Micro Health Project

Community health diagnosis is a comprehensive assessment of health status of the community in relation to its social, physical and biological environment. The purpose of community health diagnosis is to define existing problems, determine available resources and set priorities for planning, implementing and evaluating health action, by and for the community. The community health diagnosis program began on 4th September 2015 and continued till 13th September 2015 in ward no 1 and 5 Rupakot VDC, Kaski, Nepal. The program was organized in following phases: data collection, data analysis, first community presentation, prioritization of need and planning of micro health project (MHP), implementation and evaluation of MHP, and final community presentation. On the basis of the observed and the felt needs of the community, we found the real needs and prioritized them as follows. For community: Proper water purification, information about common diseases, KAP on diseases, knowledge on TB and DOTS. For school-going children: Education on environmental sanitation, education on personal hygiene - teeth brushing and hand washing, adolescent health education. We launched micro health project (MHP) on these topics, conducting school-based as well as community-based programs.  Journal of Gandaki Medical College Vol. 10, No. 1, 2017, Page: 59-6

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

ネパールにおいて分離された薬剤耐性結核菌株の特徴

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which currently presents an immense global health challenge. It ranks as the second leading cause of death from an infectious disease worldwide. An estimated one third of the world’s population is infected with the tubercle bacilli; with 95% of TB cases occur in developing countries. The World Health Organisation (WHO) estimates that there were 9 million new cases of TB and 1.4 million TB deaths globally in 2011. TB normally affects the lungs (pulmonary TB) and can affect other sites as well (extrapulmonary TB). The disease is spread by the air when people who are sick with pulmonary TB spout bacteria during coughing, sneezing and speaking. In general, infection by the pathogen does not necessarily result in the development of clinical symptoms and relatively small proportion (5-10%) of these individuals will progress to active disease each year. The remaining proportion (90-95%) of infected individuals will initially be asymptomatic and undergo latent infection, from which reactivation may occur when immune system of the patient becomes weakened.If patients are not treated properly, TB can be fatal. New cases of drug-susceptible TB are treated with a 6-month regimen of four first-line drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and pyrazinamide (PZA). RIF is a broad spectrum rifamycin derivative that interferes the synthesis of mRNA by binding to the ß subunit of RNA polymerase (RpoB) in bacterial cells. INH is a prodrug that requires activation by M. tuberculosis catalase-peroxidase (KatG), to generate a range of reactive oxygen species and reactive organic radicals, which then attack multiple targets in the tubercle bacillus. The primary target of the inhibition is the cell wall mycolic acid synthesis pathway (Figure 1). EMB inhibits the formation of mycobacterial membrane. The mechanism of action of PZA is poorly understood. The only known mechanisms are it disrupts membrane energetics and inhibits membrane transport function in M. tuberculosis.Fluoroquinolones (FQs) are considered to be important second-line drugs recommended for the treatment of multidrug-resistant TB (MDR-TB). They act by inhibiting DNA supercoiling, thus preventing replication and cell division. They block a type II topoisomerase (called DNA gyrase) of M. tuberculosis, a heterotetramer consisting of two A and B subunits coded by the gyrA and gyrB genes. Among second-line anti-TB drugs, aminoglycosides (kanamycin [KAN] and amikacin [AMK]) and cyclic peptides (capreomycin [CAP] and viomycin) inhibit protein synthesis by inhibiting the normal function of ribosomes (Figure 1).The emergence and spread of drug-resistant strains of M. tuberculosis throughout the world possess a serious threat to TB control. Resistance to anti-TB drugs arises due to a variety of reasons, such as the failure to detect resistance to TB drugs, interrupting treatment, omitting one or more drugs from the recommended prescription and suboptimal dosage. Thus, M. tuberculosis can become resistant to multiple drugs in the period of a few months. Essentially, drug resistance arises in areas with improper TB control programmes. A patient who develops active disease with a drug-resistant TB strain can transmit this form of TB to other individuals.MDR-TB, which is caused by bacteria that are resistant to least two first-line drugs including INH and RIF and, extensively drug resistant TB (XDR-TB), which is caused by bacteria that are resistant to INH and RIF as well as any FQs and any of the second-line anti-TB injectable drugs (AMK, KAN or CAP). WHO estimates that from 220,000 to 400,000 of MDR-TB cases occur among TB cases notified in the world in 2011. About 60% of these drug-resistant TB cases occur in Brazil, China, India, the Russian Federation and South Africa (that are referred as BRICS countries) (Figure 2). By the end of 2010, 68 countries had reported at least one case of XDR-TB (Figure 3).Genotyping of M. tuberculosis plays an increasing role for understanding the epidemiology and biology of TB. Genotyping techniques are important for molecular epidemiological investigations of TB such as defining chains of ongoing transmission and differentiating patient relapse from exogenous re-infection, and defining the evolutionary background of clinical isolates. Over the past years, several methods have been developed to discriminate M. tuberculosis strains: insertion sequence 6110 restriction fragment length polymorphism, spacer oligonucleotide typing (spoligotyping), variable-number tandem repeat (VNTR), single-nucleotide polymorphisms and large sequence polymorphisms.Nepal is a landlocked country in South East Asia, bounded to the north by China and to the south by India, sharing an open border with India. In Nepal, TB is a major public health problem. The incidence of all forms of TB was estimated to be 173/ 100,000 population while the incidence of new smear-positive cases was at 77 per 100,000 in 2008. The four surveillances conducted between 1996 and 2007 have indicated the fluctuating prevalence of MDR-TB among new cases of between 1.1% and 3.7% (1.1% in 1996, 3.7% in 1999, 1.4% in 2001 and 2.9% in 2007). The latest estimate of MDR-TB is 2.9% and 11.7% among new and recurrent cases, respectively.Rapid determination of the antimicrobial susceptibility pattern in clinical isolates of M. tuberculosis is important for the early administration of appropriate therapeutic agents for the prevention of additional resistance development. In this context, the molecular characterization of drug resistance by identifying mutations in associated genes will be applicable for developing a potential rapid molecular drug susceptibility test as an alternative to conventional methods.The present thesis consists of two chapters; in chapter I, I have investigated the type and frequency of drug resistance-conferring mutations that occurred among M. tuberculosis clinical isolates that were phenotypically MDR by DNA sequencing. I have also compared the frequency of different mutations with those in isolates circulating in the surrounding countries. In chapter II, I have described drug resistance-associated mutations in XDR isolates and analyzed the genetic background of these isolates by using a molecular approach

Molecular characterization of Mycobacterium orygis isolates from wild animals of Nepal

Mycobacterium orygis, a new member of the Mycobacterium tuberculosis complex, was isolated from a captive spotted deer (Axis axis) and a blue bull (Boselaphus tragocamelus) in Nepal. Analyses by spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing, region of difference and single nucleotide polymorphism of genes gyrB, mmpL6, TbD1, PPE55 and Rv2042c confirmed the isolates as M. orygis. Moreover, analyses by spoligotyping (SIT587) as well as MIRU-VNTR showed that the isolates shared a similar pattern with many reported isolates. From previous and the present studies, it can be inferred that South Asia is one of the endemic regions for M. orygis. Further investigation including a larger sample size and different host interaction will help to understand the ecology and epidemiology of M. orygis in Nepal

Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolated in Nepal

Despite being one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. To develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance in Mycobacterium tuberculosis is required. In the present study, we investigated the prevalence of mutations in rpoB and katG genes and the inhA promoter region in 158 M. tuberculosis isolates, 109 phenotypically MDR and 49 non-MDR collected in Nepal, by DNA sequencing. Mutations affecting the 81-bp rifampicin (RIF) resistance-determining region (RRDR) of rpoB were identified in 106 of 109 (97.3%) RIF-resistant isolates. The codons most frequently affected were 531, 526 and 516 with percentages of 58.7%, 15.6% and 15.6%, respectively. Of 113 isoniazid (INH)-resistant isolates, 99 (87.6%) had mutations in the katG gene, with Ser315Thr being the most prevalent (81.4%) substitution. Mutations in the inhA promoter region were detected in 14 (12.4%) INH-resistant isolates. The results from this study provide an overview of the current situation of RIF and INH resistance in M. tuberculosis in Nepal and can serve as a basis for developing or improving rapid molecular-based tests to monitor drug-resistant strains in this country

Characterization of extensively drug-resistant Mycobacterium tuberculosis in Nepal

The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global control of TB. Although molecular characterization of drug resistance-associated mutations in multidrug-resistant isolates in Nepal has been made, mutations in XDR isolates and their genotypes have not been reported previously. In this study, we identified and characterized 13 XDR Mycobacterium tuberculosis isolates from clinical isolates in Nepal. The most prevalent mutations involved in rifampicin, isoniazid, ofloxacin, and kanamycin/capreomycin resistance were Ser531Leu in rpoB gene (92.3%), Ser315Thr in katG gene (92.3%), Asp94Gly in gyrA gene (53.9%) and A1400G in rrs gene (61.5%), respectively. Spoligotyping and multilocus sequence typing revealed that 69% belonged to Beijing family, especially modern types. Further typing with 26-loci variable number of tandem repeats suggested the current spread of XDR M. tuberculosis. Our result highlights the need to reinforce the TB policy in Nepal with regard to control and detection strategies