Household contacts, or individuals who live with another person with contagious tuberculosis (TB) disease, are at increased risk of becoming sick with TB disease themselves. Those at the highest risk include children under the age of five, people living with HIV, and people with previous TB infection, a state of TB where the bacteria lies dormant in the lungs. TB prevention treatment (TPT) can be given to household contacts to prevent the development of TB disease, however prevention in household contacts of people with multi-drug resistant tuberculosis (MDR TB – infection that doesn’t get better with standard treatments), is a particular challenge.
Through the PHOENIx (Protecting Households On Exposure To Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients) Feasibility Study, also known as A5300A/I2003, we previously found a high baseline TB infection prevalence of 72% and TB disease prevalence of 12% among child and adult household contacts of adults who had recently been diagnosed with rifampin-resistant (RR)/MDR TB. We tested individuals for past infection with TB by either a blood test called an interferon-gamma release assay (IGRA) or tuberculin skin test. We sought to evaluate and characterize the number of new cases (also known as the incidence) of TB infection and TB disease in household contacts of MDR TB after one year. TB infection was defined as IGRA conversion and TB disease was defined as a confirmed, probable, or possible event.
At one-year we re-assessed 850 participants from 247 households from 16 ACTG sites in 8 countries. A total of 52 individuals tested IGRA positive, for a one-year TB infection cumulative incidence of 21.6% (95%confidence interval [CI]; 16.7-27.4). There were 16 people with TB disease (confirmed [n = 5], probable [n = 3], or possible [n = 8]). The one-year cumulative incidence of TB disease was 2.3% (all events; 95% CI 1.4.3.8) and 1.1% (confirmed/probable events; 95% CI 0.5-2.4). The TB disease relative risk compared to the not high-risk group was:
- 11.5-fold (95% CI, 1.7–78.7) higher among children under the age of five
- 10.4-fold (95% CI, 2.4–45.6) higher among people living with HIV
- 2.9-fold (95% CI, .5–17.8) higher among people with baseline TB infection
At one year, only 4% (21 of 553) of high-risk household contacts had received TPT.
This study demonstrates the importance of ongoing household contact evaluation after MDR-TB exposure and provides key evidence of ongoing TB infection and TB disease development at one year. Importantly, the highest incidence of TB disease occurred among children under the age of 5 (7.0%) and people living with HIV (6.8%). Low TPT use in these high-risk population underscores the need for effective strategies to improve their use in high-burden regions and provides evidence for key groups to target in programmatic settings. PHOENIx is ongoing and will help address the TPT gap for RR/MDR TB contacts.
Reference:
Krishnan S, Wu X, Kim S, McIntire K, Naini L, Hughes MD, Dawson R, Mave V, Gaikwad S, Sanchez J, Mendoza-Ticona A, Gonzales P, Comins K, Shenje J, Fontain SN, Omozoarhe A, Mohapi L, Lalloo UG, Garcia Ferreira AC, Mugah C, Harrington M, Shah NS, Hesseling AC, Churchyard G, Swindells S, Gupta A; AIDS Clinical Trials Group A5300/International Maternal Pediatric Adolescent AIDS Clinical Trials I2003 Protecting Households on Exposure to Newly Diagnosed Index Multidrug-resistant Tuberculosis Patients Feasibility Study Team*(Additional study group members are listed in the Acknowledgment section).1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis. Clin Infect Dis. 2023 Sep18;77(6):892-900. doi: 10.1093/cid/ciad301. PMID: 37227925; PMCID: PMC10681643.