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Exposure to TB was quantified by screening human immunodeficiency virus (HIV) exposed infants aged 3-4 months for an isoniazid prophylaxis study where tuberculosis (TB) exposure excluded enrolment. Seventy-seven (10.1%, 95%CI 8.0-12.4) of 766 infants had contact with a TB source case. Nurses and lay counsellors identified 52 infants during pre-screening and doctors identified 25 during formal screening. High exposure may contribute to high rates of TB in HIV-exposed infants. Programs to prevent mother-to-child transmission of HIV offer an important opportunity to screen for TB. In-depth assessment is required for evaluating TB exposure.

Background: Chronic otorrhoea occurs commonly in HIV-infected children. However, there are few data on incidence and severity., Objective: To document the prevalence of otorrhoea in the clinic attendees., Methods: A retrospective chart review was done of all HIVI infected children seen at the Family Clinic for HIV from 1 February 1997 to 31 December 2001, a period preceding widespread availability of antiretrovirals. Otorrhoea was classified into two groups, viz. group 1 (mild): an episode lasting less than 1 month, and group 2 (severe): an episode lasting more than 1 month or more than 1 episode of otorrhoea. The clinical and immune stages of the children were noted., Results: Of 326 children seen during the study period, 104 (32%) had otorrhoea. Forty-five (13.8%) had mild and 59 (18.1%) severe otorrhoea. Two hundred and eighty-eight (88.6%) had either Centers for Disease Control stage B or C disease. The median CD4 percentage in children with otorrhoea was 17.5% (8.3-23%) versus 21% (14-28%) in those without otorrhoea (p=0.004). The odds ratio (OR) of children in stage B or C not having severe otorrhoea was 0.1 (0.01 - 0.72, p = 0.013). The OR for immune class 2 or 3 without severe otorrhoea was 0.39 (0.18 - 0.85, p = 0.021)., Conclusions: Otorrhoea contributes to the morbidity of HIV infection in children. It is a marker for symptomatic disease and CD4 depletion and should be included in clinical classifications.

Background: Rapid HIV antibody tests are commonly used for HIV diagnosis in the developing world. These tests are generally reported as sensitive, despite paucity of evaluations in paediatric populations., Objectives: We tested specimens of paediatric patients, known to be HIV-infected, to detect any false negative tests and determine associations with such an outcome., Study Design: One hundred and fifty-three specimens, from 109 patients, recorded to be HIV-infected by standard testing, were tested on the Capillustrade mark HIV-1/HIV-2 test (Trinity Biotech, Ireland); 150 specimens also had sufficient volume to be tested on Abbott Determinetrade mark HIV1/2 assay (Abbott GmbH, Wiesbaden, Germany). Treatment information, CD4 counts and HIV-1 viral load measurements were obtained from patient files and laboratory databases., Results: Twenty-one of 153 specimens tested negative on the Capillus (sensitivity 86.3%). False negative results by Capillus were associated with antiretroviral treatment (ART) (p=0.0018) and lower HIV-1 viral load (p=0.013). Serial dilutions of some of the specimens indicated that both rapid tests, and the Capillus in particular, became negative at lower dilutions than an HIV enzyme immunoassay (EIA)., Conclusions: The Capillus test had an unexpectedly low sensitivity in a South African population of HIV-infected children that had access to antiretroviral treatment, posing a risk of false negative HIV testing.

Introduction: Inappropriate use of antibiotics for upper respiratory tract infections (URTIs), many of which are viral, adds to the burden of antibiotic resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae, responsible for most cases of acute otitis media (AOM) and acute bacterial sinusitis (ABS)., Method: The Infectious Diseases Society of Southern Africa held a multidisciplinary meeting to draw up a national guideline for the management of URTIs. Background information reviewed included randomised controlled trials, existing URTI guidelines and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. The guideline is a consensus document based upon the opinions of the working group., Output: Penicillin remains the drug of choice for tonsillopharyngitis. Single-dose parenteral administration of benzathine penicillin is effective, but many favour oral administration twice daily for 10 days. Amoxycillin remains the drug of choice for both AOM and ABS. A dose of 90 mg/ kg/day is recommended in general, which should be effective for pneumococci with high-level penicillin resistance (this is particularly likely in children < or = 2 years of age, in day-care attendees, in cases with prior AOM within the past 6 months, and in children who have received antibiotics within the last 3 months). Alternative antibiotic choices are given in the guideline with recommendations for their specific indications. These antibiotics include amoxycillin-clavulanate, some cephalosporins, the macrolide/azalide and ketolide groups of agents and the respiratory fluoroquinolones., Conclusion: The guideline should assist rational antibiotic prescribing for URTIs. However, it should be updated when new information becomes available from randomised controlled trials and surveillance studies of local antibiotic susceptibility patterns.

Tuberculosis has been a major cause of morbidity and mortality in under-resourced communities. By causing progressive immunodeficiency, the human immunodeficiency virus (HIV) increases susceptibility to tuberculosis in an already vulnerable community. Similarities in clinical presentation and radiological appearance contribute to diagnostic difficulties, as even in the absence of HIV childhood tuberculosis is not easy to diagnose. The majority of studies thus far have been descriptive and often cross-sectional, but have defined the extent of this complex interaction. There is now a need to undertake prospective diagnostic, therapeutic and prevention studies. An emerging concern is how to integrate antiretroviral with anti-tuberculosis treatment and to explore whether lessons learned in tuberculosis can support antiretroviral therapy. Interactions between therapies for both conditions also need careful study.

Background: In the year 2000 we reported possible horizontal transmission of HIV-1 infection between two siblings. An investigation of three families, each with an HIV-infected child but seronegative parents, permitted this finding. Sexual abuse and surrogate breast-feeding were thought unlikely. The children had overlapping hospitalisation in a regional hospital. Since then several cases of unexplained HIV infection in children have been reported. A registry was established at Tygerberg Children's Hospital for collection of data on the extent of horizontal or unexplained transmission of HIV in children., Study Design: Retrospective chart review., Results: Fourteen children were identified, 12 from the Western Cape and 1 each from the Eastern Cape and KwaZulu-Natal. Thirteen (92%) had been hospitalised previously. In the Western Cape, children had been hospitalised in 8 hospitals. Ten of 13 (77%) were admitted as neonates and 9 of 13 (69%) had 2 or more admissions. Intravascular cannulation and intravenous drug administration occurred in all but 2 children before HIV diagnosis., Conclusion: We have confirmed HIV infection in a number of cases where the source of infection has been inadequately explained. Circumstantial evidence supports but does not prove nosocomial transmission. Further studies and identification of medical procedures conducive to the spread of HIV are urgently needed.

We investigated the benefit of treating HIV-1-infected children with monotherapy where resources are limited. A retrospective chart review was undertaken in 12 symptomatic HIV-1-infected children treated with zidovudine or didanosine for at least 2 months. The main outcome measure was the effect on hospitalization. Anti-retroviral therapy was commenced in nine children because of prolonged or frequent hospitalization. Of three whose primary indication was bleeding secondary to thrombocytopenia, two had been hospitalized owing to severe intercurrent illness. One child had failure to thrive and another encephalopathy. Monotherapy was considered beneficial in all cases. Median duration of follow-up was 6.5 (2-31) months. The hospitalization index (days in hospital before and after start of monotherapy, divided by the total number of days before and after start of monotherapy) decreased from a median of 0.115 prior to therapy to 0.037 on therapy (p = 0.045, Wilcoxon matched pairs test). This study presents observational data supporting the investigation of monotherapy in resource-poor countries. It was associated with a significant reduction in hospitalization and appeared to result in clinical improvement. Prolonged or frequent hospitalization might represent a novel indication for use because in our setting the cost of hospitalization could potentially provide a 12-month-old infant with monotherapy for 2 months.

We report a case of an HIV-infected child with a second episode of tuberculosis 22 months after completing antituberculosis treatment. DNA fingerprinting of organisms from both episodes showed an identical strain of Mycobacterium tuberculosis. We believe this to be the first case of confirmed relapsed tuberculosis in an HIV-infected child, and suggest that a longer course of antituberculosis treatment be given to such children. ¿ 2000 The British Infection Society.

We recently experienced an outbreak of nosocomial disease due to extended spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal unit infested with cockroaches. Organisms isolated from cockroaches were indistinguishable by pulsed-field gel electrophoresis from those colonizing infants or causing clinical disease using. Cockroach elimination together with standard infection-control measures resulted in control of the outbreak. We suggest cockroaches are possible vectors of pathogenic bacteria in the hospital environment.

The importance of controlled cell death in a variety of diseases has now been recognized and apoptosis research has become one of the fastest growing fields in medical science. Scientific advances are rapidly being applied to clinical practice.

Background: Adults infected by HIV have increased susceptibility to Mycobacterium tuberculosis and progress more rapidly to disease. HIV and tuberculosis (TB) coinfection in children has been reported but often lacks bacterial confirmation. We report on the clinical picture, special investigations, clinical course and outcome of 14 children with HIV infection and culture-confirmed TB from a developing country., Methods: The clinical records of all children, from 1992 to 1997, with HIV infection and culture-proved TB were reviewed., Results: Fourteen (10.4%) of 135 children with vertically transmitted HIV infection, 93% <2 years of age, fit the criteria. Nonresolving pneumonia (4) and otorrhoea (6) were common complaints. A Mantoux test was positive (> or =15 mm) in 6 of 11 children. Extrapulmonary TB was present in 5 cases. Ear swabs were the source of M. tuberculosis culture in 3. Chest radiographs were abnormal in all with hilar and paratracheal lymphadenopathy present in 7. A source case with pulmonary TB was identified for 10. Susceptibility tests were done on 9 strains of which 1 was drug-resistant. Four children were culture-positive 4 to 10 months after initiation of TB treatment. Mortality was 21% and 3 were lost to follow-up., Conclusions: In HIV-infected children the Mantoux skin test remains useful and culture specimens should be obtained from all sources. Response to treatment is unpredictable, and for this reason repeated cultures should be taken during treatment and a 9-month course of treatment considered.

Apoptosis of CD4+ and CD8+ T cells has been shown in peripheral blood mononuclear cells (PBMCs) from HIV-infected adults analyzed after overnight culture. Because cell death may be an artifact of in vitro culture, and because there is little information on apoptosis in pediatric HIV disease, we undertook a cross-sectional analysis of apoptosis in PBMCs analyzed immediately ex vivo in HIV-infected children and adults. PBMCs from 22 children, four adolescents, and nine adults and seronegative age-matched control subjects were stained for CD4 and CD8 surface markers. Apoptotic cells were detected in a newly characterized flow cytometric assay by diminished forward and increased side scatter. Children with the most advanced disease had 9.9% (SEM 1.8) apoptotic CD4+ T cells above control, significantly higher than in asymptomatic patients [0.4% (SEM 2.3)], those with mild disease [2.2% (SEM 1.83)], and those with moderate disease [2.5 (SEM 3.6)] (p = 0.015). The percentages of both CD4+ and CD8+ T cell apoptosis were directly related to CD4+ T cell depletion (R2 = 0.23; p = 0.006; n = 32 and R2 = 0.2; p = 0.012; n = 30, respectively). Patients who responded to antiretroviral therapy with the greatest increase in CD4+ T cell percentage had the least CD4+ T cell apoptosis (R2 = 0.15; p = 0.1; n = 19). These findings show that the rate or extent of T cell death by apoptosis percentage of T cell apoptosis is significantly increased in HIV-infected children. The observed correlation of both CD4+ and CD8+ T cell apoptosis with CD4+ T cell depletion suggests that apoptosis plays a role in HIV pathogenesis and may be a useful marker of disease activity.

We have studied apoptosis in lymph node and peripheral blood mononuclear cells (PBMCs) from HIV-infected children and adults and SIV-infected rhesus macaques. In lymph nodes, we found that apoptosis and productive infection occurred only rarely in the same cell. There was, however, a direct correlation between the numbers of apoptotic and productively-infected cells. In HIV-infected children, we found a direct correlation between disease severity and percentage CD4+ T cell apoptosis (p = 0.001). Both CD4+ and CD8+ T cell apoptosis were directly related to CD4+ T cell depletion (p = 0.006 and p = 0.01, respectively). In addition, we found a trend towards diminished CD4+ T cell apoptosis on anti-retroviral agents. These findings suggest that apoptosis of uninfected cells may be important in HIV pathogenesis and that measurement of apoptosis may be a useful marker of disease activity.

Objective: There is no information on the impact and nature of telephone calls directed to subspecialists. The main objective was to document prospectively all calls directed to a first-year infectious diseases fellow, to determine their content, origin, educational value, and time allocation., Results: Three hundred fifty-nine calls were received over a 71-day period from March 24 through May 20, 1992. The mean number of daily calls was 5.1 +/- 3.3. Mean time per call was 7 +/- 5.4 minutes. Cumulatively, 41.7 hours were spent responding to telephone calls. The subgroup with the most calls (44.3%) was from pediatricians in practice. Seventy percent of calls were for advice about case management. Forty percent of calls were considered educational to the fellow., Conclusions: This study confirms the importance of the infectious disease subspecialist as a resource for primary care physicians.

Two children were hospitalized for severe chickenpox after intranasal use of corticosteroids for chronic sinusitis. One had unusually extensive cutaneous disease with delayed progression of lesions, dehydration, and prolonged fever; the other had hemorrhagic cutaneous lesions, hepatitis, and pneumonitis. Both were treated with intravenous acyclovir infusion and recovered. Systemic or local immunosuppression after intranasal corticosteroid administration may have predisposed the children to severe varicella infection.

Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mmHg, range 8.4-50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8-42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.

During 1989, of the 8,524 children admitted to the paediatric wards of Tygerberg Hospital, 165 (1.96%) had bacteraemia. The incidence of community-acquired bacteraemias was 1.6% and that of nosocomial bacteraemias 0.5%. The most important community-acquired isolates were Streptococcus pneumoniae, Staphylococcus aureus and Neisseria meningitidis. The most important nosocomial isolates were Klebsiella and Salmonella spp. Both bacteraemia (relative risk (RR) = 2.08) and severe malnutrition (RR = 3.01) were more common in black patients. Overall, severe malnutrition was more common than mild malnutrition or a normal nutritional status in bacteraemic patients (odds radio (OR) = 3.17). Nineteen patients with bacteraemia died, there was a significantly higher case-fatality rate in patients with extreme malnutrition (P = 0.03; OR = 3.7). Gram-negative bacilli were found more commonly in patients with extreme malnutrition (OR = 5.4) and patients with nosocomial bacteraemia (OR = 4.6). Three of 39 patients (7.6%) with nosocomial bacteraemia had suppurative thrombophlebitis.

The authors address a unique partnership among private and public organizations, that of the American Red Cross and the Centers for Disease Control of the Public Health Service. The partnership stimulates an integrated community response to preventing and controlling human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) at the local level. The partnership channels information and provides education to local communities through the efforts of volunteers and staff members. Information is made available as well through other partnerships established under the cooperative agreement between the American Red Cross and the Centers for Disease Control. These partnerships include other national organizations, such as the National Leadership Coalition on AIDS, the National Association of People with AIDS, the National Urban League, and the National Council of La Raza. Education and information messages are designed to complement and be consistent with information and messages from the Public Health Service through the National AIDS Information and Education Program and the "America Responds to AIDS" public information campaign. The objectives are to mobilize local community support for efforts for HIV infection and AIDS prevention and services, as well as to heighten public awareness of the issues.

Biochemical evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was documented in 17 of 24 (71%) children with tuberculous meningitis. Plasma arginine vasopressin concentrations in patients with signs of SIADH were significantly higher (median, 15.44 (range, 1.62 to greater than 24.52) pg/ml; n = 14) than those without (median, 1.91 (range, 0.44 to 4.91) pg/ml; n = 6) (P less than 0.002). Patients who developed evidence of SIADH were older than those who did not (median, 34 (range, 6 to 101) months vs. 10 (range, 6 to 38) months; P less than 0.007). Five patients with and none without died. In 9 patients evidence of SIADH developed only after hospitalization. These patients received a median of 58 (range, 28 to 109) ml/kg/day fluids (n = 7) before developing evidence of SIADH compared with 107 (range, 58 to 146) ml/kg/day received by patients who did not develop SIADH (n = 6) (P = 0.035). SIADH occurs commonly and its presence appears to influence the outcome of tuberculous meningitis in children.

In a study of ventriculoperitoneal shunt infections conducted retrospectively between 1983 and 1987 and prospectively in 1988 39 infections from 372 shunt procedures (incidence 10.5%) were identified. The most common organism isolated was Staphylococcus aureus (18; 47%) followed by S. epidermidis (10; 26%). Forty-two per cent of staphylococci were methicillin-resistant. Gram-negative infections were associated with myelomeningoceles and Gram-positive infections with other forms of hydrocephalus (P = 0.048). Lymphocyte predominance was found more frequently than polymorphonuclear predominance in cerebrospinal fluid.

Endotracheal aspirates were obtained from 51 young children for the microbiological diagnosis of pneumonia acquired in hospital or associated with measles or severe protein-energy malnutrition. The procedure proved safe and the information obtained assisted in the management of most cases. There was a fairly good correlation between the findings of Gram stain and those of culture of the aspirates, which improved when only Gram stains showing many or moderate numbers of bacteria were used. The bacteria most frequently isolated were Gram-negative enteric bacilli, Staphylococcus aureus, Streptococcus viridans, Streptococcus pneumoniae and Haemophilus influenzae, many strains of which were resistant to conventional antibiotics. The role of endotracheal aspiration in the microbiological diagnosis of pneumonia in the above-mentioned types of patients is compared with that of percutaneous lung puncture, percutaneous transtracheal aspiration and expectorated sputum.

A neonate who developed systemic candidiasis was successfully treated with oral ketoconazole (Nizoral; Janssen) and flucytosine (Alcobon; Roche). The potential benefits of this combination are discussed.

Fourteen pupils of the New Hope School in Pretoria who were considered to be responsive to methylphenidate were randomised to receive either the active drug or placebo in a double-blind trial for each of 4 weeks. Their behaviour was monitored by parents and teachers, who were required to complete a questionnaire (Conner's Abbreviated Teachers' Rating Scale) three times per week. After analysis of the data, only 2 children were identified as methylphenidate responders and 1 as a probable responder. One child showed significant deterioration on the drug while another showed deterioration that approached significance. The remaining 9 exhibited no significant response to methylphenidate.

Nosocomial infections in infants and children were prospectively studied in the general wards of a hospital serving a developing community. Of 1350 admissions in 5 months, 193 (14.3%) developed 302 infections (22.4/100 admissions). The major risk factors were malnutrition, age less than 2 years and prolonged hospitalization. The most common sites of infection were the lower respiratory and gastrointestinal tracts. The most frequently isolated organisms were Staphylococcus aureus and Klebsiella species and the site of most frequent isolation was the lower respiratory tract for which the method most commonly used was endotracheal aspiration. Seventy percent of isolates were resistant in vitro to conventional antibiotics. Thirty-one percent of infections developed while the patient was awaiting a diagnostic procedure or waiting to be sent home. During the study period 60 patients (4.4% of admissions) were admitted with a nosocomial infection acquired elsewhere (31 at this hospital and 29 from other hospitals). Measles and its complications accounted for 28 of these cases and 7 deaths. This study provides information on nosocomial infections in children from a developing community.