Non-specific sex-differential effect of DTP vaccination may partially explain the excess girl child mortality in Ballabgarh, India.

OBJECTIVE: To test the hypothesis that a gender differential exists in the effect on child mortality of BCG, DTP, measles vaccine as administered under programme conditions in Ballabgarh HDSS area. METHODS: All live births in 28 villages of Ballabgarh block in North India from 2006 to 2011 were followed until 31 December 2011 or 36 months of age whichever was earlier. The period of analysis was divided into four time periods based on eligibility for vaccines under the national immunisation schedule (BCG for tuberculosis, primary and booster doses of diphtheria-tetanus-pertussis and measles). Cox proportional hazards regression was used to assess the association between sex and risk of mortality by vaccination status using age as the timescale in survival analysis and adjusting for wealth index, access to health care, the presence of a health facility in the village, parental education, type of family, birth order of the child and year of birth. RESULTS: 702 deaths (332 boys and 370 girls) occurred among 12,142 children in the cohort in the 3 years of follow-up giving a cumulative mortality rate of 57.5 per 1000 live births with 35% excess girl child mortality. Age at vaccination for the four vaccines did not differ by sex. There was significant excess mortality among girls after immunisation with DTP, for both primary (HR 1.65; 95% CI:1.17-2.32) and DTPb (2.21; 1.24-3.93) vaccinations. No significant excess morality among girls was noted after exposure to BCG 1.06 (0.67-1.67) or measles 1.34 (0.85-2.12) vaccine. CONCLUSION: This study supports the contention that DTP vaccination is partially responsible for higher mortality among girls in this study population.

Motherhood, migration and mortality in Dikgale: modelling life events among women in a rural South African community.

OBJECTIVES: Although particular types of life events in populations are often studied separately, this study investigated the joint effects of three major event types in South African women's lives: motherhood, migration and mortality. STUDY DESIGN: Data were taken from a health and demographic surveillance site (HDSS) over an 11-year period, reflecting the entire population of a defined geographic area as an open cohort, in which individuals participated in regular longitudinal surveillance for health and demographic events. This HDSS is a member of the Indepth Network. METHODS: Multivariate Poisson regression models were built for each of the three life event types, in which individual person-time observed out of the total possible 11-year period was used as a rate multiplier. These models were used to calculate adjusted incidence rate ratios for each factor. RESULTS: In the 21,587 person-years observed for women aged 15-49 years, from 1996 to 2006, adjusted rate ratios for mortality and migration increased substantially over time, while motherhood remained fairly constant. Women who migrated were less likely to bear children; temporary migrants were at greater risk of dying, while permanent in-migrants had higher survival rates. Women who subsequently died were much less likely to bear children or migrate. CONCLUSIONS: The associations between motherhood, migration and mortality among these rural South African women were complex and dynamic. Extremely rapid increases in mortality over the period studied are presumed to reflect the effects of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. Understanding these complex interactions between various life events at population level is crucial for effective public health planning and service delivery.

Identifying humanitarian crises in population surveillance field sites: simple procedures and ethical imperatives.

OBJECTIVES: Effective early warning systems of humanitarian crises may help to avert substantial increases in mortality and morbidity, and prevent major population movements. The Butajira Rural Health Programme (BRHP) in Ethiopia has maintained a programme of epidemiological surveillance since 1987. Inspection of the BRHP data revealed large peaks of mortality in 1998 and 1999, well in excess of the normally observed year-to-year variation. Further investigation and enquiry revealed that these peaks related to a measles epidemic, and a serious episode of drought and consequent food insecurity that went undetected by the BRHP. This paper applies international humanitarian crisis threshold definitions to the BRHP data in an attempt to identify suitable mortality thresholds that may be used for the prospective detection of humanitarian crises in population surveillance sites in developing countries. STUDY DESIGN: Empirical investigation using secondary analysis of longitudinal population-based cohort data. METHODS: The daily, weekly and monthly thresholds for crises in Butajira were applied to mortality data for the 5-year period incorporating the crisis periods of 1998-1999. Days, weeks and months in which mortality exceeded each threshold level were identified. Each threshold level was assessed in terms of prospectively identifying the true crisis periods in a timely manner whilst avoiding false alarms. RESULTS: The daily threshold definition is too sensitive to accurately detect impending or real crises in the population surveillance setting of the BRHP. However, the weekly threshold level is useful in identifying important increases in mortality in a timely manner without the excessive sensitivity of the daily threshold. The weekly threshold level detects the crisis periods approximately 2 weeks before the monthly threshold level. CONCLUSION: Mortality measures are highly specific indicators of the health status of populations, and simple procedures can be used to apply international crisis threshold definitions in population surveillance settings for the prospective detection of important changes in mortality rate. Standards for the timely use of surveillance data and ethical responsibilities of those responsible for the data should be made explicit to improve the public health functioning of current sentinel surveillance methodologies.

Difficulties in getting treatment for injuries in rural Vietnam.

OBJECTIVES: Knowledge about the health-seeking behaviour of injury patients is important for the improvement of community health services. The aims of this study were: (1) to describe the healthcare-seeking behaviour of injury patients; (2) to examine factors associated with injury patients seeking care at health facilities; and (3) to describe the costs of health care for injury patients. STUDY DESIGN: This study took place in Bavi District, northern Vietnam within a longitudinal community surveillance site (FilaBavi). All non-fatal unintentional injuries occurring in a sample of 24,776 people during 2000 were recorded. METHOD: The injury questionnaire included information on care-seeking behaviour, severity and consequences of injury. Both univariate and multivariate logistic regression models were used to find associations between sociodemographic factors and utilization of any health services, as well as for each type of health service used, compared with the group who did not use any health services. RESULT: Of 24,776 persons living in the study area, 1917 reported 2079 new non-fatal debilitating injuries during the four 3-month periods of observation. Health-seeking behaviour relating to the first 1917 injuries was analysed. Self-treatment was most common (51.7%), even in cases of severe injury. There was low usage of public health services (23.2%) among injury patients. Long distances, poor economic status and residence in difficult geographic areas such as highlands and mountains were barriers for seeking health services. A large proportion of household income was spent on treating injury patients. Poor people spent a greater proportion of their income on health care than the rich, and often used less qualified or untrained private providers. CONCLUSIONS: These results demonstrate the logistical and financial difficulties associated with the treatment of injuries in rural Vietnam. This suggests the need to make public health subsidies available more efficiently and equitably. Whilst this study looked at the situation specifically in the context of injury treatment, it is likely that similar patterns apply in other areas of health care.

Ageing of a rural Ethiopian population: who are the survivors?

OBJECTIVES: This study assessed trends in survival to old age and identified the factors associated with longevity among the elderly (age > or = 65 years). STUDY DESIGN: Cohort analysis of demographic surveillance data. METHODS: The study was conducted in the Butajira Rural Health Programme Demographic Surveillance Site in Ethiopia. Using data collected between 1987 and 2004, the probability of survival to 65 years and remaining life expectancy for women and men aged 65 years were computed. Cox regression analysis was used to assess survival by different factors. RESULTS: Although the elderly represented 3% of the population, their person-time contribution increased by 48% over the 18-year period. Less than half reached 65 years of age, with remaining life expectancy at 65 years ranging from 15 years in rural men to 19 years in urban women. Rural residence, illiteracy and widowhood were associated with lower survival adjusted for other factors, whereas gender did not show a significant difference. However, the effect of these factors differed between men and women, as demonstrated by survival curves and Cox regression. Widowhood [hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.59-2.57] and illiteracy (HR 2.26, 95% CI 1.86-2.73) affected males to a greater extent than females, and rural residence was associated with poorer female survival (HR 1.68, 95% CI 1.55-1.83). CONCLUSIONS: The number of elderly people is increasing in Ethiopia, with the chance of survival into older age being similar between men and women and approaching that in developed countries. However, rural women and illiterate women and men, particularly widowers, are disadvantaged in terms of survival.

Association between body mass index and blood pressure across three populations in Africa and Asia.

Despite a growing burden of obesity and hypertension in developing countries, there is limited information on the contribution of body mass index (BMI) to blood pressure (BP) in these populations. This study examines the association between BMI and BP in three populations across Africa and Asia. Data on BMI, BP and other background characteristics of study participants were generated using the World Health Organization STEPwise approach to surveillance (STEPS), at three demographic surveillance sites in Ethiopia, Vietnam and Indonesia. BMI and BP increased along the socioeconomic gradient across the three countries. Mean (s.d.) BMI in men varied between 19.41 (2.28) in Ethiopia to 21.17 (2.86) in Indonesia. A high prevalence of overweight/obesity was noted among Indonesian women (25%) and men (10%), whereas low BMI was widely prevalent in Ethiopia and Vietnam, ranging from 33 to 43%. Mean (s.d.) systolic BP (SBP) among men varied between 117.15 (15.35) in Ethiopia to 127.33 (17.80) in Indonesia. The prevalence of hypertension was highest among women (25%) and men (24%) in Indonesia. Mean BP levels increased with increasing BMI. The risk of hypertension was higher among population groups with overweight and obesity (BMI>/=25 kg/m(2)); odds ratio (95% confidence interval); 2.47 (1.42, 4.29) in Ethiopia, 2.67 (1.75, 4.08) in Vietnam and 7.64 (3.88, 15.0) in Indonesia. BMI was significantly and positively correlated with both SBP and DBP in all the three populations, correlation coefficient (r) ranging between 0.23 and 0.27, P<0.01. High BP exists in a background of undernutrition in populations at early stages of the epidemiologic transition.

The long road to elimination: malaria mortality in a South African population cohort over 21 years.

BACKGROUND: Malaria elimination is on global agendas following successful transmission reductions. Nevertheless moving from low to zero transmission is challenging. South Africa has an elimination target of 2018, which may or may not be realised in its hypoendemic areas. METHODS: The Agincourt Health and Demographic Surveillance System has monitored population health in north-eastern South Africa since 1992. Malaria deaths were analysed against individual factors, socioeconomic status, labour migration and weather over a 21-year period, eliciting trends over time and associations with covariates. RESULTS: Of 13 251 registered deaths over 1.58 million person-years, 1.2% were attributed to malaria. Malaria mortality rates increased from 1992 to 2013, while mean daily maximum temperature rose by 1.5 °C. Travel to endemic Mozambique became easier, and malaria mortality increased in higher socioeconomic groups. Overall, malaria mortality was significantly associated with age, socioeconomic status, labour migration and employment, yearly rainfall and higher rainfall/temperature shortly before death. CONCLUSIONS: Malaria persists as a small but important cause of death in this semi-rural South African population. Detailed longitudinal population data were crucial for these analyses. The findings highlight practical political, socioeconomic and environmental difficulties that may also be encountered elsewhere in moving from low-transmission scenarios to malaria elimination.

Gender differences in prevalence and socioeconomic determinants of hypertension: findings from the WHO STEPs survey in a rural community of Vietnam.

In Vietnam, hypertension was estimated to cause a large number of deaths in hospitals. However, population-based knowledge about the magnitude of hypertension in Vietnam and its relationship with socioeconomic status, especially in the rural communities, still remains scarce. This paper, taking advantage of a study on noncommunicable disease (NCD) risk factors in Bavi district, Vietnam, using the WHO STEPs approach, estimates the prevalence of hypertension in the setting and examines its association with some socioeconomic factors. A representative sample comprising 2000 adults aged 25-64 years were selected randomly and surveyed in 2002. The JNC VII criteria for hypertension were used. Socioeconomic status of the study subjects was estimated by assessing their education, occupation and economic conditions. Descriptive techniques and multivariate logistic regression were used. The prevalence of hypertension was 14.1%. Of hypertensives, only 17.4% were aware of their hypertensive status. Men were hypertensive more often than women and age was positively associated with hypertension. The association between hypertension and socioeconomic status was complex and differed between men and women. Among men, those with lower educational and occupational status but who were richer were more likely to be hypertensive. More women with lower occupational and economic status were hypertensive.

The development of a localised HIV epidemic and the associated excess mortality burden in a rural area of South Africa.

The human immunodeficiency virus (HIV) epidemic in South Africa rapidly developed into a major pandemic. Here we analyse the development of the epidemic in a rural area of the country. The data used were collected between 1992 and 2013 in a longitudinal population survey, the Agincourt Health and Demographic Surveillance Study, in the northeast of the country. Throughout the period of study mortality rates were similar in all villages, suggesting that there were multiple index cases evenly spread geographically. These were likely to have been returning migrant workers. For those aged below 39 years the HIV mortality rate was higher for women, above this age it was higher for men. This indicates the protective effect of greater access to HIV testing and treatment among older women. The recent convergence of mortality rates for Mozambicans and South Africans indicates that the former refugee population are being assimilated into the host community. More than 60% of the deaths occurring in this community between 1992 and 2013 could be attributed directly or indirectly to HIV. Recently there has been an increasing level of non-HIV mortality which has important implications for local healthcare provision. This study demonstrates how evidence from longitudinal analyses can support healthcare planning.

Serologic responses to an Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in very young Gambian infants.

Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants, but it was not clear that this would be the case in African infants, to whom H influenzae vaccines must be given at a very early age to prevent disease caused by H influenzae. Therefore, antibody responses to an H influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine were measured in very young Gambian infants. In the first group (n = 85), to whom the vaccine was given at the ages of 1 and 3 months, the geometric mean antibody level rose from a prevaccination level of 0.23 microgram/mL to a postvaccination level of 1.27 micrograms/mL, and in the second group (n = 56), vaccinated at the ages of 2 and 4 months, the prevaccination level of 0.16 microgram/mL rose to a postvaccination level of 1.59 micrograms/mL. These two final postvaccination levels did not differ significantly, and interpolation suggests that similar antibody levels were present in both groups of infants at the age of 3 months. This is the age by which protection would need to be achieved to protect against H influenzae meningitis in The Gambia and in other countries where the infection has similar epidemiologic characteristics. No significant side effects of vaccination were noted.

Daily morbidity records: recall and reliability.

Methodological issues concerning the collection and analysis of daily morbidity data in community studies in developing countries are discussed. The effects of recall period and inter-observer variation on symptom prevalence are considered in the context of a longitudinal study in The Gambia, in which prevalence fell by about half over 1-week's recall. In the same study, many infant-days were recorded separately on two occasions, allowing an assessment of reliability in this type of morbidity diary data. The implications of these findings both in terms of data quality and cost-effectiveness are discussed, with the conclusion that weekly interviews examining the previous week's morbidity on a day-by-day basis are operationally optimal.

The relationship between anthropometric measurements and measurements of iron status and susceptibility to malaria in Gambian children.

Anthropometric measurements were made and serum iron and ferritin levels determined in a group of Gambian children at the beginning of the rainy season and these findings were related to the malaria experience of the children during the following malaria transmission season. Susceptibility to malaria was not correlated with prior weight-for-age, height-for-age, weight-for-height or serum albumin, or with serum iron, serum iron binding capacity nor serum ferritin. Thus, our findings do not provide any support for the view that poor nutritional status, as assessed by anthropometric measurements, or iron deficiency protect against malaria infection. Children who developed a clinical attack of malaria accompanied by a high level of parasitaemia tended to have a higher mean weight-for-age at the beginning of the rainy season than did children who had a clinical attack accompanied by a low level of parasitaemia, but the difference between groups was not statistically significant. However, they had a significantly higher mean serum ferritin level (P less than 0.01).

Cellular immune responses to Plasmodium falciparum antigens in children receiving long term anti-malarial chemoprophylaxis.

Fifty-two Gambian children who had received fortnightly chemoprophylaxis with maloprim, (pyrimethamine and dapsone), and 45 receiving placebo, were studied. Cellular immune responses to malaria antigens, measured by lymphoproliferative responses and interferon production, were higher in children who had received prophylaxis than in controls, although the anti-malarial antibody levels were lower. During a one-year period after termination of prophylaxis, there was no increase in the frequency of clinical episodes of malaria in the children who had received Maloprim. These results suggest that chemoprophylaxis for 3 years may lower malaria antibody levels, but does not interfere with the development of protective immunity, perhaps by enhancing cell-mediated immune responses to malaria in protected children.

Immunity to malaria in young Gambian children after a two-year period of chemoprophylaxis.

A cohort of 48 Gambian children was protected against malaria by fortnightly administration of Maloprim (pyrimethamine and dapsone) for 2 years between their 3 and 5 birthdays. A matched cohort of 47 children received placebo. During the year following the termination of prophylaxis there was no increase in the frequency of clinical attacks of malaria in the protected children compared with the control children. Antibody levels to circumsporozoite protein were measured by a radioimmunoassay and that to blood-stage antigens by a variety of techniques including an ELISA to whole blood-stage Plasmodium falciparum antigen, immunofluorescent assays (IFAT) to acetone fixed, glutaraldehyde fixed and unfixed parasites, a merozoite inhibition test and an opsonizing assay. Antibody levels were, in general, lower in protected than in control children and several differences between the two groups were statistically significant. When antibody levels were measured by ELISA and IFAT at the end of the following rainy season, when malaria transmission was intense, those in protected children had increased to comparable levels to those found in control children. Our findings suggest that chemoprophylaxis given for 2 years lowers malaria antibody levels but that it does not interfere with the development of protective immunity.

Measurement of serum haptoglobin as an indicator of the efficacy of malaria intervention trials.

Serum haptoglobin levels were measured by an enzyme-linked immunosorbent assay in Gambian children who participated in 3 malaria intervention trials with untreated or impregnated bed nets. In one study, in which a significant effect on clinical malaria was observed, the mean serum haptoglobin level was significantly higher in the intervention than in the control group. In the other 2 studies, in which no significant protection was observed, mean haptoglobin levels were similar in intervention and control groups. Measurement of serum haptoglobin may provide a useful indirect measure of the effectiveness of malaria control programmes.

Malaria chemoprophylaxis, birth weight and child survival.

Study of the effects of malaria chemoprophylaxis given during pregnancy on birthweight and investigation of the influence of birthweight on child survival suggest that, in a rural area of The Gambia, chemoprophylaxis given during pregnancy might reduce infant mortality by about one-fifth in the children of primigravidae but by less than 5% in the children of multigravidae. In malaria endemic areas, primigravidae should be protected against malaria not only for their own sake but also for that of their infants.

PIP: Over 3 years, researchers randomly assigned more than 1775 pregnant women (many in their 3rd trimester of pregnancy) from 41 villages near Farafenni, The Gambia, to receive either Maloprim (malaria chemoprophylaxis of pyrimethamine and dapsone) or a placebo to determine Maloprim's effects on birth weight and child survival. All births occurred at home. Field workers went to each home as soon as possible after delivery to weigh the newborns. The relative risks for neonatal and infant mortality were 23 for infants weighing less than 2000 gms and 12 for those who weighed at least 2500 gms. While they were 2.1 and 0.8, respectively, for infants weighing between 2000 and 2500 gms. 33.3% of low birth weight infants of primigravidae died compared with 19% of those of multigravidae. Taking Maloprim during pregnancy reduced infant mortality by 18% for infants of primigravidae and only 4% for infants of multigravidae. It reduced neonatal deaths by 42% for infants of primigravidae and by just 6% for infants of multigravidae. These results suggested that health workers should distribute antimalarial medicine to all primigravidae. Chemoprophylaxis along with other malaria control efforts, such as insecticide impregnated bed nets or a malaria vaccine, would protect mothers and their infants.

Anti-sporozoite antibodies and immunity to malaria in a rural Gambian population.

A conserved repeated epitope, (NANP)3, of the circumsporozoite protein of Plasmodium falciparum has been identified previously as a putative target for artificially induced immunity to malaria. We examined the role of humoral responses to this epitope in acquired immunity to malaria in a rural African population. Seropositivity to (NANP)3 was slow to develop (9% positive in subjects aged 1-11 years; 88% in those of 30 years and above), and responses in younger subjects were transient. The poor response in younger subjects did not appear to be due to immunosuppression by concomitant blood stage parasitization. The relationship between levels of anti-(NANP)3 antibodies and parasitaemia changed from positive to negative with age. 126 subjects age 1-11 years were followed through an entire transmission season; those who were seropositive at the beginning ended the season with lower parasite rates (20% vs 59%) and experienced fewer episodes of clinical malaria (0.43 vs 0.67). However, the trend towards increasing susceptibility to clinical malaria in subjects entering the transmission season with lower levels of anti-(NANP)3 antibodies was modest, and combined cross-sectional and longitudinal data indicated that the humoral response to (NANP)3 did not play a major role in the development of immunity to clinical malaria in the population we studied.

The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy.

A trial of malaria chemoprophylaxis given by traditional birth attendants was undertaken in a rural area of The Gambia where access to antenatal clinics is difficult. Women received one or more doses of Maloprim or placebo from a traditional birth attendant during 1049 of 1208 pregnancies (87%) recorded in 16 villages over a 3-year period. Primigravidae who received Maloprim had a lower parasite rate and a significantly higher mean packed cell volume than primigravidae who received placebo, and their babies were significantly heavier (6% low birth weight vs 22%). In multigravidae chemoprophylaxis reduced malaria parasitaemia but it had no beneficial effect on haemoglobin level and much less effect on birth weight than was observed in primigravidae. However, the mean birth weight of babies born to grandemultigravidae who received chemoprophylaxis was significantly higher than that of babies born to grandemultigravidae who did not.

Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa.

Mortality and morbidity from malaria were measured among 3000 children under the age of 7 years in a rural area of The Gambia, West Africa. Using a post-mortem questionnaire technique, malaria was identified as the probable cause of 4% of infant deaths and of 25% of deaths in children aged 1 to 4 years. The malaria mortality rate was 6.3 per 1000 per year in infants and 10.7 per 1000 per year in children aged 1 to 4 years. Morbidity surveys suggested that children under the age of 7 years experienced about one clinical episode of malaria per year. Calculation of attributable fractions showed that malaria may be responsible for about 40% of episodes of fever in children. Although the overall level of parasitaemia showed little seasonal variation, the clinical impact of malaria was highly seasonal; all malaria deaths and a high proportion of febrile episodes were recorded during a limited period at the end of the rainy season.

Lack of an association between acute gastroenteritis, acute respiratory infections and malaria in young Gambian children.

The incidence of acute gastrointestinal and acute respiratory infections was measured in 2 groups of approximately 750 Gambian children aged 3-59 months during a 3-year period. One group of children was partially protected against malaria by fortnightly chemoprophylaxis with Maloprim whilst children in the other group were infected much more frequently. Mortality from acute gastroenteritis and from acute respiratory infections was similar in the 2 groups. The proportions of children in each group who complained of gastrointestinal or severe respiratory symptoms on morbidity surveillance were also similar. Thus, no evidence was found to suggest that malaria plays either a direct or indirect role in causing acute gastrointestinal or respiratory infections in young children in The Gambia.