The World Health Organization recommends all-oral bedaquiline-based regimens for drug-resistant tuberculosis (DR-TB), including a longer M/XDR-TB regimen (18–20 months) and a shorter RR/MDR-TB regimen (9–11 months). Comparative effectiveness data under routine programmatic conditions remain limited. To compare clinical and microbiological outcomes of longer versus shorter all-oral treatment regimens. We conducted a prospective observational cohort study between January and December 2022. Patients with pulmonary or extrapulmonary RR/MDR-TB were enrolled and treated according to national programmatic guidelines. Six-month culture conversion and end-of-treatment clinical outcomes were compared between longer and shorter all-oral bedaquiline-based regimens using multivariable logistic regression adjusted for pre-specified confounders. Of 1427 patients screened, 894 (62.6

Background:Scrub typhus is a major rickettsial infection in Asia, occasionally presenting with movement disorders due to central nervous system involvement. This systematic review aimed to summarize their frequency, spectrum, diagnostic profile, treatment, and outcomes. Methods:A comprehensive search of PubMed, Embase, Scopus, and Google Scholar was conducted up to August 2025. All case reports, case series, and cohort studies reporting movement disorders associated with scrub typhus were included. Data were extracted and analyzed descriptively. The protocol was prospectively registered with PROSPERO under the identifier PROSPERO 2025 CRD420251156525. Results:Across 55 published cases, scrub typhus-associated movement disorders occurred predominantly in young adults (median age 28 years), with a male predominance (61.8%). Opsoclonus and related ocular motor disorders were the most frequent manifestations (41.8%), followed by cerebellar syndromes (34.5%), parkinsonism (12.7%), myoclonus (7.3%), and rare presentations such as ballismus, dystonia, opisthotonus, and akinetic mutism (7.3%). Associated neurological signs included cerebellar involvement (32.7%), altered sensorium (25.5%), extrapyramidal features (21.8%), and seizures (10.9%). In cohort studies including 2437 patients, 63 (2.6%) developed movement disorders, with opsoclonus-myoclonus seen in 22 (34.9%), ataxia in 17, myoclonus in 11 (17.4%), and extrapyramidal features in 25 (39.6%). Rare hyperkinetic manifestations such as hemiballismus and choreoathetoid movements were occasionally reported. Most patients had favorable outcomes, with complete recovery in 38 (69.1%), near-complete recovery in 6 (10.9%), partial recovery in 5 (9.1%), and death in 1 (1.8%). Conclusions:Movement disorders in scrub typhus, though uncommon, display a wide clinical spectrum and are often reversible.

[This corrects the article DOI: 10.7759/cureus.101805.].

We conducted a comprehensive analysis of spectrum of neuroimaging findings in Subacute Sclerosing Panencephalitis (SSPE) across case reports and cohort studies. A systematic review was conducted as per PRISMA guidelines. Electronic databases were searched from inception using predefined terms related to SSPE and neuroimaging. Eligible studies included confirmed cases with reported imaging findings from case reports, case series, and cohort studies. Among 461 reported cases, neuroimaging was performed in 456 (98.9

Fluoroquinolones (FQs) are key components of World Health Organization (WHO)-recommended regimens for multidrug-resistant tuberculosis (MDR-TB). Accurate detection of FQ resistance is essential for optimizing treatment. This study evaluated the concordance between the Second-Line Line Probe Assay (SL-LPA) and Liquid Culture Drug Susceptibility Testing (LC-DST) for detecting FQ resistance in Mycobacterium tuberculosis isolates. In this retrospective study, 1402 non-duplicate clinical isolates of MDR TB were tested using SL-LPA and LC-DST at a reference laboratory. Genotypic resistance was identified through mutations in the gyrA and gyrB genes identified by SL-LPA, while phenotypic resistance was determined using MGIT-based LC-DST at critical concentrations for fluoroquinolones. Targeted nanopore sequencing was performed on a subset of isolates with discordant molecular and phenotypic results to investigate resistance-associated mutations. SL-LPA detected FQ resistance in 907 (64.7

Background:In 2017 India introduced the 13-valent pneumococcal conjugate vaccine (PCV13; Prevenar 13®) in select high-burden sites and in 2021, transitioned to nationwide introduction of 10-valent PCV (PCV10-SII; PNEUMOSIL®). We examined data from a large sentinel paediatric meningitis surveillance network to assess early changes in pneumococcal meningitis among hospitalised children after introduction of pneumococcal vaccine. Methods:Children (1-59 months) who were hospitalised with suspected meningitis at 32 hospitals across 19 states of India were enrolled in this hospital-based surveillance from 2019 to 2022. Clinical and demographic data were collected. Cerebrospinal fluid (CSF) samples were tested for Streptococcus pneumoniae using real-time PCR. Serotypes were identified using real-time PCR in TaqMan Array Cards. Cases were categorised based on PCV implementation in their district of residence on their admission date as pre-PCV (before rollout of PCV10-SII/PCV13), early-PCV (<1 year since rollout), or post-PCV (≥1 year since rollout) group. Findings:Among 12,971 children enrolled, 303 (2.3%) had pneumococcal meningitis; 65.3% were between 1 and 11 months of age, and 60.1% were males. Among 260 children with outcome data, 93.1% recovered, while 6.9% died during hospitalisation. The proportion of children with pneumococcal meningitis decreased from 3.5% pre-PCV to 1.8% during both early- and post-PCV periods. Among serotyped pneumococcal meningitis, the proportion of PCV10-SII serotypes was 41.4% in pre-PCV, 33.3% early-PCV, and 25.9% post-PCV periods. The most common PCV10-SII serotypes were 5, 14, and 6B whereas non-PCV10-SII serotypes were 18C/18B, 8, and 10F. Interpretation:Decline in the proportion of PCV10-SII serotype among paediatric pneumococcal meningitis patients represents preliminary signals of PCV impact in India. These findings provide programmatically relevant evidence to inform ongoing evaluation of PCV implementation. Continued surveillance is essential to monitor serotype distribution and pneumococcal meningitis patterns over time. Funding:Gates Foundation (OPP1188408) and the United Nations Development Programme (00101970).

In December 2024 and early January 2025, China reported increased acute respiratory infections with increased detections of seasonal influenza, rhinovirus, RSV and hMPV during the Northern Hemisphere winter. We strengthened hMPV surveillance through the existing pan-India surveillance network for acute respiratory illness (ARI) and severe acute respiratory infection (SARI). To rapidly generate nationwide situational data without overburdening laboratories already performing routine respiratory virus surveillance, each site was asked to test up to five eligible SARI samples per week for hMPV from January to April 2025. Eligible samples were hospitalized SARI cases that were negative for influenza, SARS-CoV-2 and/or RSV, as applicable to age-based testing algorithms, across 70 laboratories. Of 8,246 enrolled SARI cases, 4,149 eligible samples were tested for hMPV under the capped weekly sampling strategy, and 59 were positive (1.42

Background & objectives The global target set by the United Nations (UN) high-level meeting on Tuberculosis (TB) for coverage of rapid molecular tests is 100 per cent by 2027. Rapid, affordable molecular tests for early detection of TB are the need of the hour. This study aimed to evaluate the diagnostic accuracy of an open real-time PCR (RT-PCR) assay, Quantiplus®, with reference to Mycobacteria Growth Indicator Tube (MGIT) liquid culture. Methods We conducted a prospective multi-centric diagnostic accuracy study of Quantiplus® assay (version 2.0) at three sites in India for the detection of pulmonary TB in sputum with culture as the reference standard, compared with Xpert® MTB/RIF. A total of 657 adults (>18 yr) with presumptive TB were enrolled consecutively. The Quantiplus® assay uses an extraction-free, quick-lysis protocol and three gene targets for RT-PCR. Results Of the 644 samples analysed, 37 per cent were culture-positive and 32 per cent were smear-positive. The sensitivity and specificity of Quantiplus® assay with reference to MGIT culture were 86 per cent [95% confidence interval (CI): 81-90] and 96 per cent (95% CI: 94-98), respectively, at Ct ≤ 38. The positive and negative predictive values (PPV/NPV) were 93 per cent (95% CI: 89-96%) and 92 per cent (95% CI: 89-94%), respectively. Among the 73 smear-negative culture-positive specimens, the sensitivity and specificity were 61.6 per cent (95% CI: 50-73) and 97 per cent (95% CI: 92-98.6), respectively. The performance of Quantiplus® assay(v2.0) was comparable to Xpert MTB/RIF® (κ=0.83, SE=0.02) at Ct ≤38. Interpretation & conclusions The flexibility of the open RT-PCR assay to be used in any RT-PCR machine makes it a very low-cost (<2 US$) alternative to the expensive cartridge-based tests. This is the first report of validation of an open system RT-PCR assay for the detection of pulmonary TB.

Objective: Japanese encephalitis (JE) is one of the most important causes of viral encephalitis in Uttar Pradesh (UP). Over 5 years (2018–2022), this study aims to find out the seropositivity for JEV in cases presenting as AES. Materials and Methods: Over 5 years, 8131 cerebrospinal fluid and 504 serum samples were tested for anti-JEV Immunoglobulin M (IgM) antibodies by IgM antibody capture (MAC) enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions (MAC ELISA kit developed by the National Institute of Virology, Pune, India. Results: A total of 526 cases (6.09%) tested positive for anti-JEV IgM antibodies during the study periods. The number of JEV positives was high in 2018 (11.25%) but decreased gradually over the next 5 years (2019 (5.71%), 2020 (5.22%), 2021 (4.36%), and 2022 (2.91%). JE positivity is declining over time in UP, India. There is an age shift from children to adults. Men are more often affected than women. Conclusion: Further JE-centric studies with an emphasis on immunization are required to determine the influence of vaccination on the incidence of Japanese encephalitis and the population shift among adults.

Objectives: Co-infections with viral, bacterial, and fungal pathogens have been reported in Corona virus disease 2019 (COVID-19) patients. A new concern is presence of co-infections with other respiratory viruses, which could complicate diagnosis, treatment, and disease outcomes. This study aimed to detect Inuenza and other respiratory viruses in COVID-19 patients and assess the association between co-infections and severity of COVID-19. Materials And Methods: A nested case-control study was conducted with 760 real-time polymerase chain reaction (RT-PCR) positive COVID-19 patients of all ages and sexes, enrolled over two consecutive years (January-March 2021 and 2022). Nasopharyngeal or oropharyngeal swabs were tested for 13 respiratory viruses using polymerase chain reaction (PCR). Association of co-infection with respiratory viruses and severity of illness was calculated. Statistical Analysis: The chi-square test was used to analyze the relationship between respiratory virus positivity and disease severity/mortality. Data analysis was performed using Statistical Package for Social Sciences (SPSS) Version 21.0. Results: Co-infections with other respiratory viruses were observed in 87 (11.44%) of the 760 COVID-19 patients. The majority of co-infections were with Inuenza A (42, 5.53%), followed by Parainuenza virus 3 (12, 1.58%) and Rhinovirus (10, 1.32%). No co-infections were observed with Respiratory Syncytial Virus (RSV) Aand B, Parainuenza 2, and Bocavirus. Co-infections were most common in patients aged 60-80 years. Signicant association between co-infection and severity of disease was observed in patients having co-infection with Inuenza virus. Poor outcome was also associated with advanced age, patients with one or more comorbidities and patients who required Intensive Care Unit (ICU) admission. Conclusion: Increased severity, mortality and higher rates of hospitalisation was seen in COVID-19 patients having co-infection with Inuenza viruses.

OBJECTIVES:Assess the effectiveness of bedaquiline, pretomanid and linezolid (BPaL) regimens with varying doses and duration of linezolid at the end of 48 weeks post treatment among drug resistant tuberculosis (DR TB) patients. METHODS:Multicentric pragmatic randomized clinical trial in which BPaL regimens were given for 26 weeks for pulmonary pre extensively drug resistant tuberculosis (PreXDR TB); bedaquiline, pretomanid and linezolid 600 mg for 26 weeks (arm1), structured dose reduction arms with linezolid dose reduction from 600 to 300 mg after nine weeks (arm2) and 13 weeks (arm3). Participants were followed up for recurrence-free cure up to 48 weeks post-treatment. Whole genome sequencing in sputum samples at baseline and recurrence differentiated relapse and reinfection. RESULTS:Of 403 enrolled, 378 were included for the modified intent-to-treat analysis based on baseline sputum culture positivity and sensitivity to medications in the study regimen. Among them, 331(88%) had recurrence-free cure at the end of 48 weeks of post-treatment follow-up; arm1:112(87%), arm2:110(88%), arm3:109(88%). Overall, 14 (12 bacteriological and 2 clinical) recurrences (arm1-four, 2-six and 3-four) occurred; 11 recurrences occurred within 24 weeks after treatment completion; four out of 11 within the first 12 weeks. Of the 10 paired sputum samples available at baseline and recurrence for comparison of lineages, there were two reinfections and eight relapses. CONCLUSION:Structured dose reduction arms had comparable recurrence free cure rates as linezolid 600 mg arm when given along with bedaquiline and pretomanid for 26 weeks in PreXDR TB. Most of the recurrences occurred within the first six months.

INTRODUCTION:Scrub typhus is a significant cause of acute encephalitis syndrome (AES) in pediatric populations, particularly in northern India. Its long-term outcomes have not been well studied to date. This study investigates the clinical profile and long-term outcomes of scrub typhus meningoencephalitis in children. METHODS:This prospective observational study was conducted at King George's Medical University, Uttar Pradesh, India, from August 2018 to October 2020. Children aged 0.3 months to 14 years who presented with AES were tested for scrub typhus using serum IgM Enzyme-Linked Immunosorbent Assay (ELISA) and polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC). Positive patients were followed up for one year to assess long-term neurological outcomes. RESULTS:Of 264 children tested for scrub typhus, 78 (29.5%) were positive. Neurological symptoms included altered sensorium (70 (89.74%)), seizures (69 (88.46%)), and focal neurological deficits 8 (10.26%). Hepato-splenomegaly (27 (34.61%)), thrombocytopenia (48 (61.5%)), and raised liver transaminases (51 (65.4%)) were the other common manifestations. Mortality occurred in 10.25% of cases. Sixty-seven cases were followed up for one year. Long-term outcomes indicated that 60 (89.55%) of the patients fully recovered, while seven (10.45%) experienced sequelae, including minor impairment in four (5.97%), moderate impairment in two (2.99%), and severe impairment in one case (1.49%). CONCLUSION:Scrub typhus is a major cause of AES in children, with significant neurological sequelae in a small number of cases.

BACKGROUND:Interstitial capillary congestion and diffuse alveolar damage (DAD) were frequently observed in patients who died from Coronavirus disease-19 (COVID-19). The research question pertains to observing these findings in COVID-19-positive patients lacking pulmonary symptoms. The histological examination of lung samples from COVID-19-positive patients who do not succumb to COVID-19-related pulmonary complications can provide an answer. This study analyzed postmortem lung autopsy samples from individuals who did not succumb to COVID-19-related pulmonary complications. The research article aimed to examine the morphological variations in postmortem lung samples of COVID-19 patients who did not succumb to the disease, and to compare these changes with those observed in cases of COVID-19-related deaths, utilizing existing English literature. METHODOLOGY:This prospective study included subjects who died without complications from COVID-19-related injuries, had positive real-time polymerase chain reaction throat swabs, and exhibited no pulmonary manifestation of COVID-19 disease. A comprehensive histomorphological analysis of the lung samples was conducted. RESULTS:A total of 20 subjects were enrolled in this study. Capillary congestion was the most prevalent histomorphological change observed in lung autopsies, seen in 90% (18/20) of cases, followed by emphysema in 75% (15/20) and the acute phase of DAD in 25% (5/20) of cases. Acute bronchopneumonia and fibrotic nodules were identified in 20% (4/20) and 10% (2/20) of the study population, respectively. CONCLUSION:In postmortem lung autopsy of COVID-19-positive patients lacking symptomatic pulmonary issues, capillary congestion, diffuse alveolar destruction, and emphysema were prevalent. The findings indicate that COVID-19 exhibits varied responses to damage and inflammation that do not correlate with mortality. This study enhances the understanding of pathophysiological lung tissue variations in COVID-19 patients who have non-COVID-19-related deaths, potentially educating forensic pathologists and supporting future research endeavors.

Problem considered Conventional diagnostic techniques for diagnosing Cutaneous tuberculosis (CTB) have variable sensitivity, specificity and are time-consuming. CB-NAAT is based on real- time PCR and can be helpful in rapid detection of mycobacterial antigens along with the detection of rifampicin resistance. Our study aims at detecting the efficacy of CB-NAAT in the diagnosis of CTB as compared to conventional diagnostic techniques like histopathology and culture. Methods Skin biopsies were taken from the representative lesions in 41 patients of CTB. One sample was sent for histopathology whereas the other sample was sent for CB-NAAT, liquid culture -DST (drug sensitivity testing) and smear microscopy. Results Out of 41 patients with cutaneous TB, CB-NAAT was positive in 6 (14.63%), culture was positive in 8 (19.5%) and histopathology was compatible in 26 (63.4%) patients. CB-NAAT was positive in 3 out of 8 culture positive cases and 4 out of 26 histopathology compatible cases. The sensitivity and specificity of gene Xpert MTB/RIF in detecting TB when compared to culture were 37.5% and 91% respectively and Positive- and Negative-predictive values were 50% and 85.7% respectively. Xpert MTB/RIF could identify an additional 3 cases, where all other microbiological investigations were negative. Out of 6 cases that were CB-NAAT positive, 3 showed Rifampicin resistance. Conclusions The CB-NAAT test has variable diagnostic accuracy in the diagnosis of CTB which can vary with the clinical specimen. It can prove as a promising tool for early detection of cutaneous TB along with drug-resistant TB especially in the high endemic zones.

ABSTRACT BACKGROUND: Human immunodeficiency virus (HIV) is the major cause of failure to reach targets of tuberculosis (TB) control in settings with high HIV load. TB on the other hand enhances the progression of HIV infection to acquired immunodeficiency syndrome (AIDS). METHODOLOGY: An observational study was conducted in which 573 patients who were newly diagnosed with HIV infection and enrolled at an antiretroviral therapy (ART) center, King Georges Medical University (KGMU), Lucknow between May 2021 to June 2022 were taken, of which 80 patients had newly diagnosed TB. These HIV-TB co-infected patients were analyzed for demographic factors. Also, clusters of differentiation 4 (CD4) counts were done at the time of enrolment on ART and then about six to eight months later. For comparison, of the 493 HIV-only patients, 50 age and sex-matched consecutive patients for whom both the baseline and follow-up CD4 counts were available and were not investigated for tuberculosis during the study period were enrolled as controls. The change from baseline CD4 count was calculated with the use of paired t-test and Wilcoxon signed rank test. RESULTS : In the present study, among HIV-TB coinfected patients, baseline CD4 levels were 194.52±162.27, and follow-up CD4 levels were 285.09±170.33. An increment of 90.57±165.60 in mean CD4 levels was observed which was statistically significant(t=4.019; p<0.001 ). Likewise, in only HIV-positive patients a statistically significant increment of 125.26±191.48 (35.75%) cells in mean CD4 levels was observed (t=4.626; p<0.001). CONCLUSION : A significant rise in CD4 counts was observed in both HIV-TB coinfected patients started on ART plus anti-tubercular treatment (ATT) and HIV-only patients started on ART. Still, the rise is significantly higher among the HIV-only group as compared to the HIV-TB co-positive group.

Introduction This study aims to evaluate the diagnostic performance of polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) methods, and gene sequencing in detecting Orientia tsutsugamushi, the causative agent of scrub typhus, in pediatric patients with acute encephalitis syndrome (AES). Methods The study was conducted at a tertiary care teaching hospital in northern India. In all, 264 children presenting with AES were enrolled between August 2018 and November 2019. Cerebrospinal fluid (CSF), serum, and peripheral blood mononuclear cell (PBMC) samples were analyzed using real-time PCR and ELISA to detect the presence of scrub typhus. The 56 kDa gene sequencing was performed in 15 samples. Results The ELISA for scrub typhus IgM demonstrated the highest cumulative positivity rate at 26.52%. In contrast, PCR testing of CSF and PBMC samples showed lower detection rates of 4.17% and 9.47%, respectively. The overall positivity for scrub typhus was 29.5%, highlighting the significant role of this pathogen in pediatric AES cases in endemic regions. The phylogenetic analysis of scrub typhus revealed many Gilliam-like strains. Conclusion ELISA for scrub typhus IgM has a high positivity rate in comparison to PCR for the detection of scrub typhus in children with AES.