intensity. A strong effect of season on MOI was observed, with infected patients harbouring higher number of parasite genotypes during the rainy season as compared to the dry season. There was a negative relationship between MOI and host age. In addition, MOI decreased with increasing parasite densities, suggesting that there was a within-host competition among co-infecting genetically distinct P. falciparum variants. Each allelic family of the msp1 and msp2 genes was present all year round with no significant monthly fluctuation. CONCLUSIONS: In high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.