Photodynamic antimicrobial chemotherapy (PACT) for the treatment of malaria, leishmaniasis and trypanosomiasis

A photodynamic effect occurs when photosensitiser molecules absorb light and dissipate the absorbed energy by transferring it to biological acceptors (usually oxygen), generating an excess of reactive species that are able to force cells into death pathways. Several tropical diseases present physiopathological aspects that are accessible to the application of a photosensitiser and local illumination. In addition, disease may be transmitted through infected blood donations, and many of the aetiological agents associated with tropical diseases have been shown to be susceptible to the photodynamic approach. However, there has been no systematic investigation of the application of photoantimicrobial agents in the various presentations, whether to human disease or to the disinfection of blood products or even as photo-insecticides. We aim in this review to report the advances in the photoantimicrobial approach that are beneficial to the field of anti-parasite therapy and also have the potential to facilitate the development of low-cost/high-efficiency protocols for underserved populations.

Atividade, seletividade e mecanismos de ação de diamidinas aromáticas e análogos sobre Trypanosoma cruzi: um enfoque sobre o kDNA / Activity, selectivity and mechanism of action of aromatic and diamidinas analogues on Trypanosoma cruzi: a focus on the kDNA

A doença de Chagas, causada pelo Trypanosoma cruzi, é endêmica na América Latina, afetando mais de 15 milhões de pessoas. Como seu tratamento apresenta eficácia limitada e considerável toxicidade novas drogas são necessárias. Neste contexto, com a colaboração de grupos de química medicinal, nosso objetivo é a investigação da atividade tripanocida, seletividade, alvos celulares e mecanismos de ação de diamidinas aromáticas (DAs) e análogos. Inicialmente avaliamos o efeito tripanocida de onze Das sobre as formas tripomastigotas e amastigotas intracelulares, assim como sua toxidade para células de mamíferos e localização intracelular no parasito. Entre estes onze compostos, 2, 5 e 7 foram os mais ativos, com valores de IC50 na faixa micromolar e um alto índice de seletividade sobre as duas formas de T. cruzi. Através de microscopia de fluorescência (MF) foi possível localizar todos os compostos em organelas ricas em DNA, núcleo e mitocôndria (kDNA) e a análise utraestrutural utilizando os compostos 5 e 7 revelou que estes compostos levam a danos mitocondriais, incluindo desorganização do kDNA em formas tripomastigotas. O acúmulo das diamidinas foi maior no kDNA do que no núcleo, porém tam acúmulo não está correlacionado a uma maior atividade tripanocida. A seguir, visando um melhor entendimento do mecanismo de ação de diamidinas e análogos, investigamos uma possível correlação entre as propriedades de ligação ao kDNA de treze compostos com a atividade tripanocida, através de estudos de desnaturação térmica (Tm) e dicroísmo circular (DiC). Nossos resultados mostram tanto com kDNA purificado de epimastigotas como com uma seqüência conservada de 22-mer presente em minicírculos de T. cruzi, que a forte interação de amidinas ao kDNA não é o fator determinante para desencadear sua atividade tripanocida.Estes dados sugerem fortemente que outros fatores podem estar envolvidos no mecanismo de ação destes compostos, operando de modo primário ou secundário a interação composto: kDNA. Outros estudos serão necessários para melhor identificar os mecanismos envolvidos na ação destes compostos, visando contribuir para o desenho racional de compostos líderes para o tratamento da doença de Chagas.

Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following outline: negative control (A), positive control (B), treatment with plasma 1 (C), treatment with plasma 2 (D), and treatment with plasma 3 (E). Mice treated with human plasma showed an increase in longevity of 40.9+/-0.3 (C), 20+/-9.0 (D) and 35.6+/-9.3 (E) days compared to the control group (B) which was 4.3+/-0.5 days. The number of surviving mice and free of the parasite (blood smear and PCR negative) at the end of the experiment was 90%, 0%, and 60% for groups C, D, and E, respectively. The quantification of APOL1 was performed due to the large difference in the treatments that differed in the source plasma. In plasmas 1, 2, and 3 was detected the concentration of 194, 99, and 115 mg/dl of APOL1, respectively. However, we believe that this difference in the treatment efficiency is related to the level of APOL1 in plasmas.

Trypanosomiasis in dog: a case report

Trypanosoma are extra-erythrocytic, protozoan parasites of domestic and wild animals. It is transmitted by biting flies and a cause of fever, anemia, myocarditis and corneal opacity. In the present study, Trypanosoma infection is reported in a male bull dog of two years age at Lahore, Pakistan. Clinical signs and symptoms of infection are recorded. Confirmation of case was done by microscopic examination of Trypanosoma organism in thick blood smear. Furthermore, their effect on certain hematological parameters was studied and concluded that there was decrease of hemoglobin [Hb] concentration and packed cell volume [PCV] while erythrocytes sedimentation rate [ESR] was increased in the infected dog. The animal was successfully treated with single dose of diminazene diaceturate at the dose rate of 3.5 mg/kg body weight, intramuscularly alongwith the supportive therapy

In vitro and in vivo therapeutic activity of Parthenium hysterophorus against Trypanosoma evansi.

Crude 50% ethanolic extract of P. hysterophorus flowers exhibited trypanocidal activity in vitro at all the four concentrations tested i.e. 5, 50, 500 and 1000 micrograms/ml. In vivo trial revealed that the extract exerted antitrypanosomal effect at doses of 100 and 300 mg/kg body wt, i.p. as evidenced by significantly reduced (P < 0.01) mean parasitaemia on days 3, 4, 5 and 6 when compared with untreated control group. Further at 100 and 300 mg/kg, body wt doses, the survival period was significantly (P < 0.05) prolonged as compared to control group. The extract was, however, found toxic to the animals at 1000 mg/kg dose.

Le traitement de la maladie du sommeil en 1994 : une situation preoccupante

Ce texte parle essentiellement des medicaments disponibles en 1994 contre la trypanosomiase en Afrique Centrale. L'auteur presente une liste rapide a etablir; il n'y en a en effet que trois a ce jour; un pour la phase lymphatico-sanguine; le Pentamidine; un pour la phase meningo-encephalitique; le melarsoprol et maintenant; le DL Alpha-Difluoromethylornithine; ou Eflornithine; ou encore D.F.M.O

Place du traitement de la trypanosomiase humaine africaine en Trypanosoma brucei gambiense dans l'elaboration de la strategie de lutte

Le but de cet article est de susciter une reflexion sur l'articulation logique des differentes activites de lutte contre la trypanosomiase humaine africaine; en fonction des moyens dont on dispose pour traiter les malades. En effet; on considere trop souvent le depistage comme une finalite; propre a satisfaire les statistiques et les bilans d'activites. L'auteur presente donc le traitement tel qu'il est administre au centre national et au centre regional de la Republique Centrafricaine

Prevalencia de Infeccion Chagasica en Universitarios de Santa Cruz de la Sierra-Bolivia / Prevalence of infection chagasic and Students of Santa Cruz de la Sierra-Bolivia

De una poblacion de 4.600 nuevos studiantes de la universidad Estatal de la ciudad de Santa Cruz de la Sierra, se tomo una muestra aleatoria de 372 estudiantes a los que se realizo un test de hemoglutinacion indirecta (HAI) para enfermedad de chagas y un electrocardiograma (ECG) convencional. El 17.2 por ciento (64/373) tenian el test HAI positivo y de esto el 16.5 por ciento (10/64) tenian algun trasntorno electrocardiografica. En el grupo con HAI negativa el 10 por ciento (31/308) presento alguna anormalidad electrocardiografica. No se observo asociacion entre serologia positiva para la enfermedad de Chagas y alteracion del ECG en general (x2=1,67 p=0.2). Se observo una asociacion positiva entre serologia para Chagas y trastornos de conduccion intraventricular (TCIV) y esta parece intensificarse entre los menores de 19 anos con un Odds Ratio de 10.4(p<0.05)

Circurating trypanosomal antigen levels in sleeping sickness patients under going treatment at Alupe

Sera from 99 sleeping sickness patients admitted to Alupe Hospital were analyzed for circulating trypanosomal antigens using a sandwich antigen-trapping enzyme immunosorbent assay. Trypanosomal antigens were detected in 83 (84) of the patients. Post-treatment antigen profile in 67 patients showed five distinct patterns: in 48 of the patients antigen levels remained elevated thoughout; in 31 of the patients antigens dropped to the; negative value; and became elevated afterward; in 6.0 of the patients antigen levels were negative initially; but became elevated later; in 7.5 of the patients antigen levels remained below the negative value thoughout. The significance of these observations in the clinical management of sleeping sickness is discussed

Tripanosomiasis aguda: report de un caso y revisión del tema / Acute tripanosomiasis: report of a case

La tripanosomiasis americana o Enfermedad de Chagas es una zoonosis común en áreas endémicas del Hemisferio Occidental, entre las que se encuentra incluída México. Esta enfermedad se caracteriza por una forma aguda frecuentemente asintomática y una forma crónica con graves secuelas cardíacas y gastrointestinales. A continuación se presenta el reporte de un caso de tripanosomiasis aguda en una paciente proveniente de área endemica y cuya evolución se vio complicada por el desarrollo de accidente vascular cerebral que la llevó a la muerte, y se realiza una revisión de los aspectos más importantes de la enfermedad