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EXPLORE IDM’S CURRENT RESEARCH PUBLICATIONS

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Victoria Nembaware, Gaston K. Mazandu, Jade Hotchkiss, Jean-Michel Safari Serufuri, Jill Kent, Andre Pascal Kengne, Kofi Anie, Nchangwi Syntia Munung, Daima Bukini, Valentina Josiane Ngo Bitoungui, Deogratias Munube, Uzima Chirwa, Catherine Chunda-Liyoka, Agnes Jonathan, Miriam V. Flor-Park, Kevin Kum Esoh, Mario Jonas, Khuthala Mnika, Chandré Oosterwyk, Upendo Masamu, Jack Morrice, Annette Uwineza, Arthemon Nguweneza, Kambe Banda, Isaac Nyanor, David Nana Adjei, Nathan Edward Siebu, Malula Nkanyemka, Patience Kuona, Bamidele O. Tayo, Andrew Campbell, Assaf P. Oron, Obiageli E. Nnodu, Vivian Painstil, Julie Makani, Nicola Mulder, Ambroise Wonkam

OMICS

Sickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs, and challenges. A major component of the workshop was new approaches to harness SCDO to harmonize data elements used by different studies. This was facilitated by a web-based platform onto which participants uploaded data elements from previous or ongoing SCD-relevant research studies before the workshop, making multisite collaborative research studies based on existing SCD data possible, including multisite cohort, SCD global clinical trials, and SCD community engagement approaches. Trainees presented proposals for systematic literature reviews in key SCD research areas. This expert review emphasizes potential and prospects of SCDO-enabled data standards and harmonization to facilitate large-scale global SCD collaborative initiatives. As the fields of public and global health continue to broaden toward planetary health, the SCDO is well poised to play a prominent role to decipher SCD pathophysiology further, and co-design diagnostics and therapeutics innovation in the field.

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Background

Absolute numbers of COVID-19 cases and deaths reported to date in the sub-Saharan Africa (SSA) region have been significantly lower than those across the Americas, Asia, and Europe. As a result, there has been limited information about the demographic and clinical characteristics of deceased cases in the region, as well as the impacts of different case management strategies.

Methods

Data from deceased cases reported across SSA through May 10, 2020 and from hospitalized cases in Burkina Faso through April 15, 2020 were analyzed. Demographic, epidemiological, and clinical information on deceased cases in SSA was derived through a line-list of publicly available information and, for cases in Burkina Faso, from aggregate records at the Centre Hospitalier Universitaire de Tengandogo in Ouagadougou. A synthetic case population was derived probabilistically using distributions of age, sex, and underlying conditions from populations of West African countries to assess individual risk factors and treatment effect sizes. Logistic regression analysis was conducted to evaluate the adjusted odds of survival for patients receiving oxygen therapy or convalescent plasma, based on therapeutic effectiveness observed for other respiratory illnesses.

Results

Across SSA, deceased cases for which demographic data are available have been predominantly male (63/103, 61.2%) and over 50 years of age (59/75, 78.7%). In Burkina Faso, specifically, the majority of deceased cases either did not seek care at all or were hospitalized for a single day (59.4%, 19/32); hypertension and diabetes were often reported as underlying conditions. After adjustment for sex, age, and underlying conditions in the synthetic case population, the odds of mortality for cases not receiving oxygen therapy was significantly higher than those receiving oxygen, such as due to disruptions to standard care (OR: 2.07; 95% CI: 1.56 – 2.75). Cases receiving convalescent plasma had 50% reduced odds of mortality than those who did not (95% CI: 0.24 – 0.93).

Conclusions

Investment in sustainable production and maintenance of supplies for oxygen therapy, along with messaging around early and appropriate use for healthcare providers, caregivers, and patients could reduce COVID-19 deaths in SSA. Further investigation into convalescent plasma is warranted, as data on its effectiveness specifically in treating COVID-19 becomes available. The success of supportive or curative clinical interventions will depend on earlier treatment seeking, such that community engagement and risk communication will be critical components of the response.

Anna Bershteyn, Monisha Sharma, Adam Akullian, Kathryn Peebles, Supriya Sarkar, R Scott Braithwaite, Edinah Mudimu

JOURNAL OF THE INTERNATIONAL AIDS SOCIETY

Introduction

Over one hundred implementation studies of HIV pre‐exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long‐acting PrEP in the setting of western Kenya, one of the world’s most heavily HIV‐affected regions.

Methods

We incorporated steps of the PrEP prevention cascade – uptake, adherence, retention and re‐engagement after discontinuation – into EMOD‐HIV, an open‐source transmission model calibrated to the demography and HIV epidemic patterns of western Kenya. Early PrEP implementation research from East Africa was used to parameterize prevention cascades for oral PrEP as currently implemented, delivery innovations for oral PrEP, and future long‐acting PrEP. We compared infections averted by PrEP at the population level for different cascade assumptions and sub‐populations on PrEP. Analyses were conducted over the 2020 to 2040 time horizon, with additional sensitivity analyses for the time horizon of analysis and the time when long‐acting PrEP becomes available.

Results

The maximum impact of oral PrEP diminished by over 98% across all prevention cascades, with the exception of long‐acting PrEP under optimistic assumptions about uptake and re‐engagement after discontinuation. Long‐acting PrEP had the highest population‐level impact, even after accounting for possible delays in product availability, primarily because its effectiveness does not depend on drug adherence. Retention was the most significant cascade step reducing the potential impact of long‐acting PrEP. These results were robust to assumptions about the sub‐populations receiving PrEP, but were highly influenced by assumptions about re‐initiation of PrEP after discontinuation, about which evidence was sparse.

Conclusions

Implementation challenges along the prevention cascade compound to diminish the population‐level impact of oral PrEP. Long‐acting PrEP is expected to be less impacted by user uptake and adherence, but it is instead dependent on product availability in the short term and retention in the long term. To maximize the impact of long‐acting PrEP, ensuring timely product approval and rollout is critical. Research is needed on strategies to improve retention and patterns of PrEP re‐initiation.

Assaf P. Oron, Dennis L. Chao, Echezona E. Ezeanolue, Loveth N. Ezenwa, Frédéric B. Piel, Osifo Telison Ojogun, Sophie Uyoga, Thomas N. Williams & Obiageli E. Nnodu 

BMC MEDICINE

Background

Most of the world’s sickle cell disease (SCD) burden is in Africa, where it is a major contributor to child morbidity and mortality. Despite the low cost of many preventive SCD interventions, insufficient resources have been allocated, and progress in alleviating the SCD burden has lagged behind other public-health efforts in Africa. The recent announcement of massive new funding for research into curative SCD therapies is encouraging in the long term, but over the next few decades, it is unlikely to help Africa’s SCD children substantially.

Main discussion

A major barrier to progress has been the absence of large-scale early-life screening. Most SCD deaths in Africa probably occur before cases are even diagnosed. In the last few years, novel inexpensive SCD point-of-care test kits have become widely available and have been deployed successfully in African field settings. These kits could potentially enable universal early SCD screening. Other recent developments are the expansion of the pneumococcal conjugate vaccine towards near-universal coverage, and the demonstrated safety, efficacy, and increasing availability and affordability of hydroxyurea across the continent. Most elements of standard healthcare for SCD children that are already proven to work in the West, could and should now be implemented at scale in Africa. National and continental SCD research and care networks in Africa have also made substantial progress, assembling care guidelines and enabling the deployment and scale-up of SCD public-health systems. Substantial logistical, cultural, and awareness barriers remain, but with sufficient financial and political will, similar barriers have already been overcome in efforts to control other diseases in Africa.

Conclusion and recommendations

Despite remaining challenges, several high-SCD-burden African countries have the political will and infrastructure for the rapid implementation and scale-up of comprehensive SCD childcare programs. A globally funded effort starting with these countries and expanding elsewhere in Africa and to other high-burden countries, including India, could transform the lives of SCD children worldwide and help countries to attain their Sustainable Development Goals. This endeavor would also require ongoing research focused on the unique needs and challenges of SCD patients, and children in particular, in regions of high prevalence.

Laura A Skrip PhD, Jamie Bedson MSSc, Sharon Abramowitz PhD, Mohammed B Jalloh MPH, Saiku Bah MSc, Mohamed F Jalloh MPH, Ollin Demian Langle-Chimal MSc, Nicholas Cheney PhD, LaurentHébert-Dufresne PhD, Benjamin M Althouse PhD

THE LANCET PLANETARY HEALTH

Background

The west African Ebola epidemic (2014–15) necessitated behaviour change in settings with prevalent and pre-existing unmet needs as well as extensive mechanisms for local community action. We aimed to assess spatial and temporal trends in community-reported needs and associations with behaviour change, community engagement, and the overall outbreak situation in Sierra Leone.

Methods

We did a retrospective, mixed-methods study. Post-hoc analyses of data from 12 096 mobiliser visits as part of the Social Mobilization Action Consortium were used to describe the evolution of satisfied and unsatisfied needs (basic, security, autonomy, respect, and social support) between Nov 12, 2014, and Dec 18, 2015, and across 14 districts. Via Bayesian hierarchical regression modelling, we investigated associations between needs categories and behaviours (numbers of individuals referred to treatment within 24 h of symptom onset or deaths responded to with safe and dignified burials) and the role of community engagement programme status (initial vs follow-up visit) in the association between satisfied versus unsatisfied needs and behaviours.

Findings

In general, significant associations were observed between unsatisfied needs categories and both prompt referrals to treatment and safe burials. Most notably, communities expressing unsatisfied capacity needs reported fewer safe burials (relative risk [RR] 0·86, 95% credible interval [CrI] 0·82–0·91) and fewer prompt referrals to treatment (RR 0·76, 0·70–0·83) than did those without unsatisfied capacity needs. The exception was expression of unsatisfied basic needs, which was associated with significantly fewer prompt referrals only (RR 0·86, 95% CrI 0·79–0·93). Compared with triggering visits by community mobilisers, follow-up visits were associated with higher numbers of prompt referrals (RR 1·40, 95% CrI 1·30–1·50) and safe burials (RR 1·08, 1·02–1·14).

Interpretation

Community-based development of locally feasible, locally owned action plans, with the support of community mobilisers, has potential to address unmet needs for more sustained behaviour change in outbreak settings.

Funding

Bill & Melinda Gates, Bill & Melinda Gates Foundation, and National Institutes of Health.

Adam Akullian , Michelle Morrison, Geoffrey P Garnett, Zandile Mnisi, Nomthandazo Lukhele, Daniel Bridenbecker, Anna Bershteyn

THE LANCET HIV

Background

The rapid scale-up of antiretroviral therapy (ART) towards the UNAIDS 90-90-90 goals over the last decade has sparked considerable debate as to whether universal test and treat can end the HIV-1 epidemic in sub-Saharan Africa. We aimed to develop a network transmission model, calibrated to capture age-specific and sex-specific gaps in the scale-up of ART, to estimate the historical and future effect of attaining and surpassing the UNAIDS 90-90-90 treatment targets on HIV-1 incidence and mortality, and to assess whether these interventions will be enough to achieve epidemic control (incidence of 1 infection per 1000 person-years) by 2030.

Methods

We used eSwatini (formerly Swaziland) as a case study to develop our model. We used data on HIV prevalence by 5-year age bins, sex, and year from the 2007 Swaziland Demographic Health Survey (SDHS), the 2011 Swaziland HIV Incidence Measurement Survey, and the 2016 Swaziland Population Health Impact Assessment (PHIA) survey. We estimated the point prevalence of ART coverage among all HIV-infected individuals by age, sex, and year. Age-specific data on the prevalence of male circumcision from the SDHS and PHIA surveys were used as model inputs for traditional male circumcision and scale-up of voluntary medical male circumcision (VMMC). We calibrated our model using publicly available data on demographics; HIV prevalence by 5-year age bins, sex, and year; and ART coverage by age, sex, and year. We modelled the effects of five scenarios (historical scale-up of ART and VMMC [status quo], no ART or VMMC, no ART, age-targeted 90-90-90, and 100% ART initiation) to quantify the contribution of ART scale-up to declines in HIV incidence and mortality in individuals aged 15–49 by 2016, 2030, and 2050.

Findings

Between 2010 and 2016, status-quo ART scale-up among adults (aged 15–49 years) in eSwatini (from 34·0% in 2010 to 74·1% in 2016) reduced HIV incidence by 43·57% (95% credible interval 39·71 to 46·36) and HIV mortality by 56·17% (54·06 to 58·92) among individuals aged 15–49 years, with larger reductions in incidence among men and mortality among women. Holding 2016 ART coverage levels by age and sex into the future, by 2030 adult HIV incidence would fall to 1·09 (0·87 to 1·29) per 100 person-years, 1·42 (1·13 to 1·71) per 100 person-years among women and 0·79 (0·63 to 0·94) per 100 person-years among men. Achieving the 90-90-90 targets evenly by age and sex would further reduce incidence beyond status-quo ART, primarily among individuals aged 15–24 years (an additional 17·37% [7·33 to 26·12] reduction between 2016 and 2030), with only modest additional incidence reductions in adults aged 35–49 years (1·99% [–5·09 to 7·74]). Achieving 100% ART initiation among all people living with HIV within an average of 6 months from infection—an upper bound of plausible treatment effect—would reduce adult HIV incidence to 0·73 infections (0·55 to 0·92) per 100 person-years by 2030 and 0·46 (0·33 to 0·59) per 100 person-years by 2050.

Interpretation

Scale-up of ART over the last decade has already contributed to substantial reductions in HIV-1 incidence and mortality in eSwatini. Focused ART targeting would further reduce incidence, especially in younger individuals, but even the most aggressive treatment campaigns would be insufficient to end the epidemic in high-burden settings without a renewed focus on expanding preventive measures.

Funding

Global Good Fund and the Bill & Melinda Gates Foundation.

BIORXIV

Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and many-to-many mappings of genotypes to phenotypes to investigate gene flow and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.

VACCINE

Since the prequalification of the Typhoid conjugate vaccine (TCV) by the WHO and subsequent position paper published in 2018, strategies for roll-out of the vaccine have been under discussion [1]. The 2018 position paper recommends the introduction of TCV to be prioritized in countries with the highest burden of typhoid disease or a high burden of antimicrobial resistant S. Typhi [1]. The paper further suggests that “Decisions on the age of TCV administration, target population and delivery strategy for routine and catch-up vaccination should be based on the local epidemiology of typhoid fever…”. However, local epidemiology of typhoid fever is often poorly documented, due to the paucity of diagnostic facilities in many high typhoid incidence settings. However, most low- and middle income- countries (LMIC) rely on ad hoc reporting of typhoid fever, and very few have data from more than one city in the country. There have been substantial efforts aimed at strengthening blood culture surveillance for typhoid fever in Africa [2], yet there are still only 13 sentinel sites in 10 countries; a similar initiative in Asia covers only four countries [3]. Data sets that are utilized to estimate global burden are therefore limited by the lack of surveillance [4][5][6][7]. Based on the prohibitive costs [2] and efforts required to strengthen blood culture surveillance in LMIC, expansion of these efforts to capture both national and sub-national trends of typhoid on a global scale are not likely on a time scale relevant to vaccine roll-out.

Incidence mapping using statistical models can aid in predicting incidence in areas without surveillance, using spatial covariates relevant to risk of disease, and has been used for diseases such as malaria [8]. This approach has been attempted for typhoid through global burden models [4], but out-of-sample validation, though accurate in some areas, was not reliable, indicating a lack of useful indicators that can be consistently used to predict typhoid incidence. Further, the current breadth of data is heavily biased by reporting from a handful of well-funded sites, so predicting sub-national incidence across large regions is a challenge. A country’s ability to roll out TCV in accordance with the WHO’s position paper is therefore hindered by a lack of knowledge of local epidemiology of the disease. Additionally, Gavi, The Vaccine Alliance, recommends that countries requesting TCV funding should submit epidemiological data from within-country whenever possible, though this is not strictly a requirement.

Alternative tools are needed for planning TCV strategies in the absence of blood culture surveillance. Of particular interest is environmental surveillance, where, instead of relying on clinical detection of the disease, catchments in the environment such as water or sewage systems are surveilled. This approach has been successfully used in the polio eradication campaign. [9] Though case-based surveillance for polio is widespread, the disease is known to undergo sub-clinical (silent) transmission. ES has enabled detection when there is not a known outbreak and has been demonstrated to be a useful tool in program decision making [10][11]. Since typhoid and polio share similarities with regards to transmission routes and sub-clinical disease, it is possible that the approach and the network of laboratories developed for polio could be adapted for typhoid.

There remain significant technical challenges to implementing typhoid environmental surveillance (ES); optimal sampling strategies and detection methods, and their reliability as an indicator of ongoing transmission, remain unclear. Historically, Moore swabs have been used to isolate S. Typhi from sewage [12][13], however present day ES initiatives have been more focused on molecular approaches, specifically polymerase chain reaction (PCR)-based detection of S Typhi [14][15][16].

Economic analyses have largely supported the cost-effectiveness of the roll out of TCV in high and medium- incidence areas, particularly when routine vaccination strategies are paired with catch-up campaigns [17][18], however, there is more uncertainty around cost-effectiveness in low-incidence areas [19]. In this study, we examine the use of a hypothetical environmental surveillance program as a method for quickly gathering evidence on which an introduction decision can be based. This is especially relevant in places where there are inadequate burden estimates or in which a national introduction may not be affordable due to funding constraints or competing priorities. Specifically, we evaluate the value of environmental sampling as a means of detecting circulating typhoid in order to guide local or national targeting of catch-up vaccination campaigns. We aim to determine the most cost-effective sampling and roll-out strategies, given the limited information and substantial uncertainty about the true underlying prevalence of typhoid.

Michelle A Bulterys, Bradley Wagner, Mael Redard-Jacot, Anita Suresh, Nira R. Pollock, Emmanuel Moreau, Claudia M. Denkinger, Paul K. Drain, Tobias Broger 

JOURNAL OF CLINICAL MEDICINE

Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample. This status update discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be prioritized.

BMC PUBLIC HEALTH

Background

Ambitious global goals have been established to provide universal access to affordable modern contraceptive methods. To measure progress toward such goals in populous countries like Nigeria, it’s essential to characterize the current levels and trends of family planning (FP) indicators such as unmet need and modern contraceptive prevalence rates (mCPR). Moreover, the substantial heterogeneity across Nigeria and scale of programmatic implementation requires a sub-national resolution of these FP indicators. The aim of this study is to estimate the levels and trends of FP indicators at a subnational scale in Nigeria utilizing all available data and accounting for survey design and uncertainty.

Methods

We utilized all available cross-sectional survey data from Nigeria including the Demographic and Health Surveys, Multiple Indicator Cluster Surveys, National Nutrition and Health Surveys, and Performance, Monitoring, and Accountability 2020. We developed a hierarchical Bayesian model that incorporates all of the individual level data from each survey instrument, accounts for survey uncertainty, leverages spatio-temporal smoothing, and produces probabilistic estimates with uncertainty intervals.

Results

We estimate that overall rates and trends of mCPR and unmet need have remained low in Nigeria: the average annual rate of change for mCPR by state is 0.5% (0.4%,0.6%) from 2012-2017. Unmet need by age-parity demographic groups varied significantly across Nigeria; parous women express much higher rates of unmet need than nulliparous women.

Conclusions

Understanding the estimates and trends of FP indicators at a subnational resolution in Nigeria is integral to inform programmatic decision-making. We identify age-parity-state subgroups with large rates of unmet need. We also find conflicting trends by survey instrument across a number of states. Our model-based estimates highlight these inconsistencies, attempt to reconcile the direct survey estimates, and provide uncertainty intervals to enable interpretation of model and survey estimates for decision-making.