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Abstract As new, efficacious respiratory syncytial virus (RSV) immunization products reach the market, affordable pricing as well as improved estimation of disease burden and the full potential and cost effectiveness of RSV prevention in the hardest hit geographies in low- and middle-income countries are critical to inform country adoption and enable maximum impact against infant disease and mortality globally. The data reported in the special issue underscore the enormous burden, and associated cost, of RSV disease in young infants in several LMICs, including Kenya and South Africa, as well as the potential for RSV maternal vaccines or long-acting monoclonal antibodies, to be cost-effective and possibly even cost-saving.

BackgroundDespite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs), but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases.Methods and findingsWe developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality-with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 3.40% [CrI: 0.75 to 8.01] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 6% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis.ConclusionsA K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.

More than 85% of Covid-19 mortality in high income countries is among people 65 years of age or older. Recent disaggregated data from the UK and US show that minority communities have increased mortality among younger age groups and in South Africa initial data suggest that the majority of deaths from Covid-19 are under 65 years of age. These observations suggest significant potential for increased Covid-19 mortality among younger populations in Africa and South Asia and may impact age-based selection of high-risk groups eligible for a future vaccine.

Background: Acute encephalitis syndrome (AES) surveillance in India has indicated that Japanese encephalitis virus (JEV) accounts for 5-35% of AES cases annually; the etiology remains unknown in the remaining cases. We implemented comprehensive AES surveillance to identify other etiological agents of AES, with emphasis on dengue virus. Methods: Serum and cerebrospinal fluid (CSF) specimens were collected from patients enrolled prospectively in AES surveillance from 2014-2017 at selected sites of three high burden states of India. All samples were initially tested for JEV IgM. Specimens negative for JEV by serology were tested for IgM to scrub typhus, dengue virus (DEN), and West Nile virus; all JEV IgM-negative CSF samples were tested by PCR for S. pneumoniae, N. meningitidis, H. influenzae, herpes simplex virus type 1, enteroviruses and DEN. Results: Of 10,107 AES patients, an etiology could be established in 49.2% of patients including JEV (16%), scrub typhus (16%) and DEN (5.2%) as the top three agents. Amongst the DEN positive cases (359/6892), seven (2%) were positive only for dengue virus RNA: one in serum and six in CSF. Conclusion: Amongst the pathogens identified, dengue accounted for 5% of all AES cases and was one of the three common etiological agents. These results underscore the importance of including dengue virus in routine testing of AES cases. Keywords: Acute encephalitis syndrome, Etiological agents, Dengue, India

Summary: Background: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. Funding: US Centers for Disease Control and Prevention.

We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection.

We investigated a large outbreak of Salmonella enterica serotype Javiana among attendees of the 2002 U.S. Transplant Games, including 1,500 organ transplant recipients. Web-based survey methods identified pre-diced tomatoes as the source of this outbreak, which highlights the utility of such investigative tools to cope with the changing epidemiology of foodborne diseases.

AbstractThe World Health Organizations HIV Drug Resistance (WHO HIVDR) Threshold survey method was used to assess transmitted HIVDR in newly diagnosed HIV-1-infected primigravida women attending the Prevention of Parent to Child Transmission (PPTCT) centers in Kakinada, in whom it is likely that the infection had recently occurred. Out of the 56 consecutively collected eligible specimens, 51 were tested using the ViroSeq RT-PCR method (Abbott Germany) to obtain 47 consecutive sequences for the HIV-1 protease (PR) and reverse transcriptase (RT) region. As per the 2009 WHO list of mutations for surveillance of transmitted HIVDR, only one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation was detected at K101E from all specimens tested, suggesting a low prevalence (<5%) of resistance to NNRTIs and no mutations were detected at other sites, suggesting a low prevalence (<5%) of resistance to nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) drug classes as well. Phylogenetic analysis showed all sequences belonged to HIV-1 subtype C. In the wake of antiretroviral treatment (ART) scale-up, future evaluation of transmitted HIVDR is essential in Kakinada as well as in other regions of India. [ABSTRACT FROM AUTHOR]

AbstractA survey for transmitted HIV drug resistance (HIVDR) was conducted according to WHO guidelines among clients newly diagnosed with HIV-1 infection at two voluntary counseling and testing centers (VCTC) in Mumbai. HIVDR testing was performed using the ViroSeq RT-PCR method (Abbott). Out of 50 successfully amplified and sequenced specimens, analysis of the first 34 consecutively collected specimens revealed no nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, or protease inhibitor mutations from the 2007 WHO list of mutations for surveillance of transmitted HIVDR, indicating that the prevalence of transmitted HIVDR to all three drug classes was <5% among recently infected VCTC clients in Mumbai. The phylogenetic analysis revealed that all samples belonged to HIV-1 subtype C. Continued ART program monitoring and further evaluation of transmitted HIV drug resistance in coming years are essential in Mumbai as well as in other regions of the country in which ART is being scaled up rapidly. [ABSTRACT FROM AUTHOR]