Estimating diarrhea mortality among young children in low and middle income countries

Background

Diarrhea remains one of the leading causes of morbidity and mortality among children under 5 years of age, but in many low and middle-income countries where vital registration data are lacking, updated estimates with regard to the proportion of deaths attributable to diarrhea are needed.

Methods

We conducted a systematic literature review to identify studies reporting diarrhea proportionate mortality for children 1–59 mo of age published between 1980 and 2009. Using the published proportionate mortality estimates and country level covariates we constructed a logistic regression model to estimate country and regional level proportionate mortality and estimated uncertainty bounds using Monte-Carlo simulations.

Findings

We identified more than 90 verbal autopsy studies from around the world to contribute data to a single-cause model. We estimated diarrhea proportionate mortality for 84 countries in 6 regions and found diarrhea to account for between 10.0% of deaths in the Americas to 31.3% of deaths in the South-east Asian region.

Discussion

Diarrhea remains a leading cause of death for children 1–59 mo of age. Published literature can be used to create a single-cause mortality disease model to estimate mortality for countries lacking vital registration data.     

Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children

Background

We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed – and thus an underestimation – whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality.

Methods and Findings

We used data on all-cause mortality (1999–2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266–958) influenza-attributed deaths; for seasonal influenza 1,956 (range 0–3,990). 15,845 years-of-life-lost were estimated for the pandemic; for an average seasonal epidemic 17,908. For 0–4 yrs of age the number of influenza-attributed deaths during the pandemic were higher than in any seasonal epidemic; 77 deaths (range 61–93) compared to 16 deaths (range 0–45). The ≥75 yrs of age showed a far below average number of deaths. Using pneumonia/influenza and respiratory/cardiovascular instead of all-cause deaths consistently resulted in relatively low total pandemic mortality, combined with high impact in the youngest age category.

Conclusion

The pandemic had an overall moderate impact on mortality compared to 10 preceding seasonal epidemics, with higher mortality in young children and low mortality in the elderly. This resulted in a total number of pandemic deaths far below the average for seasonal influenza, and a total number of years-of-life-lost somewhat below average. Comparing pandemic and seasonal influenza mortality as in our study will help assessing the worldwide impact of the 2009 pandemic.     

New Findings for Maternal Mortality Age Patterns: Aggregated Results for 38 Countries

Background

With recent results showing a global decline in overall maternal mortality during the last two decades and with the target date for achieving the Millennium Development Goals only four years away, the question of how to continue or even accelerate the decline has become more pressing. By knowing where the risk is highest as well as where the numbers of deaths are greatest, it may be possible to re-direct resources and fine-tune strategies for greater effectiveness in efforts to reduce maternal mortality.

Methods

We aggregate data from 38 Demographic and Health Surveys that included a maternal mortality module and were conducted in 2000 or later to produce maternal mortality ratios, rates, and numbers of deaths by five year age groups, separately by residence, region, and overall mortality level.

Findings

The age pattern of maternal mortality is broadly similar across regions, type of place of residence, and overall level of maternal mortality. A “J” shaped curve, with markedly higher risk after age 30, is evident in all groups. We find that the excess risk among adolescents is of a much lower magnitude than is generally assumed. The oldest age groups appear to be especially resistant to change. We also find evidence of extremely elevated risk among older mothers in countries with high levels of HIV prevalence.

Conclusions

The largest number of deaths occurs in the age groups from 20-34, largely because those are the ages at which women are most likely to give birth so efforts directed at this group would most effectively reduce the number of deaths. Yet equity considerations suggest that efforts also be directed toward those most at risk, i.e., older women and adolescents. Because women are at risk each time they become pregnant, fulfilling the substantial unmet need for contraception is a cross-cutting strategy that can address both effectiveness and equity concerns.     

Transitions from injection-drug-use-concentrated to self-sustaining heterosexual HIV epidemics: patterns in the international data

Background

Injecting drug use continues to be a primary driver of HIV epidemics in many parts of the world. Many people who inject drugs (PWID) are sexually active, so it is possible that high-seroprevalence HIV epidemics among PWID may initiate self-sustaining heterosexual transmission epidemics.

Methods

Fourteen countries that had experienced high seroprevalence (<20%) HIV epidemics among PWID and had reliable data for injection drug use (IDU) and heterosexual cases of HIV or AIDS were identified. Graphs of newly reported HIV or AIDS cases among PWID and heterosexuals were constructed to identify temporal relationships between the two types of epidemics. The year in which newly reported cases among heterosexuals surpassed newly reported cases among PWID, aspects of the epidemic curves, and epidemic case histories were analyzed to assess whether it was “plausible” or “highly unlikely” that the HIV epidemic among PWID might have initiated the heterosexual epidemic in each country.

Results

Transitions have occurred in 11 of the 14 countries. Two types of temporal relationships between IDU and heterosexual HIV epidemics were identified, rapid high incidence transitions vs. delayed, low incidence transitions. In six countries it appears “plausible” that the IDU epidemic initiated a heterosexual epidemic, and in five countries it appears “highly unlikely” that the IDU epidemic initiated a heterosexual epidemic. A rapid decline in incidence among PWID after the peak year of new cases and national income were the best predictors of the “highly unlikely” initiation of a heterosexual epidemic.

Discussion

Transitions from IDU concentrated epidemics to heterosexual epidemics are common in countries with high seroprevalence among PWID though there are distinct types of transitions. Interventions to immediately reduce HIV incidence among PWID may reduce the likelihood that an IDU epidemic may initiate a heterosexual epidemic.     

Excess mortality associated with influenza epidemics in Portugal, 1980 to 2004

Background

Influenza epidemics have a substantial impact on human health, by increasing the mortality from pneumonia and influenza, respiratory and circulatory diseases, and all causes. This paper provides estimates of excess mortality rates associated with influenza virus circulation for 7 causes of death and 8 age groups in Portugal during the period of 1980–2004.

Methodology/Principal Findings

We compiled monthly mortality time series data by age for all-cause mortality, cerebrovascular diseases, ischemic heart diseases, diseases of the respiratory system, chronic respiratory diseases, pneumonia and influenza. We also used a control outcome, deaths from injuries. Age- and cause-specific baseline mortality was modelled by the ARIMA approach; excess deaths attributable to influenza were calculated by subtracting expected deaths from observed deaths during influenza epidemic periods. Influenza was associated with a seasonal average of 24.7 all-cause excess deaths per 100,000 inhabitants, approximately 90% of which were among seniors over 65 yrs. Excess mortality was 3–6 fold higher during seasons dominated by the A(H3N2) subtype than seasons dominated by A(H1N1)/B. High excess mortality impact was also seen in children under the age of four years. Seasonal excess mortality rates from all the studied causes of death were highly correlated with each other (Pearson correlation range, 0.65 to 0.95, P<0.001) and with seasonal rates of influenza-like-illness (ILI) among seniors over 65 years (Pearson correlation rho>0.64, P<0.05). By contrast, there was no correlation with excess mortality from injuries.

Conclusions/Significance

Our excess mortality approach is specific to influenza virus activity and produces influenza-related mortality rates for Portugal that are similar to those published for other countries. Our results indicate that all-cause excess mortality is a robust indicator of influenza burden in Portugal, and could be used to monitor the impact of influenza epidemics in this country. Additional studies are warranted to confirm these findings in other settings.     

Gestational age patterns of fetal and neonatal mortality in Europe: results from the Euro-Peristat project

Background

The first European Perinatal Health Report showed wide variability between European countries in fetal (2.6–9.1‰) and neonatal (1.6–5.7‰) mortality rates in 2004. We investigated gestational age patterns of fetal and neonatal mortality to improve our understanding of the differences between countries with low and high mortality.

Methodology/Principal Findings

Data on 29 countries/regions participating in the Euro-Peristat project were analyzed. Most European countries had no limits for the registration of live births, but substantial variations in limits for registration of stillbirths before 28 weeks of gestation existed. Country rankings changed markedly after excluding deaths most likely to be affected by registration differences (22–23 weeks for neonatal mortality and 22–27 weeks for fetal mortality). Countries with high fetal mortality ≥28 weeks had on average higher proportions of fetal deaths at and near term (≥37 weeks), while proportions of fetal deaths at earlier gestational ages (28–31 and 32–36 weeks) were higher in low fetal mortality countries. Countries with high neonatal mortality rates ≥24 weeks, all new member states of the European Union, had high gestational age-specific neonatal mortality rates for all gestational-age subgroups; they also had high fetal mortality, as well as high early and late neonatal mortality. In contrast, other countries with similar levels of neonatal mortality had varying levels of fetal mortality, and among these countries early and late neonatal mortality were negatively correlated.

Conclusions

For valid European comparisons, all countries should register births and deaths from at least 22 weeks of gestation and should be able to distinguish late terminations of pregnancy from stillbirths. After excluding deaths most likely to be influenced by existing registration differences, important variations in both levels and patterns of fetal and neonatal mortality rates were found. These disparities raise questions for future research about the effectiveness of medical policies and care in European countries.     

Incidence rates of enterovirus 71 infections in young children during a nationwide epidemic in Taiwan, 2008-09

Objective

Enterovirus 71 (EV71) is causing life-threatening outbreaks in tropical Asia. In Taiwan and other tropical Asian countries, although nationwide EV71 epidemics occur cyclically, age-specific incidence rates of EV71 infections that are critical to estimate disease burden and design vaccine trials are not clear. A nationwide EV71 epidemic occurred in 2008–09 in Taiwan, which provided a unique opportunity to estimate age-specific incidence rates of EV71 infections.

Study Design

We prospectively recruited 749 healthy neonates and conducted follow-ups from June 2006 to December 2009. Sera were obtained from participants at 0, 6, 12, 24, and 36 months of age for measuring EV71 neutralizing antibody titers. If the participants developed suspected enterovirus illnesses, throat swabs were collected for virus isolation.

Results

We detected 28 EV71 infections including 20 symptomatic and 8 asymptomatic infections. Age-specific incidence rates of EV71 infection increased from 1.71 per 100 person-years at 0–6 months of age to 4.09, 5.74, and 4.97 per 100 person-years at 7–12, 13–24, and 25–36 months of age, respectively. Cumulative incidence rate was 15.15 per 100 persons by 36 months of age, respectively.

Conclusions

Risk of EV71 infections in Taiwan increased after 6 months of age during EV71 epidemics. The cumulative incidence rate was 15% by 36 months of age, and 29% of EV71 infections were asymptomatic in young children.     

Seasonal Variation of Overall and Cardiovascular Mortality: A Study in 19 Countries from Different Geographic Locations

Background

Cardiovascular diseases (CVD) mortality has been shown to follow a seasonal pattern. Several studies suggested several possible determinants of this pattern, including misclassification of causes of deaths. We aimed at assessing seasonality in overall, CVD, cancer and non-CVD/non-cancer mortality using data from 19 countries from different latitudes.

Methods and Findings

Monthly mortality data were compiled from 19 countries, amounting to over 54 million deaths. We calculated ratios of the observed to the expected numbers of deaths in the absence of a seasonal pattern. Seasonal variation (peak to nadir difference) for overall and cause-specific (CVD, cancer or non-CVD/non-cancer) mortality was analyzed using the cosinor function model. Mortality from overall, CVD and non-CVD/non-cancer showed a consistent seasonal pattern. In both hemispheres, the number of deaths was higher than expected in winter. In countries close to the Equator the seasonal pattern was considerably lower for mortality from any cause. For CVD mortality, the peak to nadir differences ranged from 0.185 to 0.466 in the Northern Hemisphere, from 0.087 to 0.108 near the Equator, and from 0.219 to 0.409 in the Southern Hemisphere. For cancer mortality, the seasonal variation was nonexistent in most countries.

Conclusions

In countries with seasonal variation, mortality from overall, CVD and non-CVD/non-cancer show a seasonal pattern with mortality being higher in winter than in summer. Conversely, cancer mortality shows no substantial seasonality.     

Deaths from Symptomatically Identifiable Furious Rabies in India: A Nationally Representative Mortality Survey

Background

It is estimated that India has more deaths from rabies than any other country. However, existing estimates are indirect and rely on non-representative studies.

Methods and Principal Findings

We examined rabies deaths in the ongoing Million Death Study (MDS), a representative survey of over 122,000 deaths in India that uses enhanced types of verbal autopsy. We estimated the age-specific mortality rates of symptomatically identifiable furious rabies and its geographic and demographic distributions. A total of 140 deaths in our sample were caused by rabies, suggesting that in 2005 there were 12,700 (99% CI 10,000 to 15,500) symptomatically identifiable furious rabies deaths in India. Most rabies deaths were in males (62%), in rural areas (91%), and in children below the age of 15 years (50%). The overall rabies mortality rate was 1.1 deaths per 100,000 population (99%CI 0.9 to 1.4). One third of the national rabies deaths were found in Uttar Pradesh (4,300) and nearly three quarters (8,900) were in 7 central and south-eastern states: Chhattisgarh, Uttar Pradesh, Odisha, Andhra Pradesh, Bihar, Assam, and Madhya Pradesh.

Conclusions and Significance

Rabies remains an avoidable cause of death in India. As verbal autopsy is not likely to identify atypical or paralytic forms of rabies, our figure of 12,700 deaths due to classic and clinically identifiable furious rabies underestimates the total number of deaths due to this virus. The concentrated geographic distribution of rabies in India suggests that a significant reduction in the number of deaths or potentially even elimination of rabies deaths is possible.     

Mortality Burden of the 2009 A/H1N1 Influenza Pandemic in France: Comparison to Seasonal Influenza and the A/H3N2 Pandemic

Background

The mortality burden of the 2009 A/H1N1 pandemic remains unclear in many countries due to delays in reporting of death statistics. We estimate the age- and cause-specific excess mortality impact of the pandemic in France, relative to that of other countries and past epidemic and pandemic seasons.

Methods

We applied Serfling and Poisson excess mortality approaches to model weekly age- and cause-specific mortality rates from June 1969 through May 2010 in France. Indicators of influenza activity, time trends, and seasonal terms were included in the models. We also reviewed the literature for country-specific estimates of 2009 pandemic excess mortality rates to characterize geographical differences in the burden of this pandemic.

Results

The 2009 A/H1N1 pandemic was associated with 1.0 (95% Confidence Intervals (CI) 0.2–1.9) excess respiratory deaths per 100,000 population in France, compared to rates per 100,000 of 44 (95% CI 43–45) for the A/H3N2 pandemic and 2.9 (95% CI 2.3–3.7) for average inter-pandemic seasons. The 2009 A/H1N1 pandemic had a 10.6-fold higher impact than inter-pandemic seasons in people aged 5–24 years and 3.8-fold lower impact among people over 65 years.

Conclusions

The 2009 pandemic in France had low mortality impact in most age groups, relative to past influenza seasons, except in school-age children and young adults. The historical A/H3N2 pandemic was associated with much larger mortality impact than the 2009 pandemic, across all age groups and outcomes. Our 2009 pandemic excess mortality estimates for France fall within the range of previous estimates for high-income regions. Based on the analysis of several mortality outcomes and comparison with laboratory-confirmed 2009/H1N1 deaths, we conclude that cardio-respiratory and all-cause mortality lack precision to accurately measure the impact of this pandemic in high-income settings and that use of more specific mortality outcomes is important to obtain reliable age-specific estimates.     

Child Deaths Due to Injury in the Four UK Countries: A Time Trends Study from 1980 to 2010

Background

Injuries are an increasingly important cause of death in children worldwide, yet injury mortality is highly preventable. Determining patterns and trends in child injury mortality can identify groups at particularly high risk. We compare trends in child deaths due to injury in four UK countries, between 1980 and 2010.

Methods

We obtained information from death certificates on all deaths occurring between 1980 and 2010 in children aged 28 days to 18 years and resident in England, Scotland, Wales or Northern Ireland. Injury deaths were defined by an external cause code recorded as the underlying cause of death. Injury mortality rates were analysed by type of injury, country of residence, age group, sex and time period.

Results

Child mortality due to injury has declined in all countries of the UK. England consistently experienced the lowest mortality rate throughout the study period. For children aged 10 to 18 years, differences between countries in mortality rates increased during the study period. Inter-country differences were largest for boys aged 10 to 18 years with mortality rate ratios of 1.38 (95% confidence interval 1.16, 1.64) for Wales, 1.68 (1.48, 1.91) for Scotland and 1.81 (1.50, 2.18) for Northern Ireland compared with England (the baseline) in 2006–10. The decline in mortality due to injury was accounted for by a decline in unintentional injuries. For older children, no declines were observed for deaths caused by self-harm, by assault or from undetermined intent in any UK country.

Conclusion

Whilst child deaths from injury have declined in all four UK countries, substantial differences in mortality rates remain between countries, particularly for older boys. This group stands to gain most from policy interventions to reduce deaths from injury in children.     

Fitting the HIV Epidemic in Zambia: A Two-Sex Micro-Simulation Model

Background

In describing and understanding how the HIV epidemic spreads in African countries, previous studies have not taken into account the detailed periods at risk. This study is based on a micro-simulation model (individual-based) of the spread of the HIV epidemic in the population of Zambia, where women tend to marry early and where divorces are not frequent. The main target of the model was to fit the HIV seroprevalence profiles by age and sex observed at the Demographic and Health Survey conducted in 2001.

Methods and Findings

A two-sex micro-simulation model of HIV transmission was developed. Particular attention was paid to precise age-specific estimates of exposure to risk through the modelling of the formation and dissolution of relationships: marriage (stable union), casual partnership, and commercial sex. HIV transmission was exclusively heterosexual for adults or vertical (mother-to-child) for children. Three stages of HIV infection were taken into account. All parameters were derived from empirical population-based data. Results show that basic parameters could not explain the dynamics of the HIV epidemic in Zambia. In order to fit the age and sex patterns, several assumptions were made: differential susceptibility of young women to HIV infection, differential susceptibility or larger number of encounters for male clients of commercial sex workers, and higher transmission rate. The model allowed to quantify the role of each type of relationship in HIV transmission, the proportion of infections occurring at each stage of disease progression, and the net reproduction rate of the epidemic (R ₀ = 1.95).

Conclusions

The simulation model reproduced the dynamics of the HIV epidemic in Zambia, and fitted the age and sex pattern of HIV seroprevalence in 2001. The same model could be used to measure the effect of changing behaviour in the future.     

Impact of Hiv-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

Objectives

To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS).

Design, Setting

Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.

Subjects, Participants

36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55–2.27).

Outcome Measures

Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation.

Results

There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21–5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97–2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74–4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), non-tuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80–3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80–3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary tuberculosis, Kaposi’s sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates.

Conclusions

A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for diagnostics, therapeutic interventions and research.     

Estimating incidence from prevalence in generalised HIV epidemics: methods and validation

Background

HIV surveillance of generalised epidemics in Africa primarily relies on prevalence at antenatal clinics, but estimates of incidence in the general population would be more useful. Repeated cross-sectional measures of HIV prevalence are now becoming available for general populations in many countries, and we aim to develop and validate methods that use these data to estimate HIV incidence.

Methods and Findings

Two methods were developed that decompose observed changes in prevalence between two serosurveys into the contributions of new infections and mortality. Method 1 uses cohort mortality rates, and method 2 uses information on survival after infection. The performance of these two methods was assessed using simulated data from a mathematical model and actual data from three community-based cohort studies in Africa. Comparison with simulated data indicated that these methods can accurately estimates incidence rates and changes in incidence in a variety of epidemic conditions. Method 1 is simple to implement but relies on locally appropriate mortality data, whilst method 2 can make use of the same survival distribution in a wide range of scenarios. The estimates from both methods are within the 95% confidence intervals of almost all actual measurements of HIV incidence in adults and young people, and the patterns of incidence over age are correctly captured.

Conclusions

It is possible to estimate incidence from cross-sectional prevalence data with sufficient accuracy to monitor the HIV epidemic. Although these methods will theoretically work in any context, we have able to test them only in southern and eastern Africa, where HIV epidemics are mature and generalised. The choice of method will depend on the local availability of HIV mortality data.     

The Shifting Demographic Landscape of Pandemic Influenza

Background

As Pandemic (H1N1) 2009 influenza spreads around the globe, it strikes school-age children more often than adults. Although there is some evidence of pre-existing immunity among older adults, this alone may not explain the significant gap in age-specific infection rates.

Methods and Findings

Based on a retrospective analysis of pandemic strains of influenza from the last century, we show that school-age children typically experience the highest attack rates in primarily naive populations, with the burden shifting to adults during the subsequent season. Using a parsimonious network-based mathematical model which incorporates the changing distribution of contacts in the susceptible population, we demonstrate that new pandemic strains of influenza are expected to shift the epidemiological landscape in exactly this way.

Conclusions

Our analysis provides a simple demographic explanation for the age bias observed for H1N1/09 attack rates, and suggests that this bias may shift in coming months. These results have significant implications for the allocation of public health resources for H1N1/09 and future influenza pandemics.     

Unequal Trends in Coronary Heart Disease Mortality by Socioeconomic Circumstances,England 1982–2006: An Analytical Study

Background

Coronary heart disease (CHD) remains a major public health burden, causing 80,000 deaths annually in England and Wales, with major inequalities. However, there are no recent analyses of age-specific socioeconomic trends in mortality. We analysed annual trends in inequalities in age-specific CHD mortality rates in small areas in England, grouped into deprivation quintiles.

Methods

We calculated CHD mortality rates for 10-year age groups (from 35 to ≥85 years) using three year moving averages between 1982 and 2006. We used Joinpoint regression to identify significant turning points in age- sex- and deprivation-specific time trends. We also analysed trends in absolute and relative inequalities in age-standardised rates between the least and most deprived areas.

Results

Between 1982 and 2006, CHD mortality fell by 62.2% in men and 59.7% in women. Falls were largest for the most deprived areas with the highest initial level of CHD mortality. However, a social gradient in the pace of fall was apparent, being steepest in the least deprived quintile. Thus, while absolute inequalities narrowed over the period, relative inequalities increased. From 2000, declines in mortality rates slowed or levelled off in the youngest groups, notably in women aged 45–54 in the least deprived groups. In contrast, from age 55 years and older, rates of fall in CHD mortality accelerated in the 2000s, likewise falling fastest in the least deprived quintile.

Conclusions

Age-standardised CHD mortality rates have declined substantially in England, with the steepest falls in the most affluent quintiles. However, this concealed contrasting patterns in underlying age-specific rates. From 2000, mortality rates levelled off in the youngest groups but accelerated in middle aged and older groups. Mortality analyses by small areas could provide potentially valuable insights into possible drivers of inequalities, and thus inform future strategies to reduce CHD mortality across all social groups.     

Recent Patterns in Population-Based HIV Prevalence in Swaziland

Background

The 2011 Swaziland HIV Incidence Measurement Survey (SHIMS) was conducted as part of a national study to evaluate the scale up of key HIV prevention programs.

Methods

From a randomly selected sample of all Swazi households, all women and men aged 18-49 were considered eligible, and all consenting adults were enrolled and received HIV testing and counseling. In this analysis, population-based measures of HIV prevalence were produced and compared against similarly measured HIV prevalence estimates from the 2006-7 Swaziland Demographic and Health. Also, measures of HIV service utilization in both HIV infected and uninfected populations were documented and discussed.

Results

HIV prevalence among adults aged 18-49 has remained unchanged between 2006-2011 at 31-32%, with substantial differences in current prevalence between women (39%) and men (24%). In both men and women, between since 2006-7 and 2011, prevalence has fallen in the young age groups and risen in the older age groups. Over a third (38%) of the HIV-infected population was unaware of their infection status, and this differed markedly between men (50%) and women (31%). Of those aware of their HIV-positive status, a higher percentage of men (63%) than women (49%) reported ART use.

Conclusions

While overall HIV prevalence remains roughly constant, age-specific changes strongly suggest both improved survival of the HIV-infected and a reduction in new HIV infections. Awareness of HIV status and entry into ART services has improved in recent years but remains too low. This study identifies opportunities to improve both HIV preventive and care services in Swaziland.     

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa

Objective

To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis.

Results

Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality.

Conclusion

In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.     

Combining Epidemiologic and Biostatistical Tools to Enhance Variable Selection in HIV Cohort Analyses

Background

Variable selection is an important step in building a multivariate regression model for which several methods and statistical packages are available. A comprehensive approach for variable selection in complex multivariate regression analyses within HIV cohorts is explored by utilizing both epidemiological and biostatistical procedures.

Methods

Three different methods for variable selection were illustrated in a study comparing survival time between subjects in the Department of Defense’s National History Study and the Atlanta Veterans Affairs Medical Center’s HIV Atlanta VA Cohort Study. The first two methods were stepwise selection procedures, based either on significance tests (Score test), or on information theory (Akaike Information Criterion), while the third method employed a Bayesian argument (Bayesian Model Averaging).

Results

All three methods resulted in a similar parsimonious survival model. Three of the covariates previously used in the multivariate model were not included in the final model suggested by the three approaches. When comparing the parsimonious model to the previously published model, there was evidence of less variance in the main survival estimates.

Conclusions

The variable selection approaches considered in this study allowed building a model based on significance tests, on an information criterion, and on averaging models using their posterior probabilities. A parsimonious model that balanced these three approaches was found to provide a better fit than the previously reported model.     

Estimating pneumonia deaths of post-neonatal children in countries of low or no death certification in 2008

Background

Pneumonia is the leading cause of child deaths globally. The aims of this study were to: a) estimate the number and global distribution of pneumonia deaths for children 1–59 months for 2008 for countries with low (<85%) or no coverage of death certification using single-cause regression models and b) compare these country estimates with recently published ones based on multi-cause regression models.

Methods and Findings

For 35 low child-mortality countries with <85% coverage of death certification, a regression model based on vital registration data of low child-mortality and >85% coverage of death certification countries was used. For 87 high child-mortality countries pneumonia death estimates were obtained by applying a regression model developed from published and unpublished verbal autopsy data from high child-mortality settings. The total number of 1–59 months pneumonia deaths for the year 2008 for these 122 countries was estimated to be 1.18 M (95% CI 0.77 M–1.80 M), which represented 23.27% (95% CI 17.15%–32.75%) of all 1–59 month child deaths. The country level estimation correlation coefficient between these two methods was 0.40.

Interpretation

Although the overall number of post-neonatal pneumonia deaths was similar irrespective to the method of estimation used, the country estimate correlation coefficient was low, and therefore country-specific estimates should be interpreted with caution. Pneumonia remains the leading cause of child deaths and is greatest in regions of poverty and high child-mortality. Despite the concerns about gender inequity linked with childhood mortality we could not estimate sex-specific pneumonia mortality rates due to the inadequate data. Life-saving interventions effective in preventing and treating pneumonia mortality exist but few children in high pneumonia disease burden regions are able to access them. To achieve the United Nations Millennium Development Goal 4 target to reduce child deaths by two-thirds in year 2015 will require the scale-up of access to these effective pneumonia interventions.