Morbidity Among Human Immunodeficiency Virus-exposed But Uninfected, Human Immunodeficiency Virus-infected, and Human Immunodeficiency Virus-unexposed Infants in Zimbabwe Before Availability of Highly Active Antiretroviral Therapy

Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 01/2011; 30(1):45-51. DOI: 10.1097/INF.0b013e3181ecbf7e
Source: PubMed


Human immunodeficiency virus (HIV) remains a major cause of pediatric morbidity in Africa. In addition, HIV-exposed, but uninfected (HEU) infants can comprise a substantial proportion of all infants born in high prevalence countries and may also be a vulnerable group with special health problems.
A total of 14,110 infants were recruited within 96 hours of birth between November 1996 and January 2000. Rates and causes of sick clinic visits and hospitalizations during infancy were investigated according to infant HIV infection group: infected-intrauterine, infected-intrapartum, postnatally-infected, HEU, and not-exposed (born to HIV-negative mother).
A total of 382 infected-intrauterine, 499 infected-intrapartum, 188 postnatally-infected, 2849 HEU, and 9207 not-exposed infants were included in the analysis. Compared with not-exposed infants, HIV-infected infants made 2.8 times more all-cause sick clinic visits and required 13.3 times more hospitalizations; they had 7.2 times more clinic visits and 23.5 times more hospitalizations for lower respiratory tract infection after the neonatal period and were 159.9 times more likely to be hospitalized for malnutrition during the second half of infancy. Compared with not-exposed infants, sick clinic visits were 1.2 times more common among HEU infants, were inversely associated with maternal CD4 cell count, and were significantly higher for all HEU infants except those whose mothers had a CD4 count ≥ 800 cells/μL, which was the mean value of HIV-negative women enrolled in the trial.
Morbidity is extremely high among HIV-infected infants. Compared with not-exposed infants, morbidity is higher among HEU infants and increases with severity of maternal disease, but is significantly higher for all mothers with CD4 cell count <800 cells/μL.

18 Reads
  • Source
    • "However, how this corresponds to clinical infection in the neonatal period is not known. Our findings are consistent with studies that demonstrate the higher risk of infectious morbidity and mortality in HIV-exposed infants compared to HIV-unexposed infants [31] [32] [33]. Recent South African studies demonstrated a high prevalence of neonatal GBS disease in a population with a high HIV burden [23] [24] [34]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background HIV-exposed uninfected infants have increased infection risk and mortality compared to HIV-unexposed infants. HIV-exposed infants may be at increased risk of invasive GBS disease due to reduced maternal antibody against GBS. Methods We quantified antibodies that bind to the surface of whole Group B Streptococcus (GBS) of serotypes Ia, Ib, II, III and V using novel flow cytometry assays in South African HIV-infected and non-infected mothers and their uninfected infants. Antibody-mediated complement C3b/iC3b deposition onto GBS of these serotypes was also quantified by a novel flow cytometry assay. Results Geometric mean concentration (GMC) of both surface-binding anti-GBS antibody and antibody-mediated complement deposition onto GBS were reduced in HIV-infected women (n = 46) compared to HIV-uninfected women (n = 58) for ST1a (surface-binding: 19.3 vs 29.3; p = 0.003; complement deposition: 2.9 vs 5.3 SU/mL; p = 0.003), STIb (24.9 vs 47.6; p = 0.003; 2.6 vs 4.9 SU/mL; p = 0.003), STII (19.8 vs 50.0; p = 0.001; 3.1 vs 6.2 SU/mL; p = 0.001), STIII (27.8 vs 60.1; p = 0.001; 2.8 vs 5.3 SU/mL; p = 0.001) and STV (121.9 vs 185.6 SU/mL; p < 0.001) and in their infants for STIa (complement deposition 9.4 vs 27.0 SU/mL; p = 0.02), STIb (13.4 vs 24.5 SU/mL; p = 0.02), STII (14.6 vs 42.7 SU/mL; p = 0.03), STIII (26.6 vs 62.7 SU/mL; p = 0.03) and STV (90.4 vs 165.8 SU/mL; p = 0.04). Median transplacental transfer of antibody from HIV-infected women to their infants was reduced compared to HIV-uninfected women for GBS serotypes II (0.42 [IQR 0.22–0.59] vs 1.0 SU/mL [0.42–1.66]; p < 0.001), III (0.54 [0.31–1.03] vs 0.95 SU/mL [0.42–3.05], p = 0.05) and V (0.51 [0.28–0.79] vs 0.75 SU/mL [0.26–2.9], p = 0.04). The differences between infants remained significant at 16 weeks of age. Conclusions Maternal HIV infection was associated with lower anti-GBS surface binding antibody concentration and antibody-mediated C3b/iC3b deposition onto GBS bacteria of serotypes Ia, Ib, II, III and V. This may render these infants more susceptible to early and late onset GBS disease.
    Full-text · Article · Dec 2014 · Vaccine
  • Source
    • "Highly effective strategies have been introduced to prevent the spread of HIV from mothers to their infants, resulting in an increased number of HIV-exposed uninfected infants [2]. These babies are at a greatly increased risk of death during the first year of life and appear to suffer from a weakness in their immune defenses [3], [4], [5], [6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway could function as an adjuvant to improve maternal-neonatal innate immunity.
    Full-text · Article · Jun 2013 · PLoS ONE
  • Source
    • "We also observed that there was considerable variation in the adjustment for potential confounders in the included studies. While 2 studies did not adjust for potential confounders (20,33), 9 studies did (15,16,19,25,37,39,40,42,43). The majority of the identified risk factors appeared to be related to poverty and hence significant collinearity is likely to exist among them. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. Methods We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. Results We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). Conclusion This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.
    Full-text · Article · Apr 2013 · Croatian Medical Journal
Show more