Short-term outcomes of down-referral in provision of paediatric antiretroviral therapy at Red Cross War Memorial Children's Hospital, Cape Town, South Africa: A retrospective cohort study.

BACKGROUND: The large scale-up of paediatric HIV care necessitated down-referral of many children receiving antiretroviral therapy (ART) from Red Cross War Memorial Children's Hospital (RCWMCH), Cape Town, South Africa. Few published data exist on the outcomes of these children. OBJECTIVES: To assess outcomes of children receiving ART in the first 12 months after down-referral to primary healthcare (PHC) clinics and identify determinants of successful down-referral. METHODS: A retrospective cohort study of children <15 years of age who initiated ART at RCWMCH and were subsequently down-referred to one of two PHC clinics between January 2006 and December 2012 was completed. Baseline characteristics of patients and caregivers as well as CD4+ counts, viral loads (VLs) and weights were collected 6 and 12 months after down-referral. Outcomes included retention in care and viral suppression. RESULTS: Of 116 children down-referred to the two study PHC clinics, 81.9% arrived at the designated PHC clinic and a further 8.6% continued care at other clinics, the remaining 9.5% being lost to follow-up. Of those successfully down-referred, 11.4% took >8 weeks to present, possibly experiencing treatment interruption. At 12 months after down-referral, only 81.0% remained in care. No factors were associated with retention in care in multivariable analysis. For children who remained in care at the designated PHC clinics, the clinical and immunological gains achieved prior to down-referral were sustained through 12 months of follow-up, and 54.7% of this cohort had documented viral suppression at 12 months. However, if only children with VL results are considered, 75.9% (41/54) were virally suppressed 12 months after down-referral. CONCLUSIONS: Down-referral of children on ART is complex, with risk of loss to follow-up and treatment interruption.

Sputum induction for microbiological diagnosis of childhood pulmonary tuberculosis in a community setting.

SETTING: Sputum induction has increasingly enabled microbiological confirmation of pulmonary tuberculosis (PTB) in hospitalised children, but it has not been evaluated in a community setting. OBJECTIVE: To investigate the yield, feasibility and safety of sputum induction for the diagnosis of TB in children in a primary health care facility. DESIGN: A prospective study in a primary health care clinic in South Africa from April 2007 to June 2009. Consecutive children with clinically suspected PTB, with a household adult PTB contact or human immunodeficiency virus infected with respiratory symptoms were enrolled. History, clinical examination, tuberculin skin test and chest X-ray results were recorded. Two sequential induced sputum specimens were obtained for smear and culture. RESULTS: A total of 270 children were enrolled (median age 38 months); sputum induction was successful in 269 (99%); 65 (24%) children were clinically diagnosed, of whom 11 (16.9%) were microbiologically confirmed. An additional 18 children not clinically diagnosed had microbiological confirmation of PTB and were placed on TB treatment thereafter, increasing the diagnostic yield by 21.6%, from 65 to 83 cases. Sputum induction procedures were well tolerated; no major adverse events occurred. CONCLUSION: Sputum induction is feasible and safe in a community setting. Sputum induction was useful for making a microbiological diagnosis, increasing the number of children diagnosed and treated for PTB.

The immunomodulatory effects of thalidomide on human immunodeficiency virus-infected children.

The safety and immune effects of low-dose thalidomide treatment (3 mg/kg/day for 28 days) were evaluated in a study involving 8 South African human immunodeficiency virus (HIV)-infected children. The children were 7-69 months old and in disease stages A1-C3. Thalidomide therapy did not affect virus load, even though none of the children was receiving antiretroviral therapy. Thalidomide stimulated CD8+ T cells in peripheral blood, which increased expression of the activation markers CD38 and human leukocyte antigen DR and of the memory cell marker CD45RO. The frequency of HIV gag-specific CD8+ T cells in peripheral blood increased in 3 of 4 children who were evaluated during treatment with thalidomide. Clinical adverse events were mild. In this study, thalidomide was found to be safe and well tolerated and caused significant immunomodulation at a low dose. This is the first report describing use of an oral drug that may enhance HIV-specific CD8+ T cell function in HIV-infected children.

Pneumocystis carinii pneumonia in South African children infected with human immunodeficiency virus.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) has been regarded as uncommon in HIV-infected patients in Africa, but diagnostic difficulties and geographic variability may partly account for this. There is little information on the incidence of PCP in HIV-infected children in Africa. AIM: To investigate (1) the incidence and associated features of PCP in African HIV-infected children and (2) the usefulness of sputum induction and nasopharyngeal aspirates (NPAs) for diagnosis of PCP. METHODS: HIV-infected children hospitalized with pneumonia were prospectively enrolled in a 1-year study in South Africa. History, examination, chest radiology and blood tests (including HIV testing) were performed. Sputum induction (5% NaCl nebulization) or nondirected bronchoalveolar lavage in intubated patients was performed for P. carinii identification using immunofluorescence and silver stain; immunofluorescence was also done on nasopharyngeal aspirates (NPAs). RESULTS: Of 151 HIV-infected children [47% female; median age, 9 (range, 3 to 23) months], 87 had been previously diagnosed with HIV whereas 64 (42.4%) were found to be HIV-positive at the time of admission. PCP occurred in 15 children (9.9%; 95% confidence interval, 5.9 to 15.5) and was the AIDS-defining infection in 13 of 64 (20.3%; 95% confidence interval, 11.8 to 31.5). Only 1 of 59 children receiving prophylaxis (1.7%) developed PCP compared with 14 of 92 (15.2%) not taking prophylaxis [relative risk, 0.11 (0.02 to 0.82), P = 0.007]. PCP-infected children were younger [3 (range, 3 to 4) vs. 10 (range, 4 to 24) months, P < 0.001] and presented with more severe pulmonary disease as indicated by a higher respiratory rate [63 (range, 60 to 73) vs. 50, (range, 40 to 60) P < 0.001], heart rate [160 (range, 136-180) vs. 140 (range, 120-152) P = 0.025] and a greater incidence of cyanosis (53% vs. 26%, P = 0.025). Clinical signs of HIV infection, occurring in 96% of children, were equally prevalent in both groups. High serum lactate dehydrogenase was the only laboratory investigation that distinguished PCP-infected from uninfected children [626 (range, 450 to 1098) vs. 307 (range, 243 to 465) units/l], P < 0.001. No radiologic features were found to be diagnostic of PCP. P. carinii was identified in 9 sputa and 6 bronchoalveolar lavage specimens, but all corresponding NPAs were negative. Seven of 15 (47%) children with PCP died while hospitalized compared with 24 of 136 (18%) without PCP [relative risk, 1.21 (range, 0.99 to 1.47), P = 0.008]. CONCLUSION: PCP is an important pathogen in HIV-infected infants in South Africa and is associated with a high mortality. Induced sputum is effective for obtaining lower respiratory tract secretions for diagnosis of PCP but an NPA is not useful.

Respiratory syncytial virus infection in children hospitalised with acute lower respiratory tract infection.

BACKGROUND: Data are lacking on respiratory syncytial virus. (RSV) respiratory tract infections in children from developing countries. OBJECTIVE: To determine the importance of RSV as a cause of acute lower respiratory tract infection (ALRTI) in Cape Town children. METHODS: Children younger than 2 years of age admitted to hospital with ALRTI over a 15-month period from 1 June 1995 to 31 August 1996 were studied prospectively. Sociodemographic data, risk factors for severe RSV disease, clinical signs, diagnosis and hospital course were documented. A nasopharyngeal aspirate (NPA) for detection of RSV by enzyme immunoassay (EIA) was obtained in all cases. The NPA of every fifth child was sent for viral culture. RESULTS: A total of 1,288 patients (60% male, 40% female) with a median age (25th-75th percentile) of 6 months (2-11 months) was enrolled; 32.4 had one or more risk factors for severe RSV infection. Pneumonia was diagnosed in 62.2%, bronchiolitis in 20.6%, laryngotracheobronchitis (LTB) in 8% and other respiratory illnesses in 9.2%. Mild disease, requiring admission to an overnight ward, was documented in 38.1%, while 48.9% and 13% respectively had moderate and severe disease requiring admission to a general ward and intensive care unit (ICU). Supplemental oxygen and mechanical ventilation were required by 68.9% and 8.5% of patients, respectively. The median duration of hospital stay was 5 days (range 1-10 days). RSV EIA was positive in 16.4% of cases, and there was no difference in detection rates according to diagnosis. Viral culture performed in 162 of the 1,288 study patients (12.6%) grew RSV in 11.7% of cases, adenovirus in 3.7%, para-influenza virus type 3 in 2.5% and influenza B virus in 0.6%. Patients who tested RSV EIA-positive did not significantly differ from those who tested negative with regard to demographic variables, clinical diagnoses, risk factors for RSV or length of hospitalisation. The only significant difference noted was the presence of hyperinflation, which occurred in 70.1% of EIA-positive patients compared with 57.1% of those testing negative (P = 0.0005). The mortality rate (2%) was similar for both groups. CONCLUSION: This study indicates that RSV is an important cause of hospitalisation in infants and young children with ALRTI. Distinguishing RSV from other ALRTIs is difficult because of similarity in clinical presentation among children.

Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa.

BACKGROUND: Bacteriological confirmation of pulmonary tuberculosis is difficult in infants and young children. In adults and older children, sputum induction has been successfully used; this technique has not been tested in younger children. AIMS: To investigate whether sputum induction can be successfully performed in infants and young children and to determine the utility of induced sputum compared to gastric lavage (GL) for the diagnosis of pulmonary tuberculosis in HIV infected and uninfected children. SUBJECTS AND METHODS: 149 children (median age 9 months) admitted to hospital with acute pneumonia who were known to be HIV infected, suspected to have HIV infection, or required intensive care unit support. Sputum induction was performed on enrollment. Early morning GL was performed after a minimum four hour fast. Induced sputum and stomach contents were stained for acid fast bacilli and cultured for Mycobacterium tuberculosis. RESULTS: Sputum induction was successfully performed in 142 of 149 children. M tuberculosis, cultured in 16 children, grew from induced sputum in 15. GL, performed in 142 children, was positive in nine; in eight of these M tuberculosis also grew from induced sputum. The difference between yields from induced sputum compared to GL was 4.3% (p = 0.08). M tuberculosis was cultured in 10 of 100 HIV infected children compared to six of 42 HIV uninfected children (p = 0.46). CONCLUSION: Sputum induction can be safely and effectively performed in infants and young children. Induced sputum provides a satisfactory and more convenient specimen for bacteriological confirmation of pulmonary tuberculosis in HIV infected and uninfected children.