Dataset Information

A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.

ABSTRACT:

Background

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.

Methods

Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and 5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays.

Results

CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.

Conclusion

This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.

SUBMITTER: Hainard A

PROVIDER: S-EPMC2696178 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Publications

A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.

Hainard Alexandre A Tiberti Natalia N Robin Xavier X Lejon Veerle V Ngoyi Dieudonné Mumba DM Matovu Enock E Enyaru John Charles JC Fouda Catherine C Ndung'u Joseph Mathu JM Lisacek Frédérique F Müller Markus M Turck Natacha N Sanchez Jean-Charles JC

PLoS neglected tropical diseases 20090616 6

<h4>Background</h4>Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammati ...[more]

PMID: 19554086

Similar Datasets

Project description: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 β-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 β-2-microglobulin in CSF of S2 patients (μg/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.

Project description:Human African trypanosomiasis (HAT), transmitted by tsetse flies, has historically infected hundreds of thousands of individuals annually in sub-Saharan Africa. Over the last decade, concerted control efforts have reduced reported cases to below 10,000 annually, bringing complete elimination within reach. A potential technology to eliminate HAT involves rendering the flies resistant to trypanosome infection. This approach can be achieved through the introduction of transgenic Sodalis symbiotic bacteria that have been modified to produce a trypanocide, and propagated via Wolbachia symbionts, which confer a reproductive advantage to the paratransgenic tsetse. However, the population dynamics of these symbionts within tsetse flies have not yet been evaluated. Specifically, the key factors that determine the effectiveness of paratransgenesis have yet to be quantified. To identify the impact of these determinants on T.b. gambiense and T.b. rhodesiense transmission, we developed a mathematical model of trypanosome transmission that incorporates tsetse and symbiont population dynamics. We found that fecundity and mortality penalties associated with Wolbachia or recombinant Sodalis colonization, probabilities of vertical transmission, and tsetse migration rates are fundamental to the feasibility of HAT elimination. For example, we determined that HAT elimination could be sustained over 25 years when Wolbachia colonization minimally impacted fecundity or mortality, and when the probability of recombinant Sodalis vertical transmission exceeded 99.9%. We also found that for a narrow range of recombinant Sodalis vertical transmission probability (99.9-90.6% for T.b. gambiense and 99.9-85.8% for T.b. rhodesiense), cumulative HAT incidence was reduced between 30% and 1% for T.b. gambiense and between 21% and 3% for T.b. rhodesiense, although elimination was not predicted. Our findings indicate that fitness and mortality penalties associated with paratransgenic symbionts, as well as tsetse migration rates, are instrumental to HAT elimination, and should be a key focus in the development of paratransgenic symbionts.

Project description:BACKGROUND:Malaria is endemic in all regions where gambiense or rhodesiense human African trypanosomiasis (HAT) is reported, and both diseases have similarities in their symptomatology. A combined test could be useful for both diseases and would facilitate integration of the screening for gambiense HAT (gHAT) and malaria diagnosis. This study aimed to evaluate a combined prototype rapid diagnostic test (RDT) for gHAT and malaria. METHODS:Blood samples were collected in the Democratic Republic of the Congo and in Uganda to evaluate the performance of a prototype HAT/Malaria Combined RDT in comparison to an individual malaria RDT based on Plasmodium falciparum (P.f.) Histidine Rich Protein II (HRP-II or HRP2) antigen (SD BIOLINE Malaria Ag P.f. RDT) for malaria detection and an individual gHAT RDT based on recombinant antigens, the SD BIOLINE HAT 2.0 RDT for HAT screening. Due to the current low prevalence of gHAT in endemic regions, the set of blood samples that were collected was used to evaluate the specificity of the RDTs for gHAT, and additional archived plasma samples were used to complete the evaluation of the HAT/Malaria Combined RDT in comparison to the HAT 2.0 RDT. RESULTS:Frozen whole blood samples from a total of 486 malaria cases and 239 non-malaria controls, as well as archived plasma samples from 246 gHAT positive and 246 gHAT negative individuals were tested. For malaria, the sensitivity and specificity of the malaria band in the HAT/Malaria Combined RDT were 96.9% (95% CI: 95.0-98.3) and 97.1% (95% CI: 94.1-98.8) respectively. The sensitivity and specificity of the SD BIOLINE malaria Ag P.f. RDT were 97.3% (95% CI: 95.5-98.6) and 97.1% (95% CI: 94.1-98.8) respectively. For gHAT, using archived plasma samples, the sensitivity and specificity were respectively 89% (95% CI: 84.4-92.6) and 93.5% (95% CI: 89.7-96.2) with the HAT/Malaria Combined RDT, and 88.2% (95% CI: 83.5-92) and 94.7% (95% CI: 91.1-97.2) with the HAT 2.0 RDT. Using the whole blood samples that were collected during the study, the specificity of the HAT/Malaria Combined RDT for gHAT was 95.8% (95% CI: 94.3-97.0). CONCLUSION:The HAT/Malaria Combined prototype RDT was as accurate as the individual malaria or gHAT RDTs. The HAT/Malaria Combined prototype RDT is therefore suitable for both malaria diagnosis and gHAT screening. However, there is a need to assess its accuracy using fresh samples in prospective clinical trials.

Project description:BackgroundAlthough human African trypanosomiasis (HAT) is uncommon among patients from non-endemic countries (NEC), there has been an increase in the number of cases reported in recent years.MethodsA systematic review of the literature was performed. The number of incoming tourists to HAT endemic countries was obtained from the United Nations World Tourism Organization. All HAT cases diagnosed in patients from NEC were included. Immigrants and refugees were excluded. We compared patients during and after the colonial period, and analyzed the relationship between the number of incoming travellers and the number of HAT cases.ResultsBetween 1902 and 2012, HAT was reported in 244 patients. Most HAT cases were reported before 1920, and after the year 2000. In the colonial era the average age of patients was lower (32.5±7.8 vs. 43.0±16.1 years, P<0.001), the proportion of females was lower (10.0% vs. 23.9%, P<0.01], most cases were diagnosed in expatriates, missionaries and soldiers (74.3%), and Gambian trypanosomiasis accounted for 86/110, (78%) of cases. In the post-colonial era most patients 91/125 (72.8%) were short-term tourists to game parks in Eastern and South-Eastern Africa (mainly in Tanzania); Rhodesian trypanosomiasis accounted for 94/123 (76.4%) of cases. Between 1995 and 2010 there has been a constant linear increase in the number of incoming tourists to Tanzania, and HAT cases occurred in small outbreaks rather than following a similar linear pattern.ConclusionsIn recent decades HAT patients from NEC are older, and more likely to be tourists who acquired the disease while visiting game-parks in Eastern and South-Eastern Africa. While Rhodesian trypanosomiasis is relatively uncommon among Africans, it now accounts for most cases reported among patients from NEC. Returning febrile travellers without an alternative diagnosis should be evaluated for HAT. Cases among travellers may serve as sentinels for Rhodesian trypanosomiasis "hot spots" in Africa.

Dataset Information

A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.

Background

Methods

Results

Conclusion

Publications

A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.

Similar Datasets

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