Risk factors for SARS-CoV-2 infection in primary and secondary school students and staff in England in the 2020/2021 school year: a longitudinal study.

OBJECTIVES: Investigate risk factors for SARS-CoV-2 infections in school students and staff. METHODS: In the 2020/2021 school year, we administered polymerase chain reaction, antibody tests, and questionnaires to a sample of primary and secondary school students and staff, with data linkage to COVID-19 surveillance. We fitted logistic regression models to identify the factors associated with infection. RESULTS: We included 6799 students and 5090 staff in the autumn and 11,952 students and 4569 staff in the spring/summer terms. Infections in students in autumn 2020 were related to the percentage of students eligible for free school meals. We found no statistical association between infection risk in primary and secondary schools and reported contact patterns between students and staff in either period in our study. Using public transports was associated with increased risk in autumn in students (adjusted odds ratio = 1.72; 95% confidence interval 1.31-2.25) and staff. One or more infections in the same household during either period was the strongest risk factor for infection in students and more so among staff. CONCLUSION: Deprivation, community, and household factors were more strongly associated with infection than contacts patterns at school; this suggests that the additional school-based mitigation measures in England in 2020/2021 likely helped reduce transmission risk in schools.

Declive en la Lepra Autóctona en la Comunidad Valenciana: Patrones y tendencias 1940-2015 / No disponible

Objetivos: El objetivo del estudio es describir los patrones y tendencias de la lepra autóctona en la Comunidad Valenciana (España). Métodos: Se incluyeron todos los casos nuevos d lepra de la Comunidad Valenciana entre los años 1940 y 2015. Se excluyeron pacientes de otros países u otras regiones españolas. Los nuevos casos se analizaron por edad, sexo, forma clínica, ocupación y distribución geográfica. Resultados: Se incluyeron 442 pacientes presumiblemente autóctonos. La incidencia disminuye de forma constante a lo largo del período de estudio. La edad media al comienzo de la enfermedad aumenta desde 34·2 años durante el período 1940-1949 hasta 59·5 años durante 2000-2015. No se detectaron nuevos casos desde 2006 y ningún caso nacidos después de 1973. Los pacientes eran mayoritariamente hombres (57·7%) y el 85·4% con tipo multibacilar. La proporción de casos multibacilares aumentó gradualmente después de 1970. La mayoría de los pacientes varones (67·9%) desarrollaban labores en el campo. La mayoría de los casos, sobre todo en los últimos períodos, se concentran en las regiones costeras. Conclusiones: Nuestros resultados concuerdan con otros estudios de otras regiones con características semejantes y sugieren que la transmisión de M. leprae en esta área ha sido interrumpida. La lepra autóctona ha sido mayoritariamente masculina con muchos casos multibacilares. Hay que investigar más porque su distribución geográfica y la elevada incidencia en trabajadores del campo sugieren posibles causas medioambientales

Objectives: The aim of this study was to describe the patterns and trends of autochthonous leprosy in the Valencia Region (Spain). Methods: : We included all new leprosy cases originating from the Valencia Region between the years 1940 and 2015. Patients originating from other countries or other Spanish regions were excluded. New cases were analysed by age, sex, clinical type, occupation, and geographic distribution.Results: A total of 442 patients with presumably autochthonous leprosy were included. Incidence rates consistently declined over the study period. Mean age at onset gradually increased from 34·2 years during the period 1940-1949 to 59·5 years during 2000-2015. There were no cases with clinical onset after 2006 and no cases born after 1973. Patients were predominantly males (57·7%) and 85·4% had multibacillary leprosy. The proportion of multibacillary cases increased gradually after 1970. The majority of male patients (67·9%) worked in agriculture. Most of the cases, especially during the later periods, were concentrated in the coastal regions. Conclusions: Our findings are consistent with trends described in other regions with declining leprosy incidence rates and suggest that the transmission of M. leprae infection in this area may well have now stopped. Autochthonous leprosy in this region has had a male predominance and a high proportion of multibacillary cases. The geographic distribution and the high incidence in agricultural workers suggest that environmental factors should be further explored (AU)

Observational study to estimate the changes in the effectiveness of bacillus Calmette-Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK.

BACKGROUND: Until recently, evidence that protection from the bacillus Calmette-Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK's universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. OBJECTIVES: To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. METHODS: Two case-control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0-19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10-29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case-cohort analysis based on Cox regression. RESULTS: In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5-10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10-15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10-15 years after vaccination and 57% (95% CI 33% to 72%) 15-20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. LIMITATIONS: The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. CONCLUSIONS: Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. FUNDING: The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

Recurrent TB: relapse or reinfection? The effect of HIV in a general population cohort in Malawi.

OBJECTIVE: To estimate rates of recurrent tuberculosis due to reinfection and relapse, by HIV status, in a general population. DESIGN: Long-term cohort study in Karonga district, rural Malawi. METHODS: All tuberculosis patients with culture-proven disease in Karonga district were followed up after treatment. HIV testing was offered and all Mycobacterium tuberculosis isolates were fingerprinted using IS6110 RFLP. Fingerprints from initial and recurrent disease episodes were compared to distinguish relapse and reinfection: a second episode was considered a relapse if the fingerprint was identical or differed by only 1-4 bands and was the first occurrence of that pattern in the population. Rates of and risk factors for recurrence, reinfection disease, and relapse were estimated using survival analysis and Poisson regression. RESULTS: Five hundred and eighty-four culture-positive episodes of tuberculosis were diagnosed and treatment was completed during 1995-2003 in patients with known HIV status; 53 culture-positive recurrences occurred by May 2005. Paired fingerprints were available for 39 of these. Reinfections accounted for 1/16 recurrences in HIV-negative and 12/23 in HIV-positive individuals. Rates of relapse were similar in HIV-positive and HIV-negative individuals. Using multiple imputation to allow for missing fingerprint information, the rate of reinfection disease in HIV-positive individuals was 2.2/100 person-years, and in HIV-negative individuals 0.4/100 person-years. CONCLUSIONS: HIV increases the rate of recurrent tuberculosis in this setting by increasing the rate of reinfection disease, not relapse.

Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

BACKGROUND: Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years. METHODS: Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents. RESULTS: HIV-negative Malawian adolescents were shown to have a lower percentage of naïve T cells (CD45RO-CD62Lhi CD11alo), a higher proportion of memory T cells and a higher percentage of CD28- memory (CD28-CD45RO+) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA-CCR7+) T cells and a higher percentage of stable memory (CD45RA+CCR7-) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naïve T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naïve and memory T cell populations were observed in cord blood samples from the two sites. CONCLUSION: It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections.

Estimating the need for antiretroviral treatment and an assessment of a simplified HIV/AIDS case definition in rural Malawi.

BACKGROUND: Surveillance in the era of antiretroviral therapy (ART) requires estimates of HIV prevalence as well as the proportion eligible for ART. We estimated HIV prevalence and assessed field staging of individuals to estimate the burden of HIV disease needing treatment in rural Malawi. METHODS: Adults aged 18-59 years in a demographic surveillance system were interviewed, examined, and HIV counselled and tested. Staging that used a simplified version of the WHO criteria ('field checklist') was compared with staging by a medical assistant using a 'clinic checklist' and to CD4 cell results. RESULTS: A total of 2129 of 2303 eligible adults (92.4%) were traced, and 2047 (96.1%) participated. Of the 1443 participants (70.5%) tested, 11.6% were HIV positive. ART eligibility classification by the field and clinic checklists were concordant in 122 of 133 HIV-positive individuals. Compared with the clinic checklist, the field checklist had a sensitivity of 50% and a specificity of 96%. Including those already known to be on ART, staging by the field and clinic checklists estimated ART eligibility at 16.3 and 17.7% of HIV-positive individuals, respectively. Using CD4 cell count under 250 cells/mul or WHO stage III/IV, the Malawi national programme criteria, 38% of HIV-positive individuals were eligible for ART, compared with 31% based on the 2006 WHO criteria of CD4 cell count under 200 cells/mul or WHO stage IV or CD4 cell count of 200-350 cells/mul and WHO stage III. CONCLUSION: The field checklist was not a suitable tool for individual staging. Criteria for ART eligibility based on clinical staging alone missed two-thirds of those eligible by clinical staging and CD4 cell count.