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Background Fungal disease is frequent in India, but its incidence and prevalence are unclear. This review aims at defining the frequency or burden of various fungal infections in India. Methods A systematic review of the literature on the PubMed, Embase, and Web of Science (WOS) databases was conducted using appropriate search strings. Deterministic modeling determined annual incidence and prevalence estimates for multiple life- and sight-threatening infections with significant morbidity. Results Literature searches yielded >2900 papers; 434 papers with incidence/prevalence/proportion data were analyzed. An estimated 57 251 328 of the 1 393 400 000 people in India (4.1%) suffer from a serious fungal disease. The prevalence (in millions) of recurrent vulvovaginal candidiasis is 24.3, allergic bronchopulmonary aspergillosis is 2.0, tinea capitis in school-age children is 25, severe asthma with fungal sensitization is 1.36, chronic pulmonary aspergillosis is 1.74, and chronic fungal rhinosinusitis is 1.52. The annual incidence rates of Pneumocystis pneumonia (58 400), invasive aspergillosis (250 900), mucormycosis (195 000), esophageal candidiasis in HIV (266 600), candidemia (188 000), fungal keratitis (1 017 100), and cryptococcal meningitis (11 500) were also determined. Histoplasmosis, talaromycosis, mycetoma, and chromoblastomycosis were less frequent. Conclusions India's fungal burden is high and underappreciated in clinical practice. [ABSTRACT FROM AUTHOR]

Diabetes is one of the leading causes of death globally. India is home to the second-largest population suffering from diabetes. This underscores the need to build capacity of primary care physicians (PCPs) for better disease management. This narrative review article aims to describe the emergence of diabetes education and capacity-building programs for PCPs and its current situation in India. The review highlighted that major emphasis on diabetes was given only when the WHO estimated that morbidity and mortality due to diabetes would increase to 35% in India. As a result, National Diabetes Control Program was launched in 1987. Yet, very little attention was paid to diabetology in under-graduation. In the last decade, few public and private institutions have developed diabetes related capacity-building programs for PCPs independently or in collaborations. These programs include 16 fellowships, 4 diplomas, 12 certificate programs, and 6 other diabetes training programs, which have their own pros and cons. As medical science is changing rapidly, PCPs need to upgrade their skills and knowledge regularly to manage NCDs such as diabetes more effectively and efficiently. This can be possible only if scientific, evidence-based, and quality-oriented capacity-building programs are provided to the healthcare workforce. [ABSTRACT FROM AUTHOR]

Our retrospective cohort study assesses the survival probability and identifies the demographic and clinical predictors of mortality in HIV patients taking antiretroviral therapy using an antiretroviral therapy centre data in Western India. Secondary data on 7532 registered HIV-infected individuals between September 2006 and January 2013 were analysed. The probability of survival at 75 months was 84.9%. Significant indicators of poor chances of survival were greater age, lower occupation class, lower CD4 count, poor functional status; higher stage of disease, lower weight, the presence and type of opportunistic infections, co-trimoxazole therapy and poor adherence to antiretroviral therapy. We thus find that, in addition to pre-ART, antiretroviral therapy clinical status and treatment adherence, socioeconomic status plays an important influence on ultimate survival of HIV patients on antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background: Clinical manifestations in people living with human immunodeficiency virus infection (PLHIV) can be protean. Methods: We studied the clinical profile, neurological, cardiac manifestations and opportunistic infections (OIs) at the time of diagnosis in PLHIV at our medical college tertiary care teaching hospital in Solapur, Maharashtra, India. Results: Majority of patients (36%) were observed in the age group of 31-40 years. The mmost common presenting complaint was fever (65%), followed by anorexia (34%), weight loss (33%), cough (22%) and fatigue (21%). Diarrhoea and headache were seen in 15% and 13% of the patients, respectively. Most of the patients had weight between 31 and 40 kg and 41 and 50 kg (48% in each). On general physical examination pallor (63%), oral thrush (30.4%) were commonly seen. Genital lesions and icterus were seen in 4.3% and 2.1% of the patients, respectively. Majority (31%) of patients had CD4+ counts (/mm3) in the range 151 and 200. Most of the of patients (30%) had respiratory system involvement. Central nervous system (CNS) and gastrointestinal system manifestations were seen in 21% and 15% of the patients, respectively. Among infections tuberculosis (TB) was most common (46%) followed by Candidiasis (18%), Pneumocystis carinii pneumonia (PCP) (9.2%) and cryptococcosis (8.7%). Other infections seen were herpes (5.2%), Cryptosporidium parvum (3.9%), Isospora belli (2.6%), toxoplasmosis (2.6%), cytomegalovirus (CMV) (1.3%), hepatitis B (1.3%) and Epstein-Barr virus (1.3%). Conclusions: TB is a common cause of morbidity in PLHIV. They further merit careful evaluation for assessing involvement of various organ systems, OIs. [ABSTRACT FROM AUTHOR]

Pneumocystis jiroveci pneumonia (PJP) is an important opportunistic infection in immunosuppressed hosts. At our center, nine transplant recipients developed PJP over a 4-month period. The median time from transplant was 56 months and none of them was on cotrimoxazole prophylaxis at the time of developing the infection. Over half had been admitted to the renal transplant ward for unrelated indications and contracted the infection in‑hospital. Diagnosis was based on microbiological demonstration of P. jiroveci in sputum and/or bronchoalveolar lavage in symptomatic patients. Atypical clinical and radiological signs were common with poor correlation of symptoms to computed tomography findings. Cotrimoxazole therapy was effective; however, patients with pre‑existing graft dysfunction developed hyperkalemia commonly (50%). Alternative treatment with clindamycin and primaquine combination was equally effective. Early diagnosis and prompt treatment resulted in low mortality rate (11%). The outbreak was halted after universal use of cotrimoxazole prophylaxis to all patients admitted to the renal transplant ward. We report the first ever outbreak of PJP in Indian renal transplant recipients with possible inter‑human transmission of infection in admitted patients. [ABSTRACT FROM AUTHOR]

Abstract: Pneumocystis jirovecii is an opportunistic pathogen that causes severe pneumonia in immunocompromised patients. To study the genetic diversity of P. jirovecii in India the upstream conserved sequence (UCS) region of Pneumocystis genome was amplified, sequenced and genotyped from a set of respiratory specimens obtained from 50 patients with a positive result for nested mitochondrial large subunit ribosomal RNA (mtLSU rRNA) PCR during the years 2005–2008. Of these 50 cases, 45 showed a positive PCR for UCS region. Variations in the tandem repeats in UCS region were characterized by sequencing all the positive cases. Of the 45 cases, one case showed five repeats, 11 cases showed four repeats, 29 cases showed three repeats and four cases showed two repeats. By running amplified DNA from all these cases on a high-resolution gel, mixed infection was observed in 12 cases (26.7%, 12/45). Forty three of 45 cases included in this study had previously been typed at mtLSU rRNA and internal transcribed spacer (ITS) region by our group. In the present study, the genotypes at those two regions were combined with UCS repeat patterns to construct allelic profiles of 43 cases. A total of 36 allelic profiles were observed in 43 isolates indicating high genetic variability. A statistically significant association was observed between mtLSU rRNA genotype 1, ITS type Ea and UCS repeat pattern 4. [Copyright &y& Elsevier]

Opportunistic infections (OIs) are a leading cause of mortality and morbidity in patients living with HIV/AIDS. Data on the proper administration of prophylactic regimes for the prevention of OIs in such patients are scarce. A total of 205 confirmed HIV-infected patients were enrolled in the study from the inpatient wards and outpatient services. The treatment given to them for the prevention of Pneumocystis carinii (jiroveci) pneumonia was compared with the established guidelines and the proportions of those receiving proper treatment were calculated. Primary prophylaxis was seen to be satisfactory in the case of P. carinii (jiroveci) pneumonia. The prophylaxis was not given properly for tuberculosis and other common OIs. Secondary prophylaxis was up to the mark. Prophylaxis in AIDS patients seems to be a major problem area and a lot of efforts need to be directed toward it since patients suffering from AIDS are bound to have a downhill course despite provision of all available treatment options. [ABSTRACT FROM AUTHOR]

Abstract: Pneumocystis pneumonia (PCP), a common and serious opportunistic infection in immunocompromised patients, is caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii f. sp. hominis). The aim of the present study was to describe the prevalence and distribution of genotypes of P. jirovecii based on sequence polymorphisms at mitochondrial large subunit ribosomal RNA (mt LSU rRNA) region in both HIV and non-HIV immunocompromised individuals with a positive PCR result for PCP in a tertiary health care centre in northern India. From January 2005 to October 2008, 50 patients [22 HIV-seropositive individuals, 10 post-renal transplant (PRT) recipients, 3 cancer patients, and 15 patients with various other kinds of immunosuppression] were found to be positive for P. jirovecii using PCR at the mt LSU rRNA gene. Genotyping of the positive samples was performed at the mt LSU rRNA locus. Genotype 2 was the most common accounting for 42% of total types. This was followed by the genotypes 3 (24%), 1 (20%), and 4 (8%). Mixed infection was observed in 3 cases (6%). The rates of genotype distribution were similar in HIV-seropositive individuals, cancer patients, and in patients with other kinds of immunosuppression. In the PRT recipients, genotype 1 was the most prevalent type (80%). This is the first study describing the prevalence of genotypes in HIV-infected and HIV-uninfected, immunocompromised patients based on the mt LSU rRNA gene from the Indian subcontinent. The most prevalent genotype observed was type 2 in contrast to many studies from other parts of the world where genotype 1 was the most prevalent type, suggesting geographical variation. [Copyright &y& Elsevier]

Abstract: Pneumocystis jirovecii is the cause of Pneumocystis pneumonia (PCP) in immuno-compromised individuals. The aim of this study was to describe the genotypes/haplotypes of P. jirovecii in immuno-compromised individuals with positive polymerase chain reaction (PCR) result for PCP. The typing was based on sequence polymorphism at internal transcribed spacer (ITS) regions of rRNA operon. Phylogenetic relationship between Indian and global haplotypes was also studied. Between January 2005 to October 2008, 43 patients were found to be positive for Pneumocystis using PCR targeting mitochondrial large subunit rRNA (mt LSU rRNA) and ITS region. Genotyping of all the positive samples was performed at the ITS locus by direct sequencing. Nine ITS1 alleles (all previously known) and 11 ITS2 alleles (nine previously defined and two new) were observed. A total of 19 ITS haplotypes, including five novel haplotypes (DEL1r, Edel2, Hr, Adel3 and SYD1a), were observed. The most prevalent type was SYD1g (16.3%), followed by types Ea (11.6%), Ec (9.3%), Eg (6.9%), DEL1r (6.9%), Ne (6.9%) and Ai (6.9%). To detect mixed infection, 30% of the positive isolates were cloned and 4–5 clones were sequenced from each specimen. Cloning and sequencing identified two more haplotypes in addition to the 19 types. Mixed infection was identified in 3 of the 13 cloned samples (23.1%). Upon construction of a haplotype network of 21 haplotypes, type Eg was identified as the most probable ancestral type. The present study is the first study that describes the haplotypes of P. jirovecii based on the ITS gene from India. The study suggests a high diversity of P. jirovecii haplotypes in the population. [Copyright &y& Elsevier]

We prospectively examined 143 clinical samples from 115 patients including both HIV infected (n=53) and HIV uninfected immunocompromized (n=62) patients, with lung infiltrates and with clinical features suggestive of Pneumocystis carinii pneumonia/ PneumoCystis Pneumonia (PcP), using both microscopic techniques as well as PCR assay. Clinical samples in the present study consisted of bronchoalveolar lavage (BAL), tracheal aspirate (TA), nasopharyngeal aspirate (NPA), sputum and gastric aspirate (GA). Another group of 21 individuals with other respiratory diseases not compatible with PcP served as control during the study period of 15 months. Overall, P. jirovecii positivity rate by PCR was 12.17% (14/115 patients) compared to 3.4% (4/115) by microscopy. None of the specimens in the control group was positive by any of the techniques used. All PCR negative patients including cases and controls showed no evidence of PcP. After resolution of the discrepant results upon review of the clinical data, the sensitivity and specificity were 100% and 99%, respectively, for PCR and 30.7% and 100%, respectively, for microscopy by GMS staining. Thus, our data support the significance of PCR assay for confirming and improving the diagnosis of PcP in high-risk patients. [ABSTRACT FROM AUTHOR]

Objectives: Pneumocystis pneumonia (PCP) remains a debilitating cause of death among HIV-infected patients. The combination trimethoprim/sulfamethoxazole (SXT) is the most effective anti-Pneumocystis treatment and prophylaxis. However, long-term use of this combination has raised alarms about the emergence of resistant organisms. This study was performed to investigate mutations in the dihydropteroate synthase (DHPS) gene and their clinical consequences in HIV-infected patients with PCP., Methods: A total of 76 clinically suspected cases of PCP among HIV-seropositive adult patients from March 2014 to March 2017 were included. Clinical samples (bronchoalveolar lavage fluid and sputum) were investigated for the detection of Pneumocystis jirovecii using both microscopy and nested PCR. DHPS genotyping and mutational analyses were performed and the data were correlated with clinical characteristics., Results: Among the 76 enrolled HIV-positive patients, only 17 (22.4%) were positive for P. jirovecii. DHPS gene sequencing showed a novel nucleotide substitution at position 288 (Val96Ile) in three patients (3/12; 25.0%). Patients infected with the mutant P. jirovecii genotype had severe episodes of PCP, did not respond to SXT and had a fatal outcome (P=0.005). All three patients had a CD4 + T-cell count <100 cells/μL, and two also had co-infections., Conclusion: This study suggests that the emergence of a mutant P. jirovecii genotype is probably associated with drug resistance and mortality. The data also suggest that DHPS mutational analyses should be performed in HIV-seropositive patients to avoid treatment failure and death due to PCP. However, the role of underlying disease severity and co-morbidities should not be underestimated., (Copyright © 2019 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

HIV has become a major health problem in India, patients commonly succumb to opportunistic infections (OIs), respiratory infections being an important cause of morbidity and their accurate diagnosis is still a challenge. Our aim was to study the occurrence of Pneumocystis pneumonia (PCP) in HIV/AIDS patients with respiratory complaints attending ART clinic and to compare various diagnostic methodologies. One hundred and twenty five HIV/AIDS patients presenting with respiratory symptoms like cough, fever, breathlessness etc, were enrolled, and induced sputum samples were collected. Samples were homogenized using glass beads and Dithiothretol. Smears were prepared and examined by Immunoflourescent staining (IFAT), Gomori methanamine silver staining (GMSS), Toludine blue O staining (TBO) and Giemsa staining for Pneumocystis jiroveci. Among the 125 patients who presented with respiratory complaints, 34 cases (27.2%) were diagnosed as having PCP. All 34 cases were detected by IFAT followed by GMSS, Giemsa and Toludine blue O staining in decreasing order. The mean CD4 count was 67.27cells/μl. PCP has become an important health problem in HIV/AIDS patients with low CD4 counts in India. IFAT remains the most sensitive method for the detection of this uncultivable organism. In resource poor settings where an immunoflourecent microscope is not available, diagnosis of PCP still remains problematic., (© The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)