Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease

Author:

Gupta Amita12ORCID,Swindells Susan3,Kim Soyeon4,Hughes Michael D5,Naini Linda6,Wu Xingye5,Dawson Rodney7,Mave Vidya12,Sanchez Jorge8,Mendoza Alberto9,Gonzales Pedro8,Kumarasamy Nagalingeswaran10,Comins Kyla11,Conradie Francesca12,Shenje Justin13,Fontain Sandy Nerette14,Garcia-Prats Anthony15,Asmelash Aida16,Nedsuwan Supalert17,Mohapi Lerato18,Lalloo Umesh G19,Ferreira Ana Cristina Garcia20,Mugah Christopher21,Harrington Mark22,Jones Lynne4,Cox Samyra R1,Smith Betsy23,Shah N Sarita24,Hesseling Anneke C15,Churchyard Gavin252627

Affiliation:

1. Johns Hopkins University, Department of Medicine, Baltimore, Maryland

2. Byramjee Jeejeebhoy Government Medical College, Johns Hopkins University Clinical Research Site, Pune, India

3. University of Nebraska Medical Center, Omaha

4. Frontier Science & Technology Research Foundation, Amherst, New York

5. Harvard T. H. Chan School of Public Health, Boston, Massachusetts

6. Social & Scientific Systems, Silver Spring, Maryland

7. University of Cape Town Lung Institute and Department of Medicine, University of Cape Town, South Africa

8. Asociación Civil Impacta Salud y Educación, Lima, Peru

9. TASK Applied Science Clinical Research Site, Bellville, South Africa

10. Chennai Antiviral Research and Treatment Clinical Research Site, India

11. TASK Applied Science Clinical Research Site, Bellville

12. University of the Witwatersrand Helen Joseph Hospital, Johannesburg, South Africa

13. South African Tuberculosis Vaccine Initiative, Cape Town, South Africa

14. GHESKIO Centers Institute of Infectious Diseases and Reproductive Health, Port-au-Prince, Haiti

15. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa

16. Gaborone Clinical Research Site, Botswana

17. PHPT-Changrai Prachanukroh Hospital, Chiang Rai, Thailand

18. Soweto Clinical Research Site, University of the Witwatersrand, Johannesburg, South Africa

19. Durban International Clinical Research Site, Durban University of Technology, South Africa

20. Instituto Nacional de Infectologia – INI/Fiocruz, Brazil

21. Kenya Medical Research Institute, Kisumu

22. Treatment Action Group, New York, New York

23. National Institutes of Health, Bethesda, Maryland

24. US Centers for Disease Control and Prevention, Atlanta, Georgia

25. Aurum Institute, Parktown, South Africa

26. University of Witwatersrand, School of Public Health

27. Advancing Care and Treatment, South African Medical Research Council, Johannesburg, South Africa

Abstract

Abstract Background We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. Methods We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing. Results From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. Conclusions The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.

Funder

National Institute of Allergy and Infectious Diseases

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute of Mental Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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