Abstract
The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas.
Highlights
Leprosy, caused by the human pathogen Mycobacterium leprae (M. leprae), causes a slowly developing granulomatous disease that affects mainly skin and peripheral nerves, resulting in disfiguring skin lesions and progressive nerve damage with subsequent muscle weakness, bone and tissue resorption, with disfigurement and disability causing stigma and social isolation
A total of 466 individuals chosen from seven different municipalities were divided into four groups: 87 newly diagnosed leprosy patients, 52 treated patients who had completed multidrug therapy (MDT), 296 household contacts (HHC) who did not have any clinical signs of disease and 31 healthy endemic control (HEC) (Table 1)
The results showed the highest frequency of double positives (PGL-I+/RLEP+) in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), HHC (46/296, 15.5%) and none for HEC (0/31, 0%)
Summary
Leprosy, caused by the human pathogen Mycobacterium leprae (M. leprae), causes a slowly developing granulomatous disease that affects mainly skin and peripheral nerves, resulting in disfiguring skin lesions and progressive nerve damage with subsequent muscle weakness, bone and tissue resorption, with disfigurement and disability causing stigma and social isolation. Over 200,000 new cases of leprosy have been diagnosed annually in the world during the last 10 years. It is still a public health problem in some endemic areas, in India, Brazil and Indonesia, where 79% of all cases were reported in 2019 [1]. Independent data allow us to conclude that the real prevalence is much higher than those reported numbers [2, 3]. Recent mathematical models predict that elimination of leprosy as a public health risk by 2061 would require over 40 years in the three regions with the highest prevalence in Brazil (North, Northeast and Midwest), primarily due to the long delay in detection of cases [5]. Brazil is still the only country in the world that has not met the WHO goal of
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