Implementation of National Leprosy Eradication Programme during COVID-19 era: A qualitative research

Introduction: The COVID-19 pandemic imposed new challenge to the implementation of the National Leprosy Eradication Programme. According to national data, after lockdown due to COVID-19, there was a 29% reduction in total leprosy cases reported in the first quarter (April-June) of 2020 in comparison to 2019. Objectives: To explore the difficulties faced by different stakeholders of the National Leprosy Eradication Programme like policy makers, doctors, grass root level health workers as well as leprosy patients during COVID-19 pandemic with respect to programme implementation and access to leprosy care. Materials and Methods: Qualitative research was undertaken including two focus-group-discussions held among six leprosy patients diagnosed after lockdown and nine ASHA workers as well as six in-depth interviews of doctors, leprologists, and programme managers. Ethics committee approval was sought and informed consent was obtained from all participants. All focus-group-discussions were electronically recorded and the in-depth interviews telephonically recorded, transcribed and translated from Bengali-to-English. Transcripts were separately coded by researchers and thematically analysed with the help of Visual-Anthropac software version 1.0. Results: Solitary focus on COVID-19 control, capacity building and information, education and communication, leprosy case search & surveillance, co-infection among health workers, transportation issues were the themes explored from focus-group-discussions of health workers and ASHA workers. Similarly, the present study identified six themes from in-depth interviews of programme manager, leprologists, programme manager as diagnostic difficulty, operational issues, rehabilitation issues, capacity building & information education and communication activities and way forward. Limitations: The research reveals the perceptions of rural population of Eastern India with high leprosy prevalence, which might not be applicable for urban areas or low prevalent districts Conclusion: The solitary focus of the administration towards COVID and shifting the infrastructure and human resource only towards the management of COVID can lead to resurgence of the leprosy. Having an organised framework of operations, catering to the need of the front-line workers in rendering services, utilizing the digital platform and social media, and focusing on rehabilitation would be needed to overcome the crisis

Effectiveness and safety of 0.5% timolol solution in the treatment of pyogenic granuloma: A randomized, double-blind and placebo-controlled study

Introduction: Pyogenic granulomas are benign vascular lesions of the skin and mucosa which are often a source of concern because of their recurrent bleeding even with minimal trauma. Current treatment for pyogenic granuloma is ablative; no medical therapy is standardized to date. Timolol, due to its vasoconstrictive effect, vascular growth factor inhibition and apoptosis promotion properties, is a potential therapeutic option. Objectives: To assess the effectiveness and safety of topical timolol in the treatment of pyogenic granulomas. Methods: A two-centre, double-blind and placebo-controlled trial (Registration CTRI/2019/04/018581) was conducted. Patients of either sex were recruited with pyogenic granuloma lesions of less than eight weeks duration. Topical treatment with 0.5% timolol or matching glycerin placebo was continued for six weeks. Changes in color, size, bleeding tendency, physicians’ and patients’ global assessments and adverse events were assessed. Results: Forty subjects were randomized between the two groups which were comparable in age, sex, duration of illness and baseline lesion size.Significant improvement was noted with timolol, with color change from first follow-up onwards and lesion size reduction from second follow-up onward. Patients’ assessment of bleeding tendency also showed imrovement from the second visit onward. Between-group comparison showed significant difference with respect to percentage reduction in size (timolol 40.9%, placebo 3.4%; P = 0.002). Rescue treatment (electrosurgery) was required in five patients on placebo and in one in the timolol group (P = 0.182). Complete resolution occurred in 2 (10%) patients with timolol and in no patients on placebo (P = 0.231). Limitations: We observed effects of treatment for only six weeks. Conclusion: Topical timolol may be a treatment option for early pyogenic granulomas but complete resolution is unlikely in six weeks. Studies of longer duration are required to assess resolution and recurrence rates

Liposomal amphotericin B is more effective in polymorphic lesions of post kala-azar dermal leishmaniasis

Background: Post kala-azar dermal leishmaniasis (PKDL) is thought to be the reservoir of infection for visceral leishmaniasis in South Asia. The development of strategies for the diagnosis and treatment of PKDL are important for the implementation of the visceral leishmaniasis elimination program. Aims: Liposomal amphotericin B (L-AMB) has been an overwhelming success in the treatment of visceral leishmaniasis. However, the empirical three-week regimen of L-AMB proposed for PKDL was shown to be inadequate, especially in the macular variant. This study aimed to delineate response of the different variants of PKDL to L-AMB. Methods: Skin biopsies were collected from PKDL cases at disease presentation and upon completion of treatment with L-AMB. Parasite DNA was detected by Internal Transcribed Spacer-1 PCR (ITS-1 PCR) and quantified by amplification of parasite kDNA. CD68 + macrophages were estimated in tissue sections by immunohistochemistry. Results: Treatment with L-AMB decreased the parasite load by 97% in polymorphic cases but only by 45% in macular cases. The median parasite load (89965 vs 5445 parasites/μg of genomic DNA) as well as infiltration by CD68+ cells before treatment was much greater in the polymorphic cases. Limitations: Although monitoring of the parasite load for 12 months post-treatment would have been ideal, this was not possible owing to logistical issues as well as the invasive nature of biopsy collection procedure. Conclusion: A dramatic decrease in the parasite burden was noted in patients with polymorphic lesions. Although patients with macular disease also had a decrease in parasite burden, this was not as marked as in the polymorphic cases. There was also a significantly greater infiltration of CD68 + macrophages in polymorphic PKDL before therapy

A double-blind, randomized controlled trial to compare the effectiveness and safety of purified protein derivative of tuberculin antigen with Mycobacterium w vaccine in the treatment of multiple viral warts

Background: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. Aims: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts. Methods: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence. Results: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann–Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann–Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann–Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study. Limitation: Unicentric trial. Conclusion: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts.

A randomized, double-blind trial of amorolfine 0.25% cream and sertaconazole 2% cream in limited dermatophytosis

Background: Dermatophytosis is becoming increasingly unresponsive to conventional antifungals. Newer topical antifungals may be more effective in these patients. Aims: To evaluate and compare the efficacy and safety of amorolfine 0.25% cream and sertaconazole 2% cream in limited tinea cruris/corporis. Methods: A single-center, randomized (1:1), double-blind, parallel group, active-controlled trial (CTRI/2014/12/005246) was performed. Sixty-six untreated adults with acutely symptomatic tinea cruris/corporis were included in the study. All patients had limited cutaneous involvement and were KOH mount positive. Group A received amorolfine 0.25% cream, and group B received sertaconazole 2% cream twice daily application to the lesions for 4 weeks. After the baseline visit, four follow-up visits were carried out. The outcome measures for effectiveness were clinical and mycological cure. Safety parameters studied were treatment-emergent adverse events and changes in routine laboratory parameters. Results: Both sertaconazole and amorolfine significantly reduced symptoms (P < 0.001) in both groups. However, improvement in symptoms (pruritus, burning sensation, erythema, scaling and crusting) was significantly greater in the sertaconazole group at every follow-up visit. Sertaconazole cream was also more effective than amorolfine cream in reducing the number of lesions (P = 0.002 at 12 weeks) and improving the Dermatology Life Quality Index (P < 0.001) at all the follow-up visits. Adverse events were similar in the two groups (P = 0.117). Fungal cultures became negative in 92.3% of the sertaconazole group as compared to 80% in the amorolfine group (P = 0.010). Limitations: Antifungal susceptibility testing could not be done. Conclusion: Sertaconazole 2% is superior to amorolfine 0.25%, both in terms of effectiveness and tolerability. Improvement can be appreciated from second week onwards.

Guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis: An Indian perspective.

Background: Stevens–Johnson syndrome and toxic epidermal necrolysis are severe, life‑threatening mucocutaneous adverse drug reactions with a high morbidity and mortality that require immediate medical care. The various immunomodulatory treatments include systemic corticosteroids, cyclosporine, intravenous immunoglobulin, cyclophosphamide, plasmapheresis and tumor necrosis factor‑α inhibitors. Aim: The ideal therapy of Stevens– Johnson syndrome/toxic epidermal necrolysis still remains a matter of debate as there are only a limited number of studies of good quality comparing the usefulness of different specific treatments. The aim of this article is to comprehensively review the published medical literature and frame management guidelines suitable in the Indian perspective. Methods: The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) assigned the task of preparing these guidelines to its special interest group on cutaneous adverse drug reactions. The group performed a comprehensive English language literature search for management options in Stevens–Johnson syndrome/toxic epidermal necrolysis across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for keywords (alone and in combination) and MeSH items such as “guidelines,” “Stevens–Johnson syndrome,” “toxic epidermal necrolysis,” “corticosteroids,” “intravenous immunoglobulin,” “cyclosporine” and “management.” The available evidence was evaluated using the strength of recommendation taxonomy and graded using a three‑point scale. A draft of clinical recommendations was developed on the best available evidence which was also scrutinized and critically evaluated by the IADVL Academy of Dermatology. Based on the inputs received, this final consensus statement was prepared. Results: A total of 104 articles (meta‑analyses, prospective and retrospective studies, reviews [including chapters in books], previous guidelines [including Indian guidelines of 2006] and case series) were critically evaluated and the evidence thus gathered was used in the preparation of these guidelines. Recommendations: This expert group recommends prompt withdrawal of the culprit drug, meticulous supportive care, and judicious and early (preferably within 72 h) initiation of moderate to high doses of oral or parenteral corticosteroids (prednisolone 1‑2 mg/kg/day or equivalent), tapered rapidly within 7‑10 days. Cyclosporine (3‑5 mg/kg/day) for 10‑14 days may also be used either alone, or in combination with corticosteroids. Owing to the systemic nature of the disease, a multidisciplinary approach in the management of these patients is helpful.

Safety and effectiveness of autoinoculation therapy in cutaneous warts: A double - blind, randomized, placebo - controlled study.

Background: In spite of the availability of multiple treatment options, viral warts are known for their persistence and recurrence, causing frustration to patients and treating physicians. Aims: To study the effectiveness and safety of autoinoculation as a treatment modality in cutaneous warts. Methods: A double‑blind, placebo‑controlled study was carried out. In the treatment group, full‑thickness warty tissue was excised, minced and implanted in a small dermal pocket. In the control group, warty tissue was only excised and not implanted, though a dermal pocket was made. Patients were evaluated every four weeks with lesion counts. The procedure was repeated at 4 and 8 weeks. Response was assessed at each visit and at 12 weeks. Results: Forty‑eight patients with cutaneous warts (male: female = 32:16) were randomized into autoinoculation and control groups. The number of warts at baseline was comparable in both groups (P = 0.293). Reduction in the number of warts was significantly more in the autoinoculation group (8.50 ± 13.88) than in the control group (10.04 ± 5.80) from 8 weeks onwards (P = 0.010). Complete resolution occurred only in the autoinoculation group, in 62.5% of cases. Adverse effects were seen in 11 patients, including infection of the donor site (5 cases), keloid formation (3) and hypopigmentation (3). Conclusion: Autoinoculation may be an effective therapeutic modality for cutaneous warts and two sessions may be required for optimum results.

Bacterial contamination of the hands of doctors: A study in the medicine and dermatology wards.

Background: Doctors' hands are a common source of bacterial contamination. Often, these organisms are found to be virulent species with multidrug-resistance patterns. These are the sources of nosocomial infections in many patients. Aims: The present study was undertaken to find out the prevalence of bacterial contamination in the hands of doctors in the Medicine and Dermatology wards of a tertiary care hospital. Methods: The hands of 44 doctors were swabbed and cultured at entry to ward and at exit. Then, tap water and alcohol swab wash techniques were used and further swabs were done at each step. Thus, each doctor was sampled four-times for the study. The antibiotic-sensitivity pattern of the organisms was determined by the disc-diffusion method. Results: There was a significant contamination of the doctors' hands at entry (59.1%) and at exit (90.9%). Overall, Staphylococcus was the predominant organism (59% at entry and 85% at exit); coagulase-negative ones were more prevalent at entry (32%) and coagulase-positive ones were more prevalent at exit (54%). There was no difference in the hand contamination rates of junior and senior doctors. Also, the contamination rates were similar in the Medicine and Dermatology wards. Among the Gram negative organisms, Escherichia coli (4.5%), Pseudomonas (4.5%), Enterococci (13.6%) and Klebsiella (9%) were the main ones isolated. Gram negative organisms were significantly more prevalent at exit (P = 0.009) compared with their numbers at entry. Hand washing techniques reduced the contamination rates significantly, 76% with tap water wash and further 16.5% with alcohol swab. The removal rate for both groups of organisms was similar. Also, coagulase-positive and -negative Staphylococci showed equal rates of removal with hand washing (P = 0.9793). The organisms were found to be resistant to most of the commonly used antibiotics; the beta-lactam group was especially largely resistant both for Gram positive and Gram negative bacteria. Both cheaper ones like cloxacillin (50-100%) and very costly ones like cefepime (100%) were equally vulnerable to resistance. Even newer antibiotics like linezolid and vancomycin showed a significant resistance to Staphylococcus. In Gram negative organisms, drugs like ceftazidime and gentamicin showed 100% resistance. Conclusion: This study shows the high level of contamination of doctors' hands. It emphasizes the need for proper hygienic measures in day to day practice in hospitals to reduce the level of nosocomial infections. Also, it shows that most of the commonly used antibiotics will be ineffective in nosocomial infections.

Epidemiology and prevention of chronic arsenicosis: an Indian perspective.

Arsenicosis is a global problem but the recent data reveals that Asian countries, India and Bangladesh in particular, are the worst sufferers. In India, the state of West Bengal bears the major brunt of the problem, with almost 12 districts presently in the grip of this deadly disease. Recent reports suggest that other states in the Ganga/Brahmaputra plains are also showing alarming levels of arsenic in ground water. In West Bengal, the majority of registered cases are from the district of Nadia, and the maximum number of deaths due to arsenicosis is from the district of South 24 Paraganas. The reason behind the problem in India is thought to be mainly geogenic, though there are instances of reported anthropogenic contamination of arsenic from industrial sources. The reason for leaching of arsenic in ground water is attributed to various factors, including excessive withdrawal of ground water for the purpose of irrigation, use of bio-control agents and phosphate fertilizers. It remains a mystery why all those who are exposed to arsenic-contaminated water do not develop the full-blown disease. Various host factors, such as nutritional status, socioeconomic status, and genetic polymorphism, are thought to make a person vulnerable to the disease. The approach to arsenicosis mitigation needs be holistic, sustainable, and multidisciplinary, with the 2 main pillars being health education and provision of 'arsenic-free water.' In the state of West Bengal, the drive for arsenic mitigation has been divided into 3 phases using various methods, including new hand pumps/tube wells at alternative deep aquifers, dug wells, arsenic removal plants, arsenic treatment units, as well as piped and surface water supply schemes. The methods have their own limitations, so it is intended that a pragmatic approach be followed in the arsenicosis prevention drive. It is also intended that the preventive measures be operationally and economically feasible for the people living in the affected areas.

Arsenicosis: diagnosis and treatment.

Diagnosis of arsenicosis relies on both clinical and laboratory criteria, but principally it can be diagnosed on the basis of its cutaneous manifestations. Cutaneous manifestations (melanosis, keratosis, and cutaneous cancers) are essential clues in the diagnosis, and trained dermatologists or arsenic experts are able to clinically confirm a case even without laboratory backup. Although systemic manifestations are not considered as diagnostic hallmarks, yet their presence serves as important telltale signs in arriving at the diagnosis. In countries where laboratory facilities are available, measuring the level of arsenic in drinking water (consumed in the last 6 months), urine, hair, and nails is of immense value. Newer biomarkers of arsenic exposure are being explored to provide early information about arsenic intoxication, of which urinary porphyrin level, blood metallothionein have shown promising results. Controlling the problem of arsenicosis depends on various factors, of which the most important is cessation of intake of arsenic-contaminated water. Deep wells, traditional dug wells, treatment of surface water, rainwater harvesting, and removing arsenic from the contaminated water by arsenic removal plant or arsenic treatment unit are the available options for providing arsenic-free drinking water. The role of nutrition and antioxidants in preventing the onset of symptoms of arsenicosis is also of importance. Nonspecific therapies (e.g., keratolytics for hyperkeratosis) cannot also be ignored and serve as palliative measures. The persons affected need to be followed up at regular intervals to detect the onset of cancers (if any) at the earliest. Role of counseling and education should never be underestimated since absence of public awareness can undermine all efforts of mitigation measures.

Pathogenesis, clinical features and pathology of chronic arsenicosis.

Arsenicosis is a multisystem disorder, with virtually no system spared from its vicious claw; though its predominant manifestations are linked to cutaneous involvement. Cutaneous effects take the form of pigmentary changes, hyperkeratosis, and skin cancers (Bowen's disease, squamous cell carcinoma, and basal cell epithelioma). Peripheral vascular disease (blackfoot disease), hypertension, ischemic heart disease, noncirrhotic portal hypertension, hepatomegaly, peripheral neuropathy, respiratory and renal involvement, bad obstetrical outcome, hematological disturbances, and diabetes mellitus are among the other clinical features linked to arsenic toxicity. The effects are mediated principally by the trivalent form of arsenic (arsenite), which by its ability to bind with sulfhydryl groups present in various essential compounds leads to inactivation and derangement of body function. Though the toxicities are mostly linked to the trivalent state, arsenic is consumed mainly in its pentavalent form (arsenate), and reduction of arsenate to arsenite is mediated through glutathione. Body attempts to detoxify the agent via repeated oxidative methylation and reduction reaction, leading to the generation of methylated metabolites, which are excreted in the urine. Understandably the detoxification/bio-inactivation process is not a complete defense against the vicious metalloid, and it can cause chromosomal aberration, impairment of DNA repair process, alteration in the activity of tumor suppressor gene, etc., leading to genotoxicity and carcinogenicity. Arsenic causes apoptosis via free radical generation, and the cutaneous toxicity is linked to its effect on various cytokines (e.g., IL-8, TGF-beta, TNF-alpha, GM-CSF), growth factors, and transcription factors. Increased expression of cytokeratins, keratin-16 (marker for hyperproliferation) and keratin-8 and -18 (marker for less differentiated epithelial cells), can be related to the histopathological findings of hyperkeratosis and dysplastic cells in the arsenicosis skin lesion.