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.     

Worldwide incidence of malaria in 2009: estimates, time trends, and a critique of methods

Background

Measuring progress towards Millennium Development Goal 6, including estimates of, and time trends in, the number of malaria cases, has relied on risk maps constructed from surveys of parasite prevalence, and on routine case reports compiled by health ministries. Here we present a critique of both methods, illustrated with national incidence estimates for 2009.

Methods and Findings

We compiled information on the number of cases reported by National Malaria Control Programs in 99 countries with ongoing malaria transmission. For 71 countries we estimated the total incidence of Plasmodium falciparum and P. vivax by adjusting the number of reported cases using data on reporting completeness, the proportion of suspects that are parasite-positive, the proportion of confirmed cases due to each Plasmodium species, and the extent to which patients use public sector health facilities. All four factors varied markedly among countries and regions. For 28 African countries with less reliable routine surveillance data, we estimated the number of cases from model-based methods that link measures of malaria transmission with case incidence. In 2009, 98% of cases were due to P. falciparum in Africa and 65% in other regions. There were an estimated 225 million malaria cases (5th–95th centiles, 146–316 million) worldwide, 176 (110–248) million in the African region, and 49 (36–68) million elsewhere. Our estimates are lower than other published figures, especially survey-based estimates for non-African countries.

Conclusions

Estimates of malaria incidence derived from routine surveillance data were typically lower than those derived from surveys of parasite prevalence. Carefully interpreted surveillance data can be used to monitor malaria trends in response to control efforts, and to highlight areas where malaria programs and health information systems need to be strengthened. As malaria incidence declines around the world, evaluation of control efforts will increasingly rely on robust systems of routine surveillance. Please see later in the article for the Editors'' Summary     

Levels and trends in cardiovascular risk factors and drug treatment in 4837 elderly Dutch myocardial infarction patients between 2002 and 2006

Background

It is important to gain insight into opportunities for secondary prevention of cardiovascular disease. Our aim was to investigate levels and trends in cardiovascular risk factors and drug treatment in Dutch post-myocardial infarction (MI) patients between 2002 and 2006 and to make comparisons with the EUROASPIRE surveys (1999–2007).

Methods

We analysed data from 4837 post-MI patients (aged 69 years, 78% men) from 32 Dutch hospitals, using baseline cross-sectional data from the Alpha Omega Trial.

Results

Between 2002 and 2006, significant declines were found in the prevalence of smoking (23% to 16%, p < 0.001), hypercholesterolaemia (≥5 mmol/l; 54% to 27%, p < 0.0001) and hypertension (≥140/90 mmHg; 58% to 48%, p < 0.001). The prevalence of antithrombotic drugs was high (97%). The prevalence of lipid-modifying drugs and antihypertensives was high, and increased (74% to 90%, p < 0.0001 and 82% to 93%, p < 0.001, respectively). The prevalence of obesity (27%) was high in 2002 and decreased to 24% in 2006, albeit not significantly. Diabetes prevalence was high and increased between 2002 and 2006 (18% to 22%, p = 0.02). In comparison with EUROASPIRE patients, who were on average 8–10 years younger, our study in 2006 included patients with lower levels of obesity, hypertension, hypercholesterolaemia, diabetes and lower use of antiplatelets and β-blockers, but similar levels of lipid-modifying drugs.

Conclusions

This study showed that older Dutch post-MI patients were adequately treated with drugs, and that risk factors reached lower levels than in the younger EUROASPIRE patients. However, there is room for improvement in diet and lifestyle, given the high prevalence of smoking, obesity, and diabetes.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-012-0248-z) contains supplementary material, which is available to authorized users.     

The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths

Background

Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.

Methods and Findings

The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.

Conclusions

Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.     

Neonatal mortality levels for 193 countries in 2009 with trends since 1990: a systematic analysis of progress, projections, and priorities

Background

Historically, the main focus of studies of childhood mortality has been the infant and under-five mortality rates. Neonatal mortality (deaths <28 days of age) has received limited attention, although such deaths account for about 41% of all child deaths. To better assess progress, we developed annual estimates for neonatal mortality rates (NMRs) and neonatal deaths for 193 countries for the period 1990–2009 with forecasts into the future.

Methods and Findings

We compiled a database of mortality in neonates and children (<5 years) comprising 3,551 country-years of information. Reliable civil registration data from 1990 to 2009 were available for 38 countries. A statistical model was developed to estimate NMRs for the remaining 155 countries, 17 of which had no national data. Country consultation was undertaken to identify data inputs and review estimates. In 2009, an estimated 3.3 million babies died in the first month of life—compared with 4.6 million neonatal deaths in 1990—and more than half of all neonatal deaths occurred in five countries of the world (44% of global livebirths): India 27.8% (19.6% of global livebirths), Nigeria 7.2% (4.5%), Pakistan 6.9% (4.0%), China 6.4% (13.4%), and Democratic Republic of the Congo 4.6% (2.1%). Between 1990 and 2009, the global NMR declined by 28% from 33.2 deaths per 1,000 livebirths to 23.9. The proportion of child deaths that are in the neonatal period increased in all regions of the world, and globally is now 41%. While NMRs were halved in some regions of the world, Africa''s NMR only dropped 17.6% (43.6 to 35.9).

Conclusions

Neonatal mortality has declined in all world regions. Progress has been slowest in the regions with high NMRs. Global health programs need to address neonatal deaths more effectively if Millennium Development Goal 4 (two-thirds reduction in child mortality) is to be achieved. Please see later in the article for the Editors'' Summary     

Estimating population cause-specific mortality fractions from in-hospital mortality: validation of a new method

Background

Cause-of-death data for many developing countries are not available. Information on deaths in hospital by cause is available in many low- and middle-income countries but is not a representative sample of deaths in the population. We propose a method to estimate population cause-specific mortality fractions (CSMFs) using data already collected in many middle-income and some low-income developing nations, yet rarely used: in-hospital death records.

Methods and Findings

For a given cause of death, a community''s hospital deaths are equal to total community deaths multiplied by the proportion of deaths occurring in hospital. If we can estimate the proportion dying in hospital, we can estimate the proportion dying in the population using deaths in hospital. We propose to estimate the proportion of deaths for an age, sex, and cause group that die in hospital from the subset of the population where vital registration systems function or from another population. We evaluated our method using nearly complete vital registration (VR) data from Mexico 1998–2005, which records whether a death occurred in a hospital. In this validation test, we used 45 disease categories. We validated our method in two ways: nationally and between communities. First, we investigated how the method''s accuracy changes as we decrease the amount of Mexican VR used to estimate the proportion of each age, sex, and cause group dying in hospital. Decreasing VR data used for this first step from 100% to 9% produces only a 12% maximum relative error between estimated and true CSMFs. Even if Mexico collected full VR information only in its capital city with 9% of its population, our estimation method would produce an average relative error in CSMFs across the 45 causes of just over 10%. Second, we used VR data for the capital zone (Distrito Federal and Estado de Mexico) and estimated CSMFs for the three lowest-development states. Our estimation method gave an average relative error of 20%, 23%, and 31% for Guerrero, Chiapas, and Oaxaca, respectively.

Conclusions

Where accurate International Classification of Diseases (ICD)-coded cause-of-death data are available for deaths in hospital and for VR covering a subset of the population, we demonstrated that population CSMFs can be estimated with low average error. In addition, we showed in the case of Mexico that this method can substantially reduce error from biased hospital data, even when applied to areas with widely different levels of development. For countries with ICD-coded deaths in hospital, this method potentially allows the use of existing data to inform health policy.     

Updated Global Burden of Cholera in Endemic Countries

BackgroundThe global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million cases and 91,000 deaths annually due to cholera in 51 endemic countries. A major limitation in our previous estimate was that the endemic and non-endemic countries were defined based on the countries’ reported cholera cases. We overcame the limitation with the use of a spatial modelling technique in defining endemic countries, and accordingly updated the estimates of the global burden of cholera.Conclusion/SignificanceThe global burden of cholera remains high. Sub-Saharan Africa accounts for the majority of this burden. Our findings can inform programmatic decision-making for cholera control.     

Diarrhea, pneumonia, and infectious disease mortality in children aged 5 to 14 years in India

Background

Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years.

Methods

A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001–03 in 1·1 million homes in India.

Results

Infectious diseases accounted for 58% of all deaths among children aged 5 to 14 years. About 18% of deaths were due to diarrheal diseases, 10% due to pneumonia, 8% due to central nervous system infections, 4% due to measles, and 12% due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24·1 and 13·9 per 100 000 respectively. Mortality was nearly 50% higher in girls than in boys for both diarrheal diseases and pneumonia.

Conclusions

Approximately 60% of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea in particular, is much higher than previously estimated.     

Estimating regional population size and annual harvest intensity of the sooty shearwater in New Zealand

Abstract

Recent comprehensive survey data from multiple New Zealand offshore islands were combined with demographic population models to produce the first formal estimate of the total population of sooty shearwaters within New Zealand territory. We estimated the total population over 1994–2005 to be 21.3 (19.0–23.6) million individual birds in the New Zealand region. This population consisted of 12.8 (12.0–13.6) million adults, 2.8 (2.5–3.1) million chicks, and 4.4 (4.2–4.7) million breeding pairs. Breeding sooty shearwaters were concentrated primarily around the southern islands of New Zealand, with 53% breeding in the Titi Islands surrounding Rakiura (Stewart Island). Rakiura Maori muttonbirders were estimated to harvest 360 000 (320 000–400 000) sooty shearwaters per year, equivalent to 18% of the chicks produced in the harvested areas and 13% of chicks in the New Zealand region. Overall, 11% of the chicks within the Titi Islands live on unharvested ground. Systematic and widespread surveys of breeding colonies in South America are needed before a reliable global sooty shearwater population estimate can be calculated.     

Relative Bioavailability of Chlorothiazide from Mucoadhesive Compacts in Pigs

The relative bioavailability of chlorothiazide from mucoadhesive polymeric compacts is compared to commercial oral suspension in pigs. A single-dose randomized study was conducted in 12 healthy pigs that are 9–10 weeks old. After overnight fasting, pigs were divided into two groups of six animals. To the first group, a reference product containing 50 mg of chlorothiazide suspension, and in the second group, test product (mucoadhesive compacts) chlorothiazide (50 mg) was administered with 75 mL of water via gastric tubes. Blood samples were collected between 0 to 24 h using catheters inserted into the jugular vein. Plasma was separated by protein precipitation, and chlorothiazide concentrations were determined using a high-performance liquid chromatography method. The mean T_max and the C_max of chlorothiazide following the administration of oral suspension and mucoadhesive compacts were 0.58 ± 0.20 h and 682.97 ± 415.69 ng/mL and 2.17 ± 0.98 h and 99.42 ± 124.08 ng/mL, respectively. The K_el and T_1/2 of chlorothiazide were found to be 1.06 ± 0.28 h⁻¹ and 0.70 ± 0.21 h from suspension and 0.95 ± 1.11 h⁻¹ and 2.05 ± 1.90 h from the compacts, respectively. The T_max of mucoadhesive compacts were significantly longer (p < 0.05; 2.17 h) than the reference products (0.58 h), whereas the C_max of compacts were significantly lower (99 ng/mL) than the reference product (683 ng/mL; p < 0.05). The area under the curve (AUC) of compacts accounts only 50.15% (404.32 ± 449.93 ng h/mL) of the reference product’s AUC (806.27 ± 395.97 ng h/mL). The relative bioavailability of the compacts was lower than that of the suspension, and this may be due to the narrow window of absorption for chlorothiazide.Key words: bioavailability, chlorothiazide, mucoadhesive compacts, pigs     

Estimating the resources needed and savings anticipated from roll-out of adult male circumcision in Sub-Saharan Africa

Background

Trials in Africa indicate that medical adult male circumcision (MAMC) reduces the risk of HIV by 60%. MAMC may avert 2 to 8 million HIV infections over 20 years in sub-Saharan Africa and cost less than treating those who would have been infected. This paper estimates the financial and human resources required to roll out MAMC and the net savings due to reduced infections.

Methods

We developed a model which included costing, demography and HIV epidemiology. We used it to investigate 14 countries in sub-Saharan Africa where the prevalence of male circumcision was lower than 80% and HIV prevalence among adults was higher than 5%, in addition to Uganda and the Nyanza province in Kenya. We assumed that the roll-out would take 5 years and lead to an MC prevalence among adult males of 85%. We also assumed that surgery would be done as it was in the trials. We calculated public program cost, number of full-time circumcisers and net costs or savings when adjusting for averted HIV treatments. Costs were in USD, discounted to 2007. 95% percentile intervals (95% PI) were estimated by Monte Carlo simulations.

Results

In the first 5 years the number of circumcisers needed was 2 282 (95% PI: 2 018 to 2 959), or 0.24 (95% PI: 0.21 to 0.31) per 10 000 adults. In years 6–10, the number of circumcisers needed fell to 513 (95% PI: 452 to 664). The estimated 5-year cost of rolling out MAMC in the public sector was $919 million (95% PI: 726 to 1 245). The cumulative net cost over the first 10 years was $672 million (95% PI: 437 to 1 021) and over 20 years there were net savings of $2.3 billion (95% PI: 1.4 to 3.4).

Conclusion

A rapid roll-out of MAMC in sub-Saharan Africa requires substantial funding and a high number of circumcisers for the first five years. These investments are justified by MAMC''s substantial health benefits and the savings accrued by averting future HIV infections. Lower ongoing costs and continued care savings suggest long-term sustainability.     

Neurocardiological differences between musicians and control subjects

Background

Exercise training is beneficial in health and disease. Part of the training effect materialises in the brainstem due to the exercise-associated somatosensory nerve traffic. Because active music making also involves somatosensory nerve traffic, we hypothesised that this will have training effects resembling those of physical exercise.

Methods

We compared two groups of healthy, young subjects between 18 and 30 years: 25 music students (13/12 male/female, group M) and 28 controls (12/16 male/female, group C), peers, who were non-musicians. Measurement sessions to determine resting heart rate, resting blood pressure and baroreflex sensitivity (BRS) were held during morning hours.

Results

Groups M and C did not differ significantly in age (21.4 ± 3.0 vs 21.2 ± 3.1 years), height (1.79 ± 0.11 vs 1.77 ± 0.10 m), weight (68.0 ± 9.1 vs 66.8 ± 10.4 kg), body mass index (21.2 ± 2.5 vs 21.3 ± 2.4 kg∙m⁻²) and physical exercise volume (39.3 ± 38.8 vs 36.6 ± 23.6 metabolic equivalent hours/week). Group M practised music daily for 1.8 ± 0.7 h. In group M heart rate (65.1 ± 10.6 vs 68.8 ± 8.3 beats/min, trend P =0.08), systolic blood pressure (114.2 ± 8.7 vs 120.3 ± 10.0 mmHg, P = 0.01), diastolic blood pressure (65.0 ± 6.1 vs 71.0 ± 6.2 mmHg, P < 0.01) and mean blood pressure (83.7 ± 6.4 vs 89.4 ± 7.1, P < 0.01) were lower than in group C. BRS in groups M and C was 12.9 ± 6.7 and 11.3 ± 5.8 ms/mmHg, respectively (P = 0.17).

Conclusions

The results of our study suggest that active music making has training effects resembling those of physical exercise training. Our study opens a new perspective, in which active music making, additionally to being an artistic activity, renders concrete health benefits for the musician.     

Treatment with atorvastatin is associated with a better prognosis in chronic heart failure with systolic dysfunction: results from The Daunia Heart Failure Registry

Background

Few works have evaluated the effect of statins on left ventricular dysfunction in patients with chronic heart failure (CHF), by using tissue Doppler imaging (TDI). We therefore aimed to investigate whether atorvastatin treatment may influence prognosis and myocardial performance evaluated by TDI in subjects with CHF.

Methods

Five hundred thirty-two consecutive CHF outpatients enrolled in a local registry, the Daunia Heart Failure Registry, were prospectively analysed. 195 patients with CHF and left ventricular ejection fraction (LVEF) ≤40 %, either in treatment with atorvastatin (N: 114) or without statins (N: 81), underwent TDI examination. Adverse events were evaluated during follow-up.

Results

The atorvastatin group showed a lower incidence of adverse events (cardiac death: 0 % vs 7 %, p < 0.01), and better TDI performance (E/E’ 15 ± 5.7 vs 18 ± 8.3, p < 001) than controls. Ischaemic CHF patients in treatment with atorvastatin also showed a lower incidence of adverse events (death: 10 % vs 26 %, p < 0.05; sustained ventricular arrhythmias: 5 % vs 19 %, p < 0.05, cardiac death: 0 vs 8 %, p < 0.05) and better TDI performance (E/E’ ratio: 15.00 ± 5.68 vs 19.72 ± 9.14, p < 0.01; St: 353.70 ± 48.96 vs 303.33 ± 68.52 msec, p < 0.01) than controls. The association between atorvastatin and lower rates of cardiac death remained statistically significant even after correction in a multivariable analysis (RR 0.83, 95 % CI 0.71–0.96, p < 0.05 in CHF with LVEF ≤40 %; RR 0.77, 95 % CI 0.62–0.95, p < 0.05 in ischaemic CHF with LVEF ≤40 %).

Conclusions

Treatment with atorvastatin in outpatients with systolic CHF is associated with fewer cardiac deaths, and a better left ventricular performance, as assessed by TDI.     

Endpiece: A newspaper

ObjectiveTo assess the cost effectiveness of ultrasound screening for abdominal aortic aneurysms.DesignPrimary analysis: four year cost effectiveness analysis based directly on results from a randomised controlled trial in which patients were individually allocated to invitation to ultrasound screening (intervention) or to a control group not offered screening. Secondary analysis: projection of the data, based on conservative assumptions, to indicate likely cost effectiveness at 10 years.SettingFour centres in the United Kingdom. Screening delivered in primary care settings with follow up and surgery offered in the main hospitalsParticipantsPopulation based sample of 67 800 men aged 65-74 years.ResultsOver four years there were 47 fewer deaths related to abdominal aortic aneurysms in the screening group than in the control group, but the additional costs incurred were £2.2m. After adjustment for censoring and discounted at 6% the mean additional cost of the screening programme was £63.39 ($97.77, €100.48) (95% confidence interval £53.31 to £73.48) per patient. The hazard ratio for abdominal aortic aneurysm was 0.58 (0.42 to 0.78). Over four years the mean incremental cost effectiveness ratio for screening was £28 400 (£15 000 to £146 000) per life year gained, equivalent to about £36 000 per quality adjusted life year. After 10 years this figure is estimated to fall to around £8000 per life year gained.ConclusionsEven at four years the cost effectiveness of screening for abdominal aortic aneurysms is at the margin of acceptability according to current NHS thresholds. Over a longer period the cost effectiveness will improve substantially, the predicted ratio at 10 years falling to around a quarter of the four year figure.

What is already known on this topic

Small trials have suggested that an ultrasound screening programme to detect abdominal aortic aneurysms in older men may be effectiveThere is uncertainty about the cost effectiveness of routine screening, with widely varying estimates

What this study adds

A cost effectiveness analysis of data from a large randomised trial with follow up over four years showed 47 fewer deaths and additional costs of £2.2m in the group invited to screeningThe adjusted net cost per patient was £63.39 and per life year gained was £28 400The projected cost per life year gained after 10 years was £8000, which is substantially lower than the perceived NHS threshold value     

Monitoring Change in Child Mortality through Household Surveys

Background

Most low- and middle-income countries lack fully functional civil registration systems. Measures of under-five mortality are typically derived from periodic household surveys collecting detailed information from women on births and child deaths. However, such surveys are expensive and are not appropriate for monitoring short-term changes in child mortality. We explored and tested the validity of two new analysis methods for less-expensive summary histories of births and child deaths for such monitoring in five African countries.

Methods and Findings

The first method we explored uses individual-level survey data on births and child deaths to impute full birth histories from an earlier survey onto summary histories from a more recent survey. The second method uses cohort changes between two surveys in the average number of children born and the number of children dead by single year of age to estimate under-five mortality for the inter-survey period. The first method produces acceptable annual estimates of under-five mortality for two out of six applications to available data sets; the second method produced an acceptable estimate in only one of five applications, though none of the applications used ideal data sets.

Conclusions

The methods we tested were not able to produce consistently good quality estimates of annual under-five mortality from summary birth history data. The key problem we identified was not with the methods themselves, but with the underlying quality of the summary birth histories. If summary birth histories are to be included in general household surveys, considerable emphasis must be placed on quality control.     

Health Gains and Financial Protection from Pneumococcal Vaccination and Pneumonia Treatment in Ethiopia: Results from an Extended Cost-Effectiveness Analysis

Background

Pneumonia and pneumococcal disease cause a large disease burden in resource-constrained settings. We pursue an extended cost-effectiveness analysis (ECEA) of two fully publicly financed interventions in Ethiopia: pneumococcal vaccination for newborns and pneumonia treatment for under-five children in Ethiopia.

Methods

We apply ECEA methods and estimate the program impact on: (1) government program costs; (2) pneumonia and pneumococcal deaths averted; (3) household expenses related to pneumonia/pneumococcal disease treatment averted; (4) prevention of household medical impoverishment measured by an imputed money-metric value of financial risk protection; and (5) distributional consequences across the wealth strata of the country population. Available epidemiological and cost data from Ethiopia are applied and the two interventions are assessed separately at various incremental coverage levels.

Results

Scaling-up pneumococcal vaccines at around 40% coverage would cost about $11.5 million and avert about 2090 child deaths annually, while a 10% increase of pneumonia treatment to all children under 5 years of age would cost about $13.9 million and avert 2610 deaths annually. Health benefits of the two interventions publicly financed would be concentrated among the bottom income quintile, where 30–40% of all deaths averted would be expected to occur in the poorest quintile. In sum, the two interventions would eliminate a total of $2.4 million of private household expenditures annually, where the richest quintile benefits from around 30% of the total private expenditures averted. The financial risk protection benefits would be largely concentrated among the bottom income quintile. The results are most sensitive to variations in vaccine price, population size, number of deaths due to pneumonia, efficacy of interventions and out-of-pocket copayment share.

Conclusions

Vaccine and treatment interventions for children, as shown with the illustrative examples of pneumococcal vaccine and pneumonia treatment, can bring large health and financial benefits to households in Ethiopia, most particularly among the poorest socio-economic groups.     

Measuring Adult Mortality Using Sibling Survival: A New Analytical Method and New Results for 44 Countries, 1974–2006

Background

For several decades, global public health efforts have focused on the development and application of disease control programs to improve child survival in developing populations. The need to reliably monitor the impact of such intervention programs in countries has led to significant advances in demographic methods and data sources, particularly with large-scale, cross-national survey programs such as the Demographic and Health Surveys (DHS). Although no comparable effort has been undertaken for adult mortality, the availability of large datasets with information on adult survival from censuses and household surveys offers an important opportunity to dramatically improve our knowledge about levels and trends in adult mortality in countries without good vital registration. To date, attempts to measure adult mortality from questions in censuses and surveys have generally led to implausibly low levels of adult mortality owing to biases inherent in survey data such as survival and recall bias. Recent methodological developments and the increasing availability of large surveys with information on sibling survival suggest that it may well be timely to reassess the pessimism that has prevailed around the use of sibling histories to measure adult mortality.

Methods and Findings

We present the Corrected Sibling Survival (CSS) method, which addresses both the survival and recall biases that have plagued the use of survey data to estimate adult mortality. Using logistic regression, our method directly estimates the probability of dying in a given country, by age, sex, and time period from sibling history data. The logistic regression framework borrows strength across surveys and time periods for the estimation of the age patterns of mortality, and facilitates the implementation of solutions for the underrepresentation of high-mortality families and recall bias. We apply the method to generate estimates of and trends in adult mortality, using the summary measure ₄₅ q ₁₅—the probability of a 15-y old dying before his or her 60th birthday—for 44 countries with DHS sibling survival data. Our findings suggest that levels of adult mortality prevailing in many developing countries are substantially higher than previously suggested by other analyses of sibling history data. Generally, our estimates show the risk of adult death between ages 15 and 60 y to be about 20%–35% for females and 25%–45% for males in sub-Saharan African populations largely unaffected by HIV. In countries of Southern Africa, where the HIV epidemic has been most pronounced, as many as eight out of ten men alive at age 15 y will be dead by age 60, as will six out of ten women. Adult mortality levels in populations of Asia and Latin America are generally lower than in Africa, particularly for women. The exceptions are Haiti and Cambodia, where mortality risks are comparable to many countries in Africa. In all other countries with data, the probability of dying between ages 15 and 60 y was typically around 10% for women and 20% for men, not much higher than the levels prevailing in several more developed countries.

Conclusions

Our results represent an expansion of direct knowledge of levels and trends in adult mortality in the developing world. The CSS method provides grounds for renewed optimism in collecting sibling survival data. We suggest that all nationally representative survey programs with adequate sample size ought to implement this critical module for tracking adult mortality in order to more reliably understand the levels and patterns of adult mortality, and how they are changing. Please see later in the article for the Editors'' Summary     

Increased In Situ Intestinal Absorption of Phytoestrogenic Diarylheptanoids from Curcuma comosa in Nanoemulsions

Curcuma comosa has long been used as a gynecological medicine. Several diarylheptanoids have been purified from this plant, and their pharmacological effects were proven. However, there is no information about the absorption of C. comosa components to support the formulation usage. In the present study, C. comosa hexane extract and the mixture of its two major compounds, (4E,6E)-1,7-diphenylhepta-4,6-dien-3-ol (DA1) and (6E)-1,7-diphenylhept-6-en-3-ol (DA2), were formulated into nanoemulsions. The physical properties of the nanoemulsions and the in situ intestinal absorptions of DA1 and DA2 were evaluated. The results demonstrated the mean particle sizes at 0.207 ± 0.001 and 0.408 ± 0.014 μm, and the zeta potential at −14.57 ± 0.85 and −10.47 ± 0.32 mV for C. comosa nanoemulsion (C.c-Nano) and mixture of diarlylheptanoid nanoemulsions (DA-Nano), respectively. The entrapments of DA1 and DA2 were 76.61% and 75.41%, and 71.91% and 71.63% for C.c-Nano and DA-Nano, respectively. The drug loading ratios of DA1 and DA2 were 351.47 and 614.53 μg/mg, and 59.48 and 126.72 μg/mg for C.c-Nano and DA-Nano. The intestinal absorption rates of DA1 and DA2 were 0.329 ± 0.015 and 0.519 ± 0.026 μg/min/cm² in C.c-Nano, and 0.380 ± 0.006 and 0.428 ± 0.036 μg/min/cm² in DA-Nano, which were five to ten times faster than those in oil. In conclusion, the formulation in nanoemulsion forms obviously increased the intestinal absorption rate of diarylheptanoids.KEY WORDS: Curcuma comosa, diarylheptanoids, intestinal absorption, nanoemulsion, phytoestrogen     

Long-term Clinical Outcome and MIBI SPECT Parameters in Percutaneous Coronary Interventions

Background and Aim

Primary percutaneous coronary intervention (PCI) is the preferred treatment option for acute myocardial infarction (MI). Off-site PCI reduces time-to-treatment, which could potentially lead to enhanced clinical outcomes. Therefore, we investigated whether off-site PCI improves 5-year clinical outcomes compared with on-site PCI and whether this is related to in-hospital ^99mTc-sestamibi single photon emission computed tomography (MIBI SPECT) parameters.

Methods

We describe the 5-year follow-up for a combined endpoint of death or re-infarction in 128 patients with acute MI who were randomly assigned to undergo primary PCI at the off-site centre (n = 68) or to transferral to an on-site centre (n = 60). Three days after PCI, MIBI SPECT was performed to estimate infarct size. A multivariate Cox regression model was created to study the relation between MIBI SPECT parameters and long-term clinical outcomes.

Results

After a mean follow-up of 5.8 ± 1.1 years, 25 events occurred. Off-site PCI significantly reduced door-to-balloon time compared with on-site PCI (94 ± 54 versus 125 ± 59 min, p = 0.003). However, infarct size (17 ± 15 versus 14 ± 12%, p = 0.34) and 5-year death or infarct rate (21% versus 18%, p = 0.75) were comparable between treatment centres. With multivariate analysis, only Killip class ≥2 and Q wave MI, but not scintigraphic data, predicted long-term clinical outcomes.

Conclusion

Off-site PCI reduced door-to-balloon time with a comparable 5-year death or infarct rate. Parameters from resting MIBI SPECT on day 3 after MI did not predict long-term clinical outcomes.