Trends and risk factors for childhood diarrhea in sub-Saharan countries (1990 2013): assessing the neighborhood inequalities

BACKGROUND: Diarrheal diseases are a major cause of child mortality and one of the main causes of medical consultation for children in sub-Saharan countries. This paper attempts to determine the risk factors and neighborhood inequalities of diarrheal morbidity among under-5 children in selected countries in sub- Saharan Africa over the period 1990 2013. DESIGN: Data used come from the Demographic and Health Survey (DHS) waves conducted in Burkina Faso (1992 93, 1998 99, 2003, and 2010), Mali (1995, 2001, 2016, and 2012), Nigeria (1990, 1999, 2003, 2008, and 2013), and Niger (1992, 1998, 2006, and 2012). Bivariate analysis was performed to assess the association between the dependent variable and each of the independent variables. Multilevel logistic regression modelling was used to determine the fixed and random effects of the risk factors associated with diarrheal morbidity. RESULTS: The findings showed that the proportion of diarrheal morbidity among under-5 children varied considerably across the cohorts of birth from 10 to 35%. There were large variations in the proportion of diarrheal morbidity across countries. The proportions of diarrheal morbidity were higher in Niger compared with Burkina Faso, Mali, and Nigeria. The risk factors of diarrheal morbidity varied from one country to another, but the main factors included the child's age, size of the child at birth, the quality of the main floor material, mother's education and her occupation, type of toilet, and place of residence. The analysis shows an increasing trend of diarrheal inequalities according to DHS rounds. In Burkina Faso, the value of the intraclass correlation coefficient (ICC) was 0.04 for 1993 DHS and 0.09 in 2010 DHS; in Mali, the ICC increased from 0.04 in 1995 to 0.16 in 2012; in Nigeria, the ICC increased from 0.13 in 1990 to 0.19 in 2013; and in Niger, the ICC increased from 0.07 in 1992 to 0.11 in 2012.IS

Opportunities and challenges for decentralised clinical trials in sub-Saharan Africa: a qualitative study

IntroductionDigital health has gained traction in research and development, and clinical decision support systems. The COVID-19 pandemic accelerated the adoption of decentralised clinical trials (DCTs) as a mitigation and efficiency improvement strategy. We assessed the opportunities and challenges of a digital transformation in clinical research in sub-Saharan Africa from different stakeholders’ perspectives.MethodsA qualitative study, including 40 in-depth semi structured interviews, was conducted with investigators of three leading research institutions in sub-Saharan Africa and Switzerland, contract research organisations and sponsors managing clinical trials in sub-Saharan Africa. A thematic approach was used for the analysis.ResultsInterviewees perceived DCTs as an opportunity for trial efficiency improvement, quality improvement and reducing the burden of people participating in clinical trials. However, to gain and maintain an optimal quality of clinical trials, a transition period is necessary to tackle contextual challenges before DCTs are being implemented. The main challenges are categorised into four themes: (1) usability and practicability of the technology; (2) paradigm shift and trial data quality; (3) ethical and regulatory hurdles and (4) contextual factors (site-specific research environment and sociocultural aspects).ConclusionThe transformation from a site to a patient-centric model with an increased responsibility of participants should be context adapted. The transformation requires substantial investment, training of the various stakeholders and an efficient communication. Additionally, commitment of sponsors, investigators, ethics and regulatory authorities and the buy-in of the communities are essential for this change

Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial.

IntroductionBiannual mass azithromycin distribution to children aged 1-59 months has been shown to reduce all-cause mortality. Children under 28 days of age were not treated in studies evaluating mass azithromycin distribution for child mortality due to concerns related to infantile hypertrophic pyloric stenosis (IHPS). Here, we report the design of a randomised controlled trial to evaluate the efficacy and safety of administration of a single dose of oral azithromycin during the neonatal period.Methods and analysisThe Nouveaux-nés et Azithromycine: une Innovation dans le Traitement des Enfants (NAITRE) study is a double-masked randomised placebo-controlled trial designed to evaluate the efficacy of a single dose of azithromycin (20 mg/kg) for the prevention of child mortality. Newborns (n=21 712) aged 8-27 days weighing at least 2500 g are 1:1 randomised to a single, directly observed, oral dose of azithromycin or matching placebo. Participants are followed weekly for 3 weeks after treatment to screen for adverse events, including IHPS. The primary outcome is all-cause mortality at the 6-month study visit.Ethics and disseminationThis study was approved by the Institutional Review Boards at the University of California, San Francisco in San Francisco, USA (Protocol #18-25027) and the Comité National d'Ethique pour la Recherche in Ouagadougou, Burkina Faso (Protocol #2018-10-123). The findings of this trial will be presented at local, regional and international meetings and published in open access peer-reviewed journals.Trial registration numberNCT03682653; Pre-results

Guillain-Barre syndrome associated with COVID-19 infection:A case series

In this communication, we reported a series of six patients presented with Guillain-Barré syndrome that associated with COVID-19 infection, which was confirmed with RT-PCR. Here we discuss the laboratory investigation and case management, as well as clinical presentation and outcome of each case. The current report demonstrated the first case series of COVID-19-associated GBS-cases in Sudan.</p

Pre-Clinical Assessment of Novel Multivalent MSP3 Malaria Vaccine Constructs

BACKGROUND: MSP3 has been shown to induce protection against malaria in African children. The characterization of a family of Plasmodium falciparum merozoite surface protein 3 (MSP3) antigens sharing a similar structural organization, simultaneously expressed on the merozoite surface and targeted by a cross-reactive network of protective antibodies, is intriguing and offers new perspectives for the development of subunit vaccines against malaria. METHODS: Eight recombinant polyproteins containing carefully selected regions of this family covalently linked in different combinations were all efficiently produced in Escherichia coli. The polyproteins consisted of one monovalent, one bivalent, one trivalent, two tetravalents, one hexavalent construct, and two tetravalents incorporating coiled-coil repeats regions from LSA3 and p27 vaccine candidates. RESULTS: All eight polyproteins induced a strong and homogeneous antibody response in mice of three distinct genotypes, with a dominance of cytophilic IgG subclasses, lasting up to six months after the last immunization. Vaccine-induced antibodies exerted a strong monocyte-mediated in vitro inhibition of P. falciparum growth. Naturally acquired antibodies from individuals living in an endemic area of Senegal recognized the polyproteins with a reactivity mainly constituted of cytophilic IgG subclasses. CONCLUSIONS: Combination of genetically conserved and antigenically related MSP3 proteins provides promising subunit vaccine constructs, with improved features as compared to the first generation construct employed in clinical trials (MSP3-LSP). These multivalent MSP3 vaccine constructs expand the epitope display of MSP3 family proteins, and lead to the efficient induction of a wider range of antibody subclasses, even in genetically different mice. These findings are promising for future immunization of genetically diverse human populations

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721

Trends and risk factors for childhood diarrhea in sub-Saharan countries (1990–2013): assessing the neighborhood inequalities

Background: Diarrheal diseases are a major cause of child mortality and one of the main causes of medical consultation for children in sub-Saharan countries. This paper attempts to determine the risk factors and neighborhood inequalities of diarrheal morbidity among under-5 children in selected countries in sub-Saharan Africa over the period 1990–2013. Design: Data used come from the Demographic and Health Survey (DHS) waves conducted in Burkina Faso (1992–93, 1998–99, 2003, and 2010), Mali (1995, 2001, 2016, and 2012), Nigeria (1990, 1999, 2003, 2008, and 2013), and Niger (1992, 1998, 2006, and 2012). Bivariate analysis was performed to assess the association between the dependent variable and each of the independent variables. Multilevel logistic regression modelling was used to determine the fixed and random effects of the risk factors associated with diarrheal morbidity. Results: The findings showed that the proportion of diarrheal morbidity among under-5 children varied considerably across the cohorts of birth from 10 to 35%. There were large variations in the proportion of diarrheal morbidity across countries. The proportions of diarrheal morbidity were higher in Niger compared with Burkina Faso, Mali, and Nigeria. The risk factors of diarrheal morbidity varied from one country to another, but the main factors included the child's age, size of the child at birth, the quality of the main floor material, mother's education and her occupation, type of toilet, and place of residence. The analysis shows an increasing trend of diarrheal inequalities according to DHS rounds. In Burkina Faso, the value of the intraclass correlation coefficient (ICC) was 0.04 for 1993 DHS and 0.09 in 2010 DHS; in Mali, the ICC increased from 0.04 in 1995 to 0.16 in 2012; in Nigeria, the ICC increased from 0.13 in 1990 to 0.19 in 2013; and in Niger, the ICC increased from 0.07 in 1992 to 0.11 in 2012. Conclusions: This suggests the need to fight against diarrheal diseases on both the local and community levels across villages

Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates.

OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. METHODS: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. RESULTS: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p < 0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. CONCLUSIONS: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity

Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial

Artemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6–59 months) with uncomplicated falciparum malaria in Burkina Faso were treated with artesunate-amodiaquine (AS-AQ) and randomized to MB (15 mg/kg/day for 3 days) or PQ (0.25 mg/kg at day 2) with the aim to show non-inferiority of the MB regimen with regard to haematological recovery at day 7 (primary endpoint). MB-AS-AQ could not be shown to be non-inferior to PQ-AS-AQ (mean Hb difference between treatment groups on day 7 was -0.352, 95% CI -0.832–0.128, p = 0.0767), however, haemoglobin recovery following treatment was alike in the two study arms (day 7: mean 0.2±1.4 g/dl vs. 0.5±0.9 g/dl, p = 0.446). Occurrence of adverse events was similar in both groups, except for vomiting, which was more frequent in the MB than in the PQ arm (20/50 vs 7/50, p = 0.003). Adequate clinical and parasitological response was above 95% in both groups, but significantly more asexual parasites were cleared in the MB arm compared to the PQ arm already on day 1 (48/50, 96%, vs 40/50, 80%, p = 0.014). Moreover, P. falciparum gametocyte prevalence and density were lower in the MB arm than in the PQ arm, which reached statistical significance on day 2 (prevalence: 2/50, 4%, vs 15/49, 31%, p<0.001; density: 9.6 vs 41.1/μl, p = 0.024). However, it should be considered that PQ was given only on day 2. MB-ACT appears to be an interesting alternative to PQ-ACT for the treatment of falciparum malaria. While there is a need to further improve MB formulations, MB-ACT may already be considered useful to reduce falciparum malaria transmission intensity, to increase treatment efficacy, and to reduce the risk for resistance development and spread