Visceral leishmaniasis (VL), a severe parasitic infection caused by Leishmania species, presents a significant challenge due to its potential for relapse despite treatment. This review aims to rationalize antirelapse therapies for VL and address diagnostic dilemmas encountered in therapeutic assessment. By evaluating current treatment strategies, examining relapse mechanisms, and highlighting diagnostic challenges, we aim to provide a comprehensive understanding of effective management and assessment of VL relapse.

The rubella virus (RUV), cytomegalovirus (CMV), and herpes simplex virus (HSV) cause mild illness in immune-competent individuals, pregnant women, and fetus/newborns. The study estimated the prevalence of RUV, CMV, and HSV infection based on IgM antibody levels, and also investigated the association of seasonal variation.

Endometrial cancer (EC) is the leading gynecologic cancer in developed nations. Recent studies suggest that trace elements like zinc and copper may be involved in cancer development due to their involvement in essential biological processes. However, there is inconsistency regarding their serum levels in EC patients. This review sought to systematically analyze and quantify the differences in serum concentrations of zinc and copper between patients with EC and healthy controls through a meta-analysis. A comprehensive search in PubMed, Embase, Scopus, and Google Scholar was performed. Studies comparing serum zinc and/or copper concentrations between confirmed EC patients and healthy controls were included. The quality of the papers was appraised using Newcastle–Ottawa Scale. Synthesis of data was done using standardized mean differences (SMD) at 95

Visceral leishmaniasis–human immunodeficiency virus (VL-HIV) co-infection has emerged as a serious concern, which could adversely affect the VL elimination efforts of the country. These patients have a poor VL therapeutic success rate, more drug-related toxicity, and relapses resulting in high mortality. Despite the emerging pattern of VL-HIV co-infection, there have been limited studies analyzing the presentation of VL-HIV co-infection in Bihar, India. The present study investigated the clinico-epidemiological features, predictors of mortality, and quality of life for people living with VL-HIV co-infection. A cross-sectional study was conducted, using retrospective data on VL-HIV cases from 2018 to 2020. A semi-structured questionnaire was used for data collection. Data analysis was done, using the IBM SPSS statistics v22. Our study included a large sample of 222 VL-HIV cases, of these one-fifth of the patients (47; 21

Viral pathogens are the main cause of acute gastroenteritis in developed and developing countries. Among viral agents of gastroenteritis, rotavirus is known to be one of the frequent etiologic agents of viral diarrhea. Rotavirus and adenovirus are the two important agents associated with infection in hospitalizeddiarrhealchildrenin worldwide.Diarrheal samples (1153) from Bihar state of India wherethe vaccination against rotavirus has not yet been practiced by regular physicians. Samples weretested for presence of rotavirus and adenovirus by EIA method.Further rotaviruses areclassified into G and P serotypes by using semi-nested reverse-transcription polymerase chain reaction.11.11% of stool specimen tested positive for rotavirus, 2.7 sample positive for Adenovirus and 1.3% sample found positive for both Adenovirus and Rotavirus. A distinct rotavirus positive peak had found in winter (December 2019 to November 2022). G1 and G2 strains were the most common strains first time identified in Bihar, India.The study emphasizes the need for continuous monitoring of viral enteropathogens for successful treatment and control of diarrhea

AIM: Dengue is an acute systemic viral disease well known globally in both endemic and epidemic transmission cycles. Main aim is to study serotypes/genotypes and lineages of dengue virus (DENV) are associated with more severe outbreaks. Many reports from India have shown an association between change in DENV genotype/lineage and magnitude of the outbreak and disease severity. Study Design. It is a hospital based cross sectional study. Place and Duration of Study: Molecular Biology laboratory in department of Microbiology, Indira Gandhi Institute of Medical Science and duration study from January2021 to January 2023. Material and Methods: This cross- sectional study was aimed to investigate the circulating DENV serotypes and genotypes in Bihar during year 2021-2023. For genetic characterization of prevalent serotypes, real-time reverse transcription polymerase chain reaction assay was used. Representative samples were sequenced for the envelope (E) gene. Results: All four prevalent serotypes, DENV-1, DENV-2, DENV-3 and DENV-4 were found to be circulating in Bihar with dominance of DENV-2. Mixed infection cases of DENV-2 with DENV-3 and DENV-1 with DENV-2 were also seen. Phylogenetic analysis based on C-prM gene revealed DENV-1 sequences to be 92% similar with Vietnam genotype I (2003) strain, DENV-2 isolates clustered with genotype IV of North India strains, Haryana (1996), Delhi (1996) and Jammu (1993) with 95%, 94% and 94% sequence similarity respectively. DENV-3 isolate was more closely related to genotype III of Indian origin (2003), Gwalior and Delhi with 98% and 99% sequence similarity respectively. Conclusion: With this background data, molecular monitoring of viruses circulating in the locality provides baseline data on the circulating serotypes/ genotypes of dengue virus (DENV). So this monitoring and early detection of changes in the circulation pattern may help in the prediction of DENV outbreaks and can augment disease control efforts.

Background: Visceral leishmaniasis (VL) and HIV coinfection constitute a growing public health challenge, especially in VL-endemic regions. In 2020, India represented 18 % of the global VL burden and held the world's third-largest burden of HIV infection. This study aimed to systematically assess the prevalence of HIV infection among VL patients in India, providing insight into the epidemiological landscape of these concomitant diseases. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an exhaustive search of PubMed, Embase, Scopus, and Google Scholar was performed, including articles published until June 2022. The random-effects model was utilized for estimating overall prevalence, and subgroup analysis was performed based on the study region. R software (version 4.2.2) was used for analysis. Results: This review included five studies, with publication years ranging from 2006 to 2021. The analysis involved 20,835 individuals diagnosed with VL, among whom 726 tested positive for HIV. The overall estimated prevalence of HIV infection among VL patients in India was 3.4 % (95 % CI: 2.0–5.8 %). However, there was substantial heterogeneity among the studies (I2 = 98 %, p < 0.01). Subgroup analysis demonstrated prevalence rates in Bihar at 3.1 % (95 % CI: 1.7–5.7 %) and in New Delhi at 5.8 % (95 % CI: 2.1–12.1 %), with no statistically significant difference between these regions (p = 0.22). Conclusion: The study found low yet substantial prevalence of HIV infection in VL patients. To combat this dual health challenge, proactive measures, including integrated interventions, surveillance, and collaboration between VL and HIV programs, are essential to improve case identification and control.

Post-kala-azar dermal leishmaniasis (PKDL) is a neglected skin disease that has tremendous epidemiological significance as a reservoir of Leishmania parasites. Relapse, drug resistance, non-compliance to prolonged treatment, poor health-seeking behaviour, along with limited therapeutic options pose a significant impact on the management of PKDL. In this study, we aimed to review the efficacy, safety and tolerability data of combination therapies for PKDL in the published literature. We have also described patients’ compliance with treatment and associated co-infections in PKDL. A comprehensive literature search was conducted in PubMed, Scopus and Google Scholar to identify the relevant articles. A total of nine studies were eligible for inclusion in this review. Drug combinations used in India were miltefosine-liposomal amphotericin-B, miltefosine-paromomycin, miltefosine-amphotericin-B, sodium stibogluconate (SSG)-immunotherapy and SSG-rifampicin. However, in Sudan, except one, all studies have used SSG-based combinations viz. SSG-rifampicin, SSG-paromomycin and SSG-immunotherapy. The efficacy and safety of miltefosine in combination with liposomal amphotericin-B as well as conventional amphotericin-B were found to be excellent in a limited number of patients. These combinations are said to have better patient compliance and shorter treatment duration. Another combination of miltefosine and paromomycin was found to be satisfactory with a final cure rate of 83.3%. SSG in combination with paromomycin had a good clinical outcome among severe PKDL patients in Sudan, though pain at the injection site was experienced by all patients. There is a lack of data on combination therapies for PKDL through large-scale randomised controlled trials (RCTs). Therefore, multicentric randomized controlled trials with a sufficiently large sample size are urgently needed to verify the efficacy, safety, and other advantages of combination therapies for PKDL. With the availability of liposomal amphotericin-B, miltefosine and immunotherapy, clinical management of PKDL appears promising.

Iron oxide nanoparticles are the most studied material approved by the Food and Drug Administration. At specific diameters (from 15 nm and no more than 100 nm), magnetic iron oxide, which is made up of magnetite, is used as drug delivery vehicles and for thermal-based therapeutics. This material can be efficiently used in biomedical applications such as diagnostics, imaging, and photothermal therapies. Properties such as biocompatibility and stability of nanoparticles fill the niche of applications that require properties unattainable by organic materials. The application of superparamagnetic iron oxide nanoparticles (SPIONs) acts as an advanced platform for antimicrobial, drug delivery, contrast agent in image diagnostics and hyperthermia treatment for cancer applications. Iron oxide nanoparticles are attributed to their exceptional properties, such as size, shape, magnetism, and biocompatibility. Iron oxide nanoparticles hold potent antibacterial activity against various gram-positive and gram-negative bacteria. In this chapter, iron oxide nanoparticles are exploited in different model organisms ranging from prokaryotes to eukaryotes, elucidating their cellular functions relative to their antibacterial activity, drug delivery, and toxicity. Current knowledge reveals that the comprehensive research can provide significant study parameters and recent developments in the nanomedicine field. Magnetic nanoparticles for biological applications are seeing a significant increase in research and development in recent years.

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.

ObjectiveMiltefosine stands as the sole oral medication approved for the treatment of leishmaniasis. The appearance of severe ophthalmic toxicities induced by miltefosine in the context of leishmaniasis treatment is a matter of significant concern. The main objective of this study is to present a comprehensive summary of the ophthalmic adverse effects associated with miltefosine when used in the treatment of leishmaniasis.MethodsA systematic search was performed on PubMed, ScienceDirect, Embase, Scopus, and Google Scholar, covering articles from inception up to June 2023, without language restrictions, to identify relevant studies documenting ocular toxicity following miltefosine treatment for leishmaniasis.ResultsA total of eight studies involving 31 leishmaniasis patients who developed ocular toxicities while undergoing miltefosine treatment were included in the analysis. These studies were conducted in various regions, with five originating from India, two from Bangladesh, and one from Nepal. Patients presented a spectrum of ophthalmic complications, including uveitis, keratitis, scleritis, and Mooren's ulcer. Commonly reported symptoms included pain, redness, excessive tearing, partial vision impairment, permanent blindness, light sensitivity, and the appearance of white spots on the eye. On average, patients received miltefosine treatment for a duration of 47 days before experiencing the onset of ocular problems. It is important to note that the risk of ocular toxicities increases with prolonged use of miltefosine.ConclusionsTherefore, to mitigate the potential for irreversible damage to the eyes, it is imperative that all individuals undergoing miltefosine therapy undergo regular eye examinations.

There is a significant research gap in India due to incomplete investigation of seroprevalence of co-infection with visceral leishmaniasis (VL), hepatitis B (HBV) and hepatitis C (HCV). This study attempts to fill this gap by providing an in-depth analysis of the prevalence and consequences of these co-infections. The study of 32 VL patients revealed that 28 (8.88%) tested positive for HBV, 1 (0.317%) for HCV and 3 (0.95%) for both HBV and HCV. These results highlight how difficult it is to treat people with two diseases at the same time. An example of how co-infection makes treatment much more difficult is the fact that a patient with both VL and HBV required six courses of anti-leishmaniasis medication. The study shows how important it is for VL patients to be tested regularly for HBV and HCV to improve treatment response and support India's plan to get rid of kala-azar. Accurate identification of co-infections is necessary to reduce the overall burden of the disease and develop effective treatment regimens. Systematic testing of VL patients for HBV and HCV not only helps in controlling and perhaps even eliminating kala-azar, but also makes it easier to treat each patient as an individual, improving their health. In areas where viral hepatitis is prevalent, this strategy is particularly important as these diseases represent a double burden on public health. Implementing integrated treatment regimens and routine screening can reduce the impact of co-infection and advance the public health goal of kala-azar elimination. To improve patient outcomes and advance public health goals, the results of this study strongly support the integration of comprehensive screening programs into existing healthcare systems to improve the treatment of VL patients.

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.

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.

SARS-CoV-2 is highly contagious, which spreads even by patients having no clinical symptoms or also from people suffering with only mild symptoms. The gold standard test for its diagnosis is reverse-transcription PCR (RT-PCR) but at times of pandemic, Rapid antigen tests (RAT) are required, which has a very less turn-around time. Evaluation of the performance of COVID-19 Rapid antigen test in comparison to SARS-CoV-2 RT-PCR using nasopharyngeal swab, in relation to RNA dependent RNA polymerase (RdRp) Cycle threshold (Ct) values. This observational and cross-sectional study was done on patients coming with features of Influenza-like illness (ILI) or for any aerosol generating procedure or on high-risk patients seeking hospitalization. Both RT-PCR and RAT for COVID-19 were done on samples collected from each patient and results were compared. Altogether, 5314 samples were tested, out of which 104 (01.95 %) & 229 (04.31 %) samples were found positive by the RAT & RT PCR test, respectively. Sensitivity, specificity, PPV and NPV of RAT were found to be 44.54%, 99.96%, 98.08% and 97.56%, respectively. 98.9 % of samples with Ct value ≤ 20 were positive by RAT, whereas only 2.2% samples having Ct value ≥ 26 were found to be positive. Cases having lower Ct values were found to be more symptomatic and vice-versa. RAT are not efficient in detecting the virus in samples showing high Ct values (Ct ≥ 26) by RT-PCR test. Patients with samples showing low Ct values (Ct ≤ 20) had more severe symptoms and vice-versa.