In Vivo Antimalarial Activity of Crude Fruit Extract of Capsicum frutescens Var. Minima (Solanaceae) against Plasmodium berghei-Infected Mice.

BACKGROUND: The alarming spread of parasite resistance to current antimalarial agents is threatening malaria controlling efforts. This, consequently, urged the scientific community to discover novel antimalarial drugs. Successful and most potent antimalarial drugs were obtained from medicinal plants. Capsicum frutescens is claimed to possess an antiplasmodial activity in Ethiopian and Ugandan folkloric medicine. However, there is a lack of pharmacological evidence for its antiplasmodial activity. This study, hence, was aimed at evaluating the in vivo antiplasmodial activity of C. frutescens in a mouse model. METHODS: The dried fruits of the plant were extracted with 80% methanol using cold maceration. A 4-day suppressive test was employed to ascertain the claimed antiplasmodial effect of the plant. Following inoculation with P. berghei, mice in treatment groups were provided with three dose levels (100, 200, and 400 mg/kg) of the extract, while 2% Tween 80 and chloroquine served as the negative and positive controls, respectively. Weight, temperature, packed cell volume, parasitemia, and survival time were then monitored. RESULTS: The acute oral toxicity study revealed that the crude extract caused no mortality and revealed no overt sign of toxicity. In the 4-day suppressive test, all dose levels of the extract were found to exhibit a significant (p < 0.05) inhibition of parasitemia compared to those of the negative control. Maximum parasite suppression (93.28%) was exerted by the highest dose (400 mg/kg/day) of extract. Also, the extract significantly (p < 0.05) prolonged survival time and prevented body weight loss and reduction in temperature and anemia compared to the vehicle-treated group. CONCLUSION: This investigation found strong evidence that the fruit extract of C. frutescens is endowed with promising antiplasmodial activity. Hence, the plant could serve as a potential source of a newer antimalarial agent.

Evidence of Impact: iCCM as a strategy to save lives of children under five.

BACKGROUND: In 2013, the World Health Organization (WHO) launched the Rapid Access Expansion (RAcE) programme in the Democratic Republic of Congo, Malawi, Mozambique, Niger, and Nigeria to increase coverage of diagnostic, treatment, and referral services for malaria, pneumonia, and diarrhea among children ages 2-59 months. In 2017, a final evaluation of the six RAcE sites was conducted to determine whether the programme goal was reached. A key evaluation objective was to estimate the reduction in childhood mortality and the number of under-five lives saved over the project period in the RAcE project areas. METHODS: The Lives Saved Tool (LiST) was used to estimate reductions in all-cause child mortality due to changes in coverage of treatment for the integrated community case management (iCCM) illnesses - malaria, pneumonia, and diarrhea - while accounting for other changes in maternal and child health interventions in each RAcE project area. Data from RAcE baseline and endline household surveys, Demographic and Health Surveys, and routine health service data were used in each LiST model. The models yielded estimated change in under-five mortality rates, and estimated number of lives saved per year by malaria, pneumonia and diarrhea treatment. We adjusted the results to estimate the number of lives saved by community health worker (CHW)-provided treatment. RESULTS: The LiST model accounts for coverage changes in iCCM intervention coverage and other health trends in each project area to estimate mortality reduction and child lives saved. Under five mortality declined in all six RAcE sites, with an average decline of 10 percent. An estimated 6200 under-five lives were saved by malaria, pneumonia, and diarrhea treatment in the DRC, Malawi, Niger, and Nigeria, of which approximately 4940 (75 percent) were saved by treatment provided by CHWs. This total excludes Mozambique, where there were no estimated under-five lives saved likely due to widespread stockouts of key medications. In all other project areas, lives saved by CHW-provided treatment contributed substantially to the estimated decline in under-five mortality. CONCLUSIONS: Our results suggest that iCCM is a strategy that can save lives and measurably decrease child mortality in settings where access to health facility services is low and adequate resources for iCCM implementation are provided for CHW services.

Effect of community-based intervention on improving access to treatment for sick under-five children in hard-to-reach communities in Niger State, Nigeria.

BACKGROUND: Access to prompt and appropriate treatment is key to survival for children with malaria, pneumonia and diarrhoea. Community-based services are vital to extending care to remote populations. Malaria Consortium supported Niger state Ministry of Health, Nigeria, to introduce and implement an integrated community case management (iCCM) programme for four years in six local government areas (LGAs). The objective was to increase coverage of effective treatment for malaria, pneumonia and diarrhoea among children aged 2-59 months. METHODS: The programme involved training, equipping, ongoing support and supervision of 1320 community volunteers (CORPs) to provide iCCM services to their communities in all six LGAs. Demand creation activities were also conducted; these included community dialogues, household mobilization, sensitization and mass media campaigns targeted at programme communities. To assess the level of changes in care seeking and treatment, baseline and endline household surveys were conducted in 2014 and 2017 respectively. For both surveys, a 30×30 multi-stage cluster sampling method was used, the sampling frame being RAcE programme communities. RESULTS: Care-seeking from an appropriate provider increased overall and for each iCCM illness from 78% to 94% for children presenting with fever (P < 0.01), from 72% to 91% for diarrhoea cases (P < 0.01), and from 76% to 89% for cases of cough with difficult or fast breathing (P < 0.05). For diagnosis and treatment, the coverage of fevers tested for malaria increased from 34% to 77% (P < 0.001) and ACT treatments from 57% to 73% (<0.005); 56% of cases of cough or fast breathing who sought care from a CORP, had their respiratory rate counted and 61% with cough or fast breathing received amoxicillin. At endline caregivers sought care from CORPs in their communities for most cases of childhood illnesses (84%) compared to other providers at hospitals (1%) or health centres (9%).This aligns with caregivers' belief that CORPs are trusted providers (94%) who provide quality services (96%). CONCLUSION: Implementation of iCCM with focused demand creation activities can improve access to quality lifesaving interventions from frontline community providers in Nigeria. This can contribute towards achieving SDGs if iCCM is scaled up to hard-to-reach areas of all states in the country.

Community engagement and mobilisation of local resources to support integrated Community Case Management of childhood illnesses in Niger State, Nigeria.

BACKGROUND: Despite strong evidence of integrated community case management (iCCM) of childhood illnesses being a proven intervention for reducing childhood morbidity and mortality, sustainability remains a challenge in most settings. Community ownership and contribution are important factors in sustainability. The purpose of this study was to document the process and scale achieved for community engagement and mobilisation to foster ownership, service uptake and sustainability of iCCM activities. METHODS: A review of data collected by the RAcE project was conducted to describe the scale and achievement of leveraging community resources to support the community-oriented resource persons (CORPs). The Rapid Access Expansion (RAcE)-supported iCCM programme in Niger state (2014-2017), aimed at improving coverage of case management services for malaria, pneumonia, and diarrhoea, among children aged 2-59 months. Resources donated were documented and costed based on the market value of goods and services at the time of donation. These monetary valuations were validated at community dialogue meetings. Descriptive statistics were used to summarise quantitative variables. The mean of the number of CORPs in active service and the percentages of the mobilised resources received by CORPs were calculated. RESULTS: The community engagement activities included 143 engagement and advocacy visits, and meetings, 300 community dialogues, reactivation of 60 ward development committees, and 3000 radio messages in support of iCCM. 79.5% of 1659 trained CORPs were still in active iCCM service at the end of the project. We estimated the costs of all support provided by the community to CORPs in cash and kind as US$ 123 062. Types of support included cash; building materials; farming support; fuel for motorcycles, and transport fares. CONCLUSIONS: The achievements of community engagement, mobilisation, and the resources leveraged, demonstrated acceptability of the project to the beneficiaries and their willingness to contribute to uninterrupted service provision by CORPs.

iCCM data quality: an approach to assessing iCCM reporting systems and data quality in 5 African countries.

BACKGROUND: Ensuring the quality of health service data is critical for data-driven decision-making. Data quality assessments (DQAs) are used to determine if data are of sufficient quality to support their intended use. However, guidance on how to conduct DQAs specifically for community-based interventions, such as integrated community case management (iCCM) programs, is limited. As part of the World Health Organization's (WHO) Rapid Access Expansion (RAcE) Programme, ICF conducted DQAs in a unique effort to characterize the quality of community health worker-generated data and to use DQA findings to strengthen reporting systems and decision-making. METHODS: We present our experience implementing assessments using standardized DQA tools in the six RAcE project sites in the Democratic Republic of Congo, Malawi, Mozambique, Niger, and Nigeria. We describe the process used to create the RAcE DQA tools, adapt the tools to country contexts, and develop the iCCM DQA Toolkit, which enables countries to carry out regular and rapid DQAs. We provide examples of how we used results to generate recommendations. RESULTS: The DQA tools were customized for each RAcE project to assess the iCCM data reporting system, trace iCCM indicators through this system, and to ensure that DQAs were efficient and generated useful recommendations. This experience led to creation of an iCCM DQA Toolkit comprised of simplified versions of RAcE DQA tools and a guidance document. It includes system assessment questions that elicit actionable responses and a simplified data tracing tool focused on one treatment indicator for each iCCM focus illness: diarrhea, malaria, and pneumonia. The toolkit is intended for use at the national or sub-national level for periodic data quality checks. CONCLUSIONS: The iCCM DQA Toolkit was designed to be easily tailored to different data reporting system structures because iCCM data reporting tools and data flow vary substantially. The toolkit enables countries to identify points in the reporting system where data quality is compromised and areas of the reporting system that require strengthening, so that countries can make informed adjustments that improve data quality, strengthen reporting systems, and inform decision-making.

A mixed-methods quasi-experimental evaluation of a mobile health application and quality of care in the integrated community case management program in Malawi.

BACKGROUND: The use of mobile health (mHealth) technology to improve quality of care (QoC) has increased over the last decade; limited evidence exists to espouse mHealth as a decision support tool, especially at the community level. This study presents evaluation findings of using a mobile application for integrated community case management (iCCM) by Malawi's health surveillance assistants (HSAs) in four pilot districts to deliver lifesaving services for children. METHODS: A quasi-experimental study design compared adherence to iCCM guidelines between HSAs using mobile application (n = 137) and paper-based tools (n = 113), supplemented with 47 key informant interviews on perceptions about QoC and sustainability of iCCM mobile application. The first four sick children presenting to each HSA for an initial consultation of an illness episode were observed by a Ministry of Health iCCM trainer for assessment, classification, and treatment. Results were compared using logistic regression, controlling for child-, HSA-, and district-level characteristics, with Holm-Bonferroni-adjusted significance levels for multiple comparison. RESULTS: HSAs using the application tended to assess sick children according to iCCM guidelines more often than HSAs using paper-based tools for cough (adjusted proportion, 98% vs 91%; P < 0.01) and five physical danger signs - chest in-drawing; alertness; palmar pallor; malnourishment; oedema (80% vs 62%; P < 0.01), but not for fever (97% vs 93%; P = 0.06), diarrhoea (94% vs 87%; P = 0.03), and three danger signs - not able to eat or drink; vomits everything; has convulsions (88% vs 79%; P = 0.01). Across illnesses and danger signs, 81% of HSAs using the application correctly classified sick children, compared to 58% of HSAs using paper-based tools (P < 0.01). No differences existed for their treatment (P = 0.27). Interview respondents corroborated these findings that using iCCM mobile application ensures protocol adherence. Respondents noted barriers to its consistent and wide use including hardware problems and limited resources. CONCLUSION: Generally, the mobile application is a promising tool for improving adherence to the iCCM protocol for assessing sick children and classifying illness by HSAs. Limited effects on treatments and inconsistent use suggest the need for more studies on mHealth to improve QoC at community level.

Lessons from the integrated community case management (iCCM) Rapid Access Expansion Program.

In 2012, the Government of Canada awarded a grant to the World Health Organization's Global Malaria Programme (GMP) to support the scale-up of integrated community case management (iCCM) of pneumonia, diarrhoea and malaria among children under 5 in sub-Saharan Africa under the Rapid Access Expansion Programme (RAcE). The two main objectives of the programme were to: (1) Contribute to the reduction of child mortality due to malaria, pneumonia and diarrhoea by increasing access to diagnostics, treatment and referral services, and (1) Stimulate policy updates in participating countries and catalyze scale-up of integrated community case management (iCCM) through documentation and dissemination of best practices. Based on the results of the implementation research and programmatic lessons, this collection provides evidence on impact and improving coverage of iCCM in routine health systems, and opportunities and challenges of implementing and sustaining delivery of iCCM at scale.

Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron deficiency can be reduced by short-term adjunctive iron supplementation.

BACKGROUND: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial. METHODS: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection. Plasma levels of the iron status markers hepcidin and fibroblast growth factor 23 were measured in animals surviving and succumbing to malaria, and accompanying tissue pathology in the liver and the spleen was assessed. RESULTS: Nutritional iron deficiency was associated with increased mortality from P. chabaudi malaria. This increased mortality could be partially offset by carefully timed, short-duration adjunctive iron supplementation. Moribund animals were characterized by low levels of hepcidin and high levels of fibroblast growth factor 23. All infected mice had extramedullary splenic haematopoiesis, and iron-supplemented mice had visually detectable intracellular iron stores. CONCLUSIONS: Blood transfusions are the only currently available means to correct severe anaemia in children with malaria. The potential of carefully timed, short-duration adjunctive iron supplementation as a safe alternative should be considered.

In vivo antimalarial activity of synthetic hepcidin against Plasmodium berghei in mice.

The present study was designed to investigate the antimalarial activity of synthetic hepcidin and its effect on cytokine secretion in mice infected with Plasmodium berghei. The mice were infected with P. berghei intravenously and treated with hepcidin according to 4-day suppression test and Rane's test. The serum levels of interleukins (IL-1ß, IL-2, IL-6, IL-10, IL-12p70, and IL-17A), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the experimental mice were determined using a cytometric bead array (CBA) kit. The survival rate of the infected mice was also registered. Additionally, the serum iron, alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted direct anti-malarial function in vivo and increased survival rate in a dose-dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2, and Th17 cytokines, TNF-α, and IFN-γ were inhibited by hepcidin. In conclusion, our results demonstrated that synthetic hepcidin exerts in vivo antimalarial activity and possesses anti-inflammatory function, which provides a basis for future design of new derivatives with ideal anti-malarial activity.

Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria.

Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high, at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patient clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO), and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate the host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.

[Cost-effectiveness analysis (CEA) regarding vitamin A in children aged less than 5 years-old in Colombia]. / Análisis de costo efectividad de la vitamina A en niños menores de 5 años en Colombia.

OBJECTIVE: Evaluating the relative cost-effectiveness of using vitamin A in children aged less than 5-years-old regarding the reduction of events involving diarrhoea, malaria and mortality from the Colombian health-related social security system (CHSSS). MATERIALS AND METHODS: A decision tree was constructed, using deaths averted as outcome. Probabilities were taken from the pertinent literature and costs from official sources. The cost-effectiveness threshold was three times greater than the per capita Colombian gross domestic product (GDP) in 2012. Probabilistic and deterministic sensitivity analyses were made and cost effectiveness acceptability curves were drawn. RESULTS: Providing a cohort of 100,000 children with vitamin A (as opposed to not doing so) would represent a saving regarding medical attention costs of $ 340,306,917 due to the number of events involving diarrhea (4,268) and malaria (76), having become reduced, as well as cases requiring hospitalization. A saving for the CHSSS was consistently obtained in sensitivity analysis. CONCLUSION: Providing vitamin supplements for children aged less than 5 years-old would seem to be the least costly and most effective (dominant) strategy for the CHSSS, i.e. compared to not doing so).

Nationwide implementation of integrated community case management of childhood illness in Rwanda.

BACKGROUND: Between 2008 and 2011, Rwanda introduced integrated community case management (iCCM) of childhood illness nationwide. Community health workers in each of Rwanda's nearly 15,000 villages were trained in iCCM and equipped for empirical diagnosis and treatment of pneumonia, diarrhea, and malaria; for malnutrition surveillance; and for comprehensive reporting and referral services. METHODS: We used data from the Rwanda health management information system (HMIS) to calculate monthly all-cause under-5 mortality rates, health facility use rates, and community-based treatment rates for childhood illness in each district. We then compared a 3-month baseline period prior to iCCM implementation with a seasonally matched comparison period 1 year after iCCM implementation. Finally, we compared the actual changes in all-cause child mortality and health facility use over this time period with the changes that would have been expected based on baseline trends in Rwanda. RESULTS: The number of children receiving community-based treatment for diarrhea and pneumonia increased significantly in the 1-year period after iCCM implementation, from 0.83 cases/1,000 child-months to 3.80 cases/1,000 child-months (P = .01) and 0.25 cases/1,000 child-months to 5.28 cases/1,000 child-months (P<.001), respectively. On average, total under-5 mortality rates declined significantly by 38% (P<.001), and health facility use declined significantly by 15% (P = .006). These decreases were significantly greater than would have been expected based on baseline trends. CONCLUSIONS: This is the first study to demonstrate decreases in both child mortality and health facility use after implementing iCCM of childhood illness at a national level. While our study design does not allow for direct attribution of these changes to implementation of iCCM, these results are in line with those of prior studies conducted at the sub-national level in other low-income countries.

Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years of age.

BACKGROUND: Zinc deficiency is prevalent in low- and middle-income countries, and contributes to significant diarrhoea-, pneumonia-, and malaria-related morbidity and mortality among young children. Zinc deficiency also impairs growth. OBJECTIVES: To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged six months to 12 years of age. SEARCH METHODS: Between December 2012 and January 2013, we searched CENTRAL, MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, Embase, African Index Medicus, Conference Proceedings Citation Index, Dissertation Abstracts, Global Health, IndMED, LILACS, WHOLIS, metaRegister of Controlled Trials, and WHO ICTRP. SELECTION CRITERIA: Randomised controlled trials of preventive zinc supplementation in children aged six months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalised children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions. DATA COLLECTION AND ANALYSIS: Two authors screened studies, extracted data, and assessed risk of bias. We contacted trial authors for missing information. MAIN RESULTS: We included 80 randomised controlled trials with 205,401 eligible participants. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes were affected by risk of bias. The risk ratio (RR) for all-cause mortality was compatible with a reduction and a small increased risk of death with zinc supplementation (RR 0.95, 95% confidence interval (CI) 0.86 to 1.05, 14 studies, high-quality evidence), and also for cause-specific mortality due to diarrhoea (RR 0.95, 95% CI 0.69 to 1.31, four studies, moderate-quality evidence), lower respiratory tract infection (LRTI) (RR 0.86, 95% CI 0.64 to 1.15, three studies, moderate-quality evidence), or malaria (RR 0.90, 95% CI 0.77 to 1.06, two studies, moderate-quality evidence).Supplementation reduced diarrhoea morbidity, including the incidence of all-cause diarrhoea (RR 0.87, 95% CI 0.85 to 0.89, 26 studies, moderate-quality evidence), but the results for LRTI and malaria were imprecise: LRTI (RR 1, 95% CI 0.94 to 1.07, 12 studies, moderate-quality evidence); malaria (RR 1.05, 95% 0.95 to 1.15, four studies, moderate-quality evidence).There was moderate-quality evidence of a very small improvement in height with supplementation (standardised mean difference (SMD) -0.09, 95% CI -0.13 to -0.06; 50 studies), but the size of this effect might not be clinically important. There was a medium to large positive effect on zinc status.Supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46, five studies, high-quality evidence). We found no clear evidence of benefit or harm of supplementation with regard to haemoglobin or iron status. Supplementation had a negative effect on copper status. AUTHORS' CONCLUSIONS: In our opinion, the benefits of preventive zinc supplementation outweigh the harms in areas where the risk of zinc deficiency is relatively high. Further research should determine optimal intervention characteristics such as supplement dose.

A description of malaria sentinel surveillance: a case study in Oromia Regional State, Ethiopia.

BACKGROUND: In the context of the massive scale up of malaria interventions, there is increasing recognition that the current capacity of routine malaria surveillance conducted in most African countries through integrated health management information systems is inadequate. The timeliness of reporting to higher levels of the health system through health management information systems is often too slow for rapid action on focal infectious diseases such as malaria. The purpose of this paper is to: 1) describe the implementation of a malaria sentinel surveillance system in Ethiopia to help fill this gap; 2) describe data use for epidemic detection and response as well as programmatic decision making; and 3) discuss lessons learned in the context of creating and running this system. CASE DESCRIPTION: As part of a comprehensive strategy to monitor malaria trends in Oromia Regional State, Ethiopia, a system of ten malaria sentinel sites was established to collect data on key malaria morbidity and mortality indicators. To ensure the sentinel surveillance system provides timely, actionable data, the sentinel facilities send aggregate data weekly through short message service (SMS) to a central database server. Bland-Altman plots and Poisson regression models were used to investigate concordance of malaria indicator reports and malaria trends over time, respectively. DISCUSSION: This paper describes three implementation challenges that impacted system performance in terms of: 1) ensuring a timely and accurate data reporting process; 2) capturing complete and accurate patient-level data; and 3) expanding the usefulness and generalizability of the system's data to monitor progress towards the national malaria control goals of reducing malaria deaths and eventual elimination of transmission. CONCLUSIONS: The use of SMS for reporting surveillance data was identified as a promising practice for accurately tracking malaria trends in Oromia. The rapid spread of this technology across Africa offers promising opportunities to collect and disseminate surveillance data in a timely way. High quality malaria surveillance in Ethiopia remains a resource intensive activity and extending the generalizability of sentinel surveillance findings to other contexts remains a major limitation of these strategies.

Quantification of food and nutrient intakes in Zambian children with and without malaria under controlled feeding conditions.

Vitamin A supplementation improves status, which may protect against malarial infection. Provitamin A carotenoid biofortified staple crops may provide a more sustainable approach to alleviate vitamin A deficiency than supplementation, but the impact of febrile illness on food intake must be considered in malaria endemic regions. Morbidity data and food logs from a three-month efficacy trial on provitamin A biofortified (orange) maize in preschool Zambian children (n = 181, age 3-5 years) were systematically analyzed over time to determine the impact of malaria on food intake. Nutrients examined included macronutrients, iron, zinc, and vitamin A. Comparisons based on individual intakes in healthy and malarial states over three-day intervals were made including children from both the orange and white maize groups (n = 100). Malaria prevalence did not differ overall or between treatment groups over time (all P > 0.05). Lower nutrient intakes were observed for all variables during malaria outbreaks (food 289 ± 412 g; energy 248 ± 346 kcal; carbohydrate 42 ± 62 g; protein 8 ± 12 g; fat 5 ± 7 g; iron 1 ± 2 mg; zinc 1 ± 1 mg; vitamin A 58 ± 100 retinol activity equivalents; all P < 0.05). No differences were observed between nutrient decreases in orange and white maize groups (P > 0.05). Considering the impact of malaria on food and nutrient intakes and increased vitamin A utilization and excretion due to the acute phase response, biofortification targets for provitamin A carotenoids may need to be elevated in malaria endemic regions.

Effects of zinc supplementation on the incidence of mortality in preschool children: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56-1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53-1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11-2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77-1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67-1.44; P = 0.917). Subgroup analysis indicated that zinc supplementation was associated with a reduction in total mortality risk if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months. CONCLUSIONS/SIGNIFICANCE: Zinc supplementation does not have an effect on total mortality, diarrhea-related mortality, pneumonia-related mortality, malaria-related mortality, or other causes of mortality. Subgroup analysis suggested that zinc supplementation can effectively reduce the risk of total mortality if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.

Patterns in coverage of maternal, newborn, and child health interventions: projections of neonatal and under-5 mortality to 2035.

BACKGROUND: Urgent calls have been made for improved understanding of changes in coverage of maternal, newborn, and child health interventions, and their country-level determinants. We examined historical trends in coverage of interventions with proven effectiveness, and used them to project rates of child and neonatal mortality in 2035 in 74 Countdown to 2015 priority countries. METHODS: We investigated coverage of all interventions for which evidence was available to suggest effective reductions in maternal and child mortality, for which indicators have been defined, and data have been obtained through household surveys. We reanalysed coverage data from 312 nationally-representative household surveys done between 1990 and 2011 in 69 countries, including 58 Countdown countries. We developed logistic Loess regression models for patterns of coverage change for each intervention, and used k-means cluster analysis to divide interventions into three groups with different historical patterns of coverage change. Within each intervention group, we examined performance of each country in achieving coverage gains. We constructed models that included baseline coverage, region, gross domestic product, conflict, and governance to examine country-specific annual percentage coverage change for each group of indicators. We used the Lives Saved Tool (LiST) to predict mortality rates of children younger than 5 years (henceforth, under 5) and in the neonatal period in 2035 for Countdown countries if trends in coverage continue unchanged (historical trends scenario) and if each country accelerates intervention coverage to the highest level achieved by a Countdown country with similar baseline coverage level (best performer scenario). RESULTS: Odds of coverage of three interventions (antimalarial treatment, skilled attendant at birth, and use of improved sanitation facilities) have decreased since 1990, with a mean annual decrease of 5·5% (SD 2·7%). Odds of coverage of four interventions--all related to the prevention of malaria--have increased rapidly, with a mean annual increase of 27·9% (7·3%). Odds of coverage of other interventions have slowly increased, with a mean annual increase of 5·3% (3·5%). Rates of coverage change varied widely across countries; we could not explain the differences by measures of gross domestic product, conflict, or governance. On the basis of LiST projections, we predicted that the number of Countdown countries with an under-5 mortality rate of fewer than 20 deaths per 1000 livebirths per year would increase from four (5%) of the 74 in 2010, to nine (12%) by 2035 under the historical trends scenario, and to 15 (20%) under the best performer scenario. The number of countries with neonatal mortality rates of fewer than 11 per 1000 livebirths per year would increase from three (4%) in 2010, to ten (14%) by 2035 under the historical trends scenario, and 67 (91%) under the best performer scenario. The number of under-5 deaths per year would decrease from an estimated 7·6 million in 2010, to 5·4 million (28% decrease) if historical trends continue, and to 2·3 million (71% decrease) under the best performer scenario. INTERPRETATION: Substantial reductions in child deaths are possible, but only if intensified efforts to achieve intervention coverage are implemented successfully within each of the Countdown countries. FUNDING: The Bill & Melinda Gates Foundation.

Polysaccharides from the Chinese medicinal herb Achyranthes bidentata enhance anti-malarial immunity during Plasmodium yoelii 17XL infection in mice.

BACKGROUND: Clinical immunity to malaria in human populations is developed after repeated exposure to malaria. Regulation and balance of host immune responses may lead to optimal immunity against malaria parasite infection. Polysaccharides (ABPS) derived from the Chinese herb ox knee Achyranthes bidentata possess immuno-modulatory functions. The aim of this study is to use the rodent malaria model Plasmodium yoelii 17XL (P. y17XL) to examine whether pretreatment with ABPS will modulate host immunity against malaria infection and improve the outcome of the disease. METHODS: To determine whether ABPS could modulate immunity against malaria, mice were pretreated with ABPS prior to blood-stage infection by P. y17XL. Host survival and parasitaemia were monitored daily. The effect of pretreatment on host immune responses was studied through the quantitation of cytokines, dendritic cell populations, and natural regulatory T cells (Treg). RESULTS: Pretreatment with ABPS prior to infection significantly extended the survival time of mice after P. y17XL infection. At three and five days post-infection, ABPS pretreated mice developed stronger Th1 immune responses against malaria infection with the number of F4/80+CD36+ macrophages and levels of IFN-γ, TNF-α and nitric oxide being significantly higher than in the control group. More importantly, ABPS-treated mice developed more myeloid (CD11c+CD11b+) and plasmacytoid dendritic cells (CD11c+CD45R+/B220+) than control mice. ABPS pretreatment also resulted in modulated expression of MHC-II, CD86, and especially Toll-like receptor 9 by CD11c+ dendritic cells. In comparison, pretreatment with ABPS did not alter the number of natural Treg or the production of the anti-inflammatory cytokine IL-10. CONCLUSION: Pretreatment with the immuno-modulatory ABPS selectively enhanced Th1 immune responses to control the proliferation of malaria parasites, and prolonged the survival of mice during subsequent malaria infection.

Estimation of malaria mortality of A District in India during 2010 by using three models.

There is no standard method for estimating annual malaria deaths in India. The degree of under-reporting in routine system is uncertain with a varied picture of 10, 15, 25 and 200 times as found in different studies/models. During October 2010 a community based cross-sectional survey was conducted by National Vector Borne Disease Control Programme (NVBDCP) in 32 villages of West Garo Hills district of Meghalaya. 'Gap filling', 'fever survey' and 'verbal autopsy' models, developed in NVBDCP were used on the data obtained from two surveys done simultaneously: 'fever survey' with 2 weeks recall period and 'death survey' with one year recall period. Inputs from demographic and epidemiological data of the district were also given. During 2010, the district has reported 32 malaria deaths. Degrees of under-reporting found in the study were 6.93, 7.53 and 12 times in three models respectively. The first two models yielded closer estimates. But, verbal autopsy model gave inflated value as the method was unreliable for diagnosing malaria deaths. First two models, if found to be replicable, can be incorporated in NVBDCP activities to evaluate malaria control measures at district level. Verbal autopsy model may be used after concordance study in those districts where Pf malaria cases occur but no death is reported.

Impact assessment of malaria vector control using routine surveillance data in Zambia: implications for monitoring and evaluation.

BACKGROUND: Malaria vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), with pyrethroids and DDT, to reduce malaria transmission has been expansively implemented in Zambia. The impact of these interventions on malaria morbidity and mortality has not previously been formally assessed at the population level in Zambia. METHODS: The impact of IRS (15 urban districts) and LLINs (15 rural districts) implementation on severe malaria cases, deaths and case fatality rates in children below the age of five years were compared. Zambian national Health Management Information System data from 2007 to 2008 were retrospectively analysed to assess the epidemiological impact of the two interventions using odds ratios to compare the pre-scaling up year 2007 with the scaling-up year 2008. RESULTS: Overall there were marked reductions in morbidity and mortality, with cases, deaths and case fatality rates (CFR) of severe malaria decreasing by 31%, 63% and 62%, respectively between 2007 and 2008. In urban districts with IRS introduction there was a significant reduction in mortality (Odds Ratio [OR] = 0.37, 95% CI = 0.31-0.43, P = 0.015), while the reduction in mortality in rural districts with LLINs implementation was not significant (OR = 0.83, 95% CI = 0.67-1.04, P = 0.666). A similar pattern was observed for case fatality rates with a significant reduction in urban districts implementing IRS (OR = 0.34, 95% CI = 0.33-0.36, P = 0.005), but not in rural districts implementing LLINs (OR = 0.96, 95% CI = 0.91-1.00, P = 0.913). No substantial difference was detected in overall reduction of malaria cases between districts implementing IRS and LLINs (P = 0.933). CONCLUSION: Routine surveillance data proved valuable for determining the temporal effects of malaria control with two strategies, IRS and LLINs on severe malaria disease in different types of Zambian districts. However, this analysis did not take into account the effect of artemisinin-based combination therapy (ACT), which were being scaled up countrywide in both rural and urban districts.