Human vaccine and immunisation research in South Africa: A bibliometric study.

BACKGROUND: Research in human vaccines and immunisation plays a crucial role in shaping national, regional and global health policies aimed at controlling vaccine preventable diseases (VPDs). To our knowledge, the landscape of human vaccine and immunisation research in South Africa (SA) is not well characterised. OBJECTIVES: To characterise research in human vaccines and immunisation in SA. METHODS: We conducted a bibliometric study. Seven electronic databases (PubMed; Scopus; Web of Science; Cochrane; CINAHL; Africa-Wide Information; and MEDLINE (via EBSCOhost)) were searched for eligible studies published in English between 1 January 2007 and 31 March 2020. Selected primary studies needed to be on human vaccine and immunisation research conducted in SA. All types of reviews were excluded. For the included studies, outcomes of interest included publication journals, publication trends, types of studies and VPDs, targeted populations, as well as author affiliations. RESULTS: A total of 9 212 studies was retrieved. After screening for eligibility, 366 studies met the inclusion criteria. The key findings were as follows: (i) a total of 54 (14.8 %) articles on human vaccine and immunisation research in SA appeared in local journals, while 312 (85.2%) were in non-SA (international) journals; (ii) the number of publications on human vaccine and immunisation research in SA increased from 13 in 2007 to 47 in 2015; (iii) there were 189 (51.7%) operational studies and 177 (48.3%) clinical studies, with 88 (49.7%) of the latter being clinical trials; (iv) human vaccine and immunisation research in SA is conducted across all age groups, with a focus on children; and (v) authors of the identified research outputs and those mostly represented were from the universities of Cape Town and the Witwatersrand, Johannesburg. CONCLUSIONS: The landscape of human vaccine and immunisation research in SA is growing and adapting to the emerging trends in vaccinology, with a focus on the duo epidemic of HIV and TB, as well as Expanded Programme on Immunisation (EPI)-related vaccinations. This research contributes to locally relevant evidence that can be used to inform future vaccine and EPI-related research.

Lessons learnt during the national introduction of human papillomavirus (HPV) vaccination programmes in 6 African countries: Stakeholders' perspectives.

BACKGROUND: Infection with human papillomavirus (HPV) significantly increases the risk of developing cervical cancer later in life. Therefore, globally, HPV vaccines targeted to pre-adolescent and adolescent girls have been on the rise since the licensure in 2006. However, the introduction of HPV vaccines has been relatively slow in Africa. At the end of 2016, only 8 of the 54 countries in Africa were reported to have introduced HPV vaccination at a national level. By 2019, the number of countries had grown marginally to 11. OBJECTIVES: To investigate stakeholders' perspectives on the experiences, challenges and lessons learnt during national HPV vaccine introduction in Africa. METHODS: A questionnaire was administered to selected participants from 8 African countries. These countries had successfully introduced HPV vaccination at a national level by the end of 2016. We used in-depth interviews and self-administered online questionnaires for data collection and analysis. Data are presented without naming the country or participants; therefore, readers will not be able to identify the results that are specific to individual countries. Narrative and thematic reporting were used to describe the results. RESULTS: We obtained results from 6 of the 8 targeted countries. The challenges reported during HPV vaccination programmes were: identifying the target population, using a school-based vaccine-delivery strategy, obtaining political support, the need to integrate HPV vaccination with existing school health programmes and engaging multiple stakeholders. These challenges were similar in all 6 countries. The lessons learnt were that a school-based delivery strategy is a successful approach for national HPV vaccination, and that identifying girls for vaccination at schools was less challenging if implemented through a class-based instead of an age-based approach. CONCLUSIONS: Most African countries do not have established platforms to deliver vaccines to pre-adolescent and adolescent populations. The successful introduction of the HPV vaccine through school-based vaccination strategies in African countries may have created a platform to deliver other adolescent vaccines. The similarity of the study findings across the 6 participating countries further strengthens the need to document and disseminate the challenges and lessons learnt during HPV vaccine introduction in Africa. Documentation and dissemination of the challenges and lessons learnt are useful to other countries in Africa that plan to introduce an HPV vaccination programme, and possibly other adolescent vaccines.

Hepatitis A seroprevalence in Western Cape Province, South Africa: Are we in epidemiological transition?

BACKGROUND: Hepatitis A virus (HAV) is the most common cause of viral hepatitis worldwide. Hepatitis A vaccine is not included in the Expanded Programme on Immunisation in South Africa (EPI-SA), as the country is considered to be highly endemic for hepatitis A. OBJECTIVES: To determine the seroprevalence of hepatitis A infection in Western Cape Province (WCP), South Africa. METHODS: We conducted a cross-sectional seroprevalence study in the 1 - 7-year age group in WCP. Our samples (N=482) were blood specimens left over after laboratory testing obtained from referral hospitals between August and October 2015. A Siemens enzyme immunoassay was used to test for total hepatitis A antibodies. We also analysed hepatitis A immunoglobulin G antibody results from the National Health Laboratory Service (NHLS) Disa*Lab database at Groote Schuur Hospital from 2009 to 2014, and included 2009 - 2014 acute hepatitis A (immunoglobulin M-positive) surveillance data from the National Institute for Communicable Diseases to look at trends in notified acute infections over the same period. RESULTS: Our cross-sectional study showed 44.1% seroprevalence in the 1 - 7-year age group. Hepatitis A data from the NHLS database indicated a seroprevalence of <90% up to age 10 years, indicating intermediate endemicity. The surveillance data showed that a substantial number of symptomatic hepatitis A infections occurred in the 7 - 40-year age group, suggesting that an increasing proportion of the population is susceptible to HAV infection. CONCLUSIONS: These results suggest an urgent need for detailed evidence-based considerations to introduce hepatitis A vaccine into the EPI-SA.

Health activism in Cape Town: a case study of the Health Workers Society.

The Health Workers Society (HWS), founded in 1980, was one of several progressive health organisations that fought for a democratic health system in South Africa. We document the sociopolitical context within which it operated and some of its achievements. HWS, many of whose members were staff and students of the University of Cape Town (UCT), provided a forum for debate on health-related issues, politics and society, and worked closely with other organisations to oppose the apartheid state's health policies and practices. They assisted with the formation of the first dedicated trade union for all healthcare workers and were one of the first to pioneer the primary healthcare approach in an informal settlement in Cape Town.

Predictive factors for latent tuberculosis infection among adolescents in a high-burden area in South Africa.

SETTING: A high tuberculosis (TB) burden area in South Africa (notification rate for all TB cases 1400 per 100 000 population). OBJECTIVE: To determine the prevalence of and predictive factors associated with latent TB infection in adolescents. DESIGN: Adolescents aged 12-18 years were recruited from high schools, clinical and demographic data were collected, and a tuberculin skin test (TST) and a QuantiFERON®-TB Gold In-Tube (QFT) assay performed. RESULTS: A total of 6363 (58.2%) of 10 942 adolescents at the schools were enrolled. After exclusions, of 5244 participants, 55.2% (95%CI 53.8-56.5) had TST ≥ 5 mm, while 50.9% (49.5-52.2) were QFT-positive. On multivariate analysis, Black/mixed race racial groups, male sex, older age, household TB contact, low income and low education level were predictive factors for both TST- and QFT-positive results. CONCLUSION: About half of the adolescents were found to be latently infected with TB in a high TB burden area with demographic and poverty-related socio-economic factors predicting the risk of TB infection. Adolescents from deprived communities should be considered an important target group for educational interventions by TB control programmes in high-burden settings.

Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants.

This document outlines the consensus agreement from the Union's BCG Working Group regarding BCG vaccination in HIV-infected infants, in response to recently revised World Health Organization (WHO) guidelines, which make HIV infection in infants a full contraindication to bacille Calmette-Guérin (BCG) vaccination. BCG is one of the most widely given vaccines globally and is safe in immunocompetent individuals. Recent evidence shows that HIV-infected infants who were routinely vaccinated with BCG at birth, when asymptomatic, and who later developed AIDS, are at high risk of developing disseminated BCG disease (estimated incidence 407-1300 per 100 000). The document outlines requirements to implement selective BCG vaccination strategies in infants born to HIV-infected women and strategies to reduce the risk of vertical HIV transmission and disseminated BCG disease in infants.

Are adolescents ready for tuberculosis vaccine trials?

Tuberculosis (TB) vaccine trials are planned in adolescents in a high tuberculosis burden rural area near Cape Town, South Africa. To determine the knowledge and attitudes of adolescents about tuberculosis, vaccines and vaccine trials, a representative sample of adolescent learners was chosen from high schools in the trial area. A questionnaire was administered and focus group discussions held with the group and a sample of their parents. The questionnaire response rate was 65%. Knowledge of tuberculosis was fair 63.7% but knowledge of vaccines poor 41.9% based on a TB and vaccine knowledge score, respectively. Willingness to participate in vaccine trials will be influenced by the type of procedures involved (60% willing to answer questions, 43% willing to be examined, 32% willing to undergo skin tests and 39% willing to undergo blood draw). In general, better knowledge was statistically associated with greater willingness to participate in study procedures except for the blood draw. The focus group discussions showed that adolescents and their parents were positive about participating in vaccine trials but concerns about safety and the provision of adequate information should be considered when planning TB vaccine trials. This study suggests that TB vaccine trials would be acceptable amongst adolescents in this community with certain provisos.

Comparison of mantoux skin test with three generations of a whole blood IFN-gamma assay for tuberculosis infection.

SETTING: A rural town in South Africa. OBJECTIVE: To compare the performance of Quanti-FERON assays with the tuberculin skin test (TST) for identifying latent tuberculosis infection (LTBI) in a high TB burden community. DESIGN: In a cross-sectional study in healthy adults, we applied the TST and took blood for the three generations of QuantiFERON assays. RESULTS: Of 358 participants whose results were analysed, 291 (81%) had a TST result of > or = 10 mm induration, and 187 (52%) > or = 15 mm. QuantiFERON-TB was positive in 215 (60%), QuantiFERON-TB Gold in 137 (38%), and QuantiFERON-TB Gold (In-Tube method) in 201 (56%). There was poor agreement between TST and QuantiFERON tests, and between the different generations of QuantiFERON tests (kappa = 0.12-0.50). Of the subset with TST indurations > or = 15 mm, 30-56% had negative QuantiFERON tests. However, positive Quanti-FERON tests were associated with males, who have a higher incidence of TB in this area. CONCLUSION: We showed poor agreement between TST and the different QuantiFERON tests in diagnosing LTBI. The surprising discordance between the Quanti-FERON TB Gold and QuantiFERON TB Gold (In-Tube method) tests needs to be investigated further.

Outcome of HIV infected children with culture confirmed tuberculosis.

BACKGROUND: Tuberculosis (TB) is an important disease in human immunodeficiency virus (HIV) infected children living in regions where TB is endemic. There are limited data on the outcome of culture confirmed TB in HIV infected children. AIMS AND METHODS: To describe the outcome on TB therapy and overall mortality in HIV infected children with culture confirmed TB through a retrospective cohort study. RESULTS: Eighty seven children, median age 24 months, contributed to 93 TB episodes; six children had two confirmed episodes. Pulmonary disease (PTB) was present in 71 episodes (76.3%), extrapulmonary disease (EPTB) in 43 (46.2%), and of these, both PTB and EPTB were present in 21 (22.6%). There was cure based on bacteriological and/or radiological criteria in 54 episodes (58.1%). Eighteen children died during TB therapy and there were a total of 34 deaths (39.1%). In univariate analysis (n = 87 patients), severe malnutrition, age < or =1 year, and a negative tuberculin skin test were significant risk factors for death during TB therapy. In multivariate survival analysis (n = 87 patients), HIV disease category, severe malnutrition at diagnosis, and lack of cure at the end of TB therapy were significantly associated with overall mortality. CONCLUSION: In the absence of antiretroviral therapy, HIV infected children with confirmed TB have poor outcomes on antituberculosis therapy and are at high risk of death during and after completion of antituberculosis therapy, especially due to non-TB related causes. There is an urgent need to optimise and monitor antituberculosis therapy in HIV infected children and to improve access to TB and other preventative therapy.

Plasma vitamin A and zinc levels in HIV-infected adults in Cape Town, South Africa.

A cross-sectional study of 132 adults attending an HIV clinic in Cape Town, South Africa, was conducted to determine predictors of low plasma vitamin A and Zn levels. No patients were on antiretroviral therapy. The possible confounding effect of the acute-phase response was controlled by including C-reactive protein levels in multivariate analysis and by excluding active opportunistic infections. Retinol levels were low (<1.05 micromol/l) in 39 % of patients with early disease (WHO clinical stages I and II) compared with 48 and 79 % of patients with WHO stage III and IV respectively (P<0.01). Plasma Zn levels were low (<10.7 micromol/l) in 20 % of patients with early disease v. 36 and 45 % with stage III and IV disease respectively (P<0.05). C-reactive protein levels were normal in 63 % of subjects. Weak, positive associations were found between CD4+ lymphocyte count and plasma levels of retinol (r 0.27; 95 % CI 0.1, 0.43) and Zn (r 0.31; 95 % CI 0.25, 0.46). Multivariate analysis showed the following independent predictors of low retinol levels: WHO stage IV (odds ratio 3.4; 95 % CI 2.1, 5.7) and body weight (odds ratio per 5 kg decrease 1.15; 95 % CI, 1.08, 1.25), while only body weight was significantly associated with low Zn levels (OR per 5 kg decrease 1.19; 95 % CI 1.09, 1.30). CD4+ lymphocyte count <200/microl was not significantly associated with either low retinol or Zn levels. In resource-poor settings, simple clinical features (advanced disease and/or weight loss) are associated with lowered blood concentrations of vitamin A and/or Zn. The clinical significance of low plasma retinol and/or Zn levels is unclear and more research is required to establish the role of multiple micronutrient intervention strategies in HIV disease.

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.

Duration of illness in ambulatory children diagnosed with bronchiolitis.

OBJECTIVES: To measure the duration of illness in ambulatory children diagnosed with bronchiolitis and to examine clinical predictors of duration of illness. DESIGN: Validation inception cohort study. Duration of follow up was 28 days. SETTING: A primary-level ambulatory department of a public sector children's hospital in Cape Town, South Africa. PATIENTS: One hundred eighty-one children aged 2 to 23 months who went to the hospital as their first contact for that episode of illness, and had a clinical diagnosis of bronchiolitis were enrolled consecutively on weekday mornings if their guardian stated that they were contactable by telephone. MAIN OUTCOME MEASURE: Resolution of symptoms, as judged by the guardian, measured by twice-weekly telephone interviews. RESULTS: Median duration of illness (calculated as the reported duration of symptoms before initial hospital visit plus the time from first consultation to recovery) was 12 days (95% confidence interval, 11-14 days). After 21 days, 18% were still ill and after 28 days, 9% were still ill. Sixty-two patients (34.2%) had unscheduled consultations within 28 days, a median of 13 days after the first consultation. There was no association of duration of illness with age, sex, z score for weight for age, or respiratory rate. CONCLUSIONS: Ambulatory children diagnosed with bronchiolitis recover with few complications, but the resolution of symptoms may take several weeks. Providing parents with this information could help reduce the high rate of unscheduled return visits as observed in this cohort.

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.

Twice weekly vs. daily chemotherapy for childhood tuberculosis.

BACKGROUND: Treating childhood tuberculosis places a large burden on health services, and ways of lessening this were sought. METHODS: A randomized controlled trial was conducted to determine the effectiveness of fully intermittent twice weekly treatment for intrathoracic childhood tuberculosis and its effect on adherence to treatment, in comparison with daily (weekday) treatment. The setting was a district of Cape Town, South Africa, an area of high incident tuberculosis. We randomized 206 children with confirmed (4%), probable (94%) and suspected (2%) intrathoracic tuberculosis: 89 (median age, 25 months) received intermittent treatment; and 117 (median age, 28 months) received daily treatment. Intermittent treatment (twice weekly for 6 months) was isoniazid 15 mg/kg/dose, rifampin 15 mg/kg/dose and pyrazinamide 55 mg/kg/dose for 2 months, followed by isoniazid and rifampin only for 4 months. Daily treatment was isoniazid 10 mg/kg/day, rifampin 10 mg/kg/day and pyrazinamide 25 mg/kg/day on weekdays for 6 months. RESULTS: At 6 months 97% of subjects were discharged, with treatment outcomes in the two groups equivalent at that time (P = 0.90) and at the 18- to 30-month follow-up. One relapse occurred in the twice weekly group (P = 0.25). Adherence was equivalent; 70 children (79%) on intermittent and 90 (77%) on daily treatment took 75% or more of the prescribed doses (P = 0.90). Nonadherence over the full course of therapy was significantly associated with nonadherence during the first month of treatment (P = 0.0002) and household crowding (P = 0.002). CONCLUSIONS: Six month fully intermittent antituberculosis treatment is an effective and acceptable alternative to daily treatment.

Effect of vitamin A therapy on serologic responses and viral load changes after influenza vaccination in children infected with the human immunodeficiency virus.

Vitamin A administered to children infected with the human immunodeficiency virus before influenza vaccination in a double-blind randomized study did not enhance vaccine serologic responses but did dampen the increase in the human immunodeficiency virus viral load 14 days after immunization (vitamin A, decrease of 0.13 +/- 0.09 log(10) copies/mL; placebo, increase of 0.14 +/- 0.08, P =.02).

Immunological manifestations of HIV-infected children.

This cross-sectional study of stable HIV-infected children was designed to document the immunological manifestations of paediatric HIV infection and to determine whether inexpensive markers of immunosuppression could be identified. Investigations included lymphocyte count and subset analysis, levels of total protein, albumin, immunoglobulins, beta-2 microglobulin and neopterin. The median age of the 74 children studied was 16.5 months and 76% and 39% had subnormal percentage CD4+ counts and absolute CD4+ counts, respectively. According to the Centers for Disease Control (CDC) guidelines, 85% were moderately or severely immunosuppressed. The majority had elevated neopterin, beta-2 microglobulin, IgG, IgM and IgA concentrations. The IgG concentration correlated positively with total globulin, IgG1 and IgG3 concentrations. On bivariate analysis, the absolute CD4+ count correlated positively with total lymphocyte count (r = 0.28 < 0.48 < 0.64) and negatively with total IgG concentration (r = -0.47 < -0.27 < -0.04), IgG1 concentration (r = -0.51 < -0.31 < -0.08), and neopterin concentration (r = -0.49 < -0.28 < -0.04). There was no correlation between CD4+ count, total globulin or beta-2 microglobulin concentration. On multiple linear regression analysis only the total lymphocyte count correlated with CD4+ count. Furthermore, on bivariate analysis total lymphocyte count correlated positively with absolute CD8+ count (r = 0.82 < 0.88 < 0.92). In conclusion, although there was a positive correlation between absolute CD4+ count and total lymphocyte count, the clinical significance is questionable as the total lymphocyte count correlated more strongly with the absolute CD8+ count.

Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time.

Survival of children in Cape Town known to be vertically infected with HIV-1.

OBJECTIVE: To determine the survival patterns of children in Cape Town known to be vertically infected with HIV. DESIGN: Retrospective record review of children diagnosed with symptomatic HIV infection during the period 1 December 1990-31 May 1995. SETTING: Hospitals in the Cape Town metropolitan area. PATIENTS: 193 children were known to be vertically HIV-infected. HIV diagnosis was based on the following criteria: two positive HIV enzyme-linked immunosorbent assays (ELISAs) in children older than 15 months and a positive ELISA together with a positive polymerase chain reaction (PCR) in younger children. The mothers of the children were known to be HIV-positive. On the basis of the presenting clinical findings children were assigned to a disease severity category (A, B or C) according to the Centers for Disease Control and Prevention (CDC)'s 1994 revised classification system for HIV infection in children. OUTCOME MEASURES: Survival was analysed according to the Kaplan-Meier method. Survival time was defined as the length of time between clinical diagnosis of HIV and death or last contact with the health services. Mortality risk in relation to specific variables at diagnosis such as age and clinical manifestations was determined by calculation of odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The median age at diagnosis was 5 months; 72% of children were aged less than 1 year at diagnosis. According to the CDC clinical classification, 47 (24%) fell into category A, 111 (58%) into category B and 35 (18%) into category C. Of the 193 patients 85 (44%) were alive at the time of review, 65 (34%) had died and 43 (22%) were lost to follow-up. Risk of death was significantly associated with age less than 6 months (OR 4.7, CI 2.1-10.3) and severe disease, i.e. CDC category C (OR 2.7; CI 1.1-6.9) at time of diagnosis. The median survival for all the children from time of diagnosis was 32 months. Infants diagnosed before 6 months of age had significantly shorter median survival (10 months) compared with 36 months for those diagnosed at 7-12 months of age. For the children over the age of 12 months the cumulative proportion surviving at 48 months was 78%. Children with severe disease (category C) had a median survival of 21 months, significantly lower than that in category B (32 months). For the children in category A the cumulative proportion surviving at 48 months was 66%. CONCLUSION: The median survival of children with HIV was 32 months from time of diagnosis, and survival was influenced by age and disease severity.

Randomised controlled trial of clinical outcome after chest radiograph in ambulatory acute lower-respiratory infection in children.

BACKGROUND: When available, chest radiographs are used widely in acute lower-respiratory-tract infections in children. Their impact on clinical outcome is unknown. METHODS: 522 children aged 2 to 59 months who met the WHO case definition for pneumonia were randomly allocated to have a chest radiograph or not. The main outcome was time to recovery, measured in a subset of 295 patients contactable by telephone. Subsidiary outcomes included diagnosis, management, and subsequent use of health facilities. FINDINGS: There was a marginal improvement in time to recovery which was not clinically significant. The median time to recovery was 7 days in both groups (95% CI 6-8 days and 6-9 days in the radiograph and control groups respectively, p=0.50, log-rank test) and the hazard ratio for recovery was 1.08 (95% CI 0.85-1.34). This lack of effect was not modified by clinicians' experience and no subgroups were identified in which the chest radiograph had an effect. Pneumonia and upper-respiratory infections were diagnosed more often and bronchiolitis less often in the radiograph group. Antibiotic use was higher in the radiograph group (60.8% vs 52.2%, p=0.05). There was no difference in subsequent use of health facilities. INTERPRETATION: Chest radiograph did not affect clinical outcome in outpatient children with acute lower-respiratory infection. This lack of effect is independent of clinicians' experience. There are no clinically identifiable subgroups of children within the WHO case definition of pneumonia who are likely to benefit from a chest radiograph. We conclude that routine use of chest radiography is not beneficial in ambulatory children aged over 2 months with acute lower-respiratory-tract infection.

PIP: The impact of chest radiographs on the diagnosis, treatment, follow-up, and clinical outcome of children with ambulatory acute lower-respiratory infections was assessed in 518 children 2-59 months old who presented to the Red Cross Hospital in Cape Town, South Africa, with symptoms consistent with the World Health Organization case definition of pneumonia. 257 were randomly assigned to receive a radiograph and 261 were controls (no diagnostic intervention). The median time to recovery, measured in a subset of 295 children whose parents were reachable by telephone, was 7 days for both cases and controls (95% confidence intervals, 6-8 and 6-9 days, respectively). The unadjusted Cox proportional hazards ratio for recovery for the radiograph group compared with controls was 1.08 (95% confidence interval, 0.85-1.34). This rate was unaffected by adjustment for age, weight for age, duration of symptoms before presentation, respiratory rate, clinician's postgraduate pediatric qualifications, and clinician's perception of the need for chest radiograph. More radiograph patients were diagnosed with pneumonia or upper-respiratory infection, while a higher proportion of controls were diagnosed as having bronchiolitis. 149 children in the radiograph group (60.8%) compared with 133 controls (52.2%) received antibiotics. There was no difference in subsequent use of health facilities. These findings indicate that there are no clinically identifiable subgroups of children likely to benefit from routine use of chest radiography.