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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 Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. Methods Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. Results During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. Interpretation Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.

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.

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.

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.

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.

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)