How geographic access to care shapes disease burden: the current impact of post-exposure prophylaxis and potential for expanded access to prevent human rabies deaths in Madagascar

Background: Post-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning. Methodology & principal findings: We use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI): 790–1120), with PEP averting an additional 800 deaths (95% PI: 640–970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust. Conclusions & significance: PEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths

An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial.

BACKGROUND: Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides. METHODS: A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague 'seasons'. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11. DISCUSSION: If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022. TRIAL REGISTRATION: ClinicalTrials.gov NCT04110340 . Registered on 1 October 2019

Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

INTRODUCTION: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test-called the Genital InFlammation Test (GIFT)-for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care. METHODS AND ANALYSIS: We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical ('diagnostic study') and a qualitative, modelling and economic ('an integration into care study') part. The diagnostic study aims to evaluate GIFT's performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms. ETHICS AND DISSEMINATION: Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d'Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484). TRIAL REGISTRATION NUMBER: NCT05723484

Determinants of COVID-19-related knowledge and disrupted habits during epidemic waves among women of childbearing age in urban and rural areas of the Malagasy Middle East

Abstract Background With regard to the coronavirus disease (COVID-19) pandemic in Madagascar, little is known about the knowledge, the perceptions and the impacts of this disease on women of childbearing age. People’s knowledge of COVID-19 can have an impact on their attitudes towards seeking care. The aim of the current study is to determine the knowledge of COVID-19 and associated determinants among women of childbearing age in Moramanga. Methods A cross-sectional study based on questionnaire administration was used among women of childbearing age. Data collection was conducted from August to October 2021. A scoring method was applied to evaluate their knowledge level and perceptions about COVID-19 and its impacts on their lives. A binary stepwise logistic regression was performed to determine the sociodemographic determinants of their knowledge level about COVID-19. Results A total of 885 women of childbearing age from urban and rural Moramanga areas were interviewed. Approximately 49.8% (441/885) lived in urban areas, and 50.2% (444/885) lived in rural areas. Approximately 35.3% (322/885) of the participants had a good level of knowledge of COVID-19. Multivariate analysis showed that the probability of having a good level of knowledge of COVID-19 had a significant statistical association (p value < 0.05) with living in an urban area [AOR: 2.89; 95% CI (1.89–4.42)], telephone ownership [AOR: 1.71; 95% CI (1.16–2.53)], radio ownership [AOR 2.2; 95% CI (1.43–3.38)], watching TV [AOR = 1.95; 95% CI (1.34–2.83)] and reading journal papers [AOR = 3.74 95% CI (1.69–8.27)]. Conclusions Almost a third of the sampled women of childbearing age had a good level of knowledge of COVID-19. Access to information through telecommunications technologies increases the chances of being better informed about the disease. To avoid the negative repercussions of infectious disease epidemics, it is necessary to improve the awareness of childbearing women about these diseases by taking demographic features of the population into account

Inequalities in cause-specific mortality in children and adolescents in the Moramanga health survey, Madagascar

Objectives One child or young adolescent dies every 10 min in Madagascar and large disparities in survival persist. We estimated cause-specific mortality in a cohort of children aged 0–14 in the Moramanga district and explored how causes of death shape these inequalities. Methods Children were followed prospectively between 2012 and 2017. Causes of death were established based on verbal autopsies. Incidence rate ratios were estimated in Poisson regression models. Results The risk of dying before age 15 was 68.1 per thousand live births. Risks of dying were highest in the first year of life (31.2‰) and lowest in children aged 10–14 (6.4‰). The male-to-female sex ratios of mortality increased with age and reached 2.3 among adolescents aged 10–14. Communicable, nutritional and neonatal causes accounted for 79.5% of deaths below age 5 and 47.0% above age 5. Mortality was positively associated with household poverty, lack of education of the household head, and rural residence. Conclusions Interventions should be designed with an equity lens to reduce large disparities in survival and be tailored to the needs of each age-group

Cohort profile: Moramanga health survey in urban and rural areas in Madagascar (MHURAM project)

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The importance of public health, poverty reduction programs and women’s empowerment in the reduction of child stunting in rural areas of Moramanga and Morondava, Madagascar

<div><p>Background</p><p>Malnutrition accounts for 45% of mortality in children under five years old, despite a global mobilization against chronic malnutrition. In Madagascar, the most recent data show that the prevalence of stunting in children under five years old is still around 47.4%. This study aimed to identify the determinants of stunting in children in rural areas of Moramanga and Morondava districts to target the main areas for intervention.</p><p>Methods</p><p>A case-control study was conducted in children aged from 6 to 59.9 months, in 2014–2015. We measured the height and weight of mothers and children and collected data on child, mother and household characteristics. One stool specimen was collected from each child for intestinal parasite identification. We used a multivariate logistic regression model to identify the determinants of stunting using backwards stepwise methods.</p><p>Results</p><p>We included 894 and 932 children in Moramanga and in Morondava respectively. Stunting was highly prevalent in both areas, being 52.8% and 40.0% for Moramanga and Morondava, respectively. Stunting was most associated with a specific age period (12mo to 35mo) in the two study sites. Infection with <i>Trichuris trichiura</i> (aOR: 2.4, 95% CI: 1.1–5.3) and those belonging to poorer households (aOR: 2.3, 95% CI: 1.6–3.4) were the major risk factors in Moramanga. In Morondava, children whose mother had activities outside the household (aOR: 1.7, 95% CI: 1.2–2.5) and those perceived to be small at birth (aOR: 1.6, 95% CI: 1.1–2.1) were more likely to be stunted, whereas adequate birth spacing (≥24months) appeared protective (aOR: 0.4, 95% CI: 0.3–0.7).</p><p>Conclusion</p><p>Interventions that could improve children’s growth in these two areas include poverty reduction, women’s empowerment, public health programmes focusing on WASH and increasing acceptability, and increased coverage and quality of child/maternal health services.</p></div

Characteristics of children included in the case-control study in Moramanga and Morondava.

<p>Characteristics of children included in the case-control study in Moramanga and Morondava.</p

Final model estimates for determinants of stunting in children 6 to 59.9 months, municipalities of Bemanonga-Morondava (n = 932).

<p>Final model estimates for determinants of stunting in children 6 to 59.9 months, municipalities of Bemanonga-Morondava (n = 932).</p