Recurrence of pulmonary tuberculosis in India: Findings from the 2019-2021 nationwide community-based TB prevalence survey.

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Prevalence and factors associated with tuberculosis infection in India.

BACKGROUND: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection. METHODS: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated. RESULTS: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 -25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29-1.73), being male (aRR:1.26; 95%CI: 1.18-1.34), residing in urban location (aRR:1.58; 95%CI: 1.03-2.43) and past history of TB (aRR:1.49; 95%CI: 1.26-1.76). CONCLUSION: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India.

Decline of Malaria Incidence in Three Villages of Thar Desert, India: The Impact of Use of Insecticide-Treated Nets.

Background: Malaria is the most important tropical and parasitic disease in the world. Endophagy of many malaria vectors advocates that impeding their entry into houses and preventing their contact with the occupants from infective bites could protect them against malaria. Methods: The study was carried out in Jaisalmer District, India and three villages were selected as test villages and three as control. Cross-sectional malaria prevalence surveys and mosquito collections were conducted in all the study villages. Insecticide-treated nets (ITNs) were tied below the beds for personal protection against the mosquito bite. Door and window curtains along with partition curtains were treated with insecticide for baring the entry of mosquito vectors. Results: Plasmodium vivax and P. falciparum were reported from the study villages. Higher malaria cases were detected in the control villages than the insecticide-treated bed net-distributed villages. The percentages of reduction of mosquito density in the houses of the ITNs distributed villages were significantly higher than the control villages. The insecticide activity was decreased slowly, and the knockdown time (KD50) values were found to be increased with the duration of usage of net. The KD50 of Anopheles subpictus s.l. was found to be more than the An. stephensi. Rooms where the ITNs were found to be significantly lower per man-hour density of mosquitoes. Conclusion: The use of alternative forms of ITNs shows a potential for preventing malaria and are making a significant contribution to the mosquito control. Effective use of ITNs could be helpful in the malaria elimination in India by 2030.

Immunity against diphtheria among children aged 5-17 years in India, 2017-18: a cross-sectional, population-based serosurvey.

BACKGROUND: Diphtheria is re-emerging as a public health problem in several Indian states. Most diphtheria cases are among children older than 5 years. In this study, we aimed to estimate age-specific immunity against diphtheria in children aged 5-17 years in India. METHODS: We used residual serum samples from a cross-sectional, population-based serosurvey for dengue infection done between June 19, 2017, and April 12, 2018, to estimate the age-group-specific seroprevalence of antibodies to diphtheria in children aged 5-17 years in India. 8309 serum samples collected from 240 clusters (122 urban and 118 rural) in 60 selected districts of 15 Indian states spread across all five geographical regions (north, northeast, east, west, and south) of India were tested for the presence of IgG antibodies against diphtheria toxoid using an ELISA. We considered children with antibody concentrations of 0·1 IU/mL or greater as immune, those with levels less than 0·01 IU/mL as non-immune (and hence susceptible to diphtheria), and those with levels in the range of 0·01 to less than 0·1 IU/mL as partially immune. We calculated the weighted proportion of children who were immune, partially immune, and non-immune, with 95% CIs, for each geographical region by age group, sex, and area of residence (urban vs rural). FINDINGS: 29·7% (95% CI 26·3-33·4) of 8309 children aged 5-17 years were immune to diphtheria, 10·5% (8·6-12·8) were non-immune, and 59·8% (56·3-63·1) were partially immune. The proportion of children aged 5-17 years who were non-immune to diphtheria ranged from 6·0% (4·2-8·3) in the south to 16·8% (11·2-24·4) in the northeast. Overall, 9·9% (7·7-12·5) of children residing in rural areas and 13·1% (10·2-16·6) residing in urban areas were non-immune to diphtheria. A higher proportion of girls than boys were non-immune to diphtheria in the northern (17·7% [12·6-24·2] vs 7·1% [4·1-11·9]; p=0·0007) and northeastern regions (20·0% [12·9-29·8] vs 12·9% [8·6-19·0]; p=0·0035). INTERPRETATION: The findings of our serosurvey indicate that a substantial proportion of children aged 5-17 years were non-immune or partially immune to diphtheria. Transmission of diphtheria is likely to continue in India until the immunity gap is bridged through adequate coverage of primary and booster doses of diphtheria vaccine. FUNDING: Indian Council of Medical Research.

SARS-CoV-2 antibody seroprevalence in India, August-September, 2020: findings from the second nationwide household serosurvey.

BACKGROUND: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. METHODS: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. FINDINGS: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case. INTERPRETATION: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country. FUNDING: Indian Council of Medical Research.

Seroprevalence of chikungunya virus infection in India, 2017: a cross-sectional population-based serosurvey.

BACKGROUND: Since its re-emergence in 2005, chikungunya virus (CHIKV) transmission has been documented in most Indian states. Information is scarce regarding the seroprevalence of CHIKV in India. We aimed to estimate the age-specific seroprevalence, force of infection (FOI), and proportion of the population susceptible to CHIKV infection. METHODS: We did a nationally representative, cross-sectional serosurvey, in which we randomly selected individuals in three age groups (5-8, 9-17, and 18-45 years), covering 240 clusters from 60 selected districts of 15 Indian states spread across all five geographical regions of India (north, northeast, east, south, and west). Age was the only inclusion criterion. We tested serum samples for IgG antibodies against CHIKV. We estimated the weighted age-group-specific seroprevalence of CHIKV infection for each region using the design weight (ie, the inverse of the overall probability of selection of state, district, village or ward, census enumeration block, and individual), adjusting for non-response. We constructed catalytic models to estimate the FOI and the proportion of the population susceptible to CHIKV in each region. FINDINGS: From June 19, 2017, to April 12, 2018, we enumerated 117 675 individuals, of whom 77 640 were in the age group of 5-45 years. Of 17 930 randomly selected individuals, 12 300 individuals participated and their samples were used for estimation of CHIKV seroprevalence. The overall prevalence of IgG antibodies against CHIKV in the study population was 18·1% (95% CI 14·2-22·6). The overall seroprevalence was 9·2% (5·4-15·1) among individuals aged 5-8 years, 14·0% (8·8-21·4) among individuals aged 9-17 years, and 21·6% (15·9-28·5) among individuals aged 18-45 years. The seroprevalence was lowest in the northeast region (0·3% [95% CI 0·1-0·8]) and highest in the southern region (43·1% [34·3-52·3]). There was a significant difference in seroprevalence between rural (11·5% [8·8-15·0]) and urban (40·2% [31·7-49·3]) areas (p<0·0001). The seroprevalence did not differ by sex (male 18·8% [95% CI 15·2-23·0] vs female 17·6% [13·2-23·1]; p=0·50). Heterogeneous FOI models suggested that the FOI was higher during 2003-07 in the southern and western region and 2013-17 in the northern region. FOI was lowest in the eastern and northeastern regions. The estimated proportion of the population susceptible to CHIKV in 2017 was lowest in the southern region (56·3%) and highest in the northeastern region (98·0%). INTERPRETATION: CHIKV transmission was higher in the southern, western, and northern regions of India than in the eastern and northeastern regions. However, a higher proportion of the population susceptible to CHIKV in the eastern and northeastern regions suggests a susceptibility of these regions to outbreaks in the future. Our survey findings will be useful in identifying appropriate target age groups and sites for setting up surveillance and for future CHIKV vaccine trials. FUNDING: Indian Council of Medical Research.

Hepatitis-B virus infection in India: Findings from a nationally representative serosurvey, 2017-18.

INTRODUCTION: India introduced a hepatitis-B (HB) vaccine in the Universal Immunization Program in 2002-2003 on a pilot basis, expanded to ten states in 2007-2008 (phase-1), and the entire country in 2011-2012 (phase-2). We tested sera from a nationally representative serosurvey conducted duing 2017, to estimate the seroprevalence of different markers of HB infection among children aged 5-17 years in India and to assess the impact of vaccination. METHODS: We tested sera from 8273 children for different markers of HB infection and estimated weighted age-group specific seroprevalence of children who were chronically infected (HBsAg and anti-HBc positive), and immune due to past infection (anti-HBc positive and HBsAg negative), and having serological evidence of HB vaccination (only anti-HBs positive). We compared the prevalence of serological markers among children born before (aged 11-17 years) and after (aged 5-10 years) introduction of HB-vaccine from phase-1 states. RESULTS: Among children aged 5-8 years, 1.1% were chronic carriers, 5.3% immune due to past infection, and 23.2% vaccinated. The corresponding proportions among children aged 9-17 years were 1.1%, 8.0%, and 12.0%, respectively. In phase-1 states, children aged 5-10 years had a significantly lower prevalence of anti-HBc (4.9% vs. 7.6%, p<0.001) and higher prevalence of anti-HBs (37.7% vs. 14.7%, p<0.001) compared to children aged 11-17 years. HBsAg positivity, however, was not different in the two age groups. CONCLUSIONS: Children born after the introduction of HB vaccination had a lower prevalence of past HBV infection and a higher prevalence of anti-HBs. The findings of our study could be considered as an interim assessment of the impact of the hepatitis B vaccine introduction in India.

Burden of dengue infection in India, 2017: a cross-sectional population based serosurvey.

BACKGROUND: The burden of dengue virus (DENV) infection across geographical regions of India is poorly quantified. We estimated the age-specific seroprevalence, force of infection, and number of infections in India. METHODS: We did a community-based survey in 240 clusters (118 rural, 122 urban), selected from 60 districts of 15 Indian states from five geographical regions. We enumerated each cluster, randomly selected (with an Andriod application developed specifically for the survey) 25 individuals from age groups of 5-8 years, 9-17 years, and 18-45 years, and sampled a minimum of 11 individuals from each age group (all the 25 randomly selected individuals in each age group were visited in their houses and individuals who consented for the survey were included in the study). Age was the only inclusion criterion; for the purpose of enumeration, individuals residing in the household for more than 6 months were included. Sera were tested centrally by a laboratory team of scientific and technical staff for IgG antibodies against the DENV with the use of indirect ELISA. We calculated age group specific seroprevalence and constructed catalytic models to estimate force of infection. FINDINGS: From June 19, 2017, to April 12, 2018, we randomly selected 17 930 individuals from three age groups. Of these, blood samples were collected and tested for 12 300 individuals (5-8 years, n=4059; 9-17 years, n=4265; 18-45 years, n=3976). The overall seroprevalence of DENV infection in India was 48·7% (95% CI 43·5-54·0), increasing from 28·3% (21·5-36·2) among children aged 5-8 years to 41·0% (32·4-50·1) among children aged 9-17 years and 56·2% (49·0-63·1) among individuals aged between 18-45 years. The seroprevalence was high in the southern (76·9% [69·1-83·2]), western (62·3% [55·3-68·8]), and northern (60·3% [49·3-70·5]) regions. The estimated number of primary DENV infections with the constant force of infection model was 12 991 357 (12 825 128-13 130 258) and for the age-dependent force of infection model was 8 655 425 (7 243 630-9 545 052) among individuals aged 5-45 years from 30 Indian states in 2017. INTERPRETATION: The burden of dengue infection in India was heterogeneous, with evidence of high transmission in northern, western, and southern regions. The survey findings will be useful in making informed decisions about introduction of upcoming dengue vaccines in India. FUNDING: Indian Council of Medical Research.

A Comparative Study of Energy Contents in Mosquito Vectors of Malaria and Dengue Prevailing in Jodhpur City (Thar Desert) of Rajasthan State, India.

BACKGROUND: Transmission of malaria and dengue in the desert part of India is mainly caused by Anopheles stephensi and Aedes aegypti respectively. The maintenance and transmission of the pathogens that cause malaria and dengue are dependent on the physiology of the mosquito vectors. We aimed to measure the energy contents in the mosquitoes transmitting malaria and dengue in the desert part of the country. METHODS: Immature stages of mosquitoes were collected from six different larval habitats situated in Jodhpur City of Rajasthan state, India. The immature stages of both the mosquitoes were collected once in fortnightly from each location. Quantitative estimations of the lipid, glucose, and glycogen of the laboratory-reared and field collected An. stephensi and Ae. aegypti were made by spectrophotometric method. The energy contents of the larvae, pupae, females, and males were estimated in triplicates on six different occasions. RESULTS: The lipid content of laboratory-reared larvae, pupae and female mosquitoes of An. stephensi and Ae. aegypti was found to be lower than their conspecific field-collected specimens. Whereas, the glycogen content in the laboratory-reared larvae, pupae and female mosquitoes of An. stephensi and Ae. aegypti was higher than that of their conspecific field-collected specimens. The glucose content in all the stages of the laboratory-reared An. stephensi was lower than their conspecific field-collected specimens except in few cases. CONCLUSION: The higher amount of lipid in field-collected mosquitoes may be because of the availability of food in the natural habitat and adaptation of mosquitoes. Mosquitoes living in desert climate are physiologically better equipped to survive in the desert environment.

Changes in glucose-6-phosphate dehydrogenase activity in Indian desert malaria vector Anopheles stephensi during aging.

Malaria parasite requires a specific time to replicate and disseminate in the mosquito's body before transmission to naïve hosts can occur. Vector control has a proven record in the prevention and control of malaria. The evaluation of vector control strategies requires accurate methods of predicting mosquito age. Anopheles stephensi is the principal malaria vector of the desert part of India. The objective of this study was to correlate the age of laboratory reared and field collected adults of An. stephensi with the glucose-6-phosphate dehydrogenase (g6pd) activity. The measurement of g6pd activity was carried out in a UV-vis spectrophotometer. The g6pd activity in the males and females An. stephensi was inversely proportional to their age. A significant correlation of the g6pd activity was recorded between the field collected and laboratory reared mosquitoes. The g6pd activity in the males An. stephensi was found to be significantly higher than the females. The finding of the present study is useful for the prediction of the age of males and females An. stephensi.

Comparative efficacy and pathogenicity of keratinophilic soil fungi against Culex quinquefasciatus larvae.

Out of seven fungal species belonging to four genera isolated from pond and wallow soils using feathers of Pavo cristatus as bait, four species viz., Aspergillus flavus, Aspergillus niger, Chrysosporium pseudomerdarium and Trichophyton ajelloi were most frequent. Chrysosporium and Trichophyton spp. were more pathogenic on Culex quinquefasciatus larvae than Aspergillus and Penicillium. The bioefficacy tests conducted as per the protocol of World Health Organization and the LC(50) values calculated by the Probit analysis showed that 3(rd)-instar C. quinquefasciatus were more susceptible to the conidia of above fungi. Highest mortality was observed in the larvae of C. quinquefasciatus when exposed to T. ajelloi. The density of fungal conidia was greatest on the ventral brush, palmate hair and anal region of the mosquito larvae after exposing for 72 hours. The potentiality of these fungi for use in the control of C. quinquefasciatus is discussed which can be exploited as a suitable biocontrol agent in the tropics.

Effects of culture media on larvicidal property of secondary metabolites of mosquito pathogenic fungus Chrysosporium lobatum (Moniliales: Moniliaceae).

In order to determine the potential role of secondary metabolites of Chrysosporium lobatum as a biological control agent for mosquitoes, effects of culture media on the larvicidal property of secondary metabolites was evaluated. The secondary metabolites of C. lobatum released in the Sabouraud's dextrose broth (SDB) and chitin broth (CB) were collected by filtering through Whatman No. 3 chr filter after 7 days of growth. First, second and third instars of Anopheles stephensi and Culex quinquefasciatus were exposed to six different concentrations of secondary metabolites for the calculation of LC(50) and LC(90) values. C. quinquefasciatus were more susceptible than A. stephensi to secondary metabolites in SDB and CB. The LC(50) and LC(90) values for first instars of both the mosquitoes were significantly lower than second and third instars. A significantly higher mortality was recorded in both the mosquitoes to the secondary metabolites in CB than SDB. In the field trial, secondary metabolites in CB reduced 56.3% of A. stephensi and 66.42% of C. quinquefasciatus populations after 5 days of application. The LT(50) of first instars of both the mosquitoes were lower than the second and third instars. The precipitates of the secondary metabolites were more effective to both the mosquitoes than the secondary metabolite and heat-shocked secondary metabolites. In addition, the insecticidal effect of the secondary metabolites was reduced after exposure for 5 min at 120 degrees C, suggesting that the bioactive compounds were proteinaceous. The secondary metabolites in CB contained proteases which may cause more mortality than the secondary metabolites in SDB.

Efficacy of culture filtrates of Metarhizium anisopliae against larvae of Anopheles stephensi and Culex quinquefasciatus.

Efficacy of culture filtrates of five strains of Metarhizium anisopliae isolated from insects were evaluated against Anopheles stephensi and Culex quinquefasciatus. The culture filtrates released from the strains of M. anisopliae in the YpSs and chitin broths were filtered and used for the bioassays after a growth of 7 days. Among the culture filtrates of five strains, M. anisopliae 892 was found to be more effective against both the mosquitoes. The LC(50) values of culture filtrates of M. anisopliae 892 in chitin broth was lower than the LC(50) of culture filtrates in YpSs broth against first and fourth instars of both the mosquitoes. The LC(50) values of culture filtrates were significantly different between first and fourth instars of A. stephensi (t test; P = 0.0001) and C. quinquefasciatus (t test; P = 0.02). The larvae of A. stephensi were more susceptible than C. quinquefasciatus except in two cases. This is the first report of efficacy of culture filtrates produced by M. anisopliae in chitin broth against mosquitoes and have potential as a biological control agent of mosquitoes.

Efficacy of female Culex quinquefasciatus with entomopathogenic fungus Fusarium pallidoroseum.

This study was conducted to isolate and identify natural entomopathogenic fungi from female Culex quinquefasciatus and to test their adulticidal activity. Field-collected female C. quinquefasciatus died early and were placed on a Saboraud's dextrose agar plates for growth and isolation of natural entomopathogenic fungi. The plates were maintained in an incubator at 24+/-2 degrees C for 3 days. Four fungal species were isolated in two genera namely, Aspergillus and Fusarium. The identified fungal species were A. niger, A. flavus, A. nidulans var acristatus (ITCC-6327.04), and F. pallidoroseum (ITCC-6324.06). Adult bioassays were carried out using spore-impregnated paper in WHO-holding tubes. F. pallidoroseum was found to be more effective than the others. Exposure of C. quinquefasciatus to spores of A. flavus and A. niger for 4 h caused 5.53% and 5.51% mortality in the mosquitoes within a week, respectively. All the female C. quinquefasciatus were killed within 4 days of exposure to F. pallidoroseum at a concentration of 1.11 x 10(10) conidia per m2. Significant difference of longevity was observed between the F. pallidoroseum-treated C. quinquefasciatus and control mosquitoes. The LT50 of F. pallidoroseum was 2.08 days for 4 h exposure to C. quinquefasciatus. Results of the present study confirm that F. pallidoroseum is one of the alternative biological control agents of adult mosquitoes.

Laboratory and field evaluation of the fungus Chrysosporium lobatum against the larvae of the mosquito Culex quinquefasciatus.

Eleven fungal species in three genera were isolated from the soil at Agra, India by the feather-baiting technique. Out of the 11 species, Chrysosporium lobatum Scharapov, a deuteromycetous (Moniliales: Moniliaceae) fungus, caused high mortality of Culex quinquefasciatus Say (Diptera: Culicidae) larvae in the laboratory. Laboratory and field trials were carried out to study the efficacy of C. lobatum against various instars of C. quinquefasciatus. In the laboratory bioassays, first, second and third instar larvae were assessed separately. Conidia of C. lobatum that were 15 days old were used both in laboratory and field bioassays. Six different concentrations were used in the laboratory bioassays (10, 10(3), 10(4), 5x10(4), 10(5) and 10(6) conidia/mL), and one concentration was tested in the field trials (10(6) conidia/mL). The LC50 values with 95% fiducial limits and probit equations were calculated by the probit analysis. Significant (analysis o.f variance (ANOVA): P<0.0001) mortality difference between the instars of C. quinquefasciatus was observed after 72 h of exposure to conidia of C. lobatum. The third instar C. quinquefasciatus were 319- and 25-fold more susceptible to C. lobatum (0.47x10(3) conidia/mL) than the first and second instars, respectively. The cuticle of the abdominal region and anal papillae were densely covered by the C. lobatum conidia. In the field trials, populations had declined significantly (t test, P=0.003) 15 days after inoculation in the four test pools. Significantly (t test, P=0.03) higher mortality was observed in the pools with water quality that was lower in total dissolved solids, hardness, chemical oxygen demand and conductivity. Based on the performance and survival in the trial, C. lobatum may be considered as a bio-control agent of mosquitoes.