The diagnostic accuracy of HAT Sero-K-SeT is adequate for T b gambiense antibody detection in local health centres and could be used for active screening whenever a cold chain and electricity supply are unavailable and CATT/T b gambiense cannot be done.
Background
Spliced Leader (SL) trypanosome RNA is detectable only in the presence of live trypanosomes, is abundant and the Trypanozoon subgenus has a unique sequence. As previously shown in blood from Guinean human African trypanosomiasis (HAT) patients, SL-RNA is an accurate target for diagnosis. Detection of SL-RNA in the cerebrospinal fluid (CSF) has never been attempted. In a large group of Congolese gambiense HAT patients, the present study aims i) to confirm the sensitivity of SL-RNA detection in the blood and; ii) to assess the diagnostic performance of SL-RNA compared to trypanosome detection in CSF.
Methodology/Principal findings
Blood and CSF from 97 confirmed gambiense HAT patients from the Democratic Republic of Congo were collected using PAXgene blood RNA Tubes. Before RNA extraction, specimens were supplemented with internal extraction control RNA to monitor the extraction, which was performed with a PAXgene Blood RNA Kit. SL-RNA qPCR was carried out with and without reverse transcriptase to monitor DNA contamination. In blood, 92/97 (94.8%) HAT patients tested SL-RNA positive, which was significantly more than combined trypanosome detection in lymph and blood (78/97 positive, 80.4%, p = 0.001). Of 96 CSF RNA specimens, 65 (67.7%) were SL-RNA positive, but there was no significant difference between sensitivity of SL-RNA and trypanosome detection in CSF. The contribution of DNA to the Cq values was negligible. In CSF with normal cell counts, a fraction of SL-RNA might have been lost during extraction as indicated by higher internal extraction control Cq values.
Conclusions/Significance
Detection of SL-RNA in blood and CSF allows sensitive demonstration of active gambiense HAT infection, even if trypanosomes remain undetectable in blood or lymph. As this condition often occurs in treatment failures, SL-RNA detection in blood and CSF for early detection of relapses after treatment deserves further investigation.
Trial registration
JXT (EO) 19 AUG 2021: This study was an integral part of the diagnostic trial "New Diagnostic Tools for Elimination of Sleeping Sickness and Clinical Trials: Early tests of Cure" (DiTECT-HAT-WP4, ClinicalTrials.gov Identifier: NCT03112655).
The impact of concurrent exposure to neurotoxic metals is a significant threat to brain function, mostly in contexts of multiple exposures as seen in the developing world. Ninety-five children (46 boys and 49 girls, 6 to 11-year old) from Congo-Kinshasa were assessed for cognition using the Kaufman Assessment Battery for Children (2nd edition) and exposure to Cr, Cu, Zn, Co, Mn, As, Cd, Se, Hg, Fe, and Pb by inductively coupled plasma mass spectrometry (ICPMS) in serum and urine collections. Concentrations of elements were all above normal ranges except for Cd, Se and Hg. General linear mixed effects models were used to predict neurocognitive outcomes with variable selection methods including backward elimination, elastic net, or subsets identified based on subject matter expertise. After adjusting for sex, age, and SES, urinary Co > 5 µg/l was associated with poor simultaneous processing (memory)(p = 0.0237). Higher excretion but normal concentration of Cd in serum was associated with better memory (p = 0.03), planning (p = 0.05), and overall performance scores (p < 0.01); thus appeared to be neuroprotective. However, higher excretion of Zn had negative influence on the overall performance scores (p = 0.02). Predictive neurotoxicology is a challenging task in contexts of multiple and concurrent exposures. Urinary Co > 5 µg/l is a risk factor for poor neurodevelopmental outcomes in such contexts. The impact of heavy metals on cognition is dependent on concentrations of and interactions between toxic and essential elements.
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