Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study (preprint)

Introduction: Three years into the pandemic, there remains significant uncertainty about the true infection and mortality burden of COVID-19 in the WHO-Africa region. High quality, population-representative studies in Africa are rare and tend to be conducted in national capitals or large cities, leaving a substantial gap in our understanding of the impact of COVID-19 in rural, low-resource settings. Here, we estimated the spatio-temporal morbidity and mortality burden associated with COVID-19 in a rural health district of Madagascar until the first half of 2021. Methods: We integrated a nested seroprevalence study within a pre-existing longitudinal cohort conducted in a representative sample of 1600 households in Ifanadiana District, Madagascar. Socio-demographic and health information was collected in combination with dried blood spots for about 6500 individuals of all ages, which were analysed to detect IgG and IgM antibodies against four specific proteins of SARS-CoV2 in bead-based multiplex immunoassay. We evaluated spatio-temporal patterns in COVID-19 infection history and its associations with several geographic, socio-economic and demographic factors via logistic regressions. Results: Eighteen percent of people had been infected by April-June 2021, with seroprevalence increasing with individuals age. COVID-19 primarily spread along the only paved road and in major towns during the first epidemic wave, subsequently spreading along secondary roads during the second wave to more remote areas. Wealthier individuals and those with occupations such as commerce and formal employment were at higher risk of being infected in the first wave. Adult mortality increased in 2020, particularly for older men for whom it nearly doubled up to nearly 40 deaths per 1000. Less than 10% of mortality in this period could be directly attributed to COVID-19 deaths given known infection fatality ratios and observed seroprevalence in the district. Conclusion: Our study provides a very granular understanding on COVID-19 transmission and mortality in a rural population of sub-Saharan Africa and suggests that the disease burden in these areas may have been substantially underestimated.

Targeting SARS-CoV-2 superspreading infections could dramatically improve the efficiency of epidemic control strategies in resource-limited contexts (preprint)

Background: Superspreading infections play an important role in the SARS-CoV-2 pandemic. Superspreading is caused primarily by heterogeneity in social contact rates, and therefore represents an opportunity for targeting surveillance and control via consideration of social network topologies, particularly in resource-limited settings. Yet, it remains unclear how to implement such surveillance and control, especially when network data is unavailable. Methods: We evaluated the efficiency of a testing strategy that targeted potential superspreading individuals based on their degree centrality on a social network compared to a random testing strategy in the context of low testing capacity. We simulated SARS-CoV-2 dynamics on two contact networks from rural Madagascar and measured the epidemic duration, infection burden, and tests needed to end the epidemics. In addition, we examined the robustness of this approach when individuals' true degree centralities were unknown and were instead estimated via readily-available socio-demographic variables. Findings: Targeted testing of potential superspreaders reduced the infection burden by 40-63% at low testing capacities, while requiring between 45-78% fewer tests compared to random testing. Further, targeted testing remained more efficient when the true network topology was unknown and prioritization was based on socio demographic characteristics. Interpretation: Incorporating social network topology into epidemic control strategies is an effective public health strategy for health systems suffering from low testing capacity and can be implemented via socio-demographic proxies when social networks are unknown.

Prioritizing COVID-19 vaccination efforts and dose allocation within Madagascar (preprint)

BackgroundWhile mass COVID-19 vaccination programs are underway in high-income countries, limited availability of doses has resulted in few vaccines administered in low and middle income countries (LMICs). The COVID-19 Vaccines Global Access (COVAX) is a WHO-led initiative to promote vaccine access equity to LMICs and is providing many of the doses available in these settings. However, initial doses are limited and countries, such as Madagascar, need to develop prioritization schemes to maximize the benefits of vaccination with very limited supplies. There is some consensus that dose deployment should initially target health care workers, and those who are more vulnerable including older individuals. However, questions of geographic deployment remain, in particular associated with limits around vaccine access and delivery capacity in underserved communities, for example in rural areas that may also include substantial proportions of the population. MethodsTo address these questions, we developed a mathematical model of SARS-CoV-2 transmission dynamics and simulated various vaccination allocation strategies for Madagascar. Simulated strategies were based on a number of possible geographical prioritization schemes, testing sensitivity to initial susceptibility in the population, and evaluating the potential of tests for previous infection. ResultsUsing cumulative deaths due to COVID-19 as the main outcome of interest, our results indicate that distributing the number of vaccine doses according to the number of elderly living in the region or according to the population size results in a greater reduction of mortality compared to distributing doses based on the reported number of cases and deaths. The benefits of vaccination strategies are diminished if the burden (and thus accumulated immunity) has been greatest in the most populous regions, but the overall strategy ranking remains comparable. If rapid tests for prior immunity may be swiftly and effectively delivered, there is potential for considerable gain in mortality averted, but considering delivery limitations modulates this. ConclusionAt a subnational scale, our results support the strategy adopted by the COVAX initiative at a global scale.

Reconciling model predictions with low reported cases of COVID-19 in Sub-Saharan Africa: Insights from Madagascar (preprint)

The COVID-19 pandemic has wreaked havoc globally, and there has been a particular concern for sub-Saharan Africa (SSA), where models suggest that the majority of the population will become infected. Conventional wisdom suggests that the continent will bear a higher burden of COVID-19 for the same reasons it suffers high burdens of other infectious diseases: ecology, socio-economic conditions, lack of water and sanitation infrastructure, and weak health systems. However, so far SSA has reported lower incidence and fatalities compared to the predictions of standard models and the experience of other regions of the world. There are three leading explanations, each with very different implications for the final epidemic burden: (1) low case detection, (2) differences in COVID-19 epidemiology (e.g. low R0), and (3) policy interventions. The low number of cases to date have led some SSA governments to relax these policy interventions. Will this result in a resurgence of cases? To understand how to interpret the lower-than-expected COVID-19 case data in Madagascar, we use a simple age-structured model to explore each of these explanations and predict the epidemic impact associated with them. We show that the current incidence of COVID-19 cases can be explained by any combination of the late introduction of first imported cases, early implementation of non-pharmaceutical interventions (NPIs), and low case detection rates. This analysis reinforces that Madagascar, along with other countries in SSA, remains at risk of an impending health crisis. If NPIs remain enforced, up to 50,000 lives may be saved. Even with NPIs, without vaccines and new therapies, COVID-19 could infect up to 30% of the population, making it the largest public health threat in Madagascar until early 2021, hence the importance of conducting clinical trials and continually improving access to healthcare. ResumeLa pandemie de COVID-19 a eu des consequences nefastes partout dans le monde, et il y a une preoccupation particuliere pour lAfrique subsaharienne (ASS), ou des modeles suggerent que la majorite de la population sera infectee. Il est craint que le continent supportera un fardeau plus elevee de COVID-19 pour les memes raisons quil souffre davantage dautres maladies infectieuses: ecologie, conditions socio-economiques, manque dinfrastructures deau et dassainissement, et faiblesse des systemes de sante. Cependant, jusqua present, lASS a rapporte une incidence et une mortalite bien inferieure a celle des previsions des modeles pour cette region, ainsi quau nombre observe dans dautres regions du monde. Il y a trois explications principales pour ce phenomene, chacune ayant des implications tres differentes pour le fardeau epidemique final: (1) detection faible des cas, (2) differences dans lepidemiologie COVID-19 (par exemple faible R0), et (3) interventions et politiques mises en place. Le faible nombre de cas a ce jour a conduit certains gouvernements dASS a assouplir ces interventions. Cela entrainera-t-il une resurgence de cas? Pour comprendre comment interpreter le fait que les cas COVID-19 rapportes sont plus faibles que prevu a Madagascar, nous utilisons un modele de transmission structure par groupe dage pour explorer chacune de ces explications et predire limpact epidemique qui leur est associe. Nous montrons que lincidence actuelle des cas de COVID-19 peut sexpliquer par leffet cumule de lintroduction tardive des premiers cas importes, la mise en uvre rapide dinterventions non pharmaceutiques (INP) et de faibles taux de detection des cas. Cette analyse renforce le fait que Madagascar, ainsi que dautres pays dAfrique subsaharienne, reste a risque dune crise sanitaire imminente. Si les INP restent appliques, jusqua 50 000 vies pourraient etre sauvees. Meme avec des INP, tant quil ny aura pas des vaccins ni des nouvelles therapies efficaces, COVID-19 pourrait infecter jusqua 30% de la population, ce qui constituerait la plus grande menace pour la sante publique a Madagascar jusquau debut de 2021, dou limportance de la realisation des essais cliniques et de lamelioration continuelle de lacces aux soins. Summary BoxO_LIThe lower-than-expected number of reported cases of COVID-19 in Madagascar can be explained by a combination of the relatively late introduction of the disease, low detection rates, and low transmission rates due to the early and effective implementation of non-pharmaceutical interventions that reduced contact rates. C_LIO_LICOVID-19 is predicted to be the largest public health problem in Madagascar in 2020, but non-pharmaceutical interventions at an effectiveness similar to those seen in the first few months could save up to 50,000 lives. C_LIO_LIHealth systems in SSA remain at risk of an impending health crisis due to COVID-19, stressing the importance of ongoing clinical trials and improving health care access. C_LI