Dataset Information

Severe anaemia is not associated with HIV-1 env gene characteristics in Malawian children.

ABSTRACT:

Background

Anaemia is the most common haematological complication of HIV and associated with a high morbidity and a poor prognosis. The pathogenesis of HIV-associated anaemia is poorly understood and may include a direct effect of HIV on erythropoiesis. In vitro studies have suggested that specific HIV strains, like X4 that uses the CXCR4 co-receptor present on erythroid precursors, are associated with diminished erythropoiesis. This co-receptor affinity is determined by changes in the hypervariable loop of the HIV-1 envelope genome. In a previous case-control study we observed an association between HIV and severe anaemia in Malawian children that could not be fully explained by secondary infections and micronutrient deficiencies alone. We therefore explored the possibility that alterations in the V1-V2-V3 fragment of HIV-1 were associated with severe anaemia.

Methods

Using peripheral blood nucleic acid isolates of HIV-infected children identified in the previous studied we assessed if variability of the V1-V2-V3 region of HIV and the occurrence of X4 strains were more common in HIV-infected children with (cases, n = 29) and without severe anaemia (controls, n = 30). For 15 cases bone marrow isolates were available to compare against peripheral blood. All children were followed for 18 months after recruitment.

Results

Phylogenetic analysis showed that HIV-1 subtype C was present in all but one child. All V1-V2-V3 characteristics tested: V3 charge, V1-V2 length and potential glycosylation sites, were not found to be different between cases and controls. Using a computer model (C-PSSM) four children (7.8%) were identified to have an X4 strain. This prevalence was not different between study groups (p = 1.00). The V3 loop characteristics for bone marrow and peripheral blood isolates in the case group were identical. None of the children identified as having an X4 strain developed a (new) episode of severe anaemia during follow up.

Conclusion

The prevalence of X4 strains in these young HIV-1-subtype-C-infected children that were most likely vertically infected and naïve to anti-retroviral therapy can be considered high compared to previous results from Malawi. It is unlikely that V1-V2-V3 fragment characteristics and HIV co-receptor affinity is an important feature in the development of severe anaemia in Malawian children.

SUBMITTER: Calis JC

PROVIDER: S-EPMC2311312 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Publications

Severe anaemia is not associated with HIV-1 env gene characteristics in Malawian children.

Calis Job C J JC Rotteveel Hellen P HP van der Kuyl Antoinette C AC Zorgdrager Fokla F Kachala David D van Hensbroek Michaël Boele MB Cornelissen Marion M

BMC infectious diseases 20080229

<h4>Background</h4>Anaemia is the most common haematological complication of HIV and associated with a high morbidity and a poor prognosis. The pathogenesis of HIV-associated anaemia is poorly understood and may include a direct effect of HIV on erythropoiesis. In vitro studies have suggested that specific HIV strains, like X4 that uses the CXCR4 co-receptor present on erythroid precursors, are associated with diminished erythropoiesis. This co-receptor affinity is determined by changes in the h ...[more]

PMID: 18312662

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Project description:In countries of sub-Saharan Africa, many children are admitted to hospital with severe forms of anaemia. The late hospital admissions of anaemic children contribute significantly to child morbidity and mortality in these countries. This qualitative study explores local health beliefs and traditional treatment practices that may hinder timely seeking of hospital care for anaemic children. In January of 2019, nine focus group discussions were conducted with 90 participants in rural communities of Malawi. The participants represented four groups of caregivers; mothers, fathers, grandmothers and grandfathers of children under the age of five. The Malawian medical landscape is comprised of formal and informal therapeutic alternatives-and this myriad of modalities is likely to complicate the healthcare choices of caregivers. When dealing with child illness, many participants reported how they would follow a step-by-step, 'multi-try' therapeutic pathway where a combination of biomedical and traditional treatment options were sought at varying time points depending on the perceived cause and severity of symptoms. The participants linked anaemia to naturalistic (malaria, poor nutrition and the local illnesses kakozi and kapamba), societal (the local illness msempho) and supernatural or personalistic (witchcraft and Satanism) causes. Most participants agreed that anaemia due to malaria and poor nutrition should be treated at hospital. As for local illnesses, many grandparents suggested herbal treatment offered by traditional healers, while the majority of parents would opt for hospital care. However, participants across all age groups claimed that anaemia caused by witchcraft and Satanism could only be dealt with by traditional healers or prayer, respectively. The multiple theories of anaemia causality combined with extensive use of and trust in traditional and complementary medicine may explain the frequent delay in admittance of anaemic children to hospital.

Project description:BackgroundTackling severe acute malnutrition (SAM) is a global health priority. Heightened risk of non-communicable diseases (NCD) in children exposed to SAM at around 2 years of age is plausible in view of previously described consequences of other early nutritional insults. By applying developmental origins of health and disease (DOHaD) theory to this group, we aimed to explore the long-term effects of SAM.MethodsWe followed up 352 Malawian children (median age 9·3 years) who were still alive following SAM inpatient treatment between July 12, 2006, and March 7, 2007, (median age 24 months) and compared them with 217 sibling controls and 184 age-and-sex matched community controls. Our outcomes of interest were anthropometry, body composition, lung function, physical capacity (hand grip, step test, and physical activity), and blood markers of NCD risk. For comparisons of all outcomes, we used multivariable linear regression, adjusted for age, sex, HIV status, and socioeconomic status. We also adjusted for puberty in the body composition regression model.FindingsCompared with controls, children who had survived SAM had lower height-for-age Z scores (adjusted difference vs community controls 0·4, 95% CI 0·6 to 0·2, p=0·001; adjusted difference vs sibling controls 0·2, 0·0 to 0·4, p=0·04), although they showed evidence of catch-up growth. These children also had shorter leg length (adjusted difference vs community controls 2·0 cm, 1·0 to 3·0, p<0·0001; adjusted difference vs sibling controls 1·4 cm, 0·5 to 2·3, p=0·002), smaller mid-upper arm circumference (adjusted difference vs community controls 5·6 mm, 1·9 to 9·4, p=0·001; adjusted difference vs sibling controls 5·7 mm, 2·3 to 9·1, p=0·02), calf circumference (adjusted difference vs community controls 0·49 cm, 0·1 to 0·9, p=0·01; adjusted difference vs sibling controls 0·62 cm, 0·2 to 1·0, p=0·001), and hip circumference (adjusted difference vs community controls 1·56 cm, 0·5 to 2·7, p=0·01; adjusted difference vs sibling controls 1·83 cm, 0·8 to 2·8, p<0·0001), and less lean mass (adjusted difference vs community controls -24·5, -43 to -5·5, p=0·01; adjusted difference vs sibling controls -11·5, -29 to -6, p=0·19) than did either sibling or community controls. Survivors of SAM had functional deficits consisting of weaker hand grip (adjusted difference vs community controls -1·7 kg, 95% CI -2·4 to -0·9, p<0·0001; adjusted difference vs sibling controls 1·01 kg, 0·3 to 1·7, p=0·005,)) and fewer minutes completed of an exercise test (sibling odds ratio [OR] 1·59, 95% CI 1·0 to 2·5, p=0·04; community OR 1·59, 95% CI 1·0 to 2·5, p=0·05). We did not detect significant differences between cases and controls in terms of lung function, lipid profile, glucose tolerance, glycated haemoglobin A1c, salivary cortisol, sitting height, and head circumference.InterpretationOur results suggest that SAM has long-term adverse effects. Survivors show patterns of so-called thrifty growth, which is associated with future cardiovascular and metabolic disease. The evidence of catch-up growth and largely preserved cardiometabolic and pulmonary functions suggest the potential for near-full rehabilitation. Future follow-up should try to establish the effects of puberty and later dietary or social transitions on these parameters, as well as explore how best to optimise recovery and quality of life for survivors.FundingThe Wellcome Trust.

Dataset Information

Severe anaemia is not associated with HIV-1 env gene characteristics in Malawian children.

Background

Methods

Results

Conclusion

Publications

Severe anaemia is not associated with HIV-1 env gene characteristics in Malawian children.

Similar Datasets

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