Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania

BACKGROUND: Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions. METHODS: Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling. RESULTS: Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4-6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses. CONCLUSIONS: The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.     

Haematological parameters of HIV-1-uninfected infants born to HIV-1-infected mothers

Aim: To investigate haematological parameters in infants born to HIV-1-infected mothers and exposed to combination antiretroviral therapy (ART) used to prevent mother-to-child transmission (MTCT). Methods: A 2-y single-centre follow-up study performed in 109 infants born to HIV-1-positive mothers. Exclusion criteria for the infants were HIV-1 infection, perinatal death, or insufficient information. Haematological parameters of the remainder of 92 infants born to HIV-1-infected mothers and exposed to ART in utero and neonatally were compared with 75 matched non-ART-exposed children. Results: Transmission rate of HIV-1 was 1.8% and occurred when the mother was not compliant with the treatment. In the HIV-1/ART-exposed children there was a long-lasting reduction in absolute neutrophil counts (ANC) until at least 8 mo of age. According to PACTG toxicity scores, 16 infants were suffering from grade II or more (moderate-to-severe) toxicity of ART on ANC. In a multivariable analysis of maternal and neonatal risk factors, pregnancy duration was correlated with moderate-to-severe toxicity on ANC. There were no clinical implications detected, e.g. increased infections or antibiotic treatment.

Conclusion: ART is successful in preventing MTCT, but alterations in haematological parameters may persist for a long period. The clinical implications remain uncertain. This suggestion increases the importance to continue prospective follow-up on the haematological parameters in ART/HIV-exposed children.     

Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi

BACKGROUND: Reference lymphocyte subset values for African children are lacking. This study documents these values as well as their alterations associated with perinatal and postnatal HIV-1 transmission and with protection from HIV-1 infection. METHODS: Lymphocyte subsets were determined for HIV-1-seronegative nonpregnant women and their children (controls) and for uninfected, perinatally infected and postnatally infected children born to HIV-1-seropositive mothers in Nairobi, Kenya. The mean, median and 5th and 95th percentile values for CD4+ and CD8+ lymphocyte counts and percentages were determined and compared at the age ranges birth to 3 months, 4 months to 1 year, yearly from 1 to 5 years and from 6 to 10 years of age. RESULTS: Among control children counts differed from published values of other populations. In all age ranges, whereas the absolute values were significantly higher than adult values, the percentages were significantly lower. Children perinatally infected with HIV-1 had clearly distinguishable differences in lymphocyte subset percentages by 3 months of age, when the median CD4+ percentage was 27.9% (5th to 95th percentile, 25.7 to 30.1%) for infected vs. 35.9% (33.3 to 38.7%) for uninfected and 39.9% (37.8 to 42.2%) for control children, P < 0.001; whereas the median CD8+ percentage was 37.0% (33.1 to 41.0%) for infected vs. 27.5% (24.2 to 30.8%) for uninfected and 27.5% (24.2 to 30.8%) for control children, P = 0.001. Differences between uninfected and control children disappeared after 1 year of age. CONCLUSIONS: Normal lymphocyte subset values among African children differ from those in other populations. Significant differences are detectable by 3 months of age in CD4+ and CD8+ lymphocyte percentages among perinatally infected infants, which may be useful as an adjunct in diagnosis. Transient differences observed among HIV-1-exposed but uninfected infants could reflect a successful immune response to HIV-1 challenge.     

Detection of infection with human immunodeficiency virus (HIV) type 1 in infants by an anti-HIV immunoglobulin A assay using recombinant proteins.

To diagnose infection with the human immunodeficiency virus (HIV) soon after birth in infants born to HIV type 1-infected women, we developed antiviral IgA Western blot and dot blot assays with recombinant HIV-1 proteins. Thirty-three infants born to HIV-1-seropositive mothers and nine infants born to HIV-1-seronegative intravenous drug-abusing mothers were followed prospectively. Infection was documented by positive virus culture. Results with the polymerase chain reaction were used for comparison. Twelve infants were found infected with HIV-1; the earliest age at which cultures became positive ranged from birth to 31 weeks of age. Of the 12 culture-positive infants, 10 had anti-HIV IgA antibodies detectable initially between birth (cord blood) and 27 weeks of age. Anti-HIV IgA was not present in the uninfected infants or in the control subjects, either by Western blot or dot blot assays. Testing for anti-HIV IgA antibodies with recombinant HIV-1 proteins is an effective method for detecting viral infection in newborn and young infants.     

Disruption in cytokine and chemokine production by T-cells in vertically HIV-1-infected children

This study measured cytokine production by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from 55 human immunodeficiency virus (HIV)-infected children born to HIV-infected mothers, and compared it with vertically exposed but uninfected age-matched children. A significant defect was observed in Th1 cytokine production [interferon-gamma and interleukin-2 (IL-2)] in HIV-infected children compared with controls, but without a concomitant increase in Th2 cytokines. Indeed, IL-5 and IL-10 production was even lower in HIV-infected children than in controls, with the decrease in IL-5 being the best predictive marker of immunodeficiency. In addition, an increased release of tumour necrosis factor-alpha (TNF-alpha) that correlated well with CD4+ levels, and a positive correlation of the TNF-alpha/IL-10 ratio with disease progression was observed. A correlation between AIDS-free status and higher %CD4+ and %CD8+ T-lymphocytes and RANTES (regulated on activation, normal T-cell expressed and secreted) production was also found. Conclusion: A dysfunctional cytokine production of PBMCs was observed in HIV-infected children in both Th1 and Th2 cytokines due to quantitative and qualitative defects induced by HIV-1. An important observation was an increased RANTES production associated with viral isolates of NSI/R5 phenotype and S/L kinetics.     

A hospital-based prospective study of perinatal infection with human immunodeficiency virus type 1.

Most infants with pediatric acquired immunodeficiency syndrome and infections with human immunodeficiency virus type 1 (HIV-1) are infected perinatally by their mothers. To determine the proportion of exposed infants who are infected, we conducted a hospital-based prospective study in HIV-1-infected women whose infants were delivered at a single metropolitan hospital in Miami, Fla. A population of uninfected women and their infants was also enrolled and followed longitudinally for 2 years to assess laboratory and clinical measurements. The median follow-up is now 18 months for 82 infants born to HIV-1-infected mothers. The proportion of infected infants in this group is 0.30 (25/82). None of the infants born to 110 HIV-1-seronegative mothers were seropositive. Infected infants were easily distinguished from noninfected infants by virus isolation. No single immunologic or hematologic measure was predictive of infection for all infants at risk for HIV-1 infection who were 6 months of age or younger. As a group, however, infected infants could be distinguished from uninfected index infants by a number of immunologic measures by 6 months of age; the absolute number of CD4+ lymphocytes and the CD4+/CD8+ lymphocyte ratio were the variables most predictive of infection. As in retrospective studies, clinical disease developed in 80% of infected infants within the first 24 months of life. This study provides documentation of HIV-1 perinatal transmission risk and early correlates of infection in young infants from a single hospital.     

Age-related changes in polymorphonuclear neutrophil characteristics in infants born to human immunodeficiency virus type 1 seropositive mothers

In infants, the major components of the innate immune system appear weakened, and it has been shown that both polymorphonuclear neutrophil (PMN) production and function are immature. This study was conducted to assess the expression of a number of receptors important to normal PMN function and the integrity of PMN degranulation in cord blood and in uninfected children of varying ages born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers. Although the expression of l-selectin (CD62L) on PMN did not differ between the infants aged 12, 15 and 18 months, the expression of the interleukin-8 (IL-8) receptors CXCR1 and CXCR2, and the complement 5a (C5a) receptor CD88 displayed a similar pattern, with the highest levels expressed on PMN from infants in the 12 month old age group, and declining with age. It was also observed that PMN from a substantial proportion of the younger infants were unresponsive to a variety of stimuli including IL-8, C5a, stromal cell-derived factor (SDF)-1alpha, SDF-1beta, and phorbol 12-myristate 13-acetate (PMA), with the proportions of children showing positive (adult-like) PMN degranulation responses increasing with age. Exposure to HIV-1 did not appear to be the cause of impaired degranulation responses, since a similar proportion of cord blood PMN from uninfected infants born to HIV-1 infected and HIV-1 uninfected mothers were unresponsive. The altered expression of these important receptors and inefficient agonist-induced degranulation in early life may contribute to the increased susceptibility of infants to secondary microbial infections.     

Reduced frequency of wheezing respiratory illness in infants with perinatal human immunodeficiency virus-type 1 infection: A model for immunologic and inflammatory mechanisms of airway obstruction?

A multivariate analysis using a logistic regression model evaluated odds ratio (OR) and 95% confidence limits (95% CL) of pediatrician-diagnosed wheezing respiratory illness in 75 infants with perinatal human immunodeficiency virus-type 1 (HIV-1) infection, 205 uninfected infants of HIV-1 infected mothers, and 1780 infants of HIV-1 uninfected mothers. Infants were prospectively followed-up for the first 2 years of life. Covariates were risk factors for wheezing respiratory illness (preterm delivery, low birth weight, maternal smoking, formula feeding, and neonatal respiratory disorders). Maternal use of illicit drugs in pregnancy, antiretroviral treatment in pregnancy, maternal HIV-1-related clinical condition at the time of delivery were also included in the models when infants of HIV-1 infected mothers were taken into account. Although the frequency of risk factors for wheezing respiratory illness was higher in infants of HIV-1 infected than in those of uninfected mothers, HIV-1 infection emerged as a protective factor [OR: 0.001 (95% CL: 0.0001–0.01); p < 0.001]. The frequency of risk factors was similarly high among infants of infected mothers, but OR was lower in HIV-1 infected than in uninfected infants of infected mothers (0.005; 95% CL: 0.0004–0.06; p < 0.001). Finally, OR was higher in uninfected infants of HIV-1 infected mothers (who evidenced a higher frequency of risk factors) than in infants of HIV-1 uninfected mothers (9.97; 95% CL: 4.87–20.40; p < 0.001). Understanding the reason why HIV-1 protects against wheezing respiratory illness could shed light on the immunologic and inflammatory mechanisms of airway obstruction.     

Immunological Follow-up in Children Born to HIV-1 Infected Mothers

ABSTRACT. From November 1985 to January 1990 we examined 156 children born to 154 HIV-1 seropositive mothers every 3 months. Eighty-seven infants were over 18 months by January 1990. Six of them met the CDC criteria of HIV-1 infection or died from AIDS; a transmission rate of 7%. Six of the children aged less than 18 months also met the CDC criteria of HIV-1 infection. These 12 infected children were compared with the 81 presumably unifected children. The perinatal findings were similar in both groups. Most of the HIV-1 infected babies showed early abnormalities in humoral and cellular immunity, hypergammaglobulinemia, low percentage of CD4 circulating lymphocytes and increased spontaneous in vitro immunoglobulin production. These changes were persistent in the HIV-1 infected children, but sporadic in those uninfected. Immunological abnormalities were frequently found before clinical symptoms appeared. We conclude that repeated immunological abnormalities in babies born to HIV-1 seropositive mothers are suggestive of HIV-1 infection.     

Immunological follow-up in children born to HIV-1 infected mothers.

From November 1985 to January 1990 we examined 156 children born to 154 HIV-1 seropositive mothers every 3 months. Eighty-seven infants were over 18 months by January 1990. Six of them met the CDC criteria of HIV-1 infection or died from AIDS; a transmission rate of 7%. Six of the children aged less than 18 months also met the CDC criteria of HIV-1 infection. These 12 infected children were compared with the 81 presumably unifected children. The perinatal findings were similar in both groups. Most of the HIV-1 infected babies showed early abnormalities in humoral and cellular immunity, hypergammaglobulinemia, low percentage of CD4 circulating lymphocytes and increased spontaneous in vitro immunoglobulin production. These changes were persistent in the HIV-1 infected children, but sporadic in those uninfected. Immunological abnormalities were frequently found before clinical symptoms appeared. We conclude that repeated immunological abnormalities in babies born to HIV-1 seropositive mothers are suggestive of HIV-1 infection.     

Current guidelines for the management of UK Infants born to HIV-1 infected mothers

Transmission of the Human Immunodeficiency Virus type 1 (HIV-1) from mother to child has been associated with maternal plasma viral load and CD4 lymphocyte count, prematurity, the mode of infant delivery, length of rupture of membranes and breast feeding. Without intervention, the transmission of HIV-1 occurs in a quarter to a third of infants born to infected mothers. During the last decade, mother-to-child transmission of HIV-1 has been reduced to less than 1%, through formula feeding, prelabour Caesarean section (PLCS) and antiretroviral therapy. With such an impressive reduction in the transmission of HIV-1, attention is turning towards the minimisation of possible drug side effects both in mothers and their infants. HIV-1-infected women are increasingly choosing to conceive on combination antiretroviral therapy, hence, infants are exposed to increasing numbers, combinations and classes of drugs, often from conception. Current guidelines on the prevention of mother to child transmission of HIV-1 are discussed.     

Mother-to-child HIV-1 transmission: Quantitative assessment of viral burden as a diagnostic tool and prognostic parameter in HIV-1-infected children

Polymerase chain reaction was performed in 251 infants born to HIV-1-seropositive mothers to diagnose HIV-1 infection. Assay specificity was invariably > 95%, regardless of age at testing, while sensitivity ranged from 15% in neonates (within 48 h of birth) to > 95% in infants over 1 month of age. Evaluation of viral burden in 43 infected infants by means of quantitative DNA-PCR disclosed that the number of HIV-1 proviruses ranged from 5 to 947 per 100,000 peripheral blood mononuclear cells. Clinical follow-up demonstrated that a high viral burden was associated significantly with disease onset.     

Risk factors for late postnatal transmission of human immunodeficiency virus type 1 in sub-Saharan Africa

BACKGROUND: We conducted secondary data analyses of a clinical trial (HIVNET 024) to assess risk factors for late postnatal transmission (LPT) of human immunodeficiency virus type 1 (HIV-1) through breast-feeding. METHODS: Data regarding live born, singleton infants of HIV-1-infected mothers were analyzed. The timing of HIV-1 transmission through 12 months after birth was defined as: in utero (positive HIV-1 RNA results at birth), perinatal/early postnatal (negative results at birth, positive at 4-6 week visit), or LPT (negative results through the 4-6 week visit, but positive assays thereafter through the 12-month visit). HIV-1-uninfected infants were those with negative HIV-1 enzyme immunoassay results at 12 months of age, or infants with negative HIV-1 RNA results throughout follow-up. RESULTS: Of 2292 HIV-1-infected enrolled women, 2052 mother/infant pairs met inclusion criteria. Of 1979 infants with HIV-1 tests, 404 were HIV-1-infected, and 382 had known timing of infection (LPT represented 22% of transmissions). Further analyses of LPT included infants who were breast-feeding at the 4-6 week visit (with negative HIV-1 results at that visit) revealed 6.9% of 1317 infants acquired HIV-1 infection through LPT by 12 months of age. More advanced maternal HIV-1 disease at enrollment (lower CD4 counts, higher plasma viral loads) were the factors associated with LPT in adjusted analyses. CONCLUSIONS: In this breast-feeding population, 6.9% of infants uninfected at 6 weeks of age acquired HIV-1 infection by 12 months. Making interventions to decrease the risk of LPT of HIV-1 available and continuing research regarding the mechanisms of LPT (so as to develop improved interventions to reduce such transmission) remain essential.     

Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children.

The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1-infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/- 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1-infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postnatal zidovudine in prevention of vertical HIV-1 transmission in a service setting

We sought to determine the efficacy of a 4-6 week course of zidovudine (ZDV) in a group of infants exposed to HIV-1. A retrospective chart review was conducted on HIV-1-exposed neonates identified from February 1998 to August 1999. These infants received ZDV and their mothers were counselled regarding the risks and benefits of breastfeeding. After informed consent was obtained, the HIV-1-status of the infant was determined by RNA-PCR after 1 month of age. Thirty-three HIV-1-exposed neonates were identified; seven infants were excluded, five because of insufficient data and two because of maternal ZDV administration. In all but three, the diagnosis was suspected because of maternal illness, 19 of 26 mothers having either stage 3 or 4 disease. The transmission rate was 15.4 per cent (4 of 26). Errors in ZDV administration were detected in 20 neonates of whom four were infected (p = 1; Fischer's exact test). Antenatal diagnosis of HIV-1 status was associated with fewer medication errors in HIV-1-exposed neonates (p = 0.017, Fisher's exact test). It was concluded that a transmission rate of 15.4 per cent in symptomatic mothers suggests efficacy. Under similar circumstances, transmission rates varying between 37 and 67 per cent have been reported. Antenatal diagnosis is significantly associated with compliance to the regimen. Early identification of at-risk neonates and familiarity with the regimen may improve the outcome.     

CD4 percentages and total lymphocyte counts as early surrogate markers for pediatric HIV-1 infection in resource-limited settings

The early diagnosis of pediatric HIV-1 infection is a critical issue in resource-limited settings to prioritize eligibility for antiretroviral therapy among HIV-1-infected children. A case-control study was performed within the ANRS 1201/1202 Ditrame Plus cohort (Abidjan, C?te d'Ivoire) to assess the usefulness of CD4+ T-cell percentage (CD4%) and total lymphocyte count (TLC) measured early in life in African children born to HIV-1-infected mothers. Using plasma HIV-1 RNA testing at 4 weeks of life as gold standard, CD4% and TLC were determined at month 3 and 6 in all 33 children HIV-1-infected in utero or intrapartum/early postpartum (cases) born to mothers receiving peripartum antiretroviral prophylaxis. Controls were 66 HIV-1-uninfected children from the same cohort. At month 3, the median CD4% was significantly lower in HIV-1-infected children (17.7%, 95% percentiles, 7.1-27.4) than in uninfected controls (34.8%, 18.5-45.3) (P < 0.001). A comparable difference was also observed at month 6. At the same time points, no significant difference was measurable for TLCs. The best threshold differentiating HIV-infected and uninfected children at month 3 was 25% CD4+. Compared to HIV-1 RNA results, sensitivity of this marker was 87.1% (95% confidence interval, 70.2-96.4) at month 3 and 88.9% (70.8-97.6) at month 6. Specificity was 78.3% (63.6-89.0) and 88.3% (77.4-95.2), respectively. Early CD4% measurement allows one to classify adequately the vast majority of exposed children according to their HIV status. CD4% should be further evaluated under field conditions for the diagnosis of pediatric HIV-1 infection and the monitoring of pediatric antiretroviral therapy.     

Semiquantitative human immunodeficiency virus antibody tests in diagnosis of vertical infection

OBJECTIVE: This study evaluated the roles of semiquantitative anti-HIV antibody tests for early diagnosis of vertical HIV-1 infection in infants. METHODS: The study included 0- to 18-month-old children of HIV-1-infected mothers. They were regularly followed up, and blood was obtained for semiquantitative anti-HIV tests using a particle agglutination (PA) test and a microparticle enzyme immunoassay (MEIA). RESULTS: One hundred forty-six children of HIV-1-infected mothers, including 104 infected and 42 uninfected infants, were studied. Using anti-HIV titer of < or = 1:100 by PA and optical values of < or = -3 by MEIA for diagnosis of not being infected, approximately 69 and 53% of the uninfected cases at age 7 to 8 months, 76 and 67% at age 9 months and 100% at age 12 months could be diagnosed. By comparison with the diagnosis by qualitative tests the figures were 16%, 8 and 11%, 70 and 74% at the same ages. All asymptomatic HIV-infected cases had persistently high PA titers and MEIA values of at least 1:5000 and 6, respectively, but 7 cases with AIDS-related manifestation at the time of tests had low anti-HIV titers. One severely ill, HIV-infected infant had a transient negative anti-HIV test at the age of 7 months. Two asymptomatic infected children, who had been breast-fed, had transient decrease in anti-HIV titers after the age of 6 months, and transient seroreversion occurred in one. CONCLUSION. Semiquantitative anti-HIV tests between the age of 6 to 12 months were very useful in diagnosis of HIV-1 infection in infants born of HIV-1-infected mothers. Interpretation must be accompanied by information about AIDS-related manifestation and history of breast-feeding.     

Immune response in HIV-1-infected children with thalassaemia given a primary course of DPT vaccine before acquiring HIV-1 infection

The effect of HIV infection on immune response to diphtheria and tetanus primary immunisation was investigated in 24 HIV-1-positive multi-transfused (MT) children with thalassaemia and compared with 48 HIV-1-negative MT thalassaemic children and 36 HIV-1-negative non-transfused (NT) children in the community. Diphtheria and tetanus antibody levels in the HIV-1-positive MT group were comparable with the two HIV-negative groups. The proportions of children with antibody titres below the protective level (i.e. <0.01 IU/ml) for antidiphtheria antibodies were 20.8, 16.6 and 16.6%, and 12.5, 12.5 and 13.9% for anti-tetanus antibodies in the three groups, respectively. On the other hand, delayed-type hypersensitivity (DTH) response to diphtheria and tetanus antigens was significantly depressed in the HIV-1-positive group compared with the HIV-negative controls. The mean percentages of both mature (CD20+) and immature (CD10+) B-cell counts were significantly higher in the HIV-1-positive group than in the HIV-negative MT and NT groups (p<0.05). Levels of serum immunoglobulins and spontaneously secreted immunoglobulins were significantly higher in the HIV-1-positive group compared with both HIV-negative groups. The HIV-1-positive group showed a mean (SD) IL-6 of 52.9 (28.8) pg/ml compared with 23.7 (12.1) pg/ml and a detection rate of 54.2% in the HIV-negative MT group, and 23.6 (8.2) pg/ml and a 50% detection rate in the HIV-negative NT group. The IL-2 level was significantly lower (p<0.05) in the HIV-1-positive group [41.7% detection rate and mean (SD) 28.8 (17.1) pg/ml] than in the HIV-negative MT and NT groups [75% and 83.3% detection rates and mean (SD) 57.2 (42.3) pg/ml and 99.3 (51.1) pg/ml, respectively]. During follow-up for 3 years, the frequency of major infections was significantly higher in the HIV-1-positive group than in the other two groups. Acute pneumonia and acute sinusitis were the predominant infections regardless of HIV status while primary bacteraemia, osteomyelitis, pyogenic meningitis and septic arthritis were common in the HIV-1-positive group. We conclude that, in HIV-1-infected children pre-immunised with DPT, DTH response to diphtheria and tetanus antigens might be more reliable than anti-diphtheria and anti-tetanus antibody levels in predicting susceptibility to major bacterial infections.     

Neonatal interleukin-1 beta, interleukin-6, and tumor necrosis factor: cord blood levels and cellular production

In a prospective study, levels of interleukin-1 beta (IL-1 beta), interleukin-6) (IL-6), and tumor necrosis factor (TNF) were measured in a blind fashion in cord blood plasma from 92 neonates by specific immunoassays, and were correlated with the clinical courses of the infants, including type of delivery and perinatal complications. Plasma IL-1 beta concentration was undetectable in infants born by normal vaginal delivery or elective cesarean section but was significantly increased in infants born after induced vaginal deliveries (142 +/- 68 pg/ml) or urgent cesarean section (290 +/- 21 pg/ml; both p less than 0.05 compared with normal deliveries). The IL-1 beta levels were elevated in infants with severe perinatal complications (282 +/- 116 pg/ml; p less than 0.001), whereas TNF and IL-6 levels were not related to these complications. Infants with isolated perinatal infectious complications had elevated levels of plasma IL-6 compared with those of sick neonates without infection (p less than 0.001). In contrast, TNF plasma levels and IL-1 beta production by cord blood leukocytes were decreased in infants with infectious complications alone (both p less than 0.05). These studies suggest that the levels of IL-1 beta, IL-6, and TNF in the cord plasma relate differentially to clinical complications in the perinatal period.     

Impact of HIV-1 status on the radiological presentation and clinical outcome of children with WHO defined community-acquired severe pneumonia.

AIMS: We compared the radiological features and outcome of WHO defined severe pneumonia among HIV infected and exposed uninfected children randomised to receive penicillin or oral amoxicillin in Durban, South Africa. METHODS: Of 425 children aged between 3 and 59 months with WHO defined severe pneumonia, 366 had anonymous HIV testing performed. Outcome was assessed by failure to improve at 48 h after enrolment or deterioration within 14 days. Chest radiographs were evaluated according to WHO defined radiological criteria for pneumonia and internationally standardised radiological criteria. Findings were stratified for HIV status. RESULTS: 82 (22.4%) children were HIV infected, 40 (10.9%) were HIV exposed and 244 (66.7%) were HIV uninfected. The day 14 outcome in children <12 months of age was significantly worse in HIV-1 infected than HIV uninfected children (OR 2.8 (95% CI 1.35 to 3.5), p = 0.002), while HIV-1 infected and uninfected children aged > or =12 months had equivalent outcomes. Parental penicillin and oral amoxicillin had equivalent response rates in all HIV groups. According to the WHO radiological classification, children who failed WHO standard antimicrobial treatment had significantly higher "other consolidates/infiltrates" than "endpoints for consolidation" in the HIV infected group (OR 5.45 (95% CI 1.58 to 21.38), p<0.002), while the reverse was true for HIV exposed uninfected children (OR 4.13 (95% CI 0.88 to 20.57), p<0.036). CONCLUSIONS: The WHO standard treatment guideline for severe pneumonia is inadequate for HIV-1 infected infants. The increased prevalence of "other consolidates/infiltrates" among HIV-1 infected children who failed standard treatment supports the addition of co-trimoxazole to WHO standard treatment.