BODY WEIGHT AS A DETERMINANT OF CLINICAL EVOLUTION IN HAMSTERS (Mesocricetus auratus) INFECTED WITH Leishmania (Viannia) panamensis

SUMMARY The clinical outcome of infection with Leishmania species of the subgenus Viannia in hamster model (Mesocricetus auratus) has shown to be different depending on experimental protocol. Body weight has been a relevant determinant of the clinical outcome of the infection in hamsters with visceral leishmaniasis but its importance as a clinical parameter in hamsters with cutaneous leishmaniasis is not known. In this study, the clinical evolution of infection with L. (V) panamensis was evaluated in juvenile and adult male hamsters during 11 weeks by comparing clinical parameters such as attitude, temperature, respiratory rate, appearance of the stool, and body weight between infected and non-infected groups. Results showed that body weight decreased in adult hamsters after infection by L. (V) panamensis; this observation supports the use of body weight as an additional parameter to define the management or treatment of cutaneous leishmaniasis in infected adult hamsters used as an animal experimental model for leishmaniasis.

The Role of the Humoral Immune Response in the Molecular Evolution of the Envelope C2, V3 and C3 Regions in Chronically HIV-2 Infected Patients

BACKGROUND: This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2-4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity RESULTS: The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites. CONCLUSION: The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size limiting the number of virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope recognition by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design.

CHICKEN COOPS, Triatoma dimidiata INFESTATION AND ITS INFECTION WITH Trypanosoma cruzi IN A RURAL VILLAGE OF YUCATAN, MEXICO

This study longitudinally investigated the association between Triatoma dimidiata infestation, triatomine infection with Trypanosoma cruzi and household/backyard environmental characteristics in 101 homesteads in Molas and Yucatan, Mexico, between November 2009 (rainy season) and May 2010 (dry season). Logistic regression models tested the associations between insect infestation/infection and potential household-level risk factors. A total of 200 T. dimidiata were collected from 35.6% of the homesteads, mostly (73%) from the peridomicile. Of all the insects collected, 48% were infected with T. cruzi. Infected insects were collected in 31.6% of the homesteads (54.1% and 45.9% intra- and peridomiciliary, respectively). Approximately 30% of all triatomines collected were found in chicken coops. The presence of a chicken coop in the backyard of a homestead was significantly associated with both the odds of finding T. dimidiata (OR = 4.10, CI 95% = 1.61-10.43, p = 0.003) and the presence of triatomines infected with T. cruzi (OR = 3.37, CI 95% = 1.36-8.33, p = 0.006). The results of this study emphasize the relevance of chicken coops as a putative source of T. dimidiata populations and a potential risk for T. cruzi transmission.

Evolution of the Human Immunodeficiency Virus Type 2 Envelope in the First Years of Infection is Associated with the Dynamics of the Neutralizing Antibody Response

Background: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results: CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.

Chromosomal structure: a selectable trait for evolution

Dissertation presented to obtain the Ph.D degree in Evolutionary Biology

Intron evolution in primates

Dissertation presented to obtain a Ph.D degree in Evolutionary Biology

Estudos sôbre reservatórios e vetores silvestres do Trypanosoma cruzi: XVII. Contribuição para o estudo dos focos naturais da tripanossomose americana, com especial referência à região nordeste do Estado de São Paulo, Brasil

Depois de acentuar que a tripanossomose americana é uma zoonose do tipo anfixenose, bem enquadrável no conceito de PAVLOVSKY de infecção com focos naturais, o Autor analisa o problema da multiplicidade e diversidade dêstes focos que são devidas ao grande número de hospedeiros e vetores naturais com hábitos variados. Descreve, em seguida, alguns focos naturais mais freqüentes e importantes, observados na região nordeste do Estado de São Paulo e áreas limítrofes do Estado de Minas Gerais, focos êstes constituídos por buracos e cavidades no solo, ocos e anfractuosidades em troncos de árvores, tufos de vegetação herbácea, touceiras de piteira e copa de palmeiras, onde triatomíneos e mamíferos convivem.

Estudos sôbre reservatórios e vetores silvestres do Trypanosoma cruzi. XXII. Modificações dos focos naturais da tripanossomose americana e suas conseqüências

Os focos naturais da tripanossomose americana, como tôda biogeocenose, podem. permanecer relativamente estáveis, sendo esta estabilidade necessária para a própria existência dêsses focos. Mas o balanço ecológico pode ser alterado, sendo muito importante aquelas alterações devidas à interferência direta ou indireta do homem ao exercer atividades ligadas ao desbravamento e à colonização. Entre as conseqüências podemos citar: 1) redução ou desaparição dos focos naturais; 2) concentração de hospedeiros e vectores em áreas favoráveis limitadas; 3) deslocamento de hospedeiros e vectores para outras áreas; 4) invasão das habitações humanas e anexos, com a instalação do ciclo doméstico da infecção. Estas possibilidades são analisadas e ilustradas com exemplos.

Estudos sôbre reservatórios e vectores silvestres do Trypanosoma cruzi. XXIV. Variação dos dados biométricos obtidos em amostras do T. cruzi isolados de casos humanos da Doença de Chagas

Estudo biométrico de 10 amostras de Trypanosoma cruzi isoladas de casos humanos da doença de CHAGAS, nove mantidas em camundongos brancos jovens e uma mantida em ratos brancos jovens, mostrou a existência de grandes variações amostrais. Assim os valores do comprimento total médio das diferentes amostras variaram entre 16,3μ e 21,8μ., enquanto os valores do índice nuclear médio oscilaram entre 0,93 e 1,52. Êstes resultados ampliam os limites de variações amostrais até agora observadas no T. cruzi, especialmente os que se referem ao índice nuclear médio.

Intention recognition, commitment and their roles in the evolution of cooperation

Dissertação para obtenção do Grau de Doutor em Informática

Splenectomy and experimental infection of mice by a virulent strain of trypanosoma cruzi

Splenectomy seems to increase susceptibility of mice to a jurther infection with a virulent strain of Trypanosoma cruzi. Parasitemia increases with splenectomy and the sooner the infection follows the operation, the greater the parasitemia. The mortality rate seems to have not been influenced by splenectomy.

Imunização de camundongos com «vacina» viva avirulenta de Trypanosoma cruzi

O Autor procura verificar qual o menor número de Trypanosoma cruzi, da cepa Y avirulenta, capaz de conferir a camundongos imunidade eficiente contra uma ulterior infecção com a cepa Y virulenta do mesmo parasita. Considerações gerais sôbre o possível mecanismo da imunização são esboçadas.

Imunização de camundongos com «vacina» viva avirulenta de Trypanosoma cruzi: II Ensaio da avaliação do tempo de eficiência da vacina

Camundongos "vacinados" com vacina viva avirulenta de T. cruzi se mostraram protegidos contra infecção virulenta, até 20 semanas após a imunização. Essa proteção foi inferior à observada avós 4 semanas de imunização e menor ainda do que a apresentada por animais infectados 4 semanas após a "vacinação" e reinfeetados 15 semanas depois. Neste último caso, a primeira infecção parece ter atuado como uma dose de reforço. O Autor assinala a dificuldade em determinar o tempo de validade da vacina, em virtude da resistência natural apresentada com a idade, mesmo pelos animais mais sensíveis.

Imunização de camundongos com "vacina" viva avirulenta do Trypanosoma cruzi: III. variação do meio de cultura

Os autores demonstram através de testes em camundongos que variando o meio de cultivo a avirulência da cepa Y, cultivada, do Trypanosoma cruzi se conserva inalterada. Diante da possibilidade de que se trate de um mutante da mesma linhagem Y virulenta, mantida em animais, sugerem a designação de PF (Pedreira de Freitas) para essa nova cepa.