The safety of influenza vaccine in clinically cured leprosy patients in China.

BACKGROUND: Leprosy is an infectious disease caused by the bacterium Mycobacterium leprae. Influenza vaccine is an important influenza prevention strategy and the preparations used display good safety and tolerability profiles. But the safety of applying influenza vaccine on the clinical cured leprosy patients is unclear. METHODS: We conducted an observational clinical study, in Wuhan between November 15, 2016 and March 1, 2017. Two groups of participants ≥50 years of age received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days observation of any solicited and unsolicited adverse events. RESULTS: A total of 134 subjects were included in the study. The total rate of reactogenicity was 5.4% [2/37] in leprosy group and 15.5% [15/ 97] in control group, the difference of reactogenicity between two groups was not significant (p = 0.1522). For solicited injection-sites adverse events (AEs), 12.4% [12/ 97] participants in the control group reported of itching, pain, erythema, swelling or induration, and no participants in leprosy group reported of any solicited injection-sites AEs. For solicited systemic AEs, 7.2% [7 / 97] participants in the control group reported of fever, malaise or headache, and 2.7% [1 / 37] participants in the leprosy group reported of fever, statistic result showed that the difference was not significant (p = 0.4438). Unsolicited AEs was reported by one male aged 76, 4 hours after vaccination administration, his plantar ulcer area began bleeding. All AEs were grade 1 or grade 2, and no recurrence of lepra reaction, AEs leading to early withdrawal from the study, or deaths were reported in this study. CONCLUSIONS: To our knowledge, the present study is the first clinical study to evaluate the safety of influenza vaccine in clinically cured leprosy patients. We concluded that clinically cured leprosy patients are relatively safe for influenza vaccine. More importantly, our study make a positive and scientific efforts to eradicate discrimination on leprosy. In our study, we described a patient with plantar ulcer undergoing bleeding for 4 hours after vaccine administration. Based on evidence we have, we interpret that this adverse event may probably associated with vaccine, and patients with ulcer and leprosy need intensive attention after vaccines administration.

Prevalence and risk factors for hepatitis B and C viruses in patients with leprosy.

It has been reported a higher seroprevalence of HBV and HCV in leprosy patients than in the general population, but the reasons for these findings are not yet clear. On the other hand, there is evidence that these viruses may influence the onset of leprosy reactional episodes, an important cause of neurological sequelae. This study aimed to determine seroprevalence and risk factors for HBV and HCV in leprosy patients and to investigate its association with leprosy reactions. Patients attended from 2015 to 2016 at a Reference Center in Leprosy in Northeastern region of Brazil, were interviewed, had their records reviewed to investigate biological, clinical, behavioral and socioeconomic factors, and underwent blood sample collection. Biological samples were tested for HBV (HBsAg, anti-HBs and anti-HBs) and HCV (anti-HCV) serological markers by ELISA and, in anti-HCV positive samples, HCV RNA was screened by real time PCR. SPSS program was used to analyze the data. A total of 403 leprosy patients were included. Although anti-HBc was positive in 14.1%, there was no detection of HBsAg, which contradicts the hypothesis that leprosy patients have immune deficit that make them more prone to chronic HBV infection. Multibacillary leprosy (0.057), health-related work (0.011) and lower educational level (0.035) were associated with anti-HBc positivity. Anti-HCV was positive in 0.5%, with no detection of HCV RNA. No association was identified between anti-HCV and the epidemiological analyzed factors. There was also no association of anti-HBc or anti-HCV with type 1 or type 2 leprosy reactions. Thus, the seroprevalence of HBV and HCV in leprosy patients was similar to that of the general population of Northeastern region of Brazil, and no association of HBV or HCV with leprosy reactions was observed.

Leprosy in a patient infected with HIV.

A 60-year-old Nigerian man, who had lived in Europe for 30 years but had returned home frequently, presented with right frontalis muscle weakness and right ulnar nerve palsy, without skin lesions. Neurophysiology showed a generalised neuropathy with demyelinating features. Blood tests were positive for HIV, with a normal CD4 count. There was nerve thickening both clinically and on MRI. Nerve biopsy showed chronic endoneuritis and perineuritis (indicating leprosy) without visible mycobacteria. His neuropathy continued to deteriorate (lepra reaction) before starting treatment with WHO multidrug therapy, highly active antiretroviral therapy and corticosteroids. There are 10 new cases of leprosy diagnosed annually in the UK. Coinfection with HIV is rare but paradoxically does not usually adversely affect the outcome of leprosy or change treatment. However, permanent nerve damage in leprosy is common despite optimal therapy. Leprosy should be considered in patients from endemic areas who present with mononeuritis multiplex.

Viral Co-infection and Leprosy Outcomes: A Cohort Study.

BACKGROUND: The role of the host immunity in determining leprosy clinical forms and complications is well recognized, implying that changes in the immune status may interfere with several aspects of the disease. Therefore, we hypothesized that the presence of viral co-infections and associated immunological changes will have a clinical impact on leprosy outcomes. The aim of our study was to determine the clinical impact of human immunodeficiency virus (HIV), human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection on the development of reactions, neuritis, neuropathy and relapses. METHODOLOGY/PRINCIPAL FINDINGS: Cohort study in 245 leprosy subjects from Bahia, Brazil. Patients were followed from the time of diagnosis until at least the end of multidrug therapy. Viral co-infection was detected in 36 out of the 245 patients (14.7%). Specific co-infection rates were 10.6% for HBV, 2.9% for HIV, 2.5% for HTLV-1 and 0.8% for HCV. All four groups of co-infected patients had higher rates of neuritis and nerve function impairment compared to non co-infected leprosy subjects. The relapse rate was also higher in the co-infected group (8.3%) versus patients without co-infection (1.9%); relative risk 4.37, 95% confidence interval 1.02-18.74. CONCLUSIONS/SIGNIFICANCE: Leprosy patients should be screened for HBV, HCV, HIV and HTLV-1 co-infections. Besides contributing to better health care, this measure will facilitate the early detection of severe complications through targeting of higher risk patients.

HIV, HCV & Leprosy co-infection.

In the era where Hansen's disease has achieved elimination status in India, co-infection with HIV can possibly cause a resurgence of this disease. A young intravenous drug abuser was found to have triple affliction, where HIV and HCV infection were discovered on testing after the patient was clinically diagnosed to have Hansen's disease. To our knowledge, there has been no case reported where leprosy was seen with HIV and HCV infection. We are reporting a patient with lepromatous Hansen's disease in type 2 reaction in whom HIV and HCV was incidentally diagnosed.

Clinical and histological features of leprosy and human immunodeficiency virus co-infection in Brazil.

BACKGROUND: Both leprosy and human immunodeficiency virus (HIV) are infectious diseases, and are an important global health problem. Patients with leprosy who are co-infected with HIV seem to be at higher risk of developing leprosy reactions. AIM: To examine the histological features of leprosy in patients with HIV and leprosy co-infection, particularly to determine whether the typical leprosy histopathology is present in skin biopsies, and to assess the histological features of leprosy reactions in co-infected patients. METHODS: This was a matched cohort study with 11 co-infected patients and 31 HIV-negative patients with leprosy. A structured protocol for skin-biopsy evaluation was followed, focusing on inflammation of the skin and dermal nerves. RESULTS: Of the 11 HIV-positive patients, 7 (63%) had borderline tuberculoid (BT) leprosy and 5 (70%) of these 7 patients had developed a type 1 reaction. The lesions in these patients were immunologically active, with 100% of biopsies having evidence of compact granulomas, 90% evidence of oedema and 30% evidence of necrosis. CONCLUSIONS: In this study, patients co-infected with HIV and M. leprae had the typical histological lesions of leprosy. There was evidence of immune activation in patients who received combination antiretroviral therapy, and these patients had BT leprosy and leprosy-upgrading reactions.

Clinical and histological features of leprosy and human immunodeficiency virus co-infection in Brazil

BACKGROUND: Both leprosy and human immunodeficiency virus (HIV) are infectious diseases, and are an important global health problem. Patients with leprosy who are co-infected with HIV seem to be at higher risk of developing leprosy reactions. AIM: To examine the histological features of leprosy in patients with HIV and leprosy co-infection, particularly to determine whether the typical leprosy histopathology is present in skin biopsies, and to assess the histological features of leprosy reactions in co-infected patients. METHODS: This was a matched cohort study with 11 co-infected patients and 31 HIV-negative patients with leprosy. A structured protocol for skin-biopsy evaluation was followed, focusing on inflammation of the skin and dermal nerves. RESULTS: Of the 11 HIV-positive patients, 7 (63%) had borderline tuberculoid (BT) leprosy and 5 (70%) of these 7 patients had developed a type 1 reaction. The lesions in these patients were immunologically active, with 100% of biopsies having evidence of compact granulomas, 90% evidence of oedema and 30% evidence of necrosis. CONCLUSIONS: In this study, patients co-infected with HIV and M. leprae had the typical histological lesions of leprosy. There was evidence of immune activation in patients who received combination antiretroviral therapy, and these patients had BT leprosy and leprosy-upgrading reactions.

The role of human T cell lymphotrophic virus type 1, hepatitis B virus and hepatitis C virus coinfections in leprosy

Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.

The role of human T cell lymphotrophic virus type 1, hepatitis B virus and hepatitis C virus coinfections in leprosy.

Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.

The role of the armadillo and sooty mangabey monkey in human leprosy.

BACKGROUND: The armadillo was the first animal model of leprosy. Its role in the transmission of leprosy remains controversial. The sooty mangabey model of leprosy led to the discovery that rhesus monkeys were more susceptible to leprosy when coinfected with simian immunodeficiency virus (SIV), but that leprosy may play a protective role against acquired immunodeficiency syndrome (AIDS) mortality. Recently, molecular methods have been developed for leprosy and may help resolve the role of zoonoses in leprosy. OBSERVATIONS: The recent identification of a case of leprosy in a native-born American on the east coast of the USA and the identification of leprosy as an immunologic reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-positive cases raise the question of what role zoonoses may play in leprosy. CONCLUSIONS: Leprosy in armadillos and sooty mangabeys has been manipulated by human experimentation. In the case of the armadillo, further study, including molecular techniques, is required to elucidate the role of the armadillo as a zoonosis in human leprosy. Experimentation with the sooty mangabey led to the discovery of an interaction between SIV and leprosy in rhesus monkeys, and prompted the continued investigation of the relationship between HIV and leprosy.

Prevalence and genotypic distribution of hepatitis GB-C/HG and TT viruses in blood donors, mentally retarded children and four groups of patients in eastern Anatolia, Turkey.

We investigated the prevalence and genotypic distribution of GB virus-C/hepatitis G virus (GBV-C/HGV) and TT virus (TTV) in blood donors, mentally retarded children and four groups of patients living in Eastern Anatolia, Turkey. The prevalence and genetic analysis of TTV were determined by using the primers of the UTR and ORF1 regions of TTV, respectively. Reverse transcription nested (RT-n)-PCR was used to amplify 5' UTR of GBV-C/HGV. Genotyping of HGV was carried out by PCR-based genotyping assay while RFLP was conducted to determine the genotypes of TTV. TTV DNA was detected in 118 of 410 sera tested, giving an overall prevalence of 28.7%; GBV-C/HGV-RNA was detected in only 17 cases, giving an overall prevalence of 4.1%. No significant differences were observed in the number of positive or negative tests for GBV-C/HGV and TTV according to duration of illness or mean duration of institutionalization in any of the groups studied. Although all samples from the study population belonged to genotypes 1 and 4, the most common TTV genotype is G2. In conclusion, our results indicate a low endemicity of GBV-C/HGV and TTV infection in Eastern Anatolia, Turkey. The presence of G2 strains reveals the limited genetic diversity of the GBV-C/HGV circulating in Turkey. We suggest that TTV infection of genotypes 1 and 4 is prevalent in the same region.

Genotype variation and stability of four variable-number tandem repeats and their suitability for discriminating strains of Mycobacterium leprae

It has not been possible to distinguish different strains of Mycobacterium leprae according to their genetic sequence. However, the genonme contais several variable-number tandem repeats (VNTR), which have been used effectively in strain typing of other bacteria. To determine their suitability for differentiating M. leprae, we developed PCR systems to amplify 5 different VNTR loci and examined a battery of 12 M. leprae strains derived from patients in different regions of the United States, Brazil, Mexico, and the Philippines, as well as from wild armadillos and sooty mangabey monkey. We found diversity at for VNTR (D = 0.74), butone system (C16G8) failed to yield reproducible results. Alleles for the GAA VNTR varied in length from 9 to 12 copies, andthose for AT17 varied in length from 13 to 20 copies. Relatively little variation was seen with interspecies transfer of bacilli or during short-term passage of strains in nude mice or armadillos. The TA18 locus was more polymorphic than other VNTR, and genotypic variation was more common after long-term expansion in armadillos. Most strain genotypes remained fairly stable in passage, but atrain Thai-53 showed reamrkable any particular genotype associable with different regions or hosts of origen. VNTR polymorphisms can be used effectively to discriminate M. leprae strains. Inclusion of additional loci and other elements will likely lead to robust typing system that can be used in community-based epidemiological studies and select clinical application

Hepatitis C virus antibody, viral RNA and genotypes in leprous patients in Japan.

BACKGROUND/METHODS: Markers of hepatitis C virus infection were tested for in 229 patients with leprosy (male 154, female 75) in Japan. RESULTS: Antibody to hepatitis C virus by a second-generation enzyme immunoassay was detected in 68 patients (30%), and RNA of hepatitis C virus in 41 (18%), in prevalence rates much higher (p < 0.001) than those in matched controls (11/923 or 1.2% and 9/923 or 1.0%, respectively). Hepatitis C virus genotypes were II/1b in 37 (90%), III/2a in three (7%) and IV/2b in one (2%), in which II/1b was more frequently (p < 0.003) represented than in hepatitis C virus carriers without leprosy in Japan (520/767 or 68%). The 41 patients with hepatitis C virus viremia had serum transaminase levels significantly higher than those in the other 188 patients without viremia (p < 0.01). CONCLUSIONS: These results indicate that leprous patients confined in institutions are at high risk of hepatitis C virus infection, and that patients infected with hepatitis C virus should be monitored for liver function and placed on interferon therapy whenever required.

Detección de infecciones subclínica en lepra

Se revisan los distintos procedimientos y técnicas inmunológicas utilizadas para la detección subclínica de la lepra resaltando qué ventajas e inconvenientes desde el punto de vista epidemiológico y de especificidad. El antígeno específico del M. leprae, glicolípido fenólico destaca como el más utilizando actualmente.

Linfadenitis lepromatosa con abcesos

Se presenta un cuadro de lepra lepromatosa típico con cintercurrencias de síndrome febril prolongado que luego de múltiples interconsultas para descartar otras patologías, y a falta de pruebas, se diagnostica como linfadenitis lepromatosa.