Background Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy over 12 months in African children. We therefore assessed a new candidate vaccine for safety and efficacy.Methods In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals before the malaria season, with a fourth dose 1 year later. All vaccines were administered intramuscularly into the thigh. Group 1 received 5 µg R21 plus 25 µg MM, group 2 received 5 µg R21 plus 50 µg MM, and group 3, the control group, received rabies vaccinations. Children were randomly assigned (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using block randomisation with variable block sizes, which was used to assign participants. Participants, their families, and the local study team were all masked to group allocation. Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety, immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6 months. Primary analyses of vaccine efficacy were based on a modified intention-to-treat population, which included all participants who received three vaccinations, allowing for inclusion of participants who received the wrong vaccine at any timepoint. This trial is registered with ClinicalTrials.gov, NCT03896724.Findings From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were excluded. 450 children were enrolled and received at least one vaccination. 150 children were allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated to group 3. The final vaccination of the primary series was administered on Aug 7, 2019. R21/MM had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the seven serious adverse events were attributed to the vaccine. At the 6-month primary efficacy analysis, 43 (29%) of 146 participants in group 1, 38 (26%) of 146 participants in group 2, and 105 (71%) of 147 participants in group 3 developed clinical malaria. Vaccine efficacy was 74% (95% CI 63-82) in group 1 and 77% (67-84) in group 2 at 6 months. At 1 year, vaccine efficacy remained high, at 77% (67-84) in group 1. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the pr...
Background With limited resources and spatio-temporal heterogeneity of malaria in developing countries, it is still difficult to assess the real impact of socioeconomic and environmental factors in order to set up targeted campaigns against malaria at an accurate scale. Our goal was to detect malaria hotspots in rural area and assess the extent to which household socioeconomic status and meteorological recordings may explain the occurrence and evolution of these hotspots. Methods Data on malaria cases from 2010 to 2014 and on socioeconomic and meteorological factors were acquired from four health facilities within the Nanoro demographic surveillance area. Statistical cross correlation was used to quantify the temporal association between weekly malaria incidence and meteorological factors. Local spatial autocorrelation analysis was performed and restricted to each transmission period using Kulldorff’s elliptic spatial scan statistic. Univariate and multivariable analysis were used to assess the principal socioeconomic and meteorological determinants of malaria hotspots using a Generalized Estimating Equation (GEE) approach. Results Rainfall and temperature were positively and significantly associated with malaria incidence, with a lag time of 9 and 14 weeks, respectively. Spatial analysis showed a spatial autocorrelation of malaria incidence and significant hotspots which was relatively stable throughout the study period. Furthermore, low socioeconomic status households were strongly associated with malaria hotspots (aOR = 1.21, 95% confidence interval: 1.03–1.40). Conclusion These fine-scale findings highlight a relatively stable spatio-temporal pattern of malaria risk and indicate that social and environmental factors play an important role in malaria incidence. Integrating data on these factors into existing malaria struggle tools would help in the development of sustainable bottleneck strategies adapted to the local context for malaria control. Electronic supplementary material The online version of this article (10.1186/s12889-019-6565-z) contains supplementary material, which is available to authorized users.
ImportanceNeonatal sepsis is a leading cause of neonatal mortality. New interventions are needed to decrease neonatal sepsis and mortality in regions with highest burden.ObjectiveTo evaluate the efficacy of intrapartum azithromycin to reduce neonatal sepsis or mortality, as well as neonatal and maternal infections.Design, Setting, and ParticipantsThis double-blind, placebo-controlled, randomized clinical trial enrolled and followed up birthing parents and their infants at 10 health facilities in The Gambia and Burkina Faso, West Africa, between October 2017 and May 2021.InterventionsParticipants were assigned at random to receive oral azithromycin (2 g) or placebo (ratio 1:1) during labor.Main Outcomes and MeasuresThe primary outcome was a composite of neonatal sepsis or mortality, with the former defined based on microbiologic or clinical criteria. Secondary outcomes were neonatal infections (skin, umbilical, eye and ear infections), malaria, and fever; postpartum infections (puerperal sepsis, mastitis), fever, and malaria; and use of antibiotics during 4-week follow-up.ResultsThe trial randomized 11 983 persons in labor (median age, 29.9 years). Overall, 225 newborns (1.9% of 11 783 live births) met the primary end point. The incidence of neonatal mortality or sepsis was similar in the azithromycin and placebo groups (2.0% [115/5889] vs 1.9% [110/5894]; risk difference [RD], 0.09 [95% CI, −0.39 to 0.57]), as was the incidence of neonatal mortality (0.8% vs 0.8%; RD, 0.04 [95% CI, −0.27 to 0.35]) and neonatal sepsis (1.3% vs 1.3%; RD, 0.02 [95% CI, −0.38 to 0.43]). Newborns in the azithromycin group compared with the placebo group had lower incidence of skin infections (0.8% vs 1.7%; RD, −0.90 [95% CI, −1.30 to −0.49]) and need for antibiotics (6.2% vs 7.8%; RD, −1.58 [95% CI, −2.49 to −0.67]). Postpartum parents in the azithromycin group had lower incidence of mastitis (0.3% vs 0.5%; RD, −0.24 [95% CI, −0.47 to −0.01]) and puerperal fever (0.1% vs 0.3%; RD, −0.19 [95% CI, −0.36 to −0.01]).Conclusions and RelevanceAzithromycin administered orally during labor did not reduce neonatal sepsis or mortality. These results do not support routine introduction of oral intrapartum azithromycin for this purpose.Trial RegistrationClinicalTrials.gov Identifier: NCT03199547
Background Studies on the determinants of carotid intima‐media thickness ( CIMT ), a marker of sub‐clinical atherosclerosis, mostly come from white, Asian, and diasporan black populations. We present CIMT data from sub‐Saharan Africa, which is experiencing a rising burden of cardiovascular diseases and infectious diseases. Methods and Results The H3 (Human Hereditary and Health) in Africa’s AWI‐Gen (African‐Wits‐INDEPTH partnership for Genomic) study is a cross‐sectional study conducted in adults aged 40 to 60 years from Burkina Faso, Kenya, Ghana, and South Africa. Cardiovascular disease risk and ultrasonography of the CIMT of right and left common carotids were measured. Multivariable linear and mixed‐effect multilevel regression modeling was applied to determine factors related to CIMT. Data included 8872 adults (50.8% men), mean age of 50±6 years with age‐ and sex‐adjusted mean (±SE) CIMT of 640±123μm. Participants from Ghana and Burkina Faso had higher CIMT compared with other sites. Age (β = 6.77, 95%CI [6.34–7.19]), body mass index (17.6[12.5–22.8]), systolic blood pressure (7.52[6.21–8.83]), low‐density lipoprotein cholesterol (5.08[2.10–8.06]) and men (10.3[4.75– 15.9]) were associated with higher CIMT. Smoking was associated with higher CIMT in men. High‐density lipoprotein cholesterol (−12.2 [−17.9– −6.41]), alcohol consumption (–13.5 [−19.1–−7.91]) and HIV (−8.86 [−15.7–−2.03]) were inversely associated with CIMT. Conclusions Given the rising prevalence of cardiovascular diseases risk factors in sub‐Saharan Africa, atherosclerotic diseases may become a major pan‐African epidemic unless preventive measures are taken particularly for prevention of hypertension, obesity, and smoking. HIV ‐specific studies are needed to fully understand the association between HIV and CIMT in sub‐Saharan Africa.
<p><strong>Background:</strong> Despite reduction in the risk of under-5 mortality in the last decade and a half, neonatal deaths have remained stable globally. Gram-positive bacterial infections are leading causes of neonatal sepsis and death. Because the mother is an important source for bacterial transmission to babies during the perinatal period, interventions that lower risk of transmission can potentially reduce invasive bacterial infections. The primary objective of the trial will assess the effect of intrapartum azithromycin on neonatal sepsis and mortality. Secondary objectives include the impact of the intervention on prevalence of carriage and resistance, puerperal infections, and infant growth.</p><p class="abstract"><strong>Methods:</strong> This is a phase III, double-blinded, placebo-controlled randomized trial in which 12,000 women in labour are randomized to either a single dose of 2 g of oral azithromycin (AZI) or placebo in The Gambia and Burkina Faso. Mother/newborn pairs are followed-up at 28-days post-delivery to assess health and mortality. Passive visits are conducted to collect adverse events including hospitalizations. When clinically indicated, samples are collected for assessment of neonatal and puerperal sepsis. A cohort of 250 mother/newborn pair per country have been included in the carriage sub-study to assess bacterial colonization at day 0, 6, 28 and 4 months. Children of the first 1000 mothers recruited in each country are followed-up at 6 and 12 months for anthropometric assessments.</p><p class="abstract"><strong>Conclusions: </strong>If successful, this simple implementable intervention has the potential to achieve wide coverage in Sub-Saharan Africa (SSA) where low-cost interventions to reduce neonatal sepsis and mortality and morbidity in mothers are urgently needed.</p><p class="abstract"><strong>Trial registration:</strong> The trial was registered at ClinicalTrials.gov: NCT03199547.</p>
Background and purpose: Resource-limited countries face challenges in setting up effective pharmacovigilance systems. This study aimed to monitor the occurrence of adverse events (AEs) after the use of artemisinin-based combination therapies (ACTs), identify potential drivers of reporting suspected adverse drug reactions (ADRs) and monitor AEs among women who were inadvertently exposed to ACTs in the first trimester of pregnancy. Patients and methods: We conducted a prospective observational study from May 2010 to July 2012 in Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso. The HDSS area was divided into active and passive surveillance areas to monitor AEs among patients (regardless of age or sex) who received a first-line ACT (artemetherlumefantrine or artesunate-amodiaquine). In the active surveillance area, patients were followed up for 28 days, while in the passive surveillance area, patients were encouraged to return voluntarily to the health facility to report any occurrence of AEs until day 28 after drug intake. We assessed the crude incidence rates of AEs in both cohorts and performed Cox regression with mixed random effects to identify potential drivers of ADR occurrence. Results: In total, 3170 participants were included in the study. Of these, 40.3% had reported at least one AE, with 39.6% and 44.4% from active and passive surveillance groups, respectively. The types of ADRs were similar in both groups. The most frequent reported ADRs were anorexia, weakness, cough, dizziness and pruritus. One case of abortion and eight cases of death were reported, but none of them was related to the ACT. The variance in random factors showed a high variability of ADR occurrence between patients in both groups, whereas variability between health facilities was low in the active surveillance group and high in passive surveillance group. Taking more than two concomitant medications was associated with high hazard in ADR occurrence, whereas the rainy season was associated with low hazard. Conclusion: This study showed that both passive and active surveillance approaches were useful tools. The HDSS allowed us to capture a few cases of exposure during the first trimester of pregnancy. The passive surveillance approach, which is more likely to be implemented by malaria control programs, seems to be more relevant in the Sub-Saharan African context.
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