Association between Biomarkers of Inflammation and Total Liver Vitamin A Reserves Estimated by 13C-Retinol Isotope Dilution among Preschool Children in 5 African Countries.

BACKGROUND: Vitamin A (VA) assessment is important for targeting public health programs. Retinol isotope dilution (RID) is a sensitive method to estimate total body VA stores (TBSs) and total liver reserves (TLRs), but the impact of subclinical inflammation on RID is unclear. OBJECTIVE: We determined the association between TBSs and TLRs, estimated by RID, and inflammation among preschool children without clinical infection in Burkina Faso, Cameroon, Ethiopia, South Africa, and Tanzania. METHODS: Five studies (n = 532; 47.9 ± 8.3 mo; 49.0% male) included 13C-RID and measurement of inflammation markers, CRP, and α1-acid glycoprotein (AGP). Spearman correlations were used to evaluate TBSs and TLRs with inflammation biomarkers. Wilcoxon and Kruskal-Wallis tests were used to compare TBSs and TLRs by inflammation categories [normal vs. elevated CRP (>5 mg/L) or AGP (>1 g/L)] and inflammation stage [reference, incubation (elevated CRP), early convalescence (elevated CRP and AGP), and late convalescence (elevated AGP)]. RESULTS: Complete data were available for 439 children. Median (Q1, Q3) TLRs ranged from 0.12 (0.07, 0.18) µmol/g in Ethiopia to 1.10 (0.88, 1.38) µmol/g in South Africa. Elevated CRP ranged from 4% in Burkina Faso to 42% in Cameroon, and elevated AGP from 20% in Tanzania to 58% in Cameroon. Pooled analysis (excluding Cameroon) showed a negative correlation between TBSs and AGP (ρ = -0.131, P = 0.01). Children with elevated AGP had higher probability of having lower TBSs (probability = 0.61, P = 0.002). TBSs differed among infection stages (P = 0.020). Correlations between TLRs and CRP or AGP were not significant. CONCLUSIONS: No indication of systematic bias in RID-estimated TLRs was found due to subclinical inflammation among preschool children. The inverse relationship between TBSs and AGP may reflect decreased stores after infection or an effect of inflammation on isotope partitioning. Further research should investigate potential confounding variables to improve TBS-estimate validity.

Comparison of Total Body Vitamin A Stores Using Individual versus Population 13C-Natural Abundance of Serum Retinol in Preschool Children and Women Residing in 6 Diverse African Countries.

BACKGROUND: Stable isotope techniques using 13C to assess vitamin A (VA) dietary sources, absorption, and total body VA stores (TBSs) require determination of baseline 13C abundance. 13C-natural abundance is approximately 1.1% total carbon, but varies with foods consumed, supplements taken, and food fortification with synthetic retinyl palmitate. OBJECTIVES: We determined 13C variation from purified serum retinol and the resulting impact on TBSs using pooled data from preschool children in Burkina Faso, Cameroon, Ethiopia, South Africa, Tanzania, and Zambia and Zambian women. METHODS: Seven studies included children (n = 639; 56 ± 25 mo; 48% female) and one in women (n = 138; 29 ± 8.5 y). Serum retinol 13C-natural abundance was determined using GC-C-IRMS. TBSs were available in 7 studies that employed retinol isotope dilution (RID). Serum CRP and α1-acid-glycoprotein (AGP) were available from 6 studies in children. Multivariate mixed models assessed the impact of covariates on retinol 13C. Spearman correlations and Bland-Altman analysis compared serum and milk retinol 13C and evaluated the impact of using study- or global-retinol 13C estimates on calculated TBSs. RESULTS: 13C-natural abundance (%, median [Q1, Q3]) differed among countries (low: Zambia, 1.0744 [1.0736, 1.0753]; high: South Africa, 1.0773 [1.0769, 1.0779]) and was associated with TBSs, CRP, and AGP in children and with TBSs in women. 13C-enrichment from serum and milk retinol were correlated (r = 0.52; P = 0.0001). RID in children and women using study and global estimates had low mean bias (range, -3.7% to 2.2%), but larger 95% limits of agreement (range, -23% to 37%). CONCLUSIONS: 13C-natural abundance is different among human cohorts in Africa. Collecting this information in subgroups is recommended for surveys using RID. When TBSs are needed on individuals in clinical applications, baseline 13C measures are important and should be measured in all enrolled subjects.

Chronic and acute hypervitaminosis A are associated with suboptimal anthropometric measurements in a cohort of South African preschool children.

BACKGROUND: Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children. OBJECTIVES: We evaluated the relation between VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort. METHODS: Primary outcomes in these children (n = 94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z scores], serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)], and inflammation defined as C-reactive protein (CRP; ≥5 mg/L) and/or α1-acid glycoprotein (AGP; ≥1 g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. RESULTS: In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001), whereas formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each time point was vitamin D deficient (<50 nmol/L). CRP and AGP were not associated with growth measurements. CONCLUSIONS: Excessive TLRs due to dietary VA intake and VAS are associated with lower anthropometric measures and bone resorption decreased after supplementation. VA supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A. This trial is registered at clinicaltrials.gov as NCT02915731.

Increasing Cervical Cancer Incidence in Rural Eastern Cape Province of South Africa From 1998 to 2012: A Population-Based Cancer Registry Study.

PURPOSE: In this study, we aimed to investigate trends in the age-standardized and age-specific incidence rates in two distinct regions (the northern and southern areas) of South Africa covered by a population-based cancer registry. In addition, trends in coverage of the cervical cancer screening program were assessed using routine health service data. METHODS: Occurrences (topography C53.0-C53.9) for the period 1998-2012 were extracted from a cancer registry database from which basic descriptive statistics and frequencies were analyzed for all variables using CanReg4. Trends over time were estimated using a direct standardization method and world standard population as a reference. Screening coverage annualized figures for women age ≥ 30 years by sub-health district were extracted from the District Health Information System. RESULTS: In the northern area, annual age-standardized incidence rates per 100,000 women increased from 24.0 (95% CI, 21.1 to 27.0) in 1998-2002 to 39.0 (95% CI, 35.6 to 42.5) in 2008-2012, with a screening coverage rate of 15% by 2012. In contrast, no increase was observed in incidence in the southern area, with rates of 20.0 (95% CI, 18.5 to 21.4) in 1998-2002 and 18.8 (95% CI, 16.2 to 21.4) in 2008-2012, and the southern area had a higher screening coverage of 41% in 2012. Overall, the percentage distribution of stage at diagnosis showed that 28.5% of occurrences were diagnosed at disease stages I and II and 35%, at III and IV; 36% had with missing stage information (2003-2012). In 77% of occurrences, a histologically verified diagnosis was made, compared with only 12.3% by cytology. CONCLUSION: This study has demonstrated an almost two-fold increase in the incidence rate in the northern area but little change in the southern area of the cancer registry.

Liver is widely eaten by preschool children in the Northern Cape province of South Africa: Implications for routine vitamin A supplementation.

Previous research has demonstrated a virtual absence of vitamin A deficiency and adequacy of vitamin A intake through consumption of liver in preschool children of a community in the Northern Cape province of South Africa where sheep farming is common, and liver, an exceptionally rich source of vitamin A, is frequently eaten. Only 60-75 g of liver per month is needed to meet the vitamin A requirement of preschool children. Because this may have implications for routine vitamin A supplementation, and because liver consumption for the rest of the province is unknown, the study aim was to establish the prevalence and frequency of liver intake in a provincial-wide survey. An unquantified liver-specific food frequency questionnaire, covering a period of 1 month, complemented by a 1-year recall, was administered to mothers of 2- to 5-year-old children (n = 2,864) attending primary health care facilities in all five districts and 26 subdistricts. A total of 86% of children were reported to eat liver, which was eaten in all districts by at least 80% of children. The overall median frequency of liver intake was 1.0 [25th, 75th percentiles: 0.5, 3.0] times per month and ranged from 1.0 [0.3, 2.0] to 2.0 [1.0, 4.0] for the various districts. Based on a previously reported portion size of 66 g, these results suggest vitamin A dietary adequacy in all districts and possibly also vitamin A intake exceeding the Tolerable Upper Intake Level in some children. Routine vitamin A supplementation in this province may not be necessary and should be reconsidered.

South African preschool children habitually consuming sheep liver and exposed to vitamin A supplementation and fortification have hypervitaminotic A liver stores: a cohort study.

BACKGROUND: In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status. OBJECTIVE: We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification. METHODS: After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 µmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography. RESULTS: At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 µmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 µmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007). CONCLUSIONS: In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731.

Overlapping vitamin A interventions in the United States, Guatemala, Zambia, and South Africa: case studies.

Vitamin A (VA) deficiency is a serious public health problem, especially in preschool children who are at risk of increased mortality. In order to address this problem, the World Health Organization recommends periodic high-dose supplementation to children 6-59 months of age in areas of highest risk. Originally, supplementation was meant as a short-term solution until more sustainable interventions could be adopted. Currently, many countries are fortifying commercialized common staple and snack foods with retinyl palmitate. However, in some countries, overlapping programs may lead to excessive intakes. Our review uses case studies in the United States, Guatemala, Zambia, and South Africa to illustrate the potential for excessive intakes in some groups. For example, direct liver analysis from 27 U.S. adult cadavers revealed 33% prevalence of hypervitaminosis A (defined as ≥1 µmol/g liver). In 133 Zambian children, 59% were diagnosed with hypervitaminosis A using a retinol isotope dilution, and 16% had ≥5% total serum VA as retinyl esters, a measure of intoxication. In 40 South African children who frequently consumed liver, 72.5% had ≥5% total serum VA as retinyl esters. All four countries have mandatory fortified foods and a high percentage of supplement users or targeted supplementation to preschool children.

Serum retinol in post-partum mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency is absent.

Serum retinol was assessed in mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency known to be absent. Paired cord and maternal blood (n = 201) were collected after delivery and analysed for serum retinol and C-reactive protein (CRP). Liver intake during pregnancy and intention to breastfeed were also assessed. Mean serum retinol was 1.03 µmol/L ± 0.40 in mothers and 0.73 ± 0.24 µmol/L in newborns, with 21.4% and 49.3% having serum retinol <0.70 µmol/L (<20 µg/dL), respectively. Raised CRP was found in 59.9% of mothers, with a significant negative correlation between serum retinol and CRP (r = -0.273; p < 0.0001). Liver was eaten by 87.6% of mothers, and 99% indicated their intention to breastfeed. Despite consumption of liver, serum retinol was low in both the mother and the newborn. The conventional cut-off for serum retinol, i.e. <0.70 µmol/L may therefore not apply for the mother and newborn in the period immediately after delivery. Serum retinol may be influenced by factors other than vitamin A status, e.g. the haemodilution of pregnancy, as well as the acute phase response induced by the birth process, as suggested by raised CRP in 60% of mothers. In the newborns, the low serum retinol is likely to increase rapidly, as liver is frequently eaten by mothers and practically all of them intended to breastfeed. Our results confirm the need for better indicators of vitamin A status or alternative cut-off values during this period.

Iodine Concentration in Breastmilk and Urine among Lactating Women of Bhaktapur, Nepal.

Adequate iodine concentration in breastmilk (BMIC) is essential for optimal neonatal thyroid hormone synthesis and neurological development in breastfed infants. For many decades, iodine deficiency has been a public health problem in Nepal. However, recently, excessive iodine intakes among Nepali infants have been reported. This study aimed to measure BMIC and urinary iodine concentration (UIC) among lactating women in a peri-urban area of Nepal. Iodine concentration was measured in spot urine (n = 485) and breastmilk samples (n = 291) of 500 randomly selected lactating women. The median (p25, p75) BMIC and median UIC were 250 (130, 370) µg/L and 230 (135-377) µg/L, respectively. Around 82% had BMIC > 100 µg/L, 61% had BMIC > 200 µg/L and 81% had UIC > 100 µg/L, 37% had >300 µg/L and 20% had >500 µg/L. In multiple linear regression models, time since birth (ß 3.0, 95% CI (0.2, 5.0)) and UIC (ß 1.0, 95% CI (0.1, 2.0)) were associated with BMIC, explaining 26% of the variance. A large proportion of the women had adequate BMIC and UIC; however, a subset had high iodine concentrations. These findings emphasize the importance of carefully monitoring iodine intake to minimize the risk of iodine excess and subsequently preventing transient iodine-induced hypothyroidism in breastfed infants.

Low intake of calcium and vitamin D, but not zinc, iron or vitamin A, is associated with stunting in 2- to 5-year-old children.

OBJECTIVES: This cross-sectional study examined the nutritional factors associated with the high levels of stunting in 2- to 5-y-old children in an impoverished South African setting where liver is frequently eaten and vitamin A deficiency known to be absent. METHODS: Children's dietary intake was assessed by a single 24-h recall. Heights and weights were measured and information was obtained on breast-feeding history, the child's habitual milk intake, as well as substance use by the mother during pregnancy (n = 150). RESULTS: The overall prevalence of stunting was 36.9% (CI 29.2, 44.6) and increased with age, being 49% in the 4- to 5-y-old age category. Birth weight correlated significantly with height-for-age z-scores (HAZ; r = 0.250, P = 0.003), and was lower in children whose mothers smoked and used alcohol during pregnancy than in children whose mothers abstained (P < 0.0001). Median intake of energy, carbohydrate and protein was adequate. Median intake for all micronutrients was at least 90% of the estimated average requirement, except for calcium, vitamin D and vitamin E, which was 21%, 15%, and 32%, respectively. Intake of fat, calcium, phosphorous, vitamin D, riboflavin, and vitamin B12 (nutrients that typically occur in milk) was significantly lower in stunted than in non-stunted children (P < 0.05). When excluding children with low birth weight, intake of calcium, vitamin D, and riboflavin were still significantly lower (P < 0.05). HAZ was higher in children who habitually drank milk compared to those who did not (P = 0.003). CONCLUSIONS: Inadequate calcium and vitamin D intake, presumably because of low intake of milk after weaning, may have contributed to stunting in this population.

Liver intake in 24-59-month-old children from an impoverished South African community provides enough vitamin A to meet requirements.

OBJECTIVE: To assess the contribution of liver to the vitamin A intake of 24-59-month-old children from an impoverished South African community where liver is frequently consumed and vitamin A deficiency previously shown to be absent. DESIGN: Cross-sectional. SETTING: Northern Cape Province, South Africa. SUBJECTS: Children aged 24-59 months (n 150). Vitamin A intake from liver was assessed using a single 24 h recall and a quantified liver frequency questionnaire. In addition, information on vitamin A intake via the national fortification programme was obtained from the 24 h recall and information on vitamin A supplementation from the Road-to-Health Chart. Height, weight and socio-economic data were also collected. RESULTS: Stunting, underweight and wasting were prevalent in 36·9 %, 25·5 % and 12·1 % of children. Mean daily vitamin A intake from liver was 537 and 325 µg retinol equivalents measured by the 24 h recall and liver frequency questionnaire, respectively. Liver was consumed in 92·7 % of households and by 84·7 % of children; liver intake was inversely related to socio-economic status (P < 0·05). The food fortification programme contributed 80 µg retinol equivalents and the vitamin A supplementation programme 122 µg retinol equivalents to daily vitamin A intake. CONCLUSIONS: The study showed that liver alone provided more than 100 % of the Estimated Average Requirement of the pre-school children in this impoverished community. The results also challenge the notion generally held by international health bodies that vitamin A deficiency, poor anthropometric status and poverty go together, and reinforces the fact that South Africa is a culturally diverse society for which targeted interventions are required.

Serum retinol in 1-6-year-old children from a low socio-economic South African community with a high intake of liver: implications for blanket vitamin A supplementation.

OBJECTIVE: To assess serum retinol, liver intake patterns, breast-feeding history and anthropometric status in pre-school children of a low socio-economic community where liver is regularly consumed. DESIGN: Cross-sectional study. SETTING: Northern Cape Province, South Africa. SUBJECTS: Children aged 1-6 years (n 243) who attended the local primary health-care facility and had not received a vitamin A supplement in the 6 months preceding the study. Non-pregnant female caregivers (n 225), below 50 years of age, were also assessed. RESULTS: Despite stunting, underweight and wasting being prevalent in 40·5%, 23·1% and 8·4% of the children, only 5·8% had serum retinol concentrations < 20 µg/dl, which is in sharp contrast to the national prevalence of 63·6%. None of the caregivers were vitamin A deficient. Liver was eaten by 89·2% of children, with 87% of households eating liver at least once monthly and 30% eating it at least once weekly; liver was introduced into the diet of the children at a median age of 18 months. Ninety-three per cent of the children were being breast-fed or had been breast-fed in the past; children were breast-fed to a median age of 18 months. A significant negative correlation was found between educational level of the caregiver and frequency of liver intake (r = -0·143, P=0·032). There was no correlation between serum retinol and indicators of anthropometric or socio-economic status. CONCLUSIONS: The blanket approach in applying the national vitamin A supplementation programme may not be appropriate for all areas in the country, even though the community may be poor and undernourished.

The effect of vitamin A and zinc supplementation on treatment outcomes in pulmonary tuberculosis: a randomized controlled trial.

BACKGROUND: Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell-mediated responses. The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain. OBJECTIVE: The objective was to assess the efficacy of vitamin A and zinc supplementation on sputum smear and culture conversion and time to culture detection in adults with sputum smear-positive pulmonary tuberculosis. DESIGN: Participants attending a primary care tuberculosis clinic in Cape Town, South Africa, were randomly assigned to receive micronutrients (single dose of 200,000 IU retinyl palmitate plus 15 mg Zn/d for 8 wk) or matching placebo. Sputum was collected weekly for 8 wk for auramine staining and culture on liquid media (BACTEC MGIT 960; Becton Dickinson, Sparks, MD). Performance status, chest radiographs, and anthropometric measures were assessed at baseline and again at 8 wk. RESULTS: The participants (n = 154) were randomly assigned to the micronutrient (n = 77) or placebo (n = 77) group. Twenty participants were HIV infected (13%), and 12 participants had an unknown HIV status (8%). No differences in time to smear or culture conversion were observed between the treatment groups by Kaplan-Meier analysis (P = 0.15 and P = 0.38, respectively; log-rank test). Log-logistic regression analysis found no significant group interaction effect in time to culture detection over the 8-wk period (P = 0.32). No significant differences in weight gain (2.3 ± 3.5 compared with 2.2 ± 2.4 kg, P = 0.68) or radiologic resolution were observed between the treatment groups. CONCLUSION: Supplementation with vitamin A and zinc did not affect treatment outcomes in participants with pulmonary tuberculosis at 8 wk. This trial was registered at controlled-trials.com as ISRCTN80852505.

Fortifying brown bread with sodium iron EDTA, ferrous fumarate, or electrolytic iron does not affect iron status in South African schoolchildren.

The choice of iron fortificant usually represents a balance between bioavailability of the compound and its tendency to cause organoleptic problems. The aim of this study was to evaluate the efficacy of sodium iron EDTA (NaFeEDTA) and ferrous fumarate at levels compatible with South African brown bread (10 mg/kg flour for NaFeEDTA and 20 mg/kg flour for ferrous fumarate) in a randomized controlled trial; electrolytic iron was evaluated at the level currently used in South Africa (35 mg/kg flour). Schoolchildren (n = 361), aged 6-11 y, from a low socioeconomic community with hemoglobin (Hb) < or = 125 g/L were randomly assigned to 1 of 4 groups that received 4 slices of brown bread supplying either: 1) no fortification iron 2) 2.35 mg iron as NaFeEDTA; 3) 4.70 mg iron as ferrous fumarate; and 4) 8.30 mg iron as electrolytic iron per intervention day. These amounts simulated a bread intake of 6 slices per day over the 34-wk study period at fortification levels of 0, 10, 20, and 35 mg/kg flour, respectively. Hb concentration and iron status were assessed at baseline and after 34 wk of intervention. The iron interventions did not affect Hb concentration, transferrin saturation, or serum ferritin, iron, or transferrin receptor concentrations relative to the control group. Our results suggest that electrolytic iron at the level currently used in South Africa is not effective in improving iron or Hb status. Neither do NaFeEDTA or ferrous fumarate appear to be suitable alternatives for the fortification of wheat flour when included at levels that do not cause color changes.

Estimating the burden of disease attributable to iron deficiency anaemia in South Africa in 2000.

OBJECTIVES: To estimate the extent of iron deficiency anaemia (IDA) among children aged 0 - 4 years and pregnant women aged 15 - 49 years, and the burden of disease attributed to IDA in South Africa in 2000. DESIGN: The comparative risk assessment (CRA) methodology of the World Health Organization (WHO) was followed using local prevalence and burden estimates. IDA prevalence came from re-analysis of the South African Vitamin A Consultative Group study in the case of the children, and from a pooled estimate from several studies in the case of the pregnant women (haemoglobin level < 11 g/dl and ferritin level < 12 microg/l). Monte Carlo simulation-modelling was used for the uncertainty analysis. SETTING: South Africa. SUBJECTS: Children under 5 years and pregnant women 15 - 49 years. OUTCOME MEASURES: Direct sequelae of IDA, maternal and perinatal deaths and disability-adjusted life years (DALYs) from mild mental disability related to IDA. Results. It is estimated that 5.1% of children and 9 - 12% of pregnant women had IDA and that about 7.3% of perinatal deaths and 4.9% of maternal deaths were attributed to IDA in 2000. Overall, about 174,976 (95% uncertainty interval 150,344 - 203,961) healthy years of life lost (YLLs), or between 0.9% and 1.3% of all DALYs in South Africa in 2000, were attributable to IDA. CONCLUSIONS: This first study in South Africa to quantify the burden from IDA suggests that it is a less serious public health problem in South Africa than in many other developing countries. Nevertheless, this burden is preventable, and the study highlights the need to disseminate the food-based dietary guidelines formulated by the National Department of Health to people who need them and to monitor the impact of the food fortification programme.

Estimating the burden of disease attributable to childhood and maternal undernutrition in South Africa in 2000.

OBJECTIVES: To estimate the disease burden attributable to being underweight as an indicator of undernutrition in children under 5 years of age and in pregnant women for the year 2000. DESIGN: World Health Organization comparative risk assessment (CRA) methodology was followed. The 1999 National Food Consumption Survey prevalence of underweight classified in three low weight-for-age categories was compared with standard growth charts to estimate population-attributable fractions for mortality and morbidity outcomes, based on increased risk for each category and applied to revised burden of disease estimates for South Africa in 2000. Maternal underweight, leading to an increased risk of intra-uterine growth retardation and further risk of low birth weight (LBW), was also assessed using the approach adopted by the global assessment. Monte Carlo simulation-modeling techniques were used for the uncertainty analysis. SETTING: South Africa. SUBJECTS: Children under 5 years of age and pregnant women. OUTCOME MEASURES: Mortality and disability-adjusted life years (DALYs) from protein- energy malnutrition and a fraction of those from diarrhoeal disease, pneumonia, malaria, other non- HIV/AIDS infectious and parasitic conditions in children aged 0 - 4 years, and LBW. RESULTS: Among children under 5 years, 11.8% were underweight. In the same age group, 11,808 deaths (95% uncertainty interval 11,100 - 12,642) or 12.3% (95% uncertainty interval 11.5 - 13.1%) were attributable to being underweight. Protein-energy malnutrition contributed 44.7% and diarrhoeal disease 29.6% of the total attributable burden. Childhood and maternal underweight accounted for 2.7% (95% uncertainty interval 2.6 - 2.9%) of all DALYs in South Africa in 2000 and 10.8% (95% uncertainty interval 10.2 - 11.5%) of DALYs in children under 5. CONCLUSIONS: The study shows that reduction of the occurrence of underweight would have a substantial impact on child mortality, and also highlights the need to monitor this important indicator of child health.

Estimating the burden of disease attributable to vitamin A deficiency in South Africa in 2000.

OBJECTIVES: To estimate the burden of disease attributable to vitamin A deficiency in children aged 0 - 4 years and pregnant women aged 15 - 49 years in South Africa in 2000. DESIGN: The framework adopted for the most recent World Health Organization comparative risk assessment (CRA) methodology was followed. Population-attributable fractions were calculated from South African Vitamin A Consultative Group (SAVACG) survey data on the prevalence of vitamin A deficiency in children and the relative risks of associated health problems, applied to revised burden of disease estimates for South Africa in the year 2000. Small community studies were used to derive the prevalence in pregnant women. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. SETTING: South Africa. SUBJECTS: Children under 5 years and pregnant women 15 - 49 years. OUTCOME MEASURES: Direct sequelae of vitamin A deficiency, including disability-adjusted life years (DALYs), as well as mortality associated with measles, diarrhoeal diseases and other infections, and mortality and DALYs associated with malaria in children and all-cause maternal mortality. RESULTS: One-third of children aged 0 - 4 years and 1 - 6% of pregnant women were vitamin A-deficient. Of deaths among young children aged 0 - 4 years in 2000, about 28% of those resulting from diarrhoeal diseases, 23% of those from measles, and 21% of those from malaria were attributed to vitamin A deficiency, accounting for some 3,000 deaths. Overall, about 110,467 ( 95% uncertainty interval 86,388 - 136,009) healthy years of life lost, or between 0.5% and 0.8% of all DALYs in South Africa in 2000 were attributable to vitamin A deficiency. CONCLUSIONS: The vitamin A supplementation programme for children and the recent food fortification programme introduced in South Africa in 2003 should prevent future morbidity and mortality related to vitamin A deficiency. Monitoring the effectiveness of these interventions is strongly recommended.

Ascaris, co-infection and allergy: the importance of analysis based on immunological variables rather than egg excretion.

The ratio of Ascaris seropositivity to the presence of eggs in the faeces was 2.44 in children residing near Cape Town, South Africa. Similar and larger ratios have previously been described for children and women living in the city. The new finding strengthens the concept that when helminthic infections occur together with non-helminthic diseases, an analysis of the interaction must include the use of disease-related immunological variables and not be based only on egg excretion status. One of the reasons is that many egg-negative people who live where helminthiasis is highly endemic are immunologically activated as a result of transitory non-patent or intermittent patent infection by Ascaris and/or other worms.

Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses.

BACKGROUND: Ascariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly. With these factors in mind, we have started to document the extent of long-term exposure to Ascaris and other helminths in a community where HIV/AIDS is highly prevalent. In more advanced studies, objectives are to analyse relevant immunological variables (e.g. cytokine activity and immunoglobulin levels). We postulate that when Ascaris is hyperendemic, analysis of possible consequences of co-infection by HIV cannot be based primarily on excretion vs non-excretion of eggs. METHODS: Recall of worms seen in faeces was documented in relation to the age of adult volunteers who were either seropositive (n = 170) or seronegative (n = 65) for HIV. Reasons for HIV testing, deworming treatments used or not used, date and place of birth, and duration of residence in Cape Town, were recorded. Confidence intervals were calculated both for group percentages and the inter-group differences, and were used to make statistical comparisons. RESULTS: In both groups, more than 70% of participants were aware of having passed worms, often both when a child and as an adult. Most of the descriptions fitted Ascaris. Evidence for significantly prolonged exposure to helminthic infection in HIV-positives was supported by more recall of deworming treatment in this group (p < 0.05). Over 90% of the participants had moved to the city from rural areas. CONCLUSION: There was a long-term history of ascariasis (and probably other helminthic infections) in both of the groups that were studied. In women in the same community, and in children living where housing and sanitation are better, Ascaris sero-prevalence exceeded egg-prevalence by two- and three-fold, respectively. For ongoing and future analyses of possible consequences of co-infection by Ascaris (and/or other helminths) and HIV/AIDS (and/or other bystander conditions), comparisons must be based mainly on disease-related immunological variables. Especially in adults, comparisons cannot be based only on the presence or absence of eggs in excreta.