Browsing by Author "Jackie Kleynhans"

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    Coronavirus Host Genomics Study: South Africa (COVIGen-SA)
    (2022-10-06) Andrew K. May; Heather Seymour; Harriet Etheredge; Heather Maher; Marta C. Nunes; ShabirA.Madhi; SimisoM. Sokhela; W. D. FrancoisVenter; Neil Martinson; Firdaus Nabeemeeah; Cheryl Cohen; Jocelyn Moyes; Sibongile Walaza; Stefano Tempia; Jackie Kleynhans; Anne von Gottberg; Jeremy Nel; Halima Dawood; Ebrahim Variava; Stephen Tollman; Kathleen Kahn; KobusHerbst; EmilyB.Wong; CarolineT.Tiemessen; Alex van Blydenstein; Lyle Murray; Michelle Venter; June Fabian; Miche´le Ramsay
    However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa’s response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA—a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. *rough this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. *is project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.
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    Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016–2018: A hidden Markov modelling study
    (2021-12-23) Deus Thindwa; Nicole Wolter; Amy Pinsent; Maimuna CarrimI; John Ojal; Stefano Tempia; Jocelyn Moyes; Meredith McMorrow; Jackie Kleynhans; Anne von Gottberg; Neil French; PHIRST group; Cheryl Cohen; Stefan Flasche
    Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant’s age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (�18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9– 80.5%) than older children (5–17 years-old) (31.7–50.0%) or adults (11.5–23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7–15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91–1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2– 12.8 vs 6.0 days, 95%CI: 5.6–6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507–714 vs 389, 95%CI: 311.1–435.5) were estimated in HIVinfected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.
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    Incidence and Transmission Dynamics of Bordetella pertussis Infection in Rural and Urban Communities, South Africa, 2016‒2018
    (2023-02-02) Fahima Moosa; Stefano Tempia; Jackie Kleynhans; Meredith McMorrow; Jocelyn Moyes; Mignon du Plessis; Maimuna Carrim; Florette K. Treurnicht; Orienka Helfersee; Thulisa Mkhencele; Azwifarwi Mathunjwa; Neil A. Martinson; Kathleen Kahn; Limakatso Lebina; Floidy Wafawanaka; Cheryl Cohen; Anne von Gottberg; Nicole Wolter
    We conducted 3 prospective cohort studies (2016–2018), enrolling persons from 2 communities in South Africa. Nasopharyngeal swab specimens were collected twice a week from participants. Factors associated with Bordetella pertussis incidence, episode duration, and household transmission were determined by using Poisson regression, Weibull accelerated time-failure, and logistic regression hierarchical models, respectively. Among 1,684 participants, 118 episodes of infection were detected in 107 participants (incidence 0.21, 95% CI 0.17–0.25 infections/100 person-weeks). Children <5 years of age who had incomplete vaccination were more likely to have pertussis infection. Episode duration was longer for participants who had higher bacterial loads. Transmission was more likely to occur from male index case-patients and persons who had >7 days infection duration. In both communities, there was high incidence of B. pertussis infection and most cases were colonized.
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    Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa
    (2022-08-19) Kaiyuan Sun; Stefano Tempia; Jackie Kleynhans; Anne von Gottberg; Meredith L McMorrow; Nicole Wolter; Jinal N. Bhiman; Jocelyn Moyes; Maimuna Carrim; Neil A Martinson; Kathleen Kahn; Limakatso Lebina; Jacques D. du Toit; Thulisa Mkhencele; Cécile Viboud; Cheryl Cohen; PHIRST group
    South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. Propelled by increased transmissibility and immune escape properties, Omicron displaced other globally circulating variants within 3 months of its emergence. Due to limited testing, Omicron’s attenuated clinical severity, and an increased risk of reinfection, the size of the Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood in South Africa and in many other countries. Using South African data from urban and rural cohorts closely monitored since the beginning of the pandemic, we analyzed sequential serum samples collected before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. Omicron BA.1/2 infection attack rates reached 65% (95% CI, 60% – 69%) in the rural cohort and 58% (95% CI, 61% – 74%) in the urban cohort, with repeat infections and vaccine breakthroughs accounting for >60% of all infections at both sites. Combined with previously collected data on pre-Omicron variant infections within the same cohorts, we identified 14 distinct categories of SARS-CoV-2 antigen exposure histories in the aftermath of the Omicron BA.1/2 wave, indicating a particularly fragmented immunologic landscape. Few individuals (<6%) remained naïve to SARS-CoV-2 and no exposure history category represented over 25% of the population at either cohort site. Further, cohort participants were more than twice as likely to get infected during the Omicron BA.1/2 wave, compared to the Delta wave. Prior infection with the ancestral strain (with D614G mutation), Beta, and Delta variants provided 13% (95% CI, -21% – 37%) , 34% (95% CI, 17% – 48%), and 51% (95% CI, 39% – 60%) protection against Omicron BA.1/2 infection, respectively. Hybrid immunity (prior infection and vaccination) and repeated prior infections (without vaccination) reduced the risks of Omicron BA.1/2 infection by 60% (95% CI, 42% – 72%) and 85% (95% CI, 76% – 92%) respectively. Reinfections and vaccine breakthroughs had 41% (95% CI, 26% – 53%) lower risk of onward transmission than primary infections. Our study sheds light on a rapidly shifting landscape of population immunity, along with the changing characteristics of SARS-CoV-2, and how these factors interact to shape the success of emerging variants. Our findings are especially relevant to populations similar to South Africa with low SARS-CoV-2 vaccine coverage and a dominant contribution of immunity from prior infection. Looking forward, the study provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus.
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    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
    (2021-12-04) Cheryl Cohen; Jackie Kleynhans; Anne von Gottberg; Meredith L McMorrow; Nicole Wolter; Jinal N Bhiman; Jocelyn Moyes; Jacques du Toit; Mignon du Plessis; Francesc Xavier Gómez-Olivé; Fatimah S Dawood; Thulisa Mkhencele; Kaiyun Sun; Cécile Viboud; Maimuna Carrim; Amelia Buys; Neil A Martinson; Kathleen Kahn; Stephen Tollman; Limakatso Lebina; Floi Wafawanaka
    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.
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    SARS-CoV-2 Seroprevalence after Third Wave of Infections, South Africa
    (2022-05) Jackie Kleynhans; Stefano Tempia; Nicole Wolter; Anne von Gottberg; Jinal N. Bhiman; Amelia Buys; Jocelyn Moyes; Meredith L. McMorrow; Kathleen Kahn; F. Xavier Gómez-Olivé; Stephen Tollman; Neil A. Martinson; Floidy Wafawanaka; Limakatso Lebina; Jacques D. du Toit; Waasila Jassat; Mzimasi Neti; Marieke Brauer; Cheryl Cohen
    By November 2021, after the third wave of severe acute respiratory syndrome coronavirus 2 infections in South Africa, seroprevalence was 60% in a rural community and 70% in an urban community. High seroprevalence before the Omicron variant emerged may have contributed to reduced illness severity observed in the fourth wave.
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    Unmasking Pneumococcal Carriage in a High Human Immunodeficiency Virus (HIV) Prevalence Population in two Community Cohorts in South Africa, 2016–2018: The PHIRST Study
    (2022-07-19) Maimuna Carrim; Stefano Tempia; Deus Thindwa; Neil A Martinson; Kathleen Kahn; Stefan Flasche; Orienka Hellferscee; Florette K Treurnicht; Meredith L McMorrow; Jocelyn Moyes; Thulisa Mkhencele; Azwifarwi Mathunjwa; Jackie Kleynhans; Limakatso Lebina; Katlego Mothlaoleng; Floidy Wafawanaka; Francesc Xavier Gómez-Olivé; Cheryl Cohen; Anne von Gottberg; Nicole Wolter
    Background Longitudinal pneumococcus colonization data in high human immunodeficiency virus (HIV) prevalence settings following pneumococcal conjugate vaccine introduction are limited. Methods In 327 randomly selected households, 1684 individuals were enrolled and followed-up for 6 to 10 months during 2016 through 2018 from 2 communities. Nasopharyngeal swabs were collected twice weekly and tested for pneumococcus using quantitative lytA real-time polymerase chain reaction. A Markov model was fitted to the data to define the start and end of an episode of colonization. We assessed factors associated with colonization using logistic regression. Results During the study period, 98% (1655/1684) of participants were colonized with pneumococcus at least once. Younger age (<5 years: adjusted odds ratio [aOR], 14.1; 95% confidence [CI], 1.8–111.3, and 5–24 years: aOR, 4.8, 95% CI, 1.9–11.9, compared with 25–44 years) and HIV infection (aOR, 10.1; 95% CI, 1.3–77.1) were associated with increased odds of colonization. Children aged <5 years had fewer colonization episodes (median, 9) than individuals ≥5 years (median, 18; P < .001) but had a longer episode duration (<5 years: 35.5 days; interquartile range, 17–88) vs. ≥5 years: 5.5 days (4–12). High pneumococcal loads were associated with age (<1 year: aOR 25.4; 95% CI, 7.4–87.6; 1–4 years: aOR 13.5, 95% CI 8.3–22.9; 5–14 years: aOR 3.1, 95% CI, 2.1–4.4 vs. 45–65 year old patients) and HIV infection (aOR 1.7; 95% CI 1.2–2.4). Conclusions We observed high levels of pneumococcus colonization across all age groups. Children and people with HIV were more likely to be colonized and had higher pneumococcal loads. Carriage duration decreased with age highlighting that children remain important in pneumococcal transmission.