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R Broadhead

Publications and source records attributed to R Broadhead.

At least 19 recordsLinked to original sources

Spectrum and presentation of pediatric malignancies in the HIV era: experience from Blantyre, Malawi, 1998-2003.

BACKGROUND: Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to document the frequency of pediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children. PROCEDURE: A retrospective audit of the spectrum and clinical presentation of cancers among children (<16 years) seen at Queen Elizabeth's Central Hospital (QECH), between 1998 and 2003. RESULTS: Seven hundred seven children with cancer were seen, the number of cases per year increased over the time period; 50% (351) had Burkitt lymphoma, 13% (89) had retinoblastoma, and 9% (61) had Kaposi sarcoma, with a variety of other tumors comprising the remainder. Kaposi sarcoma markedly increased in frequency over time. Histological verification of diagnosis was available for 49% (348). The proportion of children with cancer who were tested for HIV increased over time, but varied by cancer type. Amongst those tested, the seroprevalence was 93% (52/56) for children with Kaposi sarcoma, 4% (11/289) for those with Burkitt lymphoma, 31% (8/26) for those with other non-Hodgkin lymphomas, 7% (1/15) for those with Hodgkin disease, and 5% (5/103) for those with other cancers. CONCLUSIONS: The number of cases seen per year has increased over the study period for almost all cancers, but in particular for Kaposi sarcoma. Burkitt lymphoma remains the commonest pediatric tumor in Malawi. In the case of Burkitt lymphoma, non-Hodgkin lymphoma, and Kaposi sarcoma there is a significant difference in the presentation of HIV-seropositive and -seronegative children.

Burkitt Lymphoma↗

Effect of antibiotic treatment of subclinical mastitis on human immunodeficiency virus type 1 RNA in human milk.

Although subclinical mastitis is associated with increased HIV load in breast milk, it is not known whether empirical treatment with antibiotics will reduce breast milk HIV load. We examined the effect of antibiotic treatment for subclinical mastitis on HIV load in breast milk. Seventy-five HIV-infected post-partum women in Malawi with subclinical mastitis were treated with oral amoxicillin/clavulanic acid and were followed between 1 and 24 weeks later. Breastmilk HIV-1 load and sodium concentration were measured and microbiological studies were performed at presentation. At 1 week (n = 34), the proportion of women with elevated breast milk leukocyte counts decreased significantly to 41.2% (p < 0.0001) and there was a nonsignificant increase in breast milk HIV-1 RNA load (p = 0.9264) and sodium concentration (p = 0.08) in the affected breast. At 4 to 12 weeks (n = 63), breast milk HIV-1 RNA load and sodium concentration decreased significantly (p < 0.05) and 17.5% had elevated breast milk leukocyte counts. Treatment with amoxicillin/clavulanic acid was associated with a significant decrease in inflammation of the breast, but breast milk HIV load remained elevated despite a significant decrease from baseline. These findings have important implications regarding how mothers should be counselled on safety of resuming breastfeeding after resolution of subclinical mastitis.

Amoxicillin↗

Epidemiology and microbiology of subclinical mastitis among HIV-infected women in Malawi.

The epidemiology and microbiology of subclinical mastitis, a risk factor for perinatal HIV transmission, have not been well characterized. In all, 250 HIV-infected women were followed from two weeks to 12 months postpartum in Blantyre, Malawi, and subclinical mastitis was assessed by breast milk leukocyte counts. The point prevalence of subclinical mastitis at 2, 4, 6, 10, and 14 weeks, and 6, 9, and 12 months was 12.2%, 7.8%, 6.8%, 3.7%, 10.6%, 5.1%, 4.9%, and 1.9%, respectively (P = 0.002), and 27.2% of women had at least one episode of subclinical mastitis. There was no significant relationship between maternal plasma HIV load or parity and subclinical mastitis. Staphylococcus aureus was isolated in 30% of women with subclinical mastitis, and the proportion of women with positive cultures decreased during follow-up (P = 0.02). Subclinical mastitis is prevalent among breastfeeding mothers and further studies are needed to characterize the differences between infectious and non-infectious subclinical mastitis.

Adult↗

Changes in haemoglobin levels in infants in Malawi: effect of low birth weight and fetal anaemia.

OBJECTIVES: To examine the effect of low birth weight (LBW) and fetal anaemia (FA) on haemoglobin (Hb) patterns in infancy. To study the additional contribution of other risk factors known at birth. To examine the effect of iron supplementation during infancy on Hb levels. METHODS: A stratified cohort of infants in Malawi (83 with LBW (< 2500 g), 111 with FA (cord Hb < 125 g/l), 31 with both LBW and FA, and 176 controls) was followed during infancy. Hb levels were measured at about 2, 4, 6, 9, and 12 months of age. Repeated measures models were used to describe the changes in Hb levels over time. RESULTS: The mean Hb concentration in the control group was 95.5 g/l (95% confidence interval (CI) 92.5 to 98.5) at 2 months, 86.9 g/l (95% CI 84.4 to 89.4) at 9 months, and 898 g/l (95% CI 874 to 92.2) at 12 months. Differences between LBW infants and controls increased over time (difference at 12 months: 5.5 g/l (95% CI 1.3 to 9.7)). Infants with FA had borderline significantly lower Hb at 2 months (p = 0.07), but at 6 months their levels were similar to those of controls. The LBW infants and those with FA had the lowest Hb levels (difference from controls at 12 months 7.9 g/l). Parity, placental and maternal malaria at delivery, and sex significantly affected Hb levels after adjustment for LBW and FA. After iron supplementation, Hb significantly increased. CONCLUSIONS: Antimalarial control and iron supplementation throughout pregnancy should be increased to reduce the incidence of infant anaemia and improve child development and survival.

Anemia↗

Viral levels in newborn African infants undergoing primary HIV-1 infection.

We examined weekly changes in viral levels in seven untreated infants infected with HIV at birth. Viral levels spiked immediately but reverted quickly to plateau levels typical of infant HIV infection within 2 weeks of first detected viraemia. We speculated that the depletion of naive, susceptible cells is responsible for the rapid decrease in spike levels and that the rapid replacement of lymphocytes in infants causes the high plateau viral levels (10(5) copies/ml) to be sustained.

HIV Infections↗

Iron status and indicators of human immunodeficiency virus disease severity among pregnant women in Malawi.

The relationships among hemoglobin, ferritin, and transferrin receptor levels and 2 markers of human immunodeficiency virus (HIV) disease severity--HIV load and CD4(+) lymphocyte count--were characterized among 483 pregnant women in Malawi, Africa. The only significant correlation was an inverse correlation between hemoglobin level and plasma HIV load (r=-.104; P<.03). The prevalence of iron deficiency anemia was not significantly different across quartiles of HIV load or CD4(+) lymphocyte count. In contrast to previous studies, these data suggest that iron status is not related to markers of HIV disease severity in pregnant women in Africa.

Anemia, Iron-Deficiency↗

Impact of vitamin A supplementation on anaemia and plasma erythropoietin concentrations in pregnant women: a controlled clinical trial.

INTRODUCTION: Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans. OBJECTIVE: To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia. METHODS: A randomized, double-blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 microg retinol equivalent), iron (30 mg), and folate (400 microg) versus iron (30 mg) and folate (400 microg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa. RESULTS: Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin <110 g/L). Mean (+/-SEM) change in haemoglobin from enrollment to 38 wk was 4.7+/-1.6 g/L (p=0.003) and 7.3+/-2.3 g/L (p=0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39+/-5.00 (p=0.63) and -2.87+/-3.92 IU/L (p=0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow-up within either group. CONCLUSIONS: Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi.

Adult↗

Plasma and breast milk vitamin A as indicators of vitamin A status in pregnant women.

Breast milk vitamin A is not well characterized as an indicator of vitamin A status in women with infections. A controlled trial of vitamin A, 3 mg retinol equivalent/day, was conducted among 697 pregnant women with human immunodeficiency virus (HIV) infection in Malawi which allowed comparison of plasma versus breast milk vitamin A as indicators of vitamin A status. Retinol concentrations were measured in plasma at baseline (18-28 weeks) and 38 weeks gestation and breast milk at 6 weeks post-partum. Plasma alpha 1-acid glycoprotein (AGP) and C-reactive protein (CRP) were measured at baseline. Plasma retinol (geometric mean, SD) at 38 weeks was 0.72 (0.44, 1.18) and 0.61 (0.38, 0.98) mumol/L (P < 0.0002) and breast milk retinol was 1.32 (0.71, 2.43) and 0.95 (0.49, 1.82) mumol/L (P < 0.0001) in vitamin A and placebo groups, respectively. Women with elevated acute phase protein (AGP > 1 gm/L and/or CRP > 5 mg/L) at baseline who received vitamin A had significantly higher plasma and breast milk vitamin A at follow-up compared with placebo. Elevated acute phase proteins did not distinguish women with low body stores of vitamin A. Breast milk retinol appears to be a better indicator of vitamin A status than plasma retinol in women with infections.

Adult↗

Assessment of iron status using plasma transferrin receptor in pregnant women with and without human immunodeficiency virus infection in Malawi.

BACKGROUND: Although anemia is highly prevalent during pregnancy and is common during human immunodeficiency virus (HIV) infection, anemia and iron status have not been well characterized in HIV-infected pregnant women. OBJECTIVE: To gain insight into iron status in HIV-infected pregnant women using plasma transferrin receptor and related indicators of anemia. STUDY DESIGN: Plasma transferrin receptor, ferritin, alpha1-acid glycoprotein, C-reactive protein and hemoglobin concentrations were measured in pregnant women, gestational age 18-28 weeks, seen in an urban antenatal clinic in Blantyre, Malawi. RESULTS: The prevalence of anemia among 662 HIV-positive and 190 HIV-negative pregnant women was 73.1% and 50.0%, respectively (P<0.0001). Among HIV-positive and HIV-negative women, median plasma transferrin receptor concentrations were 24.4 and 24.1 nmol/l (P=0.5), respectively, and median plasma ferritin concentrations were 17.8 and 20.8 microg/l (P<0.05), respectively. There was a large overlap in plasma transferrin receptor concentrations among women with and without anemia. Using the combination of hemoglobin and ferritin as a standard, the sensitivity and specificity of plasma transferrin receptor in diagnosing iron deficiency anemia was estimated at 45.9% and 68.1%, respectively. CONCLUSION: The use of plasma transferrin receptor concentrations as an indicator of iron deficiency anemia may be limited in pregnant women with chronic inflammation and infection.

Adult↗

HIV transmission through breastfeeding: a study in Malawi.

CONTEXT: Understanding the risk of human immunodeficiency virus (HIV) transmission through breastfeeding is essential for advising HIV-infected mothers and formulating public health policy recommendations. OBJECTIVE: To measure the frequency, timing, and risk factors of HIV transmission through breast milk. DESIGN: Prospective cohort study conducted between 1994 and 1997, with follow-up of infants through 24 months of age. SETTING: Postnatal clinic of tertiary care hospital, Blantyre, Malawi. PARTICIPANTS: A total of 672 infants (HIV-negative at birth) born to HIV-infected women who had not received antiretroviral drugs during or after pregnancy. MAIN OUTCOME MEASURE: Incidence of HIV in breastfed infants by age and maternal and infant risk factors for HIV transmission, using proportional hazard models to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Forty-seven children became HIV-infected while breastfeeding but none after breastfeeding had stopped. The cumulative infection rate while breastfeeding, from month 1 to the end of months 5, 11,17, and 23, was 3.5%, 7.0%, 8.9%, and 10.3%, respectively. Incidence per month was 0.7% during age 1 to 5 months, 0.6% during age 6 to 11 months, and 0.3% during age 12 to 17 months (P = .01 for trend). The only factors significantly associated with low risk of postnatal HIV transmission in a multivariate model were high maternal parity (RR, 0.23; 95% CI, 0.09-0.56) and older maternal age (RR, 0.44; 95% CI, 0.23-0.84). CONCLUSIONS: Our data suggest that the risk of HIV infection is highest in the early months of breastfeeding, which should be considered in formulating breastfeeding policy recommendations.

Breast Feeding↗

Human immunodeficiency virus load in breast milk, mastitis, and mother-to-child transmission of human immunodeficiency virus type 1.

Human immunodeficiency virus (HIV) type 1 load in breast milk and mastitis were examined as risk factors for vertical transmission of HIV-1. Six weeks after delivery, HIV-1 load and sodium (an indicator of mastitis) were measured in breast milk from 334 HIV-1-infected women in Malawi. Median breast milk HIV-1 load was 700 copies/mL among women with HIV-1-infected infants versus undetectable (<200 copies/mL) among those with uninfected infants, respectively (P<. 0001). Elevated breast milk sodium levels consistent with mastitis occurred in 16.4% of HIV-1-infected women and were associated with increased vertical transmission of HIV-1 (P<.0001). Median breast milk HIV-1 load was 920 copies/mL among women with versus undetectable among those without elevated breast milk sodium levels, respectively (P<.0001). Mastitis and breast milk HIV-1 load may increase the risk of vertical transmission of HIV-1 through breast-feeding.

Adult↗

Virus levels in untreated African infants infected with human immunodeficiency virus type 1.

In developed areas, human immunodeficiency virus (HIV)-infected infants have high virus levels and rapidly progress to death. HIV levels were assessed in 1994-1997 in untreated infants in Malawi by analysis of dried blood spots tested by nucleic acid silica-bound amplification. Of 24 umbilical cord blood (CB)-positive samples, 83% had >10,000 copies/mL. The median virus level was 78,000 copies/mL. First positive sample median levels were 355,000 copies/mL among 52 perinatally infected infants and 130,000 copies/mL among 43 infants infected by breast-feeding. Virus levels were stable, and initial levels predicted levels 1 year after infection (P=.005), at which time levels did not significantly differ among in utero, perinatally, or postnatally infected infants. Thus, neither age at infection nor route of infection significantly influenced HIV levels measured 1 year after infection. Most (87%) CB-positive infants were infected before labor onset, since virus levels greatly exceeded those expected in their mothers.

Adult↗

Predictors and impact of losses to follow-up in an HIV-1 perinatal transmission cohort in Malawi.

BACKGROUND: Large simple trials which aim to study therapeutic interventions and epidemiological associations of human immunodeficiency virus (HIV) infection, including perinatal transmission, in Africa may have substantial rates of loss to follow-up. A better understanding of the characteristics and the impact of women and children lost to follow-up is needed. METHODS: We studied predictors and the impact of losses to follow-up of infants born in a large cohort of delivering women in urban Malawi. The cohort was established as part of a trial of vaginal cleansing with chlorhexidine during delivery to prevent mother-to-infant transmission of HIV. RESULTS: The HIV infection status could not be determined for 797 (36.9%) of 2156 infants born to HIV-infected mothers; 144 (6.7%) with missing status because of various sample problems and 653 (30.3%) because they never returned to the clinic. Notably, the observed rates of perinatal transmission were significantly lower in infants who returned later for determination of their infection status (odds ratio = 0.94 per month, P = 0.03), even though these infants must have had an additional risk of infection from breastfeeding. In multivariate models, infants of lower birthweight (P = 0.003) and, marginally, singletons (P = 0.09) were less likely to return for follow-up. The parents of infants lost to follow-up tended to be less educated (P < 0.001) and more likely to be in farming occupations, although one educated group, teachers and students, were also significantly less likely to return. Of these variables, infant birthweight, twins versus singletons, and maternal education were also associated with significant variation in the observed risk of perinatal transmission among infants of known HIV status. CONCLUSIONS: Several predictors of loss to follow-up were identified in this large HIV perinatal cohort. Losses to follow-up can impact the observed transmission rate and the risk associations in different studies.

DNA, Viral↗

Mastitis and immunological factors in breast milk of lactating women in Malawi.

Although an elevated sodium concentration in human milk is suggested to be an indicator of mastitis, it is unclear whether elevated sodium concentrations are associated with immunological and inflammatory mediators in human milk. We conducted a cross-sectional study to evaluate the relationships between elevated breast milk sodium concentrations and levels of lactoferrin, lysozyme, secretory leukocyte protease inhibitor (SLPI), interleukin-8 (IL-8), and RANTES (regulated on activation normal T cell expressed and secreted) in human milk at 6 weeks postpartum in 96 lactating women in Blantyre, Malawi. Mastitis, as indicated by an elevated breast milk sodium concentration, was present in 15.6% of the women. Women with and without mastitis had respective median levels of other factors as follows: lactoferrin, 1,230 versus 565 mg/liter (P < 0. 0007); lysozyme, 266 versus 274 mg/liter (P = 0.55); SLPI, 76 versus 15 microg/liter, (P < 0.0002); IL-8, 339 versus 25 ng/liter (P < 0. 0001); and RANTES, 82 versus 3 ng/liter (P < 0.0001). Elevated sodium concentrations in breast milk are associated with an increase in levels of some immunological and inflammatory factors in breast milk.

Adolescent↗

Mastitis and immunological factors in breast milk of human immunodeficiency virus-infected women.

Human milk contains important immunological factors that protect the breast from infection and are thought to protect infants from infection, including human immunodeficiency virus (HIV) infection. Human milk immunological factors have not been well characterized in HIV-infected lactating women. Lysozyme, secretory leukocyte protease inhibitor (SLPI), sodium (an indicator of mastitis), and HIV were measured in breast milk of 334 HIV-infected women at 6 weeks postpartum. Women with mastitis, as indicated by elevated breast milk sodium concentrations, had higher median levels lysozyme (290 vs 221 mg/L, p < 0.04), SLPI (38 vs 19 mg/L, p < 0.0001) and HIV (920 copies/mL vs undetectable, p < 0.0001) compared with women without mastitis. Lower total plasma carotenoid levels (p < 0.02) and higher maternal HIV load (p < 0.006) by quartile were risk factors for mastitis. Mastitis, as indicated by elevated breast milk sodium levels, is associated with high concentrations of immunological factors and higher HIV load in breast milk.

Adult↗

Carotenoid status of pregnant women with and without HIV infection in Malawi.

OBJECTIVE: To characterise the major plasma carotenoids in pregnant women with and without HIV infection attending antenatal clinic in Blantyre, Malawi. DESIGN: A cross sectional study. SETTING: Antenatal clinic of Queen Elizabeth Central Hospital, Blantyre, Malawi. SUBJECTS: Nine hundred women (697 HIV-positive and 203 HIV-negative women) in their second trimester of pregnancy. MAIN OUTCOME MEASURES: Plasma carotenoid levels as related to HIV status and level of disease progression. RESULTS: There were no significant differences in plasma carotenoid levels between HIV-positive and HIV-negative women. Median (25th, 75th percentiles) plasma levels of carotenoids for all women in the study were alpha-carotene, 0.040 (0.23, 0.071) mumol/L; beta-carotene, 0.350 (0.192, 0.595) mumol/L; beta-cryptoxanthin, 0.050 (0.029, 0.091) mumol/L; lutein/zeaxanthin 0.646 (0.426, 0.976) mumol/L; lycopene, 0.088 (0.055, 0.138) mumol/L, and total carotenoids 1.321 (0.884, 1.874) mumol/L. Mothers had higher mean plasma concentrations of alpha-carotene (p < 0.04), beta-carotene (p < 0.0001), lutein/zeaxanthin (p < 0.0001), and total carotenoids (p < 0.0001) in the wet season than the dry season. No seasonality was observed for beta-cryptoxanthin, lycopene, or retinol. CONCLUSION: This study suggests that pregnant women with and without HIV infection in Blantyre, Malawi have relatively low plasma carotenoid levels and poor dietary intake of provitamin A carotenoids.

Carotenoids↗