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BackgroundRisk factors for infection and, therefore, antibody positivity rates will be different in children compared to adults. We aim to estimate national and regional prevalence of SARS-CoV-2 antibodies in primary (4-11-year-olds) and secondary (11-15-year-olds) school children between 10 November and 10 December 2021.MethodsCross-sectional surveillance in England using two stage sampling, firstly stratifying into regions and selecting local authorities, then selecting schools according to a stratified sample within selected local authorities. Participants were sampled using a novel oral fluid validated assay for SARS-CoV-2 spike and nucleocapsid IgG antibodies.Results4,980 students from 117 state-funded schools (2,706 from 83 primary schools, 2,274 from 34 secondary schools) provided a valid sample. After weighting for age, sex and ethnicity, and adjusting for assay accuracy, the national prevalence of SARS-CoV-2 antibodies in primary school students, who were all unvaccinated, was 40.1% (95%CI; 37.3-43.0). Antibody prevalence increased with age (pConclusionsUsing a validated oral fluid assay, we estimated national and regional seroprevalence of SARS-CoV-2 antibodies in primary and secondary school students. In November 2021, 40% of primary school students and nearly all secondary school students in England had SARS-CoV2 antibodies through a combination of natural infection and vaccination.

Background Brucellosis is an important neglected zoonosis. Effective cattle vaccines are available but are infrequently used in India, where rural households commonly own one or two cattle as sources of protein and income. We assessed the prevalence of infection and risk factors in humans. Methods We conducted a cross-sectional sero-survey in randomly selected individuals in 60 villages in Punjab. Infection prevalence was assessed by positive Rose Bengal testing or immunoglobulin G enzyme-linked immunosorbent assay. Risk factors were adjusted for potential confounding using multivariable analyses. Results Of the 1927 subjects who were approached, 93% agreed to participate. Age-standardised prevalence for Brucella infection was 2.24% (95% confidence interval [CI] 1.61 to 3.11). More than 60% of households kept cattle and 10% assisted with calving or abortions. Nearly all individuals consumed boiled cow/buffalo milk from their own or neighbours' cattle and 3.3% consumed goat’s milk. There was a 2.18 times increased odds (95% CI 0.96 to 4.95) of infection with calving/abortions and a 4.26 times increased odds (95% CI 1.33 to 13.6) with goat’s milk but not bovine milk consumption. Conclusions An association with calving/abortions and goat’s milk consumption was seen. Brucella vaccination of household livestock would reduce the risk to humans in such settings. Additional measures include biosecurity training around calving/abortions, education to boil all milk and for healthcare workers to test for brucellosis.

BACKGROUND One of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this. OBJECTIVE This paper presents the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through implementation of school COVID-19 control measures. METHODS SIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. Six bio-behavioural surveys were planned among participating students and staff during the 2020/21 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick-blood for staff and oral-fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study received approvals from the UK Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (ref:22657). RESULTS Data collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals: 1,891 staff and 4,654 students from 59 primary schools and 5,852 staff and 10,188 students from 97 secondary schools participated in at least one survey. On average, across survey rounds, staff and student participation rates were 45.2% and 16.4% respectively in primary schools and 30.0% and 15.2% in secondary schools. While primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (41.7% in Round 1 and 22.1% in Round 6). While staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals and from schools in the least deprived locations (in primary schools 9.6% participants were from schools in the least deprived quintile compared with 5.7% of eligible students). CONCLUSIONS We outline the study design, methods and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered, and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools, across a range of settings in England, aims to inform national guidance and public health policy for educational settings. CLINICALTRIAL

Background One of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this issue. Objective We present the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through the implementation of school COVID-19 control measures. Methods SIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. A total of 6 biobehavioral surveys were planned among participating students and staff during the 2020-2021 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick blood for staff and oral fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study was approved by the United Kingdom Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (reference 22657). Results Data collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals—1891 staff and 4654 students from 59 primary schools and 5852 staff and 10,188 students from 97 secondary schools—participated in at least one survey. Across all survey rounds, staff and student participation rates were 45.2% and 16.4%, respectively, in primary schools and 30% and 15.2%, respectively, in secondary schools. Although primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (3165/7583, 41.7% in round 1 and 2290/10,374, 22.1% in round 6). Although staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals, and from schools in the least deprived locations (in primary schools, 446/4654, 9.6% of participating students were from schools in the least deprived quintile compared with 1262/22,225, 5.7% of eligible students). Conclusions We outline the study design, methods, and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools across a range of settings in England, aims to inform national guidance and public health policy for educational settings. International Registered Report Identifier (IRRID) RR1-10.2196/34075

ObjectivesTo design and test the psychometric properties of four context-specific norm-related scales around handwashing with soap after toilet use: (1) perceived handwashing descriptive norms (HWDN); (2) perceived handwashing injunctive norms (HWIN); (3) perceived handwashing behaviour publicness (HWP); and (4) perceived handwashing outcome expectations (HWOE).DesignScale items were developed based on previous work and pilot tested in an iterative process. Content experts and members of the study team assessed the face validity of the items. The psychometric properties of the scales were assessed in a cross-sectional study.SettingThe study was conducted in communal housing compounds in Abidjan, Côte d’Ivoire.ParticipantsA convenience sample of 201 adult residents (≥16 years old) from 60 housing compounds completed the final questionnaire.Outcome measureConfirmatory factor analysis was used to assess the goodness of fit of the global model. We assessed the internal consistency of each scale using Cronbach’s alpha (α) and the Spearman-Brown coefficient (ρ).ResultsThe results of the psychometric tests supported the construct validity of three of the four scales, with no factor identified for the HWOE (α=0.15). The HWDN and HWP scales were internally consistent with correlations of ρ=0.74 and ρ=0.63, respectively. The HWIN scale appeared reliable (α=0.83).ConclusionWe were able to design three reliable context-specific handwashing norm-related scales, specific to economically disadvantaged community settings in Abidjan, Côte d’Ivoire, but failed to construct a reliable scale to measure outcome expectations around handwashing. The social desirability of handwashing and the narrow content area of social norms constructs relating to handwashing present significant challenges when designing items to measure such constructs. Future studies attempting to measure handwashing norm-related constructs will need to take this into account when developing such scales, and take care to adapt their scales to their study context.

International audience; BackgroundInfluenza surveillance helps time prevention and control interventions especially where complex seasonal patterns exist. We assessed influenza surveillance sustainability in Africa where influenza activity varies and external funds for surveillance have decreased.MethodsWe surveyed African Network for Influenza Surveillance and Epidemiology (ANISE) countries about 2011-2017 surveillance system characteristics. Data were summarized with descriptive statistics and analyzed with univariate and multivariable analyses to quantify sustained or expanded influenza surveillance capacity in Africa.ResultsEighteen (75%) of 24 ANISE members participated in the survey; their cumulative population of 710 751 471 represent 56% of Africa's total population. All 18 countries scored a mean 95% on WHO laboratory quality assurance panels. The number of samples collected from severe acute respiratory infection case-patients remained consistent between 2011 and 2017 (13 823 vs 13 674 respectively) but decreased by 12% for influenza-like illness case-patients (16 210 vs 14 477). Nine (50%) gained capacity to lineage-type influenza B. The number of countries reporting each week to WHO FluNet increased from 15 (83%) in 2011 to 17 (94%) in 2017.ConclusionsDespite declines in external surveillance funding, ANISE countries gained additional laboratory testing capacity and continued influenza testing and reporting to WHO. These gains represent important achievements toward sustainable surveillance and epidemic/pandemic preparedness.

BackgroundTuberculosis (TB) rates in England are among the highest in high-income countries. Poverty and historic and current immigration from high TB incidence parts of the world are two major drivers of tuberculosis in England. However, little has been done in recent years to examine socio-economic trends in TB rates in England, and to disentangle the role of deprivation from that of place of birth in the current TB epidemiology.ObjectivesTo assess the association between England's 2008-2012 TB notification rates and small area-level deprivation, together and separately in the UK-born and foreign-born populations.MethodsEcological analysis of the association between quintiles of England's 2010 Index of Multiple Deprivation (IMD) and TB rates at the Lower-layer Super Output Area (LSOA; average population ~1500) level, using negative binomial and zero-inflated negative binomial regression models, adjusting for age, sex, urban/rural area classification, and area-level percentage of non-White residents.ResultsThere was a log-linear gradient between area-deprivation levels and TB rates, with overall TB rates in the most deprived quintile areas three times higher than the least deprived quintile after adjustment for age and sex (IRR = 3.35; 95%CI: 3.16 to 3.55). The association and gradient were stronger in the UK-born than the foreign-born population, with UK-born TB rates in the most deprived quintiles about two-and-a-half times higher than the least deprived quintile (IRR = 2.39; 95%CI: 2.19 to 2.61) after controlling for age, sex, urban/rural classification and percentage of non-White residents; whereas the comparable figure for foreign-born persons was 80% higher (IRR = 1.78; 95%CI: 1.66 to 1.91).ConclusionsSocio-economic deprivation continues to play a substantial role in sustaining the TB epidemic in England, especially in the UK-born population. This supports the case for further investigations of the underlying social- determinants of TB.

Summary Background Diarrhoeal diseases are an important cause of mortality in children younger than 5 years in sub-Saharan Africa. We aimed to evaluate the effect of three handwashing interventions on handwashing with soap (HWWS) after toilet use. Methods In this cluster randomised trial in Abidjan, Cote d'Ivoire, we randomly assigned communal housing compounds (1:1:1) to receive one of three interventions: a theory of normative social behaviour (TNSB) intervention, including provision of handwashing stations; handwashing stations only; and no intervention. The TNSB intervention was designed to shift the outcome expectation associated with HWWS from health to riddance of faeces-related disgust, and to increase the perceived descriptive norm and perceived handwashing publicness. Participants and fieldworkers were masked to the study objectives. The primary outcome was HWWS after toilet use, assessed at 1 month and 5 months follow-ups. Analysis was by intention to treat. This trial is registered at the Pan African Clinical Trial Registry, PACTR201501000892239. Findings Between April 10 and May 22, 2014, we identified 92 eligible compounds, of which 75 compounds were included. Follow-up data on HWWS were available for 23 compounds for the TNSB group, 25 compounds for the handwashing station-only group, and 25 compounds for the control group. The study ended in April, 2017. Compared with a frequency of 5% (29 of 604 occasions) in the control group, HWWS after toilet use increased to 9% (49 of 557 occasions; adjusted risk ratio 1·89, 95% CI 1·16–3·08) in the handwashing station-only group, and 24% (143 of 588 occasions; 4·82, 3·06–7·59) in the TNSB group, at the 1-month follow-up. The intervention effect was only sustained in the TNSB group (98 [22%] of 450 compounds; 2·68, 1·65–4·34). Interpretation A social norm-based handwashing intervention combined with disgust-inducing messages, with provision of handwashing stations, was effective at increasing HWWS after toilet use. The provision of handwashing stations alone had little effect. Future studies should investigate whether the same approach, when delivered via mass media, can have a similar effect to the face-to-face delivery used in this study. Funding None.

Addressing social determinants of tuberculosis (TB) is essential to achieve elimination, including in low-incidence settings. We measured the association between socio-economic status and intermediate social determinants of health (SDHs, including drug misuse, tobacco smoking and alcohol), and TB, taking into account their clustering in individuals. We conducted a case-control study in 23–38 years old UK-born White adults with first tuberculosis episode, and randomly selected age and sex frequency-matched community controls. Data was collected on education, household overcrowding, tobacco smoking, alcohol and drugs use, and history of homelessness and prison. Analyses were done using logistic regression models, informed by a formal theoretical causal framework (Directed Acyclic Graph). 681 TB cases and 1183 controls were recruited. Tuberculosis odds were four times higher in subjects with education below GCSE O-levels, compared to higher education (OR = 3.94; 95%CI: 2.74, 5.67), after adjusting for other TB risk factors (age, sex, BCG-vaccination and stays ≥3 months in Africa/Asia). When simultaneously accounting for respective SDHs, higher tuberculosis risk was independently associated with tobacco smoking, drugs use (especially injectable drugs OR = 5.67; 95%CI: 2.68, 11.98), homelessness and area-level deprivation. Population Attributable Fraction estimates suggested that tobacco and class-A drug use were, respectively, responsible for 18% and 15% of TB cases in this group. Our findings suggest that socio-economic deprivation remains a driver of tuberculosis in England, including through drugs misuse, tobacco smoking, and homelessness. These findings further support the integration of health and social services in high-risk young adults to improve TB control efforts.

The global burden of bovine tuberculosis (bTB) remains poorly characterized, with spill-over impacts on multiple species. The "One Health" concept is especially relevant given the bidirectional risk of cattle infecting humans with Mycobacterium bovis and humans infecting cattle with Mycobacterium tuberculosis. "Test and cull" is the traditional bTB control method, but the strategy may not be economically feasible or culturally acceptable where cattle are highly prized or their killing is a religious taboo; it is also less effective when there are wildlife reservoirs of infection. Vaccination with M. bovis bacille Calmette-Guerin (BCG) provides protection against bTB, but its use in animals has been limited. The Jerusalem One Health workshop considered key bTB knowledge gaps and innovative solutions. Knowledge gaps identified included (a) the poorly quantified prevalence of M. bovis infection and disease in cattle, domestic camelids and human populations in developing countries, (b) the absence of alternatives to a "test and cull" strategy in settings where the killing of infected animals is culturally or economically unacceptable, or where affected species are protected and (c) an understanding of the induction of mucosal immunity against bTB. We summarize discussions on the use of BCG vaccination in domestic animals and wildlife and list potential projects to address the knowledge gaps identified.

Background Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Methods Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. Results The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Conclusions Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

BackgroundEvidence of protection from childhood BCG against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation.MethodsWe conducted a population-based case-control study of protection by BCG given to children aged 12 to 13 years against tuberculosis occurring 10 to 29 years later. We recruited UK-born white subjects with tuberculosis and randomly sampled white community controls. Hazard ratios and 95% confidence intervals were estimated using case-cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE=1-hazard ratio) was assessed at successive intervals more than 10 years following vaccinationResultsWe obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10-20 years after vaccination, more evident after 20 years. VE 10 -15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently BCG protection appeared to wane; 20-25 years VE=25% (CI -14%, 51%) and 25-29 years VE= 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17% subjects) VE estimated in the same intervals after vaccination were similar (56% (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%).ConclusionsSchool-age BCG vaccination offered moderate protection against tuberculosis for at least 20 years which is longer than previously thought. This has implications for assessing the costeffectiveness of BCG vaccination and when evaluating new TB vaccines.

BackgroundUntil 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.ObjectivesTo assess the duration of protection of infant and school-age BCG vaccination against TB in the UK.MethodsTwo 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.ResultsIn 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 [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.LimitationsThe 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.ConclusionsInfant 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.FundingThe 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.

Although ivermectin treatment can induce serious adverse events (SAEs) in individuals harboring high Loa loa microfilaremia (mf), not all patients with high mf levels develop such reactions, suggesting that cofactors may be involved. A study was conducted in Cameroon to investigate the possible role of Plasmodium coinfection at the time of ivermectin treatment in the development of SAEs. Before their first ivermectin treatment, thick smears were obtained from 4,175 individuals to determine the burden of Plasmodium sp., L. loa, and Mansonella perstans. After treatment, 18 (4.3 per 1,000) patients developed a non-neurologic SAE. Logistic regression analysis, adjusting for age, sex, P. falciparum infection, and M. perstans infection intensities, confirmed that L. loa mf was the main risk factor for SAEs. We found no evidence that coinfection with P. falciparum at the time of ivermectin treatment was associated with the occurrence of Loa-related SAEs in this population.

Investigations of patients with suspected Mycoplasma pneumoniae infection have been undertaken in England since the early 1970s. M. pneumoniae is a respiratory pathogen that is a common cause of pneumonia and may cause serious sequelae such as encephalitis and has been documented in children with persistent cough. The pathogen is found in all age groups, with higher prevalence in children aged 5–14 years. In England, recurrent epidemic periods have occurred at approximately four-yearly intervals. In addition, low-level sporadic infection occurs with seasonal peaks from December to February. Voluntarily reports from regional laboratories and hospitals in England from 1975-2015 were collated by Public Health England for epidemiological analysis. Further data pertaining cases of note and specimens submitted to Public Health England from 2005-2015 for confirmation, molecular typing is included.

Onchocerciasis control is currently based on mass ivermectin treatment. Unfortunately, this drug can induce serious adverse events (SAEs) in persons with high levels of Loa loa microfilaremia (> 30,000 microfilaria/mL). A means of preventing SAEs would be to treat at risk populations with a drug that would progressively reduce the microfilarial loads before administering ivermectin. Antimalarial drugs are a potential solution because they have shown some activity against various filarial species. A controlled trial was conducted to assess the effect of standard doses of quinine, chloroquine, amodiaquine, and artesunate on L. loa microfilaremia. Ninety-eight patients were randomly allocated into five groups (one for each drug and a control group) after stratification on microfilarial load. Loa loa microfilaremia was monitored on days 0, 3, 7, 15, 30, 60, and 90. No significant change in the loads was recorded in any of the treatment groups. A comprehensive review of the effects of antimalarial drugs against filariae is also provided.

Summary Background Little is known about how long the BCG vaccine protects against tuberculosis. We assessed the long-term vaccine effectiveness (VE) in Norwegian-born individuals. Methods In this retrospective population-based cohort study, we studied Norwegian-born individuals aged 12–50 years who were tuberculin skin test (TST) negative and eligible for BCG vaccination as part of the last round of Norway's mandatory mass tuberculosis screening and BCG vaccination programme between 1962 and 1975. We excluded individuals who had tuberculosis before or in the year of screening and those with unknown TST and BCG status. We obtained TST and BCG information and linked it to the National Tuberculosis Register, population and housing censuses, and the population register for emigrations and deaths. We followed individuals up to their first tuberculosis episode, emigration, death, or Dec 31, 2011. We used Cox regressions to estimate VE against all tuberculosis and just pulmonary tuberculosis by time since vaccination, adjusted for age, time, county-level tuberculosis rates, and demographic and socioeconomic indicators. Findings Median follow-up was 41 years (IQR 32–49) for 83 421 BCG-unvaccinated and 44 years (41–46) for 297 905 vaccinated individuals, with 260 tuberculosis episodes. Tuberculosis rates were 3·3 per 100 000 person-years in unvaccinated and 1·3 per 100 000 person-years in vaccinated individuals. The adjusted average VE during 40 year follow-up was 49% (95% CI 26–65), although after 20 years, the VE was not significant (up to 9 years VE [excluding tuberculosis episodes in the first 2 years] 61% [95% CI 24–80]; 10–19 years 58% [27–76]; 20–29 years 38% [–32 to 71]; 30–40 years 42% [–24 to 73]). VE against pulmonary tuberculosis up to 9 years (excluding tuberculosis episodes in the first 2 years) was 67% (95% CI 27–85), 10–19 years was 63% (32–80), 20–29 years was 50% (−19 to 79), and 30–40 years was 40% (−46 to 76). Interpretation Findings are consistent with long-lasting BCG protection, but waning of VE with time. The vaccine could be more cost effective than has been previously estimated Funding Norwegian Institute of Public Health and London School of Hygiene & Tropical Medicine.

Background Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Methodology Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. Principal Findings None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. Conclusions/ Significance The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas., Author Summary Loiasis is a big obstacle for the elimination of onchocerciasis and lymphatic filariasis in Central Africa in areas where loiasis is endemic. In these areas, some subjects who are heavily infected (microfilaraemia > 30 000 microfilariae/ml blood) can develop severe and serious adverse reactions to ivermectin. In rare cases, these have been fatal. A way of preventing these reactions could be to administer a treatment that decreases the microfilareamia in all subjects below the risk level before mass treatment with ivermectin. Building on results of previous studies, this randomised placebo-controlled trial evaluated the efficacy and safety of two or six doses of albendazole administered every two months on the microfilaraemia of Loa loa. Six doses led to a decrease in microfilaraemia by at least 50% for at least four months in 53% of participants. However, it did not reduce the microfilaraemia below the risk level in all participants. Therefore, this regimen has not sufficient efficacy to prevent severe adverse reactions to ivermectin.

BCG uptake among infants in England has not been measured since targeted infant vaccination replaced universal schoolchildren vaccination in 2005, mainly because of the challenges in defining denominators. We estimated uptake between 2006 and 2008 by dividing number of BCG doses administered to infants by number of all live births (where BCG vaccination is universal) or ethnic minority/Eastern Europeans live births (where infant-BCG vaccination is selective). Weighted average uptake was 68% (95% CI 65% to 71%), slightly higher in primary care trusts with universal (72% (95% CI 64% to 80%)) than selective (66% (95% CI 61% to 70%)) policy; and also 13% higher in areas vaccinating in postnatal wards compared with community settings.

Objective: Assess the current BCG vaccination policies and delivery pathways for immunisation in Primary Care Trusts (PCTs) in England since the 2005 change in recommendations. Design: A survey of key informants across PCTs using a standardised, structured questionnaire. Setting: 152 PCTs in England. Results: Complete questionnaires were returned from 127 (84%) PCTs. Sixteen (27%) PCTs reported universal infant vaccination and 111 (73%) had selective infant vaccination. Selective vaccination outside infancy was also reported from 94 (74%) PCTs. PCTs with selective infant policy most frequently vaccinated on postnatal wards (51/102, 50%), whereas PCTs with universal infant vaccination most frequently vaccinated in community clinics (9/13, 69%; p=0.011). To identify and flag up eligible infants in PCTs with targeted infant immunisation, those who mostly vaccinate on postnatal wards depend on midwives and maternity records, whereas those who vaccinate primarily in the community rely more often on various healthcare professionals. Conclusions: Targeted infant vaccination has been implemented in most PCTs across the UK. PCTs with selective infant vaccination provide BCG vaccine via a greater variety of healthcare professionals than those with universal infant vaccination policies. Data on vaccine coverage would help evaluate the effectiveness of delivery. Interruptions of delivery noted here emphasise the importance of not just an agreed, standardised, local pathway, but also a named person in charge.

Background Recurrent epidemics of Mycoplasma pneumoniae infection have been reported in several countries. Factors affecting epidemic frequency and persistence have received little attention in published work. We estimated transmission parameters of M pneumoniae infection and simulated its natural dynamics to explore factors that determine the persistence of epidemic cycles. Methods First, using time-series methods, we analysed laboratory reports of M pneumoniae infections in England and Wales during 35 years, from 1975 to 2009. A linear regression model was fitted to the aggregated data to look for a long-term change in the mean number of reports. We investigated seasonal and non-seasonal cyclic variations by autocorrelation analysis; for this analysis, the time series was log-transformed to reduce the asymmetry between epidemic peaks, and long-term trends (which can dominate or hide other non-stationary parameters in the correlogram) were removed by subtracting the long-term best-fit straight line. We then used a catalytic model to estimate the basic reproduction number (R0; mean number of secondary infections from an infectious individual in a totally susceptible population). A reversible catalytic model describing the age-specific proportion of immune people was fitted to the age-specific IgG seroprevalence data by maximum likelihood to estimate the mean force of infection (rate at which susceptible people are infected) and the duration of immunity; these parameters were used to compute R0. R0 was included in a susceptible–preinfectious–infectious–recovered–(immune) susceptible model to simulate M pneumoniae natural dynamics in the population. The effect on the epidemic cycles of seasonal changes in transmissibility, chance of occurrence of events in individuals (demographic stochasticity), and randomness of environmental factors (environmental stochasticity) were explored. Findings Data from England and Wales showed cyclic epidemics with a mean duration of 18 months, recurring roughly every 4 years. This pattern was superimposed on annual seasonal fluctuations, with highest frequency in the winter and lowest during the summer. The basic reproduction number was estimated at 1·7 (95% CI 1·6–1·9), showing low transmissibility of M pneumoniae . Simulations of M pneumoniae intrinsic dynamics were qualitatively consistent with reported data, suggesting that epidemics would be expected to occur regularly, although the amplitude of epidemic peaks progressively lessened. Numerical experiments suggested that the persistence of epidemic cycles is partly explained by the interaction between the intrinsic dynamics of the infection and randomness in environmental factors that affects its transmissibility. The other factors explored did not affect the overall trend. Interpretation Our analyses propose estimates of M pneumoniae transmission parameters, and our model summarises and integrates present knowledge on its natural history. These simulations suggest that M pneumoniae epidemic cycles are intrinsic to its dynamic and are sustained by the interplay between its deterministic dynamics and randomness in environmental factors affecting its transmissibility. This study has limitations. We used laboratory reports, which are probably skewed to infected individuals with illness severe enough to need medical attention and laboratory testing; this factor underestimates the total number of infections but is unlikely to explain the pattern of recurrent epidemics. The model included simplifying assumptions and did not incorporate age-dependent mixing patterns. Quantitatively comparing model predictions with laboratory reports was also difficult because of large uncertainty around the infection-to-case ratio as well as the case-to-laboratory diagnosis ratio in the population. These factors might affect the magnitude of the simulated epidemics but are unlikely to substantially affect the general trends of epidemic cycles or the inter-epidemic interval. Funding PN-D was funded through a British Chevening Scholarship.

Highlights • Brucellosis is endemically established among dairy herds in West and Central Africa. • Brucella spp. infection is present at high levels in dairy herds in Lomé and Bamako. • Brucellosis poses a public health concern in dairy chains of West and Central Africa. • Brucellosis control programs are urgently needed in West and Central Africa., Ten herd-level cross-sectional studies were conducted in peri-urban dairy production areas of seven West and Central African countries (Burkina Faso, Burundi, Cameroon, Mali, Niger, Senegal and Togo). The objectives were to estimate herd level Brucella spp. seroprevalence and identify risk factors for seropositivity. In each of the ten study areas, herds (between 52 and 142 per area, total = 965) were selected probabilistically and a structured questionnaire was administered to gather information on their structure and management. A bulk milk sample from each herd was tested by indirect ELISA for Brucella spp. For each area, herd seroprevalence estimates were obtained after adjusting for the assumed performance of the diagnostic test. Herd level risk factors for Brucella spp. seropositivity were identified by means of stratified logistic regression, with each peri-urban zone as a stratum. Area-specific models were also explored. Estimated herd seroprevalences were: Lomé (Togo) 62.0% (95% CI:55.0–69.0), Bamako (Mali) 32.5% (95% CI:28.0–37.0), Bujumbura (Burundi) 14.7% (95%CI:9.4–20.8), Bamenda (Cameroon) 12.6% (95% CI:7.6–21.9), Ouagadougou (Burkina Faso) 3.0% (95% CI:1.0–9.1), Ngaoundere (Cameroon) 2.3% (95% CI:1.0–7.0), Thies (Senegal) 1.3% (95% CI:0.1, 5.3), Niamey (Niger) 1.2% (95% CI:0.08-5.3), Dakar (Senegal) 0.2% (95% CI:0.01–1.7) and Niakhar (Senegal)