Prevalence of Epstein Barr Virus and Herpes Simplex Virus Among Human Papillomavirus Negative Oral Cancer Patients: A Cross-Sectional Study from South India.

The high incidence of oral carcinomas is due to its multifactorial etiology and the presence of various risk factors. Human Papillomavirus (HPV) has a proven role in the pathogenesis of oral carcinomas, but in the recent times there has been an increasing incidence of oral cancers who are negative for HPV infection. Also, these patients are non-smokers and non-drinkers so it could be speculated that these oral cancers are due to some other etiological factor probably of other viral infections. Therefore, this study examined the prevalence of Epstein Barr Virus (EBV) and Herpes Simplex Virus (HSV) among oral cancer patients. This cross-sectional study was conducted from January 2019 to June 2020. Biopsy samples from 47 newly diagnosed untreated patients with oral malignancies were collected along with their demographic and clinicopathological information. DNA extracted from the biopsies was processed for nested PCR for the detection of EBV and HSV. All the samples tested negative for HPV and HSV infection. Nested PCR detected 29 cases (70.7%) to be positive for EBV. The non-cancerous adjacent tissues also were negative for HPV, EBV and HSV. The prevalence of EBV was found to be more in males (62.1%) and the highest number of cases was of the left buccal mucosa compromising 34% of the total cases. From the present study it can be concluded that EBV but not HSV infection is associated with an increased risk of developing oral cancers. Although, 70.7% of the patients were found to be positive for EBV whether the viral infection played any role in the driving the malignancy needs to be further elucidated.

Oral miltefosine for Indian post-kala-azar dermal leishmaniasis: a randomised trial.

OBJECTIVE: Standard treatment of Indian post-kala-azar dermal leishmaniasis (PKDL) is unsatisfactory because to achieve therapeutic effectiveness, heroic courses of parenteral and toxic agents have to be administered. Our objective was to evaluate oral miltefosine for its potential to provide effective as well as tolerable treatment for this disease. METHOD: Open-label, randomised, parallel-group multicentric trial. Miltefosine, 100 mg/day to all but one patient, was administered for 12 weeks or 8 weeks, with a target of 18 patients in each treatment group. Key endpoints were tolerance during treatment and efficacy at 12 months of follow-up. RESULTS: The ITT and per-protocol cure rates after 12 months of follow-up for patients receiving 12 weeks of therapy were 78% (14 of 18 patients: 95% CI = 61-88%) and 93% (14 of 15 patients: 95% CI = 71-95%), respectively, after 12 months of follow-up. The ITT and per-protocol cure rates for patients receiving 8 weeks of therapy were 76% (13 of 17 patients: 95% CI = 53-90%) and 81% (13 of 16 patients: 95% CI = 57-93%), respectively. Gastrointestinal and other adverse events were rare. CONCLUSIONS: This study suggests that oral miltefosine for 2-3 months can be considered a treatment of choice for Indian PKDL.

Liposomal amphotericin B for visceral leishmaniasis in human immunodeficiency virus-coinfected patients: 2-year treatment outcomes in Bihar, India.

BACKGROUND: Reports on treatment outcomes of visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge, none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection. We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated with liposomal amphotericin B followed by combination antiretroviral treatment (cART) in Bihar, India. METHODS: The study included all patients with newly diagnosed VL-HIV coinfection and initiating treatment with liposomal amphotericin B (20-25 mg/kg in 4-15 days) between July 2007 and September 2010. Kaplan-Meier estimates of the cumulative incidence of death/treatment failure were calculated. RESULTS: Fifty-five patients were included (83.6% male; median age, 35 years; 62% migrant laborers; median follow-up, 1 year). The median CD4 cell count at VL diagnosis was 66 cells/µL (interquartile range, 38-112). Twenty-seven patients (49.1%) presented with VL relapse of VL. The overall tolerance of liposomal amphotericin B was excellent, with no interrupted treatment. Survival by 1 and 2 years after VL treatment was estimated at 85.5%. No patients had initial treatment failure. The probabilities of VL relapse were 0%, 8.1%, and 26.5% at 0.5, 1, and 2 years after VL treatment, respectively; relapse rates were similar for primary VL and VL relapse. CD4 counts <200 cells/µL at 6 months after cART initiation were predictive of subsequent relapse. The mean CD4 cell counts at 6 and 24 months after cART initiation were 187 and 261 cells/µL, respectively. The rate for retention in HIV care was 83.6%. CONCLUSIONS: Good long-term survival and retention rates were obtained for VL-HIV-coinfected patients treated with liposomal amphotericin B and cART. Although the initial VL treatment response was excellent, VL relapse within 2 years remained frequent.

Nexus of infection with human immunodeficiency virus, pulmonary tuberculosis and visceral leishmaniasis: a case report from Bihar, India.

A 37-year-old man was diagnosed as being infected with human immunodeficiency virus (HIV), tuberculosis (TB), tuberculoma of the brain, and visceral leishmaniasis (VL) at the Rajendra Memorial Institute of Medical Sciences in Bihar, India. He had taken anti-tuberculosis therapy (ATT) for two and a half months and had episodes of convulsions with loss of consciousness, tongue bites, and incontinence of urine. The results of a neurologic examination were normal except for a left plantar extensor. He was positive for both HIV-I (confirmed by Western blot) and VL (confirmed by splenic aspirate). Treatment was initiated with amphotericin B lipid complex, a four-drug regimen (rifampicin, isoniazid, ethambutol, and pyrazinamide) of ATT, highly active antiretroviral therapy, anti-convulsants, and other supportive therapies. A repeat computed tomography scan of the brain showed the disappearance of the lesion followed by gliosis. After six months, he was also cured of VL. The triad of infections (HIV, VL, and TB) is a real threat in Bihar as an emerging combination of diseases of public health importance. Keeping these facts in mind, efforts to develop simple and cost effective diagnostic techniques coupled with affordable therapeutic facilities are urgently needed in developing countries.

Magnitude of unresponsiveness to sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar.

BACKGROUND: The Indian government proposes to eliminate kala-azar, which has been a serious public health problem in Bihar. This study aimed to assess the magnitude of unresponsiveness to sodium stibogluconate in the treatment of new cases of visceral leishmaniasis and to identify the associated factors. METHODS: Patients with clinically and parasitologically confirmed visceral leishmaniasis (n = 182) who had received no prior treatment, were enrolled for the study. The patients were treated with sodium stibogluconate (20 mg/kg body weight; upper limit 850 mg), intramuscularly for 30 days. The vital parameters and side-effects, if any, were monitored. Patients who developed toxicity during treatment were excluded from the study but were given rescue treatment with liposomal amphotericin B. All patients who completed the treatment were followed up for 6 months. RESULTS: Unresponsiveness to sodium stibogluconate at the end of treatment was 43%. It was higher in women (48%) compared to men (40%). A significant association was observed between unresponsiveness and level of endemicity (p = 0.0002), large spleen size (p = 0.04) and immune response (migration inhibition factor) (p = 0.00002). At the end of 6 months' follow up, 27% of patients relapsed, giving a total unresponsiveness rate of 58%. CONCLUSION: Unresponsiveness to sodium stibogluconate is a serious problem in the management of patients with visceral leishmaniasis. In patients with factors associated with nonresponse to sodium stibogluconate, alternative drugs such as miltefosine or amphotericin B should be considered as first-line drugs.

Iliac crest bone graft donor site hernia: not so uncommon.

A 73-year-old man, who had undergone fracture fixation of humerus with LCP plating and bone grafting, presented again with a peri-implant fracture after 1 year. A repeat surgery was contemplated and replating was performed with tricortical bone graft harvested from the iliac crest. In the postoperative period the patient developed a tender swelling at the graft site with nausea and abdominal discomfort. It was managed conservatively thinking it to be a haematoma at the graft site. In the following 2 days his symptoms worsened. A CT abdomen showed the herniation of caecum from the bone graft donor site with obstruction. The patient was taken up for emergency surgical repair, the caecum was reduced and polypropylene mesh hernioplasty was performed. The patient recovered well without recurrence in the follow-up period. Iliac crest bone graft site hernia is not so uncommon and care has to be taken while harvesting.

A rare case of Visceral leishmaniasis with multiple relapse and multi-drug unresponsive: successfully treated with combination therapy.

CASE: We report a 32-year old relapse case of Visceral leishmaniasis, treated with Paromomycin who belonged from a endemic zone of Bihar state, India. After confirmation, he was treated with Amphotericin B, followed by Liposomal Amphotericin B in full course and even in higher dose. But after each therapy, the patient either did not responded or relapsed after treatment. Ultimately, the patient was successfully treated with combination therapy of Liposomal amphotericin B and Miltefosine without any relapse. CONCLUSION: The multi-drug unresponsive Visceral leishmaniasis cases could pose a major threat to treatment strategy in the elimination program. In such situation, combination therapy seems to be a better approach that needs to be explored.

Ambisome plus miltefosine for Indian patients with kala-azar.

The combination of one intravenous administration of 5mg/kg Ambisome and oral administration of miltefosine, 2.5mg/kg/day for 14 days, was evaluated in 135 Indian patients with kala-azar. The Intent-to-Treat cure rate at 6 months was 124 of the 135 enrolled patients (91.9%: 95% CI = 86-96%), and the per protocol cure rate was 124 of 127 evaluable patients (97.6%: 95% CI = 93-100%). Side effects could be attributed to each drug separately: fevers, rigors and back pain due to Ambisome; gastrointestinal side effects due to miltefosine. This combination is attractive for reasons of efficacy, tolerance, and feasibility of administration, although the gastrointestinal side effects of miltefosine require medical vigilance. Clinical Trials.gov identification number: NCT00371995.

Asymptomatic infection with visceral leishmaniasis in a disease-endemic area in bihar, India.

A prospective study was carried out in a cohort of 355 persons in a leishmaniasis-endemic village of the Patna District in Bihar, India, to determine the prevalence of asymptomatic persons and rate of progression to symptomatic visceral leishmaniasis (VL) cases. At baseline screening, 50 persons were positive for leishmaniasis by any of the three tests (rK39 strip test, direct agglutination test, and polymerase chain reaction) used. Point prevalence of asymptomatic VL was 110 per 1,000 persons and the rate of progression to symptomatic cases was 17.85 per 1,000 person-months. The incidence rate ratio of progression to symptomatic case was 3.36 (95% confidence interval [CI] = 0.75-15.01, P = 0.09) among case-contacts of VL compared with neighbors. High prevalence of asymptomatic persons and clinical VL cases and high density of Phlebotomus argentipes sand flies can lead to transmission of VL in VL-endemic areas.

Effectiveness and safety of liposomal amphotericin B for visceral leishmaniasis under routine program conditions in Bihar, India.

We evaluated, through the prospective monitoring of 251 patients at Sadar Hospital in Bihar, India, the effectiveness and safety of 20 mg/kg body weight of liposomal amphotericin B for the treatment of visceral leishmaniasis. The treatment success rates for the intention-to-treat, per protocol, and intention-to-treat worse-case scenario analyses were 98.8%, 99.6%, and 81.3%, respectively. Nearly one-half of patients experienced mild adverse events, but only 1% developed serious but non-life-threatening lips swelling. The lost to follow-up rate was 17.5%. Our findings indicate that the 20 mg/kg body weight treatment dosage is effective and safe under routine program conditions. Given that the exorbitant cost of liposomal amphotericin B is a barrier to its widespread use, we recommend further study to monitor and evaluate a lowered dosage and a shorter treatment course.

HIV, visceral leishmaniasis and Parkinsonism combined with diabetes mellitus and hyperuricaemia: A case report.

BACKGROUND: Visceral leishmaniasis is caused by a protozoan parasite, Leishmania donovani and transmitted by the bite of female sandflies. India is endemic for this disease. On the other hand, India contributes to the largest number of cases of HIV as well. CASE PRESENTATION: We hereby report an unusual case presentation of Visceral leishmaniasis/HIV co-infection with additional features of Parkinsonism and hyperuriciemia in an Indian male patient aged about 50 years. CONCLUSION: The increasing incidence of HIV/VL co-infection in India is of utmost importance. The diagnostic and management aspects of these cases are very difficult to handle particularly in an underdeveloped country like India.