High Case Fatality Ratio Research Articles

Retrospective analysis of a large-scale cholera outbreak in Sudan

Background: Cholera outbreak is a significant public health threat in some parts of Sudan. In 2023, there was a large-scale outbreak in Gadarif State. Aim: To analyse the 2023 cholera outbreak in Sudan and recommend prevention and control measures for the future. Methods: In this retrospective study we conducted an epidemiological analysis of data from suspected and confirmed cholera cases, aged ≥ 2 years, from 138 health centres in Gadarif State, Sudan. Results: A total of 1997 cholera cases were confirmed using rapid diagnostic test between 25 August and 17 December 2023. Most patients (99.2%) had severe watery diarrhoea, and vomiting was reported in over 73% of cases. Dehydration rates were similar for men and women (≈55–60%), average attack rate was 6.7 per 10 000 population. The attack rate varied by locality but not by gender across all age groups. The outbreak lasted 20 weeks and claimed 46 lives, giving a case fatality ratio of 2.6%. Public misconception about water chlorination substantially hindered control efforts. Conclusion: The prolonged period of the outbreak and the high case fatality ratio highlight the need for better laboratory and epidemiologic surveillance as well as better preparedness and response for future outbreaks, along with educational activities to address myths and misconceptions.

Fatal and Nonfatal Firearm Injury Rates by Race and Ethnicity in the United States, 2019 to 2020.

Racial disparities in firearm injury death in the United States are well established. Less is known about the magnitude of nonfatal and total firearm injury. To combine health care data with death certificate data to estimate total firearm injuries in various racial and ethnic groups. Retrospective, cross-sectional study. Fatal injury data were collected from the Centers for Disease Control and Prevention. Data on nonfatal injuries were collected from the Nationwide Emergency Department Sample (NEDS), a 20% stratified sample of U.S. emergency department visits, weighted to provide national estimates for the United States, 2019 to 2020. All firearm injuries and deaths in the United States. Race and ethnicity were classified into 5 mutually exclusive categories: Asian or Pacific Islander, Black, Hispanic, Native American, and White. International Classification of Diseases, 10th Revision codes were used to classify firearm injury intent. Incidence of fatal and nonfatal injury in the U.S. population and case-fatality ratios (CFRs). There were 252 376 total firearm injuries, including 84 908 deaths from firearm injures. Of all firearm injuries, 37.8% were unintentional, 37.3% were assault related, 21.0% were self-harm, and 1.3% were law enforcement associated. Self-harm had the highest CFRs (90.9% overall). Unintentional injuries accounted for just 1021 (1.2%) deaths but 94 433 (56.4%) of nonfatal injuries. Rates of self-harm were highest among White persons (11.0 per 100 000 population in 2020) followed by Native Americans (8.6 per 100 000). Rates of assault were highest among Black persons (70.1 per 100 000), as were unintentional injuries (56.1 per 100 000). Findings are limited by the accuracy of discharge coding in NEDS, particularly regarding injury intent and patient race and ethnicity. From 2019 to 2020, the total burden of firearm injuries amounts to an average of 1 injury every 4 minutes and 1 death every 12 minutes in the United States. Racial disparities in firearm injury death are mirrored in nonfatal injury. None.

Structure-Guided Design of Potent Coronavirus Inhibitors with a 2-Pyrrolidone Scaffold: Biochemical, Crystallographic, and Virological Studies.

Zoonotic coronaviruses are known to produce severe infections in humans and have been the cause of significant morbidity and mortality worldwide. SARS-CoV-2 was the largest and latest contributor of fatal cases, even though MERS-CoV has the highest case-fatality ratio among zoonotic coronaviruses. These infections pose a high risk to public health worldwide warranting efforts for the expeditious discovery of antivirals. Hence, we hereby describe a novel series of inhibitors of coronavirus 3CLpro embodying an N-substituted 2-pyrrolidone scaffold envisaged to exploit favorable interactions with the S3-S4 subsites and connected to an invariant Leu-Gln P2-P1 recognition element. Several inhibitors showed nanomolar antiviral activity in enzyme and cell-based assays, with no significant cytotoxicity. High-resolution crystal structures of inhibitors bound to the 3CLpro were determined to probe and identify the molecular determinants associated with binding, to inform the structure-guided optimization of the inhibitors, and to confirm the mechanism of action of the inhibitors.

The dynamics and outcomes of AKI progression during the COVID-19 pandemic.

Acute kidney injury (AKI) associated with COVID-19 is associated with poor prognosis. This study assessed the hitherto uninvestigated impact of COVID-19 on the progression and clinical outcomes of patients with AKI. Data from 576 patients with AKI admitted between 13/3/20 and 13/5/20 were studied. Increasingly complex analyses, from logistic regressions to competing-risk and multi-state models, have revealed insights into AKI progression dynamics associated with PCR-confirmed COVID-19 acquisition and death. Meta-analyses of case fatality ratios among patients with AKI were also conducted. The overall case-fatality ratio was 0.33 [95% CI (0.20-0.36)]; higher in COVID-19 positive (COVID+) patients 0.52 [95% CI (0.46-0.58)] than in their negative (COVID-) counterparts 0.16 [95% CI (0.12-0.20)]. In AKI Stage-3 patients, that was 0.71 [95% CI (0.64-0.79)] among COVID+ patients with 45% dead within 14 days and 0.35 [95% CI (0.25-0.44)] in the COVID- group and 28% died within 14 days. Among patients diagnosed with AKI Stage-1 within 24 h, the probability of progression to AKI Stage-3 on day 7 post admission was 0.22 [95% CI (0.17-0.27)] among COVID+ patients, and 0.06 [95% CI (0.03, 0.09)] among those who tested negative. The probability of discharge by day 7 was 0.71 [95% CI (0.66, 0.75)] in COVID- patients, and 0.27 [95% CI (0.21, 0.32)] in COVID+ patients. By day 14, in AKI Stage-3 COVID+ patients, that was 0.35 [95% CI (0.25, 0.44)] with little change by day 10, that is, 0.38 [95% CI (0.29, 0.47)]. These results are consistent with either a rapid progression in severity, prolonged hospital care, or high case fatality ratio among AKI Stage-3 patients, significantly exacerbated by COVID-19 infection.

A mathematical model of Marburg virus disease outbreaks and the potential role of vaccination in control

BackgroundMarburg virus disease is an acute haemorrhagic fever caused by Marburg virus. Marburg virus is zoonotic, maintained in nature in Egyptian fruit bats, with occasional spillover infections into humans and nonhuman primates. Although rare, sporadic cases and outbreaks occur in Africa, usually associated with exposure to bats in mines or caves, and sometimes with secondary human-to-human transmission. Outbreaks outside of Africa have also occurred due to importation of infected monkeys. Although all previous Marburg virus disease outbreaks have been brought under control without vaccination, there is nevertheless the potential for large outbreaks when implementation of public health measures is not possible or breaks down. Vaccines could thus be an important additional tool, and development of several candidate vaccines is under way.MethodsWe developed a branching process model of Marburg virus transmission and investigated the potential effects of several prophylactic and reactive vaccination strategies in settings driven primarily by multiple spillover events as well as human-to-human transmission. Linelist data from the 15 outbreaks up until 2022, as well as an Approximate Bayesian Computational framework, were used to inform the model parameters.ResultsOur results show a low basic reproduction number which varied across outbreaks, from 0.5 [95% CI 0.05–1.8] to 1.2 [95% CI 1.0–1.9] but a high case fatality ratio. Of six vaccination strategies explored, the two prophylactic strategies (mass and targeted vaccination of high-risk groups), as well as a combination of ring and targeted vaccination, were generally most effective, with a probability of potential outbreaks being terminated within 1 year of 0.90 (95% CI 0.90–0.91), 0.89 (95% CI 0.88–0.90), and 0.88 (95% CI 0.87–0.89) compared with 0.68 (0.67–0.69) for no vaccination, especially if the outbreak is driven by zoonotic spillovers and the vaccination campaign initiated as soon as possible after onset of the first case.ConclusionsOur study shows that various vaccination strategies can be effective in helping to control outbreaks of MVD, with the best approach varying with the particular epidemiologic circumstances of each outbreak.

Daily changes in spatial accessibility to ICU beds and their relationship with the case-fatality ratio of COVID-19 in the state of Texas, USA

During the COVID-19 pandemic, many patients could not receive timely healthcare services due to limited availability and access to healthcare resources and services. Previous studies found that access to intensive care unit (ICU) beds saves lives, but they overlooked the temporal dynamics in the availability of healthcare resources and COVID-19 cases. To fill this gap, our study investigated daily changes in ICU bed accessibility with an enhanced two-step floating catchment area (E2SFCA) method in the state of Texas. Along with the increased temporal granularity of measurements, we uncovered two phenomena: 1) aggravated spatial inequality of access during the pandemic, and 2) the retrospective relationship between insufficient ICU bed accessibility and the high case-fatality ratio of COVID-19 in rural areas. Our findings suggest that those locations should be supplemented with additional healthcare resources to save lives in future pandemic scenarios.

Newly outbreak of Nipah virus: epidemiology, symptoms, transmission, diagnostic testing, treatment, and global health concern

Newly outbreak of Nipah virus: epidemiology, symptoms, transmission, diagnostic testing, treatment, and global health concern

Field investigation of high reported non-neonatal tetanus burden in Uganda, 2016-2017.

Despite providing tetanus-toxoid-containing vaccine (TTCV) to infants and reproductive-age women, Uganda reports one of the highest incidences of non-neonatal tetanus (non-NT). Prompted by unusual epidemiologic trends among reported non-NT cases, we conducted a retrospective record review to see whether these data reflected true disease burden. We analysed nationally reported non-NT cases during 2012-2017. We visited 26 facilities (14 hospitals, 12 health centres) reporting high numbers of non-NT cases (n = 20) or zero cases (n = 6). We identified non-NT cases in facility registers during 1 January 2016-30 June 2017; the identified case records were abstracted. During 2012-2017, a total of 24 518 non-NT cases were reported and 74% were ≥5 years old. The average annual incidence was 3.43 per 100 000 population based on inpatient admissions. Among 482 non-NT inpatient cases reported during 1 January 2016-30 June 2017 from hospitals visited, 342 (71%) were identified in facility registers, despite missing register data (21%). Males comprised 283 (83%) of identified cases and 60% were ≥15 years old. Of 145 cases with detailed records, 134 (92%) were clinically confirmed tetanus; among these, the case-fatality ratio (CFR) was 54%. Fourteen cases were identified at two hospitals reporting zero cases. Among >4000 outpatient cases reported from health centres visited, only 3 cases were identified; the remainder were data errors. A substantial number of non-NT cases and deaths occur in Uganda. The high CFR and high non-NT burden among men and older children indicate the need for TTCV booster doses across the life course to all individuals as well as improved coverage with the TTCV primary series. The observed data errors indicate the need for data quality improvement activities.

Outcomes of meningococcal serogroup B disease in children after implementation of routine infant 4CMenB vaccination in England: an active, prospective, national surveillance study

In 2015, the UK included 4CMenB, a multi-component, recombinant protein-based vaccine against meningococcal serogroup B (MenB) disease, in the national infant immunisation programme. We aimed to assess the effect of 4CMenB vaccination on the severity of MenB disease presentation and outcomes. In this active, prospective, national surveillance study, we used data from the UK Health Security Agency national surveillance of meningococcal disease. We included data from follow-up of children younger than 5 years with laboratory-confirmed MenB disease who were eligible for 4CMenB vaccination with general practice 3-6 months after disease onset. All invasive MenB isolates were tested using the Meningococcal Antigen Typing System to determine whether the isolate was potentially preventable by 4CMenB. Admission to intensive care, death, and, when possible, reported sequelae in survivors were reviewed alongside vaccine status. For the epidemiological analysis, we compared laboratory-confirmed MenB disease cases before 4CMenB implementation (Sept 1, 2010, to March 31, 2015) with those after implementation (Sept 1, 2015, to March 31, 2020). For clinical follow-up and outcomes, we included all children younger than 5 years with laboratory-confirmed MenB disease between Sept 1, 2015, and March 31, 2021. Between Sept 1, 2015, and March 31, 2021, there were 371 cases of MenB disease in children younger than 5 years, including 256 (69%) in those younger than 1 year and 128 (35%) in those younger than 3 months. After the introduction of 4CMenB, the peak age of patients with MenB disease shifted from 5-6 months to 1-3 months. Overall, 108 (29%) of 371 children were too young for vaccination, unvaccinated, or developed MenB disease within 14 days of the first dose. Of 110 meningococcal strains characterised, 11 (92%) of 12 were potentially preventable by 4CMenB in unvaccinated children compared with 53 (66%) of 80 in partly vaccinated and 11 (69%) of 16 in fully vaccinated children. 78 (21%) of 371 children required intensive care, and the case fatality ratio was 5% (17 of 371), with 11 of 17 deaths occurring before 1 year of age, including seven in infants who were too young (<8 weeks) for vaccination. Of 354 survivors, 57 (16%) had 74 sequelae reported; 45 (61%) of 74 were neurological, 17 (23%) were physical, two (3%) were behavioural or psychological, and ten (14%) were other complications. Prevalence of sequelae was similar in unvaccinated (15 [15%] of 98) and vaccinated (42 [16%] 256) children, as were composite outcomes of death or sequelae, and intensive care or death or sequelae. Cases of MenB disease in vaccine-eligible children declined after 4CMenB implementation, but morbidity in vaccinated and unvaccinated children remained unchanged, highlighting the importance of vaccination to prevent MenB disease. The lower peak age of infants with MenB disease after 4CMenB implementation, with a higher case fatality ratio in young infants, highlights the importance of timely vaccination. UK Health Security Agency.

The impact of four dominating variants and vaccine coverage on Covid-19 mortality: the Malta case

Abstract Background Disease burden can be quantified by mortality. The European Islands of Malta experienced a seesaw of Covid-19 surges in mortality and cases across the pandemic. The study aims to assess the impact of Covid-19 mortality across the four phases dominated by different variants while considering the vaccination coverage among the Malta population. Methods Covid-19 epidemiological data was obtained up till end of February 2022 from the websites of the Malta Ministry of Health and the European Centre for Disease Prevention and Control. Data was categorised into the four periods according to reported dominant Covid-19 variant. The Years of life lost (YLL) and Case-Fatality-Ratio (CFR) for each period were estimated. Correlations were performed between mortality and vaccinated age-groups. Results The original Covid-19 period (54 weeks) had the highest YLL (6633.53), followed by the Omicron variant period (12 weeks; 2,692.17). The Alpha variant period (7 weeks) had the highest CFR (1.89) followed by the Original Covid-19 (1.37). A significant negative correlation was present between two dose vaccination and the 60-69 years (p = 0.01), 70-79 years (p = &amp;lt;0.01), and 80+ years (p = &amp;lt;0.01) age groups, while a positive correlation was present between the booster dose and the 60-69 years (p = 0.01) age group. Conclusions Covid-19 variant’s infectivity, transmissibility, and the effectiveness of the vaccine against the variant play an important role in the ultimate outcome. Reducing mortality by embracing mass vaccination that targets current variants along with other non-pharmaceutical interventions remains paramount. Key messages • Mortality is an indicator for assessing the burden of an emerging variant within a population. • The effectiveness of vaccination against emerging variants plays a role in reducing mortality rates.

Spatial Modeling of COVID-19 Prevalence Using Adaptive Neuro-Fuzzy Inference System

This study is dedicated to modeling the spatial variation in COVID-19 prevalence using the adaptive neuro-fuzzy inference system (ANFIS) when dealing with nonlinear relationships, especially useful for small areas or small sample size problems. We compiled a broad range of socio-demographic, environmental, and climatic factors along with potentially related urban land uses to predict COVID-19 prevalence in rural districts of the Golestan province northeast of Iran with a very high-case fatality ratio (9.06%) during the first year of the pandemic (2020–2021). We also compared the ANFIS and principal component analysis (PCA)-ANFIS methods for modeling COVID-19 prevalence in a geographical information system framework. Our results showed that combined with the PCA, the ANFIS accuracy significantly increased. The PCA-ANFIS model showed a superior performance (R2 (determination coefficient) = 0.615, MAE (mean absolute error) = 0.104, MSE (mean square error) = 0.020, and RMSE (root mean square error) = 0.139) than the ANFIS model (R2 = 0.543, MAE = 0.137, MSE = 0.034, and RMSE = 0.185). The sensitivity analysis of the ANFIS model indicated that migration rate, employment rate, the number of days with rainfall, and residential apartment units were the most contributing factors in predicting COVID-19 prevalence in the Golestan province. Our findings indicated the ability of the ANFIS model in dealing with nonlinear parameters, particularly for small sample sizes. Identifying the main factors in the spread of COVID-19 may provide useful insights for health policymakers to effectively mitigate the high prevalence of the disease.

Assessing the impact of the four COVID-19 variants and the vaccine coverage on mortality in Malta over 2 years: An observational case study.

BackgroundMortality may quantify a population's disease burden. Malta, like other European countries, experienced COVID-19 surges in cases and mortality across the pandemic. This study assesses COVID-19's mortality impact, while exploring the effects of the four dominant COVID-19 variants and that of the vaccination coverage on the Maltese population.MethodsCOVID-19 data (cases, mortality, positivity, and vaccination rates) was obtained from the websites of the European Center for Disease Prevention and Control and the Malta Ministry of Health. Data was categorized into the four periods according to reported dominant COVID-19 variant. Years of life lost (YLL) and Case-Fatality-Ratio (CFR) for each period were estimated. CFR was also estimated for the pre-vaccine and post-vaccine periods.ResultsThe original COVID-19 period (36 weeks) had the highest YLL (4,484), followed by the Omicron variant period (12 weeks; 1,398). The Alpha variant period (7 weeks) had the highest CFR (1.89%) followed by the Original COVID-19 (1.35%). The pre-vaccine (1.59%) period had higher CFR than the post-vaccine period (0.67%).ConclusionVarious factors contributed to mortality, but the variant's infectivity, transmissibility, and the effectiveness of the vaccine against the variant play an important role. Reducing mortality by embracing mass vaccination that targets current variants along with other non-pharmaceutical interventions remains paramount.

Recent Emergence and Re-Emergence of Crimean Congo Hemorrhagic Fever and Q Fever Zoonotic Diseases: Major yet Ignored Infectious Diseases Worldwide

The continuing emergence or re-emergence of vector-borne zoonotic Q fever (caused by Coxiella burnetii) and Crimean Congo hemorrhagic fever (CCHF, caused by Orthonairovirus) include indispensable extraordinary threat around the world. Low infectious dose and long-term environmental residence are major risks. Wildlife and domestic livestock act as hosts or reservoirs of the CCHF virus and ticks are carriers. The disease also poses a threat to public health services owing to its epidemic potential, high case fatality ratio (up to 40%) as well as difficulties in treatment, prevention, and control. Q fever is another zoonotic febrile disease mainly affecting workers involved in farming livestock. The causative agent of Q fever causes abortion in livestock. The pathogen is shed in large numbers in the waste of infected animals (amniotic fluids and placenta during parturition) and is transmitted by inhalation of contaminated aerosols. Vaccination is the most effective way of protecting against Q fever. The main way to prevent Q fever is to avoid contact with animals, especially while animals are giving birth, or consumption of unpasteurized milk and contaminated dairy products. Due to the increasing importation of livestock to meet the growing demand for dairy and meat products, new diseases are likely to be introduced. In our growing globalized world, where trade between countries increases, it is necessary to conduct more research on zoonotic diseases and to monitor any possible disease introduction to new areas. A continuing surveillance program and pathogen testing are important in tracking the emergence of new pathogens.

Association Between COVID-19 Vaccination Coverage and Case Fatality Ratio: a Comparative Study - Hong Kong SAR, China and Singapore, December 2021-March 2022.

What is already known about this topic?Hong Kong Special Administrative Region (SAR), China and Singapore are both facing considerable Omicron variant epidemic. However, the overwhelmed medical system and high case fatality ratio (CFR) just occurred in Hong Kong SAR, China but not in Singapore.What is added by this report?The low vaccination coverage in Hong Kong SAR, China, especially among the older adults, is shown to be a primary reason of its recent high CFR.What are the implications for public health practice?Facing the potential epidemic risk, non-vaccinated, non-fully-vaccinated, and non-booster-vaccinated people in China, especially the elderly, should get any type of accessible vaccine, which could save lives when the infection unfortunately befalls.

Molecular docking and dynamics simulation analysis of nucleoprotein from the Crimea-Congo hemorrhagic fever virus strain Baghdad-12 with FDA approved drugs.

Crimea-Congo hemorrhagic fever virus is considered a potential public health threat due to the high case fatality ratio of the disease hemorrhagic phase and absence of approved vaccines or antiviral agents. Therefore, it is of interest to screen FDA approved drugs against the nucleoprotein crystal of Crimea-Congo hemorrhagic fever virus strain Baghdad-12 by using molecular docking and dynamics simulation. Hence, we report that the beta receptor blocker Nebivolol and the antihistamine Loratadine may bind to RNA binding region on nucleoprotein for further consideration in drug design and development.

Estimates of Japanese Encephalitis mortality and morbidity: A systematic review and modeling analysis.

BackgroundJapanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might change the JE fatality risk. However, previous estimates were from 10 years ago, using data from cases in the 10 years before this. Estimating JE disease severity is challenging because data come from countries with different JE surveillance systems, diagnostic methods, and study designs. Without precise and timely JE disease severity estimates, there is continued uncertainty about the JE disease burden and the effect of JE vaccination.MethodologyWe performed a systematic review to collate age-stratified JE fatality and morbidity data. We used a stepwise model selection with BIC as the selection criteria to identify JE CFR drivers. We used stacked regression, to predict country-specific JE CFR from 1961 to 2030. JE morbidity estimates were grouped from similar study designs to estimate the proportion of JE survivors with long-term neurological sequelae.Principal findingsWe included 82 and 50 peer-reviewed journal articles published as of March 06 2021 for JE fatality and morbidity with 22 articles in both analyses. Results suggested overall JE CFR estimates of 26% (95% CI 22, 30) in 1961–1979, 20% (95% CI 17, 24) in 1980–1999, 14% (95% CI 11, 17) in 2000–2018, and 14% (95% CI 11, 17) in 2019–2030. Holding other variables constant, we found that JE fatality risk decreased over time (OR: 0.965; 95% CI: 0.947–0.983). Younger JE cases had a slightly higher JE fatality risk (OR: 1.012; 95% CI: 1.003–1.021). The odds of JE fatality in countries with JE vaccination is 0.802 (90% CI: 0.653–0.994; 95% CI: 0.62–1.033) times lower than the odds in countries without JE vaccination. Ten percentage increase in the percentage of rural population to the total population was associated with 15.35% (95% CI: 7.71, 22.57) decrease in JE fatality odds. Ten percentage increase in population growth rate is associated with 3.71% (90% CI: 0.23, 7.18; 95% CI: -0.4, 8.15) increase in JE fatality odds. Adjusting for the effect of year, rural population percent, age of JE cases, and population growth rate, we estimated that there was a higher odds of JE fatality in India compared to China. (OR: 5.46, 95% CI: 3.61–8.31). Using the prediction model we found that, in 2000–2018, Brunei, Pakistan, and Timor-Leste were predicted to have the highest JE CFR of 20%. Bangladesh, Guam, Pakistan, Philippines, and Vietnam had projected JE CFR over 20% for after 2018, whereas the projected JE CFRs were below 10% in China, Indonesia, Cambodia, Myanmar, Malaysia, and Thailand. For disability, we estimated that 36% (min-max 0–85) JE patients recovered fully at hospital discharge. One year after hospital discharge, 46% (min-max 0%-97%) JE survivors were estimated to live normally but 49% (min-max 3% - 86%)till had neurological sequelae.ConclusionJE CFR estimates were lower than 20% after 2000. Our study provides an updated estimation of CFR and proportion of JE cases with long-term neurological sequelae that could help to refine cost-benefit assessment for JE control and elimination programs.

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status.

ObjectiveTo investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression.MethodsThe study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO2) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO2 and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching.FindingsOf 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO2: 90–93%) in 13.1% (108/826) and severe (SpO2: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5–4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality.ConclusionPresumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed.

COVID-19 death: A novel method of improving its identification when a patient has multiple diagnoses.

Assigning a primary cause of death to a deceased patient who had multiple principal diagnoses including coronavirus disease 2019 (COVID-19) is challenging because of the difficulty in selecting the most appropriate cause. To proffer a solution, the authors reviewed the literature on assigning a primary cause of death. In 2015, the Nnabuike-Jagidesa (NJ) model II was devised to improve the International Classification of Diseases and related health problems, 10th revision (ICD-10) guideline on how to assign a primary cause of death. The NJ model II stipulates that when there are multiple diagnoses with no plausible explanation that one of the illnesses could have resulted in the other clinical conditions, the single most appropriate primary cause of death is the condition with the highest case fatality ratio in that setting. In the index report, the authors opine that if the case fatality ratios are similar, the following objective criteria (listed in the order of priority) should be used to assign a primary cause of death: condition with the highest infection fatality ratio, condition that was the main indication for the last acute surgical or invasive procedure performed (during the course of the same ill-health) before the death and the disease that theoretically affects the highest number of body organs. Additionally, a clinical descriptor should be used when none of the objective criteria are satisfied. This novel approach, termed the modified NJ model II, is expected to improve the objectivity and reproducibility of the assigned primary cause of death in a deceased who had multiple diagnoses, which may include COVID-19.

Differential health impact of intervention programs for time-varying disease risk: a measles vaccination modeling study

BackgroundDynamic modeling is commonly used to evaluate direct and indirect effects of interventions on infectious disease incidence. The risk of secondary outcomes (e.g., death) attributable to infection may depend on the underlying disease incidence targeted by the intervention. Consequently, the impact of interventions (e.g., the difference in vaccination and no-vaccination scenarios) on secondary outcomes may not be proportional to the reduction in disease incidence. Here, we illustrate the estimation of the impact of vaccination on measles mortality, where case fatality ratios (CFRs) are a function of dynamically changing measles incidence.MethodsWe used a previously published model of measles CFR that depends on incidence and vaccine coverage to illustrate the effects of (1) assuming higher CFR in “no-vaccination” scenarios, (2) time-varying CFRs over the past, and (3) time-varying CFRs in future projections on measles impact estimation. We used modeled CFRs in alternative scenarios to estimate measles deaths from 2000 to 2030 in 112 low- and middle-income countries using two models of measles transmission: Pennsylvania State University (PSU) and DynaMICE. We evaluated how different assumptions on future vaccine coverage, measles incidence, and CFR levels in “no-vaccination” scenarios affect the estimation of future deaths averted by measles vaccination.ResultsAcross 2000–2030, when CFRs are separately estimated for the “no-vaccination” scenario, the measles deaths averted estimated by PSU increased from 85.8% with constant CFRs to 86.8% with CFRs varying 2000–2018 and then held constant or 85.9% with CFRs varying across the entire time period and by DynaMICE changed from 92.0 to 92.4% or 91.9% in the same scenarios, respectively. By aligning both the “vaccination” and “no-vaccination” scenarios with time-variant measles CFR estimates, as opposed to assuming constant CFRs, the number of deaths averted in the vaccination scenarios was larger in historical years and lower in future years.ConclusionsTo assess the consequences of health interventions, impact estimates should consider the effect of “no-intervention” scenario assumptions on model parameters, such as measles CFR, in order to project estimated impact for alternative scenarios according to intervention strategies and investment decisions.

Estimating the global and regional burden of meningitis in children caused by Haemophilus influenzae type b: A systematic review and meta-analysis.

BackgroundHaemophilus influenzae Type B (Hib) meningitis caused significant public health concern for children. Recent assessment in 2015 suggests vaccination has virtually eliminated invasive Hib diseases. However, many countries launched their programs after 2010, and few are yet to establish routine Hib immunisations. We therefore aimed to update the most recent global burden of Hib meningitis before the impact of COVID-19 pandemic, from 2010 to 2020, in order to aid future public health policies on disease management and prevention.MethodsEpidemiological data regarding Hib meningitis in children <5 years old were systematically searched and evaluated from PubMed and Scopus in August, 2020. We included studies published between 2010 and 2019 that reported incidence, prevalence, mortality, or case-fatality-ratio (CFR), and confirmation of meningitis by cerebrospinal fluid culture, with a minimum one year study period and ten cases. Each data was stratified by one study-year. Median study-year was used if information was not available. Quality of all studies were assessed using our adapted assessment criteria from Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from National Heart, Lung and Blood Institute (NHLBI). We constructed and visually inspected a funnel plot of standard error by the incidence rate and performed an Egger’s regression test to statistically assess publication bias. To ascertain incidence and CFR, we performed generalised linear mixed models on crude individual study estimates. Heterogeneity was assessed using I-squared statistics whilst further exploring heterogeneity by performing subgroup analysis.Results33 studies were identified. Pooled incidence of global Hib meningitis in children was 1.13 per 100 000-child-years (95% confidence interval (CI) = 0.80-1.59). Southeast Asian Region (SEAR) of World Health Organisation (WHO) region reported the highest incidence, and European Region (EUR) the lowest. Considering regions with three or more data, Western Pacific Region (WPR) had the highest incidence rate of 5.22 (95% CI = 3.12-8.72). Post-vaccination incidence (0.67 cases per 100 000-child-years, 95% CI = 0.48-0.94) was dramatically lower than Pre-vaccination incidence (4.84 cases per 100 000-child-years, 95% CI = 2.95-7.96). Pooled CFR in our meta-analysis was 11.21% (95% CI = 7.01-17.45). Eastern Mediterranean Region (EMR) had the highest CFR (26.92, 95% CI = 13.41-46.71) while EUR had the lowest (4.13, 95% CI = 1.73-9.54). However, considering regions with three or more data, African Region (AFR) had the highest CFR at 21.79% (95% CI = 13.65-32.92). Before the coronavirus disease 2019 (COVID-19) impact, the estimation for global Hib meningitis cases in 2020 is 7645 and 857 deaths.ConclusionsGlobal burden of Hib meningitis has markedly decreased, and most regions have implemented vaccination programs. Extrapolating population-at-risk from studies has possibly led to an underestimation. Continuous surveillance is necessary to monitor vaccination impact, resurgence, vaccine failures, strain variance, COVID-19 impact, and to track improvement of regional and global Hib meningitis mortality.