Prevalence of oral human papillomavirus infection among Indian HIV-positive men who have sex with men: a cross-sectional study.

BACKGROUND: Oral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population. METHODS: We tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history. RESULTS: The prevalence of oral HPV was 23.7% (95% CI: 19-29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4-6.9]) in multivariable analyses. CONCLUSIONS: This is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.

Risk Factors for Stroke in Rural Population of Telangana State of India, an Unmatched Case Control Study.

Context Stroke tops the list of causes for acquired disability among adults and is the second leading cause of death worldwide. Evidence from developed countries indicate significant decline in stroke incidence and mortality, attributable to prevention of risk factors in general population. There is limited evidence on risk factors for stroke in rural India. Aims This study aims to ascertain the risk factors for stroke in rural Telangana and provide a guide to health care providers in adopting treatment and prevention strategies. Settings and Design The study was conducted in the Moinabad mandal of Ranga Reddy District, Telangana state of India. This is a population based unmatched case-control study. Methods and Materials All the houses of Moinabad were approached by a door-to-door survey to identify cases. A total of 288 persons were enrolled in the study which included 144 cases and 144 controls. Statistical Analysis To derive age and gender adjusted odds ratios of various risk factors, binary logistic regression analysis was performed. Results The estimated crude prevalence of stroke in Moinabad mandal is 257 per lakh population. Modifiable risk factors identified were, total cholesterol, systolic blood pressure, alcohol consumption, smoking, diastolic blood pressure, low high-density lipoprotein cholesterol, and central obesity as measured by waist circumference. Nonmodifiable risk factors identified were male gender and higher age group. Conclusion The high prevalence of stroke in rural Telangana makes it an important public health challenge for the state. The identified risk factors need to be addressed at population level.

Prospective 1-year follow-up study of all cured, new sputum smear positive tuberculosis patients under the Revised National Tuberculosis Control Program in Hyderabad, Telangana State, India.

BACKGROUND: Tuberculosis (TB) is one of the leading causes of mortality in India. The Revised National Tuberculosis Control Program (RNTCP) is a robust public health system to deal with TB in India. Unless the treated patient comes back to the system with signs and symptoms of TB due to relapse or re-infection, there is no mechanism of follow-up or any method to know the relapse rate in the population. We attempted to follow the patients declared as "Cured" as per the RNTCP guidelines for 1-2 years to identify the health status of the index cases and their household contacts in posttreatment phase. MATERIALS AND METHODS: In this prospective cohort study, 187 index cases, who were declared "Cured" in six randomly selected TB units of Hyderabad district, were followed up for 1-2 years through home visits by trained staff with structured data collection forms. Data were analyzed using SPSS v20.0. RESULTS: The mean age of the index cases was 33.64 (±16.10) years, and there were 75 females and 112 males. The study sample was homogenous for gender, age, smear grade, religion, marital status, smoking status, alcohol consumption, and human immunodeficiency virus status, etc., At 1-year posttreatment follow-up of 187 index cases, 143 (76.47%) were healthy and working without any symptoms of TB. Symptoms of TB were present in 26 (13.90%) cases, and seven index cases (4.06%) were re-diagnosed with TB. The 2-year posttreatment survival was 92%. CONCLUSION: Long-term follow-up of cured, new smear-positive TB cases reinforce the effectiveness of anti-TB treatment under the RNTCP as assessed by improved health outcomes in more than two-thirds of cases and posttreatment survival of 92% of index cases. We recommend continuing such follow-up for all TB cases treated under the RNTCP for effective end-TB strategy.

High rates of latent TB infection in contacts and the wider community in South India.

Background: We aimed to compare TB transmission rates between case and community households in Vellore, South India. Methods: 359 household contacts (HHC) and 363 community contacts (CC) were assessed with tuberculin skin test (TST) and QuantiFERON TB Gold In-Tube test (QFT) between August 2010 and September 2011. Concordance test and multivariate risk factor assessment were conducted using logistic regression adjusted for clustering. Results: Latent TB infection (LTBI) positivity was similar between the two groups using both tests, with only moderate concordance observed between QFT and TST. Children of HHC (<15 years) were at a higher risk for LTBI (odds of 2.37 [1.15-4.89] and 3.02 [1.22-7.45] for TST and QFT respectively). Among adults, both age in decades (odds of 1.33 [1.14-1.15] and 1.16 [1.02-1.32] for TST and QFT, respectively) and the interaction of male gender, smoking and alcohol consumption (odds of 4.06 [1.38-11.93] and 2.59 [1.19-5.64] for TST and QFT, respectively), were associated with increased risk of LTBI. Conclusions: This study provides estimates of TB infection rates accounting for both community and household exposure that contribute to understanding of TB transmission in this setting. We suggest that assessment of risk factors for infection need increased examination as prophylactic treatment of LTBI are being considered.

Serovar prevalence of Leptospira in semirural India and the development of an IgM-based indirect ELISA.

INTRODUCTION: Leptospirosis is a major public health problem in India. However, it has been underreported and under-diagnosed due to a lack of awareness of the disease, a functional surveillance system, and appropriate laboratory diagnostic facilities. METHODOLOGY: This multicenter study aimed to understand the Leptospira serovars causing leptospirosis in seven secondary-level hospitals in six states in India. Since early and accurate diagnosis of leptospirosis is one of the challenges faced by clinicians in India due to the poor specificity and sensitivity of commercially available diagnostic systems, an in-house indirect enzyme-linked immunosorbent assay (ELISA) was developed. Genomic DNA from L. interrogans serovar Canicola was used for polymerase chain reaction amplification, cloning, and expression of the lipL32 gene in E. coli to amplify, clone, and express the lipL32 gene. RESULTS: Australis was the common serovar seen at all the study centers. Serovar Icterohaemorrhagiae was seen in samples from Tamil Nadu and Assam. In-house ELISA was standardized using the purified recombinant LipL32 polypeptide and was used to evaluate serum. Subsequently, acute serum samples from leptospirosis patients (n = 60) were screened. Compared to the gold standard, the microscopic agglutination test, sensitivity and specificity of the in-house ELISA was 95% and 90%, respectively. CONCLUSIONS: Understanding Leptospira serovars circulating in leptospirosis-endemic areas will help to formulate better vaccines. LipL32-based ELISA may serve as a valuable tool for early diagnosis of leptospirosis.

Genital Human Papillomavirus Infection in Indian HIV-Seropositive Men Who Have Sex With Men.

BACKGROUND: The incidence of penile cancer in Indian men is high. Little is known about genital human papillomavirus (HPV) infection in Indian HIV-seropositive men who have sex with men (MSM), a population that may be at particularly high risk for genital HPV infection and, potentially, penile cancer. In this study, we assessed the prevalence and risk factors for genital HPV infection in this population. DESIGN AND METHODS: Three hundred HIV-seropositive MSM were recruited from 2 clinical sites in India. They were tested for genital HPV infection using L1 HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. Participants received an interviewer-administered questionnaire that included questions on demographics and behaviors. RESULTS: Human papillomavirus data were available from 299 participants. The prevalence of any HPV type in the penis and scrotum was 55% and 54%, respectively. Human papillomavirus type 35 was the most common oncogenic HPV type followed by HPV-16. In multivariate analysis, being the insertive partner with 100+ male partners increased the odds of any penile HPV infection compared with not being insertive with any partners (odds ratio, 2.5; 95% confidence interval, 1.3-5.1). Circumcision was protective against penile HPV infection (odds ratio, 0.39; 95% confidence interval, 0.19-0.76). CONCLUSIONS: The prevalence of penile and scrotal HPV infection was high among Indian HIV-seropositive MSM. The most common oncogenic HPV type in this population, HPV-35, is not included in any currently available HPV vaccines. Insertive anal sex with men and lack of circumcision were the primary risk factors for penile HPV infection in this population.

A High Malaria Prevalence Identified by PCR among Patients with Acute Undifferentiated Fever in India.

BACKGROUND: Approximately one million malaria cases were reported in India in 2015, based on microscopy. This study aims to assess the malaria prevalence among hospitalised fever patients in India identified by PCR, and to evaluate the performance of routine diagnostic methods. METHODS: During June 2011-December 2012, patients admitted with acute undifferentiated fever to seven secondary level community hospitals in Assam (Tezpur), Bihar (Raxaul), Chhattisgarh (Mungeli), Maharashtra (Ratnagiri), Andhra Pradesh (Anantapur) and Tamil Nadu (Oddanchatram and Ambur) were included. The malaria prevalence was assessed by polymerase chain reaction (PCR), routine microscopy, and a rapid diagnostic test (RDT) with PCR as a reference method. RESULTS: The malaria prevalence by PCR was 19% (268/1412) ranging from 6% (Oddanchatram, South India) to 35% (Ratnagiri, West India). Among malaria positive patients P. falciparum single infection was detected in 46%, while 38% had P. vivax, 11% mixed infections with P. falciparum and P. vivax, and 5% P. malariae. Compared to PCR, microscopy had sensitivity of 29% and specificity of 98%, while the RDT had sensitivity of 24% and specificity of 99%. CONCLUSIONS: High malaria prevalence was identified by PCR in this cohort. Routine diagnostic methods had low sensitivity compared to PCR. The results suggest that malaria is underdiagnosed in rural India. However, low parasitaemia controlled by immunity may constitute a proportion of PCR positive cases, which calls for awareness of the fact that other pathogens could be responsible for the febrile disease in submicroscopic malaria.

Prevalence of Anal HPV Infection Among HIV-Positive Men Who Have Sex With Men in India.

BACKGROUND: India has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM. METHODS: We evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history. RESULTS: The prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1-1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)]. CONCLUSIONS: Almost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions.

Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

OBJECTIVES: Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome. METHODS: Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls (n = 31), both in the acute phase and after recovery, by enzyme immunoassays. RESULTS: Patients had markedly elevated levels of all mediators in the acute phase, differing from both healthy and infectious disease controls. During follow-up levels of ALCAM, VCAM-1, sCD14 and YKL-40 remained elevated compared to levels in healthy controls. High plasma ALCAM, VCAM-1, sCD163, sCD14, and MIF, and in particular YKL-40 were all associated with disease severity and ALCAM, sCD163, MIF and especially YKL-40, were associated with mortality. CONCLUSIONS: Our findings show that scrub typhus is characterized by elevated levels of monocyte/macrophage and endothelial related markers. These inflammatory markers, and in particular YKL-40, may contribute to disease severity and clinical outcome.

Fever in the tropics: aetiology and case-fatality - a prospective observational study in a tertiary care hospital in South India.

BACKGROUND: The objective of this study was to describe aetiology and case fatality of fever among inpatients in a tertiary care hospital in South India. METHODS: This was an observational, prospective study conducted in a tertiary care hospital in Vellore, Tamil Nadu, India. Between July 2nd 2007 and August 2nd in 2007, adult patients admitted to the hospital with temperature ≥ 38.0°C were included consecutively and followed during the hospitalisation period. Demographic and clinical data were collected and analysed for each patient. Associations were sought between death and various clinical and demographic variables. RESULTS: One hundred patients were included, 61 male and 39 female. Mean age was 37.5 (range: 16 to 84) years. Mean fever duration was 5.4 (range: 0.1 to 42.9) weeks.The following infectious aetiologies were recorded: tuberculosis (19%), lower respiratory infection (11%) including three with sepsis, urinary tract infection (10%) including three with E. coli sepsis, Plasmodium falciparum malaria (5%) including three patients with mixed P. vivax infection, scrub typhus (5%), typhoid fever (4%), cryptococcal meningitis (4%) including three HIV positive patients, endocarditis (3%) including two patients with Staphylococcus aureus sepsis, spleen abscess (2%), amoebic liver abscess (2%), sepsis undefined focus (1%), HIV infection (1%), hepatitis B (1%), rubella (1%), peritonitis (1%) and cholecystitis (1%).Non-infectious causes of fever were diagnosed in 15%, including systemic lupus erythematosus in four and malignancy in six patients. Cause of fever remained unknown in 13%.Case fatality during hospitalisation was 7% (7/100). Six of those who died were male. Five fatalities had bacterial sepsis, one spleen abscess and malignancy, and one had lymphomalignant disorder.Diabetes and increasing age were significant risk factors for fatal outcome in unadjusted analyses, but only increasing age was a risk factor for death in adjusted analysis. CONCLUSIONS: A high number of tuberculosis and bacterial infections and a high case fatality rate from sepsis were found in this cohort, underlining the importance of microbiological diagnostics and targeted antimicrobial treatment in the management of fever. P. falciparum was identified in all malaria cases, and this rapidly fatal infection should be considered in patients with acute undifferentiated fever in India.

Risk factors for tuberculosis.

The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV), malnutrition, and young age), emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli.

Risk factors for mortality in a south Indian population on generic antiretroviral therapy.

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.

Aetiology of prolonged fever in antiretroviral-naïve human immunodeficiency virus-infected adults.

BACKGROUND: Prolonged fever is a common symptom among human immunodeficiency virus (HIV) infected individuals, and is usually due to a cause that is easily treatable. Limited data are available regarding the causes of fever in HIV-infected Indian patients. In this paper, we have profiled the causes of prolonged fever in a cohort of HIV-infected Indian patients and have developed suitable algorithms to assist in an early diagnosis. METHODS: From February 1997 to October 1998 (20 months), 100 HIV-infected patients (age > 12 years) were evaluated for 100 episodes of prolonged fever (fever > 100 degrees F for more than 2 weeks in outpatients and > 3 days in inpatients). Patients with terminal acquired immunodeficiency syndrome (AIDS) were excluded. Patients were evaluated on the basis of the symptoms associated with prolonged fever and investigated according to pre-existing algorithms. RESULTS: Among such episodes of fever, infection was the major cause and included tuberculosis, especially the extra-pulmonary and disseminated forms (69%), cryptococcosis (10%) and Pneumocystis carinii pneumonia (7%). Other causes included bacterial pneumonia, amoebic liver abscess, disseminated histoplasmosis and cerebral toxoplasmosis. Patients were naïve for antiretroviral therapy and did not receive prophylaxis for opportunistic infections. The diagnostic yield of ultrasound of the abdomen (85%), fine-needle aspiration cytology of enlarged lymph nodes (75.6%) and bone marrow trephine biopsy (41.6%) were found to be high in our study. CONCLUSIONS: Tuberculosis is the commonest cause of prolonged fever in HIV-infected adults in India. Non-infectious causes were not seen in this series. We have suggested an algorithmic approach for establishing the cause of fever in these patients. In situations where laboratory evaluation does not reveal a cause for prolonged fever, a therapeutic trial with antituberculous therapy in selected patients is justified.