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Biomedical subjects

Martin Odiit

Publications and source records attributed to Martin Odiit.

6 recordsLinked to original sources

Crisis, what crisis? Control of Rhodesian sleeping sickness.

There is an urgent need for cost-effective strategies for the sustainable control of Trypanosoma brucei rhodesiense (Rhodesian) sleeping sickness, which is a fatal zoonotic disease that has caused devastating epidemics during the past century. Sleeping sickness continues to be controlled by crisis management, using active case detection, treatment and vector control - activities that occur only during major epidemics; during the intervening periods, farmers and communities must fend for themselves. There are several methods for assessing the burden of this disease and there is a series of farmer-led methodologies that can be applied to reduce the burden of human and animal trypanosomiases.

Animal Husbandry↗

Intrathecal cytokine responses in Trypanosoma brucei rhodesiense sleeping sickness patients.

Intrathecal cytokine levels and blood-cerebrospinal fluid (CSF) barrier function were studied in 91 Trypanosoma brucei rhodesiense-infected patients. The CSF concentration of the cellular immune activation marker neopterin and the cytokines IL-6 and IL-10 were increased over control and post-treatment levels in all patients, with maximal levels observed in late-stage (meningoencephalitic) individuals. Analysis of CSF/serum concentration quotients indicated that IL-10 and neopterin were derived from central nervous system synthesis in at least 25% of the patients. Blood-CSF barrier dysfunction occurred in 64% of late-stage patients but not in early-stage patients. While the high level of neopterin observed in the late-stage patient CSF is indicative of widespread cellular activation, the increased levels of IL-6 and IL-10 suggest that counter-inflammatory cellular responses may be important in the regulation of neuropathogenesis in late-stage human African trypanosomiasis.

Animals↗

Sleeping sickness in Uganda: a thin line between two fatal diseases.

OBJECTIVE: To determine, through the use of molecular diagnostic tools, whether the two species of parasite that cause human African trypanosomiasis have become sympatric. DESIGN: Blood sampling of all available patients between June 2001 and June 2005 in central Uganda and between July and September 2003 in northwest Uganda and analysis of subcounty sleeping sickness records in Uganda between 1985 and 2005. SETTING: Sleeping sickness treatment centres in central and northwest Uganda and in south Sudan. PARTICIPANTS: Patients presenting at the treatment centres and diagnosed as having sleeping sickness. MAIN OUTCOME MEASURE: Classification of parasites from patients from each disease focus as either Trypanosoma brucei rhodesiense (acute form) or T b gambiense (chronic form). RESULTS: Blood from 231 patients with sleeping sickness in central Uganda and from 91 patients with sleeping sickness in northwest Uganda and south Sudan were screened for T b rhodesiense (detection of SRA gene) and T b gambiense (detection of TgsGP gene). All samples from central Uganda were classified as T b rhodesiense, and all samples from northwest Uganda and south Sudan were identified as T b gambiense. CONCLUSIONS: The two focuses of human African trypanosomiasis remain discrete, but the area of Uganda affected by the acute form of human sleeping sickness has increased 2.5-fold since 1985, spreading to three new districts within the past five years through movement of infected livestock. Without preventive action targeted at the livestock reservoir of this zoonotic disease, it is likely that the two disease focuses will converge. This will have a major impact on diagnosis and treatment of this neglected disease. Real time monitoring is recommended, using molecular diagnostic tools (at a regional surveillance centre, for example) targeted at both livestock and human patients.

Animals↗

Using remote sensing and geographic information systems to identify villages at high risk for rhodesiense sleeping sickness in Uganda.

Geographic information systems (GIS) and remote sensing were used to identify villages at high risk for sleeping sickness, as defined by reported incidence. Landsat Enhanced Thematic Mapper (ETM) satellite data were classified to obtain a map of land cover, and the Normalised Difference Vegetation Index (NDVI) and Landsat band 5 were derived as unclassified measures of vegetation density and soil moisture, respectively. GIS functions were used to determine the areas of land cover types and mean NDVI and band 5 values within 1.5 km radii of 389 villages where sleeping sickness incidence had been estimated. Analysis using backward binary logistic regression found proximity to swampland and low population density to be predictive of reported sleeping sickness presence, with distance to the sleeping sickness hospital as an important confounding variable. These findings demonstrate the potential of remote sensing and GIS to characterize village-level risk of sleeping sickness in endemic regions.

Animals↗

Severity of human african trypanosomiasis in East Africa is associated with geographic location, parasite genotype, and host inflammatory cytokine response profile.

The mechanisms underlying virulence in human African trypanosomiasis are poorly understood, although studies with experimental mice suggest that unregulated host inflammatory responses are associated with disease severity. We identified two trypanosomiasis foci with dramatically different disease virulence profiles. In Uganda, infections followed an acute profile with rapid progression to the late stage (meningoencephalitic infection) in the majority of patients (86.8%). In contrast, infections in Malawi were of a chronic nature, in which few patients progressed to the late stage (7.1%), despite infections of several months' duration. All infections were confirmed to be Trypanosoma brucei rhodesiense by testing for the presence of the serum resistance-associated (SRA) gene, but trypanosomes isolated from patients in Uganda or Malawi were distinguished by an SRA gene polymorphism. The two disease profiles were associated with markedly different levels of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in plasma. In Uganda but not Malawi early-stage TNF-alpha was elevated, while in Malawi but not Uganda early-stage TGF-beta was elevated. Thus, rapid disease progression in Uganda is associated with TNF-alpha-mediated inflammatory pathology, whereas in the milder disease observed in Malawi this may be ameliorated by counterinflammatory cytokines. These differing host responses may result either from differing virulence phenotypes of northern and southern trypanosomes or from immune response polymorphisms in the different host populations.

Adolescent↗

Recent developments in human African trypanosomiasis.

PURPOSE OF REVIEW: Sleeping sickness has re-emerged as a serious problem in sub-Saharan Africa, with an estimated 100000 deaths each year. South Sudan, the Democratic Republic of Congo and Angola have experienced serious epidemics of the Gambian form of the disease. The control of Gambian sleeping sickness, which relies primarily on active case finding followed by chemotherapy, is being threatened by problems of drug resistance. Recently, Rhodesian sleeping sickness has also posed a health risk to travellers visiting game parks in East Africa. RECENT FINDINGS: Because of war-related constraints, which have prevented case detection, the prevalence of Gambian sleeping sickness commonly exceeds 5% and reached 29% in one focus in south Sudan. The incidence of Gambian infections refractory to melarsoprol treatment has also risen sharply in northern Uganda, northern Angola and southern Sudan, with failure rates as high as 26.9%. Molecular techniques based on the gene for human serum resistance (SRA) have enabled the identification of human infective parasites in the domestic animal reservoir. This molecular tool has shown that the Rhodesian form of the disease is being carried in cattle northwards in Uganda towards areas endemic for the Gambian form. The coalescence of distributions of the chronic and acute forms of the disease will present problems for both control and treatment. SUMMARY: This review surveys the molecular tools that are improving our understanding of the epidemiology of sleeping sickness, and highlights the search for new diagnostics and drugs to deal with the disease.

Africa South of the Sahara↗