Journal Club 11142018

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

• Latent TB and Progression to Active TB: Comparing Available Diagnostic Tests
• Reaching Zero: What Proportion of HAIs Remain Preventable?
• Tdap During Pregnancy: Safe and Protective but Blunts Infant Response to Active Immunization

Latent TB and Progression to Active TB: Comparing Available Diagnostic Tests

Reviewed by Daniel Mendoza, MD, PhD

Persons with latent tuberculosis infection (LTBI) have a 10 percent lifetime risk for progressing to active TB; half of that risk is during the first 2 years after infection (1). This information is mostly based on studies conducted in endemic countries with high rates of reinfection. Large studies in countries with low incidence of TB where reinfection risk is low are needed to determine the rates of active TB among subjects with LTBI diagnosed by currently available tests.

In Lancet Infectious Diseases, Abubakar et al recently described a prospective cohort study conducted in the UK. The authors recruited 10,045 subjects aged 16 years and older; 50.6 percent of them were contacts of cases with active TB and 49.4 percent were migrants from endemic countries. Each participant was tested with QuantiFERON-TB Gold, T-SPOT.TB, and a Mantoux test (TST). Participants were followed for a median of 2.9 years. The participants did not take preventive treatment, and 6,380 participants (66.4 percent) completed all tests and follow-up and were included in the primary analysis.

The annual incidence of TB was very low in those who tested negative, ranging from 1.2 per 1,000 person-years (95 percent confidence interval [CI], 0.6–2.0) for TST < 5 mm to 1.9 per 1,000 person-years (95 percent CI, 1.3–2.7) for QuantiFERON-TB Gold. Annual incidence in participants who tested positive was 13.2 per 1,000 person-years (95 percent CI, 9.9–17.4) for T-SPOT.TB, 11.1 per 1,000 person-years (95 percent CI, 8.3–14.6) for TST > 15 mm, and 10.1 per 1,000 person-years (95 percent CI, 7.4–13.4) for QuantiFERON-TB Gold.

This study is the largest head-to-head comparison of the three available diagnostic tests for LTBI, both in terms of the number of participants and cases with progression to active TB. The results indicate that among persons with LTBI, the overall risk for development of active TB is around 1 percent per year in a non-endemic country with a low risk for reinfection. The results are important to consider when making a decision regarding treatment of LTBI and reduction of transmission, as serious liver injury due to isoniazid or rifampin can occur in 0.3-1.7 percent of treated subjects (2,3).

(Abubakar et al. Lancet Infect Dis. 2018;18(10):1077-87.)

Additional References

1. Ann Intern Med. 2017;166(3):ITC17-ITC32.
2. LoBue and Moser. Am J Respir Crit Care Med. 2003;168(4):443-7.
3. Menzies et al. New Engl J Med. 2018;379(5):440-53.

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Reaching Zero: What Proportion of HAIs Remain Preventable?

Reviewed by Terri Stillwell, MD

With ongoing focus on patient safety and improvements in healthcare delivery, in recent years we have seen significant reductions in national healthcare-associated infection (HAI) rates. Advances in infection prevention efforts have led to smaller HAI numbers, leaving many to wonder if the goal of zero HAIs is attainable and how many remaining HAIs are truly preventable. In a recent systematic review and meta-analysis published in Infection Control & Hospital Epidemiology, the authors evaluated what proportion of HAIs can be considered preventable.

This literature review and meta-analysis included 144 studies performed in various countries and published from 2005 to 2016. To be included, a study needed to assess the impact of a multifaceted intervention (at least two or more interventions) aimed at reducing HAIs, with the infection rate being a noted outcome. The studies’ patient populations were primarily adults.

 In the studies looking at reduction in catheter-associated urinary tract infection rates, multifaceted infection prevention interventions, when compared to standard of care, had a pooled incidence rate ratio (IRR) of 0.543 (95 percent confidence interval [CI], 0.445-0.662). Central-line-associated bloodstream infection reduction studies revealed a pooled IRR of 0.459 (95 percent CI, 0.381-0.554). Ventilator-associated pneumonia reduction efforts resulted in a pooled IRR of 0.553 (95 percent CI, 0.465-0.657). Reductions in infection rates were seen across all countries involved in the studies.

As with many meta-analyses, heterogeneity between the studies and risk of bias limit interpretations. However, given available information, it appears there is potential for further reduction in HAIs, even in the setting of current advances in global infection prevention efforts. This study suggests that 35 to 55 percent of recent HAIs remain preventable, noting room for improvement in implementing current evidence-based interventions.

(Schreiber et al. Infect Control Hosp Epidemiol. 2018;39(11):1277-95.)

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Tdap During Pregnancy: Safe and Protective but Blunts Infant Response to Active Immunization

Reviewed by Jennifer Brown, MD

Receipt of the tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy is recommended to protect newborns via transplacental antibody transfer. In the October 1 issue of Clinical Infectious Diseases, Halperin et al reported the results of their study that examined the safety and immunogenicity of Tdap given during pregnancy and newborn post-immunization antibody responses. In this observer-blind trial, pregnant women were randomized to receive Tdap or tetanus-diphtheria (Td) in the third trimester. Maternal post-immunization serology and umbilical cord blood were obtained post-delivery. Maternal and infant sera were collected at the infants’ immunization visits (2, 4, 6, and 12 months of age) and 1 month after the primary vaccine series (7 months of age). Infant sera was also collected 1 month after their booster dose (13 months of age).

At all post-immunization time points Tdap-immunized women had higher concentrations of antibodies against the pertussis vaccine components (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae [FIM]) than did Td-immunized women. Compared with infants of Td recipients, infants of Tdap recipients had higher concentrations of all pertussis antibodies at birth and at 2 months of age; they also had higher FHA, PRN, and FIM antibody concentrations at 4 months. Thereafter, infants of Tdap recipients had lower antibody concentrations than did infants of Td recipients for: PT and FHA antibodies at 6 months; PT, FHA, PRN, and FIM antibodies at 7 months and 12 months (pre-booster); and PT, FHA, and FIM antibodies at 13 months (post-booster). Differences in adverse events, congenital abnormalities, neonatal complications, or infant tetanus and diphtheria antibody concentrations were not observed.

The multicenter trial, which was conducted in Canadian institutions, may not be generalizable to other populations. Nonetheless, this study highlights that Tdap given in pregnancy provides protective antibodies to newborns, but it can also blunt infant response to active immunization.

(Halperin et al. Clin Infect Dis. 2018;67(7):1063-71.)

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