The diagnosis of childhood tuberculosis in an HIV-endemic setting and the use of induced sputum.

SETTING: A hospital in the capital city of Uganda. OBJECTIVES: To determine the proportion of positive induced sputum cultures among probable childhood tuberculosis (TB) cases, to describe the laboratory and radiological features of childhood TB in the context of human immunodeficiency virus (HIV), and to determine the prevalence of HIV infection in these patients. DESIGN: Cross-sectional descriptive study. METHOD: Seven hundred and fifty children with suspected TB were evaluated clinically, by chest radiography and by tuberculin test (Mantoux). Probable cases underwent sputum induction or lymph node biopsy, HIV testing and RNA-PCR tests. RESULTS AND CONCLUSION: The Mantoux test was positive in 55/121 (45%) of the patients; low sensitivity to Mantoux was associated with HIV infection (P = 0.000). Induced sputum yielded 12/101 (12%) positive smears of Mycobacterium tuberculosis and 30/101 (30%) positive cultures. Six of the eight lymph node biopsies were culture-positive, and the histology of seven samples was supportive of TB. Most of the children with probable and confirmed TB presented with similar signs, symptoms and chest radiography patterns, irrespective of HIV status. Elevated ESR had no significant role in the diagnosis of TB in children and even more so in the presence of HIV infection. The HIV infection rate was high among children with TB (49%).

The effect of bacille Calmette-Guérin vaccination at birth on tuberculin skin test reactivity in Ugandan children.

SETTING: In Uganda, bacille-Calmette Guerin (BCG) vaccination coverage at birth is between 82 and 84%. OBJECTIVE: To evaluate the effect of neonatal BCG vaccination on tuberculin skin test positivity in Ugandan children exposed to infectious cases. DESIGN: As part of an ongoing prevalence study of household contacts of new tuberculosis cases, 365 children were evaluated to determine if BCG vaccination at birth had an impact on tuberculin skin testing. The children were classified as contacts (179) and non-contacts (186) depending on the presence of a sputum acid-fast bacilli (AFB) smear-positive adult tuberculosis case in the household. RESULTS: Regardless of prior BCG vaccination, children exposed to a smear-positive adult were more likely to have a positive skin test (purified protein derivative >5mm) (68% versus 36%, P < 0.01). BCG-vaccinated children below 1 year of age without a known household contact with active tuberculosis had a lower frequency of tuberculin skin reactions (29%) compared to their counterparts in the contact households (65%, P = 0.031). CONCLUSION: BCG vaccination at birth had no important effect on the interpretation of the tuberculin skin test reactivity in this group of Ugandan children. The tuberculin skin test remains a valuable tool for the evaluation of household contacts and suspected cases of tuberculosis in BCG-vaccinated children.

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children.

BACKGROUND: Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. METHODS: A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. RESULTS: There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). CONCLUSIONS: In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.

PIP: A prospective study of 458 infants from Kampala, Uganda, who were followed from birth to 48 months of age, documented a reduced risk of malaria in children infected with HIV-1. Included in the analysis were 77 HIV-infected children, 232 seroreverters, 125 HIV-negative children born to uninfected mothers, and 24 children of indeterminate HIV status. Thick and thin blood smears for malaria were obtained from children with fever. 51% of all children had at least 1 positive malaria smear during the study period, for a total of 653 documented malaria episodes. HIV-infected children had 3.5 episodes of malaria per 100 child months of observation compared with 5.0 episodes among seroreverters and 5.5 episodes among seronegative children. The relative rates of occurrence of malaria were 1.0 (95% confidence interval [CI], 0.8-1.2) in seroreverters and 1.1 (95% CI, 0.9-1.4) There was an increase in smears positive for malaria parasitemia among seroreverters (risk ratio, 1.5; 95% CI, 1.1-1.9) and HIV-negative controls (risk ratio, 1.6; 95% CI, 1.2-2.2) compared with HIV-infected children. Parasitemia levels during episodes of malaria were not significantly different between groups. Although the HIV-infected children had fewer episodes of malaria, they had a greater percentage of severe malaria episodes than controls and more frequent hospitalizations and blood transfusions per acute malarial episode. Within the HIV-positive group, mortality and progression to AIDS were delayed (although not significantly) among children who had malaria compared with those without malaria. It is possible that HIV-1 suppresses Plasmodium infection by creating a milieu that is suboptimal for parasite growth.

The effect of tenidap on cytokines, acute-phase proteins, and virus load in human immunodeficiency virus (HIV)-infected patients: correlation between plasma HIV-1 RNA and proinflammatory cytokine levels.

Proinflammatory cytokines may be important in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) disease. Tenidap decreases interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF) production by peripheral blood mononuclear cells and decreases IL-6 plasma levels in rheumatoid arthritis patients. In this randomized double-blind study, 43 HIV-1-infected patients received tenidap (120 mg) or placebo daily for 6 weeks and then crossed over to the alternative therapy for an additional 6 weeks. Mean entry CD4 cell count was 140/microL. Analyses were performed on cytokines, acute-phase proteins, virus load, and CD4 cell counts. With the exception of small differences in plasma TNF levels, tenidap had no significant effect on these indices. Significant correlations of plasma IL-6 and TNF levels with HIV-1 RNA were noted. Six patients discontinued tenidap due to rash. The effects of tenidap in HIV-1 infection contrast to results in arthritis patients, in whom tenidap decreased plasma levels of IL-6 and acute-phase proteins.

Human immunodeficiency virus type 1 activation after blood transfusion.

BACKGROUND: Anemia and transfusion are predictors of disease progression in AIDS patients. This study was designed to examine the effects of blood transfusion on human immunodeficiency virus type 1 (HIV-1) expression. STUDY DESIGN AND METHODS: Assays of plasma viral load were performed before and after transfusion in nine HIV-1-infected patients who required blood transfusion for refractory anemia. RESULTS: There was a modest rise in plasma HIV-1 p24 antigen and plasma HIV-1 RNA beginning 1 to 2 weeks after the blood transfusion. The mean change in plasma p24 antigen for all patients was 9.3 +/- 5.1 (mean +/- SE) pg per mL at Week 2 after transfusion and 18 +/- 11.1 pg per mL at Week 4. Plasma HIV-1 RNA levels were unchanged immediately after transfusion and exceeded pretransfusion levels with a mean rise of 84 +/- 40 percent (SE) at Week 1, 70 +/- 27 percent at Week 2, and 67 +/- 38 percent at Week 4 (p = 0.006, exact permutation test). There was no increase in spontaneous or interleukin 2-induced lymphocyte proliferation or p24 antigen production by patients' lymphocytes that were examined immediately after blood transfusion. CONCLUSION: The transfusion of blood to persons with advanced HIV-1 infection modestly increases plasma levels of HIV-1. The activation of HIV-1 expression by transfusion may help to explain the accelerated course of HIV-1 disease in recipients of blood transfusion.

Organism isolation and serum bactericidal titers in oral antibiotic therapy for pediatric osteomyelitis.

Isolation of the etiologic organism and monitoring of serum bactericidal titers are considered necessary in oral antibiotic therapy for osteomyelitis. Over a 5-year period, 26 pediatric patients with hematogenous osteomyelitis were treated with sequential parenteraloral therapy. No organism was isolated in 9 cases, and bactericidal titers were determined in only 7 cases. All patients did well, raising questions about the conventional prerequisites invoked for oral treatment of skeletal infections.

Mycobacterium tuberculosis and its purified protein derivative activate expression of the human immunodeficiency virus.

To examine the effects of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) expression, the monocytoid cell line U1 containing integrated provirus was incubated with the H37Ra strain of M. tuberculosis. This resulted in heightened expression of virus in supernatant that was partially inhibited by antibody to tumor necrosis factor-alpha (TNF-alpha). Purified protein derivative (PPD) prepared from M. tuberculosis also could activate HIV expression, and this was less affected by anti-TNF antibody. PPD could activate the HIV promoter in both U937, the monocytoid cell line from which U1 was derived, and Jurkat, a CD4+ lymphoid line. Activation was abolished by mutations in the nuclear factor (NF)-kB binding domains. Jurkat cells transfected with a plasmid construct linking 8 NF-kB binding domains to the chloramphenicol acetyltransferase (CAT) gene showed increased activity of the reporter gene after activation with PPD. Transcriptional activation of HIV expression by mycobacteria and mycobacterial products may enhance propagation of HIV in monocytoid and lymphoid cells. This may result in accelerated HIV disease progression in persons coinfected with M. tuberculosis.

Disseminated herpes simplex virus infection during pregnancy. A case report.

Hepatitis due to herpes simplex virus (HSV) developed in a pregnant women at 38 weeks' gestation. She delivered a live-born infant who had serologically documented HSV 2 infection but did well with acyclovir therapy. The mother, however, died five days postpartum from fulminant hepatic failure despite antiviral treatment, and HSV was demonstrated in the liver. Twenty-three reported cases clearly establish pregnancy as a condition that can predispose to disseminated HSV infection. The majority of cases have been due to HSV 2, and primary infection in the latter part of pregnancy appears to constitute the greatest risk. The major disease manifestations appear to be hepatitis and encephalitis. Historically, maternal and fetal mortality rates have been high, but there is a trend toward improved survival in the acyclovir era.