Characteristics of infections with ancestral, Beta and Delta variants of SARS-CoV-2 in the PHIRST-C community cohort study, South Africa, 2020-2021.

BACKGROUND: Data on the characteristics of individuals with mild and asymptomatic infections with different SARS-CoV-2 variants are limited. We therefore compared the characteristics of individuals infected with ancestral, Beta and Delta SARS-CoV-2 variants in South Africa. METHODS: We conducted a prospective cohort study in a rural and an urban site during July 2020-August 2021. 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). Differences in demographic and clinical characteristics, shedding and cycle threshold (Ct) value of infection episodes by variant were evaluated using multinomial regression. Overall and age-specific incidence rates of infection were compared by variant. RESULTS: We included 1200 individuals from 222 households and 648 rRT-PCR-confirmed infection episodes (66, 10% ancestral, 260, 40% Beta, 322, 50% Delta). Symptomatic proportion was similar for ancestral (7, 11%), Beta (44, 17%), and Delta (46, 14%) infections (p=0.4). After accounting for previous infection, peak incidence shifted to younger age groups in successive waves (40-59 years ancestral, 19-39 years Beta, 13-18 years Delta). On multivariable analysis, compared to ancestral, Beta infection was more common in individuals aged 5-12 years (vs 19-39)(adjusted odds ratio (aOR) 2.6, 95% confidence interval (CI)1.1-6.6) and PCR cycle threshold (Ct) value <30 (vs >35)(aOR 3.2, 95%CI 1.3-7.9), while Delta was more common in individuals aged <5 (aOR 6.7, 95%CI1.4-31.2) and 5-12 years (aOR 6.6 95%CI2.6-16.7)(vs 19-39) and Ct value <30 (aOR 4.5, 95%CI 1.3-15.5) and 30-35 (aOR 6.0, 95%CI 2.3-15.7)(vs >35). CONCLUSIONS: Consecutive SARS-CoV-2 waves with Beta and Delta variants were associated with a shift to younger individuals. Beta and Delta infections were associated with higher peak viral loads, potentially increasing infectiousness.

Incidence and transmission of respiratory syncytial virus in urban and rural South Africa, 2017-2018.

Data on respiratory syncytial virus (RSV) incidence and household transmission are limited. To describe RSV incidence and transmission, we conducted a prospective cohort study in rural and urban communities in South Africa over two seasons during 2017-2018. Nasopharyngeal swabs were collected twice-weekly for 10 months annually and tested for RSV using PCR. We tested 81,430 samples from 1,116 participants in 225 households (follow-up 90%). 32% (359/1116) of individuals had ≥1 RSV infection; 10% (37/359) had repeat infection during the same season, 33% (132/396) of infections were symptomatic, and 2% (9/396) sought medical care. Incidence was 47.2 infections/100 person-years and highest in children <5 years (78.3). Symptoms were commonest in individuals aged <12 and ≥65 years. Individuals 1-12 years accounted for 55% (134/242) of index cases. Household cumulative infection risk was 11%. On multivariable analysis, index cases with ≥2 symptoms and shedding duration >10 days were more likely to transmit; household contacts aged 1-4 years vs. ≥65 years were more likely to acquire infection. Within two South African communities, RSV attack rate was high, and most infections asymptomatic. Young children were more likely to introduce RSV into the home, and to be infected. Future studies should examine whether vaccines targeting children aged <12 years could reduce community transmission.

Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa.

South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. However, the size of its Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study 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. We found that the Omicron BA.1/2 wave infected more than half of the cohort population, with reinfections and vaccine breakthroughs accounting for > 60% of all infections in both rural and urban sites. After the Omicron BA.1/2 wave, we found few (< 6%) remained naïve to SARS-CoV-2 and the population immunologic landscape is fragmented with diverse infection/immunization histories. Prior infection with the ancestral strain, Beta, and Delta variants provided 13%, 34%, and 51% protection against Omicron BA.1/2 infection, respectively. Hybrid immunity and repeated prior infections reduced the risks of Omicron BA.1/2 infection by 60% and 85% respectively. Our study sheds light on a rapidly shifting landscape of population immunity in the Omicron era and provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus.

Incidence and Transmission Dynamics of Bordetella pertussis Infection in Rural and Urban Communities, South Africa, 2016‒2018.

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.

Unmasking Pneumococcal Carriage in a High Human Immunodeficiency Virus (HIV) Prevalence Population in two Community Cohorts in South Africa, 2016-2018: The PHIRST Study.

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.

Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa.

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.

SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron's impact in South African population cohorts.

Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the history of past exposures to different SARS-CoV-2 variants and vaccination in the cohort most representative of South Africa's high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modeling suggests that the Omicron wave likely infected a large fraction (44 to 81%) of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. We project that future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection.

SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-21.

BACKGROUND: By August, 2021, South Africa had been affected by three waves of SARS-CoV-2; the second associated with the beta variant and the third with the delta variant. Data on SARS-CoV-2 burden, transmission, and asymptomatic infections from Africa are scarce. We aimed to evaluate SARS-CoV-2 burden and transmission in one rural and one urban community in South Africa. METHODS: We conducted a prospective cohort study of households in Agincourt, Mpumalanga province (rural site) and Klerksdorp, North West province (urban site) from July, 2020 to August, 2021. We randomly selected households for the rural site from a health and sociodemographic surveillance system and for the urban site using GPS coordinates. Households with more than two members and where at least 75% of members consented to participate were eligible. Midturbinate nasal swabs were collected twice a week from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time RT-PCR (RT-rtPCR). Serum was collected every 2 months and tested for anti-SARS-CoV-2 antibodies. Main outcomes were the cumulative incidence of SARS-CoV-2 infection, frequency of reinfection, symptomatic fraction (percent of infected individuals with ≥1 symptom), the duration of viral RNA shedding (number of days of SARS-CoV-2 RT-rtPCR positivity), and the household cumulative infection risk (HCIR; number of infected household contacts divided by the number of susceptible household members). FINDINGS: 222 households (114 at the rural site and 108 at the urban site), and 1200 household members (643 at the rural site and 557 at the urban site) were included in the analysis. For 115 759 nasal specimens from 1200 household members (follow-up 92·5%), 1976 (1·7%) were SARS-CoV-2-positive on RT-rtPCR. By RT-rtPCR and serology combined, 749 of 1200 individuals (62·4% [95% CI 58·1-66·4]) had at least one SARS-CoV-2 infection episode, and 87 of 749 (11·6% [9·4-14·2]) were reinfected. The mean infection episode duration was 11·6 days (SD 9·0; range 4-137). Of 662 RT-rtPCR-confirmed episodes (>14 days after the start of follow-up) with available data, 97 (14·7% [11·9-17·9]) were symptomatic with at least one symptom (in individuals aged <19 years, 28 [7·5%] of 373 episodes symptomatic; in individuals aged ≥19 years, 69 [23·9%] of 289 episodes symptomatic). Among 222 households, 200 (90·1% [85·3-93·7]) had at least one SARS-CoV-2-positive individual on RT-rtPCR or serology. HCIR overall was 23·9% (195 of 817 susceptible household members infected [95% CI 19·8-28·4]). HCIR was 23·3% (20 of 86) for symptomatic index cases and 23·9% (175 of 731) for asymptomatic index cases (univariate odds ratio [OR] 1·0 [95% CI 0·5-2·0]). On multivariable analysis, accounting for age and sex, low minimum cycle threshold value (≤30 vs >30) of the index case (OR 5·3 [2·3-12·4]) and beta and delta variant infection (vs Wuhan-Hu-1, OR 3·3 [1·4-8·2] and 10·4 [4·1-26·7], respectively) were associated with increased HCIR. People living with HIV who were not virally supressed (≥400 viral load copies per mL) were more likely to develop symptomatic illness when infected with SAR-CoV-2 (OR 3·3 [1·3-8·4]), and shed SARS-CoV-2 for longer (hazard ratio 0·4 [95% CI 0·3-0·6]) compared with HIV-uninfected individuals. INTERPRETATION: In this study, 565 (85·3%) 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 was likely to have contributed to successive waves of SARS-CoV-2 infection, with more than 60% of individuals infected by the end of follow-up. FUNDING: US CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust.

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.

Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016-2018: A hidden Markov modelling study.

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 HIV-infected 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.

Cohort profile: A Prospective Household cohort study of Influenza, Respiratory syncytial virus and other respiratory pathogens community burden and Transmission dynamics in South Africa, 2016-2018.

PURPOSE: The PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and to assess household transmission. PARTICIPANTS: We enrolled 1684 individuals in 327 randomly selected households in a rural and an urban site over three consecutive influenza and two RSV seasons. A new cohort of households was enrolled each year. Participants were sampled with nasopharyngeal swabs twice-weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually. FINDINGS TO DATE: There were 122 113 potential individual follow-up visits over the 3 years, and participants were interviewed for 105 783 (87%) of these. Out of 105 683 nasopharyngeal swabs, 1258 (1%) and 1026 (1%) tested positive on polymerase chain reaction (PCR) for influenza viruses and RSV, respectively. Over one third of individuals had PCR-confirmed influenza each year. Overall, there was influenza transmission to 10% of household contacts of an index case. FUTURE PLANS: Future planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016-2018 were eligible for inclusion in a study of SARS-CoV-2 transmission initiated in July 2020. This study uses similar testing frequency to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.

Challenges and clinical relevance of molecular detection of Bordetella pertussis in South Africa.

BACKGROUND: We assessed the utility of a multi-target, real-time PCR assay for Bordetella pertussis detection and diagnosis in patients with severe respiratory illness (SRI), influenza-like illness (ILI), and asymptomatic controls. METHODS: Real-time PCR detection of IS481, pIS1001, hIS1001 and ptxS1 was performed on nasopharyngeal specimens (SRI, ILI and controls) and induced sputum (SRI) collected from June 2012 to May 2016 through respiratory illness surveillance. Using PCR cycle threshold (Ct) value cut-offs, IS481 positive cases were classified as confirmed (Ct < 35) or possible (Ct 35-39) pertussis disease. RESULTS: Among 12,922 samples, 146 (1.1%) were IS481 positive of which 62% (90/146) were classified as confirmed. The attributable fraction (AF) was 92.2% (95% CI, 65.6 to 98.2%) and 90.5% (95% CI, 57.5 to 97.9%) amongst SRI and ILI PCR-confirmed pertussis cases, respectively. Amongst possible pertussis cases, AF was 36.9% (95% CI, - 142.3 to 83.6%) and 67.5% (95% CI, - 30.6 to 91.9%) in the SRI and ILI groups, respectively. CONCLUSION: All IS481 positive specimens could be considered as B. pertussis infection, and potentially pertussis disease with supportive clinical information.

Epidemiology and Molecular Identification and Characterization of Mycoplasma pneumoniae, South Africa, 2012-2015.

During 2012-2015, we tested respiratory specimens from patients with severe respiratory illness (SRI), patients with influenza-like illness (ILI), and controls in South Africa by real-time PCR for Mycoplasma pneumoniae, followed by culture and molecular characterization of positive samples. M. pneumoniae prevalence was 1.6% among SRI patients, 0.7% among ILI patients, and 0.2% among controls (p<0.001). Age <5 years (adjusted odd ratio 7.1; 95% CI 1.7-28.7) and HIV infection (adjusted odds ratio 23.8; 95% CI 4.1-138.2) among M. pneumonia-positive persons were associated with severe disease. The detection rate attributable to illness was 93.9% (95% CI 74.4%-98.5%) in SRI patients and 80.7% (95% CI 16.7%-95.6%) in ILI patients. The hospitalization rate was 28 cases/100,000 population. We observed the macrolide-susceptible M. pneumoniae genotype in all cases and found P1 types 1, 2, and a type 2 variant with multilocus variable number tandem repeat types 3/6/6/2, 3/5/6/2, and 4/5/7/2.

Legionnaires' Disease in South Africa, 2012-2014.

During June 2012-September 2014, we tested patients with severe respiratory illness for Legionella spp. infection and conducted a retrospective epidemiologic investigation. Of 1,805 patients tested, Legionella was detected in samples of 21 (1.2%); most were adults who had HIV or tuberculosis infections and were inappropriately treated for Legionella.