Whole-genome sequencing of clinical isolates from tuberculosis patients in India: real-world data indicates a high proportion of pre-XDR cases.

Treatment decisions for tuberculosis (TB) in the absence of full drug-susceptibility data can result in amplifying resistance and may compromise treatment outcomes. Genomics of Mycobacterium tuberculosis (M.tb) from clinical samples enables detection of drug resistance to multiple drugs. We performed whole-genome sequencing (WGS) for 600 clinical samples from patients with tuberculosis to identify the drug-resistance profile and mutation spectrum. We documented the reasons reported by clinicians for referral. WGS identified a high proportion (51%) of pre-extensively drug-resistant (pre-XDR) cases followed by multidrug-resistant tuberculosis (MDR-TB) (15.5%). This correlates with the primary reason for referral, as non-response to the first-line treatment (67%) and treatment failure or rifampicin resistance (14%). Multivariate analysis indicated that all young age groups (P < 0.05), male gender (P < 0.05), and Beijing strain (P < 0.01) were significant independent predictors of MDR-TB or MDR-TB+ [pre-extensively drug-resistant tuberculosis (XDR-TB) and XDR-TB]. Ser315Thr (72.5%) in the inhA gene and Ser450Leu in the rpoB gene (65.5%) were the most prevalent mutations, as were resistance-conferring mutations to pyrazinamide (41%) and streptomycin (61.33%). Mutations outside the rifampicin resistance-determining region (RRDR), Ile491Phe and Val170Phe, were seen in 1.3% of cases; disputed mutations in rpoB (Asp435Tyr, His445Asn, His445Leu, and Leu430Pro) were seen in 6% of cases, and mutations to newer drugs such as bedaquiline and linezolid in 1.0% and 7.5% of cases, respectively. This study on clinical samples highlights that there is a high proportion of pre-XDR cases and emerging resistance to newer drugs; ongoing transmission of these strains can cause serious threat to public health; and whole-genome sequencing can effectively identify and support precision medicine for TB. IMPORTANCE: The current study is based on real-world data on the TB drug-resistance profile by whole-genome sequencing of 600 clinical samples from patients with TB in India. This study indicates the clinicians' reasons for sending samples for WGS, which is for difficult-to-treat cases and/or relapse and treatment failure. The study reports a significant proportion of cases with pre-XDR-TB strains that warrant policy makers' attention. It reflects the current iterative nature of the diagnostic tests under programmatic conditions that leads to delays in appropriate diagnosis and empirical treatment. India had an estimated burden of 2.95 million TB cases in 2020 and 135,000 multidrug-resistant cases. However, WGS profiles of M.tb from India remains disproportionately poorly represented. This study adds a significant body of data on the mutation profiles seen in M.tb isolated from patients with TB in India, mutations outside the RRDR, disputed mutations, and resistance-conferring mutations to newer drugs such as bedaquiline and linezolid.

Interplay of missed opportunity for vaccination and poor response to the vaccine led to measles outbreak in a slum area of Eastern Mumbai, India.

In the third week of September 2022, an outbreak of measles was reported from a slum in Eastern Mumbai, India. We sought to investigate whether failure to vaccinate or vaccine failure was the cause. We constructed an epidemic curve, drew a spot map, and calculated the attack rate and case-fatality ratio. We calculated vaccine effectiveness (VE) for one and two doses of measles vaccine in an unmatched case-control study and did stratified analysis by sex, availability of vaccination card, and migrant status. We identified 358 cases and four deaths with a 11.3% attack rate and 1.1% case fatality, both being highest among 0-24-month-old boys. The epidemic curve suggested a propagated mode of spread. The VE for two doses was 64% (95% confidence interval (CI): 23-73%) among under-5-year-old children and 70% (95% CI: 28-88%) among 5-15-year-old children. Failure to vaccinate, consequent to the COVID-19 pandemic, and vaccine hesitancy might have led to the accumulation of susceptible children in the community. Additionally, the occurrence of case-patients among vaccinated suggests reduced VE, which needs further investigation into humoral and cell-mediated immunity as well as contributory factors including nutritional status. Outbreak response immunization to complete immunization of missed and dropout children was carried out to control the outbreak.

Simultaneous screening for COVID-19 and tuberculosis, India.

Objective: To evaluate the implementation of new operational workflows for simultaneous screening of coronavirus disease 2019 (COVID-19) and tuberculosis at four high-volume COVID-19 testing centres located in tertiary hospitals in Mumbai, India. Methods: Each centre already offering antigen-detecting rapid diagnostic tests were equipped with a rapid molecular testing platform for COVID-19 and tuberculosis, sufficient laboratory staff, and reagents and consumables for screening. Using a verbal tuberculosis questionnaire, a patient follow-up agent screened individuals visiting the COVID-19 testing centres. Presumptive tuberculosis patients were asked to provide sputum samples for rapid molecular testing. Subsequently, we reversed our operational workflow to also screen patients visiting tuberculosis outpatient departments for COVID-19, using rapid diagnostic tests. Results: From March to December 2021, we screened 14 588 presumptive COVID-19 patients for tuberculosis, of whom 475 (3.3%) were identified as having presumptive tuberculosis. Of these, 288 (60.6%) were tested and 32 individuals (11.1%) were identified as tuberculosis positive (219 cases per 100 000 individuals screened). Of the tuberculosis-positive individuals, three had rifampicin-resistant tuberculosis. Among the remaining 187 presumptive tuberculosis cases not tested, 174 reported no symptoms at follow-up and 13 individuals either refused testing or could not be traced. Of the 671 presumptive tuberculosis cases screened for COVID-19, 17 (2.5%) were positive by antigen rapid diagnostic tests, and five (0.7%) who tested negative, later tested positive on the molecular testing platform (2483 COVID-19 cases per 100 000 individuals screened). Conclusion: Simultaneous screening for COVID-19 and tuberculosis in India is operationally feasible and can improve real-time on-site detection of COVID-19 and tuberculosis.

Retaining Patients with Drug-Resistant Tuberculosis on Treatment During the COVID-19 Pandemic - Dharavi, Mumbai, India, 2020-2022.

Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum†; historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies.

Impact of COVID-19 vaccination on transmission risk of breakthrough infections: Lessons from adapted N95 mask sampling for emerging variants and interventions.

This study used an adapted N95 mask sampling to understand the effect of COVID-19 vaccination in the context of circulating variants on infected individuals to emit the virus into the air, a key risk factor of transmission. Mask, swab, and blood samples were collected from 92 COVID-19 patients vaccinated (Covishield/COVAXIN-partial/fully) or unvaccinated between July and September 2021 during the Delta-dominated period in Mumbai. Mask/swab samples were analyzed by reverse transcription polymerase chain reaction for viral RNA. Blood was evaluated for SARS-CoV-2 anti-spike and nucleocapsid antibody responses. At <48 h of diagnosis, 93% of the patients emitted detectable viral RNA, with 40% emitting >1000 copies in 30 min (high emitters). About 8% continued to be high emitters even after 8 days of symptom onset. No significant difference was observed in emission patterns between partial, full, and unvaccinated patients. However, when vaccinated patients were stratified based on spike protein neutralization and nucleocapsid immunoglobulin G (IgG), the group with moderate/high neutralization showed a significantly lower proportion of high emitters and viral RNA copies than the group with no/low neutralization, which further reduced in the group having antinucleocapsid IgG. In conclusion, mask sampling showed that Delta infections were associated with greater virus emission in patients, which was significantly reduced only in vaccinated patients with moderate/high SARS-CoV-2 neutralization, especially with evidence of past infection. The study demonstrated that mask sampling could be useful for understanding the transmission risk of emerging variants, screening vaccine/booster candidates, and guiding control interventions.

Tuberculosis diagnosis and management in the public versus private sector: a standardised patients study in Mumbai, India.

BACKGROUND: There are few rigorous studies comparing quality of tuberculosis (TB) care in public versus private sectors. METHODS: We used standardised patients (SPs) to measure technical quality and patient experience in a sample of private and public facilities in Mumbai. RESULTS: SPs presented a 'classic, suspected TB' scenario and a 'recurrence or drug-resistance' scenario. In the private sector, SPs completed 643 interactions. In the public sector, 164 interactions. Outcomes included indicators of correct management, medication use and client experience. Public providers used microbiological testing (typically, microscopy) more frequently, in 123 of 164 (75%; 95% CI 68% to 81%) vs 223 of 644 interactions (35%; 95% CI 31% to 38%) in the private sector. Private providers were more likely to order chest X-rays, in 556 of 639 interactions (86%; 95% CI 84% to 89%). According to national TB guidelines, we found higher proportions of correct management in the public sector (75% vs 35%; (adjusted) difference 35 percentage points (pp); 95% CI 25 to 46). If X-rays were considered acceptable for the first case but drug-susceptibility testing was required for the second case, the private sector correctly managed a slightly higher proportion of interactions (67% vs 51%; adjusted difference 16 pp; 95% CI 7 to 25). Broad-spectrum antibiotics were used in 76% (95% CI 66% to 84%) of the interactions in public hospitals, and 61% (95% CI 58% to 65%) in private facilities. Costs in the private clinics averaged rupees INR 512 (95% CI 485 to 539); public facilities charged INR 10. Private providers spent more time with patients (4.4 min vs 2.4 min; adjusted difference 2.0 min; 95% CI 1.2 to 2.9) and asked a greater share of relevant questions (29% vs 43%; adjusted difference 13.7 pp; 95% CI 8.2 to 19.3). CONCLUSIONS: While the public providers did a better job of adhering to national TB guidelines (especially microbiological testing) and offered less expensive care, private sector providers did better on client experience.

Genomics of postvaccination SARS-CoV-2 infections during the Delta dominated second wave of COVID-19 pandemic, from Mumbai Metropolitan Region (MMR), India.

The present study was initiated to understand the proportion of predominant variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in postvaccination infections during the Delta dominated second wave of coronavirus disease 2019 (COVID-19) in the Mumbai Metropolitan Region (MMR) in India and to understand any mutations selected in the postvaccination infections or showing association with any patient demographics. Samples were collected (n = 166) from severe/moderate/mild COVID-19 patients who were either vaccinated (COVISHIELD/COVAXIN-partial/fully vaccinated) or unvaccinated, from a city hospital and from home isolation patients in MMR. A total of 150 viral genomes were sequenced by Oxford Nanopore sequencing and the data of 136 viral genomes were analyzed for clade/lineage and for identifying mutations. The sequences belonged to three clades (21A, 21I, and 21J) and their lineage was identified as either Delta (B.1.617.2) or Delta+ (B.1.617.2 + K417N) or sub-lineages of Delta variant (AY.120/AY.38/AY.99). A total of 620 mutations were identified of which 10 mutations showed an increase in trend with time (May-October 2021). Associations of six mutations (two in spike, three in orf1a, and one in nucleocapsid) were shown with milder forms of the disease and one mutation (in orf1a) with partial vaccination status. The results indicate a trend toward reduction in disease severity as the wave progressed.

COVID-19 Serological Survey-3 Prior to Second Wave in Mumbai, India.

Background: Subsequent to serosurveys 1 and 2 for COVID-19 carried out in three wards of Mumbai in July and August 2020, Municipal Corporation of Greater Mumbai conducted serosurvey 3 in March 2021. This was to identify the extent of exposure by testing specific IgG antibodies against COVID-19. Material and Methods: A cross-sectional study was conducted to find the prevalence of seropositivity in Mumbai, which included 10,197 samples belonging to patients visiting public dispensaries (slum population, 6006) and private (nonslum population, 4191) laboratories of Aapli Chikitsa network for blood investigations for non-COVID illnesses. The ward-wise number of unlinked anonymous samples from 24 wards was predecided by using probability proportionate sampling. The samples were collected using quota sampling technique as per predecided sample for each ward. These samples collected from nonimmunized individuals were tested for IgG antibodies at the Molecular Biology Laboratory of Kasturba Hospital for Infectious Diseases by chemiluminescence assay (CLIA) method. Results: The overall seropositivity was found to be 36.3% (41.6% in slum and 28.59% in nonslum population). It was more in city wards (38.28%) followed by western suburb (36.47%) and then eastern suburb wards (34.86%), matching with the proportion of cases in these wards during the study period. There was no significant difference in seropositivity among males and females and in different age groups. Conclusions: Seropositivity is higher in slum areas than nonslum areas. It has reduced in slum areas and increased in nonslum areas as compared to findings of serosurveys 1 and 2. This explains the detection of a greater number of cases from nonslum areas in the second wave. The average seropositivity of 36.3% justifies the necessity of immunization on a wider scale in the city. Periodic serosurveys are required at fixed intervals to monitor the trend of infection and level of herd immunity.

Interventions to respond to COVID 19 pandemic in Mumbai and way forward.

With the emergence of COVID 19 pandemic, the approach used by Municipal Corporation of Greater Mumbai (MCGM) was based on all guidelines of COVID 19 prepared by Ministry of Health and Family Welfare (MoHFW). However, Mumbai undertook a special innovate model used in the mission Mumbai - Dharavi for COVID 19. Additionally, MCGM undertook a proactive approach of "chasing the virus" with its 4Ts: 1. Tracing 2. Tracking 3. Testing 4. Treating in high-risk slum clusters and it reflects the result of declining the incidence and case fatality due to COVID 19. Establishing public health surge capacities which include active surveillance, contact-tracing and follow-up besides early detection, isolation and management of cases are important steps for fighting the COVID 19 pandemic. Collaborating with all partners and setting up a Task force for establishing clinical management protocols was unmissable.

Community transmission of SARS-CoV-2 with B.1.1.7 lineage in Mumbai, India.

The B.1.1.7 (Alpha) variant has been detected in Mumbai, India during February 2021. Subsequently, we retrieved 43 sequences from specimens of 51 COVID-19 cases from Mumbai. The sequence analysis revealed that the cases were mainly affected with Alpha variant which suggests its role in community transmission of SARS-CoV-2 in Mumbai, India.

Epidemiological study to assess the impact of COVID-19 pandemic on the occurrence of monsoon-related diseases in the city of Mumbai.

BACKGROUND: The onset of monsoons in Mumbai poses an additional health disease burden in the form of rising vector-borne and water-borne diseases such as dengue, malaria, leptospirosis, hepatitis, typhoid, chikungunya, and acute gastroenteritis. These monsoon-related illnesses are preventable with hygienic and sanitation measures that are likely to have been adopted during COVID-19 pandemic. AIM: To assess the impact of COVID-19 pandemic on the occurrence of monsoon-related diseases in the city of Mumbai and find out determinants of variations if any. MATERIAL AND METHODS: This was a retrospective descriptive study. Universal sampling was done using secondary data collected from the Epidemiological Cell of Municipal Corporation of Greater Mumbai (MCGM). Data mining was performed to obtain the trends of the monsoon-related diseases in Mumbai. RESULTS: COVID-19 pandemic has remarkably affected the city of Mumbai with approximately 3 lakh cases till December 2020. MCGM has taken a lot of efforts resulting in a recovery rate of close to 95% with less than 3% mortality. With the effective use of social behavior change communication, which focused on masks, frequent hand washing, and social distancing, there seems to be a decline in monsoon-related illnesses in the year 2020 as compared to the previous two years of 2018 and 2019. CONCLUSION: Monsoon-related illnesses are impacted by behavior and lifestyle modifications like hygiene and environmental sanitation practiced during the COVID-19 pandemic. This study highlights the importance of these universal hygienic practices and their utility in the long-term reduction of monsoon-related illnesses.

A critical appraisal of the maternal and child health scenario in a metropolitan city in India with reference to achievements of millennium development goals.

BACKGROUND: Post 2015, the Millennium Development Goals (MDGs) will undergo a transition to Sustainable Development Goals (SDGs). Therefore, it becomes necessary to assess the determinants influencing the present status of MDGs. This study was conducted to assess the progress, short comings related to the transition from MDGs to SDGs in a metropolitan city. It provides practical insights for extrapolating need based strategies related to the SDGs. METHODS: Study was conducted in a metropolitan city, Mumbai. Situational analysis of the city was done using monthly and annual performance reports and key informant's interviews at city level. Qualitative analysis was done using thematic analysis. RESULTS: The current infant mortality rate of Mumbai is 26.72 and under-five mortality rate is 38.7/1000 live births. The current MMR of mumbai is 88. The responses from the key informants' spanned three major themes: Concerns and challenges; Good practices and schemes in pipeline; and Opportunities envisioned. Eight major challenging areas were identified. Opportunities are sustainable models of public-private partnership; Involvement of NGOs and AYUSH practitioners; and IT sector involvement, HMIS, e- governance, and Corporate Social Responsibility (CSR). CONCLUSIONS: Significant progress has been made in the field of maternal and child health (MCH), and sustained efforts are required. Maternal mortality figures may be illusive because of the effect of migration and referral cases. Socio-demographic issues of development need to be addressed through governance. Mechanism for intersectoral coordination, IT support, surveillance, and tracking of pregnant mothers needs to be developed. The linkage of MCH services with developmental programs needed.

Antenatal tobacco use and iron deficiency anemia: integrating tobacco control into antenatal care in urban India.

BACKGROUND: In India, tobacco use during pregnancy is not routinely addressed during antenatal care. We measured the association between tobacco use and anemia in low-income pregnant women, and identified ways to integrate tobacco cessation into existing antenatal care at primary health centers. METHODS: We conducted an observational study using structured interviews with antenatal care clinic patients (n = 100) about tobacco use, anemia, and risk factors such as consumption of iron rich foods and food insecurity. We performed blood tests for serum cotinine, hemoglobin and ferritin. We conducted in-depth interviews with physicians (n = 5) and auxiliary nurse midwives (n = 5), and focus groups with community health workers (n = 65) to better understand tobacco and anemia control services offered during antenatal care. RESULTS: We found that 16% of patients used tobacco, 72% were anemic, 41% had iron deficiency anemia (IDA) and 29% were food insecure. Regression analysis showed that tobacco use (OR = 14.3; 95%CI = 2.6, 77.9) and consumption of green leafy vegetables (OR = 0.6; 95%CI = 0.4, 0.9) were independently associated with IDA, and tobacco use was not associated with consumption of iron-rich foods or household food insecurity. Clinics had a system for screening, treatment and follow-up care for anemic and iron-deficient antenatal patients, but not for tobacco use. Clinicians and community health workers were interested in integrating tobacco screening and cessation services with current maternal care services such as anemia control. Tobacco users wanted help to quit. CONCLUSION: It would be worthwhile to assess the feasibility of integrating antenatal tobacco screening and cessation services with antenatal care services for anemia control, such as screening and guidance during clinic visits and cessation support during home visits.