Correcting mortality for loss to follow-up: a nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa

Background

The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.

Methods and Findings

We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year.

Conclusions

The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up. Please see later in the article for the Editors'' Summary     

Prospects for malaria eradication in sub-Saharan Africa

Background

A characteristic of Plasmodium falciparum infections is the gradual acquisition of clinical immunity resulting from repeated exposures to the parasite. While the molecular basis of protection against clinical malaria remains unresolved, its effects on epidemiological patterns are well recognized. Accumulating epidemiological data constitute a valuable resource that must be intensively explored and interpreted as to effectively inform control planning.

Methodology/Principal Finding

Here we apply a mathematical model to clinical data from eight endemic regions in sub-Saharan Africa. The model provides a quantitative framework within which differences in age distribution of clinical disease are assessed in terms of the parameters underlying transmission. The shorter infectious periods estimated for clinical infections induce a regime of bistability of endemic and malaria-free states in regions of mesoendemic transmission. The two epidemiological states are separated by a threshold that provides a convenient measure for intervention design. Scenarios of eradication and resurgence are simulated.

Conclusions/Significance

In regions that support mesoendemic transmission, intervention success depends critically on reducing prevalence below a threshold which separates endemic and malaria-free regimes.     

Outlook for survivors of childhood in sub-Saharan Africa: adult mortality in Tanzania. Adult Morbidity and Mortality Project.

OBJECTIVE--To measure age and sex specific mortality in adults (15-59 years) in one urban and two rural areas of Tanzania. DESIGN--Reporting of all deaths occurring between 1 June 1992 and 31 May 1995. SETTING--Eight branches in Dar es Salaam (Tanzania''s largest city), 59 villages in Morogoro rural district (a poor rural area), and 47 villages in Hai district (a more prosperous rural area). SUBJECTS--40,304 adults in Dar es Salaam, 69,964 in Hai, 50,465 in Morogoro rural. MAIN OUTCOME MEASURES--Mortality and probability of death between 15 and 59 years of age (45Q15). RESULTS--During the three year observation period a total of 4929 deaths were recorded in adults aged 15-59 years in all areas. Crude mortalities ranged from 6.1/1000/year for women in Hai to 15.9/1000/year for men in Morogoro rural. Age specific mortalities were up to 43 times higher than rates in England and Wales. Rates were higher in men at all ages in the two rural areas except in the age group 25 to 29 years in Hai and 20 to 34 years in Morogoro rural. In Dar es Salaam rates in men were higher only in the 40 to 59 year age group. The probability of death before age 60 of a 15 year old man (45Q15) was 47% in Dar es Salaam, 37% in Hai, and 58% in Morogoro; for women these figures were 45%, 26%, and 48%, respectively. (The average 45Q15s for men and women in established market economies are 15% and 7%, respectively.) CONCLUSION--Survivors of childhood in Tanzania continue to show high rates of mortality throughout adult life. As the health of adults is essential for the wellbeing of young and old there is an urgent need to develop policies that deal with the causes of adult mortality.     

Gender differences in immune reconstitution: a multicentric cohort analysis in sub-Saharan Africa

Background

In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution.

Methods/Principal Findings

Antiretroviral-naïve adults who received ART for at least 9 months in four HIV programs in sub-Saharan Africa were included. Multivariate mixed linear models were used to examine gender differences in immune reconstitution on first line ART.A total of 21,708 patients (68% women) contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART were 149 [IQR 85–206] for women and 125 cells/µL [IQR 63–187] for men. After the first year on ART, immune recovery was higher in women than in men, and gender-based differences increased by 20 CD4 cells/µL per year on average (95% CI 16–23; P<0.001). Up to 6 years after ART start, patients with low initial CD4 levels experienced similar gains compared to patients with high initial levels, including those with CD4>250cells/µL (difference between patients with <50 cells/µL and those with >250 was 284 cells/µL; 95% CI 272–296; LR test for interaction with time p = 0.63). Among patients with initial CD4 count of 150–200 cells/µL, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4–2.5) and men after 4.5 years (95% CI 4.1–4.8) of ART use.

Conclusion

Women achieved better long-term immune response to ART, reaching CD4 level associated with lower risks of AIDS related morbidity and mortality quicker than men.     

Housing environment and early childhood development in sub-Saharan Africa: A cross-sectional analysis

BackgroundThe influence of the safety and security of environments on early childhood development (ECD) has been under-explored. Although housing might be linked to ECD by affecting a child’s health and a parent’s ability to provide adequate care, only a few studies have examined this factor. We hypothesized that housing environment is associated with ECD in sub-Saharan Africa (SSA).Methods and findingsFrom 92,433 children aged 36 to 59 months who participated in Multiple Indicator Cluster Survey (MICS) in 20 SSA countries, 88,271 were tested for cognitive and social–emotional development using the Early Childhood Development Index (ECDI) questionnaire and were thus included in this cross-sectional analysis. Children’s mean age was 47.2 months, and 49.8% were girls. Children were considered developmentally on track in a certain domain if they failed no more than 1 ECDI item in that domain. In each country, we used conditional logistic regression models to estimate the association between improved housing (housing with finished building materials, improved drinking water, improved sanitation facilities, and sufficient living area) and children’s cognitive and social–emotional development, accounting for contextual effects and socioeconomic factors. Estimates from each country were pooled using random-effects meta-analyses. Subgroup analyses were conducted by the child’s gender, maternal education, and household wealth quintiles. On-track cognitive development was associated with improved housing (odds ratio [OR] = 1.15, 95% CI 1.06 to 1.24, p < 0.001), improved drinking water (OR = 1.07, 95% CI 1.00 to 1.14, p = 0.046), improved sanitation facilities (OR = 1.15, 95% CI 1.03 to 1.28, p = 0.014), and sufficient living area (OR = 1.06, 95% CI 1.01 to 1.10, p = 0.018). On-track social–emotional development was associated with improved housing only in girls (OR = 1.14, 95% CI 1.04 to 1.25, p = 0.006). The main limitations of this study included the cross-sectional nature of the datasets and the use of the ECDI, which lacks sensitivity to measure ECD outcomes.ConclusionsIn this study, we observed that improved housing was associated with on-track cognitive development and with on-track social–emotional development in girls. These findings suggest that housing improvement in SSA may be associated not only with benefits for children’s physical health but also with broader aspects of healthy child development.

In a cross-sectional analysis of nationally representative survey data from 20 countries, Yaqing Gao and colleagues investigate associations between housing environment and cognitive and social development in children.     

Structural determinants of child mortality in sub-Saharan Africa: A cross-national study of economic and social influences from 1970 to 1997

This cross-national study seeks to understand the lagging child mortality declines in sub-Saharan Africa by using World Bank data to investigate social and economic factors at three points in time: 1970, 1985, and 1997. Women's education, foreign debt-to-export ratio, and GNP per capita are among the strongest correlates of under five mortality over time. Cross-sectional and longitudinal results suggest that female education is the best overall predictor of child mortality. Average national income does not emerge as a strong predictor, particularly since 1985. Increasing levels of foreign debt are associated with a substantial excess mortality burden. In 1997, the effect of adult HIV prevalence on child mortality was moderate and statistically significant. The study concludes that, although future gains in social factors such as female education will likely be beneficial, without simultaneously addressing high levels of foreign debt and high HIV prevalence, it may be difficult to improve child mortality rates across sub-Saharan Africa.     

Effect of investment in malaria control on child mortality in sub-Saharan Africa in 2002-2008

Background

Around 8.8 million children under-five die each year, mostly due to infectious diseases, including malaria that accounts for 16% of deaths in Africa, but the impact of international financing of malaria control on under-five mortality in sub-Saharan Africa has not been examined.

Methods and Findings

We combined multiple data sources and used panel data regression analysis to study the relationship among investment, service delivery/intervention coverage, and impact on child health by observing changes in 34 sub-Saharan African countries over 2002–2008. We used Lives Saved Tool to estimate the number of lives saved from coverage increase of insecticide-treated nets (ITNs)/indoor residual spraying (IRS). As an indicator of outcome, we also used under-five mortality rate. Global Fund investments comprised more than 70% of the Official Development Assistance (ODA) for malaria control in 34 countries. Each $1 million ODA for malaria enabled distribution of 50,478 ITNs [95%CI: 37,774–63,182] in the disbursement year. 1,000 additional ITNs distributed saved 0.625 lives [95%CI: 0.369–0.881]. Cumulatively Global Fund investments that increased ITN/IRS coverage in 2002–2008 prevented an estimated 240,000 deaths. Countries with higher malaria burden received less ODA disbursement per person-at-risk compared to lower-burden countries ($3.90 vs. $7.05). Increased ITN/IRS coverage in high-burden countries led to 3,575 lives saved per 1 million children, as compared with 914 lives in lower-burden countries. Impact of ITN/IRS coverage on under-five mortality was significant among major child health interventions such as immunisation showing that 10% increase in households with ITN/IRS would reduce 1.5 [95%CI: 0.3–2.8] child deaths per 1000 live births.

Conclusions

Along with other key child survival interventions, increased ITNs/IRS coverage has significantly contributed to child mortality reduction since 2002. ITN/IRS scale-up can be more efficiently prioritized to countries where malaria is a major cause of child deaths to save greater number of lives with available resources.     

Hospital delivery and neonatal mortality in 37 countries in sub-Saharan Africa and South Asia: An ecological study

BackgroundWidespread increases in facility delivery have not substantially reduced neonatal mortality in sub-Saharan Africa and South Asia over the past 2 decades. This may be due to poor quality care available in widely used primary care clinics. In this study, we examine the association between hospital delivery and neonatal mortality.Methods and findingsWe used an ecological study design to assess cross-sectional associations between the share of hospital delivery and neonatal mortality across country regions. Data were from the Demographic and Health Surveys from 2009 to 2018, covering 682,239 births across all regions. We assess the association between the share of facility births in a region that occurred in hospitals (versus lower-level clinics) and early (0 to 7 days) neonatal mortality per 1,000 births, controlling for potential confounders including the share of facility births, small at birth, maternal age, maternal education, urbanicity, antenatal care visits, income, region, and survey year. We examined changes in this association in different contexts of country income, global region, and urbanicity using interaction models.Across the 1,143 regions from 37 countries in sub-Saharan Africa and South Asia, 42%, 29%, and 28% of births took place in a hospital, clinic, and at home, respectively. A 10-percentage point higher share of facility deliveries occurring in hospitals was associated with 1.2 per 1,000 fewer deaths (p-value < 0.01; 95% CI: 0.82 to 1.60), relative to mean mortality of 22. Associations were strongest in South Asian countries, middle-income countries, and urban regions. The study’s limitations include the inability to control for all confounding factors given the ecological and cross-sectional design and potential misclassification of facility levels in our data.ConclusionsRegions with more hospital deliveries than clinic deliveries have reduced neonatal mortality. Increasing delivery in hospitals while improving quality across the health system may help to reduce high neonatal mortality.

In an ecological study, Anna D Gage and colleagues examine the association between hospital delivery and neonatal mortality in 37 countries in sub-Saharan Africa and South Asia.     

Ranking the direct threats to biodiversity in sub-Saharan Africa

Biodiversity and Conservation - Sub-Saharan Africa receives large investments in biodiversity conservation, and if these investments can be concentrated on the highest threats to biodiversity, the...     

A multilevel analysis of the determinants of high-risk sexual behaviour in sub-Saharan Africa

A number of authors have identified multiple concurrent sexual partnerships by both men and women to lie at the root of the HIV/AIDS epidemic in sub-Saharan Africa. This study applies multilevel models to Demographic and Health Survey data collected during 2003-2008 in 20 sub-Saharan African countries to examine the influence of social and cultural context on involvement with multiple sexual partnerships in the region, above and beyond the effects of individual characteristics. The findings provide support for the ecological argument that health behaviours are shaped and determined by societal conditions, in addition to the effects of individual and household characteristics. Involvement with multiple sex partners is most prevalent in societies in which sexual norms are widely permissive and where polygyny is common. Individual autonomy is substantial and attitudes towards sexuality are more liberal among men and women who live in communities in which sexual norms are widely permissive. Men and women who are most likely to have multiple sex partners in the sub-Saharan region are those who initiated sexual activity earlier and those who have the individual attributes (e.g. young age, urban residence, education, media exposure and working for cash and away from home) that bring to them more rights and/or decision-making autonomy, but not necessarily more financial resources and economic security (mostly among women). On the other hand, involvement with multiple partners is determined by cultural norms (i.e. permissive sexual norms) and social change (i.e. mass education, expansion of cash employment). The findings suggest a number of opportunities for more effective policy and programmatic responses to curb the prevalence of multiple partnerships in sub-Saharan Africa.     

Comparative analysis of old-age mortality estimations in Africa

Background

Survival to old ages is increasing in many African countries. While demographic tools for estimating mortality up to age 60 have improved greatly, mortality patterns above age 60 rely on models based on little or no demographic data. These estimates are important for social planning and demographic projections. We provide direct estimations of older-age mortality using survey data.

Methods

Since 2005, nationally representative household surveys in ten sub-Saharan countries record counts of living and recently deceased household members: Burkina Faso, Côte d''Ivoire, Ethiopia, Namibia, Nigeria, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe. After accounting for age heaping using multiple imputation, we use this information to estimate probability of death in 5-year intervals (₅q_x). We then compare our ₅q_x estimates to those provided by the World Health Organization (WHO) and the United Nations Population Division (UNPD) to estimate the differences in mortality estimates, especially among individuals older than 60 years old.

Findings

We obtained information on 505,827 individuals (18.4% over age 60, 1.64% deceased). WHO and UNPD mortality models match our estimates closely up to age 60 (mean difference in probability of death -1.1%). However, mortality probabilities above age 60 are lower using our estimations than either WHO or UNPD. The mean difference between our sample and the WHO is 5.9% (95% CI 3.8–7.9%) and between our sample is UNPD is 13.5% (95% CI 11.6–15.5%). Regardless of the comparator, the difference in mortality estimations rises monotonically above age 60.

Interpretation

Mortality estimations above age 60 in ten African countries exhibit large variations depending on the method of estimation. The observed patterns suggest the possibility that survival in some African countries among adults older than age 60 is better than previously thought. Improving the quality and coverage of vital information in developing countries will become increasingly important with future reductions in mortality.     

Towards control of schistosomiasis in sub-Saharan Africa

Approximately 80% of the 200 million people infected with schistosomiasis inhabit sub-Saharan Africa, and the annual mortality is estimated to be 280,000. Praziquantel is the drug of choice in the treatment of schistosomiasis and pregnant women may now be treated. It was agreed at the World Health Assembly in 2001 that at least 75% of school-aged children in high burden areas should be treated for schistosomiasis and soil-transmitted helminth infections by 2010 to reduce morbidity. A grant from the Bill and Melinda Gates Foundation to the Schistosomiasis Control Initiative, Imperial College of Science, Technology and Medicine, London has enabled control programmes to be initiated in Uganda, Tanzania, Zambia, Burkina Faso, Niger and Mali. Additional programmes have recently commenced in Zanzibar with a grant from the Health Foundation to The Natural History Museum, London and in Cameroon. Combination treatment for schistosomiasis, gastrointestinal helminths and filariasis reduces costs of control programmes. The EC Concerted Action Group on 'Praziquantel: its central role in the chemotherapy of schistosome infection' met in Yaoundé Cameroon in 2004 to discuss recent developments in laboratory and field studies. The use of standard operating procedures will enable data on drug action on schistosomes produced in different laboratories to be compared. With the ever increasing use of praziquantel there is a possibility of the development of resistance by schistosomes to the drug, hence the necessity to explore the activities of other compounds. Artemether, unlike praziquantel, is effective against immature schistosomes. The effectiveness of mirazid, an extract of myrrh, is controversial as data from different laboratories are equivocal. It is suggested that an independent body such as the World Health Organization should determine whether mirazid should be used in the treatment of schistosomiasis.     

Data-driven analyses of behavioral strategies to eliminate cysticercosis in sub-Saharan Africa

BackgroundThe multi-host taeniosis/cysticercosis disease system is associated with significant neurological morbidity, as well as economic burden, globally. We investigated whether lower cost behavioral interventions are sufficient for local elimination of human cysticercosis in Boulkiemdé, Sanguié, and Nayala provinces of Burkina Faso.Methodology/Principal findingsProvince-specific data on human behaviors (i.e., latrine use and pork consumption) and serological prevalence of human and pig disease were used to inform a deterministic, compartmental model of the taeniosis/cysticercosis disease system. Parameters estimated via Bayesian melding provided posterior distributions for comparing transmission rates associated with human ingestion of Taenia solium cysticerci due to undercooking and human exposure to T. solium eggs in the environment. Reductions in transmission via these pathways were modeled to determine required effectiveness of a market-focused cooking behavior intervention and a community-led sanitation and hygiene program, independently and in combination, for eliminating human cysticercosis as a public health problem (<1 case per 1000 population). Transmission of cysticerci due to consumption of undercooked pork was found to vary significantly across transmission settings. In Sanguié, the rate of transmission due to undercooking was 6% higher than that in Boulkiemdé (95% CI: 1.03, 1.09; p-value < 0.001) and 35% lower than that in Nayala (95% CI: 0.64, 0.66; p-value < 0.001). We found that 67% and 62% reductions in undercooking of pork consumed in markets were associated with elimination of cysticercosis in Nayala and Sanguié, respectively. Elimination of active cysticercosis in Boulkiemdé required a 73% reduction. Less aggressive reductions of 25% to 30% in human exposure to Taenia solium eggs through sanitation and hygiene programs were associated with elimination in the provinces.Conclusions/SignificanceDespite heterogeneity in effectiveness due to local transmission dynamics and behaviors, education on the importance of proper cooking, in combination with community-led sanitation and hygiene efforts, has implications for reducing morbidity due to cysticercosis and neurocysticercosis.     

Potential impact of antiretroviral therapy and screening on cervical cancer mortality in HIV-positive women in sub-Saharan Africa: a simulation

Background

Despite having high cervical cancer incidence and mortality rates, screening for cervical precancerous lesions remains infrequent in sub-Saharan Africa. The need to screen HIV-positive women because of the higher prevalence and faster progression of cervical precancerous lesions may be heightened by the increased access to highly-active antiretroviral therapy (HAART). Policymakers need quantitative data on the effect of HAART and screening to better allocate limited resources. Our aim was to quantify the potential effect of these interventions on cervical cancer mortality.

Methods and Findings

We constructed a Markov state-transition model of a cohort of HIV-positive women in Cameroon. Published data on the prevalence, progression and regression of lesions as well as mortality rates from HIV, cervical cancer and other causes were incorporated into the model. We examined the potential impact, on cumulative cervical cancer mortality, of four possible scenarios: no HAART and no screening (NHNS), HAART and no screening (HNS), HAART and screening once on HAART initiation (HSHI), and HAART and screening once at age 35 (HS35). Our model projected that, compared to NHNS, lifetime cumulative cervical cancer mortality approximately doubled with HNS. It will require 262 women being screened at HAART initiation to prevent one cervical cancer death amongst women on HAART. The magnitudes of these effects were most sensitive to the rate of progression of precancerous lesions.

Conclusions

Screening, even when done once, has the potential of reducing cervical cancer mortality among HIV-positive women in Africa. The most feasible and cost-effective screening strategy needs to be determined in each setting.     

Schistosomiasis in infants and pre-school-aged children in sub-Saharan Africa: implication for control

Until recently, the epidemiology and control of schistosomiasis in sub-Saharan Africa have focused primarily on infections in school-aged children and to a lesser extent on adults. Now there is growing evidence and reports of infection in infants and pre-school-aged children (≤ 6 years old) in Ghana, Kenya, Mali, Niger, Nigeria and Uganda, with reported prevalence from 14% to 86%. In this review, we provide available information on the epidemiology, transmission and control of schistosomiasis in this age group, generally not considered or included in national schistosomiasis control programmes that are being implemented in several sub-Saharan African countries. Contrary to previous assumptions, we show that schistosomiasis infection starts from early childhood in many endemic communities and factors associated with exposure of infants and pre-school-aged children to infection are yet to be determined. The development of morbidity early in childhood may contribute to long-term clinical impact and severity of schistosomiasis before they receive treatment. Consistently, these issues are overlooked in most schistosomiasis control programmes. It is, therefore, necessary to review current policy of schistosomiasis control programmes in sub-Saharan Africa to consider the treatment of infant and pre-school-aged children and the health education to mothers.