Effectiveness of Preventive Therapy for Persons Exposed at Home to Drug-Resistant Tuberculosis,Karachi, Pakistan

In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%.     

Extraintestinal Seeding of Salmonella enterica Serotype Typhi,Pakistan

We evaluated Salmonella enterica serotype Typhi strains isolated from all body sites in Pakistan during 2013–2018. Despite an increase in overall number of localized, extensively drug-resistant Salmonella Typhi in organ infections during 2018, there was no increase in the proportion of such isolates in comparison with non–extensively drug-resistant isolates.     

Postoperative thyroid hormone supplementation rates following thyroid lobectomy

BackgroundThyroid lobectomy is performed for symptomatic benign nodules, indeterminate nodules, or low-risk well differentiated thyroid cancer. We aimed to determine factors associated with thyroid stimulating hormone over goal (TH) following lobectomy.MethodsWe performed a retrospective single-institution cohort study of patients undergoing thyroid lobectomy from January 2016 to December 2017. TH was defined as need for thyroid hormone in accordance with guidelines. Univariate and multivariate logistic regression analysis was performed.ResultsOne hundred patients were included and 47% developed.TH73% of those with cancer, 38% with benign pathology (p = 0.002). Patients with TH were more likely to have thyroiditis 26% versus 3.8% (p = 0.002); higher preoperativeTSHmean 1.88mIU/L (SD 1.17) versus 1.16mIU/L (SD 0.77) (p = 0.0002), and smaller remnant thyroid lobe adjusted for body surface area 2.99ml/m2 versus 3.72ml/m2 (p = 0.003).ConclusionsAfter thyroid lobectomy, TH is associated with preoperative TSH level, thyroiditis, remnant thyroid volume, and malignancy. The majority of patients with final pathology of carcinoma will require thyroid hormone supplementation to achieve TSH goal.     

A Case of Large Calcifying Fibroma of Tendo-achilles Managed by En-block Resection and Tendon Reconstruction

Calcifying aponeurotic fibroma is a rare benign fibrous tumor with typical radiological and histopathological features seen in young children and adolescents. It commonly involves the extremities and is characterized by a very high chance of local recurrence. A complete excision of the tumor is considered to be the treatment of choice. We report a case of the tumor involving the substance of achilles tendon and extending up till its insertion in the calcaneum. To the best of our knowledge, this is the largest reported case of calcifying fibroma, with the tumor measuring 10 cm in its largest diameter. The tumor was excised in toto followed by reconstruction of the tendon defect with V-Y plasty of the native tendon and supplemented with semitendinosus and gracilis graft. There was no evidence of recurrence during the follow up period of 1 year.     

Determinants of Hepatitis B Virus (HBV) Infection Among University Students in Central Bangladesh

This study aimed to determine the seroprevalence and determinants of hepatitis B virus (HBV) infection among university students in Bangladesh. This cross-sectional study was conducted among 614 students from five universities in central Bangladesh. Data were collected on demographic information, immunization history, medical and blood transfusion history through the face-to-face interview. Blood samples were collected and screened for anti-HBsAg using ELISA, HBsAg Rapid Test-cassette, and immune chromatographic test. The overall seroprevalence of HBV infection was 5.0%, and vaccination coverage was 19.2% among the participants. Students having a history of surgery (OR 11.004, 95% CI 3.211–37.707), blood transfusion (OR 5.651, 95% CI 0.965–33.068), being married (OR 4.776, 95% CI 1.508–15.127), and not being vaccinated (OR 9.825, 95% CI 1.130–85.367) were at higher risk of being infected by HBV. This study showed the endemicity of HBV infection among the Bangladeshi population. Marriage, surgical or blood transfusion history, not being vaccinated were the determinants of HBV infection within the study population. Public health initiatives for preventing HBV infection at the university levels should be envisaged.

     

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.     

Dengue determinants: Necessities and challenges for universal dengue vaccine development

Dengue illness can range from mild illness to life-threatening haemorrhage. It is an Aedes-borne infectious disease caused by the dengue virus, which has four serotypes. Each serotype acts as an independent infectious agent. The antibodies against one serotype confer homotypic immunity but temporary protection against heterotypic infection. Dengue has become a growing health concern for up to one third of the world's population. Currently, there is no potent anti-dengue medicine, and treatment for severe dengue relies on intravenous fluid management and pain medications. The burden of dengue dramatically increases despite advances in vector control measures. These factors underscore the need for a vaccine. Various dengue vaccine strategies have been demonstrated, that is, live attenuated vaccine, inactivated vaccine, DNA vaccine, subunit vaccine, and viral-vector vaccines, some of which are at the stage of clinical testing. Unfortunately, the forefront candidate vaccine is less than satisfactory, and its performance depends on serostatus and age factors. The lessons from clinical studies depicted ambiguity concerning the efficacy of dengue vaccine. Our study highlighted that viral structural heterogeneity, epitope accessibility, autoimmune complications, genetic variants, genetic diversities, antigen competition, virulence variation, host-pathogen specific interaction, antibody-dependent enhancement, cross-reactive immunity among Flaviviruses, and host-susceptibility determinants not only influence infection outcomes but also hampered successful vaccine development. This review integrates dengue determinants allocated necessities and challenges, which would provide insight for universal dengue vaccine development.     

Characterization of α1-adrenoceptor subtypes mediating contractions to phenylephrine in rat thoracic aorta,mesenteric artery and pulmonary artery

1. The subtype of α₁-adrenoceptor mediating contractions to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery were investigated by use of antagonists which show selectivity between the cloned α₁-adrenoceptor subtypes in binding studies.
2. Cumulative concentration-contraction curves for phenylephrine were competitively antagonized in the rat thoracic aorta by prazosin (pA₂ 9.9), WB4101 (pA₂ 9.6), 5-methylurapidil (pA₂ 8.1), benoxathian (pA₂ 9.2) and indoramin (pA₂ 7.4). These compounds were also competitive antagonists in the mesenteric and pulmonary arteries (except for 5-methylurapidil in the pulmonary artery), (prazosin pA₂ 9.9 and 9.7; WB4101 pA₂ 9.8 and 9.6; 5-methylurapidil pA₂ 7.9 and pK_B estimate 8.0; benoxathian pA₂ 8.8 and 9.3; indoramin pA₂ 7.2 and 7.5, respectively).
3. RS 17053 was not a competitive antagonist in any blood vessel as Schild plot slopes were greater than unity. The pK_B estimates for RS 17053 were 7.1 in aorta, 7.0 in the mesenteric artery and 7.7 in the pulmonary artery.
4. The α_1D-subtype selective antagonist BMY 7378 appeared to be non-competitive with shallow Schild plot slopes. The data were better fitted with two lines in all tissues, with Schild plot slopes that were no longer different from unity, except in the pulmonary artery. The higher affinity site for BMY 7378 in the aorta had a pA₂ of 9.0, while it was 8.8 and 8.9 in the mesenteric and pulmonary arteries, respectively.
5. MDL73005EF acted in a non-competitive manner in all three blood vessels, with shallow Schild plot slopes. The pK_B estimates for MDL73005EF were 8.4 in aorta, 7.5 in the mesenteric artery and 8.0 in the pulmonary artery.
6. In all three blood vessels the functionally determined antagonist affinity estimates correlated best with published pK_i values for their displacement of [³H]-prazosin binding on membranes expressing cloned α_1d-adrenoceptors compared with α_1a- or α_1b-adrenoceptors. The antagonist affinity estimates in the aorta, mesenteric and pulmonary arteries correlated highly with their previously published pA₂ values in rat aorta (α_1D) and less well with those for α_1A- and α_1B-adrenoceptors mediating contraction of the rat epididymal vas deferens and rat spleen, respectively.
7. The results of this study suggest that the contraction to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery are mediated in part via the α_1D-subtype of adrenoceptor. The data for both BMY 7378 and MDL73005EF in all three blood vessels are consistent with receptor heterogeneity. However, the identity of the second site is unclear.