What does equitable global health research and delivery look like? Tackling Infections to Benefit Africa (TIBA) partnership as a case study.

There is a current global push to identify and implement best practice for delivering maximum impact from development research in low-income and middle-income countries. Here, we describe a model of research and capacity building that challenges traditional approaches taken by western funders in Africa. Tackling Infections to Benefit Africa (TIBA) is a global health research and delivery partnership with a focus on strengthening health systems to combat neglected tropical diseases, malaria and emerging pathogens in Africa. Partners are academic and research institutions based in Ghana, Sudan, Rwanda, Uganda, Kenya, Tanzania, Zimbabwe, Botswana, South Africa and the UK. Fifteen other African countries have participated in TIBA activities. With a starting budget of under £7 million, and in just 4 years, TIBA has had a verified impact on knowledge, policy practice and capacity building, and on national and international COVID-19 responses in multiple African countries. TIBA's impact is shown in context-specific metrics including: strengthening the evidence base underpinning international policy on neglected tropical diseases; 77% of research publications having Africa-based first and/or last authors; postgraduate, postdoctoral and professional training; career progression for African researchers and health professionals with no net brain drain from participating countries; and supporting African institutions. Training in real-time SARS-CoV-2 viral genome sequencing provided new national capabilities and capacities that contributed to both national responses and global health security through variant detection and tracking. TIBA's experience confirms that health research for Africa thrives when the agenda and priorities are set in Africa, by Africans, and the work is done in Africa. Here, we share 10 actionable recommendations for researchers and funders from our lessons learnt.

Peptide microarray IgM and IgG screening of pre-SARS-CoV-2 human serum samples from Zimbabwe for reactivity with peptides from all seven human coronaviruses: a cross-sectional study

Summary Background SARS-CoV-2 infections and deaths have been lower in Africa than in other continents, which could be attributed to previous exposure to other pathogens that induce protective cross-immunity or modify the immune phenotype. We aimed to identify and characterise pre-existing cross-reactive immune responses to SARS-CoV-2 in an African population. Methods In this cross-sectional study, we determined the prevalence of SARS-CoV-2 serological cross-reactivity of 339 previously collected pre-pandemic (2000–19) serum samples from adults living in four villages in Zimbabwe (Mupfure, Mutoko, Chiredzi, and Murewa). We tested samples with a COVID-19 rapid diagnostic test then screened for cross-reactivity with peptides from the proteomes of seven human coronaviruses. We compared peptide location, coverage, and intensity and matched peptides predicted to be B-cell epitopes to the Human Immune Epitope Database (HIED). Findings Pre-SARS-CoV-2 serum samples from Mupfure and Murewa showed an overall prevalence of cross-reactivity with the SARS-CoV-2 rapid diagnostic test of 31·9% (95% CI 26·93–37·11). Peptide analysis of samples from all four villages highlighted complex IgM and IgG response profiles against peptides in the spike, nucleocapsid, and polyprotein 1AB proteins across all coronaviruses. Interrogating SARS-CoV-2 peptides recognised by IgG and IgM from the Zimbabwean serum samples against the HIED showed that most were either unique to SARS-CoV-2 or shared only with other betacoronaviruses. However, some SARS-CoV-2 peptides shared motifs with antigens from pathogens endemic to Zimbabwe, including Trypanosoma spp and Plasmodium spp, plant and food immunogens, and human autoantigens. Interpretation The effect of these cross-reactive antibodies on SARS-CoV-2 infection or COVID-19 is unknown;however, these antibodies should be considered when interpreting SARS-CoV-2 seroepidemiology studies and evaluating outcomes of COVID-19 vaccine trials in Africa. This study also calls for further characterisation of SARs-CoV-2 immune phenotypes and responses in African populations. Funding Scottish Funding Council Global Challenges Research Fund Grant at the University of Edinburgh;UK National Institute for Health Research.

Predictors of COVID-19 epidemics in countries of the World Health Organization African Region.

Countries of the World Health Organization (WHO) African Region have experienced a wide range of coronavirus disease 2019 (COVID-19) epidemics. This study aimed to identify predictors of the timing of the first COVID-19 case and the per capita mortality in WHO African Region countries during the first and second pandemic waves and to test for associations with the preparedness of health systems and government pandemic responses. Using a region-wide, country-based observational study, we found that the first case was detected earlier in countries with more urban populations, higher international connectivity and greater COVID-19 test capacity but later in island nations. Predictors of a high first wave per capita mortality rate included a more urban population, higher pre-pandemic international connectivity and a higher prevalence of HIV. Countries rated as better prepared and having more resilient health systems were worst affected by the disease, the imposition of restrictions or both, making any benefit of more stringent countermeasures difficult to detect. Predictors for the second wave were similar to the first. Second wave per capita mortality could be predicted from that of the first wave. The COVID-19 pandemic highlights unanticipated vulnerabilities to infectious disease in Africa that should be taken into account in future pandemic preparedness planning.

Determining the burden of fungal infections in Zimbabwe.

Zimbabwe currently faces several healthcare challenges, most notably HIV and associated infections including tuberculosis (TB), malaria and recently outbreaks of cholera, typhoid fever and COVID-19. Fungal infections, which are also a major public health threat, receive considerably less attention. Consequently, there is dearth of data regarding the burden of fungal diseases in the country. We estimated the burden of fungal diseases in Zimbabwe based on published literature and 'at-risk' populations (HIV/AIDS patients, survivors of pulmonary TB, cancer, chronic obstructive pulmonary disease, asthma and patients receiving critical care) using previously described methods. Where there was no data for Zimbabwe, regional, or international data was used. Our study revealed that approximately 14.9% of Zimbabweans suffer from fungal infections annually, with 80% having tinea capitis. The annual incidence of cryptococcal meningitis and Pneumocystis jirovecii pneumonia in HIV/AIDS were estimated at 41/100,000 and 63/100,000, respectively. The estimated prevalence of recurrent vulvovaginal candidiasis (RVVC) was 2,739/100,000. The estimated burden of fungal diseases in Zimbabwe is high in comparison to other African countries, highlighting the urgent need for increased awareness and surveillance to improve diagnosis and management.

A systematic and meta-analysis review on the diagnostic accuracy of antibodies in the serological diagnosis of COVID-19.

BACKGROUND: Serological testing based on different antibody types are an alternative method being used to diagnose SARS-CoV-2 and has the potential of having higher diagnostic accuracy compared to the current gold standard rRT-PCR. Therefore, the objective of this review was to evaluate the diagnostic accuracy of IgG and IgM based point-of-care (POC) lateral flow immunoassay (LFIA), chemiluminescence enzyme immunoassay (CLIA), fluorescence enzyme-linked immunoassay (FIA) and ELISA systems that detect SARS-CoV-2 antigens. METHOD: A systematic literature search was carried out in PubMed, Medline complete and MedRxiv. Studies evaluating the diagnostic accuracy of serological assays for SARS-CoV-2 were eligible. Study selection and data-extraction were performed by two authors independently. QUADAS-2 checklist tool was used to assess the quality of the studies. The bivariate model and the hierarchical summary receiver operating characteristic curve model were performed to evaluate the diagnostic accuracy of the serological tests. Subgroup meta-analysis was performed to explore the heterogeneity. RESULTS: The pooled sensitivity for IgG (n = 17), IgM (n = 16) and IgG-IgM (n = 24) based LFIA tests were 0.5856, 0.4637 and 0.6886, respectively compared to rRT-PCR method. The pooled sensitivity for IgG (n = 9) and IgM (n = 10) based CLIA tests were 0.9311 and 0.8516, respectively compared to rRT-PCR. The pooled sensitivity the IgG (n = 10), IgM (n = 11) and IgG-IgM (n = 5) based ELISA tests were 0.8292, 0.8388 and 0.8531 respectively compared to rRT-PCR. All tests displayed high specificities ranging from 0.9693 to 0.9991. Amongst the evaluated tests, IgG based CLIA expressed the highest sensitivity signifying its accurate detection of the largest proportion of infections identified by rRT-PCR. ELISA and CLIA tests performed better in terms of sensitivity compared to LFIA. IgG based tests performed better compared to IgM except for the ELISA. CONCLUSIONS: We report that IgG-IgM based ELISA tests have the best overall diagnostic test accuracy. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type independently. Given the poor performances of the current LFIA devices, there is a need for more research on the development of highly sensitivity and specific POC LFIA that are adequate for most individual patient applications and attractive for large sero-prevalence studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020179112.

SARS-CoV-2 Serological testing in frontline health workers in Zimbabwe.

BACKGROUND: In order to protect health workers from SARS-CoV-2, there is need to characterise the different types of patient facing health workers. Our first aim was to determine both the infection status and seroprevalence of SARS-CoV-2 in health workers. Our second aim was to evaluate the occupational and demographic predictors of seropositivity to inform the country's infection prevention and control (IPC) strategy. METHODS AND PRINCIPAL FINDINGS: We invited 713 staff members at 24 out of 35 health facilities in the City of Bulawayo in Zimbabwe. Compliance to testing was defined as the willingness to uptake COVID-19 testing by answering a questionnaire and providing samples for both antibody testing and PCR testing. SARS-COV-2 antibodies were detected using a rapid diagnostic test kit and SAR-COV-2 infection was determined by real-time (RT)-PCR. Of the 713 participants, 635(89%) consented to answering the questionnaire and providing blood sample for antibody testing while 560 (78.5%) agreed to provide nasopharyngeal swabs for the PCR SARS-CoV-2 testing. Of the 635 people (aged 18-73) providing a blood sample 39.1% reported a history of past COVID-19 symptoms while 14.2% reported having current symptoms of COVID-19. The most-prevalent co-morbidity among this group was hypertension (22.0%) followed by asthma (7.0%) and diabetes (6.0%). The SARS-CoV-2 sero-prevalence was 8.9%. Of the 560 participants tested for SARS-CoV-2 infection, 2 participants (0.36%) were positive for SAR-CoV-2 infection by PCR testing. None of the SARS-CoV-2 antibody positive people were positive for SAR-CoV-2 infection by PCR testing. CONCLUSION AND INTERPRETATION: In addition to clinical staff, several patient-facing health workers were characterised within Zimbabwe's health system and the seroprevalence data indicated that previous exposure to SAR-CoV-2 had occurred across the full spectrum of patient-facing staff with nurses and nurse aides having the highest seroprevalence. Our results highlight the need for including the various health workers in IPC strategies in health centres to ensure effective biosecurity and biosafety.