Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas.

Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 (NAT2) gene and the predominant genotype-deduced acetylation profiles of Brazilians. Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon. Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states (p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast (p = 0.0396). The Southern region was significantly different from all other regions (p < 0.0001). Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions.

Reimagining leprosy elimination with AI analysis of a combination of skin lesion images with demographic and clinical data.

Background: Leprosy is an infectious disease that mostly affects underserved populations. Although it has been largely eliminated, still about 200'000 new patients are diagnosed annually. In the absence of a diagnostic test, clinical diagnosis is often delayed, potentially leading to irreversible neurological damage and its resulting stigma, as well as continued transmission. Accelerating diagnosis could significantly contribute to advancing global leprosy elimination. Digital and Artificial Intelligence (AI) driven technology has shown potential to augment health workers abilities in making faster and more accurate diagnosis, especially when using images such as in the fields of dermatology or ophthalmology. That made us start the quest for an AI-driven diagnosis assistant for leprosy, based on skin images. Methods: Here we describe the accuracy of an AI-enabled image-based diagnosis assistant for leprosy, called AI4Leprosy, based on a combination of skin images and clinical data, collected following a standardized process. In a Brazilian leprosy national referral center, 222 patients with leprosy or other dermatological conditions were included, and the 1229 collected skin images and 585 sets of metadata are stored in an open-source dataset for other researchers to exploit. Findings: We used this dataset to test whether a CNN-based AI algorithm could contribute to leprosy diagnosis and employed three AI models, testing images and metadata both independently and in combination. AI modeling indicated that the most important clinical signs are thermal sensitivity loss, nodules and papules, feet paresthesia, number of lesions and gender, but also scaling surface and pruritus that were negatively associated with leprosy. Using elastic-net logistic regression provided a high classification accuracy (90%) and an area under curve (AUC) of 96.46% for leprosy diagnosis. Interpretation: Future validation of these models is underway, gathering larger datasets from populations of different skin types and collecting images with smartphone cameras to mimic real world settings. We hope that the results of our research will lead to clinical solutions that help accelerate global leprosy elimination. Funding: This study was partially funded by Novartis Foundation and Microsoft (in-kind contribution).

Ultra-sensitive detection of Mycobacterium leprae: DNA extraction and PCR assays.

Leprosy urgently needs a precise and early diagnostic tool. The sensitivity of the direct (bacilli staining, Mycobacterium leprae DNA) and indirect (antibody levels, T cell assays) diagnostics methods vary based on the clinical form. Recently, PCR-based M. leprae DNA detection has been shown to differentially diagnose leprosy from other dermatological conditions. However, accuracy can still be improved, especially for use with less invasive clinical samples. We tested different commercial DNA extraction kits: DNeasy Blood & Tissue, QIAamp DNA Microbiome, Maxwell 16 DNA Purification, PowerSoil DNA Isolation; as well as in-house phenol-chloroform and Trizol/FastPrep methods. Extraction was performed on M. leprae-infected mouse footpads and different clinical samples of leprosy patients (skin biopsies and scrapings, lesion, oral and nasal swabs, body hair, blood on FTA cards, peripheral whole blood). We observed that the Microbiome kit was able to enrich for mycobacterial DNA, most likely due the enzymatic digestion cocktail along with mechanical disruption involved in this method. Consequently, we had a significant increase in sensitivity in skin biopsies from paucibacillary leprosy patients using a duplex qPCR targeting 16S rRNA (M. leprae) and 18S rRNA (mammal) in the StepOnePlus system. Our data showed that the presence of M. leprae DNA was best detected in skin biopsies and skin scrapings, independent of the extraction method or the clinical form. For multibacillary patients, detection of M. leprae DNA in nasal swabs indicates the possibility of having a much less invasive sample that can be used for the purposes of DNA sequencing for relapse analysis and drug resistance monitoring. Overall, DNA extracted with the Microbiome kit presented the best bacilli detection rate for paucibacillary cases, indicating that investments in extraction methods with mechanical and DNA digestion should be made.

Ultra-sensitive detection of Mycobacterium leprae: DNA extraction and PCR assays

Leprosy is difficult to diagnose since it is caused by a bacterium that does not grow in vitro. Bacilli direct detection or the presence of specific antibodies can vary greatly depending on the clinical form. M. leprae direct DNA detection can aid clinical diagnosis, although invasive skin biopsies are still necessary to detect the pathogen or histological features consistent with leprosy. Here we show that a kit combining mechanical and chemical lysis efficiently removes host DNA and enriches for M. leprae DNA, allowing better detection of paucibacillary cases. We believe our findings can contribute to improving disease diagnosis, as well as early detection and that could help monitoring strategies(AU).

DNA Sensing via TLR-9 Constitutes a Major Innate Immunity Pathway Activated during Erythema Nodosum Leprosum.

The chronic course of lepromatous leprosy may be interrupted by acute inflammatory episodes known as erythema nodosum leprosum (ENL). Despite its being a major cause of peripheral nerve damage in leprosy patients, the immunopathogenesis of ENL remains ill-defined. Recognized by distinct families of germline-encoded pattern recognition receptors, endogenous and pathogen-derived nucleic acids are highly immunostimulatory molecules that play a major role in the host defense against infections, autoimmunity, and autoinflammation. The aim of this work was to investigate whether DNA sensing via TLR-9 constitutes a major inflammatory pathway during ENL. Flow cytometry and immunohistochemistry analysis showed significantly higher TLR-9 expression in ENL when compared with nonreactional lepromatous patients, both locally in the skin lesions and in circulating mononuclear cells. The levels of endogenous and pathogen-derived TLR-9 ligands in the circulation of ENL patients were also higher. Furthermore, PBMCs isolated from the ENL patients secreted higher levels of TNF, IL-6, and IL-1ß in response to a TLR-9 agonist than those of the nonreactional patients and healthy individuals. Finally, E6446, a TLR-9 synthetic antagonist, was able to significantly inhibit the secretion of proinflammatory cytokines by ENL PBMCs in response to Mycobacterium leprae lysate. Our data strongly indicate that DNA sensing via TLR-9 constitutes a major innate immunity pathway involved in the pathogenesis and evolution of ENL. Thus, the use of TLR-9 antagonists emerges as a potential alternative to more effectively treat ENL aiming to prevent the development of nerve injuries and deformities in leprosy.

Epidemiological and clinical patterns of 92 patients co-infected with HIV and Mycobacterium leprae from Rio de Janeiro State, Brazil.

BACKGROUND: Many articles have shown that HIV infection can modify the clinical course of leprosy, but very scant epidemiological and clinical data about this co-infection are available in the peer-reviewed literature. METHODS: We herein describe the geographical distribution and demographic characteristics of 92 HIV/Mycobacterium leprae co-infected patients assisted in a Brazilian Leprosy referral center. A multivariate analysis was performed in order to establish clinical factors associated with type 1 reaction. RESULTS: Co-infected patient admissions have steadily increased over the last years at this referral center. Most patients were men, with a mean age of 32.3 years and presenting with the paucibacillary form of leprosy. The use of antiretroviral therapy (ART) was the only factor associated with type 1 reaction. Most patients were living in the metropolitan area and the north sub area of Rio de Janeiro City. CONCLUSION: Co-infected patients receiving ART have a greater chance to develop type 1 reaction. Patients living with both HIV and leprosy are likely to live in regions characterized by a high density impoverished population.

Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection.

Conflicting findings about the association between leprosy and TLR1 variants N248S and I602S have been reported. Here, we performed case-control and family based studies, followed by replication in 2 case-control populations from Brazil, involving 3162 individuals. Results indicated an association between TLR1 248S and leprosy in the case-control study (SS genotype odds ratio [OR], 1.81; P = .004) and the family based study (z = 2.02; P = .05). This association was consistently replicated in other populations (combined OR, 1.51; P < .001), corroborating the finding that 248S is a susceptibility factor for leprosy. Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs) carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when stimulated with Mycobacterium leprae but not with lipopolysaccharide or PAM3cysK4. The same effect was observed after infection of PBMCs with the Moreau strain of bacillus Calmette-Guerin but not after infection with other strains. Finally, molecular dynamics simulations indicated that the Toll-like receptor 1 structure containing 248S amino acid is different from the structure containing 248N. Our results suggest that TLR1 248S is associated with an increased risk for leprosy, consistent with its hypoimmune regulatory function.

Cutaneous and visceral syphilis: unusual presentation

Syphilis is the most common sexually transmitted disease in the world, showing a high incidence rate in our country. Its clinical course is well established and universally accepted, although there are cases in which the diversity of its signs and symptoms can make diagnosis a challenge. This is the reason why it is known as a "thousand faces" or a "great imitator" disease. Authors present a case report with hepatic involvement, which is rare when syphilis is concerned.

CD163 favors Mycobacterium leprae survival and persistence by promoting anti-inflammatory pathways in lepromatous macrophages.

Lepromatous macrophages possess a regulatory phenotype that contributes to the immunosuppression observed in leprosy. CD163, a scavenger receptor that recognizes hemoglobin-haptoglobin complexes, is expressed at higher levels in lepromatous cells, although its functional role in leprosy is not yet established. We herein demonstrate that human lepromatous lesions are microenvironments rich in IDO⁺CD163⁺. Cells isolated from these lesions were CD68⁺IDO⁺CD163⁺ while higher levels of sCD163 in lepromatous sera positively correlated with IL-10 levels and IDO activity. Different Myco-bacterium leprae (ML) concentrations in healthy monocytes likewise revealed a positive correlation between increased concentrations of the mycobacteria and IDO, CD209, and CD163 expression. The regulatory phenotype in ML-stimulated monocytes was accompanied by increased TNF, IL-10, and TGF-ß levels whereas IL-10 blockade reduced ML-induced CD163 expression. The CD163 blockade reduced ML uptake in human monocytes. ML uptake was higher in HEK293 cells transfected with the cDNA for CD163 than in untransfected cells. Simultaneously, increased CD163 expression in lepromatous cells seemed to be dependent on ML uptake, and contributed to augmented iron storage in lepromatous macrophages. Altogether, these results suggest that ML-induced CD163 expression modulates the host cell phenotype to create a favorable environment for myco-bacterial entry and survival.

Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study.

BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8-8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2-8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis.

Manifestações clínicas e sorológicas conflitantes de sófilis em coinfecção pelo HIV / Clinical manifestation of syphilis and serological conflict in coinfection with HIV

A sorologia não treponêmica possui grande valor no diagnóstico e acompanhamento terapêutico da sífilis, porém pacientes coinfectados com o vírus da imunodeficiência humana podem desenvolver respostas que suscitem dúvidas quanto à sua interpretação em relação aos resultados, podendo ser falso-negativas ou falso-positivas. Assim, os clínicos devem estar atentos a manifestações dermatológicas indicativas de sífilis, dando continuidade à conduta diagnóstica, de forma a não retardar o tratamento, evitando maiores danos ao paciente. Este relato avalia a conduta adotada frente a um paciente com clínica sugestiva de sífilis secundária com VDRL inicialmente negativo e HIV-positivo, desenvolvendo, após introdução da penicilina, títulos crescentes de VDRL.

The nontreponemal serology have great value in the diagnosis of secondary syphilis, but the patients coinfected with human immunodeficiency virus may develop abnormal responses before antigenic stimulation and therefore produce false-negative serologic responses or some false-positive infections,including syphilis. Thus, clinicians should be alert to skin lesions suggestive of syphilis and proceed performing diagnostic tests, and not delay treatment to avoid further damage to the patient. This report assesses the conduct adopted front of the patient with symptoms suggestive of secondary syphilis with VDRL initially negative and HIV positive, developing, after the introduction of penicillin, increasing titers of VDRL.

TNF -308G>A single nucleotide polymorphism is associated with leprosy among Brazilians: a genetic epidemiology assessment, meta-analysis, and functional study.

Leprosy is an infectious disease caused by Mycobacterium leprae. Tumor necrosis factor (TNF) plays a key role in the host response. Some association studies have implicated the single nucleotide polymorphism TNF -308G>A in leprosy susceptibility, but these results are still controversial. We first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308A allele (odds ratio [OR] = 0.77; P = .005). Next, results of a meta-analysis reinforced this association after inclusion of our new data (OR = 0.74; P = .04). Furthermore, a subgroup analysis including only Brazilian studies suggested that the association is specific to this population (OR = 0.63; P = .005). Finally, functional analyses using whole blood cultures showed that patients carrying the -308A allele produced higher TNF levels after lipopolysaccharide (LPS) (6 hours) and M. leprae (3 hours) stimulation. These results reinforce the association between TNF and leprosy and suggest the -308A allele as a marker of disease resistance, especially among Brazilians.

Leprosy among patient contacts: a multilevel study of risk factors.

BACKGROUND: This study aimed to evaluate the risk factors associated with developing leprosy among the contacts of newly-diagnosed leprosy patients. METHODOLOGY/PRINCIPAL FINDINGS: A total of 6,158 contacts and 1,201 leprosy patients of the cohort who were diagnosed and treated at the Leprosy Laboratory of Fiocruz from 1987 to 2007 were included. The contact variables analyzed were sex; age; educational and income levels; blood relationship, if any, to the index case; household or non-household relationship; length of time of close association with the index case; receipt of bacillus Calmette-Guérin (BGG) vaccine and presence of BCG scar. Index cases variables included sex, age, educational level, family size, bacillary load, and disability grade. Multilevel logistic regression with random intercept was applied. Among the co-prevalent cases, the leprosy-related variables that remained associated with leprosy included type of household contact, [odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.02, 1.73] and consanguinity with the index case, (OR = 1.89, 95% CI: 1.42-2.51). With respect to the index case variables, the factors associated with leprosy among contacts included up to 4 years of schooling and 4 to 10 years of schooling (OR = 2.72, 95% CI: 1.54-4.79 and 2.40, 95% CI: 1.30-4.42, respectively) and bacillary load, which increased the chance of leprosy among multibacillary contacts for those with a bacillary index of one to three and greater than three (OR = 1.79, 95% CI: 1.19-2.17 and OR: 4.07-95% CI: 2.73, 6.09), respectively. Among incident cases, household exposure was associated with leprosy (OR = 1.96, 95% CI: 1.29-2.98), compared with non-household exposure. Among the index case risk factors, an elevated bacillary load was the only variable associated with leprosy in the contacts. CONCLUSIONS/SIGNIFICANCE: Biological and social factors appear to be associated with leprosy among co-prevalent cases, whereas the factors related to the infectious load and proximity with the index case were associated with leprosy that appeared in the incident cases during follow-up.

A importância de incluir neurossífilis no diagnóstico diferencial de pacientes com déficit cognitivo e alteração do comportamento / The importance of including neurosyphilis in the differential diagnosis of patients with cognitive decline and behavior disturbances

É resultado da infecção do cérebro, das meninges ou medula espinhal pelo Treponema pallidum e desenvolve-se em cerca de 25-40% das pessoas que não são tratadas para a sífilis. A demência por neurossífilis é uma manifestação tardia da sífilis e era causa frequente de deterioração cognitiva antes do aparecimento e da disseminação do uso da penicilina no tratamento das fases iniciais da doença. Embora incomum nos dias de hoje, a demência por neurossífilis ainda constitui diagnóstico diferencial a considerar-se, diante de síndromes demenciais atípicas ou com manifestações frontais, particularmente em populações menos favorecidas socialmente. Esse caso destaca a importância do diagnóstico precoce da neurossífilis, e que os médicos devem se alertar para a possibilidade desta doença em pacientes que apresentam demência, principalmente por pertencer ao grupo das demências potencialmente reversíveis,pois o tratamento adequado pode reverter o declínio cognitivo. E ainda, pelo aumento no número de casos de sífilis na última década, particularmente pela coinfecção com HIV, que pode acelerar o curso e alterar a resposta ao tratamento da sífilis. Este aumento da incidência de sífilis, observado também na Europa e nos Estados Unidos, poderá traduzir-se num acréscimo do número de casos de neurossífilis observados na prática clínica.

Neurosyphilis results from infection of the brain, meninges or spinal cord by Treponema pallidum and develops in about 25-40% of persons who are not treated for syphilis. Dementia by neurosyphilis is a late manifestation of syphilis and was a frequent cause of dementia before the advent and widespread use of penicillin in the treatment of early stages of the disease. Although uncommon today, dementia of neurosyphilis still a differential diagnosis to consider in the face of atypical dementia or with manifestations front, particularly in socially disadvantaged populations socially. This case underscores the importance of early diagnosis of neurosyphilis, which clinicians should alert the possibility of neurosyphilis in patients who present with dementia, mainly belonging to the group of potentially reversible dementias, because proper treatment can reverse cognitive decline. And also, by increasing the number of syphilis cases in the last decade, particularly in combination with HIV, which can acelerate the course and alter the response to treatment of syphilis. This increasedincidence of syphilis, also observed in Europe and the United States, could result in an increase in the number of cases of neurosyphilis observed in clinical practice.

Pápulas perláceas penianas: apresentação clínica atípica em criança / Pearly penile papule: athypical clinical presentation in a child

As pápulas perláceas penianas (PPP), também conhecidas como glândulas de Tyson, são um tipo de angiofibroma; portanto, lesões benignas.São pápulas branco-peroladas, assintomáticas, localizadas na glande do pênis e com maior incidência na idade pós-puberal. Não necessitam de outro tratamento além da informação. Neste trabalho, apresentamos um caso de PPP com localização, idade e sintomatologia atípicas, mostrando a importância da diferenciação clínica com papilomavírus humano (HPV) e outras entidades, e da realização de exame histopatológico nas lesões de diagnóstico incerto.

Pearly penile papules (PPPs), also known as Tyson's glands, are a type of angiofibroma; thus, benign lesions. They are characterized by asymptomatic pearly white papules, located on the glans penis, most often in postpubertal males. They do not require any treatment other than reassurance.At this work, we present a case of PPP with athypical localization, age and symptomathology, showing the importance of the clinical distinction with human papillomavirus (HPV) and other diseases, and the histopathologic exam on uncertain diagnosis lesions.

The additional benefit of the ML Flow test to classify leprosy patients.

The use of the skin lesion counting classification leads to both under and over diagnosis of leprosy in many instances. Thus, there is a need to complement this classification with another simple and robust test for use in the field. Data of 202 untreated leprosy patients diagnosed at FIOCRUZ, Rio de Janeiro, Brazil, was analyzed. There were 90 patients classified as PB and 112 classified as MB according to the reference standard. The BI was positive in 111 (55%) patients and the ML Flow test in 116 (57.4%) patients. The ML Flow test was positive in 95 (86%) of the patients with a positive BI. The lesion counting classification was confirmed by both BI and ML Flow tests in 65% of the 92 patients with 5 or fewer lesions, and in 76% of the 110 patients with 6 or more lesions. The combination of skin lesion counting and the ML Flow test results yielded a sensitivity of 85% and a specificity of 87% for MB classification, and correctly classified 86% of the patients when compared to the standard reference. A considerable proportion of the patients (43.5%) with discordant test results in relation to standard classification was in reaction. The use of any classification system has limitations, especially those that oversimplify a complex disease such as leprosy. In the absence of an experienced dermatologist and slit skin smear, the ML Flow test could be used to improve treatment decisions in field conditions.

Development and validation of a severity scale for leprosy type 1 reactions.

OBJECTIVES: To develop a valid and reliable quantitative measure of leprosy Type 1 reactions. METHODS: A scale was developed from previous scales which had not been validated. The face and content validity were assessed following consultation with recognised experts in the field. The construct validity was determined by applying the scale to patients in Bangladesh and Brazil who had been diagnosed with leprosy Type 1 reaction. An expert categorized each patient's reaction as mild or moderate or severe. Another worker applied the scale. This was done independently. In a subsequent stage of the study the agreement between two observers was assessed. RESULTS: The scale had good internal consistency demonstrated by a Cronbach's alpha >0.8. Removal of three items from the original scale resulted in better discrimination between disease severity categories. Cut off points for Type 1 reaction severities were determined using Receiver Operating Characteristic curves. A mild Type 1 reaction is characterized using the final scale by a score of 4 or less. A moderate reaction is a score of between 4.5 and 8.5. A severe reaction is a score of 9 or more. CONCLUSIONS: We have developed a valid and reliable tool for quantifying leprosy Type 1 reaction severity and believe this will be a useful tool in research of this condition, in observational and intervention studies, and in the comparison of clinical and laboratory parameters.

Pure neural leprosy: steroids prevent neuropathy progression.

Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats leprosy infection but is insufficient in arresting or preventing the nerve damage that causes impairments and disabilities. This case-series study evaluates the benefits of the combined use of steroids and MDT in preventing nerve damage in patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88% male aged 20-79 years, median=41) received a daily morning dose of 60 mg prednisone (PDN) that was gradually reduced by 10 mg during each of the following 5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or PCR. A low prevalence (8.3%) of reaction was observed after release from treatment. However, most of the clinical parameters showed significant improvement; and a reduction of nerve conduction block was observed in 42% of the patients. The administration of full-dose PDN improved the clinical and electrophysiological condition of the PNL patients, contributing to the prevention of further neurological damage.