Wafaie W. Fawzi

Non-communicable diseases in sub-Saharan Africa: what we know now

BACKGROUND Sub-Saharan Africa (SSA) has a disproportionate burden of both infectious and chronic diseases compared with other world regions. Current disease estimates for SSA are based on sparse data, but projections indicate increases in non-communicable diseases (NCDs) caused by demographic and epidemiologic transitions. We review the literature on NCDs in SSA and summarize data from the World Health Organization and International Agency for Research on Cancer on the prevalence and incidence of cardiovascular diseases, diabetes mellitus Type 2, cancer and their risk factors. METHODS We searched the PubMed database for studies on each condition, and included those that were community based, conducted in any SSA country and reported on disease or risk factor prevalence, incidence or mortality. RESULTS We found few community-based studies and some countries (such as South Africa) were over-represented. The prevalence of NCDs and risk factors varied considerably between countries, urban/rural location and other sub-populations. The prevalence of stroke ranged from 0.07 to 0.3%, diabetes mellitus from 0 to 16%, hypertension from 6 to 48%, obesity from 0.4 to 43% and current smoking from 0.4 to 71%. Hypertension prevalence was consistently similar among men and women, whereas women were more frequently obese and men were more frequently current smokers. CONCLUSIONS The prevalence of NCDs and their risk factors is high in some SSA settings. With the lack of vital statistics systems, epidemiologic studies with a variety of designs (cross-sectional, longitudinal and interventional) capable of in-depth analyses of risk factors could provide a better understanding of NCDs in SSA, and inform health-care policy to mitigate the oncoming NCD epidemic.

The associations of parity and maternal age with small-for-gestational-age preterm and neonatal and infant mortality: a meta-analysis.

BackgroundPrevious studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).MethodsData from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.ResultsNulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.ConclusionsNulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.FundingFunding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis

BACKGROUND Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. METHODS For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2,015,019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. FINDINGS Pooled overall RRs for preterm were 6·82 (95% CI 3·56-13·07) for neonatal mortality and 2·50 (1·48-4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34-2·50) for neonatal mortality and 1·90 (1·32-2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11-26·12). INTERPRETATION Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4--the reduction of child mortality. FUNDING Bill & Melinda Gates Foundation.

Effects of Vitamin A Supplementation on Immune Responses and Correlation with Clinical Outcomes

SUMMARY Vitamin A supplementation to preschool children is known to decrease the risks of mortality and morbidity from some forms of diarrhea, measles, human immunodeficiency virus (HIV) infection, and malaria. These effects are likely to be the result of the actions of vitamin A on immunity. Some of the immunomodulatory mechanisms of vitamin A have been described in clinical trials and can be correlated with clinical outcomes of supplementation. The effects on morbidity from measles are related to enhanced antibody production and lymphocyte proliferation. Benefits for severe diarrhea could be attributable to the functions of vitamin A in sustaining the integrity of mucosal epithelia in the gut, whereas positive effects among HIV-infected children could also be related to increased T-cell lymphopoiesis. There is no conclusive evidence for a direct effect of vitamin A supplementation on cytokine production or lymphocyte activation. Under certain circumstances, vitamin A supplementation to infants has the potential to improve the antibody response to some vaccines, including tetanus and diphtheria toxoids and measles. There is limited research on the effects of vitamin A supplementation to adults and the elderly on their immune function; currently available data provide no consistent evidence for beneficial effects. Additional studies with these age groups are needed.

Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis

Objectives To summarise evidence on the associations of maternal anaemia and prenatal iron use with maternal haematological and adverse pregnancy outcomes; and to evaluate potential exposure-response relations of dose of iron, duration of use, and haemoglobin concentration in prenatal period with pregnancy outcomes. Design Systematic review and meta-analysis Data sources Searches of PubMed and Embase for studies published up to May 2012 and references of review articles. Study selection criteria Randomised trials of prenatal iron use and prospective cohort studies of prenatal anaemia; cross sectional and case-control studies were excluded. Results 48 randomised trials (17 793 women) and 44 cohort studies (1 851 682 women) were included. Iron use increased maternal mean haemoglobin concentration by 4.59 (95% confidence interval 3.72 to 5.46) g/L compared with controls and significantly reduced the risk of anaemia (relative risk 0.50, 0.42 to 0.59), iron deficiency (0.59, 0.46 to 0.79), iron deficiency anaemia (0.40, 0.26 to 0.60), and low birth weight (0.81, 0.71 to 0.93). The effect of iron on preterm birth was not significant (relative risk 0.84, 0.68 to 1.03). Analysis of cohort studies showed a significantly higher risk of low birth weight (adjusted odds ratio 1.29, 1.09 to 1.53) and preterm birth (1.21, 1.13 to 1.30) with anaemia in the first or second trimester. Exposure-response analysis indicated that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was 0.88 (0.84 to 0.92) (P for linear trend<0.001). Birth weight increased by 15.1 (6.0 to 24.2) g (P for linear trend=0.005) and risk of low birth weight decreased by 3% (relative risk 0.97, 0.95 to 0.98) for every 10 mg increase in dose/day (P for linear trend<0.001). Duration of use was not significantly associated with the outcomes after adjustment for dose. Furthermore, for each 1 g/L increase in mean haemoglobin, birth weight increased by 14.0 (6.8 to 21.8) g (P for linear trend=0.002); however, mean haemoglobin was not associated with the risk of low birth weight and preterm birth. No evidence of a significant effect on duration of gestation, small for gestational age births, and birth length was noted. Conclusions Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.

Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality.

Background: HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status. Methods: A total of 1078 HIV-infected pregnant women from Tanzania were randomly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks’ gestation and throughout lactation. Results: Multivitamins excluding A had no effect on the total risk of HIV-1 transmission (RR 1.04, 95% CI 0.82–1.32, P = 0.76). Vitamin A increased the risk of transmission (RR 1.38, 95% CI 1.09–1.76, P = 0.009). Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding, and mortality by 24 months among those alive and not infected at 6 weeks. Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts (RR 0.37; 95% CI 0.16–0.85, P = 0.02) compared with infants of mothers with higher counts (RR 0.99, 95% CI 0.68–1.45, P = 0.97; P-for-interaction 0.03). Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate (P-for-interaction 0.06), low hemoglobin (P-for-interaction 0.06), and low birthweight babies (P-for-interaction 0.04). Multivitamins reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status. Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months. Conclusion: Vitamin A increased the risk of HIV-1 transmission. Multivitamin (B, C, and E) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women. The provision of these supplements to HIV-infected lactating women should be considered.

Predictors of HIV-1 Serostatus Disclosure: A Prospective Study Among HIV-Infected Pregnant Women in Dar es Salaam, Tanzania

ObjectivesTo examine the socio-demographic and behavioral factors predictive of womens disclosure of an HIV-positive test result in Dar es Salaam, Tanzania. DesignFrom April 1995 to May 2000, 1078 HIV-positive pregnant women participated in an ongoing randomized trial on micronutrients and HIV-1 vertical transmission and progression. Disclosure to a partner or to a female relative was assessed 2 months after post-test counseling and at 6 monthly follow-up visits. Socio-demographic, health, behavioral and psychological factors were measured at baseline and during follow-up. MethodsPredictors of time to disclosure of HIV serostatus were determined using Cox proportional hazards regression models. ResultsPrevalence of disclosure to a partner ranged from 22% within 2 months to 40% after nearly 4 years. Women were less likely to disclose to their partners if they were cohabiting, had low wage employment, had previously disclosed to a female relative, or reported ever-use of a modern contraceptive method. Women reporting fewer than six lifetime sexual partners or knowing someone with HIV/AIDS were more likely to disclose to their partners. Disclosure to a female relative was predicted by knowing more than two individuals with HIV/AIDS, full economic dependency on their partner, high levels of social support, and prior attendance at a support group meeting. ConclusionsA substantial proportion of HIV-infected pregnant women never disclosed their result to a partner or a close female relative. Lack of disclosure may have limited their ability to engage in preventive behaviors or to obtain the necessary emotional support for coping with their serostatus or illness.

National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010

Summary Background National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Methods Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. Findings In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh. Interpretation The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. Funding Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG).

Different Rates of Disease Progression of HIV Type 1 Infection in Tanzania Based on Infecting Subtype

BACKGROUND Many different subtypes of human immunodeficiency virus (HIV) type 1 have been identified, particularly in sub-Saharan Africa. However, much remains unknown regarding the relative pathogenicity of these subtypes and their influence on the clinical progression of HIV infection. We examined prospectively the associations between HIV-1 subtypes A, C, and D and recombinant viruses, as well as the rates of disease progression in a cohort of seropositive women from Dar es Salaam, Tanzania. METHODS A total of 428 pregnant mothers participating in a larger controlled trial of the effect of vitamin supplements were selected for DNA sequencing of their HIV-1 subtype. Plasma viral load was measured at baseline, and CD4+ cell counts was assessed at baseline and at regular intervals throughout the follow-up period. Proportional hazards regression (hazards ratio [HR]) analysis was used to measure the association between viral subtype and the rate of disease progression. RESULTS Relative to patients with subtype A, patients with subtype D experienced the most rapid progression to death (HR, 2.27; 95% confidence interval [CI], 1.46-3.52) or to the World Health Organization stage 4 of illness (HR, 1.94; 95% CI, 1.20-3.14) and to a CD4+ cell count of <200 cells/mm3 (HR, 2.12; 95% CI, 1.42-3.17). After adjustment for viral load, CD4+ cell count, and other baseline covariates, the associations remained similar. CONCLUSIONS We observed heterogeneity in the rates of disease progression of HIV-1 disease in infected persons, on the basis of the infecting subtype. Subtype D was associated with the most rapid progression of the disease, relative to the other 3 categories of viruses in our cohort.

Validity of the Hopkins Symptom Checklist-25 amongst HIV-positive pregnant women in Tanzania

Objective: To validate the Hopkins Symptom Checklist‐25 (HSCL‐25) for use as a depression screen amongst human immuno‐deficiency virus (HIV) positive pregnant women.