National Center for Disease Control

. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

In Canada in late 1987 there was an outbreak of an acute illness characterized by gastrointestinal symptoms and unusual neurologic abnormalities among persons who had eaten cultivated mussels. Health departments in Canada solicited reports of this newly recognized illness. A case was defined as the occurrence of gastrointestinal symptoms within 24 hours or of neurologic symptoms within 48 hours of the ingestion of mussels. From the more than 250 reports received, 107 patients met the case definition. The most common symptoms were vomiting (in 76 percent of the patients), abdominal cramps (50 percent), diarrhea (42 percent), headache, often described as incapacitating (43 percent), and loss of short-term memory (25 percent). Nineteen patients were hospitalized, of whom 12 required intensive care because of seizures, coma, profuse respiratory secretions, or unstable blood pressure. Male sex and increasing age were associated independently with the risks of hospitalization and memory loss. Three patients died. Mussels associated with this illness were traced to cultivation beds in three river estuaries on the eastern coast of Prince Edward Island. Domoic acid, which can act as an excitatory neurotransmitter, was identified in mussels left uneaten by the patients and in mussels sampled from these estuaries. The source of the domoic acid appears to have been a form of marine vegetation, Nitzschia pungens, also identified in these waters in late 1987. The contaminated mussels from Prince Edward Island were removed from the market, and no new cases have occurred since December 1987. We conclude that the cause of this outbreak of a novel and severe intoxication was the ingestion of mussels contaminated by domoic acid, a potent excitatory neurotransmitter.

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of "variants of concern" (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential.

In September 1985, an outbreak of Escherichia coli O157:H7 enteritis affected 55 of 169 residents and 18 of 137 staff members at a nursing home. The outbreak was characterized by two phases: a primary wave whose source was probably a contaminated sandwich meal and a secondary wave compatible with person-to-person transmission of infection. Among the elderly residents, the incubation period was 4 to 9 days (mean, 5.7 +/- 1.2). Older age and previous gastrectomy increased the risk of acquiring the infection (P = 0.01 and 0.03, respectively). Antibiotic therapy during exposure was associated with acquiring a secondary infection (P = 0.001). Hemolytic uremic syndrome developed in 12 affected residents (22 percent), 11 of whom died. Overall, 19 (35 percent) of the affected residents died, 17 (31 percent) from causes attributable to their infection. Antibiotic therapy after the onset of symptoms was associated with a higher case fatality rate in the more severe cases, possibly because patients with more severe disease tended to be treated with antibiotics. There were no complications or deaths among the affected members of the staff. Evidence of infection by verotoxin-producing E. coli O157:H7 was detected in 30 of 70 cases on the basis of isolation of this organism or demonstration of free verotoxin in stools. All isolates belonged to the same phage type. The high morbidity and mortality associated with this condition emphasize the need for proper food hygiene, rapid identification of outbreaks of disease, and prompt institution of infection-control techniques among the institutionalized elderly.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves. METHODS: 466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council. RESULTS: For the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years. Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave. Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deaths compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital. CONCLUSION: There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.

BACKGROUND AND PURPOSE: The goal of this article is to clarify the proportion of stroke subtypes in China, where stoke is the most common cause of death. METHODS: A total of 16,031 first-ever strokes in subjects >or=25 years of age were identified in 1991 to 2000 from 17 Chinese populations through a community-based cardiovascular disease surveillance program in the China Multicenter Collaborative Study of Cardiovascular Epidemiology. World Health Organization diagnosis criteria were used for classification of stroke subtypes. RESULTS: CT scan rate of stroke cases reached a satisfactorily high level only after 1996 in the study populations. In 8268 first-ever stroke events from 10 populations with CT scan rate >75% in 1996 to 2000, 1.8% were subarachnoid hemorrhage, 27.5% were intracerebral hemorrhage, 62.4% were cerebral infarction, and 8.3% were undetermined stroke. The proportion of intracerebral hemorrhage varied from 17.1% to 39.4% and that for cerebral infarction varied from 45.5% to 75.9% from population to population. The ratio of ischemic to hemorrhagic stroke ranged from 1.1 to 3.9 and averaged 2.0). The 28-day fatality rate was 33.3% for subarachnoid hemorrhage, 49.4% for intracerebral hemorrhage, 16.9% for cerebral infarction, and 64.6% for undetermined stroke. CONCLUSIONS: In our study, ischemic stroke was more frequent and its proportion was higher than hemorrhagic stroke in Chinese populations. Although hemorrhagic stroke was more frequent in Chinese than in Western populations, the variation in the proportion of stroke subtypes among Chinese populations could be as large as or larger than that between Chinese and Western populations.

OBJECTIVE: To provide an estimate of the burden of postpartum depression in Indian mothers and investigate some risk factors for the condition. METHODS: We searched PubMed®, Google Scholar and Embase® databases for articles published from year 2000 up to 31 March 2016 on the prevalence of postpartum depression in Indian mothers. The search used subject headings and keywords with no language restrictions. Quality was assessed via the Newcastle-Ottawa quality assessment scale. We performed the meta-analysis using a random effects model. Subgroup analysis and meta-regression was done for heterogeneity and the Egger test was used to assess publication bias. FINDINGS: = 96.8%) and there was evidence of publication bias (Egger bias = 2.58; 95% confidence interval, CI: 0.83-4.33). The overall pooled estimate of the prevalence of postpartum depression was 22% (95% CI: 19-25). The pooled prevalence was 19% (95% CI: 17-22) when excluding 8 studies reporting postpartum depression within 2 weeks of delivery. Small, but non-significant differences in pooled prevalence were found by mother's age, geographical location and study setting. Reported risk factors for postpartum depression included financial difficulties, presence of domestic violence, past history of psychiatric illness in mother, marital conflict, lack of support from husband and birth of a female baby. CONCLUSION: The review shows a high prevalence of postpartum depression in Indian mothers. More resources need to be allocated for capacity-building in maternal mental health care in India.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

BACKGROUND: Nipah Virus (NiV) is a highly fatal emerging zoonotic virus and a potential threat to global health security. Here we describe the characteristics of the NiV outbreak that occurred in Kerala, India, during May-June 2018. METHODS: We used real-time reverse transcription polymerase chain reaction analysis of throat swab, blood, urine, and cerebrospinal fluid specimens to detect NiV. Further, the viral genome was sequenced and subjected to phylogenetic analysis. We conducted an epidemiologic investigation to describe the outbreak and elucidate the dynamics of NiV transmission. RESULTS: During 2-29 May 2018, 23 cases were identified, including the index case; 18 were laboratory confirmed. The lineage of the NiV responsible for this outbreak was closer to the Bangladesh lineage. The median age of cases was 45 years; the sex of 15 (65%) was male. The median incubation period was 9.5 days (range, 6-14 days). Of the 23 cases, 20 (87%) had respiratory symptoms. The case-fatality rate was 91%; 2 cases survived. Risk factors for infection included close proximity (ie, touching, feeding, or nursing a NiV-infected person), enabling exposure to droplet infection. The public health response included isolation of cases, contact tracing, and enforcement of hospital infection control practices. CONCLUSION: This is the first recorded NiV outbreak in South India. Early laboratory confirmation and an immediate public health response contained the outbreak.

BACKGROUND: The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. METHODS AND FINDINGS: To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. CONCLUSION: Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

Delhi, the national capital of India, experienced multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks in 2020 and reached population seropositivity of >50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant, B.1.617.2 (Delta), replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates: 1.5-fold greater transmissibility and 20% reduction in sensitivity). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi.

Abstract As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches was undertaken to identify possible new variants and gauge the fitness of current circulating strains. Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identified lineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site, revealed that these may possibly result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation against a wider panel of mAbs, sera from vaccinees and those that recovered from natural infection needs to be studied. The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Abstract Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic 1,2 . Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches 1 , while maintaining proven prevention measures using a vaccines-plus approach 2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities 3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with &gt;5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

BACKGROUND AND AIM: Hepatitis E virus (HEV) infection leading to fulminant hepatic failure (FHF) and high mortality is a common feature in Indian women during the second and third trimesters of pregnancy. An altered status of hormones and immunity are observed during pregnancy but the actual cause of high mortality is still unknown. The present study was carried out to analyze CD3, CD4 and CD8 T cell counts and to assay the level of pregnancy-related hormones such as estrogen, progesterone and beta-HCG in order to discover the role played by these factors. METHODS: One hundred patients (50 pregnant and 50 non-pregnant women) with FHF and 150 pregnant healthy females without liver disease as controls were recruited for the study. Serological tests for all viral markers using ELISA kits and detection of HEV RNA by reverse transcription-polymerase chain reaction (RT-PCR) were carried out in all cases. CD3, CD4 and CD8 T cell counts were analyzed by fluorescence activated cell sorter (FACS) while hormone assay was performed by commercially available RIA kits. RESULTS: Serologically (38/50; 76%) as well as by RT-PCR (28/50; 56%), a significantly higher HEV positivity rate was found in pregnant FHF patients compared to non-pregnant women (serologically 15/50; 30%; RT-PCR 7/50; 14%). CD4 counts were lower (P < 0.05), while CD8 counts were higher (P < 0.05), and their ratio (CD4/CD8) in HEV positive pregnant FHF patients was significantly lower (P < 0.01) when compared to that of HEV negative pregnant FHF women or controls. Levels of estrogen, progesterone and beta-HCG were also found to be higher (P < 0.001) in HEV positive pregnant FHF patients when compared to HEV negative patients or controls. HEV infected pregnant FHF patients had a significantly higher mortality rate of 65.8% (25/38) compared to 23.5% (4/15) in HEV positive non-pregnant women (P < 0.001). CONCLUSIONS: Pregnancy appears to be a potential risk factor for viral replication and an extreme low immune status of Indian/Asian pregnant women. It is suggested that diminished cellular immunity (indicated by a decrease in CD4, an increase in CD8 cell counts and lowered CD4/CD8 cell ratio) and a high level of steroid hormones that influence viral replication/expression during pregnancy appear to be the plausible reasons for severity of the disease.

BACKGROUND & OBJECTIVES: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. METHODS: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. RESULTS: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. INTERPRETATION & CONCLUSIONS: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

The SARS-CoV-2 B.1.617 variant emerged in the Indian state of Maharashtra in late 2020. There have been fears that 2 key mutations seen in the receptor-binding domain, L452R and E484Q, would have additive effects on evasion of neutralizing antibodies. We report that spike bearing L452R and E484Q confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies following either first or second dose. The effect is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. These data demonstrate reduced sensitivity to vaccine-elicited neutralizing antibodies by L452R and E484Q but lack of synergistic loss of sensitivity.

The yellow fever and dengue mosquito Aedes aegypti previously flourished around the Mediterranean and Black Sea for decades until the 1950s, and was responsible of large outbreaks of both yellow fever and dengue The first well-described large dengue outbreak in Greece in 1927-28 caused more than 1 million cases (90% of the population in Athens) with 1000-1500 fatalities. The disappearance of Ae. aegypti from the European continent in Mediterranean, Black Sea, and Macaronesian biogeographical regions [2] is not well understood and its return in these regions raises concerns about a possible resurgence of the pathogens that can be transmitted by this vector species. Besides, the tiger mosquito Aedes albopictus is extending its distribution range worldwide, and it has already invaded large parts of the Mediterranean [1].

BACKGROUND: Dengue virus type 1 (DENV-1) have been mostly circulating silently with dominant serotypes DENV-2 and DENV-3 in India. However recent times have marked an increase in DENV-1 circulation in yearly outbreaks. Many studies have not been carried out on this virus type, leaving a lacunae pertaining to the circulating genotypes, since its earliest report in India. In the present study, we sequenced CprM gene junction of 13 DENV-1 isolated from Delhi and Gwalior (North India) between 2001-2007 and one 1956 Vellore isolate as reference. For comparison, we retrieved 11 other Indian and 70 global reference sequences from NCBI database, making sure that Indian and global isolates from all decades are available for comparative analysis. RESULTS: The region was found to be AT rich with no insertion or deletion. Majority of the nucleotide substitutions were silent, except 3 non-conservative amino acid changes (I --> T, A --> T and L --> S at amino acid positions 59,114 and 155 respectively) in the Indian DENV-1 sequences, sequenced in this study. Except two 1997-98 Delhi isolates, which group in genotype I; all other Indian isolates group in genotype III. All Indian genotype III DENV-1 exhibited diversity among them, giving rise to at least 4 distinct lineages (India 1-4) showing proximity to isolates from diverse geographic locations. CONCLUSION: The extensive phylogenetic analysis revealed consistent existence of multiple lineages of DENV-1 genotype III during the last 5 decades in India.