ABSTRACT Homeless people are at high risk for sexually transmitted infections (STIs), such as human immunodeficiency virus (HIV) infection and syphilis. We investigated the epidemiology of HIV-1 infection and syphilis among homeless individuals in a large city in Central-Western Brazil. In this cross-sectional study, we interviewed and tested 355 individuals from September 2014 to August 2015. Rapid test samples positive for syphilis were retested using the Venereal Disease Research Laboratory (VDRL) test. Blood samples from HIV-infected participants were collected for POL sequencing using HIV-1 RNA extracted from plasma, reverse transcription, and nested polymerase chain reaction. Anti-HIV-1-positive samples were subtyped by sequencing the nucleotides of HIV-1 protease and part of the HIV-1 reverse transcriptase genes. Transmitted and acquired drug resistance mutations and susceptibility to antiretroviral drugs were also analyzed. Anti-HIV was positive in 14 patients (3.9%; 95% confidence interval [CI]: 2.3–6.4). HIV-1 RNA was detected in 8 of the 14 samples. Two of the eight (25%) isolates showed HIV-1 drug resistance mutations. Furthermore, 78 (22%; 95% CI: 17.9–26.5) and 29 (8.2%; 95% CI: 5.6–11.4) homeless individuals tested positive for syphilis using the rapid test and VDRL test, respectively. Two individuals were anti-HIV-1 and VDRL test positive. Daily alcohol use (adjusted odds ratio [AOR]: 3.2, 95% CI: 1.0–10.4), sex with people living with HIV (PLWH) infection (AOR: 6.8, 95% CI: 1.9–25.0), and sex with people of the same sex (AOR: 5.4, 95% CI: 1.7–17.5) were predictors of HIV infection. Age ≤35 years (AOR: 3.8, 95% CI: 1.4–10.8), previous syphilis testing (AOR: 3.5, 95% CI: 1.4–8.4), history of genital lesions (AOR: 4.9, 95% CI: 1.3–19.1), and crack use in the last six months (AOR: 3.1, 95% CI: 1.3–7.6) were predictors of syphilis. Our findings highlight the importance of STI prevention and control strategies among the homeless.

Abstract: BACKGROUND: The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs. OBJECTIVE: Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). Patients and methods: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial. RESULTS: Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported. STUDY LIMITATIONS: Loss of some monthly laboratory sample collection. CONCLUSIONS: There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.

New Mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (MDT) monitoring. This study describes seroreactivity to M. leprae proteins among participants from three highly endemic leprosy areas in Brazil: central-western Goiânia/Goiás (GO) (n = 225), Rondonópolis/Mato Grosso (MT) (n = 764) and northern Prata Village/Pará (PA) (n = 93). ELISA was performed to detect IgG to proteins (92f, 46f, leprosy IDRI diagnostic-1, ML0405, ML1213) and IgM to phenolic glycolipid-I (PGL-I). Multibacillary (MB) leprosy had positive rates for PGL-I that were similar to those for proteins; however, some anti-PGL-I-negative subjects were positive for proteins, suggesting that adding protein antigen to PGL-I can enhance the sensitivity of MB leprosy detection. In MT, different degrees of seroreactivity were observed and ranked for MB, former patients after MDT, paucibacillary (PB) leprosy, household contact (HHC) and endemic control (EC) groups. The seroreactivity of PB patients was low in GO and MT. HHCs from different endemic sites had similar IgG antibody responses to proteins. 46f and 92f were not recognised by most tuberculosis patients, ECs or HHCs within GO, an area with high BCG vaccination coverage. Low positivity in EC and HHC was observed in PA and MT. Our results provide evidence for the development of an improved serologic test that could be widely applicable for MB leprosy testing in Brazil.

INTRODUÇÃO: A contagem de células CD4+ representa marcador da resposta imune celular em pacientes infectados pelo HIV-1. Testes cutâneos de hipersensibilidade tardia (DTH) podem ser empregados para avaliar in vivo respostas celulares a antígenos comuns. MÉTODOS: DTH para derivado proteico purificado de tuberculina (PPD), esporotriquina, tricofitina, candidina e estreptoquinase/estreptodornase foram realizados. Foram testados crianças/adolescentes infectados pelo HIV-1 (n=36) e indivíduos saudáveis (n=56), soronegativos para HIV-1/HIV-2 pareados por sexo-idade, todos com cicatriz vacinal por BCG. Teste exato de Fisher foi aplicado (p<0,05). RESULTADOS: Entre as crianças/adolescentes infectados pelo HIV-1, mediana de idade=8,1 anos; 20/36 eram do sexo masculino; 35 casos de transmissão vertical; 34 casos de AIDS sob terapia antirretroviral; mediana de carga viral = 3.04lc10 cópias/ml; mediana de contagem de células CD4+ = 701 células/μl. Entre os infectados e saudáveis a reatividade DTH a pelo menos um dos antígenos foi, respectivamente, 25% (9/36) e 87,5% (49/56) (p<0,001). Reatividade à candidina predominou nos infectados (8/36, 22%) e ao PPD nos indivíduos saudáveis (40/56, 71,4%). A reatividade ao PPD entre infectados foi de 8,3% (p<0,01). A mediana da induração ao PPD foi 2,5mm (variação: 2-5mm) entre infectados e 6,0mm (variação: 3-15mm) entre os saudáveis. Não observamos correlação entre positividade ao PPD e idade. No grupo de infectados, não observamos correlação entre contagens de células CD4+ e reatividade ao DTH. CONCLUSÕES: Respostas DTH significativamente diminuídas, incluindo a reatividade ao PPD foram observadas em crianças/adolescentes infectados pelo HIV-1 comparadas com controles saudáveis, provavelmente refletindo doença avançada e supressão da imunidade mediada por células T.

INTRODUCTION: Among HIV-1-infected patients, CD4+ T cell counts are well-established markers of cell-mediated immunity. Delayed-type hypersensitivity (DTH) skin tests can be used to evaluate in vivo cell-mediated immunity to common antigens. METHODS: DTH responses to tuberculin purified protein derivative (PPD), sporotrichin, trichophytin, candidin and streptokinase/streptodornase antigens were assessed. Thirty-six HIV-1-infected children/adolescents and 56 age- and sex-matched HIV-1/HIV-2-seronegative participants were tested. All participants had a BCG scar. Fisher's exact test was used to evaluate significant differences between groups (p<0.05). RESULTS: The main characteristics of the HIV-1 patients were as follows: median age 8.1 years; 20/36 were males; 35 were vertical transmission cases; 34 were AIDS cases under antiretroviral therapy; median viral load = 3.04 log10 copies/ml; median CD4+ T cell count = 701 cells/μl. A total of 25% (9/36) and 87.5% (49/56) of HIV-1-infected and healthy participants, respectively, displayed DTH reactivity to at least one antigen (p<0.001). Among HIV-1-infected participants, reactivity to candidin predominated (8/36, 22.2%), while PPD positivity prevailed among healthy participants (40/56, 71.4%). PPD reactivity in the HIV-1-positive group was 8.3% (p<0.01). The median PPD induration was 2.5mm (range: 2-5mm) in the HIV-1 group and 6.0 mm among healthy participants (range: 3-15mm). There was no correlation between PPD positivity and age. No correlation between CD4+ T cell counts and DTH reactivity was observed among HIV-1-infected patients. CONCLUSIONS: DTH skin test responses, including PPD reactivity, were significantly lower among HIV-1-infected participants compared to healthy controls, which likely reflects advanced disease and T cell depletion.

O diagnóstico da hanseníase se baseia em manifestações clínicas e não existe teste laboratorial para diagnosticar casos assintomáticos ou para prever progressão da doença entre indivíduos expostos. Novas análises genômicas comparativas in silico e ferramentas de biologia molecular têm sido empregadas para revelar proteínas exclusivas do Mycobacterium leprae que apresentem potencial aplicação diagnóstica. A hanseníase tuberculóide paucibacilar (PB) apresenta baixo nível de anticorpos e forte resposta imune celular (RIC) tipo Th1/interferon gamma (IFN-γ). A doença lepromatosa multibacilar (MB) apresenta sorologia positiva e fraca RIC. Portanto, testes laboratoriais para diagnosticar hanseníase PB e MB devem contemplar testes de RIC e sorologia. Proteínas recombinantes do Mycobacterium leprae sorologicamente reativas podem ser incorporadas ao antígeno PGLI para melhorar o diagnóstico sorológico de pacientes MB. Proteínas recombinantes e peptídeos sintéticos do Mycobacterium leprae têm sido testados em ensaios de RIC/IFN-γ para diagnosticar casos PB. Sorologia anti-PGLI modificada incorporando novos antígenos do Mycobacterium leprae e ensaios baseados na RIC/produção de IFN-γ devem permitir a detecção precoce de casos MB e PB em países endêmicos.

Leprosy diagnosis is based mainly on clinical manifestations and no laboratory test is available to diagnose asymptomatic disease or to predict disease progression among exposed individuals. Novel comparative genomic in silico analyses and molecular biology tools have discovered unique Mycobacterium leprae proteins with potential diagnostic application. Tuberculoid paucibacillary leprosy (PB) shows low antibodies titers and strong Th1 type/ IFN-γ specific cell mediated immunity (CMI), while lepromatous multibacillary patients (MB) show high antibody titers and low CMI. Therefore, laboratory tests for PB and MB leprosy diagnosis will require CMI and antibody based assays. Serologically reactive recombinant Mycobacterium leprae proteins were identified and may be used in conjunction with PGL-I to improve MB patient diagnosis. Mycobacterium leprae recombinant proteins and synthetic peptides have been tested for CMI-interferon gamma based assays for PB diagnosis. Modified PGL-I serology incorporating new Mycobacterium leprae antigens and CMI tests based on IFN-γ γ production may permit the detection of leprosy PB and MB forms in endemic countries.

A endemia hansênica apresenta-se, na virada do milênio, no limiar da sua eliminação como problema global de saúde pública. O Brasil é o único país da América Latina onde a doença não foi eliminada, tendo sido a meta de eliminação postergada para 2005. Neste artigo discute-se o declínio da prevalência após a introdução da poliquimioterapia (PQT) para o tratamento da hanseníase, não acompanhada pela redução da incidência no mesmo período. Os progressos na área de imunologia, biologia molecular e seqüenciamento genômico do M. leprae são apresentados enquanto perspectivas de pesquisa e de aplicação potencial para diagnóstico, prognóstico e vigilância na hanseníase. Apesar do êxito das atuais estratégias de controle tem-se observado com preocupação a redução do interesse e do apoio financeiro em pesquisa na hanseníase e na desestruturação dos serviços de saúde frente ao atual cenário de eliminação. A exclusão da hanseníase da lista de doenças prioritárias é prematura, representando um perigo concreto de não se eliminar a doença, mas a pesquisa em hanseníase. Fica evidente a necessidade de investir na produção de conhecimentos de áreas básica e aplicada que viabilizem uma maior compreensão dos mecanismos de transmissão da infecção, da efetividade dos métodos de prevenção e controle, serão essenciais na "erradicação" da infecção pelo M. leprae.

At the beginning of the millennium the elimination of leprosy as a public health problem was considered an attainable goal worldwide. Brazil is the only Latin American country where leprosy is still endemic and the elimination goal has been postponed to 2005. In this review, we discuss the currently declining prevalence after the implementation of multi-drug therapy (MDT), without the reduction in incidence in the same period. The progress in the fields of immunology, molecular biology and the recent accomplishment of M. leprae genomic sequence indicate the new tools potentially applicable to leprosy diagnosis, prognosis and surveillance. Despite the success of the current public health strategy there is a global concern about the lack of interest and financial support for leprosy research, for the maintenance and improvement of field expertise in public health. The exclusion of leprosy among public health priorities was premature and represents a real threat of not eliminating leprosy, but leprosy research. It is necessary to generate knowledge on basic and applied research for understanding the mechanism of transmission of the infection, and to test new preventive and therapeutic tools in order to achieve the "eradication" of the M. leprae infection. Maintenance and field expertise are essential for leprosy surveillance during and after its elimination.

A endemia hansênica apresenta-se, na virada do milênio, no limiar da sua eliminação como problema global de saúde pública. O Brasil é o único país da América Latina onde a doença não foi eliminada, tendo sido a meta de eliminação postergada para 2005. Neste artigo discute-se o declínio da prevalência após a introdução da poliquimioterapia (PQT) para o tratamento da hanseníase, não acompanhada pela redução da incidência no mesmo período. Os progressos na área de imunologia, biologia molecular e seqüenciamento genômico do M. leprae são apresentados enquanto perspectivas de pesquisa e de aplicação potencial para diagnóstico, prognóstico e vigilância na hanseníase. Apesar do êxito das atuais estratégias de controle tem-se observado com preocupação a redução do interesse e do apoio financeiro em pesquisa na hanseníase e na desestruturação dos serviços de saúde frente ao atual cenário de eliminação. A exclusão da hanseníase da lista de doenças prioritárias é prematura, representando um perigo concreto de não se eliminar a doença, mas a pesquisa em hanseníase. Fica evidente a necessidade de investir na produção de conhecimentos de áreas básica e aplicada que viabilizem uma maior compreensão dos mecanismos de transmissão da infecção, da efetividade dos métodos de prevenção e controle, serão essenciais na "erradicação" da infecção pelo M. leprae.

At the beginning of the millennium the elimination of leprosy as a public health problem was considered an attainable goal worldwide. Brazil is the only Latin American country where leprosy is still endemic and the elimination goal has been postponed to 2005. In this review, we discuss the currently declining prevalence after the implementation of multi-drug therapy (MDT), without the reduction in incidence in the same period. The progress in the fields of immunology, molecular biology and the recent accomplishment of M. leprae genomic sequence indicate the new tools potentially applicable to leprosy diagnosis, prognosis and surveillance. Despite the success of the current public health strategy there is a global concern about the lack of interest and financial support for leprosy research, for the maintenance and improvement of field expertise in public health. The exclusion of leprosy among public health priorities was premature and represents a real threat of not eliminating leprosy, but leprosy research. It is necessary to generate knowledge on basic and applied research for understanding the mechanism of transmission of the infection, and to test new preventive and therapeutic tools in order to achieve the "eradication" of the M. leprae infection. Maintenance and field expertise are essential for leprosy surveillance during and after its elimination.