Relationship between aging and control of metabolic syndrome with telomere shortening: a cross-sectional study.

Aging is considered one of the major risk factors for several human disorders. The telomere plays a crucial role in regulating cellular responsiveness to stress and growth stimuli as well as maintaining the integrity of the Deoxyribonucleic Acid (DNA), and aging leads to the progressive decline in the telomere length (TL) due to continuous cell division. The aim of this study was to determine the relationship between TL and advancing age and the impact of metabolic syndrome (MetS) on TL. Firstly, we determined the association of advancing age and TL, by measuring telomere length (T/S ratio) in healthy volunteers (n = 90). The TL was compared between normal population and patients with metabolic syndrome (n = 298). The age matched controlled and uncontrolled MetS patients (n = 149) were also compared for their TL T/S ratio. The TL showed negative correlation with advancing age, whereas the significant change was observed at the cut-offs of 40 and 70 years defining 40 with longer TL and 70 as shorter TL. The longest T/S ratio at 2.46 was measured at the age range of 1 year in healthy volunteers, while elderly population showed considerably shorter TL. The patients older than 60 years with poor or uncontrolled MetS had shorter TL, as compared to the controlled MetS. In conclusion our findings suggest that TL was negatively correlated with advancing age. Uncontrolled metabolic syndrome appeared to have worsening effects on TL. Telomere length appears to have potential to be used a parameter to determine age. However, further large scale studies are recommended to make firm guidelines.

Multimorbidity and Its Effect on Self-Reported Adverse Effects Following COVID-19 Vaccination.

Introduction The coronavirus disease 2019 (COVID-19) vaccination has been suggested for those with comorbidities, although there are concerns regarding the vaccine's safety. This study aimed to compare the severity and incidence of post-vaccination side effects in people with and without comorbidities. Another aim of this study was also to look for the effect of multimorbidity on adverse events. Methods This observational study was conducted from November 2021 to February 2022. Data were collected from all over Pakistan using a self-administered online questionnaire that inquired about the subject's demographic, clinical, and COVID-19 vaccination profiles. Data analysis was done by using SPSS software version 22.0. (Chicago, IL, IBM Corp.). Results A total of 421 participants were included in the study, and 31.4% of individuals had underlying comorbidity. The overall mean age was 33 years (range: 13-85 years). This study included recipients of all major types of COVID-19 vaccines being used in Pakistan. Only 67.4% of the subjects had only underlying comorbidity, and hypertension was the most common one out of all comorbidities. Participants with comorbidities were not at a greater risk to produce vaccine-related adverse events when compared to those with no comorbidities. Comorbidity was also found to be statistically non-significant to the severity of the side effects. Only one subject with comorbidity produced a side effect and required hospitalization. Multimorbidity was not associated with a greater incidence of side effects. Multimorbidity was not significantly linked with the severity of the adverse effects, except muscle pain (p<0.05) and breathlessness (p<0.05). Conclusion It can be concluded that comorbidities do not affect the COVID-19 vaccine's reactogenicity but studies on an extensive scale should be conducted regarding individuals with multiple pre-existing comorbidities.

Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan.

INTRODUCTION: In April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children. It was assumed that the outbreak originated from a single source, namely a doctor at a private health facility. In this study, we performed subtype distribution, phylogenetic and drug-resistance analysis of HIV-1 sequences from 2019 outbreak in Larkana, Pakistan. METHODS: A total of 401 blood samples were collected between April-June 2019, from children infected with HIV-1 aged 0-15 years recruited into a case-control study to investigate the risk factors for HIV-1 transmission. Partial HIV-1 pol sequences were generated from 344 blood plasma samples to determine HIV-1 subtype and drug resistance mutations (DRM). Maximum-likelihood phylogenetics based on outbreak and reference sequences was used to identify transmission clusters and assess the relationship between outbreak and key population sequences between and within the determined clusters. Bayesian analysis was employed to identify the time to the most recent common recent ancestor (tMRCA) of the main Pakistani clusters. RESULTS: The HIV-1 circulating recombinant form (CRF) 02_AG and subtype A1 were most common among the outbreak sequences. Of the treatment-naïve participants, the two most common mutations were RT: E138A (8%) and RT: K219Q (8%). Four supported clusters within the outbreak were identified, and the median tMRCAs of the Larkana outbreak sequences were estimated to 2016 for both the CRF02_AG and the subtype A1 clusters. Furthermore, outbreak sequences exhibited no phylogenetic mixing with sequences from other high-risk groups of Pakistan. CONCLUSION: The presence of multiple clusters indicated a multi-source outbreak, rather than a single source outbreak from a single health practitioner as previously suggested. The multiple introductions were likely a consequence of ongoing transmission within the high-risk groups of Larkana, and it is possible that the so-called Larkana strain was introduced into the general population through poor infection prevention control practices in healthcare settings. The study highlights the need to scale up HIV-1 prevention programmes among key population groups and improving infection prevention control in Pakistan.

Evaluation of C-reactive protein and hematological parameters in smokeless tobacco users: A comparative cross-sectional study.

OBJECTIVE: To investigate the changes in levels of C-reactive protein (CRP) and hematological parameters among smokeless tobacco (SLT) users. METHODS: A comparative cross-sectional study was conducted at the community level in the coastal districts of Sindh province namely Badin, Thatta, and Sujawal from January 2017 to December 2019. The CRP and hematological parameters were evaluated by well-established methods among SLT and non-SLT users. RESULTS: There was a statistically significant difference between SLT users (mean CRP = 0.77) versus non-users (mean CRP = 0.18), p = <0.001. Among hematological parameters, white blood cells (SLT users median = 7.85 versus non-SLT users median = 8.50, p = 0.004), monocytes (SLT users median = 6.00 versus non-SLT users median = 6.00, p = 0.001) and erythrocyte sedimentation rate (SLT users median = 15.00 versus non-SLT users median = 10.00, p = 0.006) showed statistically significant difference. CONCLUSIONS: Significantly elevated CRP was observed in SLT users similarly hematological parameters also showed changes. WBCs, monocytes and ESR were significantly deranged among SLT users. Further studies looking into long term effects of these changes would be helpful.

Factors associated with HIV infection among children in Larkana District, Pakistan: a matched case-control study.

BACKGROUND: In April, 2019, an HIV outbreak predominantly affecting children occurred in Larkana District, Sindh, Pakistan. By December, 2019, 881 (4·0%) of 21 962 children screened for HIV had tested positive. We aimed to assess factors associated with HIV infection in this outbreak. METHODS: In this individually matched case-control study, we sampled 406 cases (individuals aged <16 years who had registered for paediatric HIV care at the HIV Treatment Centre at Shaikh Zayed Children's Hospital in Larkana City, Pakistan) and 406 controls (individuals without HIV matched by age, sex, and neighbourhood residence, recruited through doorknocking at houses adjacent to case participants). An interviewer-administered questionnaire was used to collect data on possible risk factors for HIV acquisition and a blood sample was collected from all participants for hepatitis B and hepatitis C serology. Mothers of all participants underwent HIV testing. Odds ratios were estimated using conditional logistic regression to assess factors associated with HIV infection. FINDINGS: 406 case-control pairs were recruited between July 3 and Dec 26, 2019. Five pairs were excluded (three pairs had an age mismatch and two pairs were duplicate cases) and 401 were analysed. The prevalence of hepatitis B surface antigen was 18·2% (95% CI 14·5-22·3) among cases and 5·2% (3·3-7·9) among controls, and the prevalence of hepatitis C antibodies was 6·5% (95% CI 4·3-9·4) among cases and 1·0% (0·3-2·5) among controls. 28 (7%) of 397 mothers of cases for whom we had data, and no mothers of 394 controls, were HIV positive. In the 6 months before recruitment, 226 (56%) of 401 cases and 32 (8%) of 401 controls reported having more than ten injections, and 291 (73%) cases and 78 (19%) controls had received an intravenous infusion. At least one blood transfusion was reported in 56 (14%) cases and three (1%) controls in the past 2 years. HIV infection was associated with a history of more injections and infusions (adjusted odds ratio 1·63; 95% CI 1·30-2·04, p<0·0001), blood transfusion (336·75; 23·69-4787·01, p<0·0001), surgery (399·75, 13·99-11 419·39, p=0·0005), the child's mother being HIV positive or having died (3·13, 1·20-8·20, p=0·020), and increased frequency of private clinic (p<0·0001) and government hospital visits (p<0·0001), adjusting for confounders. INTERPRETATION: The predominant mode of HIV transmission in this outbreak was parenteral, probably due to unsafe injection practices and poor blood safety practices. General practitioners across Pakistan need training and systems support in reducing injection use, and in providing safe injections and transfusions only when necessary. FUNDING: Department of Pediatrics and Child Health, the Aga Khan University, Karachi, Pakistan.

Investigation of an extensive outbreak of HIV infection among children in Sindh, Pakistan: protocol for a matched case-control study.

INTRODUCTION: In April 2019, 14 children were diagnosed with HIV infection by a private healthcare provider in Larkana district, Sindh province, Pakistan. Over the next 3 months, 930 individuals were diagnosed with HIV, >80% below 16 years, the largest ever outbreak of HIV in children in Pakistan. In this protocol paper, we describe research methods for assessing likely modes of HIV transmission in this outbreak and investigate spatial and molecular epidemiology. METHODS AND ANALYSIS: A matched case-control study will be conducted with 406 cases recruited. Cases will be children aged below 16 years registered for care at the HIV treatment centre at Shaikh Zayed Children Hospital in Larkana City. Controls will be children who are HIV-uninfected (confirmed by a rapid HIV test) matched 1:1 by age (within 1 year), sex and neighbourhood. Following written informed consent from the guardian, a structured questionnaire will be administered to collect data on sociodemographic indices and exposure to risk factors for parenteral, vertical and sexual (only among those aged above 10 years) HIV transmission. A blood sample will be collected for hepatitis B and C serology (cases and controls) and HIV lineage studies (cases only). Mothers of participants will be tested for HIV to investigate the possibility of mother-to-child transmission. Conditional logistic regression will be used to investigate the association of a priori defined risk factors with HIV infection. Phylogenetic analyses will be conducted. Global positioning system coordinates of participants' addresses will be collected to investigate concordance between the genetic and spatial epidemiology. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Review Committee of the Aga Khan University, Karachi. Study results will be shared with Sindh and National AIDS Control Programs, relevant governmental and non-governmental organisations, presented at national and international research conferences and published in international peer-reviewed scientific journals.

HIV infection predominantly affecting children in Sindh, Pakistan, 2019: a cross-sectional study of an outbreak.

BACKGROUND: In April 2019, an HIV screening camp for all ages was established in response to a report of an unusually large number of paediatric HIV diagnoses in Larkana, Pakistan. We aimed to understand the clinical profile of the children who registered for HIV care. METHODS: In this cross-sectional study, we review the outbreak response from the government, academia, and UN agencies in Larkana, Sindh, Pakistan. We report age-stratified and sex-stratified HIV prevalence estimated among individuals screened. For children who registered for HIV care, clinical history of previous injections and blood transfusions, HIV disease stage, hepatitis B and hepatitis C status, and CD4 count was abstracted from clinical records from Sindh AIDS Control Program HIV Clinic (Shaikh Zayed Childrens Hospital, Larkana, Pakistan) and analysed using percentages, χ2 tests, and weight-for-age Z scores. We also analysed data for parents who were tested for HIV. FINDINGS: Between April 24, and July 15, 2019, 31 239 individuals underwent HIV testing, of whom 930 (3%) tested positive for HIV. Of these, 763 (82%) were younger than 16 years and 604 (79%) of these were aged 5 years and below. Estimated HIV prevalence was 3% overall; 7% (283 of 3803) in children aged 0-2 years, 6% (321 of 5412) in children aged 3-5 years, and 1% (148 of 11 251) in adults aged 16-49 years. Of the 591 children who registered for HIV care, 478 (81%) were 5 years or younger, 379 (64%) were boys, and 315 (53%) of 590 had a weight-for-age Z score of -3·2. Prevalence of hepatitis B surface antigen was 8% (48 of 574) and hepatitis C antibody positivity was 3% (15 of 574). Of children whose mothers tested for HIV, only 39 (11%) of 371 had HIV-positive mothers. Most children (404 [89%] of 453) reported multiple previous injections and 40 (9%) of 453 reported blood transfusions. INTERPRETATION: This HIV outbreak is unprecedented among children in Pakistan: a 54% increase in paediatric HIV diagnoses over the past 13 years. The outbreak was heavily skewed towards young children younger than 5 years, with a predominance of boys. Epidemiological and molecular studies are needed to understand the full extent of the outbreak and its drivers to guide HIV control strategies. FUNDING: None.

Metabolic investigations in patients with hepatitis B and C.

AIM: To investigate the similarities and dissimilarities in patients with hepatitis B and hepatitis C, clinically and metabolically. METHODS: Fifty patients with hepatitis B virus and hepatitis C virus infection were included in this study, along with fifty healthy controls for comparison purposes. Intravenous blood (10 mL) samples from patients and healthy subjects were collected and made to clot before serum was separated and immediately levels of the enzymes, alkaline phosphatase (ALK), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), serum glutamate oxaloacetate transaminase (s-GOT) and serum glutamate pyruvate transaminase (s-GPT) were determined by a kit method. For total content of each metal the serum samples were analyzed using atomic absorption spectrophotometry. Levels of cholesterol, triglycerides, urea, creatinine and uric acid were determined using a kit method on Microlab 300. RESULTS: Serum magnesium and copper levels remained unchanged, whereas the concentration of zinc decreased and iron increased significantly in both groups of patients. Total antioxidant activity was significantly decreased in both hepatitis B and C. Among the enzymes analyzed, ALK, s-GPT, LDH and s-GOT were all significantly increased in both patients with hepatitis B and C whereas CPK was significantly decreased in patients with hepatitis B and remained unchanged in patients with hepatitis C. CONCLUSION: The information accumulated by this study will help provide a better understanding of involved metabolic processes in order to design appropriate therapeutic approaches for treating these patients, so they can recover and lead normal lives.