Barriers to the effective management and prevention of post kala-azar dermal leishmaniasis (PKDL) in the Indian subcontinent.

Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary.

Iron oxide nanoparticles based antiviral activity of H1N1 influenza A virus.

Influenza virus is a common human pathogenic agent that has caused serious respiratory illness and death over the past century and in recent year. Treatment options against pandemic influenza strain A/H1N1 are very limited and unsatisfactory. Therefore we have developed iron oxide nanoparticles (IO-NPs) with particle size in the range of 10-15 nm against pandemic influenza strain A/H1N1/Eastern India/66/PR8-H1N1. Cell viability and anti-influenza activity was measured by MTT assay, plaque inhibition and quantifying viral transcripts using quantitative real-time PCR with Iron oxide nanoparticles in a dose- and time-dependent manner. 50% cell viability (TD50) was observed at 4.25 pg ± .2 pg of Iron oxide nanoparticles. The percentage of plaque inhibition relative to the infection and the IC50 (50% virus reduction) of PR8-H1N1strain (0.5 moi) were measured in vitro by the plate forming unit (pfu) in MA104 cells. Finding were observed at 01 pg after 72 h. The Antiviral activity determined by change in viral RNA transcripts within 24 h of virus infection by RT-PCR, 08 fold reductions in virus found when treated with Iron oxide nanoparticles Thus; it opens a new avenue for use of IP-NPs against virus infections.

Prevalence of Myopia and Associated Risk Factors in Schoolchildren in North India.

SIGNIFICANCE: Studies reporting the prevalence and associated risk factors of myopia among schoolchildren in India are limited. Knowledge about the prevalence and the modifiable risk factors associated with myopia development will help in planning cost-effective strategies to prevent its progression in India. PURPOSE: The purpose of this study was to assess the prevalence and associated behavioral risk factors of myopia in schoolchildren in Gurugram, Haryana, in north India. METHODS: This cross-sectional study was conducted on schoolchildren (aged 5 to 15 years) from two private schools in Gurugram. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study chart. Myopia was defined as the spherical equivalent refractive error of at least -0.50 D in the better eye. Information on the child's habits and lifestyle, study hours, hours of playing video games, and outdoor playtime were obtained using a questionnaire. Association of behavioral risk factors was analyzed for children with and without myopia, and adjusted odds ratio (OR) for each factor was estimated. RESULTS: A total of 1234 children (mean ± SD age, 10.5 ± 3 years; 59% boys) were screened. Myopia prevalence was found to be 21.1% (n = 261; mean ± SD age, 11 ± 2 years; 52% boys). The mean ± SD myopic spherical error was -1.94 ± 0.92 D. The prevalence of myopia was found to be higher (27%; 95% confidence interval, 23 to 30.6; OR, 3.19 [2.13 to 4.76]) among older children (9 to 12 years). Prevalence of myopia was more in boys (25%; 95% confidence interval, 21.1 to 28.8) compared with girls (P < .01). A positive association of presence of myopia was observed with children studying more than 4 hours per day (P < .008) and with children playing computer/video/mobile games more than 2 hours per day (P < .001). A protective effect was observed in children with outdoor activities/play for more than 1.5 hours per day (OR, 0.01 [0.00 to 0.06]). CONCLUSIONS: Myopia is a major public health concern, and its prevalence is increasing rapidly among schoolchildren in India. There is a pressing need to develop cost-effective strategies to prevent this cause of vision impairment, which can be easily treated with optical interventions.

Therapeutic Assessment of Primaquine for Radical Cure of Plasmodium vivax Malaria at Primary and Tertiary Care Centres in Southwestern India.

Acquaintance is scanty on primaquine (PQ) efficacy and Plasmodium vivax recurrence in Udupi district, Karnataka, India. We assessed the efficacy of 14 days PQ regimen (0.25 mg/kg/day) to prevent P. vivax recurrence. Microscopically, aparasitemic adults (≥18 years) after acute vivax malaria on day 28 were re-enrolled into 15 months' long follow-up study. A peripheral blood smear examination was performed with participants at every 1-2 month interval. A nested PCR test was performed to confirm the mono-infection with P. vivax. Of 114 participants, 28 (24.6%) recurred subsequently. The median (IQR) duration of the first recurrence was 3.1 (2.2-5.8) months which ranged from 1.2 to 15.1 months, including initial 28 days. Participants with history of vivax malaria had significantly higher risk of recurrence, with hazard ratio (HR) (95% CI) of 2.62 (1.24-5.54) (P=0.012). Severity of disease (11.4%, 13/114) was not associated (P=1.00) with recurrence. Of 28 recurrence cases, the nPCR proved that P. vivax mono-infection recurrence rate was at least 72.7% (16/22) at first recurrence. In Udupi district, PQ dose of 0.25 mg/kg/day over 14 days seems inadequate to prevent recurrence in substantial proportion of vivax malaria. Patients with a history of vivax malaria are at high risk of recurrences.

Radio-modifying potential of Saraca indica against ionizing radiation: an in vitro study using Chinese hamster lung fibroblast (V79) cells.

This study demonstrated the radioprotective efficacy of extracts prepared from stem bark of Saraca indica (SI) against X-rays induced cellular damage, which was evaluated by a battery of cytotoxicity, genotoxicity, apoptotic, and biochemical assays using Chinese hamster fibroblast (V79) cells. Cell viability and surviving fraction were increased significantly when V79 cells were preconditioned with optimal concentration of hydroalcoholic extract (HE; 50 µg/mL) of SI for 2 h prior exposure to X-rays. Radiation induced cellular damage was correlated with a significant elevation in intracellular ROS and increased mitochondrial depolarization and loss of intracellular antioxidant enzymes. However, cells preconditioned with 50 µg/mL of HE reversed this effect. Pretreatment of HE resulted in inhibition of radiation induced GSH, GST, SOD, catalase levels, and lipid peroxidation to that of radiation-alone treated group. Also, a significant decrease in radiation induced DNA damage, apoptotic and necrotic cell death was observed in case of cells preconditioned with HE. Supporting to this HPLC analysis indicated the presence of ellagic acid as one of the major phytochemical present in HE. Thus, the maintenance of cellular redox status by pretreatment with HE, conferred protection of cellular DNA, oxidative stress by neutralizing free radicals generated by the cellular irradiation and resulted in increased in cell survival may be attributed to the presence of ellagic acid indicating SI's radioprotective potential.

Inhibitory role of copper and silver nanocomposite on important bacterial and fungal pathogens in rice (Oryza sativa).

Rice (Oryza sativa) being among the most important food crops in the world is also susceptible to various bacterial and fungal diseases that are the major stumbling blocks in the way of increased production and productivity. The bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae and the sheath blight disease caused by Rhizoctonia solani are among the most devastating diseases of the rice crop. In spite of the availability of array of chemical control, there are chances of development of resistance. Thus, there is a need for the nanotechnological intervention for management of disease in the form of copper and silver nano-composites. The copper (CuNPs) and silver nanoparticles (AgNPs) were synthesized using green route and characterized using different high throughput techniques, i.e., UV-Vis, FT-IR, DLS, XRD, FE-SEM, TEM. The particle size and zeta potential of synthesized CuNPs and AgNPs were found 273 nm and - 24.2 mV; 95.19 nm and - 25.5 mV respectively. The nanocomposite of CuNPs and AgNPs were prepared having particle size in the range of 375-306 nm with improved stability (zeta potential - 54.7 to - 39.4 mV). The copper and silver nanoparticle composites evaluated against Xanthomonas oryzae pv. oryzae and Rhizoctonia solani were found to have higher antibacterial (inhibition zone 13 mm) and antifungal activities (77%) compared to only the copper nanoparticle (8 mm; 62% respectively). Net house trials of nano-composite formulations against the bacterial blight of rice also corroborated the potential of nanocomposite formulation. In silico studies were carried out selecting two disease-causing proteins, peptide deformylase (Xanthomonas oryzae) and pectate lyase (Rhizoctonia solani) to perform the molecular docking. Interaction studies indicatedthat both of these proteins generated better complex with CuNPs than AgNPs. The study suggested that the copper and silver nano-composites could be used for developing formulations to control these devastating rice diseases.

Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform. METHODS: A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology. RESULTS: A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen. CONCLUSIONS: Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.

Gum Arabic enhances paracellular transport of water in amphibian everted small intestinal segments.

Gum Arabic (GA) is known for its proabsorbent activity in normal intestine as well as in animal models of diarrhea. The aim of the study was to find the effect of GA on intestinal transport of water and possible route of absorption in frog everted gut sacs. D-Mannitol was used as a marker of paracellular transport to find the route of absorption. Everted gut sacs (n = 4,5) were placed in Ringer containing GA (2.5 g/L) with or without D-Mannitol (0.5 g/L), incubated for 1 hour and analysed for change in weights of the sacs and D-Mannitol uptake. There was significant increase in uptake of water and D-Mannitol in the presence of GA compared to controls (P < 0.05). Gum Arabic improves water uptake by the intestinal mucosa, possibly by opening the paracellular pathways.

Determinants of ventilator associated pneumonia and its impact on prognosis: A tertiary care experience.

BACKGROUND: Ventilator associated pneumonia (VAP) is a major cause of poor outcome among patients in the intensive care units (ICU) world-wide. We sought to determine the factors associated with development of VAP and its prognosis among patients admitted to different ICUs of a Tertiary Care Hospital in India. METHODOLOGY: We did a matched case control study during October 2009 to May 2011 among patients, ≥18 years with mechanical ventilation. Patients who developed pneumonia after 48 h of ventilation were selected in the case group and those who did not develop pneumonia constituted the control group. Patients' history, clinical and laboratory findings were recorded and analyzed. RESULTS: There were 52 patients included in each group. Among cases, early onset ventilator associated pneumonia (EVAP) occurred in 27 (51.9%) and late onset ventilator associated pneumonia (LVAP) in 25 (48.1%). Drug resistant organisms contributed to 76.9% of VAP. Bacteremia (P = 0.002), prior use of steroid/immunosuppressant (P = 0.004) and re-intubations (P = 0.021) were associated with the occurrence of VAP. The association of Acinetobacter (P = 0.025) and Pseudomonas (P = 0.047) for LVAP was found to be statistically significant. Duration of mechanical ventilation (P = 0.001), ICU stay (P = 0.049) and requirement for tracheostomy (P = 0.043) were significantly higher in VAP. Among each case and control groups, 19 (36.5%) expired. CONCLUSION: We found a higher proportion of LVAP compared with EVAP and a higher proportion of drug resistant organisms among LVAP, especially Pseudomonas and Acinetobacter. Drug resistant Pseudomonas was associated with higher mortality.

Assessing the Prevalence of Financial Toxicity, its Predictors and Association with Health- Related Quality of Life Among Radiation Oncology Patients in India: A Cross-Sectional Patient Reported Outcome Study.

PURPOSE: Financial toxicity has been associated with several clinical outcomes such as early mortality and poor quality of life. The aim of this study was to evaluate the magnitude of financial toxicity among radiation oncology patients and its association with health-related quality of life (HRQOL) in Indian health care settings. METHODS AND MATERIALS: This cross-sectional study was conducted among patients with cancer who had completed radiation therapy, either standalone or as part of a multimodal treatment. Financial toxicity and HRQOL were assessed using the Comprehensive Score for Financial Toxicity (COST) and Functional Assessment of Cancer Therapy: General (FACT-G) measures, respectively. Associations between financial toxicity and HRQOL were assessed using Pearson correlation. Univariate and multivariate regression analyses were conducted to identify the factors associated with financial toxicity. RESULTS: A total of 350 patients were included in this study. Of the 350 participants, 57.7% were male, 95.7% had no health insurance, and 61% were diagnosed with Head & Neck cancers. The average COST score was 15.38 ± 9.18 (range, 2-35), and the average FACT-G score was 69.63 ± 12.25 (range, 33-99). Based on the total COST score, 7.4% of participants reported grade 3 and 44.9% reported grade 2 financial toxicity. A significant positive correlation was observed between the COST and FACT-G scores, with a correlation coefficient of 0.58 (P < .001), indicating a large effect size. The COST score also significantly predicted the FACT-G score (ß = 0.77; 95% confidence interval [CI], 0.66-0.88; P < .001). The results of multivariate linear regression identified annual household income (ß = 3.9; 95% CI, 3.29-4.57; P < .001) and cancer type (ß = 3.74; 95% CI, 2.33-5.14; P < .001) as significant predictors of the COST score. CONCLUSIONS: More than 80% of the participants experienced financial toxicity in this study. The results highlight the need for interventions to alleviate the growing financial toxicity among cancer survivors in India.

Acute Upper Limb Ischemia and Amputation Post Antecubital Fossa Cannulation: A Report of Two Postpartum Patients.

Upper extremity arterial thrombosis is less common than that in the lower extremity. Upper extremity arterial thrombosis, when present, is more likely to occur on the ulnar side of the circulation. Severe ischemia resulting from radial artery thrombosis is rare, but iatrogenic cannulation is the most common etiology when it occurs. The risk factors underlying this dreadful presentation are numerous and still under investigation. Pregnancy and the immediate postpartum period are physiological hypercoagulable states. Here we present unusual cases of acute limb ischemia post iatrogenic cannulation in two patients within six weeks postpartum. At four weeks postpartum, a 26-year-old para-1 live-1 female presented to the emergency department with swelling in her right upper limb for four weeks and its blackish discoloration for one week. A 24-year-old primigravida female who had a termination of a blighted ovum 12 days ago presented to the emergency department with gangrenous changes in her right hand and forearm. Both patients reported recent antecubital fossa cannulation within six weeks postpartum, triggering gangrenous hand changes. Both patients had to undergo amputation of the digits and hand ultimately. Thus we postulate the need for extra care and education of healthcare workers in the cannulation of pregnant and post-pregnancy patients to prevent limb-threatening complications.

Older PLHIV are at Higher Cardiovascular Risk with Poor Quality of Life.

BACKGROUND: People with HIV (PLHIV) face increased cardiovascular disease (CVD) risk due to inflammation and immune activation. Aging further amplifies this risk. Limited data exist on CVD risk in older PLHIV in India despite 2.14 million PLHIV with higher CVD risk factors. METHODS: In a cross-sectional study in Bihar, India, 73 PLHIV and 30 control participants were enrolled. Demographics, social factors, clinical information, and CVD risk factors were collected. HbA1c levels and lipid profiles were analyzed, and 10-year CVD risk scores were calculated using the Framingham risk score (FRS) and Qrisk3. Quality of life (QoL) was assessed using WHOQOL- HIV-BREF. RESULTS: Results showed higher LDL levels in non-HIV older participants and higher HDL levels in younger PLHIV participants. BMI differed significantly, with higher BMI in non-HIV older individuals and lower BMI in younger PLHIV individuals. Older PLHIV participants had significantly higher mean FRS and Q-Risk scores compared to older non-PLHIV and younger PLHIV groups. Among older PLHIV participants, six had higher CVD risk per FRS, while none in the other groups were classified as high CVD risk. Psychological, social relations and spirituality domains were highly deteriorated in older PLHIV, scoring 44.48, 42.72, and 41.2, respectively. The physical domain scored 57.6, and the environment scored 52.72 in the WHOQOL-HIV bref. CONCLUSION: In conclusion, older PLHIV in Bihar, India, face higher CVD risk compared to younger PLHIV and non-HIV individuals. FRS and Q-Risk scores effectively assessed CVD risk, identifying higher risk in older PLHIV. Age and BMI were significant predictors of high CVD risk. These findings emphasize CVD risk assessment and tailored management for older PLHIV. The QoL assessment findings indicate moderate deterioration in psychological, social relations, and spirituality domains among older PLHIV individuals. These results suggest greater challenges in psychological well-being, social interactions, and spirituality compared to the overall sample. Further research with larger samples and longitudinal designs is needed to confirm and extend these findings.

Host, parasite and drug determinants of clinical outcomes following treatment of visceral leishmaniasis: a protocol for individual participant data meta-analysis.

INTRODUCTION: Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes. METHODS AND ANALYSIS: The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering. ETHICS AND DISSEMINATION: This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (Exempt granted on 29 March 2023, OxTREC REF: IDDO) Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (Letter no: RMRI/EC/30/2022) on 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments. PROSPERO REGISTRATION: CRD42021284622.

Haematological dynamics following treatment of visceral leishmaniasis: a protocol for systematic review and individual participant data (IPD) meta-analysis.

INTRODUCTION: Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. Despite anaemia being a common haematological manifestation of VL, the evolution of different haematological characteristics following treatment remains poorly understood. An individual participant data meta-analysis (IPD-MA) is planned to characterise the haematological dynamics in patients with VL. METHODS AND ANALYSIS: The Infectious Diseases Data Observatory (IDDO) VL data platform is a global repository of IPD from therapeutic studies identified through a systematic search of published literature (PROSPERO registration: CRD42021284622). The platform currently holds datasets from clinical trials standardised to a common data format. Corresponding authors and principal investigators of the studies indexed in the IDDO VL data platform meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Mixed-effects multivariable regression models will be constructed to identify determinants of haematological parameters by taking clustering within study sites into account. ETHICS AND DISSEMINATION: This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (exempt granted on 29 March 2023, OxTREC REF: IDDO). Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (letter no.: RMRI/EC/30/2022) on 4 July 2022. The results of this analysis will be disseminated at conferences, the IDDO website and peer-reviewed publications in open-access journals. The findings of this research will be critically important for control programmes at regional and global levels, policymakers and groups developing new VL treatments. PROSPERO REGISTRATION NUMBER: CRD42021284622.

Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis.

BACKGROUND: The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse. METHODS: A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to <70 g/L, or an absolute drop of >50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose. RESULTS: In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to <5 mg/kg) and 0% (96 patients; 0 recurrences) following high total dose primaquine (≥5 mg/kg). In the subsequent two-stage meta-analysis of nine studies (3529 patients), the pooled proportions of P. vivax recurrences by day 180 were 12.1% (95% CI 7.7% to 17.2%), 2.3% (95% CI 0.3% to 5.4%) and 0.7% (95% CI 0% to 6.1%), respectively. No patients had a >25% drop in haemoglobin to <70 g/L. CONCLUSIONS: Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events. PROSPERO REGISTRATION NUMBER: CRD42022313730.

Clinical profile, species-specific severity grading, and outcome determinants of snake envenomation: An Indian tertiary care hospital-based prospective study.

OBJECTIVE: We undertook this study to assess the clinical profile and outcome determinants of different snake envenomation as well as to assign species-specific severity grade to different cases based on clinico - laboratory evidence scale. MATERIALS AND METHODS: A prospective clinico - epidemiologic evaluation for outcome determinants of snakebite envenomation was carried out based on a clinico - laboratory severity grading scale, among 76 patients over a period of 2 years, in a tertiary care hospital in southern India. RESULTS: Majority of patients were male agricultural workers (53.9%) followed by housewives (19.7%), and students (9.2%). Occurrence of viper snake envenomation with hemotoxic syndrome (73.68%) was highest followed by cobra and krait envenomation with neurotoxic (19.73%) and hemo - neurotoxic (5.3%) syndrome, respectively. On the contrary, maximum mortality and severity was seen in krait (60%) followed by cobra (13.33%) and viper (8.9%) envenomation. The average dose of anti-snake venom (ASV) administered varied from 9.83 (±7.22) to 20.25 (±4.92) vials throughout grade I to IV in all snake species envenomation. An increase in severity grade, ASV dose, and mortality were observed with the corresponding delay in 'bite to needle time.' Also, initial traditional treatments and krait species envenomation were significantly associated with higher grades of severity and mortality. CONCLUSION: There is an urgent need to spread awareness among the community for avoidance of traditional treatment and any delay in medical intervention in snakebite incidents.

Breast gangrene: Tale of two similar cases with two different outcomes.

Breast gangrene is rare in surgical practice. Its aetiology is variable and multifactorial. Debridement and appropriate antibiotic treatment are the mainstay of management. Two such cases presented one early and the other desperately late. We report these two cases to emphasise the potential fatality of this condition.

Knowledge, attitude and practices towards visceral leishmaniasis among HIV patients: A cross-sectional study from Bihar, India.

BACKGROUND: In the Indian state of Bihar, visceral leishmaniasis (VL) is a major public health issue that has been aggravated by the rising incidence of new Human immunodeficiency virus (HIV) infections. In endemic areas, the risk of VL infections in patients living with HIV (PLHIV) is higher. It is important to investigate the disease-related knowledge, attitude, and practices (KAP) of PLHIV in Bihar in order to monitor HIV/VL co-infection. Adequate knowledge, a positive attitude, and good practices for VL control are essential to stamp out the disease. This study investigated the KAP towards VL in HIV patients attending antiretroviral therapy (ART) clinic at ICMR-RMRIMS, Patna. METHODS: A questionnaire based cross-sectional study was performed among 120 HIV patients aged ≥18 years, to evaluate their KAP regarding visceral leishmaniasis. For the KAP indicators, each correct answer received a score of 1, while unsure and incorrect responses received a score of 0. Descriptive statistics and logistic regression were used for the analysis. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 27. RESULTS: The study population had a male (68.30%) preponderance with a mean age of 37.03 years ± 9.80 years of standard deviation. The majority (93.30%) of the study participants had previously heard about VL. Only 32.10% of those who had heard about VL knew that the disease was transmitted by the sandfly. Most (80.40%) of the study respondents were ignorant of the sandfly breeding grounds. The vast majority (75.90%) had no idea how to recognize sandflies and were unaware of their biting time, leishmaniasis transmission season, and preventive practices. Although PLHIV are vulnerable to VL, only 27.70% of them agreed that VL is a fatal disease if untreated, and 42.90% believed they wear not at risk of developing the disease. Regarding the control methods of sandflies, 28.60% of participants did not use any methods to avoid sandfly bites. The multivariable analysis revealed that occupation and family history were the two independent predictor variables of the knowledge index. Age and gender were significantly associated with attitude towards VL. Participants working as laborers had significantly lesser odds (AOR: 0.248, 95% CI: 0.073-0.844) to follow good preventive practices. There were significantly higher odds of having good practice among participants aged 18-40 years (AOR: 6.866, 95% CI: 1.694-27.834) and those residing in urban areas (AOR: 4.159, 95% CI: 1.317-13.139) than their peers. Overall, 27.7% of respondents were knowledgeable, 41.1% had a positive mindset, and 33.9% had strong VL preventive habits, according to the study. CONCLUSION: The study determined a remarkable gap in the knowledge attitude and practices towards VL among PLHIV. This underscores the need of augmented health education initiatives for PLHIV in endemic areas for good VL awareness and preventive practices.

TrypInDB: A searchable online resource of small molecule inhibitors against Trypanosoma sp.

African Trypanosomiasis and American Trypanosomiasis are the diseases affecting more than thousands of people yearly and more than twenty-five million people risk acquiring the disease. The treatment for the disease is generally expensive, and most of the available drugs are of high-toxicity and cause fatal side-effects. Hence, there is a constant need for finding new treatment strategies for Trypanosomiasis. Combination therapy and repurposing or redesigning of existing inhibitors for new drugs are of high importance to address these hurdles, particularly the drug resistance. Hence, here we report TrypInDB, a searchable online resource of small molecule inhibitors having a varying degree of activity towards Trypanosoma sp. Information of about >14,000 small molecules from >700 published research articles was collected and made as an easy-to-search database. Four major sets of information were made available for each collected inhibitors viz., General information (activity values; source of the inhibitors; enzyme targets; etc.,), Structural information, Toxicity information, and Literature information. More than 25 different information about each inhibitor were collected or predicted and made accessible for searching. The database is designed to be queried easily with multiple-field filters with the provisions to perform sub-structure search and similar FDA approved drug searches. The database supports the easy export of queried records and structure in multiple formats. In addition, the TrypInDB is actively integrated into LeishInDB. We believe that the scope of TrypInDB permits the research community to exploit the available data for repurposing the inhibitors as well as for the investigation of new therapeutics. Database URL: http://trypindb.biomedinformri.com/.

Xanthomonas axonopodis pv. punicae depends on multiple non-TAL (Xop) T3SS effectors for its coveted growth inside the pomegranate plant through repressing the immune responses during bacterial blight development.

Xanthomonas axonopodis pv. punicae (Xap), the bacterial blight pathogen of pomegranate, incurs substantial loss to yield and reduces export quality of this economically important fruit crop. During infection, the bacterium secretes six non-TAL (Xop) effectors into the pomegranate cells through a specialized type three secretion system (T3SS). Previously, we demonstrated the role of two key effectors, XopL and XopN in pathogenesis. Here, we investigate the role of rest effectors (XopC2, XopE1, XopQ and XopZ) on disease development. We generated null mutants for each individual effector and mutant bacterial suspension was infiltrated into pomegranate leaves. Compared to Xap wild, the mutant bacterial growth was reduced by 2.7-11.5 folds. The mutants produced lesser water-soaked lesions when infiltrated on leaves by 1.13-2.21 folds. Among the four effectors, XopC2 contributes highest for in planta bacterial growth and disease development. XopC2 efficiently suppressed the defense responses like callose deposition, reactive oxygen species (ROS) and the activation of immune responsive genes. Being a major contributor, we further characterize XopC2 for its subcellular localization, its protein structure and networking. XopC2 is localized to the plasma membrane of Nicotiana benthamiana like XopL and XopN. XopC2 is a 661 amino acids protein having 15 alpha and 17 beta helix. Our STRING and I-TASSER based analysis hinted that XopC2 interacts with multiple membrane localized plant proteins including transcription regulator of CCR4-NOT family, TTN of maintenance of chromosome family and serine/threonine-protein phosphatase 2A (PP2A) isoform. Based on the interaction it is predicted that XopC2 might involve in diverse functions like nuclear-transcribed mRNA catabolic process, maintenance of chromosome, hormone signaling and protein dephosphorylation activities and thereby suppress the plant immunity. Altogether, our study suggests that Xap largely depends on three non-TAL (Xop) effectors, including XopC2, XopL and XopN, to modulate pomegranate PTI for its unrestricted proliferation during bacterial blight development.