Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in Mumbai, India.

BACKGROUND:Patients on linezolid-containing drug-resistant TB (DR-TB) regimen often develop adverse-events, particularly peripheral and optic neuropathy. Programmatic data and experiences of linezolid-associated optic neuropathy from high DR-TB burden settings are lacking. The study aimed to determine the frequency of and risk-factors associated with linezolid-associated optic neuropathy and document the experiences related to treatment/care of DR-TB patients on linezolid-containing regimens. METHODS:This was a retrospective cohort study using routine clinical and laboratory data in Médecins Sans Frontières (MSF) HIV/DR-TB clinic in collaboration with Lilavati Hospital & Research Center, Mumbai, India. All DR-TB patients on linezolid-containing treatment regimens were included in the study and underwent routine evaluations for systemic and/or ocular complaints. Ophthalmological evaluation by a consultant ophthalmologist included visual-acuity screening, slit-lamp examination and dilated fundus examination. RESULTS:During January 2013-April 2016, 86 of 136 patients (with/without HIV co-infection) initiated linezolid-containing DR-TB treatment. The median age of these 86 patients was 25 (20-35) years and 47% were males. 20 percent of them had HIV co-infection. Of 86, 24 (27.9%) had at least one episode of ocular complaints (the majority blurred-vision) and among them, five (5.8%) had optic neuropathy. Patients received appropriate treatment and improvements were observed. None of the demographic/clinical factors were associated with optic neuropathy in Poissons or multivariate binary logistic-regression models. DISCUSSION:This is the first report focusing on optic neuropathy in a cohort of complex DR-TB patients, including patients co-infected with HIV, receiving linezolid-containing regimens. In our study, one out of four patients on linezolid had at least one episode of ocular complaints; therefore, systematic monitoring of patients by primary physicians/nurses, and access to specialized diagnostic-services by specialists are needed. As linezolid will be increasingly added to treatment regimens of DR-TB patients, programmes should allocate adequate resources for early diagnosis, prevention and management of this disabling adverse event

Seasonality of influenza and its association with meteorological parameters in two cities of Pakistan: A time series analysis.

BackgroundInfluenza is known to have a specific pattern of seasonality the reasons for which are yet to be fully ascertained. Temperate zones show influenza epidemic during the winter months. The tropical and subtropical regions show more diverse influenza outbreak patterns. This study explores the seasonality of influenza activity and predicts influenza peak based on historical surveillance time series data in Islamabad and Multan, Pakistan.MethodsThis is a descriptive study of routinely collected monthly influenza sentinel surveillance data and meteorological data from 2012-16 in two sentinel sites of Pakistan: Islamabad (North) and Multan (Central).ResultsMean number of cases of influenza and levels of precipitation were higher in Islamabad compared to Multan. Mean temperature and humidity levels were similar in both the cities. The number of influenza cases rose with decrease in precipitation and temperature in Islamabad during 2012-16, although the same cannot be said about humidity. The relationship between meteorological parameters and influenza incidence was not pronounced in case of Multan. The forecasted values in both the cities showed a significant peak during the month of January.ConclusionThe influenza surveillance system gave a better understanding of the disease trend and could accurately forecast influenza activity in Pakistan

Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in Mumbai, India - Fig 3

<p>Perimetric Findings of Case 4; A) Right eye at diagnosis showing centrocecal scotomas with an associated bitemporal central scotoma and B) Right eye at day 38 showing worsening. Similar findings are seen in the Left eye at diagnosis (C) and at day 38 (D).</p

Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in Mumbai, India - Fig 2

<p>Perimetric Findings of Case 2; A) Right eye at diagnosis showing centrocecal scotomas with an associated bitemporal central scotoma and B) Right eye at day 45 showing resolution. Similar findings are seen in the Left eye at diagnosis (C) and at day 45 (D).</p

Demographic and clinical characteristics of drug-resistant tuberculosis patients with linezolid-associated optic neuropathy, Mumbai, January 2013-April 2016.

<p>Demographic and clinical characteristics of drug-resistant tuberculosis patients with linezolid-associated optic neuropathy, Mumbai, January 2013-April 2016.</p

Demographic and clinical characteristics of drug-resistant tuberculosis patients on Linezolid-containing regimen in Mumbai, India, January 2013-April 2016.

<p>Demographic and clinical characteristics of drug-resistant tuberculosis patients on Linezolid-containing regimen in Mumbai, India, January 2013-April 2016.</p

Genotyping and outcomes of presumptive second line ART failure cases switched to third line or maintained on second line ART in Mumbai, India.

BackgroundHIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented.ObjectiveTo document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART.DesignRetrospective cohort study of patients referred between January 2011 and September 2017.ResultsThe cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug.ConclusionAdopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens

Routine viral load monitoring and enhanced adherence counselling at a public ART centre in Mumbai, India.

BACKGROUND:Routine viral-load (VL) measurements along with enhanced adherence counselling (EAC) are recommended to achieve virological suppression among people living with HIV/AIDS (PLHA) on anti-retroviral therapy (ART). The Mumbai Districts AIDS Control Society along with Médecins Sans Frontières has provided routine VL measurements and EAC to PLHA on ART at King Edward Memorial (KEM) hospital, Mumbai since October-2016. This study aims to describe the initial VL results and impact of EAC on viral suppression and factors associated with initial viral non-suppression among patients with an initial detectable VL, in a cohort of patients tested between October-2016 and September-2018. METHODS:This is a descriptive study of PLHA on ART who received VL testing and EAC during October-2016 to September-2018. Log-binomial regression was used to identify factors associated with a high VL. RESULTS:Among 3849 PLHA who underwent VL testing, 1603(42%) were female and median age was 42 years (IQR:35-48). Majority were referred for routine testing (3432(89%)) and clinical/immunological failure (233(6%)). Overall, 3402(88%) PLHA had suppressed VL at initial testing. Among 3432 tested for routine monitoring, 3141(92%) had VL suppressed. Of 291 with VL>1000c/ml, 253(87%) received EAC and after repeat VL, 70(28%) had VL1000c/ml and 109 have been switched to second-line ART. CD4 count1000c/ml. Factors associated with follow-up VL suppression included EAC (p<0.05) and being on second-line ART (p<0.05). CONCLUSION:Results from a routine VL program in public sector in India were encouraging and in line with UNAIDS 90-90-90 targets. Routine VL monitoring along with EAC resulted in early switch to alternative optimised regimens while also preventing unnecessary switches. Along with the vital scale up of routine VL monitoring, implementation of enhanced adherence strategies for patients with detectable viral load should be ensured