Household Contacts of Leprosy Patients in Endemic Areas Display a Specific Innate Immunity Profile

Abstract

Leprosy is a chronic infectious disease, caused by Mycobacterium leprae, that can lead to severe lifelong disabilities. The transmission of M. leprae is continuously ongoing as witnessed by the stable new case detection rate. The majority of exposed individuals does, however, not develop leprosy and is protected from infection by innate immune mechanisms. In this study the relation between innate immune markers and M. leprae infection as well as the occurrence of leprosy was studied in household contacts (HCs) of leprosy patients with high bacillary loads. Serum proteins associated with innate immunity (ApoA1, CCL4, CRP, IL-1Ra, IL-6, IP-10, and S100A12) were determined by lateral flow assays (LFAs) in conjunction with the presence of M. leprae DNA in nasal swabs (NS) and/or slit-skin smears (SSS). The HCs displayed ApoA1 and S100A12 levels similar to paucibacillary patients and could be differentiated from endemic controls based on the levels of these markers. In the 31 households included the number (percentage) of HCs that were concomitantly diagnosed with leprosy, or tested positive for M. leprae DNA in NS and SSS, was not equally divided. Specifically, households where M. leprae infection and leprosy disease was not observed amongst members of the household were characterized by higher S100A12 and lower CCL4 levels in whole blood assays of HCs in response to M. leprae. Lateral flow assays provide a convenient diagnostic tool to quantitatively measure markers of the innate immune response and thereby detect individuals which are likely infected with M. leprae and at risk of developing disease or transmitting bacteria. Low complexity diagnostic tests measuring innate immunity markers can therefore be applied to help identify who should be targeted for prophylactic treatment.

Prototype multi-biomarker test for point-of-care leprosy diagnostics

“…Separate evaluation of biomarkers, however, indicated that ApoA1 differed significantly in these patients with PB leprosy from controls, corroborating the potential of ApoA1 as a biomarker for PB leprosy ( van Hooij et al., 2019 ). M. leprae -exposed HCs in South Korea showed a similar ApoA1 response as the patients with PB leprosy, as observed previously in Bangladesh ( van Hooij et al., 2020 ). In contrast to our findings in Bangladesh ( van Hooij et al., 2020 ), R values of S100A12 in contacts and patients with PB leprosy were similar to those of healthy controls in South Korea.…”

“…M. leprae -exposed HCs in South Korea showed a similar ApoA1 response as the patients with PB leprosy, as observed previously in Bangladesh ( van Hooij et al., 2020 ). In contrast to our findings in Bangladesh ( van Hooij et al., 2020 ), R values of S100A12 in contacts and patients with PB leprosy were similar to those of healthy controls in South Korea. Leprosy is no longer endemic in this country; it has to be taken into account that the frequency of exposure to M. leprae , as well as other environmental pathogens, can definitely influence biomarker levels, stressing the importance of quantitative measurements.…”

“…For patients with PB leprosy, ApoA1 was identified as the most important biomarker ( van Hooij et al., 2019 ). ApoA1 and S100A12 levels also differentiated highly exposed contacts from endemic controls (ECs), identifying potentially M. leprae -infected individuals ( van Hooij et al., 2020 ). In addition, CCL4 showed added diagnostic value in overnight stimulated WBA samples, particularly for patients with PB leprosy ( van Hooij et al., 2019 ) and was also associated with M. leprae infection among household contacts ( van Hooij et al., 2020 ).…”

In search of biomarkers for leprosy by unraveling the host immune response to Mycobacterium leprae

“…These findings were corroborated in additional studies, also studying these CCGF in cohorts in China, Brazil, and Ethiopia with a different genetic background. 19,49 However, most PB leprosy patients and household contacts responded similarly to the M leprae antigens. Further research on the mechanisms that determine progression of M leprae infection to disease may allow the identification of biomarkers differentiating PB from healthy exposed individuals.…”

“…Exposure to M leprae also affects the innate immune response of contacts of lepromatous patients; levels of ApoA1 and S100A12 similar to those of PB patients have been observed in contacts of leprosy patients. 49 We hypothesize that in these individuals there is a constant battle between the host and the bacterium:…”