Elimination of visceral leishmaniasis in Nepal: Pipe-dreams and possibilities

Introduction: Visceral Leishmaniasis (VL) re-emerged in the Indian subcontinent in the mid-1970s after an almost complete absence in the previous fifteen or so years. The disease was first noted in Nepal in 1978 and, since 1980, it has been reported regularly in increasing numbers. Elimination of visceral leishmaniasis by 2015 has been identified as regional priority program in the level of high political commitment. Objective: The objectives of this study are the comprehensive assessment of information related to VL on the basis of past research studies conducted in Nepal, and an assessment of the prospects of control measures. Materials and methods: This was time line comprehensive VL epidemiological assessment study based on the research conducted by main author during the past ten years. During the period the studies were conducted using cross sectional, case control and exploratory study design. The statistical analysis was done using qualitative and quantitative methods. Results: In our study in the visceral leishmaniasis endemic district, Siraha, in the population of 112,029, a total of 996 clinically suspected cases were reported (with fever of long duration and splenomegaly, with no malaria) during 1998-2002. In all, 283 subjects were found positive for visceral leishmaniasis by rK39 and 284 had positive bone marrow. There was no detectable difference in the density of Phlebotomus argentipes between high, and moderate incidence village development committees (VDC: the smallest administrative unit), but collections in the low incidence areas (in winter) were negative. P. argentipes was never numerous (maximum 4.4 females collected per man-hour), and was much less common than P. papatasi. Peaks of abundance were recorded in the March and September collections. We have found that the numbers of reported cases of visceral leishmaniasis in Nepalese villages was unaffected by indoor residual spray (IRS) indicated by parallel trends in case numbers by time series analysis in treated and untreated villages. A series of maps through ten years clearly showed that the infection can move rapidly between villages, and it is impossible to predict where transmission will occur from year to year. Conclusion: If maximum benefit in relation to cost is the goal, it may be preferable to put all possible efforts into active case detection (ACD) with free treatment. ACD should involve the network of Village Health Workers or Female Community Health Volunteers and the rK39 dipstick test at health centre level. Surveillance of disease and vector, communication for behavioural impacts and insecticide spraying should be important component of elimination program. If IRS is to be a part of the intervention, it is essential that it is carried out effectively, both in areas where the disease has been reported and in neighbouring areas. Integrated vector management need to be monitored for its application and effectiveness for VL elimination.     

Visceral pain

Visceral pain, although different from somatic pain in several important features, is not as widely researched and consequently our knowledge of neurophysiologic mechanisms as well as clinical management of visceral pain states remains unsatisfactory. Several recent studies have employed different visceral pain animal models to provide insight into the peripheral and central nervous system mechanisms underlying pain originating from the urinary bladder, ureter, and gastrointestinal tract. The effects of opioid and nonopioid drugs in these models have also been evaluated and are reviewed in this article. The importance of anatomic pathways relaying pain sensation in the central nervous system, particularly the newly described dorsal column pathway, is also discussed. In human subjects, new techniques like positron emission tomography are now being used to better understand visceral pain perception. Such findings deriving from basic animal research and human studies summarized in the present overview lead to a better understanding of visceral pain states and may be helpful in developing better treatment strategies to combat visceral pain states in the clinical setting.     

Adenosine-induced ventricular asystole to induce transient profound systemic hypotension in patients undergoing endovascular therapy. Dose-response characteristics

BACKGROUND: Adenosine-induced asystole has been used to induce transient systemic hypotension for various vascular procedures. Dose-response characteristics of adenosine-induced ventricular asystole have not been determined. METHODS: During endovascular embolization of cerebral arteriovenous malformations, the authors performed a series of adenosine test injections to establish a dose-response relation in each patient. After an interval of 3-10 min, the dose was escalated by 10-20 mg for each injection to achieve an end point of 20-30 s of stable mean arterial pressure (MAP) reduction to 25-30 mmHg. All patients received constant infusion of nitroprusside (approximately 1 microgram. kg-1. min-1) throughout the procedure. RESULTS: The authors studied four adult patients (age, 22-44 yr; two patients had two separate procedures) and one pediatric patient (age, 4 yr). Twenty-three adenosine injections resulted in measurable asystole. The adenosine dose was 0. 98 +/- 0.40 mg/kg (mean +/- SD), and the dose range was 0.24-1.76 mg/kg (6-90 mg). The duration of asystole, MAP < 30 mmHg, and MAP < 50 mmHg, were 8 +/- 3 s, 18 +/- 12 s, and 50 +/- 29 s, respectively. The minimum MAP and the MAP for the first 20 s were 16 +/- 3 mmHg and 30 +/- 9 mmHg, respectively. There was a linear relation between adenosine dose and the duration of hypotension with MAP < 30 mmHg and MAP < 50 mmHg. CONCLUSIONS: In the dose range studied, a series of adenosine test injections can be used to determine optimal adenosine dose for induction of transient profound hypotension.     

Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown. PATIENTS AND METHODS: Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily; (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily. RESULTS: No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% CI, 2% to 42%) achieved a confirmed partial response. CONCLUSION: The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted.     

A Short Series of Case Reports of COVID-19 in Immunocompromised Patients

Immunocompromised individuals are at risk of prolonged SARS-CoV-2 infection due to weaker immunity, co-morbidities, and lowered vaccine effectiveness, which may evolve highly mutated variants of SARS-CoV-2. Nonetheless, limited data are available on the immune responses elicited by SARS-CoV-2 infection, reinfections, and vaccinations with emerging variants in immunocompromised patients. We analyzed clinical samples that were opportunistically collected from eight immunocompromised individuals for mutations in SARS-CoV-2 genomes, neutralizing antibody (NAb) titers against different SARS-CoV-2 variants, and the identification of immunoreactive epitopes using a high-throughput coronavirus peptide array. The viral genome analysis revealed two SARS-CoV-2 variants (20A from a deceased patient and an Alpha variant from a recovered patient) with an eight amino-acid (aa) deletion within the N-terminal domain (NTD) of the surface glycoprotein. A higher NAb titer was present against the prototypic USA/WA1/2020 strain in vaccinated immunocompromised patients. NAb titer was absent against the Omicron variant and the cultured virus of the 20A variant with eight aa deletions in non-vaccinated patients. Our data suggest that fatal SARS-CoV-2 infections may occur in immunocompromised individuals even with high titers of NAb post-vaccination. Moreover, persistent SARS-CoV-2 infection may lead to the emergence of newer variants with additional mutations favoring the survival and fitness of the pathogen that include deletions in NAb binding sites in the SARS-CoV-2 surface glycoprotein.     

Pure Sertoli cell tumor of the ovary: A case report

Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases.     

Screening for gestational diabetes,Ahmedabad, India

ObjectiveTo implement a community-based screening and awareness-raising project for gestational diabetes in Ahmedabad, India.MethodsThe project took place between April 2016 and August 2019 in Ahmedabad. Medical college faculty members and medical officers trained 3582 paramedical staff on screening for gestational diabetes. These paramedical staff tested all pregnant women 24–28 weeks gestation, who were attending village health and nutrition days – also called mamta days – in urban and rural health centres for routine antenatal care, for gestational diabetes. An oral glucose tolerance test was used and blood sugar ≥ 7.8 mmol/L was the cut-off for gestational diabetes. Women with gestational diabetes were referred for counselling and treatment and all women were followed until 6 weeks after delivery.FindingsOf 53 522 pregnant women screened, 6786 (12.7%) had gestational diabetes and were referred for nutritional therapy or medication; 836 (12.3%) of these women started medication. There was no significant difference in the prevalence of stillbirths between women with gestational diabetes (0.8%; 54/6786) and women without (0.7%; 338/46 736; P-value: 0.51). Of the women on treatment, 38 had abnormal blood glucose after delivery and continued with the medication. Two women with gestational diabetes died; they had other associated co-morbidities – pre-eclampsia and anaemia.ConclusionWe found a high prevalence of gestational diabetes, indicating the need for gestational diabetes screening and implementation of this project on a larger scale. Gestational diabetes screening at the community level is operationally feasible using the existing human resources and infrastructure of the reproductive health programmes.