Epidemiology of Culture-Negative Pulmonary Tuberculosis—Alameda County, 2010-2019

Abstract

Context: Patients with culture-negative pulmonary TB (PTB) can face delays in diagnosis that worsen outcomes and lead to ongoing transmission. An understanding of current trends and characteristics of culture-negative PTB can support earlier detection and access to care. Objective: Describe epidemiology of culture-negative PTB. Design, Setting, Participants: We utilized Alameda County TB surveillance data from 2010 to 2019. Culture-negative PTB cases met clinical but not laboratory criteria for PTB per US National Tuberculosis Surveillance System definitions. We calculated trends in annual incidence and proportion of culture-negative PTB using Poisson and weighted linear regression, respectively. We further compared demographic and clinical characteristics among culture-negative versus culture-positive PTB cases. Results: During 2010-2019, there were 870 cases of PTB, of which 152 (17%) were culture-negative. The incidence of culture-negative PTB declined by 76%, from 1.9/100 000 to 0.46/100 000 (P for trend <.01), while the incidence of culturepositive PTB reduced by 37% (6.5/100 000 to 4.1/100 000, P for trend =.1). Culture-negative PTB case-patients were more likely than culture-positive PTB case-patients to be younger (7.9% were children <15 years old vs 1.1%; P < .01), recent immigrants within 5 years of arrival (38.2% vs 25.5%; P < .01), and have a TB contact (11.2% vs 2.9%; P < .01). Culture-negative PTB case-patients were less likely than culture-positive PTB case-patients to be evaluated because of TB symptoms (57.2% vs 74.7%; P < .01) or have cavitation on chest imaging (13.1% vs 38.8%; P < .01). At the same time culture-negative PTB case-patients were less likely to die during TB treatment (2.0% vs 9.6%; P < .01). Conclusions:The incidence of culture-negative PTB disproportionately declined compared with culture-positive TB and raises concern for gaps in detection. Expansion of screening programs for recent immigrants and TB contacts and greater recognition of risk factors may increase detection of culture-negative PTB.

Characteristics of culture-negative subclinical pulmonary tuberculosis: a single-center observation

“…Figure 2 and Figure 3 reveal pre-and post-treatment chest images of two patients with culture-positive and culture-negative subclinical pulmonary TB. culture-positive ones, reflecting less extensive tissue damage [15,16]. However, the present study revealed a few such lesions exclusively in the culture-negative group, though not statistically significant due to their rarity.…”

“…This aligns with the statement that Mtb may be contained within granuloma in the early stage, resulting in minimal pathology and a lack of symptoms [ 8 ]. Interestingly, prior studies also found that individuals with culture-negative pulmonary TB had fewer cavitary lesions than culture-positive ones, reflecting less extensive tissue damage [ 15 , 16 ]. However, the present study revealed a few such lesions exclusively in the culture-negative group, though not statistically significant due to their rarity.…”

“…However, this may not be clinically important and the explanation for this association has been unclear. Most studies that compared culture-negative and culture-positive pulmonary TB did not show a remarkable association between age and culture positivity [ 15 , 16 , 21 ]. Hence, the relationship between age and culture positivity needs to be clarified, particularly in subclinical disease.…”

“…Still, the data supporting this statement has yet to be explored. Previous studies on culture-negative pulmonary TB have not solely included those asymptomatic and most presented symptoms [ 15 , 16 ]. Distinguishing its characteristics would extend the understanding of natural history and help enhance the detection rate, implicating a more efficient TB control strategy.…”