Improving Tuberculosis Preventive Therapy Uptake: A Cluster-randomized Trial of Symptom-based Versus Tuberculin Skin Test-based Screening of Household Tuberculosis Contacts Less Than 5 Years of Age.

Background: Tuberculosis preventive therapy (TPT) is highly effective at preventing tuberculosis disease in household child contacts (<5 years), but is poorly implemented worldwide. In 2006, the World Health Organization recommended symptom-based screening as a replacement for tuberculin skin testing (TST) to simplify contact evaluation and improve implementation. We aimed to determine the effectiveness of this recommendation.

The Impact of Influenza and Tuberculosis Interaction on Mortality Among Individuals Aged ≥15 Years Hospitalized With Severe Respiratory Illness in South Africa, 2010-2016.

Background: Data on the prevalence and impact of influenza-tuberculosis coinfection on clinical outcomes from high-HIV and -tuberculosis burden settings are limited. We explored the impact of influenza and tuberculosis coinfection on mortality among hospitalized adults with lower respiratory tract infection (LRTI).

Methods: We enrolled patients aged ≥15 years admitted with physician-diagnosed LRTI or suspected tuberculosis at 2 hospitals in South Africa from 2010 to 2016.

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 (C) value cut-offs, IS481 positive cases were classified as confirmed (C < 35) or possible (C 35-39) pertussis disease.

Healthcare utilization for common infectious disease syndromes in Soweto and Klerksdorp, South Africa.

Introduction: Understanding healthcare utilization helps characterize access to healthcare, identify barriers and improve surveillance data interpretation. We describe healthcare-seeking behaviors for common infectious syndromes and identify reasons for seeking care.

Methods: We conducted a cross-sectional survey among residents in Soweto and Klerksdorp, South Africa.

Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial.

Background: Delamanid is one of two recently approved drugs for the treatment of multidrug-resistant tuberculosis. We aimed to evaluate the safety and efficacy of delamanid in the first 6 months of treatment.

Methods: This randomised, double-blind, placebo-controlled, phase 3 trial was done at 17 sites in seven countries (Estonia, Latvia, Lithuania, Moldova, Peru, the Philippines, and South Africa).

Human bocavirus, coronavirus, and polyomavirus detected among patients hospitalised with severe acute respiratory illness in South Africa, 2012 to 2013.

Aim: To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa.

Methods: The study included 680 South African patients randomly selected in age-defined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real-time polymerase chain reaction assay was used to detect hBoV; hCoV-OC43, hCoV-229E, hCoV-NL63, and hCoV-HKU1; and Washington University hPyV (hPyV-WU) and Karolinska Insitute hPyV (hPyV-KI), in respiratory tract specimens collected from patients with SARI.

The Fraction of Rhinovirus Detections Attributable to Mild and Severe Respiratory Illness in a Setting of High Human Immunodeficiency Virus Prevalence, South Africa, 2013-2015.

Background: The association of rhinovirus (RV) detection to illness is poorly understood.

Methods: We enrolled case patients hospitalized with severe respiratory illness (SRI) at 2 hospitals and outpatients with influenza-like illness (ILI) and asymptomatic individuals (controls) from 2 affiliated clinics during 2013-2015. We compared the RV prevalence among ILI and SRI cases to those of controls stratified by human immunodeficiency virus (HIV) serostatus using penalized logistic regression.

Hospitalization and post-discharge care in South Africa: A critical event in the continuum of care.

Objectives: The purpose of this prospective cohort study is to characterize the event of acute hospitalization for people living with and without HIV and describe its impact on the care continuum. This study describes care-seeking behavior prior to an index hospitalization, inpatient HIV testing and diagnosis, discharge instructions, and follow-up care for patients for patients being discharged from a single hospital in South Africa.

Methods: A convenience sample of adult patients was recruited from the medical wards of a tertiary care facility.

Household Transmission of Seasonal Influenza From HIV-Infected and HIV-Uninfected Individuals in South Africa, 2013-2014.

Background: We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases.

Methods: Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every 4 days were tested by rRT-PCR.

Quantifying How Different Clinical Presentations, Levels of Severity, and Healthcare Attendance Shape the Burden of Influenza-associated Illness: A Modeling Study From South Africa.

Background: Burden estimates of medically and nonmedically attended influenza-associated illness across syndromes and levels of severity are lacking.

Methods: We estimated the national burden of medically and nonmedically attended influenza-associated illness among individuals with different clinical presentations (all-respiratory, all-circulatory, and nonrespiratory/noncirculatory) and levels of severity (mild, fatal, and severe, nonfatal) using a combination of case-based (from laboratory-confirmed influenza surveillance) and ecological studies, as well as data from healthcare utilization surveys in South Africa during 2013-2015. In addition, we compared estimates of medically attended influenza-associated respiratory illness, obtained from case-based and ecological studies.

High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen.

South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria.PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.

Value stream mapping to characterize value and waste associated with accessing HIV care in South Africa.

Introduction: Inefficient clinic-level delivery of HIV services is a barrier to linkage and engagement in care. We used value stream mapping to quantify time spent on each component of a clinic visit while receiving care following a hospital admission in South Africa.

Methods: We described time for each clinic service ("process time") and time spent waiting for that service ("lead time").

Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study.

Background: Addition of bedaquiline to treatment for multidrug-resistant tuberculosis was associated with an increased risk of death in a phase 2b clinical trial, resulting in caution from WHO. Following a compassionate access programme and local regulatory approval, the South African National Tuberculosis Programme began widespread use of bedaquiline in March, 2015, especially among patients with extensively drug resistant tuberculosis for whom no other effective treatment options were available. We aimed to compare mortality in patients on standard regimens with that of patients on regimens including bedaquiline.

Prevalence and Correlates of Snuff Use, and its Association With Tuberculosis, Among Women Living With HIV in South Africa.

Introduction: A higher proportion of people living with HIV (PLWH) smoke compared to the general population, but little information exists about the prevalence and correlates of smokeless tobacco use among PLWH. In South Africa, dry powdered tobacco is inhaled nasally as snuff.

Methods: A cross-sectional survey among PLWH attending three HIV clinics was conducted.

Performance of Surveillance Case Definitions in Detecting Respiratory Syncytial Virus Infection Among Young Children Hospitalized With Severe Respiratory Illness-South Africa, 2009-2014.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection (ALRTI) in young children, but data on surveillance case definition performance in estimating burdens have been limited.

Methods: We enrolled children aged <5 years hospitalized for ALRTI (or neonatal sepsis in young infants) through active prospective surveillance at 5 sentinel hospitals in South Africa and collected nasopharyngeal aspirates from them for RSV molecular diagnostic testing between 2009 and 2014. Clinical data were used to characterize RSV disease and retrospectively evaluate the performance of respiratory illness case definitions (including the World Health Organization definition for severe acute respiratory infection [SARI]) in identifying hospitalized children with laboratory-confirmed RSV according to age group (<3, 3-5, 6-11, 12-23, and 24-59 months).

Influenza Viral Shedding in a Prospective Cohort of HIV-Infected and Uninfected Children and Adults in 2 Provinces of South Africa, 2012-2014.

Background: Prolonged shedding of influenza viruses may be associated with increased transmissibility and resistance mutation acquisition due to therapy. We compared duration and magnitude of influenza shedding between human immunodeficiency virus (HIV)-infected and -uninfected individuals.

Methods: A prospective cohort study during 3 influenza seasons enrolled patients with influenza-like illness and a positive influenza rapid test.

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.

Indoor air pollution from secondhand tobacco smoke, solid fuels, and kerosene in homes with active tuberculosis disease in South Africa.

Objectives: Secondhand tobacco smoke (SHS), use of solid fuels, and kerosene may play an important role in perpetuating the tuberculosis (TB) epidemic. The purpose of this study was to explore the prevalence of household air pollution (HAP) from these sources in homes of someone with TB in a high HIV-prevalence setting. A convenience sample of homes and household members participating in an ongoing active case-finding study in Matlosana district townships surrounding Klerksdorp, South Africa were included.

Prevalence and Correlates of Smoking Among People Living With HIV in South Africa.

Introduction: Smoking likely exacerbates comorbidities which people living with HIV (PLWH) are predisposed. We assessed prevalence and correlates of smoking among PLWH in South Africa, which has 7 million PLWH but inadequate reporting of smoking.

Methods: A cross-sectional survey was conducted among randomly selected adults with HIV infection in Klerksdorp, South Africa.

The Burden and Clinical Presentation of Pulmonary Tuberculosis in Adults With Severe Respiratory Illness in a High Human Immunodeficiency Virus Prevalence Setting, 2012-2014.

Background: Understanding the burden and clinical presentation of tuberculosis in patients with severe respiratory illness (SRI) has important implications for anticipating treatment requirements.

Methods: Hospitalized patients aged ≥15 years with SRI at 2 public teaching hospitals in periurban areas in 2 provinces (Edendale Hospital in Pietermaritzburg, KwaZulu-Natal Province and Tshepong Hospital in Klerksdorp, North West Province) were enrolled prospectively from 2012 to 2014. Tuberculosis testing included smear microscopy, culture, or Xpert MTB/Rif.

Respiratory syncytial virus in adults with severe acute respiratory illness in a high HIV prevalence setting.

Background: There are limited data on the epidemiology of respiratory syncytial virus (RSV) illness in HIV-infected adults or the elderly in Africa. We studied the epidemiology of RSV-associated severe acute respiratory illness (SARI) hospitalizations in adults in South Africa from 2009 through 2013.

Methods: Individuals admitted to sentinel surveillance hospitals were investigated by respiratory tract swabs for RSV, using a multiplex real-time polymerase chain reaction assay.

Enterovirus genotypes among patients with severe acute respiratory illness, influenza-like illness, and asymptomatic individuals in South Africa, 2012-2014.

Enteroviruses can cause outbreaks of severe acute respiratory illness (SARI) and EV-A, -B, -C, and -D species have different pathogenic profiles and circulation patterns. We aimed to characterize and determine the prevalence of enterovirus genotypes among South African patients with respiratory illness and controls during June 2012 to July 2014. Syndromic SARI and influenza-like illness (ILI) surveillance was performed at two sentinel sites.

Multidisciplinary Point-of-Care Testing in South African Primary Health Care Clinics Accelerates HIV ART Initiation but Does Not Alter Retention in Care.

Background: Lack of accessible laboratory infrastructure limits HIV antiretroviral therapy (ART) initiation, monitoring, and retention in many resource-limited settings. Point-of-care testing (POCT) is advocated as a mechanism to overcome these limitations. We executed a pragmatic, prospective, randomized, controlled trial comparing the impact of POCT vs.