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.     

Finger clubbing in children with human immunodeficiency virus infection

We investigated the frequency of finger clubbing in 150 HIV-infected children consecutively hospitalized for acute pneumonia in South Africa and described associated clinical, laboratory and radiological features. Clubbing occurred in 30 of 150 (20%) HIV-infected children compared with one of 99 (1%) HIV-negative control patients, p < 0.001. Clubbing was associated with lower presenting heart and respiratory rates and enlarged parotid glands. Total and CD4 + lymphocytes, CD4:CD8 ratio and LDH were lower in children with clubbing, but serum protein and gammaglobulin were higher. No differences in the prevalence or type of microbial pathogens were found between the two groups. Clubbing was associated with a radiological diagnosis of LIP. Children with clubbing had a lower in-hospital mortality rate than those without clubbing (6.7% vs 24.2%, p = 0.035). In geographical areas with high HIV seroprevalence rates, the presence of clubbing in a child hospitalized for respiratory disease should raise the suspicion of HIV infection.     

Pneumocystis carinii severe pneumonia among human immunodeficiency virus-infected children in Thailand: the effect of a primary prophylaxis strategy

BACKGROUND: A knowledge of the epidemiology of Pneumocystis carinii pneumonia (PCP) is important for the development of a strategy for primary PCP prophylaxis and empiric treatment for severe pneumonia in HIV-infected children. However, little is known about the epidemiology of PCP in developing countries. Objective. To measure the relative rate of PCP among hospitalized HIV-infected children with severe pneumonia in Bangkok and evaluate the effect of a strategy of primary PCP prophylaxis in HIV-exposed infants. METHODS: All HIV-infected children hospitalized from January, 1996, to December, 1997, for severe pneumonia were investigated for PCP with the use of specimens obtained from bronchoalveolar lavage, endotracheal aspiration or lung tissue necropsy. Characteristics associated with severe pneumonia were described, and the differences between PCP and non-PCP in these severely ill children were analyzed. In June, 1996, a strategy of primary PCP prophylaxis using trimethoprim-sulfamethoxazole in all HIV-exposed infants from 1 to 6 month of age was initiated in our institution. The effect of this strategy was evaluated. RESULTS: Of 279 hospitalized HIV-infected children 128 (46%) were diagnosed with pneumonia and 26 (20%) of these had severe pneumonia. P. carinii was identified in 9 (35%) children with severe pneumonia. After June, 1996, the rate of severe pneumonia among all hospitalized children decreased from 16% from January through June, 1996, to 7% from July, 1996, through December, 1997 (P = 0.02). Cases of PCP decreased from 9 in 1996 to zero in 1997. The percentage of HIV-infected children receiving PCP prophylaxis at the time of admission increased from 53% before June, 1996, to 72% in late 1997 (P = 0.04). The overall percentage of patients with severe pneumonia receiving PCP prophylaxis at the time of admission was 34%. Breakthrough PCP occurred in 2 children with poor compliance. Patients with PCP were significantly younger than those without PCP (mean age, 10.6+/-10.6 vs. 29.8+/-28.3 months, P = 0.02). CONCLUSION: PCP occurred in one-third of cases of severe pneumonia in HIV-infected children in Bangkok. The data suggest that PCP prophylaxis can prevent both PCP and non-PCP.     

Human immunodeficiency virus and urinary tract infections in children

This was a retrospective study of HIV-infected children aged 0-12 years attending the King Edward VIII Hospital in Durban, South Africa over a 5-year period (January 1996 to December 2001) with culture-proven urinary tract infection (UTI). UTI was defined as the presence of a single bacterial growth of >10(5) colony-forming units/ml in a clean-catch, mid-stream urine sample or >10(3) organisms/ml in a catheter or suprapubic aspirate of urine. HIV/AIDS was diagnosed in accordance with World Health Organization and/or Centers for Disease Control criteria. Comparison between HIV-positive and HIV-negative children with UTI was done using the chi2 and Wilcoxon rank sum tests. Of the 55 children recruited into the study, 29 (52.1%) were HIV-positive and 26 (47.3%) HIV-negative. Escherichia coli was isolated in 50 (87.2%) children. Clinical presentation, aetiological agents, response to therapy and renal function were similar in both groups. This study showed no significant impact of HIV/AIDS on the presentation of UTI in children.     

The impact of HIV infection and trimethoprim-sulphamethoxazole prophylaxis on bacterial isolates from children with community-acquired pneumonia in South Africa

The aim of this study was to compare the type and antimicrobial resistance patterns of bacteria cultured from blood or respiratory tract secretions by HIV status and the use of trimethoprim-sulphamethoxazole (TMP-SMX) prophylaxis in children hospitalized with community-acquired pneumonia. During a 1-year prospective study in Cape Town, South Africa, 250 children [median aged 6 (3-16) months] hospitalized with pneumonia were enrolled; 151 (60.4 per cent) were HIV-infected. The incidence of bacteremia [35 of 244 cultures (14.3 per cent)] did not differ by HIV status. Bacteria were cultured in 17 of 32 (53 per cent) bronchoalveolar lavage specimens (BAL), 128 of 210 (61 per cent) induced sputa and 166 of 231 (71 per cent) nasopharyngeal specimens (NPAs). The type and number of bacteria in respiratory secretions did not differ by HIV status, except for a higher rate of Staphylococcus aureus in sputum or BAL [22 of 146 (15 per cent) vs. 3 of 96 (3 per cent), p = 0.003] and NPAs [41 of 135 (30 per cent) vs. 9 of 96 (9 per cent), p < 0.001] of HIV-positive children. The use of TMP-SMX prophylaxis in HIV-infected children was associated with an increased nasopharyngeal carriage of S. aureus [22 of 51 (43 per cent) vs. 17 of 79 (22 per cent), p = 0.009]. The rising prevalence of HIV infection and the use of TMP-SMX prophylaxis may alter the spectrum of colonizing and pathogenic bacteria in children in developing countries.     

Pathology and causes of death in a series of human immunodeficiency virus-positive and -negative pediatric referral hospital admissions in Botswana

BACKGROUND: Little is known about causes of death among children seriously affected by the AIDS epidemic in southern African countries. METHODS: Autopsies were performed on 47 children 1 month to 13 years of age in Francistown, Botswana, between July 1997 and July 1998. RESULTS: Median age was 10 months; 68% were HIV-positive. The leading cause of death was respiratory infection, accounting for 29 of 35 (83%) deaths among HIV-positive and 8 of 12 (67%) deaths among HIV-negative children. Among HIV-positive children, Pneumocystis carinii pneumonia (PCP) was responsible for 31% of all deaths and for 48% of deaths in infants < or =1 year. Among children < or =2 years with cough and dyspnea, age < or =1 year, interstitial infiltrate and HIV positivity were highly predictive of PCP (sensitivity, 100%; specificity, 63%). CONCLUSION: Respiratory disease accounted for most deaths in HIV-positive children. Children < or =1 year who are known or suspected to be HIV-positive and who have cough, dyspnea and pulmonary infiltrates should be treated presumptively for PCP.     

Paediatric hospital admissions at a South African urban regional hospital: the impact of HIV, 1992-1997

Rates of infection by the human immunodeficiency virus (HIV) have been increasing rapidly in South Africa over the last decade. This study documents the changes over time in prevalence of HIV infection amongst hospitalized children, and its effects on the profile of disease and in-hospital mortality over the period 1992-1997. Admissions to the paediatric medical wards between January 1992 and April 1997 were obtained from the routine computerized database held in the Department of Paediatrics at Chris Hani Baragwanath Hospital. HIV tests were performed on clinical indications only. Over the study period there were 22,633 admissions involving 19,918 children. Total annual admissions increased by 23.6% between 1992 and 1996. Prevalence of HIV infection increased from 2.9% in 1992 to 20% in 1997. HIV-infected children had a younger age distribution, longer median length of stay and more readmissions (p < 0.001) compared with HIV-negative and untested children. HIV-infected children accounted for the increased number of admissions for pneumonia, gastro-enteritis, malnutrition and tuberculosis, and the rise in in-hospital mortality by 42% from 4.3% in 1992 to 6.1% in 1997. Paediatric HIV infection has changed the profile of paediatric admission diagnoses and increased in-hospital mortality in the relatively short time between 1992 and 1997. Over the same period, HIV-negative children showed declining rates of malnutrition, vaccine-preventable diseases and admission to the intensive care unit.     

Comorbidities and mortality among children hospitalized with diarrheal disease in an area of high prevalence of human immunodeficiency virus infection

PURPOSE: To describe the profile of comorbidities in children admitted with diarrhea to an urban hospital with high human immunodeficiency virus (HIV) prevalence in South Africa and to examine the contribution of comorbidities to inpatient mortality. METHODS: Data from a retrospective random sample of 319 children were extracted and analyzed from a total of 1145 children hospitalized for diarrhea in 2001. We used multiple logistic regression models to determine the independent effects of HIV infection, malnutrition, pneumonia and bacteremia on inpatient mortality. RESULTS: Overall 68% of the diarrheal admissions were classified as HIV-infected and 61% were classified as malnourished, with 53% having evidence of both. HIV infection was strongly associated with malnutrition, pneumonia and bacteremia. Inpatient mortality was 14% [95% confidence interval (CI), 11-19%]. Mortality was higher among HIV-infected than among uninfected children [crude odds ratio (OR), 6.0; 95% CI 2.1-17.0]. History of low birth weight, previous admission, malnutrition, HIV infection, pneumonia, bacteremia, low hemoglobin, total white blood cell count and serum albumin were significant predictors of mortality in univariate analyses. After adjustment, severe malnutrition (OR 2.1; 95% CI 1.0-4.9), bacteremia (OR 2.9; 95% CI 1.2-7.2) and pneumonia (OR 3.9; 95% CI 1.3-12.0) remained independent predictors of mortality, whereas the association between HIV infection and mortality was significantly diminished (OR 4.0; 95% CI 0.8-18.1). CONCLUSION: In a setting of high HIV prevalence, malnutrition, bacteremia and pneumonia contribute independently to death in children hospitalized with diarrheal disease.     

Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?

Aim: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Methods: The population consisted of infants born to HIV-infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow-up visits at 1 wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infant's HIV status was assessed according to a predetermined algorithm. Results: HIV-infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91-20.63, p = 0.05]. During the first 2 mo of life, never-breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1.17-3.13, p = 0.006).

Conclusion: The significant extra morbidity experienced in the first few months by all never-breastfed infants and at all times by HIV-infected infants who are not breastfed needs to be considered in all decisions by mothers, health workers and policy makers so as not to offset any gains achieved by decreasing HIV transmission through avoiding breastfeeding.     

Bacterial aetiology of acute osteoarticular infections in children

Aim: To study the bacterial aetiology of acute osteoarticular infections in children and to analyse the efficiency of culture methods. Methods: Bacteriological data of 407 cases of clinically suspected osteoarticular infections affecting 406 children hospitalized in an orthopaedic surgery department between 1999 and 2002 were retrospectively reviewed. Results: Bacterial cultures from clinical specimens were positive in 74 cases (18%): 38 cases of septic arthritis and 36 cases of bone infections (osteitis, osteomyelitis or osteoarthritis). The use of liquid medium bottles to grow bacteria from articular fluids increased the rate of positive cultures compared to the use of standard solid media (p=0.0001). The most commonly recovered pathogen was Staphylococcus aureus (44%) followed by Kingella kingae (14%), Streptococcus pyogenes (10%) and Streptococcus pneumoniae (10%). K. kingae was most frequently isolated among children under 36 mo of age (p=0.0003), whereas S. aureus was most frequently isolated among children over 36 mo (p=0.0015).

Conclusion: By improving our culture method, we observed a recrudescence of isolation of K. kingae, but S. aureus remains the main pathogen isolated from osteoarticular infections in children. This finding is useful for the adaptation of a probabilistic antibiotic treatment of these infections.     

Pneumocystis carinii in children with severe pneumonia at Mulago Hospital, Uganda

The prevalence of Pneumocystis carinii pneumonia (PCP), its clinical and radiological features and the outcome in 121 children aged 2-60 months presenting with severe pneumonia over a 2-month period at Mulago Hospital, Kampala are described. Children presenting with severe pneumonia had sputum induction using 3% hypertonic saline. The sputum was stained using PCP monoclonal antibodies and viewed with fluorescent microscopy. Twenty children with confirmed PCP were compared with 101 without PCP. The prevalence of PCP was 16.5%, and 12 (60%) were < 6 months of age. Eighteen (42%) of 43 children infected with HIV had PCP and two of 78 not infected with HIV. The outcome in children with PCP was poor with a case fatality rate of 40% compared with 20% in those without HIV. Radiological findings were non-specific. Clinical features associated with PCP included: HIV-positive infants with a small head circumference, AIDS, a clear chest on auscultation and elevated LDH levels. PCP occurs in one in six children < 5 years with severe pneumonia in Mulago Hospital. In developing countries where investigations for PCP are not routinely available, infants suspected of PCP should be treated as an emergency.     

Effect of human immunodeficiency virus infection on episodes of diarrhea among children in South Africa

BACKGROUND: Infection with HIV is increasing among children in South Africa. Diarrhea is a common cause of morbidity and mortality in Africa, and some studies have shown that HIV-infected children have episodes of severe diarrhea with higher mortality than HIV-uninfected children. OBJECTIVES: To compare the severity, pathogens and outcome of diarrhea in HIV-infected and uninfected children. METHODS: We studied 181 children ages 3 months to 4 years admitted for gastroenteritis to the Chris Hani Baragwanath Hospital in Soweto, South Africa. Demographic details of the children were recorded, as were the details of the episode of diarrhea. Stools specimens were collected and sent for microbiologic evaluation. The clinical course of the child's admission was recorded. Children were diagnosed as being infected with HIV if they tested positive by HIV enzyme-linked immunosorbent assay (ELISA) and were >15 months of age, or if they were ELISA-positive, were < 15 months of age and had clinical signs of HIV infection. RESULTS: Of the 176 children with an HIV ELISA result, 31 (17.6%) were classified as HIV-infected. More HIV-infected children were malnourished (80.6% vs. 39.5%, P < 0.001) and more likely to have had prolonged diarrhea (16.1% vs. 5.9%, P = 0.07) compared with HIV-uninfected children. HIV-infected children had a higher rate of a codiagnosis of pneumonia (43.3% vs. 9.2%, P < 0.0001) and were more likely to require a hospital stay of >4 days (prevalence odds ratio, 5.11; 95% confidence interval, CI 1.49 to 17.52). There were no significant differences in stool pathogens or in the level of dehydration on admission between the HIV-infected and uninfected children. CONCLUSION: HIV-infected children have the same spectrum of enteric pathogens as uninfected children but require more attention because of malnutrition and comorbidity.     

Evaluation of the WHO clinical case definition for pediatric HIV infection in Bloemfontein,South Africa

The WHO clinical case definition for pediatric HIV infection has been designed to be used in countries where diagnostic laboratory resources are limited. We evaluated the WHO case definition to determine whether it is a useful instrument to discriminate between HIV-positive and HIV-negative children. In addition, clinical features not included in this case definition were recorded. We recorded clinical data from 300 consecutively admitted children in a state hospital in Bloemfontein, South Africa, and tested these children for HIV infection. A total of 222 children were included in the study; 69 children (31.1 per cent) were HIV positive. The sensitivity of the WHO case definition in this study was 14.5 per cent, the specificity was 98.6 per cent. Apart from weight loss and generalized dermatitis, the signs of the WHO case definition were significantly more often seen in HIV-positive than in HIV-negative children. Of the clinical signs not included in the WHO case definition, marasmus and hepatosplenomegaly especially occurred more frequently in HIV-positive children. Based on these findings we composed a new case definition consisting of four signs: marasmus, hepatosplenomegaly, oropharyngeal candidiasis, and generalized lymphadenopathy. HIV infection is suspected in a child presenting with at least two of these four signs. The sensitivity of this case definition was 63.2 per cent, the specificity was 96.0 per cent. We conclude that in this study the WHO case definition was not a useful instrument to discriminate between HIV-positive and HIV-negative children, mainly because its sensitivity was strikingly low. The simplified case definition we propose, proved to be more sensitive than the WHO case definition (63.2 vs. 14.5 per cent), whilst its specificity remained high.     

Impact of human immunodeficiency virus 1 infection on clinical presentation,treatment outcome and survival in a cohort of Ethiopian children with tuberculosis

BACKGROUND: Childhood tuberculosis (TB) is difficult to diagnose reliably because signs and symptoms are nonspecific and sputum for direct microscopy is difficult to obtain, especially in very young children. This diagnostic dilemma is thought to have increased with the HIV pandemic. Few studies on treatment outcome of dually infected children in high endemic countries have been reported. This study examines the impact of HIV infection on clinical presentation, diagnostic criteria and treatment outcome of TB in Ethiopian children. METHODS: A prospective cohort study of children with TB diagnosed in Addis Ababa from December 1995 to January 1997 in which HIV-positive children were compared with HIV-negative children with regard to medical history, signs and symptoms, nutritional status, chest radiography, tuberculin skin test, response to TB treatment and final outcome. Mycobacterium tuberculosis was cultured in children with pulmonary manifestations. RESULTS: HIV-positive children were younger, were underweight and had a 6-fold higher mortality than HIV-negative children. The tuberculin skin test was less sensitive and chest radiography was less specific in HIV-infected patients. Adherence to treatment was high (96%), and the cure rate was 58% for HIV-positive and 89% for HIV-negative TB patients. CONCLUSION: HIV-positive children are at risk of diagnostic error as well as delayed diagnosis of TB. TB manifestations are more severe and progression to death is more rapid than in HIV-negative children. Weight for age may be used to identify children at high risk of a fatal outcome.     

Serum immunoglobulin E levels in human immunodeficiency virus‐infected children with pneumonia

Elevated serum immunoglobulin E (IgE) levels have been reported in association with human immunodeficiency virus (HIV) infection in adults, but there is little information in children. The aim of the present study was to compare serum IgE levels in HIV‐positive and ‐negative children hospitalized with pneumonia in South Africa and to investigate whether IgE may be useful as a marker of specific infections or prognosis in HIV‐infected children. History, examination, blood tests, and induced sputum or bronchoalveolar lavage were carried out. Of 122 children [45% female, median age 8 months (3–20 months)], 81 were infected with HIV. A history of allergy or asthma was present in three children (two of whom were HIV positive). Serum IgE was higher in HIV‐infected children [83 (33–147) vs. 29 (6–113) IU/l; p = 0.011] as was immunoglobulin G (IgG) [49 (37–63) vs. 27.5 (23–34) g/l; p < 0.001]. CD4 lymphocytes [600 (330–1210) vs. 1900 (1500–3030) cells/µl], percentage CD4 cells [13.6 (9.4–20.3) vs. 40.1 (31.1–44.9)] and CD4 : CD8 ratio [0.3 (0.2–0.4) vs. 2 (1.4–2.8)] were lower in HIV‐positive children (p < 0.001 for all). Bacteremia occurred in 12 (10%) children; other specific pathogens identified included Mycobacterium tuberculosis in eight (7%) and Pneumocystis carinii in nine (7%). There was no correlation with CD4 count, CD4 : CD8 ratio, or the presence of specific pathogens, and IgE level. In‐hospital mortality (11%) did not correlate with IgE levels. HIV‐infected children with pneumonia have higher serum IgE compared with seronegative patients. In HIV‐positive children, IgE levels did not correlate with the degree of immunosuppression or with outcome.     

Efficacy of 99mTc-DTPA lung clearance test in the diagnosis of PCP in HIV-positive patients

The study aims to evaluate the efficacy of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) lung clearance test in the diagnosis of pneumocystis carinii pneumonia (PCP) in HIV-positive paediatric patients. Twenty HIV-negative patients with no chest symptoms constituted Group A, 25 HIV antibody positive asymptomatic children formed Group B, while 45 HIV antibody positive children with respiratory infections comprised Group C. Group C was subdivided into C(1) (n = 20, documented PCP on microbiology), C(2) (n = 10, tuberculosis) and C(3) (n = 15, bacterial pneumonias). The mean age group of patients in Group A, Group B and Group C was 4.7 +/- 1.9, 4.2 +/- 1.5 and 4.8 +/- 1.7 years, respectively. All patients were subjected to complete blood count, blood culture, chest radiographs, microscopic staining of sputum (PCP stains, Ziehl-Nielsen staining, Gram staining), ABG and Mantoux test. All these patients underwent dynamic lung scans using (99m)Tc-DTPA aerosols and lung clearance was calculated in terms of half-time transfer value (T(1/2)) value. T(1/2) was compared between different groups and lung scan findings were correlated with radiological and microbiological results. Patients with PCP had T(1/2) in the range of 9.02 +/- 1.35, TB 28.2 +/- 3.03 min and other bacterial pneumonias in the range of 20.5 +/- 3.1 min (range for normal individuals was 49.8 +/- 6.13 min). T(1/2) in patients with PCP was found to be significantly lower when compared with T(1/2) in other groups. Patients with PCP had characteristic biphasic curves while the rest had monophasic curves. Some patients with PCP had low T(1/2) values even when chest radiographs and arterial blood gases were normal. (99m)Tc-DTPA lung clearance test is a sensitive, safe and non-invasive diagnostic tool for the early detection of PCP in HIV-positive paediatric patients.     

Epidemiology of HIV in southern Africa

HIV/AIDS disproportionately affects sub-Saharan Africa and 90% of the children with HIV are found there. In addition, non-HIV-infected children in the region are also vulnerable with an estimated 11.4 million AIDS orphans (many of whom are also HIV-positive). South Africa has an estimated 5.5 million people infected with HIV, which is by far the highest in the world. South Africa was reluctant to accept international assistance and began to provide care and treatment much later than its neighbours, and access to care and treatment remains low. Only 36% of children with advanced AIDS living in South Africa were receiving antiretroviral drugs in 2007. This paper not only provides data expressing the extent of the HIV problem affecting children, but also compares neighbouring African countries’ successes and failures in combating the disease.     

Dysfunction of natural killer cells in human immunodeficiency virus-infected children with or without Pneumocystis carinii pneumonia.

The development of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected children with normal T-cell numbers is contrary to previous experience with HIV-infected adults, in whom low CD4+ T-cell numbers predict susceptibility to PCP. To determine whether PCP in HIV-infected children reflects a qualitative T-cell or other immune defect, we studied four HIV-infected children who also had PCP and 10 others without PCP for T-cell and natural killer (NK) cell function. Most of the HIV-infected children had normal T-cell numbers for age, and all had CD4+ T-cell numbers greater than those predictive of PCP in HIV-infected adults. All HIV-infected children had normal T-cell function in vitro. The HIV-infected children as a whole had deficient NK cell cytolysis. We obtained a significant interactive effect of age by health status for NK cell function between patients and age-matched control subjects. All HIV-infected children with defective NK cell function failed to enhance their NK cell cytolysis when their mononuclear cells were stimulated with recombinant interferon alfa (r-IFN-alpha). This NK cell defect in HIV-infected children may facilitate the development of secondary infection.     

T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents: retention of naive T lymphocytes in HIV-infected adolescents. The Adolescent Medicine HIV/AIDS Research Network

BACKGROUND: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. OBJECTIVE: To assess lymphocyte subsets in HIV-infected and high-risk HIV-negative adolescents. DESIGN: The Reaching for Excellence in Adolescent Care and Health Project of the Adolescent Medicine HIV/AIDS Research Network recruits a cohort of HIV-infected and high-risk HIV-uninfected adolescents, aged 13 to 18 years 364 days, into a study of biomedical and behavioral features of HIV infection as seen in the context of full availability of primary care and HIV-related consultative services. Lymphocyte phenotypes were determined using standard 3-color flow cytometry. SETTING: The Reaching for Excellence in Adolescent Care and Health Project is carried out at 16 clinical sites in 14 urban areas. PARTICIPANTS: T-lymphocyte subsets are reported in 192 HIV-positive and 78 HIV-negative youths. RESULTS: For HIV-positive subjects, the total CD4+ cell count and the percentage of CD4+ cells are decreased when compared with those of the HIV-negative controls (P<.001). The reduction in total CD4+ cells reflects a loss of naive, and memory, CD4+ cells compared with HIV-negative youths. Human immunodeficiency virus-infected adolescents, many of whom have been infected recently (ie, those with CD4+ cell counts > or =0.500 x 10(9)/L [500/microL]), have a significant increase in naive CD8+ cells compared with HIV-negative youths (P<.01). There also is a significant increase in memory CD8+ cells at all strata of total CD4+ cells compared with HIV-negative youths (P<.01). The increase in naive CD8+ cells in those subjects with CD4+ cell counts of 0.500 x 10(9)/L or greater is a unique finding in this cohort. CONCLUSIONS: This study demonstrates high levels of naive CD8+ cells in response to HIV infection in adolescents with CD4+ cell counts of 0.500 X 10(9)/L or greater. The presence of high levels of naive CD8+ cells suggests functioning thymic tissue in some adolescents infected with HIV. Furthermore, the normal level of naive CD4+ cells in adolescents with CD4+ levels of 0.500 x 10(9)/L or greater provides additional support for the concept of a more robust immune system in HIV-infected adolescents compared with HIV-infected adults. These observations suggest that the immune system of HIV-infected adolescents may be capable of better responses to neoantigens and cytotoxic T-lymphocyte responses to HIV than the immune system of infected children or adults. Human immunodeficiency virus-infected adolescents may have an immune system that is capable of reconstitution following highly active antiretroviral therapy.     

Tuberculosis in HIV-infected children

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected people worldwide. HIV-positive children are at risk of diagnostic error as well as delayed diagnosis of TB because of overlapping clinical and radiographic features with other lung diseases. Acute pneumonias and chronic lung diseases such as bronchiectasis and lymphocytic interstitial pneumonitis are difficult to distinguish from TB. TB manifestations are more severe in HIV-positive children and progression to death is more rapid than in HIV-negative children. The response to standard short-course therapy in HIV-positive children is not as good as in HIV-negative children due to lower cure rates and higher mortality. TB hastens the progression of HIV disease by increasing viral replication and reducing CD4 counts further. Although Bacille Calmette-Guerin vaccination could lead to disseminated Mycobacterium bovis disease in the presence of immunosuppression, this has been rarely reported. More studies are required to assess the role of newer diagnostic tests, TB preventive therapy and co-administration of anti-retroviral therapy in the control of TB among HIV-infected children.