Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

BACKGROUND: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. OBJECTIVE: Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). METHODS: Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. RESULTS: We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. CONCLUSION: The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.

Combined Retrospective-Prospective Cohort Study to Know the Risk of Sensorineural Hearing Loss in Patients of Drug Resistant TB Receiving Anti Tuberculous Treatment (ATT) at Tertiary Care Centre in South Gujarat.

Combined retrospective-prospective cohort study was done to know the risk of sensorineural hearing loss in patients of drug resistant Tuberculosis (TB) receiving Anti Tuberculous Treatment (ATT) at tertiary care centre in South Gujarat. Study was done by using retrospective and prospective data of the patients of drug resistant TB of NCHS who received injectable ATT and referred by department of Respiratory Medicine to ENT department for purpose of hearing evaluation pre and post treatment (Case cohort). Age and sex matched control cohort was also used which includes patients of non-drug resistant TB who were not receiving Injectable ATT. Incidence of SNHL in patients taking ATT for drug resistant tuberculosis in our study was 33.9%. The Relative Risk of SNHL was 14.3%. The Attributable Risk of SNHL (preventable SNHL) was 93%.

Cancer incidence among pesticide applicators exposed to permethrin in the Agricultural Health Study.

BACKGROUND: Permethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens. OBJECTIVE: In this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS). METHODS: A total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993-1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure. RESULTS: We found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76-11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41-10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups. CONCLUSIONS: This study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation.

Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study.

BACKGROUND: Chlorothalonil is a broad spectrum, non-systemic fungicide widely used to control diseases affecting over 50 fruit, vegetable, and agricultural crops. Despite its extensive use for over 30 years, little is known about the potential human carcinogenicity associated with the routine application of chlorothalonil. Rodent studies have shown evidence of renal tubular carcinomas and adenomas. We explored cancer incidence with chlorothalonil exposure using data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. METHODS: Licensed private and commercial pesticide applicators were recruited into this study from 1993 to 1997. Detailed information regarding pesticide use was obtained via self-administered questionnaires. Cancer incidence was followed through December 31, 2004. Chlorothalonil exposure was classified by lifetime exposure days and intensity-weighted lifetime exposure days, and then categorized into tertiles. The intensity-weighted lifetime exposure days metric was calculated based on a complex algorithm which includes pesticide application methods among other factors. This may increase or decrease exposure. RESULTS: Of the 47,625 pesticide applicators included in this analysis, 3657 applicators reported using chlorothalonil with a median of 3.5 application days per year. Chlorothalonil was not associated with overall cancer incidence, nor did we find any association with colon, lung, and prostate cancers--the only cancers for which we had sufficient numbers to explore associations. CONCLUSION: We did not find any strong evidence for an association between chlorothalonil and the cancers investigated. Although animal studies have suggested renal cancer may be associated with chlorothalonil, we had insufficient data to evaluate this cancer.

Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study.

OBJECTIVE: Captan is a widely used antifungal pesticide whose potential to cause cancer in humans is uncertain. METHODS: We evaluated the incidence of cancer among pesticide applicators exposed to captan in the Agricultural Health Study. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered enrollment questionnaires completed between 1993 and 1997. RESULTS: Of the 48,986 applicators enrolled 4,383 (9%) had applied captan. Median follow-up time was 9.14 years. Poisson regression analysis was used to estimate relative risks (RR) for cancer subtypes by tertiles of captan exposure. We investigated risk for all cancers combined and sites of cancer for which at least 15 cases occurred among captan-exposed applicators. These sites included cancers of the prostate, lung, and colon, blood-related cancers, and colorectal cancers. During follow-up 2,912 incident primary cases of cancer were identified. No association between the highest tertile of captan exposure (>67.375 intensity-weighted days) and development of all cancers (RR = 0.89; 95% CI, 0.71-1.13) or cancer of any specific site was observed. CONCLUSION: Although our study is limited by low numbers of observed cancer cases and follow-up time of 9.14 years, it does not provide evidence of an increased risk for the development of cancer at the investigated sites.