Validation of malaria-attributed deaths using verbal autopsy studies: a systematic review.

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.

Could vaccinating adults against malaria materially reduce adult mortality in high-transmission areas?

After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.

Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in Sierra Leone.

An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities. In this article, we first describe how the international NGO Partners In Health (PIH) partnered with the Government of Sierra Leone and Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the country's most Ebola-affected districts. We then describe how, in the aftermath of the epidemic, PIH is partnering with the public sector to strengthen the health system and resume delivery of regular health services. PIH's experience in Sierra Leone is one of multiple partnerships with different stakeholders. It is also one of rapid deployment of expatriate clinicians and logistics personnel in health facilities largely deprived of health professionals, medical supplies, and physical infrastructure required to deliver health services effectively and safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to the ongoing discussion within the international community on how to ensure emergency preparedness and build resilient health systems in settings without either.

High SARS-CoV-2 seroincidence but low excess COVID mortality in Sierra Leone in 2020-2022.

While SARS-CoV-2 infection appears to have spread widely throughout Africa, documentation of associated mortality is limited. We implemented a representative serosurvey in one city of Sierra Leone in Western Africa, paired with nationally representative mortality and selected death registration data. Cumulative seroincidence using high quality SARS-CoV-2 serological assays was 69% by July 2021, rising to 84% by April 2022, mostly preceding SARS-CoV-2 vaccination. About half of infections showed evidence of neutralizing antibodies. However, excess death rates were low, and were concentrated at older ages. During the peak weeks of viral activity, excess mortality rates were 22% for individuals aged 30-69 years and 70% for those over 70. Based on electronic verbal autopsy with dual independent physician assignment of causes, excess deaths during viral peaks from respiratory infections were notable. Excess deaths differed little across specific causes that, a priori, are associated with COVID, and the pattern was consistent among adults with or without chronic disease risk factors. The overall 6% excess of deaths at ages ≥30 from 2020-2022 in Sierra Leone is markedly lower than reported from South Africa, India, and Latin America. Thus, while SARS-CoV-2 infection was widespread, our study highlights as yet unidentified mechanisms of heterogeneity in susceptibility to severe disease in parts of Africa.

Assessing Changes in Surgical Site Infections and Antibiotic Use among Caesarean Section and Herniorrhaphy Patients at a Regional Hospital in Sierra Leone Following Operational Research in 2021.

Surgical site infections (SSIs) are a major public health threat to the success of surgery. This study assessed changes in SSIs and use of antibiotics among caesarean section (CS) and herniorrhaphy patients at a regional hospital in Sierra Leone following operational research. This was a comparative before and after study using routine hospital data. The study included all the CS and herniorrhaphy patients who underwent surgery between two time periods. Of the seven recommendations made in the first study, only one concerning improving the hospital's records and information system was fully implemented. Three were partially implemented and three were not implemented. The study population in both studies showed similar socio-demographic characteristics. The use of postoperative antibiotics for herniorrhaphy in both studies remained the same, although a significant increase was found for both pre- and postoperative antibiotic use in the CS patients, 589/596 (98.8%) in 2023 and 417/599 (69.6%) in 2021 (p < 0.001). However, a significant decrease was observed in the overall incidence of SSIs, 22/777 (2.8%) in 2023 and 46/681 (6.7%) in 2021 (p < 0.001), and the incidence of SSIs among the CS patients, 15/596 (2.5%) in 2023 and 45/599 (7.5%) in 2021 (p < 0.001). The second study highlights the potential value of timely assessment of the implementation of recommendations following operational research.

Incidence of Surgical Site Infection and Use of Antibiotics among Patients Who Underwent Caesarean Section and Herniorrhaphy at a Regional Referral Hospital, Sierra Leone.

Surgical site infections (SSIs) are common postoperative complications. Surgical antibiotic prophylaxis (SAP) can prevent the occurrence of SSIs if administered appropriately. We carried out a retrospective cohort study to determine the incidence of SSIs and assess whether SAP were administered according to WHO guidelines for Caesarean section (CS) and herniorrhaphy patients in Bo regional government hospital from November 2019 to October 2020. The analysis included 681 patients (599 CSs and 82 herniorrhaphies). Overall, the SSI rate was 6.7% among all patients, and 7.5% and 1.2% among CS patients and herniorrhaphy patients, respectively. SAP was administered preoperatively in 85% of CS and 70% of herniorrhaphy patients. Postoperative antibiotics were prescribed to 85% of CS and 100% of herniorrhaphy patients. Ampicillin, metronidazole, and amoxicillin were the most commonly used antibiotics. The relatively low rate of SSIs observed in this study is probably due to improved infection prevention and control (IPC) measures following the Ebola outbreak and the current COVID-19 pandemic. A good compliance rate with WHO guidelines for preoperative SAP was observed. However, there was a high use of postoperative antibiotics, which is not in line with WHO guidelines. Recommendations were made to ensure the appropriate administration of SAP and reduce unnecessary use of antibiotics.

Child, maternal, and adult mortality in Sierra Leone: nationally representative mortality survey 2018-20.

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.

Assessment of Infection Prevention and Control Measures at Points of Entry in Sierra Leone in 2021: A Cross-Sectional Study.

Implementing and monitoring infection prevention and control (IPC) measures at immigration points of entry (PoEs) is key to preventing infections, reducing excessive use of antimicrobials, and tackling antimicrobial resistance (AMR). Sierra Leone has been implementing IPC measures at four PoEs (Queen Elizabeth II Quay port, Lungi International Airport, and the Jendema and Gbalamuya ground crossings) since the last Ebola outbreak in 2014-2015. We adapted the World Health Organization IPC Assessment Framework tool to assess these measures and identify any gaps in their components at each PoE through a cross-sectional study in May 2021. IPC measures were Inadequate (0-25%) at Queen Elizabeth II Quay port (21%; 11/53) and Jendema (25%; 13/53) and Basic (26-50%) at Lungi International Airport (40%; 21/53) and Gbalamuya (49%; 26/53). IPC components with the highest scores were: having a referral system (85%; 17/20), cleaning and sanitation (63%; 15/24), and having a screening station (59%; 19/32). The lowest scores (0% each) were reported for the availability of IPC guidelines and monitoring of IPC practices. This was the first study in Sierra Leone highlighting significant gaps in the implementation of IPC measures at PoEs. We call on the AMR multisectoral coordinating committee to enhance IPC measures at all PoEs.

Comparative analysis of de novo transcriptome assembly.

The fast development of next-generation sequencing technology presents a major computational challenge for data processing and analysis. A fast algorithm, de Bruijn graph has been successfully used for genome DNA de novo assembly; nevertheless, its performance for transcriptome assembly is unclear. In this study, we used both simulated and real RNA-Seq data, from either artificial RNA templates or human transcripts, to evaluate five de novo assemblers, ABySS, Mira, Trinity, Velvet and Oases. Of these assemblers, ABySS, Trinity, Velvet and Oases are all based on de Bruijn graph, and Mira uses an overlap graph algorithm. Various numbers of RNA short reads were selected from the External RNA Control Consortium (ERCC) data and human chromosome 22. A number of statistics were then calculated for the resulting contigs from each assembler. Each experiment was repeated multiple times to obtain the mean statistics and standard error estimate. Trinity had relative good performance for both ERCC and human data, but it may not consistently generate full length transcripts. ABySS was the fastest method but its assembly quality was low. Mira gave a good rate for mapping its contigs onto human chromosome 22, but its computational speed is not satisfactory. Our results suggest that transcript assembly remains a challenge problem for bioinformatics society. Therefore, a novel assembler is in need for assembling transcriptome data generated by next generation sequencing technique.