SARS-CoV-2 incidence, transmission and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-2021.

BACKGROUND: By August 2021, South Africa experienced three SARS-CoV-2 waves; the second and third associated with emergence of Beta and Delta variants respectively. METHODS: We conducted a prospective cohort study during July 2020-August 2021 in one rural and one urban community. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Serum was collected every two months and tested for anti-SARS-CoV-2 antibodies. RESULTS: Among 115,759 nasal specimens from 1,200 members (follow-up rate 93%), 1976 (2%) were SARS-CoV-2-positive. By rRT-PCR and serology combined, 62% (749/1200) of individuals experienced ≥1 SARS-CoV-2 infection episode, and 12% (87/749) experienced reinfection. Of 662 PCR-confirmed episodes with available data, 15% (n=97) were associated with ≥1 symptom. Among 222 households, 200 (90%) had ≥1 SARS-CoV-2-positive individual. Household cumulative infection risk (HCIR) was 25% (213/856). On multivariable analysis, accounting for age and sex, index case lower cycle threshold value (OR 3.9, 95%CI 1.7-8.8), urban community (OR 2.0,95%CI 1.1-3.9), Beta (OR 4.2, 95%CI 1.7-10.1) and Delta (OR 14.6, 95%CI 5.7-37.5) variant infection were associated with increased HCIR. HCIR was similar for symptomatic (21/110, 19%) and asymptomatic (195/775, 25%) index cases (p=0.165). Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection. People living with HIV who were not virally supressed were more likely to develop symptomatic illness, and shed SARS-CoV-2 for longer compared to HIV-uninfected individuals. CONCLUSIONS: In this study, 85% of SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of Beta and Delta variants, likely contributed to successive waves, with >60% of individuals infected by the end of follow-up. RESEARCH IN CONTEXT: Evidence before this study: Previous studies have generated wide-ranging estimates of the proportion of SARS-CoV-2 infections which are asymptomatic. A recent systematic review found that 20% (95% CI 3%-67%) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remained asymptomatic throughout infection and that transmission from asymptomatic individuals was reduced. A systematic review and meta-analysis of 87 household transmission studies of SARS-CoV-2 found an estimated secondary attack rate of 19% (95% CI 16-22). The review also found that household secondary attack rates were increased from symptomatic index cases and that adults were more likely to acquire infection. As of December 2021, South Africa experienced three waves of SARS-CoV-2 infections; the second and third waves were associated with circulation of Beta and Delta variants respectively. SARS-CoV-2 vaccines became available in February 2021, but uptake was low in study sites reaching 5% fully vaccinated at the end of follow up. Studies to quantify the burden of asymptomatic infections, symptomatic fraction, reinfection frequency, duration of shedding and household transmission of SARS-CoV-2 from asymptomatically infected individuals have mostly been conducted as part of outbreak investigations or in specific settings. Comprehensive systematic community studies of SARS-CoV-2 burden and transmission including for the Beta and Delta variants are lacking, especially in low vaccination settings.Added value of this study: We conducted a unique detailed COVID-19 household cohort study over a 13 month period in South Africa, with real time reverse transcriptase polymerase chain reaction (rRT-PCR) testing twice a week irrespective of symptoms and bimonthly serology. By the end of the study in August 2021, 749 (62%) of 1200 individuals from 222 randomly sampled households in a rural and an urban community in South Africa had at least one confirmed SARS-CoV-2 infection, detected on rRT-PCR and/or serology, and 12% (87/749) experienced reinfection. Symptom data were analysed for 662 rRT-PCR-confirmed infection episodes that occurred >14 days after the start of follow-up (of a total of 718 rRT-PCR-confirmed episodes), of these, 15% (n=97) were associated with one or more symptoms. Among symptomatic indvidiausl, 9% (n=9) were hospitalised and 2% (n=2) died. Ninety percent (200/222) of included households, had one or more individual infected with SARS-CoV-2 on rRT-PCR and/or serology within the household. SARS-CoV-2 infected index cases transmitted the infection to 25% (213/856) of susceptible household contacts. Index case ribonucleic acid (RNA) viral load proxied by rRT-PCR cycle threshold value was strongly predictive of household transmission. Presence of symptoms in the index case was not associated with household transmission. Household transmission was four times greater from index cases infected with Beta variant and fifteen times greater from index cases infected with Delta variant compared to wild-type infection. Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection within households. People living with HIV (PLHIV) who were not virally supressed were more likely to develop symptomatic illness when infected with SARS-CoV-2, and shed SARS-CoV-2 for longer when compared to HIV-uninfected individuals.Implications of all the available evidence: We found a high rate of SARS-CoV-2 infection in households in a rural community and an urban community in South Africa, with the majority of infections being asymptomatic in individuals of all ages. Asymptomatic individuals transmitted SARS-CoV-2 at similar levels to symptomatic individuals suggesting that interventions targeting symptomatic individuals such as symptom-based testing and contact tracing of individuals tested because they report symptoms may have a limited impact as control measures. Increased household transmission of Beta and Delta variants, likely contributed to recurrent waves of COVID-19, with >60% of individuals infected by the end of follow-up. Higher attack rates, reinfection and acquisition in adolescents and prolonged SARS-CoV-2 shedding in PLHIV who were not virally suppressed suggests that prioritised vaccination of individuals in these groups could impact community transmission.

Rural South African Community Perceptions of Antibiotic Access and Use: Qualitative Evidence from a Health and Demographic Surveillance System Site.

Knowledge and practices of rural South African populations with regard to antibiotic access and use (ABACUS) remain understudied. By using the case of four villages in the north east of the country, our aim was to investigate popular notions and social practices related to antibiotics to inform patient-level social interventions for appropriate antibiotic use. To achieve this, we investigated where community members (village residents) were accessing and sourcing medication, and what they understood antibiotics and antibiotic resistance (ABR) to be. Embedded within the multicountry ABACUS project, this qualitative study uses interviews and focus group discussions. A sample of 60 community members was recruited from the Agincourt Health and Demographic Surveillance System, situated in Mpumalanga Province, from April to August, 2017. We used the five abilities of seek, reach, pay, perceive, and engage in access to healthcare as proposed by Levesque's "Access to Healthcare" framework. Respondents reported accessing antibiotics prescribed from legal sources: by nurses at the government primary healthcare clinics or by private doctors dispensed by private pharmacists. No account of the illegal purchasing of antibiotics was described. There was a mix of people who finished their prescription according to the instructions and those who did not. Some people kept antibiotics for future episodes of infection. The concept of "ABR" was understood by some community members when translated into related Xitsonga words because of knowledge tuberculosis and HIV/AIDS treatment regimens. Our findings indicate that regulation around the sale of antibiotics is enforced. Safer use of antibiotics and why resistance is necessary to understand need to be instilled. Therefore, context-specific educational campaigns, drawing on people's understandings of antibiotics and informed by the experiences of other diseases, may be an important and deployable means of promoting the safe use of antibiotics.

Outcomes of patients lost to follow-up after antiretroviral therapy initiation in rural north-eastern South Africa.

OBJECTIVE: The vital status of patients lost to follow-up often remains unknown in antiretroviral therapy (ART) programmes in sub-Saharan Africa because medical records are no longer updated once the patient disengages from care. Thus, we aimed to assess the outcomes of patients lost to follow-up after ART initiation in north-eastern South Africa. METHODS: Using data from a rural area in north-eastern South Africa, we estimated the cumulative incidence of patient outcomes (i) after treatment initiation using clinical records, and (ii) after loss to follow-up (LTFU) using data from clients that have been individually linked to Agincourt Health and Demographic Surveillance System (AHDSS) database. Aside from LTFU, we considered mortality, re-engagement and migration out of the study site. Cox proportional hazards regression was used to identify covariates of these patient outcomes. RESULTS: Between April 2014 and July 2017, 3700 patients initiated ART and contributed a total of 6818 person-years of follow-up time. Three years after ART initiation, clinical record-based estimates of LTFU, mortality and documented transfers were 41.0% (95% CI: 38.5-43.4%), 1.9% (95% CI 1.0-3.2%) and 0.1% (95% CI 0.0-0.9%), respectively. Among those who were LTFU, the cumulative incidence of re-engagement, out-migration and mortality at 3 years were 38.1% (95% CI 33.1-43.0%), 49.4% (95% CI 43.1-55.3%) and 4.7% (95% CI 3.5-6.2%), respectively. Pregnant or breastfeeding women, foreigners and those who initiated ART most recently were at an increased risk of LTFU. CONCLUSION: LTFU among patients starting ART in north-eastern South Africa is relatively high and has increased in recent years as more asymptomatic patients have initiated treatment. Even though this tendency is of concern in light of the prevention of onwards transmission, we also found that re-engagement in care is common and mortality among persons LTFU relatively low.

OBJECTIF: Le statut vital des patients perdus au suivi reste souvent inconnu dans les programmes de traitement antirétroviral (ART) en Afrique subsaharienne parce que les dossiers médicaux ne sont plus mis à jour une fois que le patient se désengage des soins. Notre objectif était d'évaluer les résultats des patients dans le nord-est de l'Afrique du Sud. MÉTHODES: A l'aide de données provenant d'une zone rurale du nord-est de l'Afrique du Sud, nous avons estimé l'incidence cumulée des résultats pour les patients (i) après le début du traitement à l'aide des dossiers cliniques et (ii) après la perte au suivi (PS) à l'aide des données des patients qui ont été reliées individuellement à la base de données du système de surveillance démographique et de santé (AHDSS) d'Agincourt. Outre les PS, nous avons pris en compte la mortalité, le réengagement et la migration hors du site de l'étude. La régression des risques proportionnels de Cox a été utilisée pour identifier les covariables de ces résultats pour le patient. RÉSULTATS: Entre avril 2014 et juillet 2017, 3.700 patients ont commencé l'ART constituant un suivi total de 6.818 années-personnes. Trois ans après le début de l'ART, les estimations des PS, de la mortalité et des transferts documentés selon les registres cliniques étaient de 41,0% (IC95%: 38,5% à 43,4%), 1,9% (IC95%: 1,0% à 3,2%) et 0,1% (IC95%: 0,0% -0,9%), respectivement. Parmi ceux qui étaient PS, l'incidence cumulative de réengagement, d'émigration et de mortalité à trois ans était de 38,1% (IC95%: 33,1% à 43,0%), 49,4% (IC95%: 43,1% à 55,3%) et 4,7% (IC95%: 3,5% -6,2%), respectivement. Les femmes enceintes ou allaitantes, les étrangers et les personnes qui ont commencé l'ART le plus récemment couraient un risque accru de PS. CONCLUSION: La PS chez les patients commençant une ART dans le nord-est de l'Afrique du Sud est relativement élevée et a augmenté ces dernières années à mesure que davantage de patients asymptomatiques ont commencé le traitement. Même si cette tendance est préoccupante à la lumière de la prévention de la transmission, nous avons également constaté que le réengagement dans les soins était courant et que la mortalité parmi les PS était relativement faible.