Disseminated mycobacteriosis secondary to intravenous Bacille Calmette-Guérin (BCG) vaccine.

Bacille Calmette-Guérin (BCG) vaccine has been used increasingly in immunotherapy, including treatment of non-muscle-invasive bladder cancer, as an adjuvant therapy in metastatic prostate cancer and metastatic melanoma. However, systemic infection from inadvertent intravenous (instead of intravesical) injection is uncommon and can have systemic ramifications. We encountered 3 patients with disseminated Mycobacterium bovis infection that ensued after intravenous BCG injection.

Prevalence and potential impact of human pegivirus-1 on HIV-1 disease progression among Indian PLHIV.

INTRODUCTION: Human pegivirus-1 (HPgV-1) influences the pathogenesis and outcome of viral infections. We investigated the prevalence and impact of HPgV-1 due to the paucity of studies on Indian people living with HIV (PLHIV). METHODOLOGY: Samples were collected from 347 treatment-naïve PLHIV; and 100 blood donors negative for HIV, HBV, and HCV. CD4+ T-cell and HIV-1 viral load were measured using flow-cytometry and quantitative polymerase chain reaction (qPCR), respectively. HPgV-1 was quantified and genotyped by qPCR and Sanger sequencing, respectively. RESULTS: HPgV-1 viremia in PLHIV and controls was 11% (38/347) and 1% (1/100), respectively. We found HPgV-1 genotype-2a in PLHIV and genotype-2b in controls. Male preponderance was seen in HIV-1 mono-infection and co-infection groups (166 vs. 143 and 33 vs. 5; p < 0.0001). The peak prevalence of HPgV-1 was at 31-50 years (p = 0.02). CD4+ T-cell count (245.5 vs. 240; p = 0.59) and HIV-1 log viral load (4.7 vs. 4.9; p = 0.50) were not significantly different between the HIV-1 mono-infected and coinfected individuals. However, a direct correlation existed between HpgV-1 viral load and CD4+ T-cell count (r = 0.27, p = 0.05) and an inverse correlation with HIV-1 viral load (r = -0.21, p = 0.10). CONCLUSIONS: This is the first study in India to estimate the HPgV-1 prevalence in PLHIV with the predominance of genotype-2a. HPgV-1 viremia had a moderate impact on CD4+ T-cells and HIV-1 viral load, which requires a longitudinal study to identify the beneficial influence on HIV-1 disease progression and outcome.

Evaluation of Molecular Assays for Diagnosis of Amoebic Liver Abscess in India with Bayesian Latent Class Analysis.

Amoebic liver abscess (ALA) is the most common extra-intestinal complication of Entamoeba histolytica, accounting for 50,000 deaths annually, and is endemic in South Asia. Diagnosis based on microscopic examination is insensitive, and serological assays are not discerning of current infections in endemic settings with high exposure. For a rapid and confirmatory laboratory diagnosis of ALA, the performance of a polymerase chain reaction (PCR), quantitative real time PCR (qPCR), digital droplet PCR (ddPCR), and a loop-mediated isothermal amplification (LAMP) assay that detects E. histolytica DNA in liver abscess pus, and a lectin antigen detection ELISA were evaluated against clinical diagnosis (based on predefined criteria) as the gold standard. Owing to the lack of a laboratory gold standard, a Bayesian latent class analysis approach was also used to determine sensitivity and specificity of these assays. In the latent class analysis, qPCR and ddPCR showed the highest sensitivity (98% and 98.1%) and specificity (both 96.6%), and although clinical diagnosis had a comparable sensitivity to qPCR and ddPCR (95.2%), poorer specificity (64.3%) was seen. Kappa agreement analysis showed that qPCR and ddPCR had a perfect agreement of 1 followed by an agreement of 0.76 (95% CI: 0.64-0.88) with PCR. Considering the performance characteristics and relative ease of setting up qPCR as well as the wide availability of qPCR equipment needed, this would be the most optimal assay for rapid, confirmatory, molecular diagnosis of ALA in the tertiary care laboratory setting in India, whereas further optimization of LAMP or antibody-based detection is required for use at smaller or secondary hospitals.

Primary Aortoenteric Fistula Due to Salmonella typhi-related Mycotic Aneurysm.

Primary aortoenteric fistulas (AEF) are rare. The majority of these are due to atherosclerotic aortic aneurysms. Mycotic aortic aneurysms leading to primary AEF are exceedingly uncommon. Here we report a rare case of primary AEF secondary to Salmonella-related mycotic aneurysm and discuss the diagnostic and therapeutic issues.

Central nervous system infections in the tropics.

PURPOSE OF REVIEW: Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality. RECENT FINDINGS: In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics. SUMMARY: A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.

Favipiravir for treating COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19. OBJECTIVES: To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023. SELECTION CRITERIA: We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.

Clinico-Radiological Evaluation for Longitudinal Assessment in Central Skull Base Osteomyelitis: Proposal of Novel Scoring System.

This study aims to evaluate clinical, radiological and laboratory parameters for longitudinal assessment and prognostication in central skull base osteomyelitis (CSBO). Novel radiological score and cranial nerve assessment score (CNAS) have been proposed and analysed along with pain score (VAS), ESR, CRP, WBC count, and HbA1c for utility in disease-monitoring and predicting outcome in CSBO. CSBO cases managed in a tertiary care centre from January 2018 to November 2020, with a minimum follow-up of 6 months were included. The parameters were recorded at presentation, 3-month, 6-month postoperative follow-up, and at completion of therapy, for statistical analysis. Significant positive correlation was found amongst pain score, CNAS, radiological score, ESR, and CRP at different timelines. On longitudinal assessment, there was a statistically significant reduction in above-mentioned parameters, in the cases who recovered. Those with initial radiological score < 30, pain score ≤ 7, and CNAS < 10 showed early clinical improvement, required shorter duration of antimicrobial therapy, and exhibited higher probability of becoming disease-free at an earlier time, compared to those presenting with higher scores. We propose the use of pain score, a novel cranial nerve assessment score, and a novel radiological score for longitudinal assessment in CSBO. The trend in these parameters along with ESR and CRP are useful to monitor the disease process. The initial assessment scores can predict duration of antimicrobial therapy and probability of early recovery. WBC count and HbA1c were neither useful for disease-monitoring nor predicting outcome.

Establishing an effective antimicrobial stewardship program at four secondary-care hospitals in India using a hub-and-spoke model.

Background: The high burden of antimicrobial resistance in India necessitates the urgent implementation of antimicrobial stewardship programs (ASPs) in all healthcare settings in India. Most ASPs are based at tertiary-care centers, with sparse data available regarding the effectiveness of an ASP in a low-resource primary/secondary-care setting. Methods: We adopted a hub-and-spoke model to implement ASPs in 4 low-resource, secondary-care healthcare settings. The study included 3 phases measuring antimicrobial consumption data. In the baseline phase, we measured days on antimicrobial therapy (DOTs) with no feedback provided. This was followed by the implementation of a customized intervention package. In the postintervention phase, prospective review and feedback were offered by a trained physician or ASP pharmacist, and days of therapy (DOT) were measured. Results: In the baseline phase, 1,459 patients from all 4 sites were enrolled; 1,233 patients were enrolled in the postintervention phase. Both groups had comparable baseline characteristics. The key outcome, DOT per 1,000 patient days, was 1,952.63 in the baseline phase and significantly lower in the post-intervention period, at 1,483.06 (P = .001). Usage of quinolone, macrolide, cephalosporin, clindamycin, and nitroimidazole significantly decreased in the postintervention phase. Also, the rate of antibiotic de-escalation was significantly higher in the postintervention phase than the baseline phase (44% vs 12.5%; P < .0001), which suggests a definite trend toward judicious use of antibiotics. In the postintervention phase, 79.9% of antibiotic use was justified. Overall, the recommendations given by the ASP team were fully followed in 946 cases (77.7%), partially followed in 59 cases (4.8%), and not followed in 137 cases (35.7%). No adverse events were noted. Conclusion: Our hub-and-spoke model of ASP was successful in implementing ASPs in secondary-care hospitals in India, which are urgently needed.

Global Landscape of Encephalitis: Key Priorities to Reduce Future Disease Burden.

Encephalitis affects people across the lifespan, has high rates of mortality and morbidity, and results in significant neurological sequelae with long-term consequences to quality of life and wider society. The true incidence is currently unknown due to inaccurate reporting systems. The disease burden of encephalitis is unequally distributed across the globe being highest in low- and middle-income countries where resources are limited. Here countries often lack diagnostic testing, with poor access to essential treatments and neurological services, and limited surveillance and vaccination programs. Many types of encephalitis are vaccine preventable, whereas others are treatable with early diagnosis and appropriate management. In this viewpoint, we provide a narrative review of key aspects of diagnosis, surveillance, treatment, and prevention of encephalitis and highlight priorities for public health, clinical management, and research, to reduce the disease burden.