Child Mortality Estimation: Methods Used to Adjust for Bias due to AIDS in Estimating Trends in Under-Five Mortality

In most low- and middle-income countries, child mortality is estimated from data provided by mothers concerning the survival of their children using methods that assume no correlation between the mortality risks of the mothers and those of their children. This assumption is not valid for populations with generalized HIV epidemics, however, and in this review, we show how the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) uses a cohort component projection model to correct for AIDS-related biases in the data used to estimate trends in under-five mortality. In this model, births in a given year are identified as occurring to HIV-positive or HIV-negative mothers, the lives of the infants and mothers are projected forward using survivorship probabilities to estimate survivors at the time of a given survey, and the extent to which excess mortality of children goes unreported because of the deaths of HIV-infected mothers prior to the survey is calculated. Estimates from the survey for past periods can then be adjusted for the estimated bias. The extent of the AIDS-related bias depends crucially on the dynamics of the HIV epidemic, on the length of time before the survey that the estimates are made for, and on the underlying non-AIDS child mortality. This simple methodology (which does not take into account the use of effective antiretroviral interventions) gives results qualitatively similar to those of other studies.     

Child Mortality Estimation: Consistency of Under-Five Mortality Rate Estimates Using Full Birth Histories and Summary Birth Histories

Background

Given the lack of complete vital registration data in most developing countries, for many countries it is not possible to accurately estimate under-five mortality rates from vital registration systems. Heavy reliance is often placed on direct and indirect methods for analyzing data collected from birth histories to estimate under-five mortality rates. Yet few systematic comparisons of these methods have been undertaken. This paper investigates whether analysts should use both direct and indirect estimates from full birth histories, and under what circumstances indirect estimates derived from summary birth histories should be used.

Methods and Findings

Usings Demographic and Health Surveys data from West Africa, East Africa, Latin America, and South/Southeast Asia, I quantify the differences between direct and indirect estimates of under-five mortality rates, analyze data quality issues, note the relative effects of these issues, and test whether these issues explain the observed differences. I find that indirect estimates are generally consistent with direct estimates, after adjustment for fertility change and birth transference, but don''t add substantial additional insight beyond direct estimates. However, choice of direct or indirect method was found to be important in terms of both the adjustment for data errors and the assumptions made about fertility.

Conclusions

Although adjusted indirect estimates are generally consistent with adjusted direct estimates, some notable inconsistencies were observed for countries that had experienced either a political or economic crisis or stalled health transition in their recent past. This result suggests that when a population has experienced a smooth mortality decline or only short periods of excess mortality, both adjusted methods perform equally well. However, the observed inconsistencies identified suggest that the indirect method is particularly prone to bias resulting from violations of its strong assumptions about recent mortality and fertility. Hence, indirect estimates of under-five mortality rates from summary birth histories should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past. Please see later in the article for the Editors'' Summary.     

Child Mortality Estimation: A Comparison of UN IGME and IHME Estimates of Levels and Trends in Under-Five Mortality Rates and Deaths

Background

Millennium Development Goal 4 calls for a reduction in the under-five mortality rate (U5MR) by two-thirds between 1990 and 2015. In 2011, estimates were published by the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) and the Institute for Health Metrics and Evaluation (IHME). The difference in the U5MR estimates produced by the two research groups was more than 10% and corresponded to more than ten deaths per 1,000 live births for 10% of all countries in 1990 and 20% of all countries in 2010, which can lead to conflicting conclusions with respect to countries'' progress. To understand what caused the differences in estimates, we summarised differences in underlying data and modelling approaches used by the two groups, and analysed their effects.

Methods and Findings

UN IGME and IHME estimation approaches differ with respect to the construction of databases and the pre-processing of data, trend fitting procedures, inclusion and exclusion of data series, and additional adjustment procedures. Large differences in U5MR estimates between the UN IGME and the IHME exist in countries with conflicts or civil unrest, countries with high HIV prevalence, and countries where the underlying data used to derive the estimates were different, especially if the exclusion of data series differed between the two research groups. A decomposition of the differences showed that differences in estimates due to using different data (inclusion of data series and pre-processing of data) are on average larger than the differences due to using different trend fitting methods.

Conclusions

Substantial country-specific differences between UN IGME and IHME estimates for U5MR and the number of under-five deaths exist because of various differences in data and modelling assumptions used. Often differences are illustrative of the lack of reliable data and likely to decrease as more data become available. Improved transparency on methods and data used will help to improve understanding about the drivers of the differences. Please see later in the article for the Editors'' Summary.     

Validation of a Low-Cost Paper-Based Screening Test for Sickle Cell Anemia

Background

The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age.

Methods and Findings

In a population of healthy volunteers and SCA patients in the United States (n = 55) the test identified individuals whose blood contained any HbS (HbAS and HbSS) with 100% sensitivity and 100% specificity for both visual evaluation and automated analysis, and detected SCA (HbSS) with 93% sensitivity and 94% specificity for visual evaluation and 100% sensitivity and 97% specificity for automated analysis. In a population of post-partum women (with a previously unknown SCA status) at a primary obstetric hospital in Cabinda, Angola (n = 226) the test identified sickle cell trait carriers with 94% sensitivity and 97% specificity using visual evaluation (none of the women had SCA). Notably, our test permits instrument- and electricity-free visual diagnostics, requires minimal training to be performed, can be completed within 30 minutes, and costs about $0.07 in test-specific consumable materials.

Conclusions

Our results validate the paper-based SCA test as a useful low-cost tool for screening adults and children for sickle trait and disease and demonstrate its practicality in resource-limited clinical settings.     

Progress toward Global Reduction in Under-Five Mortality: A Bootstrap Analysis of Uncertainty in Millennium Development Goal 4 Estimates

Background

Millennium Development Goal 4 calls for an annual rate of reduction (ARR) of the under-five mortality rate (U5MR) of 4.4% between 1990 and 2015. Progress is measured through the point estimates of the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME). To facilitate evidence-based conclusions about progress toward the goal, we assessed the uncertainty in the estimates arising from sampling errors and biases in data series and the inferior quality of specific data series.

Methods and Findings

We implemented a bootstrap procedure to construct 90% uncertainty intervals (UIs) for the U5MR and ARR to complement the UN IGME estimates. We constructed the bounds for all countries without a generalized HIV epidemic, where a standard estimation approach is carried out (174 countries). In the bootstrap procedure, potential biases in levels and trends of data series of different source types were accounted for. There is considerable uncertainty about the U5MR, particularly for high mortality countries and in recent years. Among 86 countries with a U5MR of at least 40 deaths per 1,000 live births in 1990, the median width of the UI, relative to the U5MR level, was 19% for 1990 and 48% for 2011, with the increase in uncertainty due to more limited data availability. The median absolute width of the 90% UI for the ARR from 1990 to 2011 was 2.2%. Although the ARR point estimate for all high mortality countries was greater than zero, for eight of them uncertainty included the possibility of no improvement between 1990 and 2011. For 13 countries, it is deemed likely that the ARR from 1990 to 2011 exceeded 4.4%.

Conclusions

In light of the upcoming evaluation of Millennium Development Goal 4 in 2015, uncertainty assessments need to be taken into account to avoid unwarranted conclusions about countries'' progress based on limited data. Please see later in the article for the Editors'' Summary     

Development and Internal Validation of a Predictive Model Including Pulse Oximetry for Hospitalization of Under-Five Children in Bangladesh

Background

The reduction in the deaths of millions of children who die from infectious diseases requires early initiation of treatment and improved access to care available in health facilities. A major challenge is the lack of objective evidence to guide front line health workers in the community to recognize critical illness in children earlier in their course.

Methods

We undertook a prospective observational study of children less than 5 years of age presenting at the outpatient or emergency department of a rural tertiary care hospital between October 2012 and April 2013. Study physicians collected clinical signs and symptoms from the facility records, and with a mobile application performed recordings of oxygen saturation, heart rate and respiratory rate. Facility physicians decided the need for hospital admission without knowledge of the oxygen saturation. Multiple logistic predictive models were tested.

Findings

Twenty-five percent of the 3374 assessed children, with a median (interquartile range) age of 1.02 (0.42–2.24), were admitted to hospital. We were unable to contact 20% of subjects after their visit. A logistic regression model using continuous oxygen saturation, respiratory rate, temperature and age combined with dichotomous signs of chest indrawing, lethargy, irritability and symptoms of cough, diarrhea and fast or difficult breathing predicted admission to hospital with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval -CI: 0.87 to 0.90). At a risk threshold of 25% for admission, the sensitivity was 77% (95% CI: 74% to 80%), specificity was 87% (95% CI: 86% to 88%), positive predictive value was 70% (95% CI: 67% to 73%) and negative predictive value was 91% (95% CI: 90% to 92%).

Conclusion

A model using oxygen saturation, respiratory rate and temperature in combination with readily obtained clinical signs and symptoms predicted the need for hospitalization of critically ill children. External validation of this model in a community setting will be required before adoption into clinical practice.     

Strengthening Community-Based Vital Events Reporting for Real-Time Monitoring of Under-Five Mortality: Lessons Learned from the Balaka and Salima Districts in Malawi

Background

Malawi ratified a compulsory birth and death registration system in 2009. Until it captures complete coverage of vital events, Malawi relies on other data sources to calculate mortality estimates. We tested a community-based method to estimate annual under-five mortality rates (U5MR) through the Real-Time Monitoring of Under-Five Mortality (RMM) project in Malawi. We implemented RMM in two phases, and conducted an independent evaluation of phase one after 21 months of implementation. We present results of the phase two validation that covers the full project time span, and compare the results to those of the phase one validation.

Methods and Findings

We assessed the completeness of the counts of births and deaths and the accuracy of disaggregated U5MR from the community-based method against a retrospective full pregnancy history for rolling twelve-month periods after the independent evaluation. We used full pregnancy histories collected through household interviews carried out between November 2013 and January 2014 as the validation data source. Health Surveillance Agents (HSAs) across the 160 catchment areas submitted routine reports on pregnancies, births, and deaths consistently. However, for the 15-month implementation period post-evaluation, average completeness of birth event reporting was 76%, whereas average completeness of death event reporting was 67% relative to that expected from a comparable pregnancy history. HSAs underestimated the U5MR by an average of 21% relative to that estimated from a comparable pregnancy history.

Conclusions

On a medium scale, the community-based RMM method in Malawi produced substantial underestimates of annualized U5MR relative to those obtained from a full pregnancy history, despite the additional incentives and quality-control activities. We were not able to achieve an optimum level of incentive and support to make the system work while ensuring sustainability. Lessons learned from the implementation of RMM can inform programs supporting community-based interventions through HSAs in Malawi.     

Validation of qPCR Methods for the Detection of Mycobacterium in New World Animal Reservoirs

Zoonotic pathogens that cause leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis complex, MTBC) continue to impact modern human populations. Therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. Here we tested for mycobacterial-specific single- and multi-copy loci using qPCR. In a trial study in which armadillos were artificially infected with M. leprae, these techniques were specific and sensitive to pathogen detection, while more traditional ELISAs were only specific. These assays were then employed in a case study to detect M. leprae as well as MTBC in wild marmosets. All marmosets were negative for M. leprae DNA, but 14 were positive for the mycobacterial rpoB gene assay. Targeted capture and sequencing of rpoB and other MTBC genes validated the presence of mycobacterial DNA in these samples and revealed that qPCR is useful for identifying mycobacterial-infected animal hosts.     

Using Re-Sampling Methods in Mortality Studies

Traditional methods of computing standardized mortality ratios (SMR) in mortality studies rely upon a number of conventional statistical propositions to estimate confidence intervals for obtained values. Those propositions include a common but arbitrary choice of the confidence level and the assumption that observed number of deaths in the test sample is a purely random quantity. The latter assumption may not be fully justified for a series of periodic “overlapping” studies. We propose a new approach to evaluating the SMR, along with its confidence interval, based on a simple re-sampling technique. The proposed method is most straightforward and requires neither the use of above assumptions nor any rigorous technique, employed by modern re-sampling theory, for selection of a sample set. Instead, we include all possible samples that correspond to the specified time window of the study in the re-sampling analysis. As a result, directly obtained confidence intervals for repeated overlapping studies may be tighter than those yielded by conventional methods. The proposed method is illustrated by evaluating mortality due to a hypothetical risk factor in a life insurance cohort. With this method used, the SMR values can be forecast more precisely than when using the traditional approach. As a result, the appropriate risk assessment would have smaller uncertainties.     

Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero,One and Five in India: A Decomposition Analysis

Objectives

Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover.

Methods

We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981–2009 for 16 Indian states by sex (comprising of India’s 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under-five mortality towards crossover.

Findings

India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women).

Conclusions

For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1–59 months in high child mortality areas can help India to attain this crossover early.     

Time Trends and Inequalities of Under-Five Mortality in Nepal: A Secondary Data Analysis of Four Demographic and Health Surveys between 1996 and 2011

Background

Inequalities in progress towards achievement of Millennium Development Goal four (MDG-4) reflect unequal access to child health services.

Objective

To examine the time trends, socio-economic and regional inequalities of under-five mortality rate (U5MR) in Nepal.

Methods

We analyzed the data from complete birth histories of four Nepal Demographic and Health Surveys (NDHS) done in the years 1996, 2001, 2006 and 2011. For each livebirth, we computed survival period from birth until either fifth birthday or the survey date. Using direct methods i.e. by constructing life tables, we calculated yearly U5MRs from 1991 to 2010. Projections were made for the years 2011 to 2015. For each NDHS, U5MRs were calculated according to child''s sex, mother’s education, household wealth index, rural/urban residence, development regions and ecological zones. Inequalities were calculated as rate difference, rate ratio, population attributable risk and hazard ratio.

Results

Yearly U5MR (per 1000 live births) had decreased from 157.3 (95% CIs 178.0-138.9) in 1991 to 43.2 (95% CIs 59.1-31.5) in 2010 i.e. 114.1 reduction in absolute risk. Projected U5MR for the year 2015 was 54.33. U5MRs had decreased in absolute terms in all sub groups but relative inequalities had reduced for gender and rural/urban residence only. Wide inequalities existed by wealth and education and increased between 1996 and 2011. For lowest wealth quintile (as compared to highest quintile) hazard ratio (HR) increased from 1.37 (95% CIs 1.27, 1.49) to 2.54 ( 95% CIs 2.25, 2.86) and for mothers having no education (as compared to higher education) HR increased from 2.55 (95% CIs 1.95, 3.33) to 3.75 (95% CIs 3.17, 4.44). Changes in regional inequities were marginal and irregular.

Conclusions

Nepal is most likely to achieve MDG-4 but eductional and wealth inequalities may widen further. National health policies should address to reduce inequalities in U5MR through ‘inclusive policies''.     

Measuring Maternal Mortality: Three Case Studies Using Verbal Autopsy with Different Platforms

Background

Accurate measurement of maternal mortality is needed to develop a greater understanding of the scale of the problem, to increase effectiveness of program planning and targeting, and to track progress. In the absence of good quality vital statistics, interim methods are used to measure maternal mortality. The purpose of this study is to document experience with three community-based interim methods that measure maternal mortality using verbal autopsy.

Methods

This study uses a post-census mortality survey, a sample vital registration with verbal autopsy, and a large-scale household survey to summarize the measures of maternal mortality obtained from these three platforms, compares and contrasts the different methodologies employed, and evaluates strengths and weaknesses of each approach. Included is also a discussion of issues related to death identification and classification, estimating maternal mortality ratios and rates, sample sizes and periodicity of estimates, data quality, and cost.

Results

The sample sizes vary considerably between the three data sources and the number of maternal deaths identified through each platform was small. The proportion of deaths to women of reproductive age that are maternal deaths ranged from 8.8% to 17.3%. The maternal mortality rate was estimable using two of the platforms while obtaining an estimate of the maternal mortality ratio was only possible using one of the platforms. The percentage of maternal deaths due to direct obstetric causes ranged from 45.2% to 80.4%.

Conclusions

This study documents experiences applying standard verbal autopsy methods to estimate maternal mortality and confirms that verbal autopsy is a feasible method for collecting maternal mortality data. None of these interim methods are likely to be suitable for detecting short term changes in mortality due to prohibitive sample size requirements, and thus, comprehensive and continuous civil registration systems to provide high quality vital statistics are essential in the long-term.     

Improving the Quality of Adult Mortality Data Collected in Demographic Surveys: Validation Study of a New Siblings' Survival Questionnaire in Niakhar,Senegal

Background

In countries with limited vital registration, adult mortality is frequently estimated using siblings'' survival histories (SSHs) collected during Demographic and Health Surveys (DHS). These data are affected by reporting errors. We developed a new SSH questionnaire, the siblings'' survival calendar (SSC). It incorporates supplementary interviewing techniques to limit omissions of siblings and uses an event history calendar to improve reports of dates and ages. We hypothesized that the SSC would improve the quality of adult mortality data.

Methods and Findings

We conducted a retrospective validation study among the population of the Niakhar Health and Demographic Surveillance System in Senegal. We randomly assigned men and women aged 15–59 y to an interview with either the DHS questionnaire or the SSC. We compared SSHs collected in each group to prospective data on adult mortality collected in Niakhar. The SSC reduced respondents'' tendency to round reports of dates and ages to the nearest multiple of five or ten (“heaping”). The SSC also had higher sensitivity in recording adult female deaths: among respondents whose sister(s) had died at an adult age in the past 15 y, 89.6% reported an adult female death during SSC interviews versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was similar to that of the DHS questionnaire, i.e., it did not increase the number of false reports of deaths. However, the SSC did not improve the reporting of adult deaths among the brothers of respondents. Study limitations include sample selectivity, limited external validity, and multiple testing.

Conclusions

The SSC has the potential to collect more accurate SSHs than the questionnaire used in DHS. Further research is needed to assess the effects of the SSC on estimates of adult mortality rates. Additional validation studies should be conducted in different social and epidemiological settings.

Trial Registration

Controlled-Trials.com ISRCTN06849961 Please see later in the article for the Editors'' Summary     

Measuring Cultural Identity: Validation of a Modified Cortes,Rogler and Malgady Bicultural Scale in Three Ethnic Groups in New York

Cultural identity is central to health. Acculturation may be formulated with a bicultural model, assessing in parallel the degree of identification with both the original and the host culture. The Cortes, Rogler and Malgady Bicultural Scale (CRM-BS) is composed of two subscales: “original” culture and “mainstream-United States” (US) culture. It was modified into three ethnic versions: Latino, Korean and Chinese. Validation of the CRM-BS was conducted using health professionals and psychiatric patients from the above three ethnic groups and a control sample of mainstream-US (main-US) health professionals in New York City (n = 394). Mean time of completion was 3.7 min and 73% judged it to be easy to use. Strong test–retest reliability correlation coefficients were found (original culture, 0.78; mainstream-US, 0.82). The internal consistency was documented by high Cronbach’s alpha values (original culture, 0.88; mainstream-US, 0.80). Factorial analysis revealed two factors, the first one involving all the items of the original culture and the second all of the mainstream-US items. Concerning its discriminant validity, non-main-US subjects scored significantly higher than main-US subjects on the original culture subscale, and vice versa. Construct validity was assessed comparing intergenerational mean scores on both subscales; as generations become older, mean scores for the original culture decreased, while those for the “host” culture increased. Results for each specific ethnic version are also presented. Cutoff scores were calculated to categorize the involvement with the original culture or the host culture, both of them, or neither.