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1.
J Infect Dis ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433587

RESUMO

Novel coronavirus SARS-CoV2, causing coronavirus disease 2019 or COVID-19, led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to a severe disease with acute respiratory distress syndrome (ARDS) and an associated systemic hyper-inflammation. First to characterize key cytokines and their dynamics in this hyper-inflammatory condition, we assessed abundance and correlative expression of a panel of forty eight cytokines in patients progressing to ARDS, as compared to patients with mild disease. Then in an ongoing randomized control trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics, as a correlate for the level of hypoxia experienced by the patients. We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. Neutralizing antibodies as well as reductions in circulating interleukin-6 and interferon gamma induced protein 10, contributed to marked rapid reductions in hypoxia in response to CPT.

2.
Sci Rep ; 11(1): 511, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436908

RESUMO

Dengue is an arboviral infection with high rates of morbidity and mortality throughout the tropics and sub-tropics. This work studied the status of pentraxin (CRP/SAP) protein, ferritin, TNF-α and IL-1ß levels in Dengue patients of different pathophysiological manifestations. Accordingly, clinically confirmed Dengue cases (n = 97) were enrolled and subsequently blood parameters were studied by Haematology cell counter and Biochemistry Autoanalyser. CRP, SAP, ferritin, TNF-α and IL-1ß ELISA were done in all the samples by using standard ELISA kits. Statistical Analysis was done in all the experiments. The levels of CRP (p < 0.0001), SAP (p < 0.0001), ferritin (p < 0.0001), TNF-α (p < 0.0001) and IL-1ß (p < 0.0001) were high in patients with Severe Dengue as compared to Dengue without warning signs. High levels of SGOT, SGPT and decreased platelet counts were found in severe patients as compared to Healthy donor. CRP/SAP as well as TNF-α/IL-1ß were independently associated with both dengue severity and overall disease manifestation. Statistically significant increased CRP, SAP, ferritin, TNF-α and IL-1ß titres were correlated in patients with severe clinical manifestations as compared to mild disease forms of dengue. Elevated levels of pentraxin, TNF-α/IL-1ß in blood during dengue infection could act as an early predictor in Severe Dengue infection.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32528904

RESUMO

Background: Post Kala Azar Dermal Leishmaniasis (PKDL) is a non-fatal dermal sequel of Visceral Leishmaniasis (VL), affecting individuals worldwide. Available diagnostic tools lack sensitivity and specificity toward identifying macular (MAC) PKDL patients, due to low parasite load in patients' sample. Confirmatory test like punch biopsy are invasive and painful. Considering the rural nature of this disease and the prevailing situation of diagnostic scenario, PKDL patients mostly remains unattended from receiving proper medical care. They in turn act as "mobile parasite reservoir," responsible for VL transmission among healthy individuals (HI). This study aims to identify PKDL disease specific glycated protein biomarkers, utilizing the powerful LC-MS/MS technology, which is the tool of choice to efficiently identify and quantify disease specific protein biomarkers. These identified PKDL disease specific novel glycoproteins could be developed in future as immunochromatographic based assay for efficient case detection. Methodology: Previously our lab had identified importance of glycated (Circulating Immune Complexes) CICs, among PKDL patients. This study aims to further characterize disease specific glycated protein biomarkers, among MAC PKDL patients for both diagnostic and prognostic evaluation of the disease. LC-MS/MS based comparative spectral count analysis of MAC PKDL to polymorphic (POLY) PKDL, HI, and Cured (CR) individuals were performed. Proteins level alterations among all study groups were confirmed by Western blot and enzyme-linked immunosorbant Assay (ELISA). Results: Among MAC PKDL patients 43, 60, 90 proteins were altered compared to POLY PKDL, HI, and CR groups, respectively. Filtering for the most significant proteins, Plasminogen (PLG) and Vitronectin (VTN) were identified which promisingly identified MAC PKDL cases. Active surveillance results from endemic districts of West Bengal revealed drastic rise of MAC PKDL cases, alarming the urgency for field adaptive efficient biomarker. Conclusion: This current study aims to establish PLG and VTN as novel diagnostic and prognostic protein biomarker for MAC and POLY PKDL cases management.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30264743

RESUMO

This case report series alerts to the atypical manifestations of dermal leishmaniasis in an area endemic for post kala-azar dermal leishmaniasis, the sequel to visceral leishmaniasis. We have reported two cases with multiple skin lesions, wherein the rK39 strip test, polymerase chain reaction and parasite load confirmed the presence of Leishmania parasites. The causative parasite was identified as Leishmania major by restriction fragment length polymorphism of the ribosomal DNA Internal Transcribed Spacer-1, overruling the clinical suspicion of post kala-azar dermal leishmaniasis. The third case presented with fever and extensive hypopigmented patches in the upper extremities; parasites were identified in blood and skin by polymerase chain reaction and typed by restriction fragment length polymorphism as Leishmania donovani, establishing this as a case of visceral leishmaniasis concomitant with dermal leishmaniasis, secondary to dissemination of viscerotropic L. donovani. The present case series emphasizes the importance of molecular tools to identify the Leishmania species in order to ensure appropriate treatment.


Assuntos
Leishmania/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/parasitologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição
5.
J Educ Health Promot ; 8: 226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31867390

RESUMO

INTRODUCTION: HIV/AIDS is a serious challenge globally. A plethora of morbidities due to crippling immune system reduces quality of life (QOL). The advent of highly active antiretroviral treatment has changed this deadly disease to a chronic manageable illness with focus shifting from fighting virus to ensuring a good QOL. OBJECTIVE: To assess the QOL among people living with HIV/AIDS (PLHA) and factors influencing, if any in Indian setting. MATERIALS AND METHODS: An institutional-based cross-sectional study was carried out among 220 PLHA (male >15 years) attending Anti-Retroviral Therapy Centre of the center of excellence in HIV care in India (Calcutta School of Tropical Medicine, Kolkata) from May 2012 to April 2013. QOL was assessed using WHO-QOL-BREF questionnaire from January 2013 to December 2013. Statistical analysis was done using SPSS version 16; multivariate logistic regression was computed with adjusted odds ratio in 95% confidence interval; P < 0.05 was considered statistically significant. RESULTS: In this study, all 220 PLHA men participated (response rate 96.5%) where more than half (55.5%) participants rated their QOL as neither poor nor good; only 28.2% replied good. One-third (38.6%) were dissatisfied while only one-fifth (19.1%) satisfied and 41.4% mentioned neither satisfied nor dissatisfied with their health. Mean score ± standard deviation on various domains and facets of WHOQOL-BREF were physical health score 56.2 ± 9.8, psychological health 63.1 ± 8.7, social relationship 48.9 ± 14.8, and environmental health 51.3 ± 13.7. CONCLUSION: PLHA had good QOL on psychological, physical, and environmental domain that reflects better services provided at Calcutta School of Tropical Medicine (CSTM), Kolkata, but they scored poorly in social relationship domain, which may be suggestive of ineffective social services network. This study concludes that increase existing social and emotional support with innovation should be implemented to improve their QOL.

6.
Indian J Dermatol Venereol Leprol ; 85(6): 578-589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31397399

RESUMO

Background: Elimination of kala azar from India is challenging as there are potential reservoirs of Leishmania donovani in patients with post-kala-azar dermal leishmaniasis (PKDL). The vast repertoire of carbohydrate moieties on L. donovani is known to elicit specific and strong humoral responses in patients with kala azar. Aim: The present study was undertaken to evaluate the diagnostic performances of anti-gal antibodies using enzyme-linked immunosorbent assay for successful serological diagnosis of PKDL in Indian patients and to differentiate cases of past cured visceral leishmaniasis infections. Methods: We developed Gal enzyme-linked immunosorbent assay to measure specific anti-gal IgG isotype in the sera of 71 Indian patients with PKDL. The diagnostic efficacy of the newly developed assay was evaluated for precision, sensitivity and accuracy. Results: Gal2 enzyme-linked immunosorbent assay revealed three-fold increased anti-gal titers in 71 patients with active PKDL compared to controls. Subclass enzyme-linked immunosorbent assay analysis further revealed enhanced IgG2 and IgG3 anti-gal titers in patients with PKDL compared to control subjects. The rank order for specificity and sensitivity for IgG subclasses was IgG3>IgG2>IgG4>IgG1. The area under the curve values of 0.98 and 0.99 were obtained for IgG and IgG3 Gal2 enzyme-linked immunosorbent assays respectively. Overall sensitivity and specificity were 95.7% (95% CI: 88.1-99.1) and 98.1% (95% confidence interval: 90.1-99.9), and 98.5% (95% CI: 92.4-99.9) and 98.1% (95% CI: 90.1-99.9), respectively. Intra-assay coefficient of variation was 1.5% and inter-assay coefficient of variation was 11.7%. Limitations: The Gal2 enzyme-linked immunosorbent assay needs to be further investigated in mass surveys. Conclusion: Taken together, anti-gal titers detected through Gal2 enzyme-linked immunosorbent assay can serve as an effective diagnostic tool in disease elimination setting and help in better case management in endemic districts.


Assuntos
Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/sangue , Leishmaniose Cutânea/diagnóstico , Leishmaniose Visceral/sangue , Leishmaniose Visceral/diagnóstico , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Testes Diagnósticos de Rotina/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suínos , Adulto Jovem
7.
J Med Virol ; 91(10): 1873-1876, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31243775

RESUMO

Dengue is the most common arboviral infection globally, but its pathogenesis is poorly explored. Vascular endothelial growth factor (VEGF) has an essential role in the host defense against viral infection. However, not much information is available regarding its status in dengue patients from the eastern zone of India. In the present investigation, the level of VEGF was investigated for its possible utility as a dengue severity marker. Accordingly, confirmed dengue cases were enrolled during 2016-2018. Serum from all the study subjects was subjected to the standard enzyme-linked immunosorbent assay test for VEGF analysis. In addition, we assessed the association of VEGF to dengue severity. The study revealed that VEGF titers (P < .0001) were significantly increased in severe dengue (SD) patients in contrast to those with a milder form of dengue. An association was obtained between VEGF and increased SGOT (r = 0.517 with P < .0001) while VEGF had a negative correlation with platelets in SD patients (r = -0.331 with P = .001). Enhanced VEGF titers along with decreased platelets had a good association with SD. The investigation revealed that high VEGF titers are novel indicators of dengue severity. However, our results must be verified in a study evaluating a larger number of dengue patients.


Assuntos
Dengue/sangue , Dengue/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue , Estudos de Casos e Controles , Dengue/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Am J Dermatopathol ; 41(12): 897-907, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30998516

RESUMO

Galectin-3, a ß-galactoside-binding lectin, has been implicated in vast repertoire of inflammatory and immunomodulatory processes including skin diseases. However, galectin-3 has not been comprehensively studied in infectious diseases. This study emphasizes on fascinating aspects of galectin-3 expression in dermal infection by studying post-kala-azar dermal leishmaniasis (PKDL), an intracellular infection caused by Leishmania donovani. Indian PKDL is a well-recognized parasitic dermatosis, with a high risk of anthroponotic transmission of L. donovani in causing leishmaniasis. This study aims to investigate the levels of galectin-3 and galectin-3-binding site expression in circulation of different forms of Indian patients with PKDL. Thirty-seven confirmed untreated PKDL patients, comprising 20 polymorphic and 17 macular PKDL manifestations, were evaluated for the levels of sera galectin-3 with respect to 28 age- and sex-matched healthy controls from endemic areas. Result shows a significant increment (P < 0.001) in circulatory galectin-3 levels in PKDL variants as compared to healthy controls. In addition, there were heightened levels of galectin-3 and galectin-3-binding sites on cellular infiltrates on lesional sites. Furthermore, there was a positive correlation between frequencies of mononuclear cells and galectin-3 during microcirculation in lesions. Data were well corroborated with positive correlation of IL-10 and IFN-γ with sera galectin-3 levels. Moreover, flow cytometry demonstrated the enhanced expression levels of the galectin-3-binding site in circulation in patients with PKDL as compared to healthy controls. Taken together, elevated levels of galectin-3 reflect its involvement in PKDL pathogenesis.


Assuntos
Galectina 3/sangue , Leishmaniose Cutânea/sangue , Leishmaniose Visceral/sangue , Pele/metabolismo , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Microambiente Celular , Criança , Citocinas/sangue , Feminino , Humanos , Imunidade Celular , Índia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Ligantes , Masculino , Ligação Proteica , Pele/imunologia , Pele/parasitologia , Regulação para Cima , Adulto Jovem
9.
Indian J Dermatol ; 64(2): 97-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30983603

RESUMO

Background: Vitiligo is one of the common depigmenting disorders causing disfigurement and affecting the quality of life. Redox imbalance is known to play a contributory role in melanocyte destruction. Serum sialic acid (SA) is an important marker of the acute-phase response and is associated with oxidative protein damage. Aim: The aim of this study was to analyze the status of oxidative stress markers and serum SA in vitiligo patients and to correlate the same with disease activity. Materials and Methods: The different oxidative stress parameters namely superoxide dismutase (SOD), malondialdehyde (MDA), and serum SA were measured spectrophotometrically using standard biochemical methodologies in all the study subjects. Results: Serum SOD and MDA values were higher in patients with active vitiligo (n = 23) as compared to stable vitiligo (n = 20) and healthy controls (n = 20). The MDA/SOD ratio was higher in patients with active vitiligo (P<0.0001). Serum SA was increased in active vitiligo as compared to stable vitiligo and healthy controls (P<0.0001). Conclusion: This study indicates that patients with active vitiligo demonstrate enhanced MDA/SOD ratio and increased serum SA. The studied parameters can serve as an important tool to monitor disease activity in vitiligo.

10.
PLoS Negl Trop Dis ; 13(3): e0007249, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30856178

RESUMO

BACKGROUND: Post Kala-azar Dermal Leishmaniasis (PKDL) develops in patients apparently cured of Visceral Leishmaniasis (VL), and is the strongest contender for being the disease reservoir. Therefore, existence of a few cases is sufficient to trigger an epidemic of VL in a given community, emphasizing the need for its active detection and in turn ensuring success of the current elimination program. This study explored the impact of active surveillance on the demographic profile of PKDL patients in West Bengal. METHODOLOGY/PRINCIPAL FINDINGS: Patients with PKDL were recruited through passive (2003-date, n = 100) and active surveillance (2015-date, n = 202), the former from outpatient departments of dermatology in medical colleges in West Bengal and the latter through an active door-to-door survey in four VL hyper-endemic districts of West Bengal. Passive surveillance indicated a male preponderance and a predominance of polymorphic lesions, whereas active surveillance indicated absence of any gender bias and more importantly, macular PKDL constituted almost 50% of the population burden. In terms of polymorphic vs. macular PKDL, the former appeared at a later age, their disease duration was longer and had a higher parasite burden. In the polymorphic variant, the lesional distribution was asymmetrical, comprised of papules/nodules/macules that were present mainly in sun-exposed areas whereas in macular cases, the hypopigmented patches were diffusely present all over the body. CONCLUSIONS/SIGNIFICANCE: Active surveillance unraveled a disease component whose demographic profile showed important differences with PKDL cases who sought treatment in government hospitals. Detection of a higher proportion of macular cases indicates that this variant is not an uncommon presentation as conventionally stated in text books, and should be studied in greater detail to ensure success of the ongoing Leishmaniasis elimination programme.


Assuntos
Monitoramento Epidemiológico , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/patologia , Leishmaniose Visceral/complicações , Pele/patologia , Adolescente , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Fatores de Risco , Fatores Sexuais , Adulto Jovem
11.
Acta Trop ; 190: 73-79, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30395811

RESUMO

Dengue fever is an acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations. Descriptions of the role of circulating immune modulators such as cytokines or chemokines in dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from West Bengal, eastern India, with respect to clinical profile and pro-inflammatory and inflammatory cytokines. We evaluated the profile of both inflammatory and anti-inflammatory cytokines (IFNγ, IL6, IL10, IL12 and TGFß) and chemokines (IL8, CXCL9, CXCL10 and RANTES) in 100 hospitalized NS1/IgM confirmed Dengue patients during the epidemic in West Bengal during 2017. Additionally, all necessary blood investigations of the study subjects were performed. The patients mostly hailed from Kolkata, followed by Nadia, 24 Parganas (North and South), Murshidabad and Midnapore. The most common presentations apart from fever and bodyache were gastrointestinal symptoms. An elevated levels of cytokines IL6 and IL10 chemokine IL8 and CXCL10 along with decreased RANTES were found in the patients with Severe Dengue as compared to mild forms of dengue (p < 0.0001) during 3-6 days of infections. A significant association was obtained between most of cytokine and increased SGPT, haematocrit, albumin and decreased platelet count, whereas a negative correlation with the level of RANTES to haematocrit (r=-0.220 with p = 0.029) was found in severe dengue cases with altered liver function parameters. This is the first study demonstrating cytokine and chemokine association with dengue severity from the eastern part of India. Taken together, this study demonstrated that the altered expression levels of IL6, IL10, IL8, CXCL10 and RANTES had significant associations with dengue severity parameters.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Dengue/imunologia , Quimiocina CCL5 , Feminino , Humanos , Masculino , Dengue Grave/imunologia
12.
J Assoc Physicians India ; 66(5): 22-5, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30477057

RESUMO

Background and Aims: Scrub typhus is the commonest of the rickettsial diseases in India and is difficult to diagnose. Untreated cases have fatality rates of 30-45%. Eschar is present in 7-97% cases. Pneumonia and acute respiratory distress syndrome (ARDS) are frequent complications. Serum immunoglobulin M capture ELISA is the most sensitive test. Doxycycline is the drug of choice. Our objectives were to study the socio-demographic and clinic-epidemiological profiles of scrub typhus cases in two tertiary care hospitals in Kolkata, India. This was the first study of scrub typhus in Southern West Bengal and its neighboring areas. . Methods: Study was conducted over 16 months and all fever cases of Tropical Medicine / Medicine outpatients' clinics were evaluated. Results: Fourteen cases were diagnosed. 78.6% were from rural areas and 35.7% were farmers. Headache and fever were the commonest presenting complaints while eschar was found in only 21.4%. Serum IgM scrub typhus antibody was positive in all cases . Conclusion: Scrub typhus should be a differential diagnosis in acute febrile illness cases, as early diagnosis and therapy prevents complications.


Assuntos
Orientia tsutsugamushi , Tifo por Ácaros , Demografia , Humanos , Índia , Tifo por Ácaros/epidemiologia , Centros de Atenção Terciária
13.
Indian J Med Microbiol ; 36(2): 217-223, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30084414

RESUMO

Background: Combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and efavirenz (EFV) is preferred in the treatment of HIV/hepatitis B virus (HBV) coinfection. We postulated that a HBV active nucleoside reverse transcriptase (RT) inhibitor/nucleotide RT inhibitor backbone of adefovir dipivoxil (ADV) +3TC would be as effective as TDF +3TC for the Indian population. Objective: ADV + 3TC could be an alternative option for these HIV/HBV coinfected individuals, preserving the dually active TDF + 3TC as second-line nucleoside backbone following failure of the first-line ART. Materials and Methods: This randomised control trial (CTRI/2012/03/002471) was carried out at the ART Centre of Calcutta School of Tropical Medicine, India. Seventy-eight (39 on each arm) treatment-naïve HIV/HBV coinfected patients were randomised to receive either the combination of lamivudine + tenofovir + EFV or lamivudine + adefovir + zidovudine + EFV and followed up for 120 weeks. Results: Median age of the study participants was 36 years (21-62), majority were male (61/78; 78.2%) and heterosexually (39/78; 50%) infected. Baseline characteristics were identical in both arms. There was no statistically significant difference in median aspartate aminotransferase (37 vs. 29.5 U/L), alanine aminotransferase (ALT) (36 vs. 34.5 U/L), ALT normalisation rate (80 vs. 70%), AST to platelet ratio index (0.45 vs. 0.33), CD4 count (508 vs. 427 cells/mm3), HBV DNA suppression (81.8 vs. 70%), hepatitis B e antigen loss (9 vs. 5%), hepatitis B surface antigen seroclearance rate (6.06 vs. 18.75%) and death (3 vs. 3) at 120 weeks between TDF (n = 33) and ADV (n = 32), respectively. Conclusions: Adefovir plus lamivudine is an effective alternative of tenofovir plus lamivudine in long-term HBV treatment outcome in HIV/HBV coinfected patients.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Tenofovir/uso terapêutico , Adenina/uso terapêutico , Adulto , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Virusdisease ; 29(3): 375-379, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30159374

RESUMO

Chikungunya (CHIK) is an arboviral infection having huge global burden affecting the life style of the patient badly due to debilitating polyarthralgia. This study aims to evaluate intracellular reactive oxygen species (ROS) in peripheral blood of patients suffering with persisting polyarthralgia post CHIK infection and the potential of Tinospora cordifolia leaf extract in scavenging those free radicals in peripheral blood mononuclear cells (PBMC) of the patient. Peripheral blood was collected from written informed consented patients and intracellular ROS was measured in PBMC of patients suffering with persisting polyarthralgia 3 months post CHIK infection followed by the study of free radical scavenging by T. cordifolia leaf extract in those cells through flow cytometry. Control population comprising healthy donors were also included in the study. As compared to healthy subjects, twofold higher Intracellular ROS (17.89 ± 1.007 vs. 37.96 ± 1.510, P < 0.0001) was found in patient PBMC. Ex-vivo treatment of those PBMC with ethanolic extract of T. cordifolia leaf (1 µg/mL) decreased intracellular ROS significantly by twofold (P < 0.0001). This study reports that CHIK infection produces high level of intracellular ROS in the patients suffering with persisting polyarthralgia, which was significantly scavenged by ex vivo treatment with T. cordifolia leaf extract.

16.
Trans R Soc Trop Med Hyg ; 112(6): 294-299, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29992273

RESUMO

Background and objectives: The HIV-associated renal diseases represent a spectrum. Indian data on this is sparse. This study was undertaken to find out the prevalence and clinicopathological spectrum of renal involvement in HIV among antiretroviral therapy (ART) naïve patients (Group 1) and among those on ART (Group 2). Methods: Systematic random sampling was undertaken to select 109 patients each from virology outpatient department (VOPD) and ART centre of a tertiary care hospital. They were screened and further investigated if renal involvement was found. Results: Renal involvement was present in 25/109 (22.94%) and 15/109 (13.76%) patients of Groups 1 and 2, respectively. Among patients of Groups 1 and 2, 9/24 (37.5%) and 2/13 (15.4%), respectively, had clinically significant proteinuria, but none in the nephrotic range. Statistically significant relationships of renal involvement were observed with CD4 count <100/µl and with low BMI. Of the patients of Group 2, 20% of those on a tenofovir-based regimen had renal involvement with tubular changes, while only 4.6% of those on other regimens had renal involvement. This difference was statistically significant (p<0.05; OR=5.25). Conclusion: Renal involvement was less common among those on ART. Low CD4 count and body mass index (BMI) were associated with renal dysfunction. Patients on a tenofovir-based regimen had more renal involvement compared with not on a tenofovir-based regimen.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Proteinúria/virologia , Insuficiência Renal/virologia , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/epidemiologia , Centros de Atenção Terciária
17.
PLoS One ; 13(2): e0192302, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29420575

RESUMO

BACKGROUND: Post Kala Azar Dermal Leishmaniasis (PKDL) occurs as dermal consequence of previous Visceral Leishmaniasis (VL) infection and serves as an important reservoir for transmission of VL. Diagnosis of PKDL is often challenging for its symptomatic resemblance to other co-endemic diseases like Leprosy or Vitiligo. Parasitological examination by slit-skin smear and culture are the standard methods but lack high sensitivity. Thus, for efficient control of VL, reliable diagnostic and prognostic assay of PKDL are required. OBJECTIVE: Previously, glycoproteins (9-OAcSA) have been reported as promising biomarkers of Indian VL patients. However, till date, the status of glycans in Indian PKDL patients remains unexplored. Accordingly, in this study, the glyco-profile of PKDL Circulating Immune Complexes (CICs) as compared to other cross diseases like Vitiligo and Leprosyhas been investigated. Further, a novel Glyco CIC assay has been developed for efficient Indian PKDL patient diagnosis. METHODS/PRINCIPAL FINDING: In the present study, 90 PKDL patients were enrolled from 3 VL endemic districts of West Bengal during 2015-16. Glycosylation profile of isolated CICs from sera of PKDL patients were initially analyzed through gradient SDS gel electrophoresis followed by PAS silver double staining, which revealed the presence of several glycan rich PKDL specific proteins of varying molecular weights. To further characterize the glyco-profile of acid dissociated affinity purified immuno-reactive antigens present in the CICs, glycosylation was demonstrated in these purified CIC antigens by DIG glycan differentiation kit with or without glycosidase as well as neuraminidase treatment. Diagnostic evaluation of the newly developed colorimetric Glyco CIC assay through Receiver Operating Characteristic (ROC) curve analysis revealed excellent (0.99) AUC value as compared to other conventional serodiagnostic assays like PEG CIC, Parasite ELISA (IgG and IgM). Additionally, longitudinal monitoring of 18 PKDL patients further revealed its good prognostic utility. CONCLUSION: These results highlight the glycosylation status of CICs among Indian PKDL patients present in all the studied endemic districts of West Bengal. These PKDL biomarkers were completely absent in cross diseases like Vitiligo and Leprosy. Further, the newly developed Glyco CIC assay had an improved sensitivity of 95.6%, specificity of 99.3%, NPV of 97.1% and PPV of 98.9%.


Assuntos
Complexo Antígeno-Anticorpo/sangue , Biomarcadores/sangue , Glicoproteínas/sangue , Leishmaniose Cutânea/sangue , Leishmaniose Visceral/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia/epidemiologia , Leishmania donovani/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Clin Infect Dis ; 66(3): 404-410, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29020350

RESUMO

Background: The potential reservoirs of leishmaniasis in South Asia include relapsed cases of visceral leishmaniasis (VL), patients with post-kala-azar dermal leishmaniasis (PKDL), and an asymptomatically infected population. Therefore, assessment of cure in terms of parasite clearance, early detection of PKDL, and asymptomatic VL are pivotal for ensuring elimination. This study aimed to monitor the efficacy of miltefosine and liposomal amphotericin B (LAmB) in PKDL based on parasite load. Methods: Patients with PKDL were recruited from the dermatology outpatient departments or during active field surveys. Skin biopsies were collected at disease presentation, immediately at the end of treatment, and 6 months later. The presence of parasite DNA was assessed by internal transcribed spacer-1 polymerase chain reaction, and quantified by amplification of parasite kinetoplastid DNA. Results: At disease presentation (n = 184), the median parasite load was 5229 (interquartile range [IQR], 896-50898)/µg genomic DNA (gDNA). Miltefosine cleared the parasites to <10 in the macular (n = 17) and polymorphic (n = 21) variants, and remained so up to 6 months later (<10 parasites). LAmB reduced the parasite burden substantially in macular (n = 34; 2128 [IQR, 544-5763]/µg gDNA) and polymorphic PKDL (n = 36; 2541 [IQR, 650-9073]/µg gDNA). Importantly, in patients who returned 6 months later (n = 38), a resurgence of parasites was evident, as the parasites increased to 5665 (IQR, 1840-17067)/µg gDNA. Conclusions: This study established that quantifying parasite load is an effective approach for monitoring patients with PKDL, wherein miltefosine demonstrated near-total parasite clearance and resolution of symptoms. However, in cases treated with LAmB, the persistence of parasites suggested treatment inadequacy. This needs immediate redressal in view of the leishmaniasis elimination program targeted for 2020.


Assuntos
Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Carga Parasitária , Adolescente , Adulto , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Infecções Assintomáticas/epidemiologia , Biópsia , DNA Intergênico/genética , DNA de Protozoário/genética , Feminino , Humanos , Índia/epidemiologia , Leishmaniose Cutânea/epidemiologia , Leishmaniose Visceral/epidemiologia , Masculino , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Reação em Cadeia da Polimerase , Pele/parasitologia , Pele/patologia , Adulto Jovem
19.
Indian J Pharmacol ; 49(3): 223-228, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29033481

RESUMO

BACKGROUND: Besides unparalleled benefits, highly active antiretroviral therapy is also associated with wide range of potential adverse drug reactions (ADRs), which hinders treatment adherence. The present study was thus designed to monitor and explore the pattern of occurrence of ADRs to various antiretroviral therapy (ART) regimens in a tertiary care ART setup. MATERIALS AND METHODS: A prospective, observational clinical study was carried out in the outpatient setting of nodal ART center of Eastern India. A total of 610 patients on various ART regimens were studied for suspected ADRs over 12 months. Adverse event history, medication history, and other relevant details were captured. Causality and severity of each reported ADR were duly assessed. RESULTS: 32.45% patients of total study participants presented with a total of 330 ADRs. Patients from zidovudine-based regimens presented with majority of ADRs such as anemia (up to 36%), central nervous system (CNS), and gastrointestinal (GI) side effects. Tenofovir-based regimens were, however, found to be mildly safer. The combination with Efavirenz was associated with majorly CNS side effects while that of nevirapine was associated with rash and pigmentation of nails. Atazanavir boosted second-line regimens were notably associated with increased serum lipid levels followed by other GI and CNS adverse effects. Increased liver enzymes were found in atazanavir-based second-line ART. CONCLUSION: The study enables to obtain information on the incidence and pattern of ADRs associated with various antiretroviral regimens, thereby reducing its occurrence and protecting the patient population from avoidable harm. Need of intensive monitoring for ADRs in ARTs thus seems to be a mandate.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Adolescente , Adulto , Idoso , Causalidade , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Infecções por HIV/complicações , Humanos , Incidência , Índia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção Terciária , Adulto Jovem
20.
PLoS One ; 12(6): e0179035, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28591184

RESUMO

Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection. Discrete differences were also observed with respect to quasispecies divergence. Additionally, subgenotype D1 was most frequent in occult infection, while D2 was widespread during chronic infection. The majority (~90%) of occult D1 sequences had the sQ129R mutation in the surface gene. This study highlights several distinct features of OBI in India and underscores the need for additional HBV DNA screening in HIV-positive individuals.


Assuntos
Doenças Transmissíveis/sangue , Infecções por HIV/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/sangue , Adolescente , Adulto , Idoso , Antígenos CD4/sangue , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/virologia , DNA Viral/sangue , Feminino , HIV/patogenicidade , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite B/epidemiologia , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Atenção Terciária à Saúde , Adulto Jovem
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