Antimicrobial stewardship in the era of the COVID-19 pandemic: A systematic review protocol on the opportunities and challenges for Sub-Saharan Africa.

BACKGROUND: Antimicrobial resistance (AMR) remains one of the leading threats to global public health and this may increase following COVID-19 pandemic. This is particularly the case in Africa where regulations on antimicrobial usage are weak. This protocol outlines the steps to undertake a systematic review to synthesize evidence on drivers of AMR and evaluate existing approaches to strengthening antimicrobial stewardship (AMS) programs in Sub-Saharan Africa (SSA). On the basis of the evidence generated from the evidence synthesis, the overarching goal of this work is to provide recommendations to support best practices in AMS implementation in SSA. METHODS: A systematic search will be conducted using the following databases: Global Health Library, PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, Google Scholar, Global Health, Embase, African Journals Online Library, Web of Science, antimicrobial databases (WHO COVID-19, TrACSS, NDARO, and JPIAMR), and the Cochrane databases for systematic reviews. Studies will be included if they assess AMR and AMS in SSA from January 2000 to January 31, 2023. RESULTS: The primary outcomes will include the drivers of AMR and approaches to AMS implementation in SSA. The Preferred Reporting Items for Systematic Reviews and Meta-analyses will guide the reporting of this systematic review. CONCLUSIONS: The findings are expected to provide evidence on best practices and resource sharing for policy consideration to healthcare providers and other stakeholders both at the local and international levels. Additionally, the study seeks to establish drivers specific to AMR during the COVID-19 era in the SSA, for example, with the observed increasing trend of antimicrobial misuse during the first or second year of the pandemic may provide valuable insights for policy recommendation in preparedness and response measures to future pandemics. PROSPERO REGISTRATION NUMBER: CRD42022368853.

Pre-existing immunity to SARS-CoV-2 before the COVID-19 pandemic era in Cameroon: A comparative analysis according to HIV-status.

Background: The lower burden of COVID-19 in tropical settings may be due to preexisting cross-immunity, which might vary according to geographical locations and potential exposure to other pathogens. We sought to assess the overall prevalence of SARS-CoV-2 antibodies and determine SARS-CoV-2 seropositivity according to HIV-status before the COVID-19 pandemic era. Methods: A cross-sectional and comparative study was conducted at the Chantal BIYA International Reference Centre (CIRCB) on 288 stored plasma samples (163 HIV-positive versus 125 HIV-negative); all collected in 2017-2018, before the COVID-19 pandemic era. Abbott Panbio™ COVID-19 IgG/IgM assay was used for detecting SARS-CoV-2 immunoglobulin G (IgG) and M (IgM). Among people living with HIV (PLHIV), HIV-1 viral load and TCD4 cell count (LTCD4) were measured using Abbott Real Time PCR and BD FACSCalibur respectively. Statistical analyses were performed, with p<0.05 considered statistically significant. Results: The median [IQR] age was 25 [15-38] years. Overall seropositivity to SARS-CoV-2 antibodies was 13.5% (39/288) of which 7.3% (21) was IgG, 7.3% (21) IgM and 1.0% (3) IgG/IgM. According to HIV-status in the study population, SARS-CoV-2 seropositivity was 11.0% (18/163) among HIV-positive versus 16.8% (21/125) among HIV-negative respectively, p=0.21. Specifically, IgG was 6.1% (10/163) versus 8.8% (11/125), p=0.26; IgM was 5.5% (9/163) versus 9.6%, (12/125), p=0.13 and IgG/IgM was 0.6% (1/163) versus 1.6% (2/125) respectively. Among PLHIV, SARS-CoV-2 seropositivity according to CD4 count was 9.2% (≥500 cells/µL) versus 1.8% (200-499 cells/µL), (OR=3.5; p=0.04) and 0.6% (<200 cells/µL), (OR=17.7; p<0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (≥40 copies/mL) versus 4.9% (<40 copies/mL), (OR= 3.8; p<0.01). Conclusion: Before COVID-19 in Cameroon, cross-reactive antibodies to SARS-CoV-2 were in circulation, indicating COVID-19 preexisting immunity. This preexisting immunity may contribute in attenuating disease severity in tropical settings like Cameroon. Of relevance, COVID-19 preexisting immunity is lower with HIV-infection, specifically with viral replication and poor CD4-cell count. As poor CD4-count leads to lower cross-reactive antibodies (regardless of viral load), people living with HIV appear more vulnerable to COVID-19 and should be prioritized for vaccination.

Serologic response to SARS-CoV-2 in an African population.

Official case counts suggest Africa has not seen the expected burden of COVID-19 as predicted by international health agencies, and the proportion of asymptomatic patients, disease severity, and mortality burden differ significantly in Africa from what has been observed elsewhere. Testing for SARS-CoV-2 was extremely limited early in the pandemic and likely led to under-reporting of cases leaving important gaps in our understanding of transmission and disease characteristics in the African context. SARS-CoV-2 antibody prevalence and serologic response data could help quantify the burden of COVID-19 disease in Africa to address this knowledge gap and guide future outbreak response, adapted to the local context. However, such data are widely lacking in Africa. We conducted a cross-sectional seroprevalence survey among 1,192 individuals seeking COVID-19 screening and testing in central Cameroon using the Innovita antibody-based rapid diagnostic. Overall immunoglobulin prevalence was 32%, IgM prevalence was 20%, and IgG prevalence was 24%. IgM positivity gradually increased, peaking around symptom day 20. IgG positivity was similar, gradually increasing over the first 10 days of symptoms, then increasing rapidly to 30 days and beyond. These findings highlight the importance of diagnostic testing and asymptomatic SARS-CoV-2 transmission in Cameroon, which likely resulted in artificially low case counts. Rapid antibody tests are a useful diagnostic modality for seroprevalence surveys and infection diagnosis starting 5-7 days after symptom onset. These results represent the first step towards better understanding the SARS-CoV-2 immunological response in African populations.

Performance and operational feasibility of antigen and antibody rapid diagnostic tests for COVID-19 in symptomatic and asymptomatic patients in Cameroon: a clinical, prospective, diagnostic accuracy study.

BACKGROUND: Real-time PCR is recommended to detect SARS-CoV-2 infection. However, PCR availability is restricted in most countries. Rapid diagnostic tests are considered acceptable alternatives, but data are lacking on their performance. We assessed the performance of four antibody-based rapid diagnostic tests and one antigen-based rapid diagnostic test for detecting SARS-CoV-2 infection in the community in Cameroon. METHODS: In this clinical, prospective, diagnostic accuracy study, we enrolled individuals aged at least 21 years who were either symptomatic and suspected of having COVID-19 or asymptomatic and presented for screening. We tested peripheral blood for SARS-CoV-2 antibodies using the Innovita (Biological Technology; Beijing, China), Wondfo (Guangzhou Wondfo Biotech; Guangzhou, China), SD Biosensor (SD Biosensor; Gyeonggi-do, South Korea), and Runkun tests (Runkun Pharmaceutical; Hunan, China), and nasopharyngeal swabs for SARS-CoV-2 antigen using the SD Biosensor test. Antigen rapid diagnostic tests were compared with Abbott PCR testing (Abbott; Abbott Park, IL, USA), and antibody rapid diagnostic tests were compared with Biomerieux immunoassays (Biomerieux; Marcy l'Etoile, France). We retrospectively tested two diagnostic algorithms that incorporated rapid diagnostic tests for symptomatic and asymptomatic patients using simulation modelling. FINDINGS: 1195 participants were enrolled in the study. 347 (29%) tested SARS-CoV-2 PCR-positive, 223 (19%) rapid diagnostic test antigen-positive, and 478 (40%) rapid diagnostic test antibody-positive. Antigen-based rapid diagnostic test sensitivity was 80·0% (95% CI 71·0-88·0) in the first 7 days after symptom onset, but antibody-based rapid diagnostic tests had only 26·8% sensitivity (18·3-36·8). Antibody rapid diagnostic test sensitivity increased to 76·4% (70·1-82·0) 14 days after symptom onset. Among asymptomatic participants, the sensitivity of antigen-based and antibody-based rapid diagnostic tests were 37·0% (27·0-48·0) and 50·7% (42·2-59·1), respectively. Cohen's κ showed substantial agreement between Wondfo antibody rapid diagnostic test and gold-standard ELISA (κ=0·76; sensitivity 0·98) and between Biosensor and ELISA (κ=0·60; sensitivity 0·94). Innovita (κ=0·47; sensitivity 0·93) and Runkun (κ=0·43; sensitivity 0·76) showed moderate agreement. An antigen-based retrospective algorithm applied to symptomatic patients showed 94·0% sensitivity and 91·0% specificity in the first 7 days after symptom onset. For asymptomatic participants, the algorithm showed a sensitivity of 34% (95% CI 23·0-44·0) and a specificity of 92·0% (88·0-96·0). INTERPRETATION: Rapid diagnostic tests had good overall sensitivity for diagnosing SARS-CoV-2 infection. Rapid diagnostic tests could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and onward viral transmission. FUNDING: Médecins Sans Frontières WACA and Médecins Sans Frontières OCG. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Socioeconomic correlates of trauma: An analysis of emergency ward patients in Yaoundé, Cameroon.

INTRODUCTION: Injury is a significant and increasingly common cause of morbidity and mortality in sub-Saharan Africa; however, the social and economic factors underlying these trends are not well understood. We evaluated the relationship between socioeconomic status (SES) and trauma outcomes using a prospective registry of patients presenting to the largest trauma hospital in Yaoundé, Cameroon. METHODS: Trauma patients (n=2855) presenting to the emergency ward at Central Hospital, Yaoundé between April 15 and October 15, 2009 were surveyed regarding demographic and socioeconomic background, nature and severity of injuries, treatment, and disposition. A wealth score was estimated for each patient, corresponding to an SES index constructed using principle components analysis of the urban Cameroonian Demographic and Health Survey. Logistic regression was used to evaluate the effects of SES on care-seeking behaviour, injury severity, and treatment outcome. MAIN OUTCOME MEASURES: SES wealth score, care-seeking prior to visiting hospital, injury severity, treatment outcome. RESULTS: Patients aged 1-89 presented with road traffic injuries (59.83%), falls (7.76%), and penetrating trauma (6.16%), and had higher SES than the broader urban Cameroonian population. Within the Yaoundé sample, being in the lowest SES quintile was associated with an increased likelihood of having sought care elsewhere before presenting to the hospital (aOR=3.28, p<0.001), after controlling for background and injury characteristics. Patients in the lowest SES quintile were also more likely to present with moderate/severe injuries (aOR=4.93, p<0.001), and were more likely to be transferred to the operating room. CONCLUSIONS: Patients presenting to this trauma centre were wealthier than the broader community, suggesting the possibility of barriers to accessing care. Poorer patients were more likely to have severe injuries and more likely to need surgery, but were less likely to seek care from a major trauma centre immediately. Substantial differences in SES between the sample visiting the hospital and the broader community suggest a need for community-based sampling approaches in future trauma research.

Analysis of prospective trauma registry data in Francophone Africa: a pilot study from Cameroon.

INTRODUCTION: Injury rates in sub-Saharan Africa are among the highest in the world, but prospective, registry-based reports from Cameroon are limited. We aimed to create a prospective trauma registry to expand the data elements collected on injury at a busy tertiary center in Yaoundé Cameroon. METHODS: Details of the injury context, presentation, care, cost, and disposition from the emergency department (ED) were gathered over a 6-month period, by trained research assistants using a structured questionnaire. Bivariate and multivariate models were built to explore variable relationships and outcomes. RESULTS: There were 2,855 injured patients in 6 months, comprising almost half of all ED visits. Mean age was 30 years; 73 % were male. Injury mechanism was road traffic injury in 59 %, fall in 7 %, penetrating trauma in 6 %, and animal bites in 4 %. Of these, 1,974 (69 %) were discharged home, 517 (18 %) taken to the operating room, and 14 (1 %) to the intensive care unit. The body areas most severely injured were pelvis and extremity in 43 %, head in 30 %, chest in 4 %, and abdomen in 3 %. The estimated injury severity score (eISS) was <9 in 60 %, 9-24 in 35 %, and >25 in 2 %. Mortality was 0.7 %. In the multivariate analysis, independent predictors of mortality were eISS ≥9 and Glasgow Coma Score ≤12. Road traffic injury was an independent predictor for the need to have surgery. Trauma registry results were presented to the Ministry of Health in Cameroon, prompting the formation of a National Injury Committee. CONCLUSIONS: Injuries comprise a significant proportion of ED visits and utilization of surgical services in Yaoundé. A prospective approach allows for more extensive information. Thorough data from a prospective trauma registry can be used successfully to advocate for policy towards prevention and treatment of injuries.