Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Pulmonary Versus Extrapulmonary Tuberculosis Associated Factors: A Case-Case Study.

BACKGROUND: Tuberculosis (TB) incidence remains low in health departments of Castellon and La Plana-Vila-real, but TB elimination is challenging. The objective of this study was to estimate associated factors of pulmonary tuberculosis (PTB) compared with extrapulmonary tuberculosis (ETB) and investigate epidemiological characteristics of these pathologies to orient control and prevention actions. MATERIALS AND METHODS: A prospective case-case study was implemented by comparing PTB and ETB incidences during 2013-2016 from notification reports, epidemiological surveillance, and microbiological results of hospitals' laboratories Hospital General Castellon and La Plana-Vila-Real in the province of Castellon of Valencia region in Spain. In this design, cases were patients with PTB and controls were patients with ETB. Directed acyclic graph approach was used for selection of potential risk and confounding factors. Adjusted odds ratios (AORs) were estimated by logistic regression models. RESULTS: The study included 136 patients with PTB and 57 patients with ETB, with microbiological confirmation of 93.4% and 52.6%, and the annual median of incidence rates were 7.5 and 3.1 per 100 000 inhabitants, respectively. In general, patients with PTB were younger with higher male proportion than patients with ETB. Risk factors of PTB were smoking tobacco (AOR = 3.98; 95% confidence interval [CI] = 1.66-9.56), social problems (social marginalization, homeless, residence in shelters for the poor, or stay in prison) (AOR = 3.39; 95% CI = 1.05-10.94), and contact with patients with TB (AOR = 2.51; 95% CI = 1.06-5.95). No-smoking tobacco and no-drug abuse interaction decrease PTB risk (AOR = 0.27; 95% CI = 0.12-0.64). From these results, specific measures of health promotion and prevention can be addressed. CONCLUSIONS: The estimated associated factors of PTB may be prevented, and it was demonstrated that the case-case design is useful in the study of TB.

Descriptive epidemiology of Yersinia enterocolitica infection in a high-incidence area over an 8-year period, 2006-2013. EDICS project. / Epidemiología descriptiva de infección por Yersinia enterocolitica en un área de alta incidencia durante 8 años, 2006-2013. Proyecto EDICS.

Descriptive epidemiology of Yersinia enterocolitica infection in an area of Castellón (Spain) between 2006 and 2013 from Yersinia enterocolitica strains isolated in the area and confirmed by the Spanish national reference laboratory. There were a total of 144 cases. The estimated incidence was 9.7 cases per 105 person-year. The age group most affected was 0-4 years (rate 110.3 per 105 p-y), with a maximum in infants aged 6 to 11 months of age (190.4 per 105 p-y). The average duration of the disease was 15.5 days. 7% of the patients were hospitalised. Only 2 outbreaks of a family nature related to the consumption of pork were detected. The temporal evolution reflects higher incidence during the winter season (January). The most common exposure factor among the cases was the consumption of dried pork sausage (50% of the cases interviewed). The 58 typed strains were all of the biotype 4, serotype O:3, except one O:9. We distinguished 21 pulsotypes grouped in 8 clusters with a similarity of 97%. Over a number of years, a substitution of some pulsotypes for others was observed. Yersiniosis has a high incidence in our area, with a clear seasonality of winter predominance. It affects very young children, in particular. The strains are of the same serotype, but the variety of pulsotypes changed over time. As an exposure factor for further analytical studies, the consumption of some pork products is proposed, without ruling out other factors.

Comparison of sporadic cases of Salmonella Typhimurium with other Salmonella serotypes in Castellon (Spain): case-case study.

INTRODUCTION: Salmonella infections (SI) are common in Spain. The aim of this study was to appraise risk factors and the clinical characteristics of sporadic Salmonella Typhimurium infections compared with other sporadic salmonella serotype infections (OSI). METHODS: From September 2014 to August 2015, a case-case study was carried out by the Epidemiology Division of the Public Health Centre of Castellon. Case 1 consisted of patients with sporadic S. Typhimurium infections, while case 2 comprised OSI patients, assessed according to the stool cultures analyzed by the Microbiology Laboratories of Hospital General de Castellon and Hospital de La Plana in Vila-real. Patients from detected outbreaks were not included. The salmonella serotype was identified by the National Centre of Microbiology (Madrid). RESULTS: The total number of SI patients reported was 327, 242 of whom were studied (74.0%). 148 patients had sporadic S. Typhimurium infection and 64 had OSI, with median ages of 4 and 8.5 years, respectively. Sporadic S. Typhimurium infection patients presented more blood in feces and diarrhea episodes. Consumption of pork meat (OR=2.22; 95% CI 1.12-4.43), cold pork meats (OR=2.49; 95% CI 1.32-4.68) and playing in the dirt (OR=3.02; 95% CI 1.55-5.88), were associated with sporadic S. Typhimurium infection. In the 0-4 year-old group, the associated factors were consumption of cold pork meats, omelets and female gender. In the 5-year-old and over group, only playing in soil was associated with sporadic S. Typhimurium infection. CONCLUSIONS: The consumption of pork and omelets, as well as playing in the dirt, were the main factors associated with infection. Children were most affected by sporadic S. Typhimurium infection.

Reactive arthritis and other musculoskeletal sequelae following an outbreak of Salmonella hadar in Castellon, Spain.

OBJECTIVE: In 2005 a large outbreak of Salmonella hadar occurred in Spain following the consumption of commercial precooked roast chicken. We estimated the incidence and risk factors for reactive arthritis (ReA) and other musculoskeletal sequelae in the patients of this outbreak in 2 health departments of Castellon province. METHODS: A prospective cohort study of the patients and their families was carried out. Clinical infection with Salmonella was considered as the exposure factor. The cohort was studied for ReA symptoms using a telephone questionnaire. Telephone interviews or medical examinations of subjects with musculoskeletal symptoms were conducted by a rheumatologist. Robust Poisson regression models were used in the analysis. RESULTS: From the cohort of 262 people, 248 (94.7%) participated in the telephone survey, 155 with clinical salmonellosis (infected), 78 noninfected, and 15 with some symptoms but not clinical salmonellosis. One hundred one infected patients (65%) reported musculoskeletal symptoms, compared to 19 noninfected (24%) (adjusted relative risk = 2.60, 95% CI 1.73-3.90). Of the infected group, 16 ReA (incidence 10%, 95% CI 6.0-16.2), 7 enthesopathies, and 2 arthralgias were detected, and zero in the noninfected group. The risk factors for ReA were age, weight loss, and duration of diarrhea. Antibiotic treatment for the infection protected against symptoms of peripheral or axial arthritis (adjusted relative risk = 0.73, 95% CI 0.55-0.98). CONCLUSION: The incidence of ReA and musculoskeletal symptoms after the infection was high. The use of antibiotics for S. hadar infection offered some protection against musculoskeletal symptoms.

Risk factors and prevalence of asthma in schoolchildren in Castellon (Spain): a cross-sectional study.

BACKGROUND: Research on potential risk factors of asthma can enhance our understanding of geographic differences and inform decisions on preventive strategies. METHODS: In 2002, a cross-sectional population-based study was carried out in the area of Castellon (Spain), following the International Study of Asthma and Allergies in Childhood (ISAAC) Phase III methodology. Asthma symptoms and related risk factor questionnaires were completed by parents of 6-7 year-old schoolchildren. Logistic regression was used in the analysis. RESULTS: Participation rate was 88 % (4492 of 4872 schoolchildren). Prevalence of wheeze in the past year, asthma ever, and physician-diagnosed asthma were 8 %, 7 % and 6 %, respectively. Risk factors independently associated with all three asthma case definitions were history of bronchitis or pneumonia, allergic rhinitis, family members with atopic disease, and residing in an industrialised area. Risk factors for asthma ever and physician-diagnosed asthma were male sex, atopic eczema and presence of a dog at home; exclusive breast-feeding and the presence of another animal (not a dog or cat) were protective factors. Maternal age was inversely related to physician-diagnosed asthma. Residence in an area of heavy truck traffic and the father smoking at home were associated with asthma ever. Risk factors for wheeze in the past year were low social class, history of sinusitis and the father smoking at home. CONCLUSIONS: Environmental factors are related to the presence of asthma. Preventive measures should be directed to improving air pollution, promoting breast-feeding and reducing smoking in the home.

Varicella vaccine effectiveness during an outbreak in a partially vaccinated population in Spain.

BACKGROUND: An outbreak of varicella occurred between December 2004 and April 2005 in the primary school and day-care center of a town of 5430 inhabitants in Spain. Although the varicella vaccine is not included in the infant vaccination program, some children had been vaccinated before the outbreak. STUDY AIM: The aim of this study was to estimate varicella vaccine effectiveness during an outbreak that took place in a partially vaccinated population of children. METHODS: A cohort study was carried out. Cases were identified through notification by doctors and active search. Information was gathered on the current disease, history of varicella and previous vaccinations together with age, course, school year and other sociodemographic factors. The relative risk (RR) of varicella and the contribution of the previously mentioned factors to the probability of contracting the disease was estimated for vaccinated and unvaccinated children. RESULTS: Participation reached 96.5% (387 of 401 children) in the school and 91.2% (31 of 34 children) in the day-care center. Of 269 children with no history of varicella and with a documented vaccination record, 96 (35.7%) had been previously vaccinated. During the outbreak, 148 cases of varicella were observed. The overall attack rate was 54.4%, 22.9% in vaccinated and 72.8% in unvaccinated children. RR of varicella in vaccinated children was 0.31 (95% confidence interval [CI] = 0.21-0.46). The overall adjusted vaccine effectiveness against varicella was 69.5% (95% CI = 50.5-81.5%) and 96.9% (95% CI = 77.5-99.6%) against mild and severe forms. Only time since vaccination was associated with vaccine failure. CONCLUSIONS: In the varicella outbreak studied, we conclude that vaccine was effective in the prevention of the disease, particularly in its moderate and severe forms, but because the proportion of vaccinated children was low, an outbreak still occurred.