| 1. |
- Ikuta, K. S., et al.
(author)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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In: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Journal article (peer-reviewed)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 6. |
- Irum, S., et al.
(author)
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Cutaneous Leishmaniasis (CL) : A Cross-Sectional Community Based Survey on Knowledge, Attitude and Practices in a Highly Endemic Area of Waziristan (KPK Province), Pakistan
- 2021
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In: Acta Tropica. - : Elsevier. - 0001-706X .- 1873-6254. ; 213
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Journal article (peer-reviewed)abstract
- Recent outbreaks of Cutaneous Leishmaniasis (CL) in Waziristan make the disease a public health concern in Khyber Pakhtunkhwa (KPK) province, Pakistan. The awareness and behavior of local community towards the disease is an important factor towards effective control and management of CL in endemic areas of Pakistan. A cross-sectional community based survey was piloted in new emerging district of North Waziristan Agency (KPK province), Pakistan from August 2019- February 2020. The study aimed to examine the Knowledge, Attitude and Practices (KAP) of the local community members regarding CL. The results revealed that majority of the participants were male. Only 48.2% participants have knowledge about CL and the respondents had a moderate knowledge of CL vector and the disease. Few of the respondents were aware that CL is caused by sand flies, their breeding place, biting time, transmission of CL and control measures. Skin infection and sand-flies were the main disease symptoms and disease vector were known to some of the respondents. Most of the respondents showed positive attitude towards disease seriousness and believed that the disease could be cured and can be treated through modern medicines. Admission to hospitals, cleanliness and use of bed nets were the treatment measures for the disease in suspected patients, whereas some believed that the use of bed nets could be helpful in preventing the leishmaniasis. Moderate knowledge of the CL and its transmission in the study area emphasize the need to initiate health education and awareness campaigns to reduce the disease risk and burden in this highly endemic area in near future.
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| 12. |
- Jarde, A, et al.
(author)
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Addressing TB multimorbidity in policy and practice: An exploratory survey of TB providers in 27 high-TB burden countries
- 2022
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In: PLOS global public health. - : Public Library of Science (PLoS). - 2767-3375. ; 2:12, s. e0001205-
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Journal article (peer-reviewed)abstract
- In people with TB, co-existence of long-term conditions (e.g., depression, diabetes and HIV) and risk factors (e.g.,alcohol misuse, malnutrition, and smoking) are associated with increased mortality and poor treatment outcomes including delayed recovery, TB treatment failure and relapse. However, it is unclear as to what extent these comorbidities are addressed in TB policy and practice. Between August and October 2021, we conducted an online cross-sectional survey in high-TB burden countries. We recruited a purposive sample of TB health workers, managers, policy makers, advisors and advocates from these countries. The survey enquired about the extent to which various comorbid conditions are: (a) mentioned in TB policies, plans, and guidelines; (b) screened, diagnosed, treated or referred to specialist services by TB healthcare workers. We summarised using descriptive analysis. Of the 1100 potential respondents contacted in 33 countries, 543 responded but only 446 (41%) from 27 countries provided sufficient data for inclusion in the study. We found no notable differences between these providing insufficient data and those completing the survey. HIV, diabetes mellitus, depression and tobacco and alcohol use disorders were identified as the most common and concerning comorbid conditions in TB. HIV was screened for and managed by TB services in most countries. Screening for diabetes and/or tobacco and alcohol use disorders was offered by almost half of all TB services but only a few offered relevant treatments. Depression was rarely screened for, almost never treated, and only infrequently referred to specialist services. Most respondents felt confident in screening/diagnosing these comorbid conditions but not in treating these conditions. With the exception of HIV, chronic comorbid conditions are only partially screened for and rarely managed within TB services. Mental health conditions are for the most part neglected. Given their adverse impact on TB outcomes, integrating screening and management of these comorbidities within TB programmes offers a significant opportunity to meet TB targets, address non-communicable diseases and improve patient well-being.
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| 15. |
- Naz, S, et al.
(author)
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Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD
- 2019
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In: Metabolites. - : MDPI AG. - 2218-1989. ; 9:10
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Journal article (peer-reviewed)abstract
- Increased activity of indoleamine 2,3-dioxygenase (IDO) and tryptophan hydroxylase (TPH) have been reported in individuals with chronic obstructive pulmonary disease (COPD). We therefore investigated the effect of gender stratification upon the observed levels of tryptophan metabolites in COPD. Tryptophan, serotonin, kynurenine, and kynurenic acid were quantified in serum of never-smokers (n = 39), smokers (n = 40), COPD smokers (n = 27), and COPD ex-smokers (n = 11) by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). The individual metabolite associations with lung function, blood, and bronchoalveolar lavage (BAL) immune-cell composition, as well as chemokine and cytokine levels, were investigated. Stratification by gender and smoking status revealed that the observed alterations in kynurenine and kynurenic acid, and to a lesser extent serotonin, were prominent in males, irrespective of COPD status (kynurenine p = 0.005, kynurenic acid p = 0.009, and serotonin p = 0.02). Inferred serum IDO activity and kynurenine levels decreased in smokers relative to never-smokers (p = 0.005 and p = 0.004, respectively). In contrast, inferred tryptophan hydroxylase (TPH) activity and serotonin levels showed an increase with smoking that reached significance with COPD (p = 0.01 and p = 0.01, respectively). Serum IDO activity correlated with blood CXC chemokine ligand 9 (CXCL9, p = 0.0009, r = 0.93) and chemokine (C-C motif) ligand 4 (CCL4.(p = 0.04, r = 0.73) in female COPD smokers. Conversely, serum serotonin levels correlated with BAL CD4+ T-cells (%) (p = 0.001, r = 0.92) and CD8+ T-cells (%) (p = 0.002, r = −0.90) in female COPD smokers, but not in male COPD smokers (p = 0.1, r = 0.46 and p = 0.1, r = −0.50, respectively). IDO- and TPH-mediated tryptophan metabolites showed gender-based associations in COPD, which were primarily driven by smoking status.
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| 16. |
- Naz, S, et al.
(author)
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Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD
- 2017
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 49:6
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Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence.
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| 17. |
- Nobre, Liana, et al.
(author)
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Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition
- 2020
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In: JCO Precision Oncology. - 2473-4284. ; 3, s. 561-571
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Journal article (peer-reviewed)abstract
- © 2020 by American Society of Clinical Oncology PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy (P, .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively (P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.
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| 20. |
- Reinke, SN, et al.
(author)
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Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study
- 2022
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 59:6
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Journal article (peer-reviewed)abstract
- Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.MethodsBaseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.ResultsA total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.ConclusionsThis is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma.
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| 27. |
- Kalia, Lorraine V, et al.
(author)
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Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease.
- 2015
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:1, s. 100-105
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Journal article (peer-reviewed)abstract
- Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD.
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| 28. |
- Khan, Aisha, et al.
(author)
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Epidemiological and Pathological Characteristics of Cutaneous Leishmaniasis from Baluchistan Province of Pakistan
- 2021
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In: Parasitology. - : Cambridge University Press. - 0031-1820 .- 1469-8161. ; 148:5, s. 591-597
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Journal article (peer-reviewed)abstract
- Cutaneous Leishmaniasis (CL) is considered a neglected tropical disease which in Pakistan can now be considered as growing public health problem. The exact figures on the magnitude of disease are lacking both at national and regional level and only a few health centers are available for diagnosis of CL. The present study was designed to identify the epidemiology of CL infection from August 2018 to December 2019 and to assess clinical aspects of CL in Baluchistan Province of Pakistan. A total of 4072 clinically suspected CL cases were analysed statistically. The highest number of CL cases were reported in May, followed by April, January and then July, February, and June and lowest number of cases were observed in March and November. The highest prevalence rate was found in males where 38% of reported cases were aged 0-9 years. The majority (24.4%) of lesions were found on the hands followed by the face in which cheeks, ears and nose were the effected organs. About 50% of the participants have single lesion while 14% of the participants had two and nearly 3% of the participants have six lesions. The atypical clinical presentations were observed in Baluchistan and common unusual presentations were lupus erythematosus. The study findings suggest that more epidemiological studies and health education campaigns are needed for the population awareness regarding CL in Baluchistan. It is recommended that risk factors should be evaluated to establish the control and management strategies to prevent disease at individual and community level.
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| 29. |
- Nabi, M. H., et al.
(author)
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Low back pain among professional bus drivers : a cross-sectional study from Bangladesh
- 2023
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In: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Journal article (peer-reviewed)abstract
- Background: Low back pain (LBP) is a common condition contributing to impaired quality of life among professional vehicle drivers. Our study aimed to assess LBP prevalence and associated factors among professional bus drivers in Bangladesh. Methods: A cross-sectional study was conducted among 368 professional bus drivers using a semi-structured questionnaire. A Nordic Musculoskeletal Questionnaire (NMQ) subscale was used to measure LBP. Multivariable logistic regression analysis was used to identify the factors associated with LBP. Results: In the last month, 127 (34.51%) participants reported experiencing pain or discomfort in the lower backside. Multivariable logistic regression analysis showed that age of more than 40 years (adjusted odds ratio (aOR): 2.07, 95% confidence interval (CI): 1.14 to 3.75), the income of more than 15,000 BDT per month (aOR: 1.91, 95% CI: 1.11 to 3.26), work duration more than ten years (aOR: 2.53, 95% CI: 1.12 to 5.70), working more than 15 days per month (aOR: 1.93, 95% CI: 1.02 to 3.65), working more than 10 h per day (aOR: 2.46, 95% CI: 1.05 to 5.75), poor condition of the driving seat (aOR: 1.80, 95% CI: 1.08 to 3.02), current smoking habit (aOR: 9.71, 95% CI: 1.25 to 75.15), illicit substances use (aOR: 1.97, 95% CI: 1.11 to 3.48), and four hours or less sleeping time per day (aOR: 1.83, 95% CI: 1.09 to 3.06) were positively associated with LBP. Conclusion: The high burden of LBP among the participants calls for a focus on this vulnerable group's occupational health and safety, with particular emphasis on implementing standard measures.
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| 32. |
- Reinke, SN, et al.
(author)
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Metabolomics analysis identifies different metabotypes of asthma severity
- 2017
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 49:3
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Journal article (peer-reviewed)abstract
- In this study, we sought to determine whether asthma has a metabolic profile and whether this profile is related to disease severity.We characterised the serum from 22 healthy individuals and 54 asthmatics (12 mild, 20 moderate, 22 severe) using liquid chromatography–high-resolution mass spectrometry-based metabolomics. Selected metabolites were confirmed by targeted mass spectrometry assays of eicosanoids, sphingolipids and free fatty acids.We conclusively identified 66 metabolites; 15 were significantly altered with asthma (p≤0.05). Levels of dehydroepiandrosterone sulfate, cortisone, cortisol, prolylhydroxyproline, pipecolate and N-palmitoyltaurine correlated significantly (p<0.05) with inhaled corticosteroid dose, and were further shifted in individuals treated with oral corticosteroids. Oleoylethanolamide increased with asthma severity independently of steroid treatment (p<0.001). Multivariate analysis revealed two patterns: 1) a mean difference between controls and patients with mild asthma (p=0.025), and 2) a mean difference between patients with severe asthma and all other groups (p=1.7×10−4). Metabolic shifts in mild asthma, relative to controls, were associated with exogenous metabolites (e.g. dietary lipids), while those in moderate and severe asthma (e.g. oleoylethanolamide, sphingosine-1-phosphate, N-palmitoyltaurine) were postulated to be involved in activating the transient receptor potential vanilloid type 1 (TRPV1) receptor, driving TRPV1-dependent pathogenesis in asthma.Our findings suggest that asthma is characterised by a modest systemic metabolic shift in a disease severity-dependent manner, and that steroid treatment significantly affects metabolism.
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| 33. |
- Shahzadi, I., et al.
(author)
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Hydrothermal Synthesis of Fe-Doped Cadmium Oxide Showed Bactericidal Behavior and Highly Efficient Visible Light Photocatalysis
- 2023
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In: ACS Omega. - 2470-1343. ; 8:33, s. 30681-30693
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Journal article (peer-reviewed)abstract
- Cationic dyes presentin industrial effluents significantlyreducethe effectiveness of remediation operations. Considering the terribleimpact of these pollutants on environment and biodiversity, investigatingstrategies to remove potentially harmful compounds from water is becomingan increasingly intriguing issue. In this work, we employed a simplehydrothermal technique to synthesize Fe-doped CdO (2, 4, and 6 wt%) nanostructures and assessed their efficacy in degrading methyleneblue (MB) dye and inhibiting the growth of Staphylococcusaureus and Escherichia coli, respectively. Structural, morphological, and optical characterizationof produced nanomaterials was also performed using X-ray diffraction,TEM, and UV absorption spectra. The photocatalytic decomposition ofMB was significantly enhanced (58.8%) by using Fe (6 wt %)-doped CdOcatalysts for 80 min under irradiation. In addition, 2.05-5.05mm inhibitory zones were seen against Gram-positive bacteria (S. aureus), whereas the range for Gram-negative bacteria(E. coli) was 1.65-2.75 mm.These nanostructures were shown to be very effective inhibitors ofbeta-lactamase, d-alanine-d-alanine ligase B, andfatty acid synthase inhibitor by in silico molecular docking investigations.
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| 34. |
- Thobani, Rozina S., et al.
(author)
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Field evaluation of typhoid conjugate vaccine in a catch-up campaign among children aged 9 months to 15 years in Sindh, Pakistan
- 2022
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In: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 40:36, s. 5391-5398
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Journal article (peer-reviewed)abstract
- Background: Typhoid conjugate vaccine (TCV) has recently been introduced in the expanded program for immunization (EPI) in Pakistan. Before its introduction in routine immunization, a onetime catchup cam-paign among children 9 months to 15 years old was conducted in November 2019. We performed field evaluation of TCV against culture confirmed Salmonella Typhi (S. Typhi) among 9 months to 15 years old children during the catch up campaign in Karachi and Hyderabad.Methods: A rapid assessment of blood culture confirmed S. Typhi was performed. Age eligible cases of culture confirmed S. Typhi were identified from the laboratory networks of Aga Khan University Hospital Karachi and Hyderabad, Kharadar General Hospital Karachi, and Liaqat University of Medical & Health Sciences (LUMHS) Hyderabad. Information on sociodemographic, typhoid vaccination history and antimicrobial resistance was collected using a structured questionnaire.Patient medical records and lab reports were also reviewed to collect information on diagnosis and antimicrobial susceptibility information. Information about the population vaccination coverage during catch-up campaign was obtained from the provincial EPI office. Field performance of TCV in catchup cam-paign was measured by calculating the effectiveness using rapid screening method which is less resource-intensive technique of calculating vaccine effectiveness (VE). Results: Overall, 968 culture confirmed typhoid cases were enrolled. Among them, 82% (793/968) were from Karachi and 18% (175/968) from Hyderabad. The average age of the participants was 5.68 years, and 54% (523/968) were male. 6% (62/968) of the culture confirmed S. Typhi cases were multidrug resis-tant (MDR), and 61% (586/968) were extensively drug resistant (XDR). The VE using the TCV coverage data provided by EPI was 98%. Conclusion: TCV is effective against culture confirmed S. Typhi among children aged 9 months to 15 years in the catch-up campaign setting. While typhoid vaccination can significantly decrease the burden of typhoid disease, improvements in sanitation and hygiene are necessary for the prevention of spread of enteric fever. Longer term follow up will be needed to assess the duration of protection and requirement for booster doses of TCV.(c) 2022 Elsevier Ltd. All rights reserved.
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| 35. |
- ul Ain, N, et al.
(author)
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Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant
- 2018
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In: Journal of medical genetics. - : BMJ. - 1468-6244 .- 0022-2593. ; 55:6, s. 403-407
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Journal article (peer-reviewed)abstract
- Heterozygous mutations in COL10A1 underlie metaphyseal chondrodysplasia, Schmid type (MCDS), an autosomal dominant skeletal dysplasia.ObjectiveTo identify the causative variant in a large consanguineous Pakistani family with severe skeletal dysplasia and marked lower limb deformity.MethodsWhole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. In silico variant pathogenicity predictions and amino acid conservation analyses were performed.ResultsA homozygous c.133 C>T (p.Pro45Ser) variant was identified in COL10A1 in all six severely affected individuals (adult heights 119–130 cm, mean ~−6.33 SD). The individuals heterozygous for the variant had mild phenotype of short stature (adult heights 140–162 cm, mean ~−2.15 SD) but no apparent skeletal deformities. The variant was predicted to be pathogenic by in silico prediction tools and was absent from public databases and hundred control chromosomes. Pro45 is conserved in orthologues and is located in the non-collagenous 2 domain of COL10A1, variants of which have never been associated with skeletal dysplasia.ConclusionsThis first report of individuals with a homozygous variant in COL10A1 defines a new type of autosomal recessive skeletal dysplasia. The observations in COL10A1 variant carriers suggest a phenotypic overlap between the mildest forms of MCDS and idiopathic short stature.
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