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

PurposeThe 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.ParticipantsWe 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 DateThere 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 PlansFuture 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.     

The effects of the attributable fraction and the duration of symptoms on burden estimates of influenza‐associated respiratory illnesses in a high HIV prevalence setting,South Africa, 2013‐2015

Background

The attributable fraction of influenza virus detection to illness (INF‐AF) and the duration of symptoms as a surveillance inclusion criterion could potentially have substantial effects on influenza disease burden estimates.

Methods

We estimated rates of influenza‐associated influenza‐like illness (ILI) and severe acute (SARI‐10) or chronic (SCRI‐10) respiratory illness (using a symptom duration cutoff of ≤10 days) among HIV‐infected and HIV‐uninfected patients attending 3 hospitals and 2 affiliated clinics in South Africa during 2013‐2015. We calculated the unadjusted and INF‐AF‐adjusted rates and relative risk (RR) due to HIV infection. Rates were expressed per 100 000 population.

Results

The estimated mean annual unadjusted rates of influenza‐associated illness were 1467.7, 50.3, and 27.4 among patients with ILI, SARI‐10, and SCRI‐10, respectively. After adjusting for the INF‐AF, the percent reduction in the estimated rates was 8.9% (rate: 1336.9), 11.0% (rate: 44.8), and 16.3% (rate: 22.9) among patients with ILI, SARI‐10, and SCRI‐10, respectively. HIV‐infected compared to HIV‐uninfected individuals experienced a 2.3 (95% CI: 2.2‐2.4)‐, 9.7 (95% CI: 8.0‐11.8)‐, and 10.0 (95% CI: 7.9‐12.7)‐fold increased risk of influenza‐associated illness among patients with ILI, SARI‐10, and SCRI‐10, respectively. Overall 34% of the estimated influenza‐associated hospitalizations had symptom duration of >10 days; 8% and 44% among individuals aged <5 and ≥5 years, respectively.

Conclusion

The marginal differences between unadjusted and INF‐AF‐adjusted rates are unlikely to affect policies on prioritization of interventions. HIV‐infected individuals experienced an increased risk of influenza‐associated illness and may benefit more from annual influenza immunization. The use of a symptom duration cutoff of ≤10 days may underestimate influenza‐associated disease burden, especially in older individuals.     

Rift Valley Fever Virus Seroprevalence among Humans,Northern KwaZulu-Natal Province,South Africa, 2018–2019

We detected Rift Valley fever virus (RVFV) IgM and IgG in human serum samples collected during 2018–2019 in northern KwaZulu-Natal Province, South Africa. Our results show recent RVFV circulation and likely RVFV endemicity in this tropical coastal plain region of South Africa in the absence of apparent clinical disease.     

Epidemiology of Influenza Virus Types and Subtypes in South Africa, 2009–2012

To determine clinical and epidemiologic differences between influenza caused by different virus types and subtypes, we identified patients and tested specimens. Patients were children and adults hospitalized with confirmed influenza and severe acute respiratory illness (SARI) identified through active, prospective, hospital-based surveillance from 2009–2012 in South Africa. Respiratory specimens were tested, typed, and subtyped for influenza virus by PCR. Of 16,005 SARI patients tested, 1,239 (8%) were positive for influenza virus. Patient age and co-infections varied according to virus type and subtype, but disease severity did not. Case-patients with influenza B were more likely than patients with influenza A to be HIV infected. A higher proportion of case-patients infected during the first wave of the 2009 influenza pandemic were 5–24 years of age (19%) than were patients infected during the second wave (9%). Although clinical differences exist, treatment recommendations do not differ according to subtype; prevention through vaccination is recommended.     

Genetic diversity and molecular epidemiology of human rhinoviruses in South Africa

Background

Rhinoviruses (RV) are a well-established cause of respiratory illness. RV-C has been associated with more severe illness. We aimed to characterize and compare the clinical presentations and disease severity of different RV type circulating in South Africa.

Method

We performed two analyses of RV-positive specimens identified through surveillance in South Africa across all age groups. First, RV-positive specimens identified through severe acute respiratory illness (SARI) surveillance in four provinces was randomly selected from 2009 to 2010 for molecular characterization. Second, RV-positive specimens identified through SARI, influenza-like illness (ILI) and control surveillance at hospitals and outpatient clinics in during 2012–2013 were used to determine the association of RV type with severe disease. Selected specimens were sequenced, and phylogenetic analysis was performed.

Results

Among the 599 sequenced specimens from 2009 to 2010 and 2012 to 2013, RV-A (285, 48%) and RV-C (247, 41%) were more commonly identified than RV-B (67, 11%), with no seasonality and a high genetic diversity. A higher prevalence of RV infection was identified in cases with SARI [515/962 (26%); aRRR = 1·6; 95% CI 1·21; 2·2] and ILI [356/962 (28%); aRRR = 1·9; 95% CI 1·37; 2·6] compared with asymptomatic controls (91/962, 22%). There was no difference in disease severity between the different type when comparing SARI, ILI and controls.

Conclusion

All three type of RV were identified in South Africa, although RV-A and RV-C were more common than RV-B. RV was associated with symptomatic respiratory illness; however, there was no association between RV type and disease severity.     

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.     

Human respiratory syncytial virus diversity and epidemiology among patients hospitalized with severe respiratory illness in South Africa, 2012–2015

BackgroundWe aimed to describe the prevalence of human respiratory syncytial virus (HRSV) and evaluate associations between HRSV subgroups and/or genotypes and epidemiologic characteristics and clinical outcomes in patients hospitalized with severe respiratory illness (SRI).MethodsBetween January 2012 and December 2015, we enrolled patients of all ages admitted to two South African hospitals with SRI in prospective hospital‐based syndromic surveillance. We collected respiratory specimens and clinical and epidemiological data. Unconditional random effect multivariable logistic regression was used to assess factors associated with HRSV infection.ResultsHRSV was detected in 11.2% (772/6908) of enrolled patients of which 47.0% (363/772) were under the age of 6 months. There were no differences in clinical outcomes of HRSV subgroup A‐infected patients compared with HRSV subgroup B‐infected patients but among patients aged <5 years, children with HRSV subgroup A were more likely be coinfected with Streptococcus pneumoniae (23/208, 11.0% vs. 2/90, 2.0%; adjusted odds ratio 5.7). No significant associations of HRSV A genotypes NA1 and ON1 with specific clinical outcomes were observed.ConclusionsWhile HRSV subgroup and genotype dominance shifted between seasons, we showed similar genotype diversity as noted worldwide. We found no association between clinical outcomes and HRSV subgroups or genotypes.