Intensive care inequity in Rio de Janeiro: the effect of spatial distribution of health services on severe acute respiratory infection. / Desigualdades na terapia intensiva no Rio de Janeiro: efeitos da distribuição espacial dos serviços de saúde na infecção respiratória aguda grave.

OBJECTIVE: To analyze the distribution of adult intensive care units according to geographic region and health sector in Rio de Janeiro and to investigate severe acute respiratory infection mortality in the public sector and its association with critical care capacity in the public sector. METHODS: We evaluated the variation in intensive care availability and severe acute respiratory infection mortality in the public sector across different areas of the city in 2014. We utilized databases from the National Registry of Health Establishments, the Brazilian Institute of Geography and Statistics, the National Mortality Information System and the Hospital Admission Information System. RESULTS: There is a wide range of intensive care unit beds per capita (from 4.0 intensive care unit beds per 100,000 people in public hospitals in the West Zone to 133.6 intensive care unit beds per 100,000 people in private hospitals in the Center Zone) in the city of Rio de Janeiro. The private sector accounts for almost 75% of the intensive care unit bed supply. The more developed areas of the city concentrate most of the intensive care unit services. Map-based spatial analysis shows a lack of intensive care unit beds in vast territorial extensions in the less developed regions of the city. There is an inverse correlation (r = -0.829; 95%CI -0.946 to -0.675) between public intensive care unit beds per capita in different health planning areas of the city and severe acute respiratory infection mortality in public hospitals. CONCLUSION: Our results show a disproportionate intensive care unit bed provision across the city of Rio de Janeiro and the need for a rational distribution of intensive care.

Sporotrichoid leishmaniasis: a cross-sectional clinical, epidemiological and laboratory study in Rio de Janeiro State, Brazil.

BACKGROUND: Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (SL), which is clinically described as a primary ulcer combined with lymphangitis and nodules and/or ulcerated lesions along its pathway. AIMS: To assess the differences between patients with sporotrichoid leishmaniasis and typical cutaneous leishmaniasis (CL). METHODS: From January 2004 to December 2010, 23 cases of SL (4.7%) were detected among 494 CL patients diagnosed at a reference center for the disease in Rio de Janeiro State, Brazil. These 23 cases were compared with the remaining 471 patients presenting CL. RESULTS: SL predominated in female patients (60.9%, p = 0.024), with older age (p = 0.032) and with lesions in upper limbs (52.2%, p = 0.028). CL affected more men (64.5%), at younger age, and with a higher number of lesions exclusively in lower limbs (34.8%). CONCLUSIONS: Differences in clinical and epidemiological presentation were found between SL patients as compared to CL ones, in a region with a known predominance of Leishmania (Viannia) braziliensis. The results are similar to the features of most of the sporotrichosis patients as described in literature, making the differential diagnosis between ATL and sporotrichosis more important in overlapping areas for both diseases, like in Rio de Janeiro State.

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil.

BACKGROUND: Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. METHODS: A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924. RESULTS: Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7-29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1-31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony. CONCLUSIONS: Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.

Sporotrichoid leishmaniasis: a cross-sectional clinical, epidemiological and laboratory study in Rio de Janeiro State, Brazil

ABSTRACT Background Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (SL), which is clinically described as a primary ulcer combined with lymphangitis and nodules and/or ulcerated lesions along its pathway. Aims To assess the differences between patients with sporotrichoid leishmaniasis and typical cutaneous leishmaniasis (CL). Methods From January 2004 to December 2010, 23 cases of SL (4.7%) were detected among 494 CL patients diagnosed at a reference center for the disease in Rio de Janeiro State, Brazil. These 23 cases were compared with the remaining 471 patients presenting CL. Results SL predominated in female patients (60.9%, p = 0.024), with older age (p = 0.032) and with lesions in upper limbs (52.2%, p = 0.028). CL affected more men (64.5%), at younger age, and with a higher number of lesions exclusively in lower limbs (34.8%). Conclusions Differences in clinical and epidemiological presentation were found between SL patients as compared to CL ones, in a region with a known predominance of Leishmania (Viannia) braziliensis. The results are similar to the features of most of the sporotrichosis patients as described in literature, making the differential diagnosis between ATL and sporotrichosis more important in overlapping areas for both diseases, like in Rio de Janeiro State.

PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS.

American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.

Health education in South America recarding leishmaniasis: a systematic review

Leishmaniases are important anthropozoonoses, representing a disease complex with highmorbidity and mortality in Brazil as well as worldwide. The aim of this study was to perform asystematic review on the production of scientific knowledge in South America related to health education on leishmaniasis. The following databases were used: PubMed, Literatura LatinoAmericana/Caribeem Ciências da Saúde (LILACS), Scopus, Science Direct, Web of Knowledgeand Scielo. An analytical matrix for the evaluation of the selected studies was elaborated consideringthe education categories: frameworks and models; educational intervention; educational proposal,assessment of policies, educational programs and projects. Studies were considered for analysiswhen they included at least two of these categories. We found 389 suitable manuscripts, of which54 were included for full reading. Six studies were approved and selected for data extraction. Ofthese, four were conducted in Brazil, one in Colombia and one in Peru. Four of the six studiesaddressed cutaneous leishmaniasis and the other two were related to visceral leishmaniasis. Amongthe selected manuscripts five were of intervention and one was a survey. The findings suggest thatstudies on health education in leishmaniasis, in Brazil as well as in other South American countries,should be encouraged because of the wide dispersion and great impact of these diseases in theaffected populations. Educational interventions on health occupy an important place regarding thecontrol of neglected diseases because they interfere with several epidemiological components of thedisease, presenting potential for transformation.

As leishmanioses são importantes antropozoonoses que representam um complexo de doenças com elevada morbimortalidade no Brasil e no mundo. O objetivo do estudo foi realizar uma revisão sistemática sobre a produção de conhecimento na educação em saúde na América do Sul referente às leishmanioses. Utilizamos as bases de dados: Pubmed, Literatura Latino-Americanae do Caribe em Ciências da Saúde (LILACS), Scopus, Science Direct, Web of Knowledge e Scielo. Para a avaliação dos estudos selecionados elaboramos uma matriz analítica considerando as seguintes categorias educacionais: referenciais e modelos; intervenção educativa; proposta educativa; avaliação de políticas, programas e projetos educativos. Foram considerados adequadosos estudos que contemplaram pelo menos duas das categorias indicadas. A pesquisa resultou em 389 registros e 54 foram incluídos para leitura na íntegra. Seis estudos da América do Sul foramaprovados e selecionados para extração dos dados. Destes, quatro foram realizados no Brasil, umna Colômbia e um no Peru. Quatro dos seis estudos eram sobre leishmaniose cutânea e dois eram sobre leishmaniose visceral. Dos artigos selecionados cinco eram de intervenção e um inquérito. Os resultados obtidos sugerem que estudos na área de educação em saúde em leishmaniose, tanto noBrasil como nos países da América do Sul devem ser incentivados devido a dispersão e o grande impacto dessa doença na população afetada. Intervenções educativas em saúde ocupam um lugarde importância no controle das doenças negligenciadas, porque interferem com os diferentes componentes epidemiológicos da doença, apresentando um potencial transformador.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

Montenegro skin test and age of skin lesion as predictors of treatment failure in cutaneous leishmaniasis.

A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb(5+)/kg/day of intramuscular meglumine antimoniate (Sb(5+)) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.

Montenegro skinttest and age of skin lesion as redictors of treatment failure in cutaneous leishmaniasis / Intensidade da intradermorreação de Montenegro e tempo de evolução da lesão como preditores de falha na resposta terapêutica da leishmaniose cutânea

A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb5+/kg/day of intramuscular meglumine antimoniate (Sb5+) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.

Conduzimos estudo caso-controle que verificou a associação entre a intradermorreação de Montenegro (IDRM), o tempo de evolução da lesão e a resposta terapêutica em pacientes com leishmaniose cutânea (LC) atendidos no Instituto de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brasil. Para cada caso com má resposta à terapêutica foram selecionados aleatoriamente dois controles que evoluíram com cicatrização das lesões após o tratamento, pareados por sexo e idade. Todos os pacientes realizaram tratamento com antimoniato de meglumina (Sb5+) IM, na dose de 5 mg Sb5+/kg/dia, continuamente, por 30 dias. Pacientes com LC apresentaram aproximadamente cinco vezes mais chance de falhar quando as lesões apresentavam menos de dois meses de evolução no primeiro dia de atendimento. Pacientes com falha terapêutica apresentaram reações de IDRM menos intensas que pacientes que evoluíram para a cura clínica. A cada 10 milímetros de aumento na resposta à IDRM, houve uma redução de 26% na chance de ocorrência de falha. O tratamento precoce, traduzido pelo tempo de evolução da lesão menor que dois meses no primeiro dia de atendimento, e resposta de imunidade celular deficiente, traduzida por IDRM menos intensa, demonstraram contribuir para a ocorrência de falha terapêutica na leishmaniose cutânea.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature.

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

Análise molecular da epidemia pelo subtipo F do HIV-1 no mundo / Molecular analysis of the HIV-1 sub-subtype F1 epidemic in the world

A epidemia pelo vírus da imunodeficiência humana (HIV) é uma das mais importantes causas de morte no mundo. Segundo as estimativas da Organização Mundial da Saúde, na atualidade existem mais de 40 milhões de pessoas infectadas pelo HIV, sendo que 95% são de países em desenvolvimento. Os HIV são classificados em 2 tipos (HIV-1 e HIV-2). Os integrantes do grupo M do HIV-1 são os principais responsáveis pela pandemia. De forma geral alguns subtipos do HIV-1 parecem ter-se expandido amplamente abarcando extensas áreas geográficas, enquanto outros ficaram mais restritos a regiões menores. o sub subtipo F1 é um exemplo visível deste último grupo, estando presente em proporções epidêmicas, unicamente em três regiões do mundo: África Central, Romênia e a parte da região sul-americana que inclui os países de Brasil, Argentina e Uruguai. Este trabalho objetivou: 1) analisar a origem geográfica e identificar os possíveis caminhos evolutivos do sub subtipo F1 do HIV-1 no mundo, através de análises filogenéticas e dados epidemiológicos; 2) discutir as possíveis hipóteses relacionadas com os processos evolutivos do sub subtipo F1, assim como os fatores associados a sua dinâmica de dispersão demográfica. Para isto um total de 167 seqüências da região genética do env C2-V3, foram analidsadas. Informações epidemiológicas foram incorporadas na análise com o intuito de possibilitar inferências mais detalhadas e precisas. Nossos resultados sustentam a hipótese de uma origem africana da edipedima mundial pelo sub subtipo F1, mais especificamente a República Democrática do Congo (anteriormente chamado Zaire). Além disso, é altamente provável que esta variante F1 tenha saído do continente africano pela via sexual, especialmente heterossexual. O fato de que as seqüências romenas se agrupam separadamente das representantes da América do Sul indica que se trata de suas introduções separadas sem aparente conexão epidemiológica entre elas...