Immune suppression associated with reduced risk of TB transmission to household contacts of people with HIV/TB co-infection

HIV-related immune suppression is associated with a reduced risk of tuberculosis (TB) transmission to household contacts, according to research published in the online edition of Clinical Infectious Diseases. Researchers in Lima, Peru, compared the risk of TB transmission to household contacts of people newly diagnosed with TB according to HIV infection status, and for the people with HIV, according to CD4 cell count. People living with HIV who had a CD4 cell count below 250 cells/mm³ were 50% less likely to transmit TB to contacts than people who did not have HIV.

“Our results suggest that HIV-induced immunosuppression reduces the risk of TB transmission from HIV co-infected index cases within households,” write the authors. “Possible biological explanations are that immunosuppressed patients are infectious for shorter periods of time and that the reduced TB bacillary load and tissue destruction typical of late stage HIV reduced the likelihood of spread.”

Globally, TB is a leading cause of death among people with HIV, and several studies have shown that HIV is contributing to worsening TB epidemics in a number of settings. However, the impact of HIV co-infection on the transmission of TB to household contacts is unclear. Some studies have shown that HIV co-infection status has no impact on the risk of transmission, whereas others have shown that people with HIV are less likely to pass on TB.

A possible reason for the inconsistency in study results is that many of the existing studies did not take into account the CD4 cell counts of the HIV-positive patients. Immune suppression has been associated with reduced TB infectiousness.

Taking this factor into account, investigators in Lima designed an observational study, comparing rates of TB transmission to household contacts according to HIV infection status, and, for the people with HIV according to immune suppression (CD4 cell count below vs above 250 cells/mm³).

All the index patients had sputum smear-positive TB and were diagnosed with the infection between September 2009 and August 2012.

Nurses visited household contacts and those with TB were identified using tuberculin skin tests. Contacts with previous active TB or a positive tuberculin skin test were excluded.

The study population comprised 1608 index patients (3% HIV positive) with active TB, and 4841 household contacts (2% HIV positive).

The prevalence of TB in household contacts was 45% in adults and 23% in children.

The factors associated with a positive tuberculin skin test among household contacts included three or more BCG vaccinations scars, being related to the index patients and living in an apartment or sub-standard accommodation. These factors remained significant in multivariate analysis.

This analysis also showed that household contacts of people with HIV with CD4 cell counts below 250 cells/mm³ were half as likely to have TB compared to contacts of HIV-negative TB patients (RR = 0.49; 95% CI, 0.24-0.96).

This finding was unaltered when the investigators controlled for sputum smear status, delay in initiating TB therapy, and cavitary disease status.

People living with HIV who had a CD4 cell count above 250 cell/mm³ were as likely to transmit TB to household contacts as HIV-negative patients (RR = 0.90; 95% CI, 0.55-1.47).

No child under the age of 15 who was exposed to an HIV-positive index patient with a CD4 cell count below 250 cells/mm³ was infected with TB, compared to 22% of those in contact with HIV-negative patients. The risk of TB infection for children exposed to a non-immune suppressed HIV-positive individual was not significantly different to the risk for children in contact with HIV-negative patients.

The investigators offer three explanations for the reduced infectiousness of TB patients with low CD4 cell counts:

• Shorter period of infectiousness, as immune suppression is associated with more rapid diagnosis or progression to death.
• Increased likelihood of being sputum smear negative and therefore less infectious.
• Lower risk of having lung tissue damage. The extent of damage has been associated with infectiousness in other research.

“We found that [household contacts] exposed to HIV-positive TB patients whose CD4 counts were < 250 cells/mm³ had half the risk of TB infection compared to [household contacts] exposed to HIV-negative index cases,” comment the investigators.