Tuberculosis prevalence, incidence and prevention in a south african cohort of children living with HIV.

BACKGROUND: We describe tuberculosis (TB) disease among antiretroviral treatment (ART) eligible children living with HIV (CLHIV) in South Africa to highlight TB prevention opportunities. METHODS: In our secondary analysis among 0- to 12-year-old ART-eligible CLHIV in five Eastern Cape Province health facilities from 2012 to 2015, prevalent TB occurred 90 days before or after enrollment; incident TB occurred >90 days after enrollment. Characteristics associated with TB were assessed using logistic and Cox proportional hazards regression with generalized estimating equations. RESULTS: Of 397 enrolled children, 114 (28.7%) had prevalent TB. Higher-income proxy [adjusted odds ratio (aOR) 1.8 [95% confidence interval (CI) 1.3-2.6] for the highest, 1.6 (95% CI 1.6-1.7) for intermediate]; CD4+ cell count <350 cells/µl [aOR 1.6 (95% CI 1.1-2.2)]; and malnutrition [aOR 1.6 (95% CI 1.1-2.6)] were associated with prevalent TB. Incident TB was 5.2 per 100 person-years and was associated with delayed ART initiation [hazard ratio (HR) 4.7 (95% CI 2.3-9.4)], malnutrition [HR 1.8 (95% CI 1.1-2.7)] and absence of cotrimoxazole [HR 2.3 (95% CI 1.0-4.9)]. Among 362 children with data, 8.6% received TB preventive treatment. CONCLUSIONS: Among these CLHIV, prevalent and incident TB were common. Early ART, cotrimoxazole and addressing malnutrition may prevent TB in these children.

BACKGROUND: We describe tuberculosis (TB) in children living with HIV (CLHIV) eligible for HIV treatment in South Africa to highlight opportunities to prevent TB. METHODS: We analyzed additional data from our original study of CLHIV who were 0­12 years old and due to start HIV treatment in five health facilities in Eastern Cape Province from 2012 to 2015 and assessed characteristics associated with existing and new TB. RESULTS: Of 397 enrolled children, 114 (28.7%) had existing TB. Children with a higher measure of household income had higher odds of existing TB. CD4+ cell count <350 cells/µl and malnutrition were also associated with existing TB. There were 5.2 new cases of TB for every 100 child-years. New TB was 4.7 times more likely for children with delayed HIV treatment start, 1.8 times more likely for children with malnutrition and 2.3 times more likely for children who did not get cotrimoxazole. Among 362 children with data, 8.6% received treatment to prevent TB. CONCLUSIONS: Among these CLHIV, existing and new TB were common. Early HIV treatment, cotrimoxazole and addressing malnutrition may prevent TB in these children.

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa.

INTRODUCTION: There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low-resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa. METHODS: The Pediatric Enhanced Surveillance Study enrolled HIV-infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub-distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date. RESULTS: Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight-for-age z-score (WAZ) was -1.7 (interquartile range (IQR):-3.1 to -0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty-four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub-distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds. CONCLUSIONS: We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

High risk of loss to follow-up among South African children on ART during transfer, a retrospective cohort analysis with community tracing.

INTRODUCTION: Decentralization of HIV care for children has been recommended to improve paediatric outcomes by making antiretroviral treatment (ART) more accessible. We documented outcomes of children transferred after initiating ART at a large tertiary hospital in the Eastern Cape of South Africa. METHODS: Electronic medical records for all children 0-15 years initiating ART at Dora Nginza Hospital (DNH) in Port Elizabeth, South Africa January 2004 to September 2015 were examined. Records for children transferred to primary and community clinics were searched at 16 health facilities to identify children with successful (at least one recorded visit) and unsuccessful transfer (no visits). We identified all children lost to follow-up (LTF) after ART initiation: those LTF at DNH (no visit >6 months), children with unsuccessful transfer, and children LTF after successful transfer (no visit >6 months). Community tracing was conducted to locate caregivers of children LTF and electronic laboratory data were searched to measure reengagement in care, including silent transfers. RESULTS: 1,582 children initiated ART at median age of 4 years [interquartile range (IQR): 1-8] and median CD4+ of 278 cells/mm3 [IQR: 119-526]. A total of 901 (57.0%) children were transferred, 644 (71.5%) to study facilities; 433 (67.2%) children had successful transfer and 211 (32.8%) had unsuccessful transfer. In total, 399 children were LTF: 105 (26.3%) from DNH, 211 (52.9%) through unsuccessful transfer and 83 (20.8%) following successful transfer. Community tracing was conducted for 120 (30.1%) of 399 children LTF and 66 (55.0%) caregivers were located and interviewed. Four children had died. Among 62 children still alive, 8 (12.9%) were reported to not be in care or taking ART and 18 (29.0%) were also not taking ART. Overall, 65 (16.3%) of 399 children LTF had a laboratory result within 18 months of their last visit indicating silent transfer and 112 (28.1%) had lab results from 2015 to 2016 indicating current care. CONCLUSION: We found that only two-thirds of children on ART transferred to primary and community health clinics had successful transfer. These findings suggest that transfer is a particularly vulnerable step in the paediatric HIV care cascade.

WHO guidelines for management of severe malnutrition in rural South African hospitals: effect on case fatality and the influence of operational factors.

BACKGROUND: WHO case-management guidelines for severe malnutrition aim to improve the quality of hospital care and reduce mortality. We aimed to assess whether these guidelines are feasible and effective in under-resourced hospitals. METHODS: All children admitted with a diagnosis of severe malnutrition to two rural hospitals in Eastern Cape Province from April, 2000 to April, 2001, were studied and their case-fatality rates were compared with the rates in a period before guidelines were implemented (March, 1997 to February, 1998). Quality of care was assessed by observation of medical and nursing practices, review of medical records, and interviews with carers and staff. A mortality audit was used to identify cause of death and avoidable contributory factors. FINDINGS: At Mary Theresa Hospital, case-fatality rates fell from 46% before implementation to 21% after implementation. At Sipetu Hospital, the rates fell from 25% preimplementation to 18% during 2000, but then rose to 38% during 2001, when inexperienced doctors who were not trained in the treatment of malnutrition were deployed. This rise coincided with less frequent prescribing of potassium (13% vs 77%, p<0.0001), antibiotics with gram-negative cover (15% vs 46%, p=0.0003), and vitamin A (76% vs 91%, p=0.018). Most deaths were attributed to sepsis. For the two hospitals combined, 50% of deaths in 2000-01 were due to doctor error and 28% to nurse error. Weaknesses within the health system--especially doctor training, and nurse supervision and support--compromised quality of care. INTERPRETATION: Quality of care improved with implementation of the WHO guidelines and case-fatality rates fell. Although major changes in medical and nursing practice were achieved in these under-resourced hospitals, not all tasks were done with adequate care and errors led to unnecessary deaths.

WHO guidelines for severe malnutrition: are they feasible in rural African hospitals?

AIMS: To assess the feasibility of implementing and sustaining the WHO guidelines for inpatient management of severe malnutrition in under-resourced rural South African hospitals, and to identify any constraints. INTERVENTION: Three 2-day training workshops were held in 1998, followed by monthly 1-day visits for 5 months, ending in March 1999, in two rural district hospitals with limited resources in Eastern Cape Province, South Africa. METHODS: A 12-month observational study was conducted from April 2000 to April 2001 in Mary Theresa and Sipetu hospitals (Eastern Cape Province, South Africa), including 1011 child-hours of observation on the wards, medical record reviews, interviews with carers and staff, and inventories of essential supplies. All admissions (n = 193) for severe malnutrition to the two hospitals were studied. The main outcomes were the extent to which the 10 steps for routine care of severely malnourished children were implemented, proficiency of performance and constraining factors. RESULTS: The hospitals made the changes required in clinical and dietary management, but the tasks were not always performed fully or with sufficient care. Play and stimulation and an effective system of follow-up were not implemented. Doctors' poor knowledge, nurses' inattentiveness and insufficient interaction with carers were constraints to optimal management. The underlying factors were inadequate undergraduate training, understaffing, high doctor turnover and low morale. CONCLUSIONS: Guidelines for severe malnutrition are largely feasible but training workshops are insufficient to achieve optimal management as staff turnover and an unsupportive health system erode the gains made and doctors treat cases without having being trained. Medical and nursing curricula in Africa must include treatment of severe malnutrition.