The yield of nasopharyngeal bacteria from culture compared to polymerase chain reaction in South African children with lower respiratory tract infection

Background Lower respiratory tract infection (LRTI) is a major cause of morbidity and mortality in children under 5 years of age. Bacterial pathogens contribute significantly to this process. Culture of respiratory tract specimens is labour-intensive and slow. Polymerase chain reaction (PCR) is comparatively, a rapid, sensitive method of detecting low levels of nucleic acid for clinically relevant bacteria. This study compares the yield of bacteria obtained from culture and the FTDResp33 multiplex PCR of nasopharyngeal swabs (NPs) during LRTI episodes in children, in the Drakenstein Child Health Study. Methods At each episode of LRTI, 2 NPs were obtained, one for culture and one for PCR testing. Bacterial yields and concordance for the 5 commonest bacteria were compared using frequencies and proportions. Results From 13th August 2012 to 23rd November 2020, there were 859 episodes of LRTI in 434 children [median age 9.2 (IQR 3.8; 18.9) months; 0.2% HIV-infected]. S. pneumoniae, S. aureus, M. catarrhalis, H. influenzae and K. pneumoniae were the predominant bacteria detected by either method. Concordance between culture and PCR for S. pneumoniae, S. aureus, and K. pneumoniae was 84.9%, 89.7% and 86.3% respectively. Culture and PCR for H. influenzae had a concordance of 76.9%. The greatest discordance between culture and PCR was for the detection of M. catarrhalis (34.4%). Median bacterial loads on PCR for all 5 organisms were significantly associated with semi-quantitative culture results (p<0.001 for each). Adjusting for age and hospitalization, children on antibiotics at the time of sampling, had a reduced chance of having a positive culture (OR 0.1; 95% CI 0.1-0.4), and a reduction in PCR yield (OR 0.8; 95% CI 0.4-1.6). Conclusion: Significant concordance existed between PCR and culture for 4 of the 5 common bacteria, affirming PCR as a comparable method of testing to culture

Short-term treatment outcomes of children starting ART in the ICU, general medical wards and outpatient HIV clinics at Red Cross War Memorial Children’s Hospital (RCWMCH): a retrospective cohort study

Includes bibliographical references.Short-term treatment outcomes of children starting ART in the ICU, general medical wards and outpatient HIV clinics at Red Cross War Memorial Children’s Hospital (RCWMCH): A Retrospective Cohort Study. Background: Antiretroviral therapy (ART) has proven to decrease morbidity and mortality in HIV-infected children and improve immunologic, virologic and clinical outcomes. As clinical management policies evolved, an emphasis on early infant testing was adopted resulting in an increasing number of children being diagnosed and commenced on therapy before the onset of severe disease progression. However, a fair proportion still remain untested and subsequently present to hospital with advanced immunosuppression and severe disease. Since the advent of the 2013 national Standard Treatment Guidelines which encourage expedited initiation of ART within 7 days of HIV diagnosis in all children under the age of 12 months and in those with advanced immunosuppression, it is likely that many HIV-infected children are being initiated on ART during hospitalisation in South Africa. No local published data on these outcomes exist. We assessed the short-term outcomes of children initiated on ART in the intensive care unit (ICU), general medical wards (GMWs) and outpatient HIV clinics (OHCs) at RCWMCH. Methods: Structured Literature Review A Pubmed search looking at outcomes of treatment naïve HIV-infected children and adolescents up to 19 years of age living in South Africa commenced on 1st line ART regimens in accordance to the national guidelines presiding at the time, over a 10 year period was performed. This served to identify gaps in knowledge around paediatric ART in a South African context warranting further research. Retrospective Cohort Study We conducted a retrospective cohort study of HIV-infected children <13 years of age, commenced on first line ART between January 2008 and December 2011 at RCWMCH. Outcome measures included death, virologic suppression and changes in CD4 count and percentage. Kaplan-Meier estimates, multivariate Cox proportional hazard ratios and logistic regression were used to estimate outcomes 6 months after ART initiation. Results: Structured Literature Review This review identified several knowledge gaps. One of these gaps, the treatment outcomes of children started on ART at different service levels within tertiary health care settings was addressed in our retrospective cohort study and described in section C of this dissertation Retrospective Cohort Study Seven hundred and forty-nine children were included: 106 were commenced on ART in the ICU, 509 in the GMWs and 127 in the OHCs. Four hundred and ninety-two (65.7%) children were <12 months old. Children in the ICU and GMW cohorts were significantly younger than the OHC cohort (median ages: 3 and 5 months respectively vs. 22 months) and had lower WAZ scores (-2.48 and -2.33 respectively vs -1.14). Three hundred and eighty-five (51.4%) children qualified for rapid ART initiation within 7 days of HIV diagnosis or hospitalisation, based on CD4 criteria in the 2013 national Standard Treatment Guidelines. Overall mortality was 6.4% (CI: 4.9 - 8.4). Mortality was significantly higher in the ICU cohort i.e. 14 (13.2%) deaths compared to 28 (5.5%) and 5 (3.9%) deaths in the GMWs and OHCs cohorts, logrank p=0.004. Predictors of mortality included being moderately underweight HR 2.4 (CI: 1.1 – 5.2; p=0.02), severely underweight HR 3.2 (CI: 1.6 – 6.5; p=0.001), absence of caregiver counselling sessions HR 2.9 (CI: 1.4 – 6.0; p=0.005) and ART initiation in ICU HR 2.6 (CI: 1.4 – 4.9; p=0.003). Conclusion: The findings of our retrospective cohort study serve as a basis for understanding the implications of ART initiation in children during hospitalisation

Short-term treatment outcomes of children starting antiretroviral therapy in the intensive care unit, general medical wards and outpatient HIV clinics at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa: A retrospective cohort study

Background. Many HIV-infected children are initiated on antiretroviral therapy (ART) during hospitalisation in South Africa (SA). No published data on these outcomes exist.Objectives. To assess the short-term outcomes of children initiated on ART in the intensive care unit (ICU), general medical wards (GMWs) and outpatient HIV clinics (OHCs) at Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, SA.Methods. We conducted a retrospective cohort study of HIV-infected children aged &lt;13 years commenced on first-line ART between January 2008 and December 2011. Outcomes included death, virological suppression and changes in CD4 count. Kaplan-Meier estimates, multivariate Cox proportional hazard ratios and logistic regression were used to estimate outcomes at 6 months.Results. One hundred and six children were commenced on ART in the ICU, 509 in the GMWs and 127 in the OHCs; 65.7% of all children were &lt;12 months old. Of children qualifying for rapid ART initiation according to the 2013 national treatment guidelines, 182 (24.9%) started therapy within 7 days of diagnosis. Overall mortality was 6.4% (95% confidence interval (CI) 4.9 - 8.4). Of children remaining in care at RCWMCH, 51.0% achieved a CD4 percentage ≥25% and 62.3% a viral load ≤50 copies/mL 6 months after ART initiation. Mortality was higher in the ICU cohort (13.2%) than in the GMW and OHC cohorts (5.5% and 3.9%, respectively, log-rank p=0.004). Predictors of mortality included moderate underweight (adjusted hazard ratio (aHR) 2.4; 95% CI 1.1 - 5.2), severe underweight (aHR 3.2; 95% CI 1.6 - 6.5), absence of caregiver counselling sessions (aHR 2.9; 95% CI 1.4 - 6.0) and ART initiation in the ICU (aHR 2.6; 95% CI 1.4 - 4.9).Conclusion. These results highlight the importance of understanding the context in which children initiate ART, when comparing outcomes in different settings

Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

A ten-year review of ESBL and non-ESBL Escherichia coli bloodstream infections among children at a tertiary referral hospital in South Africa.

INTRODUCTION:There are few studies describing Escherichia coli (E. coli) bloodstream infection (BSI) among children in Africa, yet E.coli is increasing in importance as a cause of antibiotic resistant infection in paediatric settings. METHODS:In this retrospective, descriptive study aspects of E. coli BSI epidemiology are described over a 10-year period including incidence risk, risk factors for extended-spectrum β-lactamase (ESBL)-producing E. coli BSI, antibiotic susceptibility of the bacterial isolates and outcome including risk factors for severe disease. RESULTS:There were 583 new E. coli BSI episodes among 217,483 admissions, an overall incidence risk of 2.7 events/1,000 hospital admissions. Of 455 of these E. coli BSI episodes that were analysed, 136 (29.9%) were caused by ESBL-producing isolates. Risk factors for ESBL-producing E. coli BSI included hospitalization in the 28-day period preceding E. coli BSI episodes, having an underlying chronic illness other than HIV infection at the time of the E. coli BSI and having a temperature of 38° Celsius or higher at the time of the E. coli BSI. None of the E. coli isolates were resistant to carbapenems or colistin. The mortality rate was 5.9% and admission to the intensive care unit was required in 12.3% of BSI episodes. Predictors of severe disease included age less than 1 month, hospitalization in the 28-day period preceding E. coli BSI and BSI without a definable focus. CONCLUSIONS:These findings extend our understanding of E. coli BSI in a sub-Saharan African setting, provide useful information that can guide empiric treatment choices for community- and hospital-acquired BSI and help inform prevention strategies

Bloodstream infections at a tertiary level paediatric hospital in South Africa

Background: Bloodstream infection (BSI) in children causes significant morbidity and mortality. There are few studies describing the epidemiology of BSI in South African children. Methods: A retrospective descriptive cohort study was conducted at a paediatric referral hospital in Cape Town, South Africa. The National Health Laboratory Service (NHLS) microbiology database was accessed to identify positive blood culture specimens during the period 2011–2012. Demographic and clinical details, antimicrobial management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the NHLS database. Results: Of the 693 unique bacterial and fungal BSI episodes identified during the study period, 248 (35.8%) were community-acquired (CA), 371 (53.5%) hospital-acquired (HA) and 74 (10.7%) healthcare-associated (HCA). The overall risk was 6.7 BSI episodes per 1000 admissions. Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae were the most frequent causes of CA-BSI and Klebsiella pneumoniae, Acinetobacter baumanii and S. aureus were most commonly isolated in HA-BSI. On multivariable analysis, severe underweight, severe anaemia at the time of BSI, admission in the ICU at the time of BSI, and requiring ICU admission after BSI was diagnosed were significantly associated with 14-day mortality. Conclusion: This study adds to the limited literature describing BSI in children in Africa. Further studies are required to understand the impact that BSI has on the paediatric population in sub-Saharan Africa