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5. Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

Author

Gafar, F., Wasmann, R.E., McIlleron, H.M., Aarnoutse, R.E., Schaaf, H.S., Marais, B.J., Agarwal, D., Antwi, S., Bang, N.D., Bekker, A., Bell, D.J., Chabala, C., Choo, L., Davies, G.R., Day, J.N., Dayal, R., Denti, P., Donald, P.R., Engidawork, E., Garcia-Prats, A.J., Gibb, D., Graham, S.M., Hesseling, A.C., Heysell, S.K., Idris, M.I., Kabra, S.K., Kinikar, A., Kumar, A.K.H., Kwara, A., Lodha, R., Magis-Escurra, C., Martinez, N., Mathew, B.S., Mave, V., Mduma, E., Mlotha-Mitole, R., Mpagama, S.G., Mukherjee, A., Nataprawira, H.M., Peloquin, C.A., Pouplin, T., Ramachandran, G., Ranjalkar, J., Roy, V., Ruslami, Rovina, Shah, I., Singh, Y., Sturkenboom, M.G., Svensson, E.M., Swaminathan, S., Thatte, U., Thee, S., Thomas, T.A., Tikiso, T., Touw, D.J., Turkova, A., Velpandian, T., Verhagen, L.M., Winckler, J.L., Yang, H., Yunivita, V., Taxis, K., Stevens, J., Alffenaar, J.C., Gafar, F., Wasmann, R.E., McIlleron, H.M., Aarnoutse, R.E., Schaaf, H.S., Marais, B.J., Agarwal, D., Antwi, S., Bang, N.D., Bekker, A., Bell, D.J., Chabala, C., Choo, L., Davies, G.R., Day, J.N., Dayal, R., Denti, P., Donald, P.R., Engidawork, E., Garcia-Prats, A.J., Gibb, D., Graham, S.M., Hesseling, A.C., Heysell, S.K., Idris, M.I., Kabra, S.K., Kinikar, A., Kumar, A.K.H., Kwara, A., Lodha, R., Magis-Escurra, C., Martinez, N., Mathew, B.S., Mave, V., Mduma, E., Mlotha-Mitole, R., Mpagama, S.G., Mukherjee, A., Nataprawira, H.M., Peloquin, C.A., Pouplin, T., Ramachandran, G., Ranjalkar, J., Roy, V., Ruslami, Rovina, Shah, I., Singh, Y., Sturkenboom, M.G., Svensson, E.M., Swaminathan, S., Thatte, U., Thee, S., Thomas, T.A., Tikiso, T., Touw, D.J., Turkova, A., Velpandian, T., Verhagen, L.M., Winckler, J.L., Yang, H., Yunivita, V., Taxis, K., Stevens, J., and Alffenaar, J.C.

Abstract

Item does not contain fulltext, BACKGROUND: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. METHODS: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC(0-24)) and peak plasma concentration (C (max)) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC(0-24) and C (max) were assessed with linear mixed-effects models. RESULTS: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC(0-24) were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L(-1)), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L(-1)), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L(-1)) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L(-1)). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC(0-24) for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC(0-24) for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC(0-24) and slow acetylators had higher isoniazid AUC(0-24) than intermediate acetylators. Determinants of C (max) were generally similar to those for AUC(0-24). CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specif

Published
2023

6. Survival of Persons Living With HIV/AIDS: A Multicentric Study From India

Author

Sinha, Sanjeev, primary, Abdul Samad, Sameer, additional, Bansal, Garima, additional, Verma, Saurav, additional, Sangle, Shashikala Anant, additional, Guha, Subhasish Kamal, additional, Rajput, Neetu, additional, Pandey, Ravindra Mohan, additional, Ranjan, Sanjay, additional, Salvi, Sonali, additional, Mundhe, Sanjay, additional, More, Monika, additional, Modak, Dolanchampa, additional, Datta, Kalpana, additional, Kabra, S.K., additional, Lodha, Rakesh, additional, Nischal, Neeraj, additional, and Das, Bimal Kumar, additional

Published
2023
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9. Response

Author

Jat, Kana Ram, primary, Ghimire, Jagat Jeevan, additional, Lodha, Rakesh, additional, and Kabra, S.K., additional

Published
2022
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10. The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study

Author

García-Marcos, L. Asher, M.I. Pearce, N. Ellwood, E. Bissell, K. Chiang, C.-Y. El Sony, A. Ellwood, P. Marks, G.B. Mortimer, K. Martínez-Torres, A.E. Morales, E. Perez-Fernandez, V. Robertson, S. Rutter, C.E. Silverwood, R.J. Strachan, D.P. Masekela, R. Badellino, H. Urrutia-Pereira, M. Ndikum, A.E. Mallol, J. Soto-Martínez, M.E. Cabrera Aguilar, A. Douros, K. Sosa Ferrari, S.M. Mohammad, S. Singh, M. Singh, V. Ghoshal, A.G. Sukumaran, T.U. Awasthi, S. Mahesh, P.A. Kabra, S.K. Salvi, S. Tavakol, M. Behniafard, N. Alomary, S.A. Bucaliu-Ismajli, I. Pajaziti, L. Gashi, V. Kurhasani, X. Gacaferri-Lumezi, B. Ahmetaj, L.N. Zhjeqi, V. Sanchez Coronel, M.G. Moreno Gardea, H.L. Ochoa-Lopez, G. García-Almaráz, R. Sacre Hazouri, J.A. Rodriguez-Perez, N. Mérida-Palacio, J.V. Del Río Navarro, B.E. Hernández-Mondragón, L.O. González-Díaz, S.N. Garcia-Muñoz, R. Pineda, M.J. García, B.R. Escalante-Dominguez, A.J. Linares-Zapién, F.J. Navarrete-Rodriguez, E.M. Santos Lozano, J. Asher, I. Sánchez, J.F. Falade, A.G. Brożek, G. Kyzmicheva, K. Zar, H.J. López-Silvarrey Varela, A. González Díaz, C. Bercedo Sanz, A. Pellegrini Belinchon, J. Ranasinghe, J.C. Kudagammana, S.T. El Sadig, H. Nour, M. Alkhayer, G. Dib, G. Mohammad, Y. Huang, J. Chinratanapisit, S. Solé, D. Soto-Quirós, M.E. Althagafi, W.A. Vichyanond, P. The Global Asthma Network Phase I Study Group Global Asthma Network Study Group Global Asthma Network Steering Group Global Asthma Network Principal Investigators and García-Marcos, L. Asher, M.I. Pearce, N. Ellwood, E. Bissell, K. Chiang, C.-Y. El Sony, A. Ellwood, P. Marks, G.B. Mortimer, K. Martínez-Torres, A.E. Morales, E. Perez-Fernandez, V. Robertson, S. Rutter, C.E. Silverwood, R.J. Strachan, D.P. Masekela, R. Badellino, H. Urrutia-Pereira, M. Ndikum, A.E. Mallol, J. Soto-Martínez, M.E. Cabrera Aguilar, A. Douros, K. Sosa Ferrari, S.M. Mohammad, S. Singh, M. Singh, V. Ghoshal, A.G. Sukumaran, T.U. Awasthi, S. Mahesh, P.A. Kabra, S.K. Salvi, S. Tavakol, M. Behniafard, N. Alomary, S.A. Bucaliu-Ismajli, I. Pajaziti, L. Gashi, V. Kurhasani, X. Gacaferri-Lumezi, B. Ahmetaj, L.N. Zhjeqi, V. Sanchez Coronel, M.G. Moreno Gardea, H.L. Ochoa-Lopez, G. García-Almaráz, R. Sacre Hazouri, J.A. Rodriguez-Perez, N. Mérida-Palacio, J.V. Del Río Navarro, B.E. Hernández-Mondragón, L.O. González-Díaz, S.N. Garcia-Muñoz, R. Pineda, M.J. García, B.R. Escalante-Dominguez, A.J. Linares-Zapién, F.J. Navarrete-Rodriguez, E.M. Santos Lozano, J. Asher, I. Sánchez, J.F. Falade, A.G. Brożek, G. Kyzmicheva, K. Zar, H.J. López-Silvarrey Varela, A. González Díaz, C. Bercedo Sanz, A. Pellegrini Belinchon, J. Ranasinghe, J.C. Kudagammana, S.T. El Sadig, H. Nour, M. Alkhayer, G. Dib, G. Mohammad, Y. Huang, J. Chinratanapisit, S. Solé, D. Soto-Quirós, M.E. Althagafi, W.A. Vichyanond, P. The Global Asthma Network Phase I Study Group Global Asthma Network Study Group Global Asthma Network Steering Group Global Asthma Network Principal Investigators

Abstract

Aims There have been no worldwide standardised surveys of prevalence and severity of asthma, rhinoconjunctivitis and eczema in school children for 15 years. The present study aims to provide this information. Methods Following the exact International Study of Asthma and Allergies in Childhood (ISAAC) methodology (cross-sectional questionnaire-based survey), Global Asthma Network (GAN) Phase I was carried out between 2015 and 2020 in many centres worldwide. Results The study included 157784 adolescents (13-14 years of age) in 63 centres in 25 countries and 101777 children (6-7 years of age) in 44 centres in 16 countries. The current prevalence of symptoms, respectively, was 11.0% and 9.1% for asthma, 13.3% and 7.7% for rhinoconjunctivitis and 6.4% and 5.9% for eczema. The prevalence of asthma ever was 10.5% and 7.6%, hay fever ever was 15.2% and 11.1% and eczema ever was 10.6% and 13.4%, respectively. Centres in low or lower middle gross national income countries (LICs or LMICs) had significantly lower prevalence of the three disease symptoms and diagnoses (except for hay fever). In children, the prevalence of asthma and rhinoconjunctivitis symptoms was higher in boys, while the reverse occurred among adolescents. For eczema, while the prevalence among female adolescents was double that of males, there was no sex difference among children. Centre accounted for non-negligible variability in all disease symptoms (10-20%). Conclusion The burdens of asthma, rhinoconjunctivitis and eczema vary widely among the limited number of countries studied. Although symptom prevalence is lower in LICs and LMICs, it represents a considerable burden everywhere studied. © The authors 2022.

Published
2022

15. Effect of micronutrient deficiency on QuantiFERON-TB gold In-Tube test and tuberculin skin test in diagnosis of childhood intrathoracic tuberculosis

Author

Mukherjee, A., Saini, S., Kabra, S.K., Gupta, N., Singh, V., Singh, S., Bhatnagar, S., Saini, D., Grewal, H.M.S., and Lodha, R.

Subjects
Diagnosis, Physiological aspects, Methods, Health aspects, Micronutrients -- Physiological aspects -- Health aspects, Pediatric diseases -- Diagnosis, Skin tests -- Methods, Medical research, Tuberculosis -- Diagnosis, Children -- Diseases, Medicine, Experimental
Abstract

INTRODUCTION Childhood tuberculosis (TB) is a common cause of morbidity in developing countries. It is a challenging disease, difficult to diagnose, as the gold standard diagnostic test of demonstration of [...], BACKGROUND/OBJECTIVES: Data on performance of QuantiFERON-TB Gold In-Tube test (QFT) and tuberculin skin test (TST) in children with active tuberculosis from high burden countries in the context of micronutrient deficiency are scarce. The objective of this study was to evaluate the effect of micronutrient deficiency on the performance of TST and QFT in children with intrathoracic tuberculosis. SUBJECTS/METHODS: Children with probable intrathoracic tuberculosis underwent TST, QFT, gastric lavages and induced sputum examination for AFB (Acid-Fast Bacilli) smear and culture. Zinc, copper, ferritin and vitamin D were measured on stored serum samples. The study used cross-sectional data at initiation of anti-tubercular therapy. RESULTS: Three hundred and sixty-two children (median age 115.5 months (interquartile range: 73, 144), 200 (55.3%) girls) were enrolled in the study. Microbiological confirmation of tuberculosis could be obtained in 128 patients. TST and QFT were positive in 337 (93%) and 297 (82%) children, respectively. Performance of both the tests was unaffected by weight-for-age and height-for-age 'z-scores' or by serum copper levels. TST was not affected by serum zinc and ferritin levels. Children with negative QFT results had lower mean serum zinc level (P = 0.01) and higher ferritin levels (P = 0.007) as compared to those with positive test. Higher proportion of children with positive TST were vitamin D deficient/insufficient (P = 0.003). CONCLUSION: Micronutrient status, especially serum levels of zinc, may influence the performance of QFT in children with intrathoracic tuberculosis. Considering the high prevalence of zinc deficiency in developing countries, QFT should be used cautiously for diagnosing tuberculosis. European Journal of Clinical Nutrition (2014) 68, 38-42; doi: 10.1038/ejcn.2013.216; published online 30 October 2013 Keywords: pediatric tuberculosis; tuberculin skin test; interferon gamma release assay; zinc deficiency; vitamin D status

Published
2014
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21. Dengue haemorrhagic fever in children in Delhi

Author

Kabra, S.K., Verma, I.C., Arora, N.K., Jain, Y., and Kalra, V.

Subjects
Dengue -- Diagnosis, Delhi, India (City) -- Health aspects
Abstract

An epidemic of dengue haemorrhagic fever occurred in Delhi during 1988. A total of 21 paediatric patients with dengue haemorrhagic fever/dengue shock syndrome were evaluated from September to November 1988. All the patients had fever, restlessness, ecchymotic spots and ascites. Pleural effusion occurred in 19 patients (90%), and 18 (86%) exhibited each of the following: vomiting, thrombocytopenia, and haemoconcentration. Hepatomegaly was observed in 15 patients (71%) and splenomegaly in three (14%). Titres of haemagglutination inhibition (HI) antibodies against dengue virus type 2 were raised in all the 15 cases from whom sera were collected during the acute stage. Convalescent sera from five patients had increased titres of HI antibodies to dengue virus type 2. The remaining 10 cases exhibited raised IgM antibody levels against dengue virus type 2. The fatality rate for serologically proven cases was 13% (2 of 15 patients), while for all patients (including those diagnosed clinically (6) and serologically (15)) it was 33.3% (7 of 21). Patients who survived had no sequelae, except one who had transient hypertension that lasted for two weeks.

Published
1992

29. Abstract P-367

Author

Shubham, S., primary, Lodha, R., additional, Kabra, S.K., additional, Gulati, S., additional, Jaryal, A.K., additional, Sankar, J., additional, Chakrabarty, B., additional, Singh, A., additional, Dhochak, N., additional, and Patel, S.K., additional

Published
2018
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31. Multiple locus sequence typing of Salmonella Typhi, isolated in north India - a preliminary study

Author

Dahiya, Sushila, Kapil, Arti, Kumar, Ramesh, Das, Bimal Kumar, Sood, Seema, Chaudhry, Rama, Kabra, S.K., and Lodha, R.K.

Subjects
sequence type, Genotype, India, Multi locus sequence typing, Microbial Sensitivity Tests, Sequence Analysis, DNA, Salmonella typhi, bacterial infections and mycoses, Anti-Bacterial Agents, Drug Resistance, Multiple, Bacterial, Salmonella Infections, bacteria, Humans, Original Article, Typhoid Fever, Phylogeny, Multilocus Sequence Typing
Abstract

Background & objectives: In India enteric fever is a major public health problem and Salmonella Typhi is the most common aetiologic agent. Any control strategy for such infections depends to a large extent on the understanding of the disease and relatedness of strains across the world. Multi locus sequence typing (MLST) is one such method of genotyping of bacteria based upon housekeeping genes of known function and chromosome position. MLST data of pathogens are important to determine the molecular evolution by a stable and reproducible method. This study was undertaken to determine the sequence types of representatives S. Typhi isolates obtained from enteric fever patients in a tertiary care centre in north India, over a period of 20 years (1990-2010). Methods: A total of 30 representative isolates of S. Typhi identified by biochemical and serological tests were subjected to multi locus sequence typing (MLST). Seven housekeeping genes of known function and chromosome position were used for the typing by MLST. Sequencing was carried out by using an automated DNA sequencer and results were analyzed to generate phylogenetic tree. Results: MLST pattern grouped S. Typhi into two sequence types- ST1 and ST2. ST1 was predominantly present followed by ST2. Interpretation & conclusions: By MLST the presence of both sequence types, ST1 and ST2, was found in S. Typhi isolates in our region. Predominately ST1 was present followed by ST2. These preliminary results corroborate the global distribution of both sequence types of S. Typhi and also emphasize for the continuous screening of S. Typhi.

Published
2013

34. Longitudinal analysis of early HIV-1-specific neutralizing activity and mapping epitope specificities in plasma of chronic HIV-1 clade C infected ART naïve children from India

Author

Makhdoomi, Muzamil A., primary, Nair, Ambili, additional, Kumar, Sanjeev, additional, Aggarwal, Heena, additional, Sharma, Sonal, additional, Lodha, Rakesh, additional, Singh, Ravinder, additional, Shah, Nipum, additional, Kabra, S.K., additional, Luthra, Kalpana, additional, and Singla, Mohit, additional

Published
2016
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40. ABSTRACT 250

Author

Lodha, R., primary, Shah, R., additional, Gupta, N., additional, Irshad, M., additional, and Kabra, S.K., additional

Published
2014
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42. 749

Author

Shah, Satish, primary, Irshad, M., additional, Nandita, Gupta, additional, Kabra, S.K, additional, and Lodha, Rakesh, additional

Published
2013
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