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Abstract Background Ghana is a malaria-endemic country with the entire population at risk. The Northern region of the country recorded the highest malaria case fatality rate (CFR) for two consecutive years: 1.11% in 2013 and 1.07% in 2014. Even though the National Malaria Elimination Programme (NMEP) has achieved a reduction in malaria mortality, the existence of high case fatality in the Northern region was alarming. This study, therefore, aimed to determine the factors associated with malaria mortality in the northern region of Ghana to institute control measures. Methods An unmatched case control study was conducted from July 2015 to August 2015. The study population consisted of patients admitted to health facilities for severe malaria in the Northern region of Ghana. A case was defined as a patient diagnosed with severe malaria at an eligible health facility who died as a result of malaria. A control was a patient diagnosed with severe malaria admitted to an eligible health facility who did not die. Health facilities that recorded CFRs of 1.0% and above were randomly sampled for this study, after which, 10 cases and 20 controls were recruited from each health facility. Information on cases and controls was then abstracted from hospital records using an electronically deployed abstraction tool. Continuous variables were expressed as means and medians, and categorical variables as frequencies and proportions. Multivariable logistic regression was used to assess the strength of the association between malaria mortality and factors predictive of malaria mortality. A p-value of

Background: Ghana is a malaria-endemic country with the entire population at risk. The Northern region of the country recorded the highest malaria case fatality rate (CFR) for two consecutive years: 1.11% in 2013 and 1.07% in 2014. Even though the National Malaria Elimination Programme (NMEP) has achieved a reduction in malaria mortality, the existence of high case fatality in the Northern region was alarming. This study, therefore, aimed to determine the factors associated with malaria mortality in the northern region of Ghana to institute control measures. Methods: An unmatched case control study was conducted from July 2015 to August 2015. The study population consisted of patients admitted to health facilities for severe malaria in the Northern region of Ghana. A case was defined as a patient diagnosed with severe malaria at an eligible health facility who died as a result of malaria. A control was a patient diagnosed with severe malaria admitted to an eligible health facility who did not die. Health facilities that recorded CFRs of 1.0% and above were randomly sampled for this study, after which, 10 cases and 20 controls were recruited from each health facility. Information on cases and controls was then abstracted from hospital records using an electronically deployed abstraction tool. Continuous variables were expressed as means and medians, and categorical variables as frequencies and proportions. Multivariable logistic regression was used to assess the strength of the association between malaria mortality and factors predictive of malaria mortality. A p-value of < 0.05 was considered statistically significant. Results: In all, a total of 95 cases and 190 controls participated in this study. The median ages of cases and controls were 4.1 years (IQR = 21.6) and 5.7 years (IQR = 18.2), respectively. Fifty-four (56.8%) cases were females, while 93 (49.0%) of the controls were females. Factors associated with malaria mortality included: duration of hospital stay less than 24 h [aOR: 12.0, 95% CI (5.9–24.6)], severe pallor [aOR: 2.3, 95% CI (1.1–4.6)], children under 5 years [aOR: 2.8, 95% CI (1.4–5.6)], oral Artesunate/Amodiaquine administration [aOR: 0.4, 95% CI (0.2–0.9)] and sepsis as an additional diagnosis [aOR: 4.1, 95% CI (1.8–9.5)]. Conclusion: Predictors of malaria mortality in the Northern region include children under 5 years, severe pallor, sepsis as an additional diagnosis, and use of oral anti-malarial. Patients with severe pallor and sepsis as co-morbidities should receive proactive management. The NMEP and its partners should implement measures to strengthen the referral system, anaemia prevention and management, and retrain health workers on malaria case management. Malaria control interventions targeted at under five children in the region should be reviewed and enhanced. [ABSTRACT FROM AUTHOR]

Abstract Background To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. Methods An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children

Malaria is highly prevalent in Nigeria and accounts for approximately 40% of global malaria mortality. However, most reports on severe malaria in Nigeria are from hospital-based studies without accurate information from communities; thus, malaria-related deaths in the community are left untracked. This study aimed to describe the prevalence and pattern of severe malaria in a community in Northwestern Nigeria. A cross-sectional study was conducted among 2–10-year-old children in Sokoto, in August and December 2016, to determine the endemicity of malaria based on Plasmodium falciparum prevalence rate (PfPR2-10) and to describe the disease pattern. Severe malaria was diagnosed according to the World Health Organisation criteria. Data were described using Stata version 15. The prevalence of non-anaemia severe malaria was higher than expected (2.6%), considering the endemicity pattern which was mesoendemic based on a PfPR2-10 of 34.8%. The mean age of children with severe malaria was 3.73 years, and the male—female ratio was 2:1. However, 54.0% of the patients had hyperparasitaemia. A relatively high prevalence of non-anaemia severe malaria was found in Wamakko. This finding suggests the need to identify and treat cases in the community using modifications of current strategies, particularly seasonal malaria chemoprophylaxis. [ABSTRACT FROM AUTHOR]

Abstract Background India has a substantial burden of malaria, concentrated in specific areas and population groups. Spatio-temporal modelling of deaths due to malaria in India is a critical tool for identifying high-risk groups for effective resource allocation and disease control policy-making, and subsequently for the country’s progress towards United Nations 2030 Sustainable Development Goals. Methods In this study, a spatio-temporal model with the objective of understanding the spatial distribution of malaria mortality rates and the rate of temporal decline, across the country, has been constructed. A spatio-temporal “random slope” model was used, with malaria risk depending on a spatial relative risk surface and a linear time effect with a spatially-varying coefficient. The models were adjusted for urban/rural status (residence of the deceased) and Normalized Difference Vegetation Index (NDVI), using 2004–13 data from the Million Death Study (MDS) (the most recent data available), with nationwide geographic coverage. Previous studies based on MDS had focused only on aggregated analyses. Results The rural population had twice the risk of death due to malaria compared to the urban population. Malaria mortality in some of the highest-risk regions, namely the states of Odisha and Jharkhand, are declining faster than other areas; however, the rate of decline was not uniformly correlated with the level of risk. The overall decline was faster after 2010. Conclusion The results suggest a need for increased attention in high-risk rural populations, which already face challenges like inadequate infrastructure, inaccessibility to health care facilities, awareness, and education around malaria mortality and prevalence. It also points to the urgent need to restart the MDS to document changes since 2013, to develop appropriate malaria control measures.

Background: To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems.Methods: An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment.Results: Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35-6.92 and aOR=2.16, 95% CI 1.11-4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45-0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%).Conclusions: Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed.Trial Registration: The study is registered on ClinicalTrials.gov : NCT03568344. [ABSTRACT FROM AUTHOR]

Background: Anaemia and malaria are leading causes of paediatric hospitalisation and inpatient mortality in sub-Saharan Africa. However, there is limited empirical data on survival following hospital discharge. We aimed to estimate independent effects of anaemia and malaria parasitaemia on inpatient and 1 year postdischarge mortality among Kenyan children., Methods: A retrospective cohort study among children admitted to Kilifi County Hospital (KCH) from 2010 to 2019 and followed-up for 1 year postdischarge in Kilifi Health and Demographic Surveillance System (KHDSS). The main exposures were anaemia and malaria parasitaemia at the time of hospital admission while inpatient and 1 year postdischarge mortality were the outcomes., Results: We included 9431 admissions among 7578 children (43% girls), median (IQR) age 19 (9.9‒23) months. 2069 (22%), 3893 (41%) and 1140 (12%) admissions had mild, moderate and severe anaemia, whereas 366 (3.9%), 779 (8.3%) and 224 (2.4%) had low, medium and high malaria parasitaemia, respectively. Overall, there were 381 (4.0%) inpatient deaths: 317/381 (83%) and 47/381 (12%) among children with any level of anaemia and malaria parasitaemia, respectively. Moderate and severe, but not mild anaemia, were positively associated with inpatient death. Low and high level parasitaemia were positively associated with inpatient mortality, while medium level parasitaemia was negatively associated. There were 228 (3.1%) postdischarge deaths: 32.8 (95% CI 28.8‒37.3) deaths/1000 child-years. 180/228 (79%) deaths occurred within 6 months after index discharge and 99/228 (43%) occurred in the community. Overall, 180/228 (79%) and 10/228 (4.4%) postdischarge deaths occurred among children with any level of anaemia and malaria parasitaemia, respectively. Severe anaemia was positively associated with postdischarge mortality (adjusted HR 1.94 (95% CI 1.11‒3.40)), while medium level parasitaemia was negatively associated., Conclusion: Interventions to create awareness of postdischarge risks, improve uptake of existing interventions and improved discharge processes targeting high-risk groups such as children admitted with severe anaemia, need to be prioritised., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Importance: A prompt malaria diagnosis is crucial for the management of children with febrile illness in sub-Saharan African countries, where malaria remains a leading cause of mortality among children younger than 5 years of age. The development and distribution of point-of-care rapid diagnostic tests (RDTs) for malaria has transformed practice, but limited systematic evidence exists on how malaria RDTs have affected the management of febrile illness and mortality for children younger than 5 years of age across sub-Saharan Africa countries., Objective: To evaluate the association between the distribution of malaria RDTs and the management of febrile illness and mortality among children younger than 5 years of age in sub-Saharan African countries., Design, Setting, and Participants: This quasi-experimental study used a novel dataset linking malaria RDT distribution to 165 nationally representative household surveys across 35 sub-Saharan African countries with mortality data. The sample comprised approximately 3.9 million child-year observations and approximately 260 000 febrile illness episodes in children younger than 5 years of age between 2000 and 2019., Main Outcomes and Measures: Fixed-effects linear probability models were used to analyze the association between variation in malaria RDTs distributed per child younger than 5 years of age (by country per year) and blood testing, antimalarial drug use, antibiotic use, use of symptomatic treatments, and mortality rates. Variation in the effects of testing and treatment was also assessed across the sub-Saharan African countries that had varying prevalence of malaria., Results: The mortality sample included 1 317 866 children and the fever sample included 256 292 children. The mean age of the children with febrile illness was 2.4 years (SD, 1.3 years) and 49% were female. Each additional malaria RDT distributed per child younger than 5 years of age was associated with an increase of 3.5 percentage points (95% CI, 3.2-3.8 percentage points) in blood testing, an increase of 1.5 percentage points (95% CI, 1.2-1.8 percentage points) in the use of antimalarial drugs, an increase of 0.4 percentage points (95% CI, 0.1-0.6 percentage points) in antibiotic use, and a decrease of 0.4 percentage points (95% CI, 0.1-0.8 percentage points) in the use of treatments for symptoms. Each additional malaria RDT distributed per child younger than 5 years of age was associated with a reduction in child mortality of 0.34 deaths per 1000 child-years (95% CI, 0.15-0.52 deaths per 1000 child-years). The effects of malaria RDT distribution on medication use and child mortality varied across prevalence settings (low vs high) for malaria; there were survival improvements only in areas that had a high prevalence of malaria., Conclusions and Relevance: Increasing distribution of malaria RDTs was associated with increased blood testing, increased use of antimalarial drugs, and modestly improved survival in children younger than 5 years of age in sub-Saharan African countries. However, malaria RDTs were associated with increases in the rates of antibiotic use that were already high, suggesting that more comprehensive approaches to case management of febrile illness are needed.

Background: In February 2022, the Ministry of Health received reports of more than 100 child deaths from a 'strange disease' in Namutumba District over a period of 6 months from politicians through the media. Preliminary investigations by the district rapid response team confirmed the strange disease to be severe malaria. The scope of severe malaria deaths was investigated, associated factors identified, and recommendations made for control measures to inform early malaria treatment strategies in Namutumba District., Methods: A retrospective study was conducted in March 2022 in the most affected subcounty (Ivukula Subcounty) involving cases and controls. A case was defined as a death with a positive malaria test, fever and any of the following: convulsions, difficulty breathing, yellowing of eyes or palms, tea-coloured urine, anaemia (evidenced by pale eyes or palms, or clinically-identified in medical records), loss of consciousness, or reduced urine output (very little or no urine in a day) in a child ≤ 12 years from September 2021 to February 2022 in Ivukula Subcounty, Namutumba District. Controls were survivors with the same signs and symptoms, recruited in a 2:1 ratio with cases. Cases and controls were actively searched using a door-to-door approach with the help of community health workers. Caretakers were interviewed to obtain data on signs and symptoms, socio-demographic information, health-seeking behaviours and health system risk factors. Drugs and bloodstock status information was obtained from health workers using an interview guide. Factors associated with death were identified using multivariate logistic regression and thematic analysis for qualitative data., Results: Among 46 cases, 29 (63%) were < 5 years, and 23 (50%) were female. Death among children with severe malaria was significantly associated with treatment non-completion (aOR = 9.7, 95%CI 1.8-53) and inability to receive blood transfusion for anaemic patients (aOR = 7.1, (95%CI 1.4-36). Healthcare workers reported that inability to reach referral sites due to transport costs, stockouts of anti-malarials and blood products at health facilities, and absence of integrated community case management of childhood illnesses (iCCM) contributed to deaths among children with severe malaria., Conclusion: Lack of access to anti-malarial treatment and to blood transfusions among anaemic patients due to stockouts were associated with severe malaria deaths among children ≤ 12 years in Ivukula Subcounty. Recommendations made were: accurate quantification of anti-malarials for health facilities, offering transport support to severe patients referred to higher-level facilities, and increasing access to blood products. Activation of iCCM could facilitate public health efforts against severe malaria in the district., (© 2024. The Author(s).)

Background: Azithromycin has been shown to be beneficial in preventing infectious diseases, including malaria, infectious diarrhoea and pneumonia. A cluster randomised control trial on azithromycin MDA in children in Niger, Malawi and Tanzania found a reduction in all-cause under-five (U5) mortality in communities who received azithromycin compared to placebo. However, the reduction was largest and statistically significant only in Niger. The purpose of this trial is to evaluate the impact of azithromycin plus intermittent preventive treatment in infants (IPTi), recently renamed by the World Health Organisation as perennial malaria chemoprevention (PMC), with sulfadoxine-pyrimethamine (SP) on all-cause mortality up to 18 months of age in children living in areas of high mortality burden through the Expanded Program on Immunisation (EPI) in Sierra Leone., Methods: The Improving Care through Azithromycin Research for Infants in Africa (ICARIA) trial is a phase III two-arm, individually randomised, double-blinded, placebo-controlled trial administering oral AZI (20 mg/kg bodyweight) at three time points to children attending EPI visits in Sierra Leone. A total of 20,560 infants attending the first EPI contact at around 6 weeks of age are recruited and randomised to AZI or placebo in a 1:1 ratio. The second and third AZI/placebo doses are given at 9 and 15 months of age. The primary outcome of the trial is all-cause mortality rate at 18 months of age assessed through mortality surveillance. Other trial outcomes include the impact on antimicrobial resistance, and on the immune response to certain key routine EPI immunisations, the safety of the intervention, the prevalence of SP resistance markers and the feasibility, and acceptability of adding AZI to the EPI programme., Discussion: The trial will provide the evidence needed to inform policy regarding the adoption and large-scale implementation of AZI in areas of high-mortality burden in sub-Saharan Africa., Trial Registration: ClinicalTrials.gov NCT04235816. Registered on 22 January 2020. Pan-African Clinical Trials Registry PACTR202004540256535. Registered on 14 April 2020., (© 2024. The Author(s).)

Background: Malaria mortality is influenced by several factors including climatic and environmental factors, interventions, socioeconomic status (SES) and access to health systems. Here, we investigated the joint effects of climatic and non-climatic factors on under-five malaria mortality at different spatial scales using data from a Health and Demographic Surveillance System (HDSS) in western Kenya., Methods: We fitted Bayesian spatiotemporal (zero-inflated) negative binomial models to monthly mortality data aggregated at the village scale and over the catchment areas of the health facilities within the HDSS, between 2008 and 2019. First order autoregressive temporal and conditional autoregressive spatial processes were included as random effects to account for temporal and spatial variation. Remotely sensed climatic and environmental variables, bed net use, SES, travel time to health facilities, proximity from water bodies/streams and altitude were included in the models to assess their association with malaria mortality., Results: Increase in rainfall (mortality rate ratio (MRR)=1.12, 95% Bayesian credible interval (BCI): 1.04-1.20), Normalized Difference Vegetation Index (MRR=1.16, 95% BCI: 1.06-1.28), crop cover (MRR=1.17, 95% BCI: 1.11-1.24) and travel time to the hospital (MRR=1.09, 95% BCI: 1.04-1.13) were associated with increased mortality, whereas increase in bed net use (MRR=0.84, 95% BCI: 0.70-1.00), distance to the nearest streams (MRR=0.89, 95% BCI: 0.83-0.96), SES (MRR=0.95, 95% BCI: 0.91-1.00) and altitude (MRR=0.86, 95% BCI: 0.81-0.90) were associated with lower mortality. The effects of travel time and SES were no longer significant when data was aggregated at the health facility catchment level., Conclusion: Despite the relatively small size of the HDSS, there was spatial variation in malaria mortality that peaked every May-June. The rapid decline in malaria mortality was associated with bed nets, and finer spatial scale analysis identified additional important variables. Time and spatially targeted control interventions may be helpful, and fine spatial scales should be considered when data are available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: India has a substantial burden of malaria, concentrated in specific areas and population groups. Spatio-temporal modelling of deaths due to malaria in India is a critical tool for identifying high-risk groups for effective resource allocation and disease control policy-making, and subsequently for the country's progress towards United Nations 2030 Sustainable Development Goals. Methods: In this study, a spatio-temporal model with the objective of understanding the spatial distribution of malaria mortality rates and the rate of temporal decline, across the country, has been constructed. A spatio-temporal "random slope" model was used, with malaria risk depending on a spatial relative risk surface and a linear time effect with a spatially-varying coefficient. The models were adjusted for urban/rural status (residence of the deceased) and Normalized Difference Vegetation Index (NDVI), using 2004–13 data from the Million Death Study (MDS) (the most recent data available), with nationwide geographic coverage. Previous studies based on MDS had focused only on aggregated analyses. Results: The rural population had twice the risk of death due to malaria compared to the urban population. Malaria mortality in some of the highest-risk regions, namely the states of Odisha and Jharkhand, are declining faster than other areas; however, the rate of decline was not uniformly correlated with the level of risk. The overall decline was faster after 2010. Conclusion: The results suggest a need for increased attention in high-risk rural populations, which already face challenges like inadequate infrastructure, inaccessibility to health care facilities, awareness, and education around malaria mortality and prevalence. It also points to the urgent need to restart the MDS to document changes since 2013, to develop appropriate malaria control measures. [ABSTRACT FROM AUTHOR]

Background: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA., Methods: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990-March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted., Results: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%., Conclusions: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible., (© 2024. The Author(s).)

In the context of the end of restrictions due to the COVID-19 pandemic, the renewed increase in international travel was accompanied by a disproportionate rise in deaths due to importated malaria in Germany. The COVID-19 pandemic has led to a delay in establishing the diagnosis of imported malaria, which is associated with a deterioration in the prognosis. In order to significantly reduce the number or completely avoid malaria deaths in Germany in the future, there is an urgent need to raise awareness among those involved in the healthcare system.Measures to effectively communicate the risk and appropriate measures to prevent malaria to travellers are necessary to reverse the negative trend. Rapid diagnosis and adequate management are important to improve survival. For this reason early presentation in the healthcare system in case of fever after returning from the tropics is necessary., Competing Interests: MR ist Sprecher des Leitlinienausschusses der Deutschen Gesellschaft für Tropenmedizin, Reisemedizin und Internationale Gesundheit. Diese Position ist ehrenamtlich., (Thieme. All rights reserved.)

Abstract Background Lack of valid and reliable data on malaria deaths continues to be a problem that plagues the global health community. To address this gap, the verbal autopsy (VA) method was developed to ascertain cause of death at the population level. Despite the adoption and wide use of VA, there are many recognized limitations of VA tools and methods, especially for measuring malaria mortality. This study synthesizes the strengths and limitations of existing VA tools and methods for measuring malaria mortality (MM) in low- and middle-income countries through a systematic literature review. Methods The authors searched PubMed, Cochrane Library, Popline, WHOLIS, Google Scholar, and INDEPTH Network Health and Demographic Surveillance System sites’ websites from 1 January 1990 to 15 January 2016 for articles and reports on MM measurement through VA. Inclusion criteria: article presented results from a VA study where malaria was a cause of death; article discussed limitations/challenges related to measurement of MM through VA. Two authors independently searched the databases and websites and conducted a synthesis of articles using a standard matrix. Results The authors identified 828 publications; 88 were included in the final review. Most publications were VA studies; others were systematic reviews discussing VA tools or methods; editorials or commentaries; and studies using VA data to develop MM estimates. The main limitation were low sensitivity and specificity of VA tools for measuring MM. Other limitations included lack of standardized VA tools and methods, lack of a ‘true’ gold standard to assess accuracy of VA malaria mortality. Conclusions Existing VA tools and methods for measuring MM have limitations. Given the need for data to measure progress toward the World Health Organization’s Global Technical Strategy for Malaria 2016–2030 goals, the malaria community should define strategies for improving MM estimates, including exploring whether VA tools and methods could be further improved. Longer term strategies should focus on improving countries’ vital registration systems for more robust and timely cause of death data.

Abstract Background The United Nation’s sustainable development goal for 2030 is to eradicate the global malaria epidemic, primarily as the disease continues to be one of the major concerns for public health in sub-Saharan Africa. In 2015, the region accounted for 90% of malaria deaths. Mozambique recorded a malaria mortality rate of 42.75 (per 100,000). In Chimoio, Mozambique’s fifth largest city, malaria is the fourth leading cause of death (9.4%). Few data on malaria mortality exists in Mozambique, particularly in relation to Chimoio. The objective of this study was to characterize malaria mortality trends and its spatial distribution in Chimoio. Methods Malaria mortality data and climate data were extracted from the Chimoio Civil Registration records, and the Regional Weather station, from 2010 to 2014. The malaria crude mortality rate was calculated. ANOVA, Tukey’s, Chi square, and time series were carried out and an intervention analysis ARIMA model developed. Results A total of 944 malaria death cases were registered in Chimoio, 729 of these among Chimoio residents (77%). The average malaria mortality by gender was 44.9% for females and 55.1% for males. The age of death varied from 0 to 96 years, with an average age of 25.9 (SE = 0.79) years old. January presented the highest average of malaria deaths, and urban areas presented a lower crude malaria mortality rate. Rural neighbourhoods with good accessibility present the highest malaria crude mortality rate, over 85 per 100,000. Seasonal ARMA (2,0)(1,0)12 fitted the data although it was not able to capture malaria mortality peaks occurring during malaria outbreaks. Intervention effect properly fit the mortality peaks and reduced ARMA’s root mean square error by almost 25%. Conclusion Malaria mortality is increasing in Chimoio; children between 1 and 4 years old represent 13% of Chimoio population, but account for 25% of malaria mortality. Malaria mortality shows seasonal and spatial characteristics. More studies should be carried out for malaria eradication in the municipality.

Objective: To observe the evolution in malaria case-fatality rate among children under 5 years of age receiving care at the Bittou district hospital (CMA) after an improvement of the care practices. The management team implemented an emergency plan in 2016 with 5 components: i) health facilities staff sensitization to enable rapid referral of severe malaria cases to CMA; ii) reorganization of CMA paediatric emergencies to make a physician as the mainpoint of contact; iii) ensuring availability of supplies for severe malaria case management, including the availability of blood; iv) daily medical check-ups of hospitalized patients; v) reinforcement of clinical staff skills at all peripheral health facilities. At the same time were introduced i) free care for children under 5 years; ii) municipality involvement to finance ambulance fuel for the referrals of patients; iii) free blood collection in professional schools and soldiers; iv) a free telephone line between the health structures; v) presence of 5 medical doctors at the CMA., Material and Methods: Analysis of data collected from the statistical yearbooks of the Ministry of Health of Burkina Faso from 2014 to 2021., Results: The malaria case-fatality rate (CFR) in under-five in the Bittou health district (1.39% and 1.52% in 2014 and 2015) was higher than the average for all districts in this region (1.08%). After implementation of the emergency plan, the malaria CFR in Bittou declined to 0% in 2016 and 2017, 0.2% in 2018, 0% in 2019, 0.07% in 2020 and 0.05% in 2021. The same trend was observed at the CMA level with 2.94% and 2.59% in 2014 and 2015, 0% in 2016 and 2017, 0.38% in 2018, 0% in 2019, then 0.17% and 0.47% in 2020 and 2021., Conclusion: Malaria control remains a challenge in Burkina Faso. However, the improved malaria CFRs observed in Bittou show that effective involvement of health district teams could potentially contribute to substantial reductions in malaria case-fatality risk., (Copyright © 2024 SFMTSI.)

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions., Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention., Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities., Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023., Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census., Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months., Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference., Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Malaria is a major public health problem and causing high morbidity and mortality worldwide especially in India and South Africa. To study the mortality of patients due to malaria. This cross sectional and retrospective study was conducted over a period of one year in a tertiary care hospital. All the patients with fever and chills as major complain who had attended OPD and IPD of Medicine. Patient's clinical history was recorded for comparing the severity of the disease and comorbidity. Data were analyzed in the computer software Statistical Package for Social Sciences (SPSS) version 17.0. Slide Positivity Rate (SPR) and Slide Falciparum Rate (SFR) was 16.58% and 8.50% respectively. Plasmodium falciparum was 45.24% of the total positive cases. Mortality analysis-male to female ratio was 3:1.Age wise malaria mortality was recorded maximum in the age group of 21 to 30 years 38.46%), followed by 11 to 20 years 23.08%, 41 to 50 and 50 and above was 15.38% each, lowest was age group 31 to 40 years 7.69%, however no death cases found in the age group of 0 to 10 years. P. falciparum was 73.08% than P. vivax 26.92%. Falciparum to vivax ratio in mortality was 3:1. Complications and causes of death involved in malaria mortality was terminal cardio respiratory arrest in 20 cases, followed by cerebral malaria 4 cases, Acute Respiratory Distress Syndrome (ARDS) 4 cases, multi organ failure 5 cases, dengue (co-infection) 3 cases, Sub Dural Haematoma, Sinus Thrombosis and Myocardial Infarction 1 case each. The study revealed underreporting of malaria episodes and deaths to the formal health system, with the consequent underestimation of malaria burden. Adult age group had the highest mortality rate, emphasizing the known effect of malaria on this population group. Males lost more than females in all age groups, which altered the picture displayed by the incidence rates alone. Complications and causes of death involved highest in malaria mortality was terminal cardio respiratory arrest. The epidemiological estimates in this study form a basis for comparing interventions that affect mortality and morbidity differently, by comparing the amount of burden averted by them. Apart from P. falciparum, P. vivax infection also tends to severe complications. There is a need to do study on malaria mortality by P. vivax malaria. [ABSTRACT FROM AUTHOR]

In 2016, an estimated 445,000 deaths and 216 million cases of malaria occurred worldwide, while 70% of the deaths occurred in children under five years old. Changes in climatic exposures such as temperature and precipitation make malaria one of the most climate sensitive outcomes. Using a global malaria mortality dataset for 105 countries between 1980 and 2010, we find a non-linear relationship between temperature and malaria mortality and estimate that the global optimal temperature threshold beyond which all-age malaria mortality increases is 20.8 °C, while in the case of child mortality; a significantly lower optimum temperature of 19.3° is estimated. Our results also suggest that this optimal temperature is 28.4 °C and 26.3 °C in Africa and Asia, respectively - the continents where malaria is most prevalent. Furthermore, we estimate that child mortality (ages 0-4) is likely to increase by up to 20% in some areas due to climate change by the end of the 21st century. [ABSTRACT FROM AUTHOR]

Background: Lack of valid and reliable data on malaria deaths continues to be a problem that plagues the global health community. To address this gap, the verbal autopsy (VA) method was developed to ascertain cause of death at the population level. Despite the adoption and wide use of VA, there are many recognized limitations of VA tools and methods, especially for measuring malaria mortality. This study synthesizes the strengths and limitations of existing VA tools and methods for measuring malaria mortality (MM) in low- and middle-income countries through a systematic literature review. Methods: The authors searched PubMed, Cochrane Library, Popline, WHOLIS, Google Scholar, and INDEPTH Network Health and Demographic Surveillance System sites' websites from 1 January 1990 to 15 January 2016 for articles and reports on MM measurement through VA. Inclusion criteria: article presented results from a VA study where malaria was a cause of death; article discussed limitations/challenges related to measurement of MM through VA. Two authors independently searched the databases and websites and conducted a synthesis of articles using a standard matrix. Results: The authors identified 828 publications; 88 were included in the final review. Most publications were VA studies; others were systematic reviews discussing VA tools or methods; editorials or commentaries; and studies using VA data to develop MM estimates. The main limitation were low sensitivity and specificity of VA tools for measuring MM. Other limitations included lack of standardized VA tools and methods, lack of a 'true' gold standard to assess accuracy of VA malaria mortality. Conclusions: Existing VA tools and methods for measuring MM have limitations. Given the need for data to measure progress toward the World Health Organization's Global Technical Strategy for Malaria 2016-2030 goals, the malaria community should define strategies for improving MM estimates, including exploring whether VA tools and methods could be further improved. Longer term strategies should focus on improving countries' vital registration systems for more robust and timely cause of death data. [ABSTRACT FROM AUTHOR]

Background: The United Nation's sustainable development goal for 2030 is to eradicate the global malaria epidemic, primarily as the disease continues to be one of the major concerns for public health in sub-Saharan Africa. In 2015, the region accounted for 90% of malaria deaths. Mozambique recorded a malaria mortality rate of 42.75 (per 100,000). In Chimoio, Mozambique's fifth largest city, malaria is the fourth leading cause of death (9.4%). Few data on malaria mortality exists in Mozambique, particularly in relation to Chimoio. The objective of this study was to characterize malaria mortality trends and its spatial distribution in Chimoio. Methods: Malaria mortality data and climate data were extracted from the Chimoio Civil Registration records, and the Regional Weather station, from 2010 to 2014. The malaria crude mortality rate was calculated. ANOVA, Tukey's, Chi square, and time series were carried out and an intervention analysis ARIMA model developed. Results: A total of 944 malaria death cases were registered in Chimoio, 729 of these among Chimoio residents (77%). The average malaria mortality by gender was 44.9% for females and 55.1% for males. The age of death varied from 0 to 96 years, with an average age of 25.9 (SE = 0.79) years old. January presented the highest average of malaria deaths, and urban areas presented a lower crude malaria mortality rate. Rural neighbourhoods with good accessibility present the highest malaria crude mortality rate, over 85 per 100,000. Seasonal ARMA (2,0)(1,0)12 fitted the data although it was not able to capture malaria mortality peaks occurring during malaria outbreaks. Intervention effect properly fit the mortality peaks and reduced ARMA's root mean square error by almost 25%. Conclusion: Malaria mortality is increasing in Chimoio; children between 1 and 4 years old represent 13% of Chimoio population, but account for 25% of malaria mortality. Malaria mortality shows seasonal and spatial characteristics. More studies should be carried out for malaria eradication in the municipality. [ABSTRACT FROM AUTHOR]

Background: Although malaria decline has been observed in most sub-Saharan African countries, the disease still represents a significant public health burden in Tanzania. There are contradictions on the effect of ownership of at least one mosquito net at household on malaria mortality. This study presents a Bayesian modelling framework for the analysis of the effect of ownership of at least one mosquito net at household on malaria mortality with environmental factors as confounder variables. Methods: The analysis used longitudinal data collected in Rufiji and Ifakara Health Demographic Surveillance System (HDSS) sites for the period of 1999-2011 and 2002-2012, respectively. Bayesian framework modelling approach using integrated nested laplace approximation (INLA) package in R software was used. The space time models were established to assess the effect of ownership of mosquito net on malaria mortality in 58 villages in the study area. Results: The results show that an increase of 10 % in ownership of mosquito nets at village level had an average of 5.2 % decrease inall age malaria deaths (IRR = 0.948, 95 % CI = 0.917, 0.977) in Rufiji HDSS and 12.1 % decrease in all age malaria deaths (IRR = 0.879, 95 % CI = 0.806, 0.959) in Ifakara HDSS. In children under 5 years, results show an average of 5.4 % decrease of malaria deaths (IRR = 0.946, 95 % CI = 0.909, 0.982) in Rufiji HDSS and 10 % decrease of malaria deaths (IRR = 0.899, 95 % CI = 0.816, 0.995) in Ifakara HDSS. Model comparison show that model with spatial and temporal random effects was the best fitting model compared to other models without spatial and temporal, and with spatial-temporal interaction effects. Conclusion: This modelling framework is appropriate and provides useful approaches to understanding the effect of mosquito nets for targeting malaria control intervention. Furthermore, ownership of mosquito nets at household showed a significant impact on malaria mortality. [ABSTRACT FROM AUTHOR]

Background: Although, malaria control interventions are widely implemented to eliminate malaria disease, malaria is still a public health problem in Tanzania. Understanding the risk factors, spatial and space-time clustering for malaria deaths is essential for targeting malaria interventions and effective control measures. In this study, spatial methods were used to identify local malaria mortality clustering using verbal autopsy data. Methods: The analysis used longitudinal data collected in Rufiji and Ifakara Health Demographic Surveillance System (HDSS) sites for the period 1999-2011 and 2002-2012, respectively. Two models were used. The first was a non-spatial model where logistic regression was used to determine a household's characteristic or an individual's risk of malaria deaths. The second was a spatial Poisson model applied to estimate spatial clustering of malaria mortality using SaTScan™, with age as a covariate. ArcGIS Geographical Information System software was used to map the estimates obtained to show clustering and the variations related to malaria mortality. Results: A total of 11,462 deaths in 33 villages and 9328 deaths in 25 villages in Rufiji and Ifakara HDSS, respectively were recorded. Overall, 2699 (24 %) of the malaria deaths in Rufiji and 1596 (17.1 %) in Ifakara were recorded during the study period. Children under five had higher odds of dying from malaria compared with their elderly counterparts aged five and above for Rufiji (AOR = 2.05, 95 % CI = 1.87-2.25), and Ifakara (AOR = 2.33, 95 % CI = 2.05-2.66), respectively. In addition, ownership of mosquito net had a protective effect against dying with malaria in both HDSS sites. Moreover, villages with consistently significant malaria mortality clusters were detected in both HDSS sites during the study period. Conclusions: Clustering of malaria mortality indicates heterogeneity in risk. Improving targeted malaria control and treatment interventions to high risk clusters may lead to the reduction of malaria deaths at the household and probably at country level. Furthermore, ownership of mosquito nets and age appeared to be important predictors for malaria deaths. [ABSTRACT FROM AUTHOR]

Severe malaria (SM) increases the risk of invasive bacterial infection, and there is evidence to suggest increased gastrointestinal permeability. Studies have shown sequestration of infected erythrocytes in intestinal microvasculature, and in vivo studies of rectal mucosa have demonstrated disruption of microvascular blood flow. However, the extent of intestinal injury in pediatric malaria is not well characterized. In this study, two serum biomarkers of intestinal injury, trefoil factor 3 (TFF3) and intestinal fatty acid binding protein (I-FABP), were analyzed in 598 children with SM and 120 healthy community children (CC), 6 months to 4 years of age. Serum was collected at enrollment and 1 month for laboratory studies, and participants were monitored for 12 months. Intestinal injury biomarkers were significantly elevated in children with SM, with 18.1% having levels of TFF3 and/or I-FABP greater than the 99th percentile of CC levels. TFF3 levels continued to be elevated at 1 month, while I-FABP levels were comparable to CC levels. Both markers predicted in-hospital mortality {odds ratio (OR) (95% confidence interval [CI]), 4.4 (2.7, 7.3) and 2.3 (1.7, 3.1)} for a natural log increase in TFF3 and I-FABP, respectively. TFF3 was also associated with postdischarge mortality (OR, 2.43 [95% CI, 1.1, 4.8]). Intestinal injury was associated with acute kidney injury (AKI), acidosis ( P  < 0.001 for both), and angiopoietin 2, a maker of endothelial activation. In conclusion, intestinal injury is common in pediatric severe malaria and is associated with an increased mortality. It is strongly associated with AKI, acidosis, and endothelial activation. IMPORTANCE In children with severe malaria, intestinal injury is a common complication associated with increased mortality. Intestinal injury is associated with acute kidney injury, acidosis, and endothelial activation. Interventions promoting intestinal regeneration and repair represent novel approaches to improve outcomes.

Background: Malaria is one of the foremost public health problems in India. Aims: To assess the syndromic diagnosis of fever in pediatrics patients. Method: The longitudinal hospital – based study was conducted in Pediatric ward of New Civil Hospital, Ahmedabad .Information was collected on a pretested semi structured schedule. After collection, the whole data was compiled; analyzed and appropriate statistical tests like simple proportions and chi-square (x2) test were applied. Result: A total of 4,515 children were admitted to the three Paediatric wards in New Civil Hospital from August 2009 to July 2010, of whom 584 (12.94 %) had three clinical symptoms. males were 2.5 times more brought than females, but the malaria rate was almost same in both sexes. Of the 584 clinical malaria admission, 15 died (C.F.R.: 2.6 %). The case fatality rate of males 9 (3 %) did not differ significantly from that of females (2.11 %). Conclusion the children presenting with a sequence of the symptoms of malaria, have been given radical treatment at home, 84-100% would have been correctly treated, 0-16% may have been false positive and unnecessarily treated.

Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) play critical roles in the innate immunity against infectious diseases and are required to link pathogen DNA sensing to immune responses. However, the mechanisms by which cGAS-STING-induced cytokines suppress the adaptive immune response against malaria infections remain poorly understood. Here, cGAS-STING signaling is identified to play a detrimental role in regulating anti-malaria immunity. cGAS or STING deficiency in mice markedly prolongs mouse survival during lethal malaria Plasmodium yoelii nigeriensis N67C infections by reducing late interleukin (IL)-6 production. Mechanistically, cGAS/STING recruits myeloid differentiation factor 88 (MyD88) and specifically induces the p38-dependent signaling pathway for late IL-6 production, which, in turn, expands CD11b + Ly6C hi proinflammatory monocytes to inhibit immunity. Moreover, the blockage or ablation of the cGAS-STING-MyD88-p38-IL-6 signaling axis or the depletion of CD11b + Ly6C hi proinflammatory monocytes provides mice a significant survival benefit during N67C and other lethal malaria-strain infections. Taken together, these findings identify a previously unrecognized detrimental role of cGAS-STING-MyD88-p38 axis in infectious diseases through triggering the late IL-6 production and proinflammatory monocyte expansion and provide insight into how targeting the DNA sensing pathway, dysregulated cytokines, and proinflammatory monocytes enhances immunity against infection., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

We conducted a series of studies on the northern Pacific coast of Peru to determine environmental risk factors for malaria. We report in this paper the results of both a descriptive study of incidence and a prevalence survey of malaria. Both studies showed that the area was at low risk for malaria. The malaria incidence rate was 40/1000 p.a. during the study period, and the prevalence of infection was 0.9% (95% CI: 0.4-1.7) before and 1.4% (95% CI: 0.8-2.2) after the high incidence period. However, the risk of malaria varied according to season, village and even house within a single village. Incidence rates increased from February (2.6/1000 p.a.) to May (12.9/1000 p.a.) and decreased during the second part of the year. Most of the cases were clustered in four villages that constituted only 21% of the total population of the area. Houses where multiple cases were recorded were often located near a source of water. Our observations suggested that environmental factors, and particularly the presence of water for irrigation around villages and houses, played a major role in determining the risk of malaria. These observations were extended through an entomological study and a case-control study, to be published elsewhere. [ABSTRACT FROM AUTHOR]

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger., (© 2022. The Author(s).)

Background: It has been hypothesized that in high-transmission settings, malaria control in early childhood (<5 years of age) might delay the acquisition of functional immunity and shift child deaths from younger to older ages., Methods: We used data from a 22-year prospective cohort study in rural southern Tanzania to estimate the association between early-life use of treated nets and survival to adulthood. All the children born between January 1, 1998, and August 30, 2000, in the study area were invited to enroll in a longitudinal study from 1998 through 2003. Adult survival outcomes were verified in 2019 through community outreach and mobile telephones. We used Cox proportional-hazards models to estimate the association between the use of treated nets in early childhood and survival to adulthood, adjusting for potential confounders., Results: A total of 6706 children were enrolled. In 2019, we verified information on the vital status of 5983 participants (89%). According to reports of early-life community outreach visits, approximately one quarter of children never slept under a treated net, one half slept under a treated net some of the time, and the remaining quarter always slept under a treated net. Participants who were reported to have used treated nets at half the early-life visits or more had a hazard ratio for death of 0.57 (95% confidence interval [CI], 0.45 to 0.72) as compared with those who were reported to have used treated nets at less than half the visits. The corresponding hazard ratio between 5 years of age and adulthood was 0.93 (95% CI, 0.58 to 1.49)., Conclusions: In this long-term study of early-life malaria control in a high-transmission setting, the survival benefit from early-life use of treated nets persisted to adulthood. (Funded by the Eckenstein-Geigy Professorship and others.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Sierra Leone's child and maternal mortality rates are among the highest in the world. However, little is known about the causes of premature mortality in the country. To rectify this, the Ministry of Health and Sanitation of Sierra Leone launched the Sierra Leone Sample Registration System (SL-SRS) of births and deaths. Here, we report cause-specific mortality from the first SL-SRS round, representing deaths from 2018 to 2020., Methods: The Countrywide Mortality Surveillance for Action platform established the SL-SRS, which involved conducting electronic verbal autopsies in 678 randomly selected villages and urban blocks throughout the country. 61 surveyors, in teams of four or five, enrolled people and ascertained deaths of individuals younger than 70 years in 2019-20, capturing verbal autopsies on deaths from 2018 to 2020. Centrally, two trained physicians independently assigned causes of death according to the International Classification of Diseases (tenth edition). SL-SRS death proportions were applied to 5-year mortality averages from the UN World Population Prospects (2019) to derive cause-specific death totals and risks of death nationally and in four Sierra Leone regions, with comparisons made with the Western region where Freetown, the capital, is located. We compared SL-SRS results with the cause-specific mortality estimates for Sierra Leone in the 2019 WHO Global Health Estimates., Findings: Between Sept 1, 2019, and Dec 15, 2020, we enrolled 343 000 people and ascertained 8374 deaths of individuals younger than 70 years. Malaria was the leading cause of death in children and adults, nationally and in each region, representing 22% of deaths under age 70 years in 2020. Other infectious diseases accounted for an additional 16% of deaths. Overall maternal mortality ratio was 510 deaths per 100 000 livebirths (95% CI 483-538), and neonatal mortality rate was 31·1 deaths per 1000 livebirths (95% CI 30·4-31·8), both among the highest rates in the world. Haemorrhage was the major cause of maternal mortality and birth asphyxia or trauma was the major cause of neonatal mortality. Excess deaths were not detected in the months of 2020 corresponding to the peak of the COVID-19 pandemic. Half of the deaths occurred in rural areas and at home. If the Northern, Eastern, and Southern regions of Sierra Leone had the lower death rates observed in the Western region, about 20 000 deaths (just over a quarter of national total deaths in people younger than 70 years) would have been avoided. WHO model-based data vastly underestimated malaria deaths and some specific causes of injury deaths, and substantially overestimated maternal mortality., Interpretation: Over 60% of individuals in Sierra Leone die prematurely, before age 70 years, most from preventable or treatable causes. Nationally representative mortality surveys such as the SL-SRS are of high value in providing reliable cause-of-death information to set public health priorities and target interventions in low-income countries., Funding: Bill & Melinda Gates Foundation, Canadian Institutes of Health Research, Queen Elizabeth Scholarship Program., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests.

Background: Malaria, pneumonia and diarrhoea continue to be the leading causes of death in children under the age of five years (U5) in Uganda. To combat these febrile illnesses, integrated community case management (iCCM) delivery models utilizing community health workers (CHWs) or drug sellers have been implemented. The purpose of this study is to compare the cost-effectiveness of delivering iCCM interventions via drug sellers versus CHWs in rural Uganda., Methods: This study was a cost-effectiveness analysis to compare the iCCM delivery model utilizing drug sellers against the model using CHWs. The effect measure was the number of appropriately treated U5 children, and data on effectiveness came from a quasi-experimental study in Southwestern Uganda and the inSCALE cross-sectional household survey in eight districts of mid-Western Uganda. The iCCM interventions were costed using the micro-costing (ingredients) approach, with costs expressed in US dollars. Cost and effect data were linked together using a decision tree model and analysed using the Amua modelling software., Results: The costs per 100 treated U5 children were US$591.20 and US$298.42 for the iCCM trained-drug seller and iCCM trained-CHW models, respectively, with 30 and 21 appropriately treated children in the iCCM trained-drug seller and iCCM trained-CHW models. When the drug seller arm (intervention) was compared to the CHW arm (control), an incremental effect of 9 per 100 appropriately treated U5 children was observed, as well as an incremental cost of US$292.78 per 100 appropriately treated children, resulting in an incremental cost-effectiveness ratio (ICER) of US$33.86 per appropriately treated U5 patient., Conclusion: Since both models were cost-effective compared to the do-nothing option, the iCCM trained-drug seller model could complement the iCCM trained-CHW intervention as a strategy to increase access to quality treatment., (© 2021. The Author(s).)

The MORDOR study, a masked, community-level randomized clinical trial conducted in Niger, Malawi and Tanzania (2015 to 2017), showed that biannual administration of single-dose azithromycin to preschool children reduced all-cause mortality. We sought to evaluate its impact on causes of death in children aged 1-59 months in Tanzania. A random sampling of 614 communities was conducted in Kilosa District, Tanzania, with simple random assignment of communities to receive either azithromycin or placebo. In these communities, a census was carried out every 6 months and children aged 1-59 months received biannual (every 6 months), single-dose azithromycin (~20mg/kg) or placebo depending on community assignment, over a 2-year period. Mortality was determined at the time of the biannual census. For child deaths, a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. A total of 190- (0.58 /100 person-years) and 200 deaths (0.59/100 person-years) were reported in the azithromycin and placebo arms, respectively. Malaria, pneumonia and diarrhea, accounted for 71% and 68% of deaths in the respective arms. Overall, the mortality was not different by treatment arm, nor were the distribution of causes of death after adjusting for community clustering. The cause-specific mortality for diarrhea/pneumonia was no different over time. In children aged 1-5 months, 32 deaths occurred in the placebo arm and 25 deaths occurred in the azithromycin arm; 20 (62.5%) deaths in the placebo- and 10 (40%) in the azithromycin arm were attributed to diarrhea or pneumonia. Neither differences in the number of deaths nor the diarrhea/pneumonia attribution was statistically significant after adjusting for community clustering. In conclusion, azithromycin was not associated with a significant decline in deaths by specific causes compared to placebo. The non-significant lower rates of diarrhea or pneumonia in children <6 months who received azithromycin merit further investigation in high-mortality settings. Trial registration: NCT02048007., Competing Interests: The authors have no relevant conflicts of interest to disclose.

Background: South Africa (SA) is currently experiencing a significant increase in malaria cases despite having shifted focus from malaria control towards malaria elimination. The clinical features of malaria are nonspecific, but their relative frequency on presentation are not well described. HIV and malaria are both independently associated with high mortality in sub-Saharan Africa. There are important interactions between HIV and malaria., Objectives: To describe the population characteristics of patients with malaria at Chris Hani Baragwanath Academic Hospital, Johannesburg, SA, clinical and biochemical features of severity, the proportion of patients with HIV infection, management and outcomes., Methods: A prospective observational study was conducted whereby patients with a confirmed laboratory diagnosis of malaria were identified, approached and consented for study inclusion over the time period January 2017 - January 2018. Clinical and biochemical data were collected at the time of consent and later analysed., Results: The mean (standard deviation) age was 35.7 (12.98) years, and 72 (70.6%) of the 102 patients were male. Peak admissions for malaria were in January, with 58 patients (56.9%) admitted during January 2017 and 2018. All malaria cases were imported, with 74.5% associated with travel to Mozambique. The majority of the patients (61.8%) were expatriates living in SA. The most common presenting symptoms were chills (95.1%), weakness (94.1%), fever (91.2%), headache (90.2%) and lethargy (88.2%). The most common clinical signs were dehydration (31.4%), prostration (19.6%) and jaundice (13.7%). Among the 40 patients (39.2%) who had severe malaria, prostration was the most common feature of severity (19.6%), 8 (7.8%) were admitted to an intensive care unit, and 6 (5.9%) required haemodialysis. The median (interquartile range) duration of hospital stay was 5 (3 -6) (range 2 - 35) days. HIV status was known in 83 patients (81.4%), of whom 32 (38.6%) were HIV-positive. Malaria prophylaxis had been taken by only 8 patients. The all-cause mortality rate was 4.9%, and mortality attributable to malaria 3.9%., Conclusions: There was a high proportion of complicated malaria cases, particularly in January. The majority of patients were young expatriate males with a history of travel to southern Mozambique or Limpopo Province, with very few taking malaria prophylaxis. Most clinical signs and symptoms were constitutional and nonspecific. A large number of patients were found to be HIV-positive, and most were newly diagnosed. Mortality was high, at around five times the national average, and may have been an underestimate.

Background: The COVID-19 pandemic has resulted in unprecedented challenges to health systems worldwide, including the control of non-COVID-19 diseases. Malaria cases and deaths may increase due to the direct and indirect effects of the pandemic in malaria-endemic countries, particularly in sub-Saharan Africa (SSA). This scoping review aims to summarize information on public health-relevant effects of the COVID-19 pandemic on the malaria situation in SSA., Methods: Review of publications and manuscripts on preprint servers, in peer-reviewed journals and in grey literature documents from 1 December, 2019 to 9 June, 2021. A structured search was conducted on different databases using predefined eligibility criteria for the selection of articles., Results: A total of 51 papers have been included in the analysis. Modelling papers have predicted a significant increase in malaria cases and malaria deaths in SSA due to the effects of the COVID-19 pandemic. Many papers provided potential explanations for expected COVID-19 effects on the malaria burden; these ranged from relevant diagnostical and clinical aspects to reduced access to health care services, impaired availability of curative and preventive commodities and medications, and effects on malaria prevention campaigns. Compared to previous years, fewer country reports provided data on the actual number of malaria cases and deaths in 2020, with mixed results. While highly endemic countries reported evidence of decreased malaria cases in health facilities, low endemic countries reported overall higher numbers of malaria cases and deaths in 2020., Conclusions: The findings from this review provide evidence for a significant but diverse impact of the COVID-19 pandemic on malaria in SSA. There is the need to further investigate the public health consequences of the COVID-19 pandemic on the malaria burden. Protocol registered on Open Science Framework: https://doi.org/10.17605/OSF.IO/STQ9D., (© 2021. The Author(s).)

Competing Interests: We declare no competing interests.

Background: To reduce the malaria burden and improve the socioeconomic status of its citizens, the Democratic Republic of Congo scaled up key malaria control interventions, especially insecticide-treated nets (ITNs), between 2005 and 2014. Since then, the effects of these interventions on malaria mortality and morbidity have not been assessed. This study aimed to measure the impact of the National Malaria Control Programme's efforts and to inform future control strategies., Methods: The authors used data from the Demographic and Health Surveys 2007 and 2013-2014 to assess trends in all-cause childhood mortality (ACCM) against trends in coverage of malaria interventions at national and subnational levels. The authors used the plausibility argument to assess the impact of the malaria control interventions and used Kaplan-Meier survival probability and Cox proportional hazard models to examine the effect of ITN ownership on child survival. Contextual factor trends affecting child survival were also considered., Results: Countrywide, household ownership of at least one ITN increased, from 9% in 2007 to 70% in 2013-2014. All provinces experienced similar increases, with some greater than the national level. ITN use increased between 2007 and 2013-2014 among children under five (6% to 55%). Severe anaemia (haemoglobin concentration < 8 g/dl) prevalence among children aged 6-59 months significantly decreased, from 11% (95% confidence interval [CI] 9-13%) in 2007 to 6% (95% CI 5-7%) in 2013-2014. During the same period, ACCM declined, from 148 (95% CI 132-163) to 104 (95% CI 97-112) deaths per 1000 live births. The decline in ACCM was greater among children aged 6-23 months (relative reduction of 36%), compared to children aged 24-59 months (relative reduction of 12%). Cox regression indicated that household ownership of at least one ITN reduced the risk of mortality by 24% among children under five (risk ratio = 0.76, 95% CI 0.64-0.90). Contextual factor analysis revealed marginal improvements in socioeconomic indicators and other health interventions., Conclusions: Given the patterns of the coverage of malaria control interventions, patterns in ACCM by province, and marginal improvements in contextual factors, the authors conclude that the malaria control interventions have plausibly contributed to the decrease in ACCM in the Democratic Republic of Congo from 2005 to 2014.