Spectrum of clinical disease in a series of 135 hospitalised HIV-infected patients from north India

BACKGROUND: Literature on the spectrum of opportunistic disease in human immunodeficiency virus (HIV)-infected patients from developing countries is sparse. The objective of this study was to document the spectrum and determine the frequency of various opportunistic infections (OIs) and non-infectious opportunistic diseases, in hospitalised HIV-infected patients from north India. METHODS: One hundred and thirty five consecutive, HIV-infected patients (age 34 ± 10 years, females 17%) admitted to a tertiary care hospital in north India, for the evaluation and management of an OI or HIV-related disorder between January 2000 and July 2003, were studied. RESULTS: Fever (71%) and weight loss (65%) were the commonest presenting symptoms. Heterosexual transmission was the commonest mode of HIV-acquisition. Tuberculosis (TB) was the commonest OI (71%) followed by candidiasis (39.3%), Pneumocystis jiroveci pneumonia (PCP) (7.4%), cryptococcal meningitis and cerebral toxoplasmosis (3.7% each). Most of the cases of TB were disseminated (64%). Apart from other well-recognised OIs, two patients had visceral leishmaniasis. Two cases of HIV-associated lymphoma were encountered. CD4+ cell counts were done in 109 patients. Majority of the patients (82.6%) had CD4+ counts <200 cells/μL. Fifty patients (46%) had CD4+ counts <50 cells/μL. Only 50 patients (37%) received antiretroviral therapy. Twenty one patients (16%) died during hospital stay. All but one deaths were due to TB (16 patients; 76%) and PCP (4 patients; 19%). CONCLUSIONS: A wide spectrum of disease, including both OIs and non-infectious opportunistic diseases, is seen in hospitalised HIV-infected patients from north India. Tuberculosis remains the most common OI and is the commonest cause of death in these patients

What are the factors driving antimicrobial resistance? Perspectives from a public event in London, England.

BACKGROUND: Antimicrobial resistance is driven by multiple factors. Resolving the threat to human and animal health presented by drug-resistant infections remains a societal challenge that demands close collaboration between scientists and citizens. We compared current public views about key contributing factors to antimicrobial resistance with those expressed by experts. METHODS: Overarching factors contributing to antimicrobial resistance were identified following a review of literature. The factors were then described in plain language and attached to ballot boxes at a public engagement event organised by a university. Responses to each factor were counted at the end of the event. RESULTS: Four hundred five responses were received from 3750 visitors (11 % response rate). Nearly half of responses (192/405, 47 · 4 %) considered the misuse/overuse of antibiotics in humans as the main determinant of antimicrobial resistance. The misuse of antibiotics in animal health obtained 16 · 3 % (66/405) responses. However, the lack of quick tests to diagnose infections received 10/405 votes (2 · 47 %), and the lack of effective vaccines received one vote (0 · 25 %). CONCLUSIONS: The majority of responses ascribed the emergence of drug-resistant infections to the misuse of antibiotics in human and animals. Suboptimal dosing, availability of diagnostics and environmental contamination were considered less influential on the development of antimicrobial resistance. The growing recognition of broader multifaceted drivers of drug resistance by experts is not yet echoed in the public mind

Incidence and Risk Factors of Serious Adverse Events during Antituberculous Treatment in Rwanda: A Prospective Cohort Study

BACKGROUND: Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa. In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome. METHODS AND FINDINGS: Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009. Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28-40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm(3) (IQR 44-248 cells/mm(3)). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23). HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4-8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1-3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1-3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0-2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3-3.0). CONCLUSION: Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections

The Diagnostic Sensitivity of Dengue Rapid Test Assays Is Significantly Enhanced by Using a Combined Antigen and Antibody Testing Approach

Dengue is a serious public health concern with around 3 billion people at risk of infection. Severe forms of the infection can be fatal and with no licensed vaccine or effective therapeutic currently available, early detection is important to assist with the clinical management of symptoms. Isolation of the virus and the detection of viral RNA using RT-PCR are commonly used methods for early diagnosis but are time-consuming, expensive and require skilled operation. Rapid immunochromatographic tests (ICT) are relatively simple, inexpensive and easy to perform at or near the point of care. Here, we report on the clinical performance of a new rapid ICT for the non-structural protein 1 (NS1) of dengue virus, a marker of acute infection. At two clinical study sites, NS1 was detected in 60–70% of laboratory-confirmed dengue cases and specificity of the test was >95%. We have also shown that a combined testing approach for both circulating NS1 antigen and antibody responses to the glycoprotein E of the virus can significantly improve diagnostic sensitivity compared to the detection of NS1 alone. Importantly, the combined antigen and antibody testing approach also provides an expanded window of detection from as early as day 1 post-onset of illness

Cancer risk in persons with HIV/AIDS in India: a review and future directions for research

Background India has a large and evolving HIV epidemic. Little is known about cancer risk in Indian persons with HIV/AIDS (PHA) but risk is thought to be low. Methods To describe the state of knowledge about cancer patterns in Indian PHA, we reviewed reports from the international and Indian literature. Results As elsewhere, non-Hodgkin lymphomas dominate the profile of recognized cancers, with immunoblastic/large cell diffuse lymphoma being the most common type. Hodgkin lymphoma is proportionally increased, perhaps because survival with AIDS is truncated by fatal infections. In contrast, Kaposi sarcoma is rare, in association with an apparently low prevalence of Kaposi sarcoma-associated herpesvirus. If confirmed, the reasons for the low prevalence need to be understood. Cervical, anal, vulva/vaginal and penile cancers all appear to be increased in PHA, based on limited data. The association may be confounded by sexual behaviors that transmit both HIV and human papillomavirus. Head and neck tumor incidence may also be increased, an important concern since these tumors are among the most common in India. Based on limited evidence, the increase is at buccal/palatal sites, which are associated with tobacco and betel nut chewing rather than human papillomavirus. Conclusion With improving care of HIV and better management of infections, especially tuberculosis, the longer survival of PHA in India will likely increase the importance of cancer as a clinical problem in India. With the population's geographic and social diversity, India presents unique research opportunities that can be embedded in programs targeting HIV/AIDS and other public health priorities

A New Approach to Dengue Fatal Cases Diagnosis: NS1 Antigen Capture in Tissues

Dengue manifestations may vary from asymptomatic to potentially fatal complications. With an increasing number of Dengue Hemorrhagic fever (DHF) and fatal cases, the availability of new approaches useful for cases confirmation plays an important role for the disease surveillance. The diagnosis of fatal cases in frozen and fixed tissues from autopsies can be determined by techniques such as viral RT-PCR, in situ hybridization, viral proteins detection by immunohistochemistry and NS3 specific immunostaining. We aimed to assess for the first time the usefulness of NS1 capture tests as a diagnostic technique to demonstrate DENV antigens in human tissue specimens. The highest sensitivity was obtained by a rapid ICT which was also the most sensitive in liver, lung, kidney, brain, spleen and thymus. Despite a number of studies demonstrating the usefulness of DENV NS1 antigen detection by different ELISAs in plasma and/or sera of dengue patients, no research has been done previously to demonstrate NS1 presence in tissues of fatal dengue cases. Moreover, the application of NS1 kits to demonstrate the presence of DENV may provide a better understanding of viral tropism in fatal cases and may be useful for studies of pathogenesis in vivo and in experimental animals

Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders

Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD

Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa.

Immune reconstitution inflammatory syndrome (IRIS) is a widely recognised complication of antiretroviral therapy (ART), but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa

Pneumocystis jirovecii pneumonia in tropical and low and middle income countries: a systematic review and meta-regression

Objective: Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings. Design Systematic review and meta-regression. METHODS: Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies). RESULTS: The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×10 3/ ml. CONCLUSIONS: There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii , ubiquitous in all settings, then becomes a greater relative threat