Historical review of studies on the effect of treating latent tuberculosis.

Tuberculosis Preventive Therapy (TPT) is widely used in particular among high-risk populations such as close contacts and immunosuppressed people mostly in high-income settings. TPT is widely recommended for high-risk populations including HIV-infected and household contacts globally, but is not widely used. Historical trials on risk groups as well as the general population have documented a marked effect on reductions in incidence of active disease among those treated, as well as on prevalence of latent TB infection (LTBI) in populations where massive roll-out of TPT has previously taken place. This review summarizes the results of large historical trials conducted more than 50 years ago among Inuit and African populations as well as risk groups in the USA and Europe exhibiting similarities with current high-burden populations with current limited use of TPT. The trials demonstrated a 27-95% reduction in incidence of active TB among those receiving preventive treatment compared with placebo, with efficacy depending somewhat on length of treatment but mostly on adherence rates. It was possible to achieve satisfactory adherence rates in most of the trial populations and liver toxicity rates were generally low. The historical trials on preventive treatment for LTBI have documented that large-scale TPT is possible and effective even in high-burden populations in high-incidence areas and is therefore a relevant tool to consider in striving to eliminate the TB epidemic.

Simple Estimates for Local Prevalence of Latent Tuberculosis Infection, United States, 2011-2015.

We used tuberculosis genotyping results to derive estimates of prevalence of latent tuberculosis infection in the United States. We estimated <1% prevalence in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This method for estimating prevalence could be applied in any jurisdiction with an established tuberculosis surveillance system.

Clemens von Pirquet: A Remarkable Life and Career.

From 1908 to 1929, Clemens von Pirquet was one of the world's most acclaimed pediatricians. Von Pirquet (1874-1929) trained at Vienna's Universitäts Kinderklinic under Theodor Escherich, the first Pediatric Infectious Diseases physician [1], and became the first Professor and Chair of Pediatrics at Johns Hopkins in 1909. He then succeeded his mentor Escherich as Professor and Chair of Pediatrics in Vienna, the most prestigious European pediatric position, when Escherich died unexpectedly in 1911. He held that position in Vienna until his shocking double suicide at age 54 with his wife in 1929. Von Pirquet's pioneering contributions from 1903 to 1910 related to host reactions to foreign substances, providing much of the foundation for modern "Immunology". In 1905, he and his student Bela Schick described and named "serum sickness" in children administered animal antiserum. He recognized that animal antiserum resulted in both protection against an infection but also sensitization (sometimes with serious or fatal consequences), ie, that immune responses caused some diseases. In 1906, he proposed the term "allergy" for the altered reactivity induced by what he termed an "allergen", a foreign substance. He recognized that sensitization to an allergen leads to accelerated responses on subsequent allergen administration, analogous to differences between primary and subsequent smallpox vaccine responses. In 1908, von Pirquet presented his invention, the "tuberculin skin test", recognizing its ability to identify individuals with previous tuberculosis infection, then the most prevalent infectious disease. This led to the new understanding that many or most tuberculosis-infected individuals are asymptomatic but at risk for future active disease, introducing the concept of "latent tuberculosis". Von Pirquet was a consummate pediatrician-scientist, translating scientific discoveries directly into improved care of children, and he also pioneered study of the social, nutritional, and public health aspects of pediatrics, especially during and after World War I.