Characterization of the novel Trypanosoma brucei inosine 5'-monophosphate dehydrogenase.

There is an alarming rate of human African trypanosomiasis recrudescence in many parts of sub-Saharan Africa. Yet, the disease has no successful chemotherapy. Trypanosoma lacks the enzymatic machinery for the de novo synthesis of purine nucleotides, and is critically dependent on salvage mechanisms.

Genetic analysis of influenza B viruses isolated in Uganda during the 2009-2010 seasons.

Background: Influenza B viruses can cause morbidity and mortality in humans but due to the lack of an animal reservoir are not associated with pandemics. Because of this, there is relatively limited genetic sequences available for influenza B viruses, especially from developing countries. Complete genome analysis of one influenza B virus and several gene segments of other influenza B viruses isolated from Uganda from May 2009 through December 2010 was therefore undertaken in this study.

Capacity-building efforts by the AFHSC-GEIS program.

Capacity-building initiatives related to public health are defined as developing laboratory infrastructure, strengthening host-country disease surveillance initiatives, transferring technical expertise and training personnel. These initiatives represented a major piece of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) contributions to worldwide emerging infectious disease (EID) surveillance and response. Capacity-building initiatives were undertaken with over 80 local and regional Ministries of Health, Agriculture and Defense, as well as other government entities and institutions worldwide.

Genetic analysis of H3N2 influenza A viruses isolated in 2006-2007 in Nairobi, Kenya.

Background: Minimal influenza surveillance has been carried out in sub-Saharan Africa to provide information on circulating influenza subtypes for the purpose of vaccine production and monitoring trends in virus spread and mutations.

Objective: The aim of this study was to investigate a surveillance program in Kenya to isolate and characterize influenza viruses.

Results: In the 2006-2007 influenza season, nine influenza A viruses were isolated.

Unified parasite lactate dehydrogenase and histidine-rich protein ELISA for quantification of Plasmodium falciparum.

There is a need for more objective and quantitative tools to replace microscopy in malaria diagnosis. Emphasis has recently been placed on alternative methods such as immunochromatography-based rapid tests. However, these tests provide only qualitative results.

Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya.

Objective: The antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine.

A novel exo-antigen-based ELISA for the detection of canine leishmaniasis.

Dogs which are infected with leishmania parasites serve as major reservoir hosts for zoonotic visceral leishmaniasis. The incidence of zoonotic visceral leishmaniasis is rising in many countries. This may be associated with the continuing drift of people and their pets from rural areas into peri-urban settings, particularly at the fringe of large cities.

Enzyme-linked immunosorbent assay for detection of Plasmodium falciparum histidine-rich protein 2 in blood, plasma, and serum.

Microscopy, the gold standard for the detection and quantification of malaria parasites in blood, is in many aspects deficient for this purpose. The method is poorly reproducible and can be inaccurate because Plasmodium falciparum parasites sequester for a portion of each asexual cycle. Due to these deficiencies, biomarkers such as P.

Protection of susceptible BALB/c mice from challenge with Leishmania major by nucleoside hydrolase, a soluble exo-antigen of Leishmania.

Leishmania major culture-derived, soluble, exogenous antigens have been shown to be a source of vaccine targets for the parasite. We have previously reported that L. major culture-derived, soluble, exogenous antigens can immunize BALB/c mice against challenge with L.

The utility of exoantigens for detection of Leishmania infections.

Exoantigens released by Leishmania promastigotes were the subject of a workshop held in Mombasa, Kenya. Investigators from the Walter Reed Army Institute of Research (Silver Spring, Maryland) met with scientists from government and academic institutes and industry to review the current global status of leishmaniasis and to explore the potential role of exoantigens in the detection of Leishmania in the vertebrate host and arthropod vector. Some encouraging data, particularly in the immunodiagnosis of leishmaniasis, were shared.

Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.

Objective: Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine.

Design: This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator.

Spatial clustering and epidemiological aspects of visceral leishmaniasis in two endemic villages, Baringo District, Kenya.

Visceral leishmaniasis (VL) seroprevalence in Kenya is unknown because of the lack of a practical and accurate diagnostic test or surveillance system. A novel serological assay was used to estimate the seroprevalence of Leishmania-specific antibodies, and Global Information System and spatial clustering techniques were applied to study the presence of spatial clusters in Parkarin and Loboi villages in Baringo District in 2001. VL seroprevalences were 52.

Antichagasic activity of komaroviquinone is due to generation of reactive oxygen species catalyzed by Trypanosoma cruzi old yellow enzyme.

A novel potent trypanocidal diterpene, komaroviquinone, was reduced by Trypanosoma cruzi old yellow enzyme (TcOYE) to its semiquinone radical. The reductase activity in trypanosome lysates was completely immunoabsorbed by anti-TcOYE antibody. Since TcOYE is expressed throughout the T.

Structural and mutational analysis of Trypanosoma brucei prostaglandin H2 reductase provides insight into the catalytic mechanism of aldo-ketoreductases.

Trypanosoma brucei prostaglandin F2alpha synthase is an aldo-ketoreductase that catalyzes the reduction of prostaglandin H2 to PGF2alpha in addition to that of 9,10-phenanthrenequinone. We report the crystal structure of TbPGFS.NADP+.

Kola acuminata proanthocyanidins: a class of anti-trypanosomal compounds effective against Trypanosoma brucei.

Human African trypanosomiasis is undergoing an alarming rate of recrudescence in many parts of sub-Saharan Africa. Yet, there is no successful chemotherapy for the disease due to a limited number of useful drugs, side effects and drawbacks of the existing medication, as well as the development of drug resistance by the parasite. Here we describe a new lead anti-trypanosomal compound isolated from Kola acuminata (Makasu).

Immunization with Leishmania major exogenous antigens protects susceptible BALB/c mice against challenge infection with L. major.

The potential of Leishmania major culture-derived soluble exogenous antigens (SEAgs) to induce a protective response in susceptible BALB/c mice challenged with L. major promastigotes was investigated. Groups of BALB/c mice were immunized with L.

Prostaglandin production from arachidonic acid and evidence for a 9,11-endoperoxide prostaglandin H2 reductase in Leishmania.

Lysates of Leishmania promastigotes can metabolise arachidonic acid to prostaglandins. Prostaglandin production was heat sensitive and not inhibited by aspirin or indomethacin. We cloned and sequenced the cDNA of Leishmania major, Leishmania donovani, and Leishmania tropica prostaglandin F(2alpha) synthase, and overexpressed their respective 34-kDa recombinant proteins that catalyse the reduction of 9,11-endoperoxide PGH(2) to PGF(2alpha).

Prostaglandin production from arachidonic acid and evidence for a 9,11-endoperoxide prostaglandin H2 reductase in Leishmania.

Lysates of Leishmania promastigotes can metabolise arachidonic acid to prostaglandins. Prostaglandin production was heat sensitive and not inhibited by aspirin or indomethacin. We cloned and sequenced the cDNA of Leishmania major, Leishmania donovani, and Leishmania tropica prostaglandin F(2alpha) synthase, and overexpressed their respective 34-kDa recombinant proteins that catalyse the reduction of 9,11-endoperoxide PGH(2) to PGF(2alpha).

A key role for old yellow enzyme in the metabolism of drugs by Trypanosoma cruzi.

Trypanosoma cruzi is the etiological agent of Chagas' disease. So far, first choice anti-chagasic drugs in use have been shown to have undesirable side effects in addition to the emergence of parasite resistance and the lack of prospect for vaccine against T. cruzi infection.

Enzyme-linked immunosorbent assay based on soluble promastigote antigen detects immunoglobulin M (IgM) and IgG antibodies in sera from cases of visceral and cutaneous leishmaniasis.

Leishmaniasis causes significant morbidity and mortality in areas where it is endemic. In areas where it is nonendemic, global travel and increased incidence of the disease in human immunodeficiency virus and intravenous-drug user populations are also causes for concern. The unavailability of rapid and reliable tests for diagnosis of the various leishmaniases makes patient management difficult.