http://www.kinetoplastids.com The most accessed research articles published by Kinetoplastid Biology and Disease 2007-08-17T00:00:00Z Background: The protozoan pathogen, Trypanosoma brucei, undergoes complex cycles of differentiation and multiplication in its vector, the tsetse fly, genus Glossina. Flies are refractory to infection and resistance mechanisms operate at a number of levels and timepoints. Here we have used highly conspicuous green fluorescent trypanosomes to study the early events in establishment of infection in the fly midgut. Results: Less than 10% of the bloodstream form trypanosomes in the infected feed differentiated into viable procyclics. Up to day 3, trypanosomes were found in the bloodmeal in every fly examined, and increased in number between days 1 and 3. Flies dissected on days 5 and 6 fell into 2 clearly distinct groups: those with high numbers of trypanosomes and those with undetectable infection. Trypanosomes were found in the ectoperitrophic space and proventriculus from 6 days following the infective feed. Conclusion: Trypanosomes that have undergone successful differentiation appear to experience an environment within the midgut suited to their unrestricted growth for the first 3 days. After this time, a process of attrition is evident in some flies, which leads to the complete elimination of infection. By day 5, flies fall into 2 groups according to the level of infection: high or undetectable. This timecourse coincides with lectin secretion, development of the PM and the digestion and movement of the bloodmeal along the gut. Further experiments are needed to discriminate between these factors. http://www.kinetoplastids.com/content/2/1/1 Wendy Gibson Mick Bailey Kinetoplastid Biology and Disease 2003, null:1 2003-04-10T00:00:00Z doi:10.1186/1475-9292-2-1 /content/figures/1475-9292-2-1-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 1 2003-04-10T00:00:00Z XML According to the Series Editors, "The World Class Parasites book series are written for researchers, students and scholars who enjoy reading about excellent research on problems of global significance. Each volume focuses on a parasite, or group of parasites, that has a major impact on human health, or agricultural productivity, and against which we have no satisfactory defense. The volumes are intended to supplement more formal texts that cover taxonomy, life cycles, morphology, vector distribution, symptoms and treatment. They integrate vector, pathogen and host biology and celebrate the diversity of approach that comprises modern parasitological research."Three volumes deal with kinetoplastid disease: Volume 1 - the African Trypanosomes, Volume 4 - Leishmaniasis, Volume 7 - American Trypanosomiasis. We asked 5 independent experts to assess the quality of these volumes and the extent to which they had met their stated aims. http://www.kinetoplastids.com/content/2/1/9 Frank Cox Diane McMahon-Pratt Kwang-Poo Chang Samuel Goldenberg Julio Scharfstein Kinetoplastid Biology and Disease 2003, null:9 2003-10-28T00:00:00Z doi:10.1186/1475-9292-2-9 /content/figures/1475-9292-2-9-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 9 2003-10-28T00:00:00Z XML Kinetoplastida are protozoan organisms that probably diverged early in evolution from other eukaryotes. They are characterized by a number of unique features with respect to their energy and carbohydrate metabolism. These organisms possess peculiar peroxisomes, called glycosomes, which play a central role in this metabolism; the organelles harbour enzymes of several catabolic and anabolic routes, including major parts of the glycolytic and pentosephosphate pathways. The kinetoplastid mitochondrion is also unusual with regard to both its structural and functional properties.In this review, we describe the unique compartmentation of metabolism in Kinetoplastida and the metabolic properties resulting from this compartmentation. We discuss the evidence for our recently proposed hypothesis that a common ancestor of Kinetoplastida and Euglenida acquired a photosynthetic alga as an endosymbiont, contrary to the earlier notion that this event occurred at a later stage of evolution, in the Euglenida lineage alone. The endosymbiont was subsequently lost from the kinetoplastid lineage but, during that process, some of its pathways of energy and carbohydrate metabolism were sequestered in the kinetoplastid peroxisomes, which consequently became glycosomes. The evolution of the kinetoplastid glycosomes and the possible selective advantages of these organelles for Kinetoplastida are discussed. We propose that the possession of glycosomes provided metabolic flexibility that has been important for the organisms to adapt easily to changing environmental conditions. It is likely that metabolic flexibility has been an important selective advantage for many kinetoplastid species during their evolution into the highly successful parasites today found in many divergent taxonomic groups.Also addressed is the evolution of the kinetoplastid mitochondrion, from a supposedly pluripotent organelle, attributed to a single endosymbiotic event that resulted in all mitochondria and hydrogenosomes of extant eukaryotes. Furthermore, indications are presented that Kinetoplastida may have acquired other enzymes of energy and carbohydrate metabolism by various lateral gene transfer events different from those that involved the algal- and α-proteobacterial-like endosymbionts responsible for the respective formation of the glycosomes and mitochondria. http://www.kinetoplastids.com/content/2/1/11 Veronique Hannaert Frederic Bringaud Fred Opperdoes Paul Michels Kinetoplastid Biology and Disease 2003, null:11 2003-10-28T00:00:00Z doi:10.1186/1475-9292-2-11 /content/figures/1475-9292-2-11-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 11 2003-10-28T00:00:00Z XML Background: Leishmania (Leishmania) amazonensis infection in man results in a clinical spectrum of disease manifestations ranging from cutaneous to mucosal or visceral involvement. In the present study, we have investigated the genetic variability of 18 L. amazonensis strains isolated in northeastern Brazil from patients with different clinical manifestations of leishmaniasis. Parasite DNA was analyzed by sequencing of the ITS flanking the 5.8 S subunit of the ribosomal RNA genes, by RAPD and SSR-PCR and by PFGE followed by hybridization with gene-specific probes. Results: ITS sequencing and PCR-based methods revealed genetic heterogeneity among the L. amazonensis isolates examined and molecular karyotyping also showed variation in the chromosome size of different isolates. Unrooted genetic trees separated strains into different groups. Conclusion: These results indicate that L. amazonensis strains isolated from leishmaniasis patients from northeastern Brazil are genetically diverse, however, no correlation between genetic polymorphism and phenotype were found. http://www.kinetoplastids.com/content/6/1/5 Joao Paulo de Oliveira Flora Fernandes Angela Cruz Viviane Trombela Elisangela Monteiro Anamaria Camargo Aldina Barral Camila de Oliveira Kinetoplastid Biology and Disease 2007, null:5 2007-06-21T00:00:00Z doi:10.1186/1475-9292-6-5 /content/figures/1475-9292-6-5-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 5 2007-06-21T00:00:00Z XML Background: A meeting was organized by Drugs for Neglected Diseases initiative (DNDi) and the Institute Pasteur (IP), Paris, to review the treatment for all forms of cutaneous leishmaniasis (CL) and to propose a strategy for the development of new efficacious and affordable treatments.MethodThe global burden of CL was discussed with respect to financial impact; relation to poverty; the stigma of CL lesions and scars (particularly in young women); lack of effective, affordable, easily implemented tools and political will and resources to implement available control tools; and lack of input from pharmaceutical and biotechnology companies to develop new drugs and vaccines. Results: According to the experts from different endemic countries present, the financial and social burdens of CL are high, but we have limited quantitative data. The analysis of published trials indicates that the quality of most trials is poor and requires both improvement and standardization. The available drugs are inadequate. Criteria by which different CL types could be prioritized as target disease were set. These criteria included: severity of the disease; lack of response to available drugs; overall incidence and prevalence of the disease; sequelae of the disease, (including recidivans and mucosal leishmaniasis); the impact of treatment of individuals on control of transmission and lack of other major parties involved in drug development. Based on these, the anthroponotic CL and its sequel "recidivans" caused by L. tropica and CL caused by L. braziliensis and its sequel, mucosal leishmaniasis were considered to be the target diseases.The mechanism for controlling Leishmania infection to reach a stable self healing process is a balanced immune response. Immune stimulation during chemotherapy can enhance cure. There is no adequately effective vaccine, but some encouraging results have been obtained with whole killed Leishmania parasites or imiquimod (an immuno-modulator) plus antimonials. Further studies are needed. One safety/immunogenicity clinical trial is currently ongoing with a Second Generation Vaccine (SGV).Conclusions and recommendationsThere is an urgent need for new treatments for all CL types. CL should be considered as a neglected disease and organizations, such as DNDi, should include it in their list of target diseases. It was agreed that immuno-chemotherapy (with "therapeutic" vaccines or immunomodulators) has a strong potential to make an impact as a new therapy of CL with the view of shortening/reducing duration and dose of drug treatment and preventing resistance. There is also a need for safe, affordable and efficacious new chemotherapeutics. The quality of clinical trials needs to be enhanced and standardized. Short and long-term objectives and activities were defined as a part of meeting recommendations. http://www.kinetoplastids.com/content/6/1/3 Farrokh Modabber Pierre Buffet Els Torreele Genevieve Milon Simon Croft Kinetoplastid Biology and Disease 2007, null:3 2007-04-24T00:00:00Z doi:10.1186/1475-9292-6-3 /content/figures/1475-9292-6-3-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 3 2007-04-24T00:00:00Z XML Members of the Trypanosomatidae family comprise a large number of species that are causative agents of important diseases such as sleeping sickness, Chagas' disease and Leishmaniasis. These organisms are also of biological interest since they are able to change the morphology according to the environment where they live, through a process of reversible cell transformation, and possess structures and organelles that are not found in mammalian cells. This review analyses the process of transformation, which takes place during the life cycle of Trypanosoma cruzi in the vertebrate and invertebrate hosts. Special attention is given to the interaction of the parasite with vertebrate cells. In addition, the present knowledge of structures and organelles such as the nucleus, the plasma membrane, the sub-pellicular microtubules, the flagellum, the kinetoplast-mitochondrion complex, the peroxisome (glycosome), the acidocalcisome and the structures and organelles involved in the endocytic pathway, is reviewed from a cell biology perspective. The possible use of available data for the development of new anti parasite drugs is also discussed. http://www.kinetoplastids.com/content/1/1/3 Wanderley de Souza Kinetoplastid Biology and Disease 2002, null:3 2002-05-31T00:00:00Z doi:10.1186/1475-9292-1-3 /content/figures/1475-9292-1-3-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 3 2002-05-31T00:00:00Z XML Phylogenetic analyses of the family Trypanosomatidae have been conducted using both 18S rRNA gene sequences and a variety of protein sequences. Using a variety of phylogenetic methods, 18S rRNA phylogenies indicate that the genus Trypanosoma is not monophyletic. Rather, they suggest that the American and African trypanosomes constitute distinct clades. By contrast, phylogenetic analyses of available sequences in 42 protein families gene generally supported monophyly of the genus Trypanosoma. One possible explanation for these conflicting results is poor taxon sampling in the case of protein coding genes, most of which have been sequenced for only a few species of Trypanosomatidae. http://www.kinetoplastids.com/content/2/1/15 Austin Hughes Helen Piontkivska Kinetoplastid Biology and Disease 2003, null:15 2003-10-28T00:00:00Z doi:10.1186/1475-9292-2-15 /content/figures/1475-9292-2-15-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 15 2003-10-28T00:00:00Z XML Background: Post kala azar dermal leishmaniasis (PKDL) is a disease that appears after treatment of visceral leishmaniasis (VL). The highest incidence of PKDL in the world is in Sudan. Many patients heal spontaneously within 6 months but those who don't are difficult to treat, often requiring months of daily injections. These patients harbour parasite in their skin and are believed to be a source of infection and possibly epidemics. Present treatment modalities of PKDL are inadequate and impractical due to cost, duration of treatment required and side effects. New approach for treatment of PKDL is required. A joint meeting of the UNICEF/UNDP/World Bank/WHO Special Programme for research and training in Tropical Disease (TDR) and the Infectious Disease Research Institute (IDRI) Seattle, USA was held to review the progress of therapeutic vaccines and plan the development of treatment modalities for PKDL. Methods: The history of leishmaniasis vaccine development for prophylaxis and therapy was reviewed. Other than previous infection – simulated by inoculation of live Leishmania as a vaccine (leishmanization), none of the preparations of killed parasite with or without adjuvants have shown significant prophylactic efficacy. Killed L. major absorbed with alum and mixed with BCG remains to be tested as a prophylactic vaccine. Results: Killed parasite preparations i.e. L. mexicana mixed with BCG and L. amazonensis (combined with low dose of antimonial), have shown efficacy in immunotherapy and immuno-chemotherapy, respectively. In addition combined full antimonial plus alum-absorbed autoclaved L. major vaccine has been shown to significantly improve therapy of refractory PKDL patients. These are all crude preparations of parasites and are difficult to define and standardize. However, there is now a new, second generation vaccine, Leish-111f + MPL-SE, composed of a recombinant protein comprising three leishmanial antigens and a defined adjuvant in clinical development.Conclusion and recommendationsImmuno-chemotherapy has the potential of becoming a practical and affordable treatment modality for PKDL and other forms of leishmaniasis. The encouraging results with alum-autoclaved L. major + antimonial should be pursued. However, before further trials, availability of the vaccine and its production under Good Manufacturing Product, hence quality control must be assured. Following satisfactory safety profile of Leish-111f+MPL-SE, clinical trials using this vaccine initially with antimonials should be initiated. Similarly immunotherapy of VL should be considered with the view to controlling development of PKDL. Some immunological studies are required prior to initiation of immunotherapy in VL patients. http://www.kinetoplastids.com/content/6/1/7 Hashim Ghalib Farrokh Modabber Kinetoplastid Biology and Disease 2007, null:7 2007-08-17T00:00:00Z doi:10.1186/1475-9292-6-7 /content/figures/1475-9292-6-7-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 7 2007-08-17T00:00:00Z XML Background: Genetic exchange occurs between Trypanosoma brucei strains during the complex developmental cycle in the tsetse vector, probably within the salivary glands. Successful mating will depend on the dynamics of co-infection with multiple strains, particularly if intraspecific competition occurs. We have previously used T. brucei expressing green fluorescent protein to study parasite development in the vector, enabling even one trypanosome to be visualized. Here we have used two different trypanosome strains transfected with either green or red fluorescent proteins to study the dynamics of co-infection directly in the tsetse fly. Results: The majority of infected flies had both trypanosome strains present in the midgut, but the relative proportion of red and green trypanosome strains varied considerably between flies and between different sections of the midgut in individual flies. Colonization of the paired salivary glands revealed greater variability than for midguts, as each gland could be infected with red and/or green trypanosome strains in variable proportions. Salivary glands with a mixed infection appeared to have a higher density of trypanosomes than glands containing a single strain. Comparison of the numbers of red and green trypanosomes in the proventriculus, salivary exudate and glands from individual flies showed no correlation between the composition of the trypanosome population of the proventriculus and foregut and that of the salivary glands. For each compartment examined (midgut, foregut, salivary glands), there was a significantly higher proportion of mixed infections than expected, assuming the null hypothesis that the development of each trypanosome strain is independent. Conclusion: Both the trypanosome strains used were fully capable of infecting tsetse, but the probabilities of infection with each strain were not independent, there being a significantly higher proportion of mixed infections than expected in each of three compartments examined: midgut, proventriculus and salivary glands. Hence there was no evidence of competition between trypanosome strains, but instead co-infection was frequent. Infection rates in co-infected flies were no different to those found routinely in flies infected with a single strain, ruling out the possibility that one strain enhanced infection with the other. We infer that each fly is either permissive or non-permissive of trypanosome infection with at least 3 sequential checkpoints imposed by the midgut, proventriculus and salivary glands. Salivary glands containing both trypanosome strains appeared to contain more trypanosomes than singly-infected glands, suggesting that lack of competition enhances the likelihood of genetic exchange. http://www.kinetoplastids.com/content/6/1/4 Lori Peacock Vanessa Ferris Mick Bailey Wendy Gibson Kinetoplastid Biology and Disease 2007, null:4 2007-06-06T00:00:00Z doi:10.1186/1475-9292-6-4 /content/figures/1475-9292-6-4-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 4 2007-06-06T00:00:00Z XML Background: The direct agglutination test (DAT) has proved to be a very important sero-diagnostic tool combining high levels of intrinsic validity and ease of performance. Otherwise, fast agglutination screening test (FAST) utilises only one serum dilution making the test very suitable for the screening of large populations. Results: We have tested FAST and DAT for the detection anti-Leishmania antibodies in serum samples from patients with American visceral (AVL) and cutaneous leishmaniases (ACL) in Minas Gerais State, Brazil. The DAT on serum and blood samples of confirmed AVL patients found all samples positive at a serum dilution of ≥ 1:800. This dilution was subsequently used as cut off value in the study. The blood and serum samples of these confirmed patients could also be clearly read in FAST using a 1:100 dilution with the same high sensitivity. DAT and FAST were not able to detect significant amounts of antibodies in samples from ACL patients and are not suitable for the diagnosis of this manifestation of the disease. Conclusion: We suggest that both DAT and FAST are very practical diagnostic tools for the sero-diagnosis of AVL under rural conditions as both serological tests do not require sophisticated equipment, a cold chain and are very simple to perform. http://www.kinetoplastids.com/content/4/1/4 Eduardo Silva Gerard Schoone Celia Gontijo Reginaldo Brazil Raquel Pacheco Henk Schallig Kinetoplastid Biology and Disease 2005, null:4 2005-06-14T00:00:00Z doi:10.1186/1475-9292-4-4 /content/figures/1475-9292-4-4-toc.gif Kinetoplastid Biology and Disease 1475-9292 ${item.volume} 4 2005-06-14T00:00:00Z XML