An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection.

The spleen plays a pivotal role in the pathogenesis of visceral leishmaniasis. In severe forms of the disease, the spleen undergoes changes that can compromise its function in surveilling blood-circulating pathogens. In this study, we present an integrated analysis of the structural and gene expression alterations in the spleens of three patients with relapsing visceral leishmaniasis, two of whom were coinfected with HIV. Our findings reveal that the IL6 signaling pathway plays a significant role in the disorganization of the white pulp, while BCL10 and ICOSLG are associated with spleen organization. Patients coinfected with HIV and visceral leishmaniasis exhibited lower splenic CD4+ cell density and reduced expression of genes such as IL15. These effects may contribute to a compromised immune response against L. infantum in coinfected individuals, further impacting the structural organization of the spleen.

The skin secretion of the amphibian Phyllomedusa nordestina: a source of antimicrobial and antiprotozoal peptides.

Antimicrobial peptides (AMPs) from the dermaseptin and phylloseptin families were isolated from the skin secretion of Phyllomedusa nordestina, a recently described amphibian species from Northeastern Brazil. One dermaseptin and three phylloseptins were chosen for solid phase peptide synthesis. The antiprotozoal and antimicrobial activities of the synthetic peptides were determined, as well as their cytotoxicity in mouse peritoneal cells. AMPs are being considered as frameworks for the development of novel drugs inspired by their mechanism of action.

Serum cytokines associated with severity and complications of kala-azar.

OBJECTIVES: Recent clinical data suggest that severe kala-azar (or visceral leishmaniasis) is an exaggerated innate immune response mediated by inflammatory cytokines, leading to a systemic inflammatory syndrome similar to what is observed in malaria, sepsis and other diseases. We tested this hypothesis by measuring serum cytokines in individuals with kala-azar. METHODS: We compared patients with severe kala-azar (i.e. hemorrhagic manifestations, n = 38) with patients without evidence of hemorrhage (n = 96). We conducted a detailed clinical and laboratory evaluation, measuring serum IL-1beta, IL-6, IL-8, IL-10, IL-12, interferon-gamma, and TNF-alpha, and markers of disseminated intravascular coagulation (DIC). RESULTS: Infants had higher levels of inflammatory cytokines, while HIV-infected patients had lower concentrations of IL-10 and interferon-gamma. Higher levels of IL-6, interferon-gamma, and IL-8 were found among deceased patients. IL-8 and interferon-gamma were independently associated with bleeding. Several cytokines were associated with different signs of severe clinical and laboratory manifestations, including DIC. IL-6 was highly positively and independently associated with IL-1beta, IL-8, IL-10, and negatively associated with TNF-alpha. IL-1beta and TNF-alpha were also highly independently associated with disease severity. CONCLUSION: In its severe form, kala-azar, a neglected tropical disease, initiates a systemic inflammatory response that leads to DIC and other manifestations. Children may have higher risk of death due to the more intense cytokine release. The data supports the notion that IL-6 is the central cytokine that is associated with lethal disease, but interferon-gamma, IL1beta, IL-8, and TNF-alpha are also involved with disease severity. Inhibition of IL-6 is a potential target of adjuvant therapy for severe or pediatric forms of this disease.

Avaliação da efetividade das estratégias de controle da leishmaniose visceral na cidade de Teresina, Estado do Piauí, Brasil: resultados do inquérito inicial – 2004 / Assessment of the effectiveness of control strategies for visceral leishmaniasis in the city of Teresina, State of Piauí, Brazil: baseline survey results – 2004

Este artigo apresenta e discute as implicações dos resultados do inquérito inicial de um estudo de intervenção comunitária para avaliar a efetividade de medidas de controle para a leishmaniose visceral. O estudo foi realizado em dez localidades da cidade de Teresina, Estado do Piauí, Brasil. As localidades foram subdivididas em quadras, quatro delas selecionadas e alocadas aleatoriamente para diferentes intervenções a serem implementadas após o inquérito inicial. No inquérito inicial, realizado no primeiro semestre de 2004, os participantes (n=1.105) responderam a um questionário e tiveram avaliada sua reação ao teste de intradermorreação com antígeno de Montenegro (IDRM). A prevalência global de infecção foi de 36,7 por cento – com tendência a aumentar com a idade –, significativamente mais alta nos homens. A prevalência variou de 24,0 a 47,0 por cento entre localidades. O processo de randomização mostrou-se relativamente satisfatório para variáveis sociodemográficas; houve, entretanto, diferenças significativas na prevalência de positividade na IDRM entre áreas de intervenção. A não-comparabilidade das áreas, no que diz respeito às taxas basais de transmissão, elemento fundamental para inferência causal em doenças infecciosas, pode afetar a validade do estudo de intervenção...

Factors associated to Montenegro skin test positivity in Teresina, Brazil.

Visceral leishmaniasis (VL) is an emerging infectious disease of urban areas in Brazil. To better understand this process, we have studied the association between reaction to the Montenegro skin test (MST), and demographic, socioeconomic and environmental factors in an urban area with high force of transmission. Associations between variables were expressed by prevalence ratios and their respective 95% confidence intervals estimated by using Poisson regression models with robust variance. Higher prevalence of positivity to MST was detected among male and older participants, and among subjects who owned dogs for 3 or more years. Individuals with higher literacy and living in households with three or more persons showed lower prevalence of MST reaction. These results suggest that the identification of high-risk groups might be feasible and useful for targeting interventions.

Genotypes of the mannan-binding lectin gene and susceptibility to visceral leishmaniasis and clinical complications.

BACKGROUND: Visceral leishmaniasis (VL) is almost always lethal if not treated, but most infections with the causative agents are clinically silent. Mannan-binding lectin (MBL), an opsonin, is a candidate molecule for modifying progression to VL because it may enhance infection with intracellular pathogens. Mutations in the MBL2 gene decrease levels of MBL and may protect against development of VL. This case-control study examines genotypes of MBL2 and levels of MBL in individuals presenting with different outcomes of infection with Leishmania chagasi. METHODS: Genotypes for MBL2 and levels of serum MBL were determined in uninfected control subjects (n=76) and in individuals presenting with asymptomatic infection (n=90) or VL (n=69). RESULTS: Genotypes resulting in high levels of MBL were more frequent (odds ratio [OR], 2.5 [95% confidence interval [CI], 1.3-5.0]; P=.006) among individuals with VL than among those with asymptomatic infections and were even more frequent (OR, 3.97 [95% CI, 1.10-14.38]; P=.043) among cases of VL presenting with clinical complications than among those with uneventful courses. Serum levels of MBL were higher (P=.011) in individuals with VL than in asymptomatic infections . CONCLUSIONS: Genotypes of the MBL2 gene predict the risk for developing VL and clinical complications in infections with L. chagasi.

Sensitivity of bone marrow aspirates in the diagnosis of visceral leishmaniasis.

Bone marrow aspirates are believed to provide a safer but less sensitive method in the diagnosis of visceral leishmaniasis (VL) compared with splenic aspirates. We examined the effect of the number of fields and the time of observation on bone marrow smear sensitivity and compared it to our experience with spleen aspiration. Bone marrow smears of 98 patients and splenic aspirates from 120 patients were examined. Among 87 patients with VL, the sensitivity of bone marrow aspirates was 40.2%, 65.5%, 89.7%, 92%, and 95.4% at 1, 5, 20, 30, and 60 minutes, respectively. The sensitivity of spleen aspirate examination was 93% for 114 patients. One patient died of shock after spleen aspiration. A bone marrow smear is very sensitive if examined thoroughly, reaching a sensitivity similar to that of spleen aspirate. We propose that a bone marrow smear be established as the technique of choice for the parasitologic diagnosis of VL.

Epidemia de leishmaniose visceral no Estado de Piauí, Brasil, 1980-1986 / Visceral leishmaniasis in Piaui State, Brazil, 1980-1986

Analisou-se a epidemia de calazar ocorrida no Estado do Piauí, no período de 1980-1986. Os dados foram coletados pela SUCAM-Piauí, òrgäo do Ministério da Saúde para o controle de endemias, pela busca ativa na rede de assistência à saúde do Estado. A epidemia iniciou-se em municípios do centro e do norte, em 1980. No interior, ao contrário do período endêmico, quando predominou em áreas de maior altitude e clima semi-árido, a epidemia grassou nos vales de rios e em regiäo mais úmida, de clima tropical. A capital do Piauí, Teresina, foi atingida em 1981, com pico epidêmico em 1984 e tendo sido responsável por mais de 60 por cento dos 1.509 casos de todo o Estado. Foram feitas tentativas de controle de uso intensivo de inseticidas e eliminaçäo de cäes. Nas outras regiöes do Piauí, borrifadas intensivamente para o controle da doença de Chagas e da malária, a epidemia foi pouco importante e cedeu espontaneamente. Nem a casuística e nem a populaçäo flebotomínica de Teresina apresentaram variaçöes sazonais significativas, mas estiveram moderadamente correlacionadas entre si. Houve maior prevalência em menores de cinco anos, principalmente nos anos de maior incidência, e menor em maiores de 40 anos. A distribuiçäo geográfica do processo epidêmico e a concomitância de seu início com seca prolongada acompanhada de emigraçäo de pessoas e animais domésticos procedentes de regiöes endêmicas para aquelas epidêmicas, sugerem que estesd movimentos migratòrios desencadearam a epidemia. O fato de o processo epidêmico ter cedido espontaneamente em áreas onde näo se tentou o seu controle indica que näo se pode atribuir a apenas às medidas de controle o fim da epidemia. A partir da análise dos coeficientes de incidência específicos por faixa etária, é discutida a possibilidade da progressiva reduçäo na proporçäo de suscetíveis, determinada tanto por um grande número de infecçöes assintomáticas como pela ocorrência de imunidade duradoura, ter contribuído para a extinçäo da epidemia

Epidemia de leishmaniose visceral no Estado do Piaui, Brasil: 1980-1986 / Visceral leishmaniasis epidemic in the state of Piaui, Brazil: 1980-1986

Analisa a epidemia de Calazar, ocorrida no Estado do Piauí, no período de 1980-1986. Os dados foram coletados pela SUCAM-PIAUI, órgão do Ministério da Saúde para o controle de endemias, pela busca ativa na rede de assistência a saúde do Estado. A epidemia iniciou-se em municípios do Centro e do Norte, em 1980. No interior, ao contrário do período endêmico, quando predominou em áreas de maior altitude e clima semi-árido, a epidemia grassou nos vales de rios e em região mais úmida, de clima tropical. A capital do Piaui, Teresina, foi atingida em 1981, com pico epidêmico em 1984, responsável por mais de 60 por cento dos 1.509 casos de todo o Estado. Foram feitas tentativas de controle pelo uso intensivo de inseticidas e eliminação de cães. Nas outras regiões do Piaui, borrifadas intensivamente para o controle da Doenca de Chagas e da Malaria, a epidemia foi pouco importante e cedeu espontaneamente. A partir da análise dos coeficientes de incidência específicos por faixa etária, e discutida a possibilidade da progressiva redução na proporção de suscetiveis, determinada tanto por um grande número de infecções assintomáticas como pela ocorrência de imunidade duradoura, ter contribuído para extinção da epidemia.(AU)