COVID-19 vaccine effectiveness and variants in Nepal: study protocol for a test-negative case-control study with SARS-CoV-2 genetic sequencing.

INTRODUCTION: Inactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants. METHODS AND ANALYSIS: This is a hospital-based, prospective test-negative case-control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.

Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study.

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization.

Progress in the overall understanding of typhoid fever: implications for vaccine development.

INTRODUCTION: Typhoid fever continues to have a substantial impact on human health, especially in Asia and sub-Saharan Africa. Access to safe water, and adequate sanitation and hygiene remain the cornerstone of prevention, but these are not widely available in many impoverished settings. The emergence of antibiotic resistance affects typhoid treatment and adds urgency to typhoid control efforts. Vaccines provide opportunities to prevent and control typhoid fever in endemic settings. AREAS COVERED: Literature search was performed looking for evidence concerning the global burden of typhoid and strategies for the prevention and treatment of typhoid fever. Cost of illness, available typhoid and paratyphoid vaccines and cost-effectiveness were also reviewed. The objective was to provide a critical overview of typhoid fever, in order to assess the current understanding and potential future directions for typhoid treatment and control. EXPERT COMMENTARY: Our understanding of typhoid burden and methods of prevention has grown over recent years. However, typhoid fever still has a significant impact on health in low and middle-income countries. Introduction of typhoid conjugate vaccines to the immunization schedule is expected to make a major contribution to control of typhoid fever in endemic countries, although vaccination alone is unlikely to eliminate the disease.