Diversity of trypanosome species in small ruminants, dogs and pigs from three sleeping sickness foci of the south of Chad.

Despite considerable data generated on livestock trypanosomoses in tsetse-infested areas, little attention was paid for animal African trypanosomosis (AAT) in sleeping sickness foci. This study aimed to fill this gap by determining the diversity and prevalence of trypanosome species in animals from three Chadian human African trypanosomosis (HAT) foci. Blood samples were collected from 443 goats, 339 sheep, 228 dogs and 98 pigs of the Mandoul, Maro and Moissala HAT foci in the south of Chad. Capillary tube centrifugation (CTC) and specific primers were used to search trypanosomes. The prevalence of trypanosome infections was 6.3% for CTC and 22.7% for PCR. Trypanosomes of the sub-genus Trypanozoon had the highest prevalence (16.6%) while T. congolense savannah (1.9%) was least prevalent. Significant differences were recorded between the prevalence of trypanosome species (χ2 = 8.34; p = 0.04) and HAT foci (χ2 = 24.86; p ≤0.0001). Maro had the highest prevalence (32.7%) and Mandoul the lowest (17.4%). Significant differences were also recorded for T. congolense forest (χ2 = 45.106; p < 0.0001) and all T. congolense (χ2 = 34.992; p < 0.0001). Goats had the highest prevalence (26.9%) and sheep the lowest one (18.6%). Between animals, significant differences were recorded for trypanosomes of the sub-genus Trypanozoon (χ2 = 9.443; p = 0.024), T. congolense forest (χ2 = 10.476; p = 0.015) and all T. congolense (χ2 = 12.152; p = 0.007). Of the 251 animals carrying trypanosome infections, 88.8% had single infections while 11.2% had more than one trypanosome species. The overall prevalence of single and mixed trypanosome infections were respectively 20.1% and 2.6% in animal taxa of all foci. This study highlighted a diversity of trypanosomes in animal taxa of all HAT foci. It showed that AAT constitutes a threat for animal health and animal breeding in Chadian HAT foci. In these tsetse infested areas, reaching the elimination of AAT requires the designing and the implementation of control measures against trypanosome infections.

Molecular characterization of early breast cancer onset to understand disease phenotypes in African patients.

Female breast cancer (BC) is the leading cause of cancer-related deaths worldwide with higher mortality rates and early onset in developing countries. The molecular basis of early disease onset is still elusive. We recruited 472 female breast cancer from two sub-Saharan African countries (Cameroon and Congo) between 2007 and 2018 and collected clinical data from these patients. To investigate the molecular drivers of early disease onset, we analyzed publicly available breast cancer molecular data from the cancer genome atlas (TCGA) and the gene expression omnibus (GEO) for copy number alteration, mutation and gene expression. Early BC onset (EOBRCA) (diagnosis before 45 years) was higher in African women compared with the TCGA cohort (51.7% vs 15.6%). The tumor grade, mitotic index, HER2 + phenotype, basal-like phenotype and ki67 were higher in EOBRCA for all cohorts. BC risk factors such as parity, breastfeeding early onset of menarche and use of hormonal contraceptives were significantly associated with EOBRCA (p < 0.05). EOBRCA was equally associated with copy number alterations in several oncogenes including CDH6 and FOXM1 and tumor suppressor including TGM3 and DMBT1 as well as higher TP53 mutation rates (OR: 2.93, p < 0.01). There was a significant enrichment of TGFß signaling in EOBRCA with TGM3 deletions, which was associated with high expression of all SMAD transcription factors as well as WNT ligands. The Frizzled receptors FZD1, FZD4 and FZD6 were significantly upregulated in EOBRCA, suggesting activation of non-canonical WNT signaling. Our data, suggest the implication of TGM3 deletion in early breast cancer onset. Further molecular investigations are warranted in African patients.

Molecular identification of Trypanosoma brucei gambiense in naturally infected pigs, dogs and small ruminants confirms domestic animals as potential reservoirs for sleeping sickness in Chad.

Human African trypanosomiasis (HAT) has been targeted for zero transmission to humans by 2030. Animal reservoirs of gambiense-HAT could jeopardize these elimination goals. This study was undertaken to identify potential host reservoirs for Trypanosoma brucei gambiense by detecting its natural infections in domestic animals of Chadian HAT foci. Blood samples were collected from 267 goats, 181 sheep, 154 dogs, and 67 pigs. Rapid diagnostic test (RDT) and capillary tube centrifugation (CTC) were performed to search for trypanosomes. DNA was extracted from the buffy coat, and trypanosomes of the subgenus Trypanozoon as well as T. b. gambiense were identified by PCR. Of 669 blood samples, 19.4% were positive by RDT and 9.0% by CTC. PCR revealed 150 animals (22.4%) with trypanosomes belonging to Trypanozoon, including 18 (12%) T. b. gambiense. This trypanosome was found in all investigated animal species and all HAT foci. Between animal species or villages, no significant differences were observed in the number of animals harboring T. b. gambiense DNA. Pigs, dogs, sheep and goats appeared to be potential reservoir hosts for T. b. gambiense in Chad. The identification of T. b. gambiense in all animal species of all HAT foci suggests that these animals should be considered when designing new control strategies for sustainable elimination of HAT. Investigations aiming to decrypt their specific role in each epidemiological setting are important to achieve zero transmission of HAT.

TITLE: L'identification moléculaire de Trypanosoma brucei gambiense chez les porcs, les chiens et les petits ruminants naturellement infectés confirme les animaux domestiques comme réservoirs potentiels de la maladie du sommeil au Tchad. ABSTRACT: La trypanosomiase humaine africaine (THA) a été ciblée pour une interruption de sa transmission en 2030. Le réservoir animal de la THA à Trypanosoma brucei gambiense pourrait compromettre ces objectifs d'élimination. Cette étude a été entreprise pour identifier des potentiels hôtes réservoirs de Trypanosoma brucei gambiense en détectant ses infections naturelles chez des animaux domestiques des foyers tchadiens de la THA. Des échantillons de sang ont été prélevés chez 267 chèvres, 181 moutons, 154 chiens et 67 porcs. Le test de diagnostic rapide (TDR) et la centrifugation en tube capillaire (CTC) ont été utilisés pour mettre en évidence les trypanosomes. L'ADN a été extrait des couches leucocytaires et les trypanosomes du sous-genre Trypanozoon ainsi que T. b. gambiense ont été identifiés par PCR. Sur les 669 échantillons de sang analysés, 19,4& % étaient positifs au TDR et 9,0& % à la CTC. La PCR a révélé 150 (22,4& %) animaux avec des trypanosomes du sous-genre Trypanozoon donc 18 (12& %) portant l'ADN de T. b. gambiense. Ce dernier a été identifié chez toutes les espèces animales de tous les foyers de la THA. Entre les espèces animales ou les villages, aucune différence significative n'a été observée entre le nombre d'animaux ayant l'ADN de T. b. gambiense. Les porcs, les chiens, les moutons et les chèvres sont apparus comme des hôtes réservoirs potentiels de T. b. gambiense au Tchad. L'identification de T. b. gambiense, chez toutes les espèces animales étudiées dans tous les foyers, suggère de considérer ces animaux dans la conception des nouvelles stratégies de lutte visant une élimination durable de la THA. Des investigations visant à décrypter leur rôle spécifique dans chaque contexte épidémiologique sont nécessaires pour parvenir à une transmission nulle de la THA.