Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil

Jones-López, Edward C.; Acuña-Villaorduña, Carlos; Fregona, Geisa; Marques-Rodrigues, Patrícia; White, Laura F.; Hadad, David Jamil; Dutra-Molina, Lucilia Pereira; Vinhas, Solange Alves; Gaeddert, Mary; Ribeiro‐Rodrigues, Rodrigo; Salgame, Padmini; Palaci, Moisés; Alland, David; Ellner, Jerrold J.; Dietze, Reynaldo

doi:10.1186/s12879-017-2675-3

Cited by 16 publications

(17 citation statements)

References 28 publications

(48 reference statements)

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“…These results were then used to estimate the range of possible mutation rates and generation times of M. tuberculosis during LTBI. In a previously described HHC study performed in Vitória, Brazil between February 2008 and October 2013 22 , we had identified 160 households that fit the case definition of containing a highly infectious case of acid-fast bacilli (AFB) smear-positive pulmonary TB, had at least three HHCs, and did not fulfill any exclusion criteria. Between the beginning of the HHC study in 2008 and the end of the study in 2015, 72 HHCs associated with 62 of these ICs were found to have developed active TB ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We obtained M. tuberculosis cultures from participants enrolled in a HHC study performed at the Núcleo do Doenças Infecciosas (NDI) located in Vitória, the capital city of the State of Espírito Santo, Brazil. Participant enrollment and sample collection has been described 22 . In brief, the NDI has organized a network of 16 TB clinics in the metropolitan region of Vitória 28 , which facilitated the identification of index TB cases as well as secondary TB cases in HHCs after initial ascertainment.…”

Section: Methodsmentioning

confidence: 99%

“…In brief, the NDI has organized a network of 16 TB clinics in the metropolitan region of Vitória 28 , which facilitated the identification of index TB cases as well as secondary TB cases in HHCs after initial ascertainment. All consecutive HIV-uninfected, pulmonary TB patients attending NDI clinics with a first episode of TB and a sputum with ≥2+ AFB smear and ≥3 HHCs who did not meet previously described exclusion criteria 22 were eligible for enrollment as IC. A HHC was defined using culturally adapted criteria of close contact 22 .…”

Section: Methodsmentioning

confidence: 99%

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Mycobacterium tuberculosis progresses through two phases of latent infection in humans

et al. 2020

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Little is known about the physiology of latent Mycobacterium tuberculosis infection. We studied the mutational rates of 24 index tuberculosis (TB) cases and their latently infected household contacts who developed active TB up to 5.25 years later, as an indication of bacterial physiological state and possible generation times during latent TB infection in humans. Here we report that the rate of new mutations in the M. tuberculosis genome decline dramatically after two years of latent infection (two-sided p < 0.001, assuming an 18 h generation time equal to log phase M. tuberculosis, with latency period modeled as a continuous variable). Alternatively, assuming a fixed mutation rate, the generation time increases over the latency duration. Mutations indicative of oxidative stress do not increase with increasing latency duration suggesting a lack of host or bacterial derived mutational stress. These results suggest that M. tuberculosis enters a quiescent state during latency, decreasing the risk for mutational drug resistance and increasing generation time, but potentially increasing bacterial tolerance to drugs that target actively growing bacteria.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Mycobacterium tuberculosis progresses through two phases of latent infection in humans

et al. 2020

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“…As illustrated in Table 1 , studies with at least two years of longitudinal observation of HC conversion of TST demonstrated a frequency of early clearance ranging from 3.4% 14 to 26.8%, both in Uganda 15 . Whereas the TB Network study that followed HC conversion of IGRA demonstrated that about 58% of exposed HCs lacked evidence of immune sensitization, other studies had a less rigorous definition, as they varied by time of follow-up with individual as well as the likelihood of exposure to TB 16 – 20 . Presumably, in some of these studies, higher rates of TST- and IGRA-negative HCs could be explained by diminished exposure to Mtb.…”

Section: Evidence For Early Clearancementioning

confidence: 99%

Early clearance versus control: what is the meaning of a negative tuberculin skin test or interferon-gamma release assay following exposure to Mycobacterium tuberculosis?

Meermeier

Lewinsohn

2018

F1000Res

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The elimination of tuberculosis (TB) cannot reasonably be achieved by treatment of individual cases and will require an improved vaccine or immunotherapy. A challenge in developing an improved TB vaccine has been the lack of understanding what is needed to generate sterilizing immunity against Mycobacterium tuberculosis (Mtb) infection. Several epidemiological observations support the hypothesis that humans can eradicate Mtb following exposure. This has been termed early clearance and is defined as elimination of Mtb infection prior to the development of an adaptive immune response, as measured by a tuberculin skin test or interferon-gamma release assay. Here, we examine research into the likelihood of and possible mechanisms responsible for early clearance in household contacts of patients with active TB. We explore both innate and adaptive immune responses in the lung. Enhanced understanding of these mechanisms could be harnessed for the development of a preventative vaccine or immunotherapy.

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“…Using binomial risk models (9) and data from (2), we evaluated two plausible mechanisms by which reinfection during this early, critical period can account for the increased disease risk: an independent effect of each infection on risk of progression (reinfection model) and a high risk of progression once the cumulative number of exposures exceeds a threshold value (threshold model). Contacts of TB cases producing aerosols with high burdens of Mycobacterium tuberculosis are more likely to become cases (10)(11)(12), suggesting an inoculum effect as a plausible biological mechanism for both these models. Both models are consistent with the observed data, though neither fully accounts for the observed high risk of active disease in this population following an initial exposure.…”

Section: Introductionmentioning

confidence: 99%

Multiple Exposures, Reinfection, and Risk of Progression to Active Tuberculosis

Ackley

Lee

Worden

et al. 2018

Preprint

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A recent study reported on a tuberculosis outbreak in a largely Inuit village. Among recently infected individuals, exposure to additional active cases was associated with an increasing probability of developing active disease within a year. Using binomial risk models, we evaluated two potential mechanisms by which multiple infections during the first year following initial infection could account for increasing disease risk with increasing exposures. In the reinfection model, multiple exposures have an independent risk of becoming an infection, and infections contribute independently to active disease. In the threshold model, disease risk follows a sigmoidal function with small numbers of exposures conferring a low risk of active disease and large numbers of exposures conferring a high risk. To determine the dynamic impact of reinfection during the early phase of infection, we performed simulations from a modified ReedFrost model of TB dynamics following spread from an initial number of cases. We parameterized this model with the maximum likelihood estimates from the reinfection and threshold models in addition to the observed distribution of exposures among recent infections. We find that both models can plausibly account for the observed increase in disease risk with increasing exposures, but the threshold model confers a better fit than a nested model without a threshold (p=0.04). Our simulations indicate that multiple exposures during this critical time period can lead to dramatic increases in outbreak size. In order to decrease TB burden in highprevalence settings, it may be necessary to implement measures aimed at preventing repeated exposures, in addition to preventing primary infection.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil

Cited by 16 publications

References 28 publications

Mycobacterium tuberculosis progresses through two phases of latent infection in humans

Mycobacterium tuberculosis progresses through two phases of latent infection in humans

Early clearance versus control: what is the meaning of a negative tuberculin skin test or interferon-gamma release assay following exposure to Mycobacterium tuberculosis?

Multiple Exposures, Reinfection, and Risk of Progression to Active Tuberculosis

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