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Harare, Zimbabwe

To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery. Prospective cohort study. Urban Zimbabwe. 14110 women and infants enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001). Mother to child transmission of HIV, and breast milk and maternal plasma HIV load during the postpartum period. Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log(10) copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log(10) copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log(10) copies/mL 0-30 days after infection, but rapidly declined to 2.0 log(10) copies/mL and <1.5 log(10) copies/mL by 31-90 days and more than 90 days, respectively. Among women whose plasma sample collected soon after delivery tested negative for HIV with ELISA but positive with PCR (n=17), 75% of their infants were infected or had died by 12 months. An estimated 18.6% to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO trial occurred among mothers who seroconverted postnatally. Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the "window period" of an antibody based test, when she would test HIV negative using one of these tests. Trial registration Clinical trials.gov NCT00198718. Source

Gregson S.,Imperial College London | Gregson S.,Biomedical Research and Training Institute | Gonese E.,AIDS and TB Unit | Hallett T.B.,Imperial College London | And 8 more authors.
International Journal of Epidemiology | Year: 2010

Background: Recent data from antenatal clinic (ANC) surveillance and general population surveys suggest substantial declines in human immunodeficiency virus (HIV) prevalence in Zimbabwe. We assessed the contributions of rising mortality, falling HIV incidence and sexual behaviour change to the decline in HIV prevalence. Methods: Comprehensive review and secondary analysis of national and local sources on trends in HIV prevalence, HIV incidence, mortality and sexual behaviour covering the period 1985-2007. Results: HIV prevalence fell in Zimbabwe over the past decade (national estimates: from 29.3% in 1997 to 15.6% in 2007). National census and survey estimates, vital registration data from Harare and Bulawayo, and prospective local population survey data from eastern Zimbabwe showed substantial rises in mortality during the 1990s levelling off after 2000. Direct estimates of HIV incidence in male factory workers and women attending pre- and post-natal clinics, trends in HIV prevalence in 15-24-year-olds, and back-calculation estimates based on the vital registration data from Harare indicated that HIV incidence may have peaked in the early 1990s and fallen during the 1990s. Household survey data showed reductions in numbers reporting casual partners from the late 1990s and high condom use in non-regular partnerships between 1998 and 2007. Conclusions: These findings provide the first convincing evidence of an HIV decline accelerated by changes in sexual behaviour in a southern African country. However, in 2007, one in every seven adults in Zimbabwe was still infected with a life-threatening virus and mortality rates remained at crisis level. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved. Source

Grundmann N.,Stanford University | Iliff P.,ZVITAMBO Project | Stringer J.,Center for Infectious Disease Research in Zambia | Wilfert C.,Elizabeth Glaser Pediatric AIDS Foundation
Bulletin of the World Health Organization | Year: 2011

Objective To develop a new algorithm for the presumptive diagnosis of severe disease associated with human immunodeficiency virus (HIV) infection in children less than 18 months of age for the purpose of identifying children who require antiretroviral therapy (ART). Methods A conditional probability model was constructed and non-virologic parameters in various combinations were tested in a hypothetical cohort of 1000 children aged 6 weeks, 6 months and 12 months to assess the sensitivity, specificity, and positive and negative predictive values of these algorithms for identifying children in need of ART. The modelled parameters consisted of clinical criteria, rapid HIV antibody testing and CD4+ T-lymphocyte (CD4) count. Findings In children younger than 18 months, the best-performing screening algorithm, consisting of clinical symptoms plus antibody testing plus CD4 count, showed a sensitivity ranging from 71% to 80% and a specificity ranging from 92% to 99%. Positive and negative predictive values were between 61% and 97% and between 95% and 96%, respectively. In the absence of virologic tests, this alternate algorithm for the presumptive diagnosis of severe HIV disease makes it possible to correctly initiate ART in 91% to 98% of HIV-positive children who are at highest risk of dying. Conclusion The algorithms presented in this paper have better sensitivity and specificity than clinical parameters, with or without rapid HIV testing, for the presumptive diagnosis of severe disease in HIV-positive children less than 18 months of age. If implemented, they can increase the number of HIV-positive children successfully initiated on ART. Source

Smith L.E.,Cornell University | Smith L.E.,Queen Mary, University of London | Stoltzfus R.J.,Cornell University | Stoltzfus R.J.,Queen Mary, University of London | Prendergast A.,ZVITAMBO Project
Advances in Nutrition | Year: 2012

Childhood stunting is an important and intractable public health problem that underlies ~20% of deaths among children aged <5 y in developing countries. Environmental enteropathy (EE), a subclinical condition of the small intestine characterized by reduced absorptive capacity and increased intestinal permeability, is almost universal among children in developing countries and may mediate stunting. However, the etiology of EE is poorly understood. Mycotoxins are metabolites of fungi that frequently contaminate the staple foods of children living in developing countries. We review evidence from human and animal studies that exposure to mycotoxins, particularly aflatoxin (AF), fumonisin (FUM), and deoxynivaenol (DON), may impair child growth. Although these toxins have distinct actions, they all mediate intestinal damage through: 1) inhibition of protein synthesis (AF, DON); 2) an increase in systemic proinflammatory cytokines (DON); and 3) inhibition of ceramide synthase (FUM). The intestinal pathology that arises from mycotoxin exposure is very similar to that of EE. We propose that future studies should address the role of mycotoxins in the pathogenesis of EE and evaluate interventions to limit mycotoxin exposure and reduce childhood stunting. © 2012 American Society for Nutrition. Source

Prendergast A.,ZVITAMBO Project | Prendergast A.,University of Lusaka | Prendergast A.,Queen Mary, University of London | Kelly P.,ZVITAMBO Project | And 2 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2012

A spectrum of enteropathies, characterized by small intestinal inflammation, reduced absorptive capacity, and increased intestinal permeability, commonly affect people in developing countries. This subclinical intestinal pathology facilitates microbial translocation across the compromised intestinal barrier, leading to chronic systemic inflammation that may adversely impact health. Environmental enteropathy (EE), ubiquitous among people living in unhygienic conditions, likely mediates two interlinked public health problems of childhood, stunting and anemia, and underlies poor oral vaccine efficacy in developing countries. Human immunodeficiency virus (HIV) enteropathy, which frequently overlaps with EE, may contribute to immune activation and modulate HIV disease progression. The interacting effects of infection and enteropathy drive a vicious cycle that can propagate severe acute malnutrition, which underlies almost half of under-5-y deaths. Enteropathies are therefore highly prevalent, interacting causes of morbidity and mortality in developing countries. Interventions to prevent or ameliorate enteropathies have potential to improve the health of millions of people in developing countries. Copyright © 2012 by The American Society of Tropical Medicine and Hygiene. Source

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