Patan Academy of Health Sciences

Abstract Background Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. Methods We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I 2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. Findings We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S . Typhi and 29,731 S . Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S . Typhi in South Asia, which declined between 1990 and 2018, and MDR S . Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. Interpretation Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S . Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S . Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. Trial registration PROSPERO CRD42018029432 .

BACKGROUND: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. METHODS: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. RESULTS: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae. CONCLUSIONS: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.

BACKGROUND: Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19. METHODS: In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. The trial took place at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150 mg aspirin once per day until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28 day mortality. All analyses were done by intention to treat. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between Nov 1, 2020, and March 21, 2021, 14 892 (66%) of 22 560 patients enrolled into the RECOVERY trial were eligible to be randomly allocated to aspirin. 7351 patients were randomly allocated (1:1) to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) of 7351 patients allocated to aspirin and 1299 (17%) of 7541 patients allocated to usual care died within 28 days (rate ratio 0·96, 95% CI 0·89-1·04; p=0·35). Consistent results were seen in all prespecified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days, IQR 5 to >28, vs 9 days, IQR 5 to >28) and a higher proportion were discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, 95% CI 1·02-1·10; p=0·0062). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs 22%; risk ratio 0·96, 95% CI 0·90-1·03; p=0·23). Aspirin use was associated with a reduction in thrombotic events (4·6% vs 5·3%; absolute reduction 0·6%, SE 0·4%) and an increase in major bleeding events (1·6% vs 1·0%; absolute increase 0·6%, SE 0·2%). INTERPRETATION: In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28 day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days. FUNDING: UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with onset in early childhood. It is a clinically heterogenous condition with comorbidity posing a distinct challenge to diagnosing and managing these children and adolescents. This review aims to provide an overview of comorbidity with ADHD including other neurodevelopmental disorders, learning disorders, externalising and internalising disorders. Challenges in screening for, diagnosing and managing comorbidity with ADHD are summarised. Also, methodological challenges and future directions in research in this interesting field are highlighted.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

BACKGROUND: In South and Southeast Asian countries, tobacco is consumed in diverse forms, and smoking among women is very low. We aimed to provide national estimates of prevalence and social determinants of smoking and smokeless tobacco use among men and women separately. METHODS: Data from Demographic and Health Surveys completed in nine countries (India, Pakistan, Nepal, Bangladesh, Maldives, Philippines, Cambodia, Indonesia, and Timor Leste) were analyzed. Current smoking or smokeless tobacco use was assessed as response "yes" to one or more of three questions, such as "Do you currently smoke cigarettes?" Weighted country-level prevalence rates for socio-economic subgroups were calculated for smoking and smokeless tobacco use. Binary logistic regression analyses were done on STATA/IC (version 10) by 'svy' command. RESULTS: Prevalence and type of tobacco use among men and women varied across the countries and among socio-economic sub groups. Smoking prevalence was much lower in women than men in all countries. Smoking among men was very high in Indonesia, Maldives, and Bangladesh. Smokeless tobacco (mainly chewable) was used in diverse forms, particularly in India, among both men and women. Chewing tobacco was common in Nepal, Bangladesh, Maldives, and Cambodia. Both smoking and smokeless tobacco use were associated with higher age, lower education, and poverty, but their association with place of residence and marital status was not uniform between men and women across the countries. CONCLUSION: Policymakers should consider type of tobacco consumption and their differentials among various population subgroups to implement country-specific tobacco control policies and target the vulnerable groups. Smokeless tobacco use should also be prioritized in tobacco control efforts.

Enteric fever, an infection caused by Salmonella enterica serovar Typhi and serovar Paratyphi A, is common and endemic in many areas of the Asian and African continents. In endemic areas, diagnostic tests are needed to diagnose acute cases for clinical management, to detect convalescent and chronic fecal carriage and for contact tracing. A suitable test may also allow an assessment of disease burden in a community to determine the need for vaccination programs. Each specific role may warrant a dedicated test, utilizing different samples, targets and methods to serve their respective purpose. Current diagnostic methods are poor. Blood culture is insufficiently sensitive and technically demanding, and bone marrow culture, although more sensitive, is infrequently performed. Antibody- and antigen-detection tests lend themselves to point-of-care format but remain insufficiently sensitive and specific for this role. There are concerns about the sensitivity of nucleic acid amplification tests and they have not become widely adopted. However, new approaches using genomics, proteomics, transcriptomics, in vivo-induced antigen and immunoaffinity proteomics-based technologies are being employed to identify new antigens, gene targets and metabolic products that could be used as a basis for more effective diagnostic tests. If novel tests are to be credible and widely used they require rigorous evaluation in endemic areas in studies with appropriate selection of patients, adequate sample sizes and proper attention to a gold standard reference. Here, we discuss the range of methods currently used for diagnosing enteric fever in endemic locations and we suggest new technologies which may improve enteric fever diagnostics over the coming years.

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.

BACKGROUND: Community-based primary-level workers (PWs) are an important strategy for addressing gaps in mental health service delivery in low- and middle-income countries. OBJECTIVES: To evaluate the effectiveness of PW-led treatments for persons with mental health symptoms in LMICs, compared to usual care. SEARCH METHODS: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, ICTRP, reference lists (to 20 June 2019). SELECTION CRITERIA: Randomised trials of PW-led or collaborative-care interventions treating people with mental health symptoms or their carers in LMICs. PWs included: primary health professionals (PHPs), lay health workers (LHWs), community non-health professionals (CPs). DATA COLLECTION AND ANALYSIS: Seven conditions were identified apriori and analysed by disorder and PW examining recovery, prevalence, symptom change, quality-of-life (QOL), functioning, service use (SU), and adverse events (AEs). Risk ratios (RRs) were used for dichotomous outcomes; mean difference (MDs), standardised mean differences (SMDs), or mean change differences (MCDs) for continuous outcomes. For SMDs, 0.20 to 0.49 represented small, 0.50 to 0.79 moderate, and ≥0.80 large clinical effects. Analysis timepoints: T1 (<1 month), T2 (1-6 months), T3 ( >6 months) post-intervention. MAIN RESULTS: Description of studies 95 trials (72 new since 2013) from 30 LMICs (25 trials from 13 LICs). Risk of bias Most common: detection bias, attrition bias (efficacy), insufficient protection against contamination. Intervention effects *Unless indicated, comparisons were usual care at T2. "Probably", "may", or "uncertain" indicates "moderate", "low," or "very low" certainty evidence. Adults with common mental disorders (CMDs) LHW-led interventions a. may increase recovery (2 trials, 308 participants; RR 1.29, 95%CI 1.06 to 1.56); b. may reduce prevalence (2 trials, 479 participants; RR 0.42, 95%CI 0.18 to 0.96); c. may reduce symptoms (4 trials, 798 participants; SMD -0.59, 95%CI -1.01 to -0.16); d. may improve QOL (1 trial, 521 participants; SMD 0.51, 95%CI 0.34 to 0.69); e. may slightly reduce functional impairment (3 trials, 1399 participants; SMD -0.47, 95%CI -0.8 to -0.15); f. may reduce AEs (risk of suicide ideation/attempts); g. may have uncertain effects on SU. Collaborative-care a. may increase recovery (5 trials, 804 participants; RR 2.26, 95%CI 1.50 to 3.43); b. may reduce prevalence although the actual effect range indicates it may have little-or-no effect (2 trials, 2820 participants; RR 0.57, 95%CI 0.32 to 1.01); c. may slightly reduce symptoms (6 trials, 4419 participants; SMD -0.35, 95%CI -0.63 to -0.08); d. may slightly improve QOL (6 trials, 2199 participants; SMD 0.34, 95%CI 0.16 to 0.53); e. probably has little-to-no effect on functional impairment (5 trials, 4216 participants; SMD -0.13, 95%CI -0.28 to 0.03); f. may reduce SU (referral to MH specialists); g. may have uncertain effects on AEs (death). Women with perinatal depression (PND) LHW-led interventions a. may increase recovery (4 trials, 1243 participants; RR 1.29, 95%CI 1.08 to 1.54); b. probably slightly reduce symptoms (5 trials, 1989 participants; SMD -0.26, 95%CI -0.37 to -0.14); c. may slightly reduce functional impairment (4 trials, 1856 participants; SMD -0.23, 95%CI -0.41 to -0.04); d. may have little-to-no effect on AEs (death); e. may have uncertain effects on SU. Collaborative-care a. has uncertain effects on symptoms/QOL/SU/AEs. Adults with post-traumatic stress (PTS) or CMDs in humanitarian settings LHW-led interventions a. may slightly reduce depression symptoms (5 trials, 1986 participants; SMD -0.36, 95%CI -0.56 to -0.15); b. probably slightly improve QOL (4 trials, 1918 participants; SMD -0.27, 95%CI -0.39 to -0.15); c. may have uncertain effects on symptoms (PTS)/functioning/SU/AEs. PHP-led interventions a. may reduce PTS symptom prevalence (1 trial, 313 participants; RR 5.50, 95%CI 2.50 to 12.10) and depression prevalence (1 trial, 313 participants; RR 4.60, 95%CI 2.10 to 10.08); b. may have uncertain effects on symptoms/functioning/SU/AEs. Adults with harmful/hazardous alcohol or substance use LHW-led interventions a. may increase recovery from harmful/hazardous alcohol use although the actual effect range indicates it may have little-or-no effect (4 trials, 872 participants; RR 1.28, 95%CI 0.94 to 1.74); b. may have little-to-no effect on the prevalence of methamphetamine use (1 trial, 882 participants; RR 1.01, 95%CI 0.91 to 1.13) and functional impairment (2 trials, 498 participants; SMD -0.14, 95%CI -0.32 to 0.03); c. probably slightly reduce risk of harmful/hazardous alcohol use (3 trials, 667 participants; SMD -0.22, 95%CI -0.32 to -0.11); d. may have uncertain effects on SU/AEs. PHP/CP-led interventions a. probably have little-to-no effect on recovery from harmful/hazardous alcohol use (3 trials, 1075 participants; RR 0.93, 95%CI 0.77 to 1.12) or QOL (1 trial, 560 participants; MD 0.00, 95%CI -0.10 to 0.10); b. probably slightly reduce risk of harmful/hazardous alcohol and substance use (2 trials, 705 participants; SMD -0.20, 95%CI -0.35 to -0.05; moderate-certainty evidence); c. may have uncertain effects on prevalence (cannabis use)/SU/AEs. PW-led interventions for alcohol/substance dependence a. may have uncertain effects. Adults with severe mental disorders *Comparisons were specialist-led care at T1. LHW-led interventions a. may have little-to-no effect on caregiver burden (1 trial, 253 participants; MD -0.04, 95%CI -0.18 to 0.11); b. may have uncertain effects on symptoms/functioning/SU/AEs. PHP-led or collaborative-care a. may reduce functional impairment (7 trials, 874 participants; SMD -1.13, 95%CI -1.78 to -0.47); b. may have uncertain effects on recovery/relapse/symptoms/QOL/SU. Adults with dementia and carers PHP/LHW-led carer interventions a. may have little-to-no effect on the severity of behavioural symptoms in dementia patients (2 trials, 134 participants; SMD -0.26, 95%CI -0.60 to 0.08); b. may reduce carers' mental distress (2 trials, 134 participants; SMD -0.47, 95%CI -0.82 to -0.13); c. may have uncertain effects on QOL/functioning/SU/AEs. Children with PTS or CMDs LHW-led interventions a. may have little-to-no effect on PTS symptoms (3 trials, 1090 participants; MCD -1.34, 95%CI -2.83 to 0.14); b. probably have little-to-no effect on depression symptoms (3 trials, 1092 participants; MCD -0.61, 95%CI -1.23 to 0.02) or on functional impairment (3 trials, 1092 participants; MCD -0.81, 95%CI -1.48 to -0.13); c. may have little-or-no effect on AEs. CP-led interventions a. may have little-to-no effect on depression symptoms (2 trials, 602 participants; SMD -0.19, 95%CI -0.57 to 0.19) or on AEs; b. may have uncertain effects on recovery/symptoms(PTS)/functioning. AUTHORS' CONCLUSIONS: PW-led interventions show promising benefits in improving outcomes for CMDs, PND, PTS, harmful alcohol/substance use, and dementia carers in LMICs.

One of the UN sustainable development goals is to achieve universal access to safe and affordable drinking water by 2030. It is locations like Kathmandu, Nepal, a densely populated city in South Asia with endemic typhoid fever, where this goal is most pertinent. Aiming to understand the public health implications of water quality in Kathmandu we subjected weekly water samples from 10 sources for one year to a range of chemical and bacteriological analyses. We additionally aimed to detect the etiological agents of typhoid fever and longitudinally assess microbial diversity by 16S rRNA gene surveying. We found that the majority of water sources exhibited chemical and bacterial contamination exceeding WHO guidelines. Further analysis of the chemical and bacterial data indicated site-specific pollution, symptomatic of highly localized fecal contamination. Rainfall was found to be a key driver of this fecal contamination, correlating with nitrates and evidence of S. Typhi and S. Paratyphi A, for which DNA was detectable in 333 (77%) and 303 (70%) of 432 water samples, respectively. 16S rRNA gene surveying outlined a spectrum of fecal bacteria in the contaminated water, forming complex communities again displaying location-specific temporal signatures. Our data signify that the municipal water in Kathmandu is a predominant vehicle for the transmission of S. Typhi and S. Paratyphi A. This study represents the first extensive spatiotemporal investigation of water pollution in an endemic typhoid fever setting and implicates highly localized human waste as the major contributor to poor water quality in the Kathmandu Valley.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case–control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10−12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a ‘helper virus’ to support AAV2 replication) and disease susceptibility related to HLA class II status. A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

BACKGROUND: Anemia remains a major public health challenge with high prevalence among women in South and Southeast Asian countries. Reductions in anemia rates have been stalled, despite the implementation of different maternal health and nutrition programs. This study aimed to assess the prevalence and factors associated with anemia among women of reproductive age in seven selected South and Southeast Asian countries. METHODS: This cross-sectional analysis utilized data from the most recent demographic and health surveys from seven selected South and Southeast Asian countries (Bangladesh, Cambodia, India, Maldives, Myanmar, Nepal, and Timor-Leste) between 2011 and 2016. This study included 726,164 women of reproductive age. Multiple logistic regression was performed to assess the factors associated with anemia among women for each country separately. RESULTS: The combined prevalence of anemia was 52.5%, ranged from 22.7% in Timor-Leste to 63% in the Maldives. Results from multiple logistic regression suggest that likelihood of anemia is significantly higher among younger women (15-24 years), women with primary or no education, women from the poorest wealth quintile, women without toilet facilities and improved water sources, underweight women, and women with more than one children born in last five years in most of the countries. CONCLUSIONS: The prevalence of anemia is high among women of reproductive age in the seven selected South and Southeast Asian countries. The results of this study suggest that various household, environmental and individual factors contribute to the increased likelihood of anemia. Evidence-based, multidisciplinary policies and programs targeting mothers' health and nutrition status, in addition to scaling-up women's education and socioeconomic status, are warranted to combat anemia.

BACKGROUND AND OBJECTIVES: Women living with HIV/AIDS, in particular, have been positioned as a latent source of infection, and have captivated culpability and blame leading to a highly stigmatised and discriminated life. Despite the situation, women and their particular concerns have largely been ignored in HIV/AIDS research literature. This review aims to examine and analyze the feelings, experiences and perceptions of Women living with HIV/AIDS (WLHA) and will also access the role of support group as a coping strategy on the basis of 7 primary researches conducted in or on different parts of the world. METHODOLOGY: A systematic literature search was carried out on major data bases ASSIA, CINAHL, Science Direct, Web of Knowledge, Wiley Inter Science, AMED, Pub Med/Bio Med Central, MEDLINE and Cochrane Library. The articles included for review purpose were gauged against the pre-defined inclusion/exclusion criteria and quality assessment checklist resulting in a final 7 papers. FINDINGS/RESULTS: The findings were compiled into five thematic areas: (1) Disclosure as a sensitive issue; (2) Stigma and Discrimination associated with HIV/AIDS and the multidimensional effects on women's health and wellbeing; (3) Internalised Stigma; (4) Women living with HIV/AIDS experiences of being rejected, shunned and treated differently by physicians, family and close friends; (5) Support Group as among the best available interventions for stigma and discrimination. CONCLUSION: Support groups should be offered as a fundamental part of HIV/AIDS services and should be advocated as an effective and useful intervention. Further research is needed to examine the effect of support groups for women living with HIV/AIDS. A community based randomised controlled trial with support group as an intervention and a control group could provide further evidence of the value of support groups.

BACKGROUND: Neonatal sepsis, one of the leading causes of mortality in neonatal intensive care units (NICU) of developing countries like Nepal, is often not extensively studied. In order to decrease the morbidity and mortality associated with neonatal sepsis, neonatologists should have a keen knowledge of the existing bacteriological flora and their antibiotic susceptibility pattern. In this study, we aim to determine the bacteriological profile and antibiotic susceptibility pattern of culture positive neonatal sepsis in the NICU of a tertiary teaching hospital in Nepal. METHODS: This was a retrospective cross-sectional study of all blood culture positive sepsis cases among neonates admitted to the neonatal intensive care unit of Patan Hospital, Nepal between April 15, 2014 and April 15, 2017. All neonates with a clinical suspicion of sepsis with a positive blood culture were identified. Patient demographics, clinical details, maternal risk factors, and laboratory data including bacteriological profiles and antimicrobial susceptibilities were recorded and analyzed. RESULTS: Of the 336 neonates admitted in the NICU, 69 (20.5%) had culture-positive sepsis. The majority were early-onset sepsis (n = 54, 78.3%) and were among the preterm babies (n = 47, 68.1%). Most bacterial isolates were gram-negative, predominantly the Klebsiella species (n = 23, 33.3%). Klebsiella showed high resistance to commonly used antibiotics such as; Cefotaxime (90.5%), Gentamicin (75%), Ciprofloxacin (76.2%), Ofloxacin (72.2%) and Chloramphenicol (65%). However, they showed good susceptibility to Carbapenems (100%), Colistin (88.8%) and Tigecycline (81.8%). Among cultures with gram-positive species, Coagulase-negative Staphylococci (CONS) (n = 14, 20.3%) predominated. CONS showed high resistance to Oxacillin (80%), Cefotaxime (66.7%) and Meropenem (80%) but good susceptibility (100%) to Vancomycin and Linezolid. Prevalence of multidrug-resistant strain was 73.9%. CONCLUSIONS: Klebsiella species and CONS were the most common causes of neonatal sepsis in our study. A significant proportion of the isolates were multidrug resistant strains, which pose a great threat to neonatal survival, and thereby, warrant modification of existing empirical therapy. Implementation of effective preventive strategies to combat the emergence of antibiotic resistance is urgently needed. We recommend a combination of Piperacillin-Tazobactam and Ofloxacin as the first line therapy and combination of Vancomycin and Meropenem as the second line empirical therapy in our NICU.

Inflammation is a normal physiological defense against pathogen infection and tissue damage and quickly ends under normal circumstances.However, in many chronic conditions, the inflammatory response continues and leads to significant tissue and organ damage.Recently, increasing evidences have shown that the abnormal inflammatory response is closely associated with many chronic diseases, especially in autoimmune diseases, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), gout, and diabetes [1][2][3].Although the importance of inflammatory dysregulation in chronic illnesses has been reported in recent studies, the pathogenesis of inflammation dysfunction in the autoimmune diseases remains elusive.Knowledge of the mechanism of inflammation regulation will lead to significant clinical benefits for the treatment of autoimmune disease.This special issue showcases a number of original research articles and review papers on the topic of inflammatory regulation in autoimmune diseases.T cell-mediated inflammatory responses have long been recognized to play an essential role in the development of autoimmune diseases, including Th1, Th2, and Th17 cell responses.Recent compelling evidence has shown that abnormal T cell immune response, including Th1, Th2, and Th17 cell responses, was actually having a crucial role in the inflammation of autoimmune diseases [4].Recent studies showed that vasoactive intestinal peptide (VIP) modulates the pathogenic activity of diverse cell subpopulations involved in RA, including lymphocytes, fibroblast-like synoviocytes (FLS), and macrophages [5].In this special issue, R. Villanueva-Romero

BACKGROUND: Although the Framework Convention on Tobacco Control prioritizes monitoring of tobacco use by population-based surveys, information about the prevalence and patterns of tobacco use in sub-Saharan Africa is limited. We provide country-level prevalence estimates for smoking and smokeless tobacco (SLT) use and assess their social determinants. METHODS: We analyzed population-based data of the most recent Demographic Health Surveys performed between 2006 and 2013 involving men and women in 30 sub-Saharan African countries. Weighted country-level prevalence rates were estimated for 'current smoking' (cigarettes, pipe, cigars, etc.) and 'current SLT use' (chewing, snuff, etc.). From the pooled datasets for men and women, social determinants of smoking and SLT use were assessed through multivariate analyses using a dummy country variable as a control and by including a within-country sample weight for each country. RESULTS: Among men, smoking prevalence rates were high in Sierra Leone (37.7%), Lesotho (34.1%), and Madagascar (28.5%); low (<10%) in Ethiopia, Benin, Ghana, Nigeria, and Sao Tome & Principe; the prevalence of SLT use was <10% in all countries except for Madagascar (24.7%) and Mozambique (10.9%). Among women, smoking and SLT prevalence rates were <5% in most countries except for Burundi (9.9%), Sierra Leone (6%), and Namibia (5.9%) (smoking), and Madagascar (19.6%) and Lesotho (9.1%) (SLT use). The proportion of females who smoked was lower than SLT users in most countries. Older age was strongly associated with both smoking and SLT use among men and women. Smoking among both men and women was weakly associated, but SLT use was strongly associated, with education. Similarly, smoking among men and women was weakly associated, but SLT use was strongly associated, with the wealth index. Smoking and SLT use were also associated with marital status among both men and women, as well as with occupation (agriculturists and unskilled workers). CONCLUSIONS: Prevalence of smoking among women was much lower than in men, although the social patterns of tobacco use were similar to those in men. Tobacco control strategies should target the poor, not/least educated, and agricultural and unskilled workers, who are the most vulnerable social groups in sub-Saharan Africa.

We report two cases which highlight the fact how poor communication leads to dangerously poor health outcome. We present the case of a 50-year-old woman recently diagnosed with rheumatoid arthritis from Southern Nepal presented to Patan hospital with multiple episodes of vomiting and oral ulcers following the intake of methotrexate every day for 11 days, who was managed in the intensive care unit. Similarly, we present a 40-year-old man with ileo-caecal tuberculosis who was prescribed with anti-tubercular therapy (ATT) and prednisolone, who failed to take ATT due to poor communication and presented to Patan Hospital with features of disseminated tuberculosis following intake of 2 weeks of prednisolone alone. These were events that could have been easily prevented with proper communication skills. Improvement of communication between doctors and patients is paramount so that life-threatening events like these could be avoided.

BACKGROUND: Menstrual hygiene management (MHM) is an essential aspect of hygiene for women and adolescent girls between menarche and menopause. Despite being an important issue concerning women and girls in the menstruating age group MHM is often overlooked in post-disaster responses. Further, there is limited evidence of menstrual hygiene management in humanitarian settings. This study aims to describe the experiences and perceptions of women and adolescent girls on menstrual hygiene management in post-earthquake Nepal. METHODS: A mixed methods study was carried out among the earthquake affected women and adolescent girls in three villages of Sindhupalchowk district of Nepal. Data was collected using a semi-structured questionnaire that captured experiences and perceptions of respondents on menstrual hygiene management in the aftermath of the Nepal earthquake. Quantitative data were triangulated with in-depth interview regarding respondent's personal experiences of menstrual hygiene management. RESULTS: Menstrual hygiene was rated as the sixth highest overall need and perceived as an immediate need by 18.8% of the respondents. There were 42.8% women & girls who menstruated within first week of the earthquake. Reusable sanitary cloth were used by about 66.7% of the respondents before the earthquake and remained a popular method (76.1%) post-earthquake. None of the respondents reported receiving menstrual adsorbents as relief materials in the first month following the earthquake. Disposable pads (77.8%) were preferred by respondents as they were perceived to be clean and convenient to use. Most respondents (73.5%) felt that reusable sanitary pads were a sustainable choice. Women who were in the age group of 15-34 years (OR = 3.14; CI = (1.07-9.20), did not go to school (OR = 9.68; CI = 2.16-43.33), married (OR = 2.99; CI = 1.22-7.31) and previously used reusable sanitary cloth (OR = 5.82; CI = 2.33-14.55) were more likely to use the reusable sanitary cloth. CONCLUSIONS: In the immediate aftermath of the earthquake, women and girls completely depended on the use of locally available resources as adsorbents during menstruation. Immediate relief activities by humanitarian agencies, lacked MHM activities. Understanding the previous practice and using local resources, the reusable sanitary cloth is a way to address the menstrual hygiene needs in the post-disaster situations in Nepal.

Typhoid is a systemic infection caused by Salmonella Typhi and Salmonella Paratyphi A, human-restricted bacteria that are transmitted faeco-orally. Salmonella Typhi and S. Paratyphi A are clonal, and their limited genetic diversity has precluded the identification of long-term transmission networks in areas with a high disease burden. To improve our understanding of typhoid transmission we have taken a novel approach, performing a longitudinal spatial case-control study for typhoid in Nepal, combining single-nucleotide polymorphism genotyping and case localization via global positioning. We show extensive clustering of typhoid occurring independent of population size and density. For the first time, we demonstrate an extensive range of genotypes existing within typhoid clusters, and even within individual households, including some resulting from clonal expansion. Furthermore, although the data provide evidence for direct human-to-human transmission, we demonstrate an overwhelming contribution of indirect transmission, potentially via contaminated water. Consistent with this, we detected S. Typhi and S. Paratyphi A in water supplies and found that typhoid was spatially associated with public water sources and low elevation. These findings have implications for typhoid-control strategies, and our innovative approach may be applied to other diseases caused by other monophyletic or emerging pathogens.

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource-poor hospital settings. Through whole-genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high-dependency wards in a hospital in Kathmandu during 2012 with a case-fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage-specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward-specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM-1 containing lineage in 2011 would have alerted the high-dependency ward staff to intervene. We argue that some form of real-time genetic characterisation, alongside clade-specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high- and low-income settings.