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ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2 . This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15-20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene ( EVER1 :c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.
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Epidermodisplasia Verruciforme , Proteínas de la Membrana , Linaje , Adulto , Humanos , Masculino , Análisis Mutacional de ADN , Epidermodisplasia Verruciforme/genética , Epidermodisplasia Verruciforme/patología , Mutación del Sistema de Lectura , Predisposición Genética a la Enfermedad , Homocigoto , India , Proteínas de la Membrana/genética , Fenotipo , Eliminación de SecuenciaRESUMEN
BACKGROUND: Conidiobolomycosis is a rare tropical rhinofacial fungal infection which has not been well characterised. The available evidence in its management is sparse due to lack of clinical studies and the limited data on antifungal susceptibility patterns. OBJECTIVE: To analyse the clinical manifestations, antifungal treatment and outcomes of patients with conidiobolomycosis and to determine antifungal susceptibility profiles of the isolates. PATIENTS/METHODS: Retrospective analysis of data of all patients with a diagnosis of conidiobolomycosis confirmed by histopathology and culture at a tertiary care hospital from 2012 to 2019 was done. RESULTS: There were 22 patients, 21 males and one female, with a mean age of 37.1 years. Most common presenting symptom was nasal obstruction, found in 20 (90.90%) patients. Patients who presented within 12 months had a better cure rate (85%) compared to those who presented late (67%). Among the 19 patients who had a follow-up, good outcome was seen in 15 of the 17 (88.24%) patients who were on itraconazole or potassium iodide containing regimen. Of the six patients who received additional trimethoprim-sulphamethoxazole (co-trimoxazole), 67% showed good outcome with two patients showing complete cure and two patients still on treatment with significant improvement. High minimum inhibitory concentration (MIC) values were noted for azoles and amphotericin B, whereas co-trimoxazole showed lowest MIC ranges. CONCLUSION: Itraconazole and potassium iodide are reasonable first-line options for the treatment of conidiobolomycosis. Good clinical response to KI and comparatively lower MIC of co-trimoxazole are promising. Further studies are required for developing clinical breakpoints that can predict therapeutic outcomes.
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Antifúngicos/uso terapéutico , Conidiobolus/efectos de los fármacos , Enfermedades Raras/microbiología , Cigomicosis/tratamiento farmacológico , Cigomicosis/microbiología , Adulto , Manejo de la Enfermedad , Cara/microbiología , Cara/patología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Enfermedades Nasales/tratamiento farmacológico , Enfermedades Nasales/microbiología , Enfermedades Raras/tratamiento farmacológico , Estudios Retrospectivos , Centros de Atención Terciaria/estadística & datos numéricos , Adulto JovenRESUMEN
Background: Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. Methodology: This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Results: Univariate analysis showed significant association with 1) Self-reported nonadherence<95% [OR 12.81 (95%CI 1.54-281.45)]. 2) Treatment interruptions in adherent cases (OR 9.56 (95% CI 1.11-213.35)]. 3) Past inappropriate therapies [OR 9.65 (95% CI 1.12-215.94)]. 4) Diarrhoea [OR 16.40 (95% CI 2.02-3.55.960]. 5) GI opportunistic infections (OR 11.06 (95% CI 1.31 -244.27)] and 6) Drug Toxicity [OR 3.69 (95% CI 1.15-12.35).In multiple logistic regression analysis, we found independent risk factors of treatment failure to be: Self-reported non-adherence (<95%) with OR 15.46(95%CI 1.55 - 154.08), drug toxicity - OR 4.13(95%CI 1.095 - 15.534) and history of diarrhoea - OR 23.446(95%CI 2.572 - 213.70). Conclusion: This study reveals that besides adherence to therapy, presence of diarrhoea and occurrence of drug toxicity are significant risk factors associated with failure of anti-retroviral therapy. There is a need for further prospective studies to assess their role in development of treatment failure on ART and thus help development of targeted interventions.
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Antirretrovirales , Infecciones por VIH , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Estudios de Casos y Controles , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Humanos , Cumplimiento de la Medicación , Estudios Prospectivos , Factores de Riesgo , Insuficiencia del TratamientoRESUMEN
Hyperacute GVHD (HaGVHD) is a rare complication of hematopoietic stem cell transplantation (HSCT) occurring before engraftment, a syndrome commonly involving skin and/or gut and/or liver, with increased morbidity and mortality. Myeloablative conditioning (MAC) regimes and mismatched donor transplants have an increased risk for HaGVHD. There is a higher chance of steroid-refractoriness and chronic GVHD in those who develop HaGVHD. There is limited literature about HaGVHD, especially in the paediatric age group. This retrospective single-centre case series included five paediatric patients who underwent HSCT between 1st April 2013 and 31st July 2015 at a tertiary care centre in South India, who fulfilled the criteria for HaGVHD as per criteria by Kim et al. and whose follow up data was available. We noted their risk factors, clinical course and prognosis. There were five paediatric HaGVHD patients. The risk factors noted among them were MAC regimen in three and mismatched unrelated donor sources in three. Two had steroid-refractory disease, four went on to develop chronic GVHD and three died of GVHD or treatment-related complications. A high index of suspicion is necessary to recognize HaGVHD, especially in patients with known risk factors developing a fever with rash post-HSCT.
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BACKGROUND: Antiretroviral treatment (ART) programs from low-income countries utilizing standardized ART regimens, simplified approaches to clinical decision making and basic lab monitoring have reported high mortality rates. We determined the risk factors for mortality among HIV-infected adults following the initiation of ART from a single center in south India. METHODS: ART-naive HIV-infected south Indian adults attending the Infectious Diseases clinic in a 2000-bed academic medical center in south India who were initiated on ART (generic, fixed-dose combinations) as per the national guidelines were followed up. Cases (32 patients who died) were compared with age and sex matched controls. RESULTS: Eight-hundred and twenty-two patients were started on ART from January 1, 2000 to December 31, 2008. The cumulative mortality was 6.8% (56/822). Among the cases mean age was 44 years, 18% were women and mean CD4 counts was 107 cells/microl. Among the controls mean age was 41 years, 18% were women and mean CD4 counts were 113 cells/microl. Stavudine based ART was predominant 62.5% in the cases vs 37.5% in the controls, followed by zidovudine based therapy in 31.2% of cases and 43.7% in the controls. Tenofovir based therapy was used in 6.2% of cases vs 18.7% in the controls. The commonest causes of death were drug toxicity 19%, advanced Acquired Immunodeficiency Syndrome (AIDS) in 37%, Immune Reconstitution Inflammatory Syndrome (IRIS) in 16%, non AIDS related deaths in 22% and malignancies 6%. In a univariate analysis, absolute lymphocyte count <1200 cells/cmm (p=0.03), development of immune reconstitution inflammatory syndrome (IRIS) (p=0.000) and mean CD4 cell count increase <75 cells/microl after 1 year of ART (p=0.001) were significantly associated with mortality. CONCLUSIONS: The mortality among our patients was comparable to that reported from other low-income countries. Earlier initiation of ART may reduce the high mortality rates observed.
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Síndrome de Inmunodeficiencia Adquirida/mortalidad , Antirretrovirales/efectos adversos , Países en Desarrollo , Síndrome Inflamatorio de Reconstitución Inmune/mortalidad , Neoplasias/mortalidad , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Antirretrovirales/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/mortalidad , Femenino , Humanos , India , Masculino , Factores de RiesgoRESUMEN
PURPOSE: Hand Foot and mouth disease (HFMD) is a major childhood exanthematous disease causing outbreaks that have become a major public health threat in recent years. In Vellore district of Tamil Nadu, south India, occasional outbreaks are common among the paediatric age group, most commonly in those under 5years of age (U5s). CoxsackieA6, A4, A5, A9, A10, B2 and B5 are the common serotypes causing outbreaks. This study aimed to identify the molecular serotype of the causative agent, co-circulating in this region. METHODS: Adapting the WHO case definition, cases during an HFMD outbreak between October and December 2017, were identified by a clinical criterion of fever, mouth ulcers and rash in the extremities. Vesicle fluid from these lesions were collected in viral transport medium and transported cold to the Clinical Virology laboratory of a tertiary care hospital in Vellore. Identification of the causative agent was undertaken by two real time PCRs (EV1 and EV2) followed by sequencing the VP1-2C region and constructing a phylogenetic tree. RESULTS: Among the 31 HFMD patients included in this study, 23 (74.2%) were U5s, 3 (9.7%) were between 6 and 15 years and the remaining 5 (16.1%) were adolescents (>15 âyrs). The outbreak ran a mild clinical course, with 22(71%) patients having fever as a prodromal symptom. Papulovesicular lesions characteristic of HFMD were present on all 31 (100%) patients' palms and soles, buttocks of 19 (61.3%), oral mucosa of 12 (38.7%), and all over the body in 4 (12.9%) patients. Coxsackie A6(75%) and Coxsackie A16(25%) were the pathogens associated with this outbreak. CONCLUSIONS: Changing epidemiology of HFMD was seen in this outbreak since; other serotypes apart from the classical Coxsackievirus serotypes causing HFMD outbreak were also found co-circulating. EV1 PCR was a better screening assay than EV2 PCR in this region. Continued surveillance and molecular serotyping are necessary for HFMD outbreaks in any region.
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Enterovirus , Enfermedad de Boca, Mano y Pie , Adolescente , Niño , Preescolar , China/epidemiología , Brotes de Enfermedades , Enterovirus/genética , Enfermedad de Boca, Mano y Pie/epidemiología , Humanos , India/epidemiología , Filogenia , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Currently, there is a global contemplation to end the AIDS epidemic by 2030. HIV-2 poses unique challenges to this end. The burden of HIV-2 is higher in resource-limited countries, and it is intrinsically resistant to NNRTI drugs. In addition, there is no FDA-approved plasma viral load assay to monitor disease progression and therapeutic efficacy. To overcome these challenges, we have developed and evaluated an in-house quantitative HIV-2 viral load assay. METHODS: Blood samples were collected from 28 HIV-2 treatment-naïve monoinfected individuals and tested using an in-house qPCR HIV-2 viral load assay. The extracted RNA was amplified using Quantifast pathogen + IC kit. RESULTS: The in-house qPCR has a limit of detection of 695 copies/ml. The intra- and inter-assay variation (% CV) of the assay was 0.61 and 0.95, respectively. The in-house assay quantified HIV-2 NIBSC accurately (1000 IU) with a mean of 1952 copies/mL. Among the 28 samples tested by in-house qPCR assay, 11 (39.2%) samples were quantified, whereas 17 (60.7%) samples were not detected. In comparison with Altona RealStar HIV-2 RT PCR and Exavir Load RT assay, the results were 96.4% and 69.6% concordant, respectively. No significant (p = 0.99 and p = 0.13) difference in quantifying viral load between the three assays. Based on clinical and immunological (CD4) staging, the performance characteristics were comparable. CONCLUSION: To the best of our knowledge, this is the first in-house qPCR developed in India. The performance characteristics of the in-house assay are comparable to the commercial assays, and they can be used assertively to monitor HIV-2 patients.
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Infecciones por VIH , VIH-2 , Humanos , Carga Viral , VIH-2/genética , Juego de Reactivos para Diagnóstico , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN Viral , Sensibilidad y EspecificidadRESUMEN
Since 2000, a resurgence of syphilis has been noted in many developed and developing countries, especially among men who have sex with men (MSM). Incidence and prevalence of syphilis in pregnant women have been reduced drastically by mandatory screening in early pregnancy. Insufficient data in other populations especially from developing countries limit targeted public health interventions. This study aimed to describe the clinical and epidemiological profile of serologically confirmed syphilis cases among the non-pregnant high-risk group reporting to a tertiary care center in Southern India. A retrospective study was carried out in a tertiary care center in Southern India for 6 years from 2015 to 2020. A total of 265 serologically confirmed syphilis patients were included. A statistically significant increase in positivity from 0.52 to 2.1% was observed in this study (2015 to 2020). Among risk factors, high-risk behavior with multiple heterosexual partners was the commonest (51.3%), followed by marital partners who tested positive (9.4%) and MSM (7.5%). The majority of the patients were diagnosed at the latent stage (79%), followed by secondary syphilis (10%) and tertiary syphilis (8%). A quarter of patients (23%) were coinfected with HIV. Serological non-responsiveness was more common among HIV infected (47 vs. 24%). Sixteen had neurosyphilis and six had ocular involvement. HIV co-infection complicated 50% (8/16) of neurosyphilis patients. Syphilis is still prevalent, especially in high-risk groups including those are attending STI clinics. Further prospective multicentric studies are needed to identify and implement public health measures.
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Infecciones por VIH , Neurosífilis , Minorías Sexuales y de Género , Sífilis , Adulto , Femenino , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , India/epidemiología , Masculino , Neurosífilis/complicaciones , Embarazo , Estudios Retrospectivos , Sífilis/diagnóstico , Sífilis/epidemiología , Sífilis/prevención & control , Centros de Atención TerciariaRESUMEN
CONTEXT: Sarcoidosis is a systemic disorder characterized histologically by noncaseating granulomas. There is paucity of Indian data on cutaneous sarcoidosis. AIMS: To describe the clinical, histopathological findings, and extracutaneous involvement in cutaneous sarcoidosis. MATERIALS AND METHODS: A retrospective study was done in patients of cutaneous sarcoidosis who had attended the dermatology clinic of a tertiary health care center in India from May 2009 to April 2015. The clinical details, histopathological findings, treatment, and response were reviewed. RESULTS: There were 38 patients with cutaneous sarcoidosis. Mean age was 48 ± 13 years; 58% were female. Median duration of disease was 11 months (IQR 4-48 months). More than one morphology was seen in 28.9%, commonest being plaques (65.7%), and papules (50%). Erythema nodosum was rare. More than one site was involved in 55.3%, most commonly trunk (52.6%). Six patients had isolated cutaneous sarcoidosis. Commonest extracutaneous organs involved were lung (73.7%) and lymph nodes (68.4%). Histopathologically, classical naked sarcoidal granulomas were found in only 55.3%. Angiotensin converting enzyme (ACE) levels were elevated in 74.3% (26/35) with significant association with extracutaneous disease. Treatment included topical and/or systemic corticosteroids, hydroxychloroquine, and tacrolimus. STATISTICS: Pearson's Chi-square test was done to analyze associations between the skin lesions, ACE levels, and systemic involvement; P < 0.05 was considered significant. CONCLUSIONS: Cutaneous manifestations of sarcoidosis are varied, commonest being erythematous plaques. Even though most patients had systemic involvement, we found no significant association of the type and number of skin lesions with extracutaneous involvement or prognosis. Elevated ACE levels were significantly associated with systemic involvement.
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BACKGROUND: Chronic immune activation is one of the most widely recognized hallmarks of HIV infection. T-cells that express CD38+ and HLA-DR+ show poor proliferative potential, signal transduction, and increased apoptotic potential. This affects HIV pathogenesis and its outcome and further complicates with a coinfection like HBV. METHODS: Study Design: cross-sectional. Blood samples were collected and analyzed for virological markers using ELISA for HBeAg and RT-PCR for HIV&HBV Viral load. Chronic immune activation markers of CD8+ and CD4+ T cells were measured by Flow cytometry for both HIV and HBV. RESULTS: There was a significant increase in HBV replication shown by higher HBV DNA (p=0.002), a higher proportion of HBeAg (p=0.0049), and lower CD4 counts (p=0.04) among HIV/HBV coinfected individuals, compared to the monoinfected groups. The frequencies of CD4+ CD38+ HLA-DR+ and CD8+ CD38+ HLA-DR+ in the HIV/HBV coinfection were significantly higher than HBV monoinfected group (P< 0.0001) and in the HIV monoinfected group (P < 0.0001). The Liver fibrosis score APRI and FIB-4, were higher in the coinfected group compared with HBV monoinfected group (0.67 vs. 0.25, p = 0.0085; 3.48 vs. 0.98, p = 0.0026) respectively. The cytokine levels of IL-17, Fas-L,TNF -α, IL-10, IL-2 and Granzyme B were also measured and compared among the study groups. CONCLUSION: Our data suggest that HIV probably influences immune activation of CD4+ and CD8+ T cells and this may play a significant role in accelerating the disease outcome among HIV/HBV coinfected individuals.
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Coinfección , Infecciones por VIH , VIH-1 , Estudios Transversales , Infecciones por VIH/complicaciones , Virus de la Hepatitis B , Humanos , India , Carga ViralRESUMEN
OBJECTIVE: The health care utilisation pattern among Indian leprosy patients accessing a tertiary care centre over an 18 month period was studied. DESIGN: A study was conducted at the Dermatology Outpatient Clinic at the Christian Medical College, Vellore, from January 2005 to June 2006. The profile of patients was assessed and a subgroup was interviewed on their healthcare use, including any delays and costs incurred. RESULTS: 198 patients presented of which 115 patients (58.1%) were on treatment for leprosy or a leprosy reaction (active) including 35 new patients (17.7%), and 83 (41.9%) patients were not on active treatment (inactive). 81 patients were interviewed in depth, 14 (17.3%) were new patients included among 54 (66.7%) patients with active disease, and 27 (33.3%) with inactive disease. The average delay from the onset of symptoms to starting treatment in those interviewed was 13.4 months, 7.9 months of which was a patient-related delay and 5.4 months of which was the health care system-related delay. In patients who had been released from treatment, 78.6% (22/28) required care after cure. CONCLUSIONS: Improved awareness is required to reduce patient-related delays and systems for sustained training need to be in place to tackle the problem of health care system-related delays. Care after cure is a felt need for many patients released from treatment.
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Atención a la Salud/estadística & datos numéricos , Disparidades en Atención de Salud/organización & administración , Lepra/diagnóstico , Lepra/terapia , Atención Primaria de Salud/estadística & datos numéricos , Distribución por Edad , Pueblo Asiatico/estadística & datos numéricos , Femenino , Servicios de Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/economía , Humanos , India , Entrevistas como Asunto , Lepra/economía , Lepra/etnología , Masculino , Mycobacterium leprae , Atención Primaria de Salud/economía , Distribución por Sexo , Factores Sexuales , Factores Socioeconómicos , Factores de TiempoRESUMEN
Leishmaniasis is endemic in the Indian subcontinent with predominance of visceral leishmaniasis (VL) due to Leishmania donovani. Cutaneous leishmaniasis (CL) is uncommon, and mucocutaneous leishmaniasis (MCL) is rarely reported in this region. Recent reports reveal a changing epidemiology and atypical manifestations. A retrospective study of 52 suspected cases with cutaneous and mucosal involvement seen from January 2008 to December 2018 in a tertiary care setting in a non-endemic state in southern India is reported. Twelve patients were confirmed to have leishmaniasis; seven had MCL, two had CL, and three had post-kala-azar dermal leishmaniasis (PKDL). All cases were male, with a median age of 41.5 years (interquartile range, 30-55.5 years), and the median duration of the disease was 6 years (interquartile range, 1-9.5 years). Patients with MCL had mucosal involvement including destructive ulcero-proliferative lesions due to delayed diagnosis; none had a history of travel to countries endemic for MCL and all were attributable to L. donovani species. On the other hand, Leishmania major which was the causative species in both CL patients was associated with travel to the Middle East. Patients with PKDL presented with multiple plaques and hypopigmented patches; one had concomitant VL and all were from endemic areas. Hitherto uncommon MCL, caused by potentially atypical variants of L. donovani, has emerged as a new manifestation of leishmaniasis in this region. A high index of suspicion based on lesions seen and history of travel combined with PCR-based diagnostics are required to confirm diagnosis for the various skin manifestations of leishmaniasis.
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Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/patología , Leishmaniasis Mucocutánea/epidemiología , Leishmaniasis Mucocutánea/patología , Piel/patología , Adolescente , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Gluconato de Sodio Antimonio/uso terapéutico , Antiprotozoarios/uso terapéutico , Ácido Desoxicólico/uso terapéutico , Combinación de Medicamentos , Humanos , India/epidemiología , Itraconazol/uso terapéutico , Leishmania donovani , Leishmania major , Leishmaniasis Cutánea/parasitología , Leishmaniasis Mucocutánea/parasitología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: The hypothesis to be tested was that the prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasia would be significantly higher in HIV seropositive women as compared with seronegative controls. Secondary aims were to determine the risk factors for HPV and cervical intraepithelial neoplasia and the HPV types in HIV-positive women. MATERIALS AND METHODS: A cross-sectional study of women 18 to 49 years old was done. Seventy-five women who were HIV seropositive and 58 seronegative women, of whom 27 had HIV-positive partners, participated in the study. A Pap smear and a cervical swab for HPV were done. Women with Pap smear abnormality underwent colposcopy and large loop excision procedures if indicated. RESULTS: Ten (13.3%) HIV-positive women had high-grade squamous intraepithelial lesion as compared with 2 (3.4%) seronegative women (odds ratio [OR] 4.3; 95% CI = 0.9-41.7; p =.048). Among the HIV-positive women, 28 (37.3%) had high-risk HPV, whereas only 9 (15.5%) had high-risk HPV among seronegative women (OR 3.2; 95% CI = 1.3-8.3; p =.009). Among women who were positive for high-risk HPV, the HIV-positive women were significantly more likely to have more than 1 HPV type (OR 7.4; 95% CI = 1.4-43.7; p =.005). Women who had coitus at less than 18 years of age were more likely to have high-risk HPV infection (OR 2.9; 95% CI = 1.2-6.2; p =.013) even after controlling for HIV status. CONCLUSIONS: HIV-positive women have a higher risk for multiple HPV infections as compared with seronegative women. Behavioral factors dominate HIV in determining HPV infections and resultant cervical neoplasia.
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Anticuerpos Anti-VIH/inmunología , Seropositividad para VIH/complicaciones , Papillomaviridae/inmunología , Infecciones por Papillomavirus/epidemiología , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adolescente , Adulto , Estudios Transversales , Femenino , Seropositividad para VIH/epidemiología , Humanos , India/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Prevalencia , Factores de Riesgo , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/complicaciones , Displasia del Cuello del Útero/virologíaRESUMEN
OBJECTIVES: To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. METHODS: In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. RESULTS: Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. CONCLUSIONS: The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.
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Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto , Antirretrovirales/efectos adversos , Recuento de Linfocito CD4 , Estudios de Cohortes , Intervalos de Confianza , Progresión de la Enfermedad , Medicamentos Genéricos , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/mortalidad , Humanos , Incidencia , India/epidemiología , Modelos Logísticos , Masculino , Oportunidad Relativa , Estudios Prospectivos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Linfocitos TRESUMEN
Delusional parasitosis is a rare psycho-dermatological disorder that lacks standard management guidelines. We report a case of an elderly woman with long standing multiple dermatological illnesses who later developed delusional parasitosis. We highlight the pertinent diagnostic and therapeutic challenges. We support multidisciplinary collaborative care combining effective pharmacotherapy with efficient non-pharmacological measures.
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Antipsicóticos/uso terapéutico , Deluciones , Infestaciones Ectoparasitarias/psicología , Enfermedades Parasitarias/psicología , Risperidona/uso terapéutico , Anciano , Deluciones/diagnóstico , Deluciones/tratamiento farmacológico , Deluciones/psicología , Infestaciones Ectoparasitarias/diagnóstico , Infestaciones Ectoparasitarias/tratamiento farmacológico , Femenino , Humanos , Enfermedades Parasitarias/diagnóstico , Enfermedades Parasitarias/tratamiento farmacológico , Psicoterapia , Resultado del TratamientoRESUMEN
Aims: Cervical cancer is one of the leading causes of cancer among women, worldwide. HIV-positive women tend to have persistent infection and infection with multiple human papillomavirus (HPV) types. There is a need for affordable HPV DNA tests as viable alternatives to the existing costly commercial assays. The aim of the study was to establish PGMY-CHUV reverse hybridization assay as a cost-effective tool for HPV genotyping. Study Design: This was a prospective study conducted in a tertiary care centre from March 2011 to July 2012. Subjects and Methods: Fifty cervical brush samples from HIV-infected women and 43 WHO reference samples were tested by both the CHUV assay and linear array (LA). Results: The CHUV assay in comparison to the LA showed a sensitivity of 91%, specificity of 52% and a moderate agreement for all samples that were compared. However, most high-risk HPV types were identified amongst the clinical samples, and the entire range of genotypes in the WHO reference panel was detected. Statistical Analysis: The accuracy indices such as sensitivity, specificity, positive predictive value and negative predictive value were calculated. The level of agreement (kappa value) between the two assays was also calculated. Conclusion: The CHUV assay had an acceptable sensitivity, but it lacked specificity for HPV detection. Despite the lower rates of detection of multiple infections from clinical samples, better results were obtained with the WHO reference samples and the ability of the assay to identify the entire range of genotypes suggests that it can be an efficient tool for genotyping.
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Técnicas de Genotipaje/métodos , Infecciones por VIH/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Adolescente , Adulto , Cuello del Útero/virología , Análisis Costo-Beneficio , ADN Viral/genética , Femenino , Genotipo , Seropositividad para VIH , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/virología , Adulto JovenRESUMEN
Purpose: The sequence variation of human immunodeficiency virus (HIV) capsid region may influence and alter the susceptibility to human tripartite motif 5α protein (huTRIM5α). Materials and Methods: Molecular docking was carried out with huTRIM5α SPRY domain by the use of ClusPro and Hex docking program for HIV-1 and HIV-2 capsid sequences. Results: The sequence analysis on HIV-1 and HIV-2 capsid gag gene identified 35 (19.7%) single-nucleotide polymorphisms (SNPs) in HIV-1 and 8 (4.5%) SNPs in HIV-2. The variations observed in the HIV-2 capsid region were significantly lower than HIV-1 (P < 0.001). The molecular docking analysis showed that HIV-1 wild type used V1 loop, while HIV-2 used V3 loop of huTRIM5α for interaction. HIV-1 with A116T SNP and HIV-2 with V81A SNP use V3 and V1 loop of huTRIM5α for interaction respectively. The reduced huTRIM5α inhibition may lead to a faster progression of disease among HIV-1-infected individuals. However, in case of HIV-2, increased inhibition by huTRIM5α slows down the disease progression. Conclusion: Polymorphisms in the capsid protein with both HIV-1- and HIV-2-monoinfected individuals showed the difference in the docking energy from the wild type. This is the first study which documents the difference in the usage of loop between the two HIV types for interaction with huTRIM5α. Variations in the capsid protein result in alteration in the binding to the restriction factor huTRIM5α.
Asunto(s)
Aminoácidos/genética , Infecciones por VIH/genética , VIH-1/genética , VIH-2/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genética , Factores de Restricción Antivirales , Proteínas de la Cápside/genética , Estudios Transversales , Infecciones por VIH/virología , VIH-1/patogenicidad , VIH-2/patogenicidad , Humanos , Simulación del Acoplamiento Molecular/métodosRESUMEN
The thickened folded skin of Touraine-Solente-Golé syndrome can result in cosmetic and functional deformities. The treatment of pachydermoperiostosis is usually centered around improving the cosmetic appearance through plastic surgery. We describe the case of a 27-year-old male who had pachydermoperiostosis with a leonine facies that was managed with frontal rhytidectomy. A greatly improved cosmetic appearance was achieved with this procedure.