Household contacts of leprosy patients are the group with the highest risk of developing the disease, and although many risk or prevention factors have been identified, they have not been employed in leprosymonitoring programs. This investigation aimed to establish the relative risks or the preventive effects of the presence of BCG vaccination, the Mitsuda test, and the ML-Flow assay. Household contacts (1,396) were monitored for a 5-year period. Twenty-eight contacts (2%) developed leprosy and had their clinical and operational classifications established. All immunological tests were performed, and intradermal BCG vaccination was given after the BCG scar count. Of the affected contacts, 75% developed the disease in the first year, and 71.4% were classified as having paucibacillary forms. Contacts of lepromatous leprosy patients presented a 3.8-fold-higher risk of developing leprosy. BCG vaccination and the Mitsuda test showed a protective effect against leprosy of 0.27 (at least one scar) and 0.16 (>7 mm), respectively, and the positive ML-Flow test indicated a relative risk approximately sixfold higher for occurrence of the disease. All unfavorable combinations of two and three assays generated significant risk values that ranged from 5.76 to 24.47, with the highest risk given by the combination of no BCG scar, negative Mitsuda test, and positive ML-Flow test. We suggest that the BCG vaccination may be given to stimulate Mitsuda test positivity, reducing the patient's risk of developing multibacillary forms. The high significance of these tests may have a great impact on programs to monitor contacts and should be used to improve early detection and treatment.

Our findings strongly suggest that the aerosol route of infection and transmission is predominant and that HHCs contribute to the infection risk to themselves and probably to others.

No abstract

Leprosy is a curable disease with well-defined etiology, but lacks better diagnostic tools, preventive and therapeutic strategies. The continued application of the Ridley-Jopling clinical classification that recognizes the natural diversity of the immune response has provided the basis for understanding leprosy, and this review proposes its implementation in all Reference Centers in order to standardize the diagnostic resources, aiming at the improvement of the disease control. Due to the broad bioepidemiological aspects of infection its eradication is difficult, and proper diagnosis of the disease and the correct clinical classification are required to ensure proper treatment. Tools and markers for diagnosis and prognosis, and the novel use of nanotechnology, as well as strategies for disease control and monitoring populations at higher risk are still continuous challenges, which will be specifically reviewed with additional insights. The use of the current diagnostic tools, such as ELISA and PCR has a very limited approach for leprosy that has been considered as a marginal disease; therefore, the current diagnostic tools must be applied extensively in the routine to accumulate clinical experience in order to improve their precise application, like what has been done in many other infectious diseases. Since a vaccine for leprosy presents an unpredictable future, the proposed chemoprophylaxis of contacts (healthy carriers and/or with subclinical infection) must also be employed in referral centers of endemic countries not only to evaluate its efficacy, but also because of the favorable cost-benefit ratio, given that there is no other available approach, besides the multi-drug therapy of patients. This strategy should readily be applied as a public health policy, and may lead to a substantial breakage of the transmission chain aiming a world without leprosy.

Leprosy transmission still occurs despite the availability of highly effective treatment. The next step towards successfully eliminating leprosy is interrupting the chain of transmission of the aetiological agent, Mycobacterium leprae. In this investigation, we provide evidence that household contacts (HHCs) of leprosy patients might not only have subclinical infections, but may also be actively involved in bacilli transmission. We studied 444 patients and 1,352 contacts using anti-phenolic glycolipid-I (PGL-I) serology and quantitative polymerase chain reaction (qPCR) to test for M. leprae DNA in nasal swabs. We classified the patients according to the clinical form of their disease and the contacts according to the characteristics of their index case. Overall, 63.3% and 34.2% of patients tested positive by ELISA and PCR, respectively. For HHCs, 13.3% had a positive ELISA test result and 4.7% had a positive PCR test result. The presence of circulating anti-PGL-I among healthy contacts (with or without a positive PCR test result from nasal swabs) was considered to indicate a subclinical infection. DNA detected in nasal swabs also indicates the presence of bacilli at the site of transmission and bacterial entrance. We suggest that the concomitant use of both assays may allow us to detect subclinical infection in HHCs and to identify possible bacilli carriers who may transmit and disseminate disease in endemic regions. Chemoprophylaxis of these contacts is suggested

Several discoveries about leprosy indicate that Mycobacterium leprae transmission mainly occurs by inhalation, and the nose is major port of entry and exit. The present study evaluated the clinical application of PCR for detection of M. leprae DNA in nasal mucosa biopsies in untreated leprosy patients (52) and their contacts (99) from the State Reference Center in Sanitary Dermatology and Leprosy, Uberlandia, MG, Brazil. PCR detection of a 372-base pair DNA fragment from M. leprae was accomplished in 36 (69.2%) patients, from which 34 (91.9%) of them were multibacillaries. Furthermore, PCR was positive in 3 (16.7%) of 18 slit-skin smear negative, 4 (25.0%) of 16 skin lesion BI negative, 8 (33.3%) of 24 nasal mucosa BI negative patients, and 10 of 99 contacts (10.1%). The presence of bacilli in 10.1% of the contacts may potentially reflect an occult leprosy, and these patients must be accompanied, followed by a chemoprophylaxy treatment. Considering all PCR results against clinical and BI classification of patients and controls, we have found a sensitivity of 69.2%, a specificity of 89.9%, and an accuracy of 82.8%. It has been demonstrated here through PCR of nasal biopsies that the bacillus invades the mucosa, passing through the nasal inferior turbinate to reach peripheral blood. Therefore, the molecular investigation of invasive nasal biopsies by PCR tests has proven to be useful in defining patients of higher risk of transmission and risk-group contacts, which is an important step to reach the World Health Organization objective towards the elimination of leprosy as a public health problem.

Wheatgrasses (species of Agropyron complex) have previously been reported to be resistant to barley yellow dwarf virus (BYDV). To introgress this resistance into wheat, Triticum aestivum x Thinopyrum (Agropyron) intermedium hybrids were advanced through a backcrossing program and reaction to BYDV, as determined by enzyme-linked immunosorbent assay (ELISA), is reported for the first time in backcross populations of wide hybrids between wheat and wheatgrasses. ELISA values revealed highly resistant to highly susceptible segregants in backcrosses. BYDV resistance was expressed in some backcross derivatives. Continued selection, based on cytology and ELISA in each generation, eliminated most of the unwanted wheatgrass chromosomes and produced self-fertile BYDV resistant wheat lines. The BYDV resistant lines with 2n = 42 had normal chromosome pairing similar to wheat, and their F1 hybrids with wheat had two univalents. DNA analyses showed that the source of alien chromatin in these BYDV resistant wheat lines is distinguishable from that in other Th. intermedium derived BYDV resistant wheat lines. Chromosome pairing and restriction fragment length polymorphism analyses indicated that the 42 chromosome resistant Purdue wheat lines are substitution lines in which chromosome 7D was replaced by a chromosome from Th. intermedium that was carrying gene(s) for BYDV resistance.

Leprosy epidemiological studies have been restricted to Mycobacterium leprae DNA detection in nasal and oral mucosa samples with scarce literature on peripheral blood. We present the largest study applying quantitative real‐time PCR (qPCR) for the detection of M. leprae DNA in peripheral blood samples of 200 untreated leprosy patients and 826 household contacts, with results associated with clinical and laboratory parameters. To detect M. leprae DNA a TaqMan qPCR assay targeting the M. leprae ML0024 genomic region was performed. The ML0024 qPCR in blood samples detected the presence of bacillus DNA in 22.0% (44/200) of the leprosy patients: 23.2% (16/69) in paucibacillary (PB), and 21.4% (28/131) in multibacillary (MB) patients. Overall positivity among contacts was 1.2% (10/826), with similar percentages regardless of whether the index case was PB or MB. After a follow‐up period of 7 years, 26 contacts have developed leprosy. Comparing the results of healthy contacts with those that become ill, ML0024 qPCR positivity at the time of diagnosis of their index case represented an impressive 14.78‐fold greater risk for leprosy onset (95% CI 3.6–60.8; p <0.0001). In brief, contacts with positive PCR in blood at diagnosis of index cases are at higher risk of later leprosy onset and this marker might be combined with other prognostic markers for management of contacts, which requires further studies.