Models for predicting the risk of illness in leprosy contacts in Brazil: Leprosy prediction models in Brazilian contacts.

OBJECTIVE: This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. METHODS: A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. RESULTS: Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. CONCLUSIONS: Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

Molecular Evidence for the Aerial Route of Infection of Mycobacterium leprae and the Role of Asymptomatic Carriers in the Persistence of Leprosy.

BACKGROUND: Leprosy persists as a public health problem. The chain of transmission and mechanism of infection are not completely understood. In the current study, we investigated the route of infection and of disease onset, from airway exposure, colonization, and bloodstream dissemination. METHODS: Mycobacterium leprae DNA was detected through quantitative polymerase chain reaction in nasal vestibule, nasal turbinate mucosa, and peripheral blood samples, along with anti-phenolic glycolipid I serology and skin tests from the same individual, from 113 leprosy patients and 104 household contacts of patients (HHCs). Bivariate statistics and multiple correspondence analysis were employed. RESULTS: The rates of DNA positivity among patients were 66.4% (75 of 113) for nasal swab samples, 71.7% (81 of 113) for nasal turbinate biopsy samples, 19.5% (22 of 113) for blood samples, with seropositivity of 62.8% (71 of 113 samples) and with increasing incidences toward the multibacillary pole of the clinical spectrum. Positivity among HHCs were as follows: 49% (51 of 104) for nasal swab samples, 53.8% (56 of 104) for nasal biopsy samples, 6.7% (7 of 104) for blood samples, and 18.3% (19 of 104 samples) for anti-phenolic glycolipid I serology. During the follow-up of 5-7 years, out of 104 HHCs, 7 developed leprosy (6.7%). Risk for the disease outcome was estimated by comparing results in HHCs who develop leprosy with those not affected. Neither nasal passage nor mucosa positivity was determinant of later disease onset; however, blood presence increased the risk for disease development (relative risk/positive likelihood ratio, 5.54; 95% confidence interval, 1.30-23.62), as did seropositivity (positive likelihood ratio, 3.69 [1.67-8.16]; relative risk, 5.97 [1.45-24.5]). CONCLUSIONS: 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.

Asymptomatic Leprosy Infection among Blood Donors May Predict Disease Development and Suggests a Potential Mode of Transmission.

Blood donor samples (1,007) were assessed for anti-phenolic glycolipid 1 (PGL-1) IgM antibodies and Mycobacterium leprae DNA presence, which had 3.8% and 0.3% positivity, respectively. After a 5-year follow-up period, six individuals with positive markers developed leprosy, raising the hypothesis that asymptomatic infection among blood donors may be an undisclosed mode of leprosy transmission via transfusion.

Antigen-specific assessment of the immunological status of various groups in a leprosy endemic region.

BACKGROUND: Serological tests can be important tools to assist in the diagnosis of leprosy and can contribute to an earlier diagnosis. The aim of this study was to evaluate the antibody responses against phenolic glycolipid-1 (PGL-1), natural disaccharide linked to human serum albumin via an octyl (NDO-HSA), Leprosy IDRI Diagnostic-1 (LID-1) and natural disaccharide octyl--Leprosy IDRI Diagnostic-1 (NDO-LID) in leprosy patients, household contacts of patients and the general population. METHODS: Enzyme-linked immunosorbent assays were used to analyze the antigen-specific antibody responses of 94 leprosy cases, 104 household contacts of cases and 2.494 individuals from the general population. RESULTS: A positive correlation was observed for the antibody responses to all antigens studied. A higher proportion of seropositivity for all antigens, along with stronger magnitude of response, was observed in multibacillary (MB) leprosy patients and household contacts of MB leprosy patients compared with the levels observed in paucibacillary (PB) leprosy patients and household contacts of PB leprosy patients. A substantial and significant positive correlation was found between seropositivity and the bacterial index for the leprosy patients. Anti-PGL-1 tests were more frequently positive than anti-NDO-HSA tests among patients with all clinical forms of leprosy and among the group of household contacts. The LID-1 and NDO-LID antigens showed a greater capacity to identify household contacts and individuals from the general population infected with M. leprae. CONCLUSIONS: Tests that measure the antibody responses against LID-1, NDO-LID, NDO-HSA and PGL-1 were effective tools for the detection of patients with MB leprosy. Our data indicate that the anti-LID-1 and anti-NDO-LID responses were more effective than an anti-NDO-HSA response for the identification of individuals with subclinical infection.

Application of the SRQ20 and the protocol of psychological assessment in patients with leprosy in a Reference Centre in Brazil.

This study aims to apply the protocol of psychological assessment (PAP) and the SRQ-20 to analyse the psychological profile of 130 leprosy patients, in order to evaluate the incidence of Common Mental Disorders (CMD), and screen patients with higher risk of psychological distress. The following results were found in the PAP: 31.53%, 23.8% and 16.9% reported an unsatisfactory childhood, adolescence and adulthood, respectively; 31.53% are afraid of being discriminated against and 16.9% experienced discrimination. Also, 13.07% reported drastic life changes due to leprosy; 29.23% have low self-esteem, 31.53% have real fear and 22.3% have phantasmal fear. In the SRQ-20, the prevalence of CMDs was 32.3%, with the majority being female, married, with low education (primary education), low self-esteem, and with a drastic change in life. Conclusion: This is one of the few studies on the psychological profile of leprosy patients demonstrating the importance of the application of investigative technologies in psychopathological screening, aiming on adherence to treatment and psychotherapy planning. Furthermore, it provides support for reflection on the integrality of healthcare for leprosy patients and the importance of psychologists in health teams.

Adverse reactions induced by MDT/WHO (Rifampicin+Clofazimine+Dapsone) and ROM (Rifampicin+Ofloxacin+Minocycline) regimens used in the treatment of leprosy: a cohort study in a National Reference Center in Brazil.

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

Bartonella henselae DNA detection in patients with type 1 leprosy reactions for more than six months.

Leprosy reactions are among the main causes of physical disability resulting from an infectious disease and can culminate in irreversible physical disabilities, therefore they should be considered a clinical emergency, as well as the elucidation of its cause. Co-infections are considered one of the main triggering causes of leprosy reactions, aggravating and maintaining these reactions for longer in these patients. After reporting a high rate of Bartonella henselae infection in patients with chronic type 2 leprosy reaction, 19/47 (40.4 %) compared to the control group, 9/50 (18.0 %), p = 0.0149, we conducted this study to observe the rate of infection by Bartonella sp. in a group of patients with chronic type 1 leprosy reactions. Blood samples from 14 patients with chronic type 1 leprosy reactions were analyzed by molecular and microbiological tests and compared. The results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has a high proportion of B. henselae infection 6/14 (42.9 %), p = 0.88. We conclude that these bacteria can trigger chronic leprosy reactions and should be investigated in all chronic leprosy reactions patients. Summary Line: Our results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has the same proportion of B. henselae DNA detection 6/14 (42.9 %), p = 0.88.

Bacterial load in the nose and its correlation to the immune response in leprosy patients.

INTRODUCTION: Leprosy, whose etiologic agent is M. leprae, has its clinical manifestations correlated with distinct immunologic forms. The mechanism of infectivity and dissemination of the disease are not completely known, although the nasal mucosa is supposed to have an important role in pathogenesis. OBJECTIVE: To correlate the clinical and bacteriological parameters with that of nasal biopsy and immunological tests, such as lepromin and ML-Flow results, in untreated leprosy patients. MATERIAL AND METHOD: Two hundred and twenty-two patients were evaluated, clinically classified and subjected to skin smear, nasal biopsy, ML-Flow, and Mitsuda test. RESULTS: 689% of the cases were borderline cases. Nasal biopsy revealed 91.4% positivity in those who had specific antibodies against M. leprae on blood sample. Lepromatous leprosy cases were 100% positive on ML-flow test, had a large involvement in the nasal mucosa (91%), positive skin smears (100%) and negative Mitsuda test. Nasal bacillary index showed a good correlation with ML-Flow and had similar results when compared to skin smear. The tests agreement was good, revealing that nasal biopsy can be reliable in the diagnosis of multibacillary clinical forms and in the evaluation of the immunological status of leprosy patients. CONCLUSION: The presence of disseminated bacilli in the nasal mucosa was similar to skin involvement, when correlated with Mitsuda test and ML-Flow. As a result, the role of nasal bacillary index may play an important role in the clinical and immunologic characterization of leprosy patients.

Identification of clinical, epidemiological and laboratory risk factors for leprosy reactions during and after multidrug therapy.

This cross-sectional retrospective study evaluated 440 leprosy patients; 57% (251/440) had leprosy reactions during and/or after multidrug therapy, 80.5% (202/251) of whom presented with multibacillary leprosy. At diagnosis, positive bacterial index (BI) [odds ratio (OR) = 6.39; 95% confidence interval (CI): 4.1-10.1)] or polymerase chain reaction (PCR) (OR = 9.15; 95% CI: 5.4-15.5) in skin smears, anti-phenolic glycolipid-1 (anti-PGL-1) ELISA (OR = 4.77; 95% CI: 2.9-7.9), leucocytosis (OR = 9.97; 95% CI: 3.9-25.7), thrombocytopenia (OR = 5.72; 95% CI: 2.3-14.0) and elevated lactate dehydrogenase (OR = 2.38; 95% CI: 1.4-4.0) were potential markers for the development of reactions during treatment. After treatment, positive BI (OR = 8.47; 95% CI: 4.7-15.3) and PCR (OR = 6.46; 95% CI: 3.4-12.3) in skin smears, anti-PGL-1 ELISA (OR = 2.25; 95% CI: 1.3-3.9), anaemia (OR = 2.36; 95% CI: 1.2-4.5), leucocytosis (OR = 4.14; 95% CI: 1.5-11.6) and thrombocytopenia (OR = 3.70; 95% CI: 1.3-2.2) were risk factors for the occurrence of reactions during the study period. The identification of groups with an increased risk for developing reactions will allow for the timely development of a treatment plan to prevent nerve damage and, therefore, the appearance of the disabling sequelae associated with the stigma of leprosy.

Early diagnosis of neural impairment in seropositive leprosy household contacts: The experience of a reference center in Brazil.

Introduction: Leprosy is an infectious disease that remains with a high number of new cases in developing countries. Household contacts have a higher risk for the development of the disease, but the neural impairment in this group is not well elucidated yet. Here, we measured the chance of occurrence of peripheral neural impairment in asymptomatic leprosy household. Methods: Contacts who present anti-PGL-I IgM seropositivity, through electroneuromyography (ENMG) evaluation. We recruited 361 seropositive contacts (SPC) from 2017 to 2021, who were subjected to an extensive protocol that included clinical, molecular, and electroneuromyographic evaluations. Results: Our data revealed a positivity of slit skin smear and skin biopsy qPCR of 35.5% (128/361) and 25.8% (93/361) respectively. The electroneuromyographic evaluation of the SPC showed neural impairment in 23.5% (85/361), with the predominance of a mononeuropathy pattern in 62.3% (53/85). Clinical neural thickening was observed in 17.5% (63/361) of seropositive contacts, but among the individuals with abnormal ENMG, only 25.9% (22/85) presented neural thickening in the clinical exam. Discussion: Ours results corroborates the need to make the approach to asymptomatic contacts in endemic countries more timely. Since leprosy in its early stages can present an indolent and subclinical evolution, serological, molecular, and neurophysiological tools are essential to break the disease transmission chain.

Description of electroneuromiographic and laboratorial findings in leprosy neuropathy, according to its clinical forms: the confirmation of a spectral disease.

Introduction: Leprosy is one of the most common infectious cause of peripheral neuropathy in the world and can lead to sequelae and physical disabilities. Electroneuromyography (ENMG) is the gold-standard test for evaluating neural impairment, detecting from subclinical abnormalities to advanced lesions. This study aims to describe the electroneuromyographic findings in patients with leprosy, according to their clinical forms. Methods: The study is a retrospective observational analysis of the medical records of patients with leprosy, of a National Reference Center of Sanitary Dermatology and Leprosy in Brazil between 2014 and 2022. 513 patients underwent ENMG at leprosy diagnosis and also underwent a clinical, serological and molecular evaluation of the disease. Results: The electroneuromyographic findings showed 2,671 altered nerves, with an average of 6.9 (±5.1) altered nerves per patient. The most affected sensory nerves were the superficial peroneal (25.0%; 413/1649), sural (15.1%; 397/2627) and ulnar (13.8%; 363/2627), with average of 4.3 (±3.2) affected sensory nerves per patient. The most affected motor nerves were the ulnar (33.1%; 338/1022) and common peroneal (12.1%; 319/2627), with average of 2.6 (±2.5) motor nerves affected per patient. 126 patients presented normal ENMG and, among the 387 with abnormalities in the exam, 13.2% (51/387) had mononeuropathy and 86.8% (336/387) had multiple mononeuropathy. Axonal involvement was more frequent in primary neural leprosy, borderline-tuberculoid, borderline-lepromatous and lepromatous forms. Discussion: Our findings support that leprosy is a spectral disease, characterized by a balance between host immunity and bacillary load. Therefore, the impairment and electroneuromyographic characteristics are distinct and may vary according to the clinical form.

High-resolution ultrasonography for early diagnosis of neural impairment in seropositive leprosy household contacts.

Leprosy household contacts (HC) represent a high-risk group for the development of the disease. Anti-PGL-I IgM seropositivity also increases the risk of illness. Despite significant advances in leprosy control, it remains a public health problem; and early diagnosis of this peripheral neuropathy represents one of the main goals of leprosy programs. The present study was performed to identify neural impairment in leprosy HC by analyzing differences in high-resolution ultrasonographic (US) measurements of peripheral nerves between leprosy HC and healthy volunteers (HV). Seventy-nine seropositive household contacts (SPHC) and 30 seronegative household contacts (SNHC) underwent dermato-neurological examination and molecular analysis, followed by high-resolution US evaluation of cross-sectional areas (CSAs) of the median, ulnar, common fibular and tibial nerves. In addition, 53 HV underwent similar US measurements. The US evaluation detected neural thickening in 26.5% (13/49) of the SPHC and only in 3.3% (1/30) among the SNHC (p = 0.0038). The CSA values of the common fibular and tibial nerves were significantly higher in SPHC. This group also had significantly greater asymmetry in the common fibular and tibial nerves (proximal to the tunnel). SPHC presented a 10.5-fold higher chance of neural impairment (p = 0.0311). On the contrary, the presence of at least one scar from the BCG vaccine conferred 5.2-fold greater protection against neural involvement detected by US (p = 0.0184). Our findings demonstrated a higher prevalence of neural thickening in SPHC and support the role of high-resolution US in the early diagnosis of leprosy neuropathy. The combination of positive anti-PGL-I serology and absence of a BCG scar can identify individuals with greater chances of developing leprosy neuropathy, who should be referred for US examination, reinforcing the importance of including serological and imaging methods in the epidemiological surveillance of leprosy HC.

Identification of types of wound bed tissue as a percentage and total wound area by planimetry in neuropathic and venous ulcers.

BACKGROUND: Neuropathic and venous leg ulcers are chronic wounds associated with devitalized tissue and recurrent infection. Management should be guided by accurate tissue assessment, including the use of planimetry, which provides tissue types as a percentage of the total wound bed surface area. OBJECTIVE: This innovative study aimed to assess and identify the wound bed tissues, as a percentage, of neuropathic and venous ulcers using digital planimetry, providing support to nurses optimize the management of necrotic tissues and, consequently, to avoid wound infection. METHODS: This cross-sectional study enrolled 24 patients with chronic wounds who were assessed from January to March 2021 at the Wound Outpatients Clinic. The wound photographs were analyzed using Image J 1.53e and a smartphone with WoundDoc Plus® 2.8.2 via digital planimetry. Statistical analyses were performed using the binomial test, t-test, and Mann-Whitney. RESULTS: Median wound areas (p=0.3263) did not differ between the group with 2 or 3 risk factors for delayed healing (Md: 31.7) and the group with up to 1 risk factor (Md: 5.3). A low exudate level was associated with the up-to-1-risk-factor-for-delayed-healing group (p=0.0405), while a medium level was associated with the two-or-three-risk-factor group (p=0.0247). A heat map displayed the tissue percentages in the wound bed. In the group with 2 or 3 risk factors for delayed healing, 91.7% (11/12) had less than 70% granulation tissue, which was the primary factor for this group (p<0.0001). Additionally, 66.7% (8/12) of patients with 2 or 3 risk factors for delayed healing exhibited discolored and/or dark red granulation tissue as the primary factor (p=0.0130). CONCLUSION: This novel identification of wound area and tissue types as a percentage, using digital planimetry, can play a crucial role in assisting nurses in decision-making related to the appropriate management of devitalized tissues. Furthermore, this measurements may facilitate the conducting of virtual wound consultations and offer valuable support in the development of protocols aimed at preventing infection and biofilm formation in the wound bed.

HSP60 mimetic peptides from Mycobacterium leprae as new antigens for immunodiagnosis of Leprosy.

The early diagnosis of leprosy serves as an important tool to reduce the incidence of this disease in the world. Phage display (PD) technology can be used for mapping new antigens to the development of immunodiagnostic platforms. Our objective was to identify peptides that mimic Mycobacterium leprae proteins as serological markers using phage display technology. The phages were obtained in the biopanning using negative and positive serum from household contacts and leprosy patients, respectively. Then, the peptides were synthesized and validated in silico and in vitro for detection of IgG from patients and contacts. To characterize the native protein of M. leprae, scFv antibodies were selected against the synthetic peptides by PD. The scFv binding protein was obtained by immunocapture and confirmed using mass spectrometry. We selected two phase-fused peptides, MPML12 and MPML14, which mimic the HSP60 protein from M. leprae. The peptides MPML12 and MPML14 obtained 100% and 92.85% positivity in lepromatous patients. MPML12 and MPM14 detect IgG, especially in the multibacillary forms. The MPML12 and MPML14 peptides had positivity of 11.1% and 16.6% in household contacts, respectively. There was no cross-reaction in patient's samples with visceral leishmaniasis, tuberculosis and other mycobacteriosis for both peptides. Given these results and the easy obtainment of mimetic antigens, our peptides are promising markers for application in the diagnosis of leprosy, especially in endemic and hyperendemic regions.

Bartonella henselae as a putative trigger for chronic type 2 leprosy reactions.

Leprosy reactions are an acute inflammatory phenomenon that can arise before diagnosis, during treatment, or after cure of leprosy. These reactions are considered one of the main diseases that cause physical disabilities. Immunosuppressive treatment for these immune responses makes these patients susceptible to coinfections, which can trigger new leprosy reactions. The main objective of this study was to evaluate the occurrence of infection by Bartonella sp. in blood samples from 47 patients who had untreatable episodes of type 2 leprosy reactions for more than six months, comparing them with a control group. Cultures and molecular methods (PCR) were used. Amplicons from species-specific reactions and sequencing showed a higher prevalence of Bartonella henselae infection in patients, 19/47 (40.4 %), compared to control, 9/50 (18.0 %), p = 0.0149. Five patients accepted treatment for coinfection, and all showed improvement in leprosy reactions with treatment for B. henselae infection. We conclude that these bacteria can trigger chronic reactions of type 2 leprosy and should be investigated in these patients. SUMMARY LINE: Patients who have chronic type 2 leprosy reactions are more susceptible to Bartonella henselae infection than controls: 19/47 (40.4 %) compared 9/50 (18.0 %), p = 0.0149.

Unveiling healthy carriers and subclinical infections among household contacts of leprosy patients who play potential roles in the disease chain of transmission.

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.

Type 2 leprosy reaction presenting as a monoarthritis post multidrug therapy.

Type 2 leprosy reaction, or erythema nodosum leprosum (ENL), involves a complex interaction between the host's immune system and Mycobacterium leprae. It may occur before, during, or after treatment and have a variable clinical presentation involving different body systems, such as skin, osteoarticular, kidneys, and others. Thus, the differential diagnosis, depending on its clinical presentation, can be broad and challenging. The authors report a case of a severe monoarthritis during a type 2 reaction after the multidrug therapy (MDT) was discharged and the investigation of the differential diagnoses.

Fever of Unknown Origin, Wasting Syndrome and Bone Marrow Involvement: A Leprosy Case Report.

Mycobacterium leprae, the etiologic agent of leprosy, is an acid-fast-staining and slow-growing bacilli that infect macrophages and Schwann cells individually or through forming globi. The clinical presentation of leprosy is broad and depends on the host immune response. We report a case of a 42-year-old Brazilian man presenting with fever of unknown origin (FUO), anemia, wasting syndrome, and neuropathy. The diagnosis of lepromatous leprosy was made after an extensive investigation revealed the presence of M. leprae in the bone marrow. Bone marrow involvement in leprosy is rare and some authors believe the presence of M. leprae in the bone marrow can act as a reservoir of the disease facilitating future relapses. It is important to investigate bone marrow involvement in leprosy, especially when the patient presents with cytopenias and positive epidemiologic history.

Leprosy Relapse: A Retrospective Study on Epidemiologic, Clinical, and Therapeutic Aspects at a Brazilian Referral Center.

OBJECTIVES: We aimed to characterize the profile of patients diagnosed with leprosy relapse and understand the influence of different multidrug therapy (MDT) treatments and initial disease presentation. METHODS: This retrospective study included patients diagnosed with leprosy relapse at a referral center in Brazil from 2013 to 2018. We analyzed their clinico-epidemiologic characteristics, laboratory data, and bacilloscopic tests. Survival analysis was used to determine the time elapsed until relapse according to the previous treatment and clinical forms of the disease. RESULTS: A total of 126 cases of relapse were analyzed, which comprised 11.89% (126/1059) of the cases. The median time elapsed until a relapse was 10 years, and most patients had previously undergone 12 doses of MDT (40.48%; 51/126). Undergoing 24 doses of MDT was associated with a better prognosis regarding relapse over time compared with 6 or 12 doses of MDT therapy. Most cases of relapse were classified as multibacillary (96.03%; 121/126). CONCLUSION: The incidence of relapse was greater than observed in other studies. The high percentage of multibacillary patients who had negative bacillary indices demonstrated that the bacillary index cannot be considered to be an essential criterion for relapse, especially concerning making an early diagnosis.

Clinical, epidemiological, and laboratory prognostic factors in patients with leprosy reactions: A 10-year retrospective cohort study.

Introduction: Leprosy reactions, the main cause of neural damage, can occur up to 7 years after starting multidrug therapy. We aimed to approach the prognostic factors that may influence the leprosy reactions over the follow-up time. Methods: Retrospective cohort study, encompassing 10 years of data collection, composed of 390 patients, divided into 201 affected by reactions and 189 reaction-free individuals. Epidemiological, clinical, and laboratory variables were approached as prognostic factors associated with leprosy reactions. The association among variables was analyzed by a binomial test and survival curves were compared by the Kaplan-Meier and Cox proportional-hazards regression. Results: 51.5% (201/390) of patients were affected by leprosy reactions. These immunological events were associated with lepromatous leprosy (16.2%; 63/390; p < 0.0001) and multibacillary group (43%; 169/390; p < 0.0001). This study showed that survival curves for the prognostic factor anti-PGL-I, comparing positive and negative cases at diagnosis, differed in relation to the follow-up time (Log Rank: p = 0.0760; Breslow: p = 0.0090; Tarone-Ware: p = 0.0110). The median survival times (time at which 50% of patients were affected by leprosy reactions) were 5 and 9 months for those reactional cases with negative (26/51) and positive serology (75/150), respectively. The time-dependent covariates in the cox proportional-hazards regression showed anti-PGL-I as the main prognostic factor to predict leprosy reactions (hazard ratio=1.91; p = 0.0110) throughout the follow-up time. Conclusions: Finally, these findings demonstrated that anti-PGL-I serology at diagnosis is the most important prognostic factor for leprosy reactions after starting multidrug therapy, thus enabling prediction of this immunological event.