Options for Field Diagnosis of Human African Trypanosomiasis

Chappuis, François; Loutan, Louis; Simarro, Pere P.; Lejon, Veerle; Büscher, Philippe

doi:10.1128/cmr.18.1.133-146.2005

Cited by 297 publications

(333 citation statements)

References 99 publications

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“…Examination of cerebrospinal fluid is necessary in all patients to assess whether the parasites have penetrated into the brain (21). The obvious drawbacks of this method are that it is labor-intensive and invasive.…”

Section: Discussionmentioning

confidence: 99%

Global metabolic responses of mice to Trypanosoma brucei brucei infection

Wang

Utzinger²,

Saric

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

126

185

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Human African trypanosomiasis (HAT) is transmitted by tsetse flies and, if untreated, is fatal. Treatment depends on infection stage, and early diagnosis is crucial for effective disease management. The systemic host biochemical changes induced by HAT that enable biomarker discovery or relate to therapeutic outcome are largely unknown. We have characterized the multivariate temporal responses of mice to Trypanosoma brucei brucei infection, using 1 H nuclear magnetic resonance (NMR) spectroscopic metabolic phenotyping of urine and plasma. Marked alterations in plasma metabolic profiles were detected already 1 day postinfection. Elevated plasma concentrations of lactate, branched chain amino acids, and acetylglycoprotein fragments were noted. T. brucei brucei-infected mice also had an imbalance of plasma alanine and valine, consistent with differential gluconeogenesis (parasite)-ketogenesis (host) pathway counterflux, involving stimulated host glycolysis, ketogenesis, and enhanced lipid oxidation in the host. Histopathologic evidence of T. brucei brucei-induced extramedullary hepatic hemopoiesis, renal interstitial nephritis, and a provoked inflammatory response was also noted. Metabolic disturbance of gut microbiotal activity was associated with infection, as indicated by changes in the urinary concentrations of the microbial co-metabolites, including hippurate. Concluding, parasite infection results in multiple systemic biochemical effects in the host and disturbance of the symbiotic gut microbial metabolic interactions. Investigation of these transgenomic metabolic alterations may underpin the development of new diagnostic criteria and metrics of therapeutic efficacy. diagnosis ͉ metabonomics ͉ NMR spectroscopy ͉ trypanosomiasis

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Section: Discussionmentioning

confidence: 99%

Global metabolic responses of mice to Trypanosoma brucei brucei infection

Wang

Utzinger²,

Saric

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

126

185

View full text Add to dashboard Cite

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“…In both forms of the disease, parasites are initially localized in the blood stream, lymph, and peripheral tissues; this is the first or hemolymphatic stage (S1). During this stage, patients present generic clinical features that are common to other infectious diseases such as human immunodeficiency virus (HIV), malaria, and tuberculosis (TB), which can coexist with HAT, thus making its early diagnosis difficult (2). If treatment is not carried out, the disease progresses to the second or meningoencephalitic stage (S2) after trypanosomes cross the blood-brain barrier (BBB) and invade the central nervous system (CNS).…”

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confidence: 99%

Discovery and Verification of Osteopontin and Beta-2-microglobulin as Promising Markers for Staging Human African Trypanosomiasis

Tiberti¹,

Hainard²,

Lejon

et al. 2010

Molecular & Cellular Proteomics

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Human African trypanosomiasis, or sleeping sickness, is a parasitic disease endemic in sub-Saharan Africa, transmitted to humans through the bite of a tsetse fly. The first or hemolymphatic stage of the disease is associated with presence of parasites in the bloodstream, lymphatic system, and body tissues. If patients are left untreated, parasites cross the blood-brain barrier and invade the cerebrospinal fluid and the brain parenchyma, giving rise to the second or meningoencephalitic stage. Stage determination is a crucial step in guiding the choice of treatment, as drugs used for S2 are potentially dangerous. Current staging methods, based on counting white blood cells and demonstrating trypanosomes in cerebrospinal fluid, lack specificity and/or sensitivity. In the present study, we used several proteomic strategies to discover new markers with potential for staging human African trypanosomiasis. Cerebrospinal fluid (CSF) samples were collected from patients infected with Trypanosoma brucei gambiense in the Democratic Republic of Congo. The stage was determined following the guidelines of the national control program. The proteome of the samples was analyzed by two-dimensional gel electrophoresis (n ‫؍‬ 9), and by sixplex tandem mass tag (TMT) isobaric labeling (n ‫؍‬ 6) quantitative mass spectrometry. Overall, 73 proteins were overexpressed in patients presenting the second stage of the disease. Two of these, osteopontin and ␤-2-microglobulin, were confirmed to be potential markers for staging human African trypanosomiasis (HAT) by Western blot and ELISA. The two proteins significantly discriminated between S1 and S2 patients with high sensitivity (68% and 78%, respectively) for 100% specificity, and a combination of both improved the sensitivity to 91%. The levels of osteopontin and ␤-2-microglobulin in CSF of S2 patients (g/ml range), as well as the fold increased concentration in S2 compared with S1 (3.8 and 5.5 respectively) make the two markers good candidates for the development of a test for staging HAT patients. Molecular & Cellular Proteomics 9:2783-2795, 2010.

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“…This in part reflects the inherent delay for seroconversion (3-4 weeks). 8 In addition, occasional cases of false positive serology in travelers have been documented. 9 Multiple blood smears were taken during our patient's illness, but were negative until the third bout of fever.…”

Section: Commentmentioning

confidence: 99%

Human African Trypanosomiasis in a Traveler: Diagnostic Pitfalls

Meltzer

Leshem²,

Steinlauf³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. An Israeli traveler returning from Tanzania presented with a relapsing febrile illness. A diagnosis of Trypanosoma brucei rhodesiense infection was established by blood smear after nearly a month. Blood polymerase chain reaction failed to provide an early diagnosis of human African trypanososmiasis. Recognition of suggestive signs should prompt physicians to perform repeated tests before ruling out human African trypanososmiasis.

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Options for Field Diagnosis of Human African Trypanosomiasis

Cited by 297 publications

References 99 publications

Global metabolic responses of mice to Trypanosoma brucei brucei infection

Global metabolic responses of mice to Trypanosoma brucei brucei infection

Discovery and Verification of Osteopontin and Beta-2-microglobulin as Promising Markers for Staging Human African Trypanosomiasis

Human African Trypanosomiasis in a Traveler: Diagnostic Pitfalls

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