IntroductionEnteric fever is widespread in many regions of developing countries. Despite low sensitivity, blood culture remains the gold standard diagnostic test for enteric fever. Diagnostic tests like Widal lack the desired specificity; hence, patients are overtreated many times. Inaccessibility to proper medical care in developing countries further poses a challenge to diagnosis by these conventional methods, promoting the needless intake of over-the-counter drugs by people. Although rapid kit-based tests are available, the reliability of these diagnostic tests in terms of specificity and sensitivity is quite variable. We aimed to validate the reliability of Typhipoint EIA (ELISA-based test) against blood clot nested PCR for enteric fever, as a gold standard, in view of the reported variable culture yield by calculating the sensitivity, specificity, and likelihood ratio.MethodsA total of 100 patients were included in the study out of 152 patients screened, based on the inclusion criteria. The clinical profile of provisional enteric fever was recorded along with the amplification of the DNA fragment of flagellin (H1-d), and the stkG gene of Salmonella typhi and Salmonella paratyphi A, respectively, by nested PCR performed on blood clots, urine, and stool samples. Further validation of the ELISA-based test, i.e., Typhipoint EIA, was done considering nested PCR as a gold standard. The control group consisted of 40 healthy subjects.ResultsNested PCR of the blood clots showed 84% positivity. Total culture positivity was found in 89 samples (combined), and among all samples for culture, clot culture was positive in 52 (52%), urine culture in 5 (5%), and stool culture in 32 (32%) cases. The total number of Typhipoint EIA IgM-positive cases was 83 (83%). The validation of Typhipoint EIA IgM showed 92.9% sensitivity and 68.8% specificity against blood clot PCR for Salmonella typhi.DiscussionThe Typhipoint EIA test for the diagnosis of enteric fever is quite sensitive as well as specific. It may be advised that two to three specific antigens of S. typhi should be spotted on the test kit for a satisfactory level of diagnosis of enteric fever in field conditions. This will help achieve the desired accuracy of the rapid test to avoid unnecessary antimicrobial therapy and costly investigations.
Preventive variables for childhood leukemia incidence (LI) remain unknown. Past assertions that childhood vaccinations, especially BCG, may be potentially protective have remained disputed for over five decades because of the lack of a unifying framework to explain variable outcomes in different studies. An examination of the early childhood LI for 2020 in European Region countries with supposedly similar underlying confounders but differential childhood vaccination coverage displays negative covariation with prevailing Mycobacterium spp. exposure in BCG-vaccinated children. The childhood LI in 0-4-year-old populations with >90% childhood BCG vaccination coverage is found to be strongly but negatively correlated with prevailing tuberculin immunoreactivity [r(24): -0.7868, p-value: < 0.0001]. No such correlation existed for the LI in 0-4-year-old populations without BCG vaccinations, though weak associations are hinted at by the available data for MCV2, PCV3, and DTP3 vaccinations. We hypothesize that early childhood BCG vaccination "priming" and subsequent "trained immunity" augmentation by "natural" boosting from Mycobacterium spp. exposure play a preventive and protective role in childhood LI. The non-consideration of prevailing "trained immunity" could have been a cause behind the conflicting outcomes in past studies. Exploratory studies, preferably performed in high-burden countries and controlling for the trained-immunity correlate and other potential confounders, would be warranted in order to establish a role for BCG vaccination and early-life immune training (or lack thereof) in childhood LI and help put the current controversy to rest.
AbstractEndeavors to identify potentially protective variables for COVID‐19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID‐19 impact on populations to their Bacillus–Calmette–Guérin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID‐19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous ‘trained immunity’ (TI) conferred by exposure to Mycobacterium spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI in populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (24), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID‐19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase‐matched COVID‐19 incidences (r(24): −0.79 to −0.57; p‐value < .004), mortality (r(24): −0.63 to −0.45; p‐value < .03), and interim case fatality rates (i‐CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID‐19, the ongoing or planned randomized controlled trials should consciously consider including measures of TI as: (a) all individuals immunized do not respond equally, (b) small study groups from higher background TI could fail to indicate any protective effect.
Fever remains an integral part of acute infectious diseases management, especially for those without effective therapeutics, but the widespread myths about “fevers” and the presence of confusing guidelines from different agencies, which have heightened during the coronavirus disease 2019 (COVID-19) pandemic and are open to alternate interpretation, could deny whole populations the benefits of fever. Guidelines suggesting antipyresis for 37.8–39°C fever are concerning as 39°C boosts the protective heat-shock and immune response (humoral, cell-mediated, and nutritional) whereas ≥40°C initiates/enhances the antiviral responses and restricts high-temperature adapted pathogens, e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strains of influenza, and measles. Urgent attention is accordingly needed to address the situation because of the potential public health consequences of the existence of conflicting guidelines in the public domain. We have in this article attempted to restate the benefits of fever in disease resolution, dispel myths, and underline the need for alignment of national treatment guidelines with that of the WHO, to promote appropriate practices and reduce the morbidity and mortality from infectious diseases, such as COVID-19.
The parasites of the genus Leishmania survive and proliferate in the host phagocytic cells by taking control over their microbicidal functions. The parasite also promotes differentiation of antigen-specific anti-inflammatory cytokines producing effector T cells, which eventually results in disease pathogenesis. The mechanisms that parasites employ to dominate host adaptive immunity are largely unknown. For the first time, we report that L. donovani, which causes visceral leishmaniasis in the Indian subcontinent, upregulates the expression of an immune inhibitory receptor i.e., CD300a on antigen presenting and phagocytic cells to dampen their effector functions. The blocking of CD300a signals in leishmania antigens activated macrophages and dendritic cells enhanced the production of nitric oxide, pro-inflammatory cytokines along with MHCI/II genes expression, and reduced parasitic uptake. Further, the abrogation of CD300a signals in Leishmania infected mice benefited antigen-experienced, i.e., CD4+CD44+ and CD8+CD44+ T cells to acquire more pro-inflammatory cytokines producing phenotypes and helped in the early clearance of parasites from their visceral organs. The CD300a receptor blocking also enhanced the conversion of CD4+ T effectors cells to their memory phenotypes i.e., CCR7high CD62Lhigh up to 1.6 and 1.9 fold after 14 and 21 days post-infection, respectively. These findings implicate that CD300a is an important determinant of host phagocytic cells functions and T cells differentiation against Leishmania antigens.
Background: Idiopathic vasculitides or arteritis have very few or none treatment options. Identification of infective arteritis based on high clinical suspicion opens a window for treatment of such cases . Although these are occasional clinical scenario. Aims and Objectives: To identify the treatable cause of arteritis and starting initial treatment based on clinical suspicion. Material and Methods: Based on high clinical suspicion we aim to identify chronic infective cause of arteritis among patients of SS Hospital from 2019 to 2020 coming in EOPD. Results and Discussion: Three cases of reversible hypertension from different clinical setup relating to a common infective etiology, i.e., tuberculosis identified during the said duration, all cases presented with constitutional symptoms for 2–6 months with headache, loss of appetite, fever, and malaise. The first case presented as acute abdomen in EOPD having mesenteric ischemia and hypertension. The second case presented in antenatal care OPD with hypertension which was nonrelated to pregnancy. The third case presented in medicine OPD as a case of young hypertensive without mood changes. Partial renal artery stenosis relating to infective arteritis was a common finding in all cases. All cases responded well with the firstline antitubercular medication and became normotensive (without medication) in the follow up. Conclusion: The cause of renal artery stenosis appeared to be related to tubercular arteritis of vessel with either a past history of pulmonary TB or TB contact. Renovascular tubercular arteritis has been defined in only a few literatures and only handful of cases being reported making worth presentation.
Diabetes mellitus implies a group of common metabolic disorders that share a phenotype of hyperglycemia. Peripheral insulin resistance and impaired insulin secretion forms two legs of this common, globally important non communicable disorder. Adiponectin is a hormone released by adipocytes which aids in enhancing insulin sensitivity, decreasing inflammatory mediators. Baseline adiponectin can predict diabetes and change in its value with change in metabolic parameters highlights the gravity of this molecule in more refined diagnosis and treatment of diabetes.AIMS:The objective was to ascertain change in adiponectin value in diabetics who were given either DPP-4 inhibitors or SU group drugs. Another objective was to find out correlation of serum adiponectin levels with various parameters involved in sugar and fat metabolism such as FBS, PPBS, HbA1c, LDL, HDL, VLDL, TG.MATERIAL:Total of 50 participants were taken, out of which 40 were diabetics and 10 were controls. They were selected using inclusion and exclusion criteria. Diabetics were divided into two arms with 20 participants each (a. dpp group b.su group). Clinical history, examination, sample collection was done. Serum adiponectin assay was performed using RayBio ELISA kit.OBSERVATION:Serum adiponectin levels in dpp group was higher at end of third month as compared to 0 month (45.9 +/- 5.9 vs. 39.8 +/- 4.1 mcg/dl; p<0.05). Likewise, adiponectin levels in su group was higher at end of third month as compared to 0 month (43.9 +/- 3.6 vs. 39.8 +/- 3.5 mcg/dl; p<0.05).CONCLUSION:Improvement in glycemic parameters (HbA1c, FBS, PPBS) is associated with rise in serum levels of adiponectin. General population possess higher levels of adiponectin as compared to diabetics. Adiponectin can serve as a marker for early diagnosis to diabetes. It can also aid in targeted therapy for metabolic disorders.
Fever remains an integral part of the acute clinical diseases management, esp. viral, for which effective therapeutics remain desired. However, the presence of often confusing fever reduction recommendations for COVID-19 in the public domain during the pandemic, as late as 28 April 2021, seems to suggest the reduction of any ‘uncomfortable’ fever ranging from 37.8 - 39oC, as opposed to WHO fever reduction guidelines (≥39oC), urgently need attention. The confusion could percolate down into different agencies who look up to these agencies for guidance in framing their own, denying the benefits of fever to populations, and effectively undo whatever successive WHO’s guidelines have achieved in the last two decades. The existence of conflicting guidelines in public domains which are open to interpretations has consequences to public health and the healthcare infrastructure, on implementation. For controlling acute infectious diseases, esp. viral, the fever remains the most important enabler. Historically, our chief obstacles to harnessing the benefits of fever in acute clinical diseases with limited therapeutics had been: a) widespread myths about ‘fevers’ arising from a general misunderstanding of basic facts; b) presence of confusing guidelines by different agencies which are open to alternate interpretation. The article attempts to briefly indicate the benefits of fever in disease resolution, dispel myths, underline vagueness in illustrative national guidelines and the need to align them with evidence-based WHO guidelines, as it has the potential to perpetuate myths/confusion in masses leading to adverse impact on disease management – more morbidity and mortality from diseases including COVID-19.
Endeavors to identify potentially protective variables for COVID-19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID-19 impact on populations to their bacillus Calmette-Guerin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID-19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous ′trained immunity′ (TI) conferred by exposure to Mycobacterium spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI of populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (twenty-four), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID-19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase-matched COVID-19 incidences (r(24): -0.79 to -0.57; p-value: <0.004), mortality (r(24): -0.63 to -0.45; p-value: <0.03), and interim case fatality rates(i-CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID-19, the ongoing/planned randomized controlled trials should consciously consider including measures of TI as - a) all individuals immunized do not respond equally, b) small study groups from higher background TI could fail to indicate any protective effect.
ABSTRACTA potential protective role of vitamin D serum levels on overall adverse outcomes of SARS-CoV-2 infection or COVID-19 on populations had been suggested previously based upon single-point cross-sectional analysis of 8 April 2020 data from 20 European countries assuming comparable underlying confounding variables for these populations, at an early stage of the current pandemic. Comparative time-series cross-sectional analysis of the COVID-19 data from 12 March (early pre-peak) to 26 July (late post-peak of infections) 2020 was performed to assess the strength of the assertion. The study subjects included 1,829,634 COVID-19 cases (11.11% of total worldwide) and 179,135 associated deaths (27.45 % of total worldwide) on 26 July 2012. Previously suggested cross-sectional study design and methodology could not consistently and significantly (p-value≥0.05) support the notion of the potential protective role of the mean serum vitamin D levels of the populations on COVID-19 incidence and mortality. However, the exponential correlative model, as well as alternative simple regression analysis on ln and Log10 transformed COVID-19 data for the time period indicated improved consistently negative covariation with vitamin D levels. Additionally, the later methodology increased the predictive potential for explaining the variability in data [R2 by 1.27-1.96 fold, adjusted-R2 by 1.33-2.47, p-value=0.0457-0.0035, for cases/million; R2 by 1.81-2.67, adjusted-R2 by 2.21-3.74 fold for deaths/million, p-value=0.0049-0.0228). Considering, the established role of vitamin D in immune system functioning randomized well-controlled trials may be suggested to evaluate/assess the potential protective role of vitamin D in reducing the COVID-19 impact on populations.
Background: Typhoid is mainly a disease of developing country, and inappropriately treated most of time due to lack of highly skilled diagnostic tools specially at primary level. So to validate most easy and rapid investigation Typhidot EIA with nested PCR may prove quite necessary due to low yield of culture reports.Aims: The objective was to evaluate the clinical profile and immediate diagnostic tool typhidot considering nested PCR as gold standard due to it’s high sensitivity and specificity rates.Material and Methods: Clinical profile of 100 case of provisional enteric fever recorded along with amplification of The DNA fragment of flagellin (H1-d) and stkG gene for salmonella typhi and salmonella paratyphi A respectively by nested PCR done in blood clot,unine and stool sample, along with blood clot culture,urine and stool culture done. Further validation of ELISA card test i.e. typhidot EIA done considering nested PCR as gold standard, for validation of test control group consisted of 40 health subjects.Results: Nested PCR which showed overall 84% positivity. Total Culture positivity was 60 among all samples and among that Clot culture 35(35%),urine culture 3(3%)and stool culture yield was 22(22%) respectively .Validation of Typhipoint EIA IgM showed 92.8% sensitivity and 68.7% specificity.Conclusion: It may be advised that 2-3 specific antigens of S. Typhi are spotted on the membrane and ELISA based detection should be carried out to reach the satisfactory level of diagnosis of enteric fever in field condition for more accuracy in rapid test to avoid inappropriate antimicrobial therapy and costly investigations.Funding Statement: None.Declaration of Interests: None.Ethics Approval Statement: The study was conducted as a part of dissertation in collaboration with department of general medicine and department of microbiology at I.M.S , B.H.U Varanasi. The well informed consent was taken from each of the participants and the study plan was approved by the Institute Ethics Committee.
The lacuna in the knowledge of immunobiology, especially in visceral infections that are fatal if left untreated, are a major hurdle in getting a vaccine candidate for leishmaniasis. Till date, only a few drugs are available to combat human leishmaniasis and a vaccine candidate either prophylactic or preventive is still awaited. Therefore, identification of host and parasitic factors involved in the regulation of specific immune mechanisms are essentially needed. In this study, we observed that CD200-CD200R immune inhibitory axis regulates host macrophages effectors properties and helps antigen experienced T cells (CD4+CD44+ T cells) to acquire anti-inflammatory cytokines (IL-4, IL-10, TGF-β, IL-27) producing abilities in an NFkB independent manner. After CD200 blocking the macrophages effectively inhibited proliferation of Leishmania amastigotes and also induced the production of IL-12, IFN-γ, TNF-α and nitric oxide (NOx). Further, the blocking of CD200 signaling also restored macrophages MHC-II expression and helped CD4+CD44+ T cells to produce pro-inflammatory cytokines like IL-2, IL-12 and IFN-γ. The finding of this study suggested the importance of immune inhibitory mechanisms in controlling Leishmania growth and survival and therefore, requires more studies to understand its role in vaccine induced immunity.
Prognostic tool or a test of cure to monitor drugs response is not available for leishmaniasis till date.Individuals suffering with visceral leishmaniasis (VL) show seropositivity to all currently used diagnostic antigens even after years of successful cure.In this study, we explored a 13kDa excretory-secretory component of L. donovani, which showed seronegativity with serum obtained from patients on completion of treatment.Leishmania donovani promastigotes were grown in Dulbecco's modified eagle media.The leishmanial excretory-secretory antigens (LESAs) were prepared and recovered from parasites free culture supernatant.The diagnostic and prognostic applicability of 13kDa protein was evaluated by enzyme linked immunosorbent assay.Result indicates that patient's sera bears seropositivity for 13kDa protein before treatment and found to be antibodies negative after completion of treatment.The sera samples of various controls did not show seropositivity with this protein.The ELISA sensitivity of this protein was observed to be 100% at absorbance cut-offs 0.180 and 0.360.The specificity at absorbance cut-off 0.180 in nonendemic, endemic and disease control groups was observed to be 98%, 92% and 94%, respectively.The homology modeling predicted its homology with ubiquitin like protein.The identified protein was found to be highly sensitive and specific for serum antibodies present in VL patients.The findings also indicated its prognostic potential, which can also be exploited to monitor drug responses.
Context: Aging has impact on immune system both quantitatively as well as qualitatively, leading to deregulated response in different states ranging from infection, autoimmunity, inflammation, and excessive tissue damage.Aims: The present study is done to observe the immunosenescence-related changes in monocytes-/macrophages-mediated production of nitric oxide (NO), interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, anti-inflammatory cytokine IL-10 after stimulation with lipopolysaccharide (LPS), and interferon (IFN)-γ, evaluating the innate immunity of a group of healthy Indian elderly from a single institution.Settings and Design: The study was conducted on life-term prisoners in Central Jail, Varanasi, India, and the Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, among the three groups, namely study group (>70 years old), control Group 1 (60–70 years), and control Group 2 (30–40 years).Subjects and Methods: Mononuclear cells were separated, and NO production, pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α, and anti-inflammatory cytokine IL-10 from these cells were estimated by enzyme-linked immunosorbent assay after stimulation with LPS and IFN-γ.Statistical Analysis Used: Mean and standard deviation were calculated, and Student's t-test was applied. Results were considered statistically significant forP < 0.05.Results: A statistically significant rise in NO production (P < 0.001) was observed after stimulation as compared to control Groups 1 and 2 (P < 0.001). The study group showed a significant decrease in IL-1 production (P < 0.03) following stimulation. The basal TNF-α level was low in the study group, but there was a significant increase in TNF-α following stimulation. The basal level of IL-6 in the study group was higher than the control Group 1 (not significant, P = 0.21) but lower than the control Group 2 (not significant, P = 0.18). There were no significant inter- or intra-group changes in IL-6 level.Conclusions: There is a qualitative as well as quantitative defect in elderly monocytes/macrophages reflecting abnormal inflammatory response. This could be due to abnormal immunity with aging, which may be responsible for increased frequency of chronic diseases such as diabetes, hypertension, congestive heart failure, asymptomatic infections, and Alzheimer's disease in geriatric population.
According to International Diabetes Federation, the worldwide prevalence of impaired glucose tolerance (IGT) in adults is 318 million and is expected to reach 482 million by 2040. With increasing burden of prediabetes and their expectant progression in diabetes has compounded the problem. Now question is that how we can identify the subjects at high risk to develop prediabetic state and among them who will rapidly progress into diabetes? Once a person diagnosed to be a diabetic then there are only few marker which can depict development of diabetes related complications and also to help in preventing such diabetes related complication progression. In this article, we will review several biomarkers used to predict the risk of progression to prediabetes, diabetes states in context to their mechanism of action, sensitivity, specificity, advantages, disadvantages and association with dysglycemia. The risk stratification arising due to insulin resistance by novel biomarker will improve clinical outcome both in prediabetics and diabetics.
Leishmaniases are endemic in 98 countries and a serious threat to approximately 310 million people living in endemic regions of affected countries. Out of 53 described species of Leishmania parasites, 20 are known to cause human pathogenesis and may produce three discreet clinical manifestations, that is, cutaneous (CL), mucocutaneous (MCL), and visceral (VL) leishmaniasis that differ in their immunopathologies and degree of morbidity and mortality. It is estimated that approximately 0.7–1.2 million new CL and 0.2–0.4 million of new VL cases occur each year in disease endemic countries. The current treatment options comprise only three drugs, viz. pentavalent antimonials, amphotericin B (and its liposomal formulation, AmBisome), and miltefosine that also produce severe side effects. These drugs do not produce a sterile cure, leaving behind a possible and potent source of parasitic reservoirs for further disease transmission along with the emergence of drug-resistant parasites. The limited drug regimen, coupled with the unavailability of a licensed vaccine, necessitates the development of a true antileishmanial drug to combat increasing incidences of leishmaniasis. In this chapter, we summarize a wide range of compounds isolated from various natural sources that are worth screening to develop a true antileishmanial drug along with a short discussion on the limitations of current drugs.
Background: Chronic infection has a known effect on the cytokine levels of the body which adversely affects erythropoiesis. Aim: The aim of this study is to compare hematological parameters among participants with and without chronic periodontitis which also is a known infectious inflammatory disease of the gums. Materials and Methods: Forty patients with severe chronic periodontitis (Group A) and forty periodontally healthy participants (Group B) in the age group of 30–55 years presenting to the Outpatient Department of the Faculty of Dental Sciences, Banaras Hindu University, were recruited in the study and were assessed for various hematological and periodontal parameters. SPSS 17.0 version was used. Student's t-test (unpaired) was used. P < 0.05 was considered statistically significant. Results: Group A showed lower hemoglobin (Hb, 13.47 ± 1.05, P = 0.019), erythrocyte count (4.63 ± 0.40, P = 0.002), and mean corpuscular Hb concentration (32.58 ± 0.90, P = 0.003) values compared to Group B (13.95 ± 0.70, 4.90 ± 0.33, and 33.18 ± 0.81, respectively). Conclusion: Within the limitations of the study, it can be safely deduced that a positive relationship exists between the hematological parameters and severity of chronic periodontal disease, suggesting that long-standing chronic periodontitis may lead to the development of signs of anemia.
BACKGROUND:Homocysteinemia in PCOS may impair implantation by interfering with endometrial blood flow and has been documented to increase the adverse pregnancy outcome.AIMS:The objective was to evaluate the relationship between insulin resistance and serum homocysteine in subjects with polycystic ovarian syndrome (PCOS).MATERIAL AND METHODS:Cross sectional Case Control observational study done in Department of Obstetrics and Gynecology, KGMU Lucknow. Cases were 50 PCOS women as a study group and 40 women with infertility due to isolated male cause as a control group. Serum homocysteine levels compared in PCOS patients.RESULTS:Mean homocysteine raised in cases (11.8 ± 5.5μmol/L) than control (7.8 ± 2.2 μmol/L), p< 0.001 Considering 11 μmol/l cut off level for normal homocysteine, 36% of PCOS patients (18 of 50) and 10%of control (4 out of 40) had high homocysteine levels, p< 0.001. 8% of PCOS patients without insulin resistance (4 out of 50) had a high homocysteine level, while 28%of PCOS patients with insulin resistance (14 out of 50) had homocysteinemia. Mean plasma homocysteine level was very high in insulin resistant case group subjects (13.9 ± 5.6 μmol/L) than non insulin resistant subjects in case group (8.2 ± 2.7), p< 0.001.CONCLUSION:Insulin resistance and hyperinsulinaemia in patients with PCOS is associated with elevated plasma homocysteine This finding may have important implications in the short-term reproductive outcome, and the long-term cardiovascular complications associated with insulin-resistant PCOS.
Elimination of visceral leishmaniasis is a priority programme in Indian subcontinent. The World Health Organization has set a new target to eliminate kala-azar by the year 2020 as previous target elimination year (2015) has passed. The elimination programme has successfully curbed the rate of infection in endemic regions; however, there are still few challenges in its route. The current drug control regime is extremely limited and comprises only two (amphotericin B and miltefosine) drugs, which are also susceptible for parasites resistance. Moreover, these drugs do not produce sterile cure, and cured patients may develop post kala-azar dermal leishmaniasis even after a decade of cure leaving behind a potent source of parasitic reservoirs for further disease transmission. A significant proportion of endemic population remain seropositive but aymptomatic for many years without any clinical symptom that serve as latent parasitic reservoirs. The lack of tools to identify live parasites in asymptomatic infections and there association in disease transmission, parameters of sterile cure along with post kala-azar dermal leishmaniasis progression remain a major threat in its elimination. In this review, we discuss the potential of host immune inhibitory mechanisms to identify immune correlates of protective immunity to understand the mystery of asymptomatic infections, sterile cure and post kala azar dermal leishmaniasis.