Onychomycosis in eastern Nepal

ABSTRACT Onychomycosis, a fungal infection of the nail is responsible for up to 50.0% of all nail diseases. Though, dermatophytes are most frequently implicated as the causative agents in onychomycosis, yeast and molds are increasingly recognized as causative pathogens. This study was aimed to know the clinical and mycological pattern of onychomycosis in eastern Nepal. Eighty-two clinically diagnosed patients of onychomycosis attending the Dermatology Outpatient department of a tertiary hospital over a period of one year were enrolled in this study. Clipping from the severely affected nail and skin scrapping from active border of the skin lesions if associated were collected from each patient and subjected to microscopy and culture for identification of fungi. The commonest affected age group was 21-40 years. The male: female ratio was 2.7:1. Fifty-one patients had isolated fingernail involvement, while involvement of toenails was seen in 15 patients. Distolateral subungual onychomycosis (67%) was the commonest clinical type followed in decreasing order by superficial white onychomycosis (14.6%), proximal subungual onychomycosis (9.8%), candidal onychomycosis (7.4%) and total dystrophic onychomycosis (1.2%). Trichophyton mentagrophytes (28.8%) was the most common pathogen isolated followed by Trichophyton rubrum (21.2%), Trichophyton tonsurans (11.5%), Candida albicans (11.5%), Trichospron beigelii, (9.6%), Epidermophyton floccosum (7.7%), Trichophyton violaceum (5.8%), and Aspergillus flavus (3.9%). Distolateral subungual onychomycosis was the most common clinical presentation and T. mentagrophytes and T. rubrum were the most frequently isolated fungi for onychomycosis in eastern Nepal

Prevalence of Shigella Species and Their Antimicrobial Resistance Patterns in Eastern Nepal

The study was conducted to determine the prevalence of Shigella species and their antimicrobial resistance patterns in eastern Nepal. Stool samples submitted to the diagnostic laboratory of B.P. Koirala Institute of Health Sciences, Nepal, during August 2000-July 2004, were cultured for Shigella species and were confirmed by biochemical and serological tests. Of 53 Shigella species isolated, Shigella dysenteriae type 1 was the most predominant isolate (73.7%), followed by S. flexneri (23%) and S. boydii (4%). The majority (79%) of Shigella species were isolated from children aged less than five years. An overall high resistance was observed for trimethoprim-sulphamethoxazole, ampicillin, nalidixic acid, mecillinam, and ciprofloxacin. There was a statistically significant(p<0.001) increasing trend in the prevalence of ciprofloxacin resistance in S. dysenteriae type 1. The results suggest reconsideration of the empiric use of these antimicrobial agents for shigellosis. A further study is required to evaluate additional antimicrobial agents

Antimicrobial Susceptibility Patterns of Salmonella enterica Serotype Typhi in Eastern Nepal

The aim of the present study was to evaluate antimicrobial susceptibility patterns with special reference to multidrug resistance, susceptibility to ciprofloxacin, and bacteriophage typing of Salmonella enterica serotype Typhi isolated from blood sent for culture in a tertiary-care teaching hospital in eastern Nepal during January 2000\u2013December 2004. In total, 132 strains of S. enterica Typhi, isolated from 2,568 blood culture samples collected from cases of suspected enteric fever, were tested for susceptibility to commonly-used antimicrobials by the disc-diffusion method. There were 35 multidrug-resistant strains. None of the isolates were resistant to ciprofloxacin.Of 52 isolates tested for minimum inhibitory concentration (MIC) of ciprofloxacin, 36 (69.23%) showed reduced susceptibility (MIC 650.25 mg/L). Of 112 strains tested for nalidixicacid susceptibility,86(76%) were resistant. Strains with reduced susceptibility to ciprofloxacin and resistance to nalidixic acid could be correlated. The commonest phage type was E1. Nalidixic acid susceptibility could be a useful screening test for the detection of decreased susceptibility of S. Typhi to ciprofloxacin, a drug which is commonly used even for minor ailments in this area

Single locus genotyping to track Leishmania donovani in the Indian subcontinent: Application in Nepal

Background We designed a straightforward method for discriminating circulating Leishmania populations in the Indian subcontinent (ISC). Research on transmission dynamics of visceral leishmaniasis (VL, or Kala-azar) was recently identified as one of the key research priorities for elimination of the disease in the ISC. VL in Bangladesh, India, and Nepal is caused by genetically homogeneous populations of Leishmania donovani parasites, transmitted by female sandflies. Classical methods to study diversity of these protozoa in other regions of the world, such as microsatellite typing, have proven of little use in the area, as they are not able to discriminate most genotypes. Recently, whole genome sequencing (WGS) so far identified 10 different populations termed ISC001-ISC010. Methodology / Principle findings As an alternative to WGS for epidemiological or clinical studies, we designed assays based on PCR amplification followed by dideoxynucleotide sequencing for identification of the nonrecombinant genotypes ISC001 up to ISC007. These assays were applied on 106 parasite isolates collected in Nepal between 2011 and 2014. Combined with data from WGS on strains collected in the period 2002–2011, we provide a proof-of-principle for the application of genotyping to study treatment outcome, and differential geographic distribution. Conclusions / Significance Our method can aid in epidemiological follow-up of visceral leishmaniasis in the Indian subcontinent, a necessity in the frame of the Kala-azar elimination initiative in the region

Long-lasting Insecticidal Nets to Prevent Visceral Leishmaniasis in the Indian Subcontinent; Methodological Lessons Learned from a Cluster Randomised Controlled Trial

In a recent paper, Nagpal et al. voiced concerns about the limited or biased use of scientific evidence to support public health interventions to control neglected tropical diseases (NTDs). Visceral leishmaniasis (VL), also known as kala-azar, is one of the major NTDs and does not escape this problem. Transmission is vector-borne and the Indian subcontinent is the region reporting most of the VL cases worldwide. In this region, the main causative species is Leishmania donovani and Phlebotomus argentipes is the vector. Transmission is considered anthroponotic and peridomestic—occurring at night when female sand flies bite people sleeping inside their house. The World Health Organization and the governments of India, Nepal, and Bangladesh set out in 2005 to eliminate VL from the region by 2015 through a combination of early treatment of cases and vector control. However, while recent advances in diagnostic tools and drugs have significantly improved case management strategies, the available vector control tools against P. argentipes remain limited. The elimination initiative promotes the use of indoor residual spraying (IRS) of households and cattle sheds to reduce vector density, but the evidence underpinning the effectiveness of IRS in this region is scanty. Historical observations show that L. donovani transmission declined concomitantly with dichlorodiphenyltrichloroethane (DDT) spraying during the 1950s–60s to eradicate malaria. In the aftermath of this malaria eradication campaign, very few VL cases were observed in endemic regions until the mid-seventies, when there was resurgence of a VL epidemic in India. To date, there are no randomized trials showing the effect of IRS on the incidence of clinical VL, though some studies showed a reduction in vector density. When the VL elimination initiative was launched in 2005, there were no clear alternatives for IRS as a vector control strategy. Insecticide treated nets (ITNs) were proposed as an alternative or complement to IRS on the basis of analogy arguments regarding their given efficacy against malaria or on data from observational studies suggesting ITNs reduce the risk of VL; but as for IRS, there were no randomized trials evaluating the effect of ITNs on L. donovani transmission. In this context, a number of field studies were conducted in the Indian subcontinent in the past decade to evaluate the effectiveness and impact of ITNs and other vector control tools on VL. Most of these studies have been reviewed in detail in two recent papers. The only two studies evaluating the impact of vector control interventions on clinical outcomes found conflicting results. First, the KALANET project, a cluster randomised controlled trial (CRT) in India and Nepal, showed that mass-distribution of ITNs did not reduce the risk of L. donovani infection or clinical VL. Then, an intervention trial in Bangladesh suggested that widespread bed net impregnation with slow-release insecticide may reduce the frequency of VL. Technical (e.g., type of nets and insecticides, lack of replicas and randomisation in Bangladesh) and biological factors (e.g., insecticide susceptibility and sand fly behaviour) may explain the different results observed. This apparent contradiction raises the question about the role that ITN may play in controlling VL in the Indian subcontinent but has also triggered a lot of discussion on methodology and evidence levels required when evaluating vector control tools for VL. In this paper, we would like to summarise the lessons learned from the KALANET CRT in terms of methodology to inform the generation of future evidence and discuss interpretation of findings against this background

Longlasting insecticidal nets for prevention of Leishmania donovani infection in India and Nepal: paired cluster randomised trial

Objective To test the effectiveness of large scale distribution of longlasting nets treated with insecticide in reducing the incidence of visceral leishmaniasis in India and Nepal

Domestic Animals and Epidemiology of Visceral Leishmaniasis, Nepal

Proximity of Leishmania donovani–positive goats is a risk factor for human infection

A Multi-Country, Single-Blinded, Phase 2 Study to Evaluate a Point-of-Need System for Rapid Detection of Leishmaniasis and Its Implementation in Endemic Settings

With the advancement of isothermal nucleic acid amplification techniques, detection of the pathogenic DNA in clinical samples at point-of-need is no longer a dream. The newly developed recombinase polymerase amplification (RPA) assay incorporated in a suitcase laboratory has shown promising diagnostic efficacy over real-time PCR in detection of leishmania DNA from clinical samples. For broader application of this point-of-need system, we undertook a current multi-country diagnostic evaluation study towards establishing this technique in different endemic settings which would be beneficial for the ongoing elimination programs for leishmaniasis. For this study purpose, clinical samples from confirmed visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) patients were subjected to both real-time PCR and RPA assay in Bangladesh, India, and Nepal. Further skin samples from confirmed cutaneous leishmaniasis (CL) patients were also included from Sri Lanka. A total of 450 clinical samples from VL patients, 429 from PKDL patients, 47 from CL patients, and 322 from endemic healthy/healthy controls were under investigation to determine the diagnostic efficacy of RPA assay in comparison to real-time PCR. A comparative sensitivity of both methods was found where real-time PCR and RPA assay showed 96.86% (95% CI: 94.45–98.42) and 88.85% (95% CI: 85.08–91.96) sensitivity respectively in the diagnosis of VL cases. This new isothermal method also exhibited promising diagnostic sensitivity (93.50%) for PKDL cases, when a skin sample was used. Due to variation in the sequence of target amplicons, RPA assay showed comparatively lower sensitivity (55.32%) than that of real-time PCR in Sri Lanka for the diagnosis of CL cases. Except for India, the assay presented absolute specificity in the rest of the sites. Excellent concordance between the two molecular methods towards detection of leishmania DNA in clinical samples substantiates the application of RPA assay incorporated in a suitcase laboratory for point-of-need diagnosis of VL and PKDL in low resource endemic settings. However, further improvisation of the method is necessary for diagnosis of CL

Post-Kala-azar Dermal Leishmaniasis in Nepal: A Retrospective Cohort Study (2000–2010)

Post-kala-azar dermal leishmaniasis (PKDL) is a skin disorder seen in patients treated for Leishmania donovani visceral leishmaniasis (VL), a neglected tropical disease that is fatal if left untreated. In the Indian subcontinent, PKDL is seen in 5–10% of all past VL cases and is also reported in some without history of VL. As persons with PKDL do not feel sick, the disease has only cosmetic significance for the individual and treatment is rarely sought. However, PKDL lesions harbour parasites and therefore could represent a source of transmission, through the bite of female sand flies. Our study shows that the occurrence of PKDL in patients with past treated VL is low in Nepal compared to neighboring countries. Treatment of the original VL episode with SSG (sodium stibogluconate), inadequate treatment and treatment on ambulatory basis were significantly associated with PKDL. Though SSG has since been replaced by other drugs, counseling and supervision of adherence to the prescribed VL treatment is of vital importance to reduce risk of treatment failure and relapse as well as later development of PKDL. Policy makers should include surveillance and case management of PKDL in the VL elimination program

A multicentric evaluation of dipstick test for serodiagnosis of visceral leishmaniasis in India, Nepal, Sri Lanka, Brazil, Ethiopia and Spain

Author Correction: A multicentric evaluation of dipstick test for serodiagnosis of visceral leishmaniasis in India, Nepal, Sri Lanka, Brazil, Ethiopia and Spain PMID: 33574485Visceral leishmaniasis (VL) is one of the leading infectious diseases affecting developing countries. Colloidal gold-based diagnostic tests are rapid tools to detect blood/serum antibodies for VL diagnosis. Lack of uniformity in the performance of these tests in different endemic regions is a hurdle in early disease diagnosis. This study is designed to validate a serum-based dipstick test in eight centres of six countries, India, Nepal, Sri Lanka, Brazil, Ethiopia and Spain with archived and fresh sera from 1003 subjects. The dipstick detects antibodies against Leishmania donovani membrane antigens (LAg). The overall sensitivity and specificity of the test with 95% confidence intervals were found to be 97.10% and 93.44%, respectively. The test showed good sensitivity and specificity in the Indian subcontinent (>95%). In Brazil, Ethiopia, and Spain the sensitivity and specificity of the dipstick test (83.78-100% and 79.06-100%) were better as compared to the earlier reports of the performance of rK39 rapid test in these regions. Interestingly, less cross-reactivity was found with the cutaneous form of the disease in Spain, Brazil, and Sri Lanka demonstrating 91.58% specificity. This dipstick test can therefore be a useful tool for diagnosing VL from other symptomatically similar diseases and against cutaneous form of leishmaniasis.S