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Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study.

ABSTRACT: BACKGROUND: Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy. METHODS: We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth. RESULTS: At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by approximately 90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points. CONCLUSION: HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months.

SUBMITTER: Miller MF

PROVIDER: S-EPMC1361802 | biostudies-other | 2006

REPOSITORIES: biostudies-other

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Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study.

Miller Melissa F MF Humphrey Jean H JH Iliff Peter J PJ Malaba Lucie C LC Mbuya Nkosinathi V NV Stoltzfus Rebecca J RJ

BMC infectious diseases 20060103

<h4>Background</h4>Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy.<h4>Methods</h4>We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months ...[more]

PMID: 16390553

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Project description:BackgroundHigh-risk human papillomavirus HPV (HR-HPV) modifies cervical cancer risk in people living with HIV, yet African populations are under-represented. We aimed to compare the frequency, multiplicity and consanguinity of HR-HPVs in HIV-negative and HIV-positive Zimbabwean women.MethodsThis was a cross-sectional study consisting of women with histologically confirmed cervical cancer attending Parirenyatwa Group of Hospitals in Harare, Zimbabwe. Information on HIV status was also collected for comparative analysis. Genomic DNA was extracted from 258 formalin fixed paraffin embedded tumour tissue samples, and analysed for 14 HR-HPV genotypes. Data was analysed using Graphpad Prism and STATA.ResultsForty-five percent of the cohort was HIV-positive, with a median age of 51 (IQR = 42-62) years. HR-HPV positivity was detected in 96% of biospecimens analysed. HPV16 (48%), was the most prevalent genotype, followed by HPV35 (26%), HPV18 (25%), HPV58 (11%) and HPV33 (10%), irrespective of HIV status. One third of the cohort harboured a single HPV infection, and HPV16 (41%), HPV18 (21%) and HPV35 (21%) were the most prevalent. HIV status did not influence the prevalence and rate of multiple HPV infections (p>0.05). We reported significant (p<0.05) consanguinity of HPV16/18 (OR = 0.3; 95% CI = 0.1-0.9), HPV16/33 (OR = 0.3; 95% CI = 0.1-1.0), HPV16/35 (OR = 3.3; 95% CI = 2.0-6.0), HPV35/51 (OR = 6.0; 95%CI = 1.8-15.0); HPV39/51 (OR = 6.4; 95% CI = 1.8-15), HPV31/52 (OR = 6.2; 95% CI = 1.8-15), HPV39/56 (OR = 11 95% CI = 8-12), HPV59/68 (OR = 8.2; 95% CI = 5.3-12.4), HPV66/68 (OR = 7; 95% CI = 2.4-13.5), independent of age and HIV status.ConclusionWe found that HIV does not influence the frequency, multiplicity and consanguinity of HR-HPV in cervical cancer. For the first time, we report high prevalence of HPV35 among women with confirmed cervical cancer in Zimbabwe, providing additional evidence of HPV diversity in sub-Saharan Africa. The data obtained here probes the need for larger prospective studies to further elucidate HPV diversity and possibility of selective pressure on genotypes.

Project description:BackgroundIn South Africa, within-country migration is common. Mobility affects many of the factors in the pathway for entry to or retention in care among people living with HIV. We characterized the patterns of migration (i.e., change in residency) among peripartum women from rural South Africa and their association with first-year postpartum mortality.Methods and findingsAll pregnant women aged ≥15 years were followed-up during pregnancy and the first year postpartum in a population-based longitudinal demographic and HIV surveillance program in KwaZulu-Natal, South Africa, from 2000 to 2016. During the household surveys (every 4-6 months), each household head was interviewed to record demographic components of the household, including composition, migration, and mortality. External migration was defined as moving (i.e., change in residency) into or out of the study area. For women of reproductive age, detailed information on new pregnancy and birth was recorded. Maternal death was ascertained via verbal autopsy and HIV status at delivery via annual HIV surveys. We fitted mixed-effects Cox regression models adjusting for multiple pregnancies per individual. Overall, 19,334 women had 30,291 pregnancies: 3,339 were HIV-positive, 10,958 were HIV-negative, and 15,994 had unknown HIV status at delivery. The median age was 24 (interquartile range: 20-30) years. During pregnancy and the first year postpartum, 64% (n = 19,344) and 13% (n = 3,994) did not migrate and resided within and outside the surveillance area, respectively. Of the 23% who had externally migrated at least once, 39% delivered outside the surveillance area. Overall, the mortality rate was 5.8 per 1,000 person-years (or 831 deaths per 100,000 live births) in the first year postpartum. The major causes of deaths were AIDS- or tuberculosis-related conditions both within 42 days of delivery (53%) and during the first year postpartum (62%). In this study, we observed that HIV-positive peripartum women who externally migrated and delivered outside the surveillance area had a hazard of mortality more than two times greater (hazard ratio = 2.74; 95% confidence interval 1.01-7.40, p-value = 0.047)-after adjusting for age, time period (before or after 2010), and sociodemographic status-compared to that of HIV-positive women who continuously resided within the surveillance area. Study limitations include lack of data on access to antiretroviral therapy (ART) care and social or clinical context at the destinations among mobile participants, which could lead to unmeasured confounding. Further information on how mobile postpartum women access and remain in care would be instructive.ConclusionsIn this study, we found that a substantial portion of peripartum women moved within the country around the time of delivery and experienced a significantly higher risk of mortality. Despite the scale-up of universal ART and declining trends in maternal mortality, there is an urgent need to derive a greater understanding of the mechanisms underlying this finding and to develop targeted interventions for mobile HIV-positive peripartum women.

Project description:Study was performed to improve understanding of erythropoiesis (EP) induced by acute anemia in Atlantic salmon. Fish was injected with a low dose of hemolytic compound phenylhydrazine (PHZ). Treatment resulted in moderate but significant reduction of hematocrit (Hct) and increased transcription of cardiac erythropoietin (epo) at 2 days post challenge (dpc), and epo receptor (epor) in spleen from 2 to 4 dpc. Oligonucleotide microarrays were used to characterize the events of EP in the spleen. These results were compared to gene expression profiles of untreated mature red blood cells (RBC) in order to search for erythroid-specific genes. Splenic responses suggested a prevalence of protective mechanisms at the first stage, characterized by induced xenobiotic metabolism and responses to oxidative and protein stress. Erythroid-specific regulation was evident at 2 dpc and enhanced by 4 dpc, and gene expression profiles witnessed a rapid establishment of RBC phenotype although Hct levels remained low. A large group of genes showed a strong correlation to globins by expression profiles. In addition to epor this included genes of heme and iron metabolism, scavengers of free radicals and chaperones, channels and transporters, markers of erythrocytes, regulators of proliferation and cell cycle arrest and many genes with unidentified roles in RBC differentiation. Induced EP in spleen was characterized by specific features, such as upregulation of virus-responsive genes and sustained high expression of proapoptotic genes including caspases. Transcriptome changes suggested an association between EP and suppression of several developmental programs including adaptive immune responses. In conclusion, acute hemolysis and resulting anemia rapidly induced EP in the spleen of Atlantic salmon, which showed both common characteristics for all vertebrates as well as fish-specific properties. Atlantic salmon was injected with a single dose of PHZ (6 mg/kg body mass) or saline. Spleen samples for microarray analyses were collected after 2 and 4 days. Additonally, red blood cells (RBC) were compared with spleen

Dataset Information

Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study.

Publications

Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study.

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