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The tsetse fly vector transmits the protozoan Trypanosoma brucei, responsible for Human African Trypanosomiasis, one of the most neglected tropical diseases. Despite a recent decline in new cases, it is still crucial to develop alternative strategies to combat this disease. Here, we review the literature on the factors that influence trypanosome transmission from the fly vector to its vertebrate host (particularly humans). These factors include climate change effects to pathogen and vector development (in particular climate warming), as well as the distribution of host reservoirs. Finally, we present reports on the relationships between insect vector nutrition, immune function, microbiota and infection, to demonstrate how continuing research on the evolving ecology of these complex systems will help improve control strategies. In the future, such studies will be of increasing importance to understand how vector-borne diseases are spread in a changing world. [ABSTRACT FROM AUTHOR]

Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II) and without (stage I) brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II), 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested) showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology. [ABSTRACT FROM AUTHOR]

Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II) and without (stage I) brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II), 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested) showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology. [ABSTRACT FROM AUTHOR]

Background: African trypanosomiases are vector-borne diseases that affect humans and livestock in sub-Saharan Africa. Although data have been collected on tsetse fauna as well as trypanosome infections in tsetse flies and mammals in foci of sleeping sickness in Chad, the situation of tsetse fly-transmitted trypanosomes remains unknown in several tsetse-infested areas of Chad. This study was designed to fill this epidemiological knowledge gap by determining the tsetse fauna as well as the trypanosomes infecting tsetse flies in the area of Lake Iro in southeastern Chad. Methods: Tsetse flies were trapped along the Salamat River using biconical traps. The proboscis and tsetse body were removed from each fly. DNA was extracted from the proboscis using proteinase K and phosphate buffer and from the tsetse body using Chelex 5%. Tsetse flies were identified by amplifying and sequencing the cytochrome c oxydase I gene of each tsetse fly. Trypanosome species were detected by amplifying and sequencing the internal transcribed spacer 1 of infecting trypanosomes. Results: A total of 617 tsetse flies were trapped; the apparent density of flies per trap per day was 2. 6. Of the trapped flies, 359 were randomly selected for the molecular identification and for the detection of infecting trypanosomes. Glossina morsitans submorsitans (96.1%) was the dominant tsetse fly species followed by G. fuscipes fuscipes (3.1%) and G. tachinoides (0.8%). Four trypanosome species, including Trypanosoma vivax, T. simiae, T. godfreyi and T. congolense savannah, were detected. Both single infection (56.7%) and mixed infections of trypanosomes (4.6%) were detected in G. m. submorsitans. The single infection included T. simiae (20.5%), T. congolense savannah (16.43%), T. vivax (11.7%) and T. godfreyi (9.8%). The trypanosome infection rate was 61.4% in G. m. submorsitans, 72.7% in G. f. fuscipes and 66.6% in G. tachinoides. Trypanosome infections were more prevalent in tsetse bodies (40.6%) than in the proboscis (16.3%). Conclusion: This study revealed the presence of different tsetse species and a diversity of trypanosomes pathogenic to livestock in the area of Lake Iro. The results highlight the risks and constraints that animal African trypanosomiasis pose to livestock breeding and the importance of assessing trypanosome infections in livestock in this area. [ABSTRACT FROM AUTHOR]

A good understanding of tsetse fly population structure and migration is essential to optimize the control of sleeping sickness. This can be done by studying the genetics of tsetse fly populations. In this work, we estimated the genetic differentiation within and among geographically separated Glossina palpalis palpalis populations from Cameroon, the Democratic Republic of the Congo and Ivory Coast. We determined the demographic history of these populations and assessed phylogenetic relationships among individuals of this sub-species. A total of 418 tsetse flies were analysed: 258 were collected in four locations in Cameroon (Bipindi, Campo, Fontem and Bafia), 100 from Azaguié and Nagadoua in Ivory Coast and 60 from Malanga in the Democratic Republic of the Congo. We examined genetic variation at three mitochondrial loci: COI, COII-TLII, and 16S2. 34 haplotypes were found, of which 30 were rare, since each was present in <5% of the total number of individuals. No haplotype was shared among Cameroon, Ivory Coast and the Democratic Republic of the Congo populations. The fixation index F ST of 0.88 showed a high genetic distance between Glossina palpalis palpalis populations from the three countries. That genetic distance was correlated to the geographic distance between populations. We also found that there is substantial gene flow between flies from locations separated by over 100 km in Cameroon and between flies from locations separated by over 200 km in Ivory Coast. Demographic parameters suggest that the tsetse flies from Fontem (Cameroon) had reduced in population size in the recent past. Phylogenetic analysis confirms that Glossina palpalis palpalis originating from the Democratic Republic of the Congo are genetically divergent from the two other countries as already published in previous studies. • There is substantial gene flow between some Glossina palpalis palpalis populations. • Tsetse flies from Fontem (Cameroon) would have been subjected to earlier substantial reductions in population size. • Tsetse samples from Cameroon and Ivory Coast seem to be phylogenetically related compared to tsetse collected in DRC. [ABSTRACT FROM AUTHOR]

Addressing the problems linked to tsetse-transmitted trypanosomiases requires considerable data on tsetse distribution and trypanosome infections. Although efforts to map tsetse and trypanosome infections have been undertaken at continental level, published data are still rare in wildlife reserves of West and Central Africa. To fill this gap, data on tsetse distribution and trypanosome infections were generated in the wildlife reserve of Santchou. For this study, each tsetse caught was identified and its DNA extracted. Different trypanosome species were identified by PCR. Entomological and parasitological data were transported onto a satellite image in order to visualize their distributions. From 195 Glossina palpalis palpalis that were caught, 33.8% (66/195) carried trypanosome infections with 89.4% (59/66) of single infections and 10.6% (7/66) mixed infections. From the 66 flies with trypanosome infections, 54.5% (36/66), 27.3% (18/66) and 18.2% (12/66) were respectively due to Trypanosoma congolense, Trypanosoma brucei s.l. and Trypanosoma vivax. The global infection rates were 18.5% (36/195) for Trypanosoma congolense (forest and savannah), 9.2% (18/195) for Trypanosoma brucei s.l. and 6.1% (12/195) for Trypanosoma vivax. The maps generated show the distribution of tsetse and trypanosome infections. This study showed an active transmission of trypanosomes in the wildlife reserve of Santchou. The maps enabled to identify areas with high transmission risk and where control operations must be implemented in order to eliminate tsetse and the diseases that they transmit. [ABSTRACT FROM AUTHOR]

Storage of stools for the detection of soil-transmitted helminths (STH) remains challenging for the molecular diagnostic testing of STH infections. This study aimed to overcome this challenge by assessing the capacity of Whatman filter papers to store stools for the molecular detection of STHs. Stool samples were collected from school-aged children of soil-transmitted helminthiasis endemic areas of Cameroon and then, analysed using Kato Katz technique. For this study, 128 and 40 stool samples respectively with and without STH eggs were analysed. From each sample, 10, 20, 40 and 80 mg of stool were weighted and spread on 6 grades of Whatman filter papers that were stored at room temperature from one to ten weeks. DNA was extracted from spread stool using CTAB based-method. The amount of stool to spread on filter papers and the grade of filter paper offering good storage were determined by amplifying specific DNA fragments of Ascaris lumbricoides. The capacity of filter papers to store stool samples for several weeks before the molecular detection of STH species was assessed by amplifying specific DNA fragments of different STHs. The amplification rates of A. lumbricoides were significantly higher (P < 0.0001) for 10 and 20 mg of stored stools. Stools spread on Whatman paper grade 2 yielded the highest amplification rate of 100% for A. lumbricoides, T. trichiura and hookworm. PCR revealed STH infections in all the 128 spread stools carrying STH eggs. It also revealed Necator americanus and Ancylostoma duodenale respectively in 10 and 13 of 15 spread stools contained hookworm eggs. PCR confirmed the co-infections of these hookworm species as well as that of A. lumbricoides and Trichuris trichiura in 7 spread stools. Out of 40 stools without STH eggs, PCR revealed that 5 (12.5%) and 9 (22.5%) had respectively A. lumbricoides and T. trichiura infections. The amplification rate of each STH species was 100% from one to 8 weeks and decreased to 86.7% after 10 weeks of storage. This study highlighted the capacity of filter papers to store stools for the molecular detection of STHs. Storing stools on these papers will enable to monitor and evaluate control programs and ensure post-elimination surveillance. • Whatman filter paper is efficient for stool storage for the molecular diagnostic testing ofsoil-transmitted helminthiasis. • 10 mg of stool can be stored on Whatman paper for the molecular diagnostic testing of soil-transmitted helminthiasis. • Stool on Whatman paper can be stored at room temperature for 8 months before the molecular diagnostic testing of soil-transmitted helminthiasis. • Storage of stools on Whatman filter paper improved the sensitivity of the diagnostic of soil-transmitted helminthiasis. • Storing stools on Whatman filter paper will be useful during the post elimination monitoring period. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Eliminating schistosomiasis as a public health problem by 2030 requires a better understanding of the disease transmission, especially the asymmetric distribution of worm burden in individuals living and sharing the same environment. It is in this light that this study was designed to identify human genetic determinants associated with high burden of S. mansoni and also with the plasma concentrations of IgE and four cytokines in children from two schistosomiasis endemic areas of Cameroon. In school-aged children of schistosomiasis endemic areas of Makenene and Nom-Kandi of Cameroon, S. mansoni infections and their infection intensities were evaluated in urine and stool samples using respectively the Point-of-care Circulating Cathodic Antigen test (POC-CCA) and the Kato Katz (KK) test. Thereafter, blood samples were collected in children harbouring high burden of schistosome infections as well as in their parents and siblings. DNA extracts and plasma were obtained from blood. Polymorphisms at 14 loci of five genes were assessed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system. The ELISA test enabled to determine the plasma concentrations of IgE, IL-13, IL-10, IL-4 and IFN-γ. The prevalence of S. mansoni infections was significantly higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in Makenene (48.6% for POC-CCA and 7.9% for KK) compared to Nom-Kandi (31% for POC-CCA and 4.3% for KK). The infection intensities were also higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in children from Makenene than those from Nom-Kandi. The allele C of SNP rs3024974 of STAT6 was associated with an increased risk of bearing high burden of S. mansoni both in the additive (p = 0.009) and recessive model (p = 0.01) while the allele C of SNP rs1800871 of IL10 was protective (p = 0.0009) against high burden of S. mansoni. The alleles A of SNP rs2069739 of IL13 and G of SNP rs2243283 of IL4 were associated with an increased risk of having low plasma concentrations of IL-13 (P = 0.04) and IL-10 (P = 0.04), respectively. This study showed that host genetic polymorphisms may influence the outcome (high or low worm burden) of S. mansoni infections and also the plasma concentrations of some cytokines. • Prevalence and infection intensities of S. mansoni vary between sampling sites. • Polymorphisms within STAT6 and IL10 genes were associated with high burden of S. mansoni. • Low plasmatic concentration of IL13 and IL10 was associated with the polymorphim of IL13 and IL4 genes. • Genetic polymorphisms of some cytokines influence S. mansoni infection outcomes and plasmatic concentrations of IL13 and IL10. • Plasmatic concentration of IgE, IL13 and IFNG was correlated with the infection intensities of S. mansoni. [ABSTRACT FROM AUTHOR]

Although several protocols were developed to extract DNA for soil-transmitted helminthiasis diagnostic, amplifying these extracts remains challenging due to DNA polymerase inhibitors. This study aimed to assess a DNA extraction method for efficient detection of soil-transmitted helminth species by determining stool mass and the type of DNA polymerase that can be used for this extraction method. For this study, 141 stool samples harbouring soil-transmitted eggs and 50 samples without egg were obtained from school-aged children of Makenene in the Centre region of Cameroon. DNA was extracted from 10, 20, 40 and 80 mg of stool using commercial kit and/or cetyltrimethylammonium bromide (CTAB)-based method. The amount of stool for molecular diagnostic of soil-transmitted helminthiasis was determined by amplifying Ascaris lumbricoides DNA. The performances of three DNA polymerases and CTAB-based method were assessed by amplifying DNA of different soil-transmitted helminth species. For this study, 94 stools with A. lumbricoides eggs, 39 with Trichuris trichuria and 15 with hookworm were analyzed. DNA of A. lumbricoides, T. trichuria, Necator americanus and Ancylostoma duodenale were detected in 97.9% of extracts from stools harbouring soil-transmitted helminth eggs. Soil-transmitted helminth DNAs were significantly (X 2 = 17.66; df = 3; p 〈00001) more amplified in extracts from 10 and 20 mg than those from 40 and 80 mg. The amplification rate with "Q5 high fidelity DNA polymerase" was significantly (X 2 = 30.54; df = 2; p < 0.00001) higher than that of other DNA polymerases. Multiplex-PCR confirmed co-infections of A. lumbricoides with either T. trichuria or N. americanus. The extraction cost for the CTAB-based method was $1.45. This method appearedis reliable and 3 times cost effective than commercial kit. Its combination with the "Q5 high fidelity DNA polymerase" may improve soil-transmitted helminthiasis diagnostic. • CTAB-based method is reliable and cost-effective to extract DNA of soil-transmitted helminths • Ten milligrams of stool can be used for molecular detection of soil-transmitted helminths • Q5 high fidelity DNA polymerase" can improve soil-transmitted helminthiasis diagnostic • Multiplex PCR can be performed on DNA extracts from CTAB-based method [ABSTRACT FROM AUTHOR]

Structural variants are responsible for a large part of genomic variation between individuals and play a role in both common and rare diseases. Databases cataloguing structural variants notably do not represent the full spectrum of global diversity, particularly missing information from most African populations. To address this representation gap, we analysed 1,091 high-coverage African genomes, 545 of which are public data sets, and 546 which have been analysed for structural variants for the first time. Variants were called using five different tools and datasets merged and jointly called using SURVIVOR. We identified 67,795 structural variants throughout the genome, with 10,421 genes having at least one variant. Using a conservative overlap in merged data, 6,414 of the structural variants (9.5%) are novel compared to the Database of Genomic Variants. This study contributes to knowledge of the landscape of structural variant diversity in Africa and presents a reliable dataset for potential applications in population genetics and health-related research., Competing Interests: Additional Declarations: There is NO Competing Interest.

Although several primers targeted to the internal transcribed-spacer 1 (ITS1) of the ribosomal DNA (rDNA) have been designed to improve the detection of African trypanosomes, no study tried to compare their agreement level and ability to amplify different trypanosome species in tsetse flies and mammals in various epidemiological settings. This study was designed to fill this gap, by targeting tsetse-infested areas of Cameroon. For this, archived DNA samples reporting at-least one trypanosome species with species-specific PCR primers were reviewed. Ten sets of primers targeting different ITS1 rDNA sequences of trypanosomes were selected for assessment using single-round and nested-PCR method. Amplification rates (sensitivity) and agreement level of different ITS1 assays were compared using Cohen's-Kappa and McNemar's x 2 statistic. Little agreement level (k = 0.05-0.52) were observed between different ITS1-primers PCRs detection of African trypanosome species despite significant (X 2 =54.3, p = 0.0001) high amplification rate 91.6 % (339/370). This sensitivity varied from quite low for T. simiae (11.9 %) and T. vivax (27.3 %) to fairly good for T. congolence (51.9 %), Trypanozoon (32.4 %) and T. theileri (40.3 %). Primers set targeting ITS1-A sequence of trypanosome species recorded the highest sensitivity (50.5 %) with fairly good agreement compared to 39.2 % for ITS1-C (k = 0.52), 32.4 % for ITS1-R (k = 0.47), 29.7 % for ITS1-N (k = 0.48) and 23.0 % for ITS1-KIN (k = 0.43) respectively. This study revealed a diversity in the sensitivity of different trypanosome species with different sets of ITS-primers enhancing the need to use the same sets of primers in different bio-ecological settings. The use of nested-PCR instead of single-round PCR enabled improvement of trypanosome infections detection in both tsetse and mammals. Among the sets of ITS1-primers tested, those designed by to amplify ITS1-A can be considered as the most appropriate for the detection of trypanosome infections in mammals and tsetse flies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing personal relationships or financial interests that could have appeared to influence the work reported in this paper. Authors also confirm that the manuscript has been read and approved by all named authors. Also that there are no other person who satisfied the criteria for authorship but are no listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vector control remains one of the best strategies to prevent the transmission of trypanosome infections in humans and livestock and, thus, a good way to achieve the elimination of human African trypanosomiasis and animal African trypanosomiasis. A key prerequisite for the success of any vector control strategy is the accurate identification and correct mapping of tsetse species. In this work, we updated the tsetse fly species identification and distribution in many geographical areas in Cameroon. Tsetse flies were captured from six localities in Cameroon, and their species were morphologically identified. Thereafter, DNA was extracted from legs of each tsetse fly and the length polymorphism of internal transcribed spacer-1 (ITS1) region of each fly was investigated using PCR. ITS1 DNA fragments of each tsetse species were sequenced. The sequences obtained were analysed and compared to those available in GenBank. This enabled to confirm/infirm results of the morphologic identification and then, to establish the phylogenetic relationships between tsetse species. Morphologic features allowed to clearly distinguish all the tsetse species captured in the South Region of Cameroon, that is, Glossina palpalis palpalis, G. pallicera, G. caliginea and G. nigrofusca. In the northern area, G. morsitans submorsitans could also be distinguished from G. palpalis palpalis, G. tachinoides and G. fuscipes, but these three later could not be distinguished with routine morphological characters. The ITS1 length polymorphism was high among most of the studied species and allowed to identify the following similar species with a single PCR, that is, G. palpalis palpalis with 241 or 242 bp and G. tachinoides with 221 or 222 bp, G. fuscipes with 236 or 237 bp. We also updated the old distribution of tsetse species in the areas assessed, highlighting the presence of G. palpalis palpalis instead of G. fuscipes in Mbakaou, or in sympatry with G. morsitans submorsitans in Dodeo (northern Cameroon). This study confirms the presence of G. palpalis palpalis in the Adamawa Region of Cameroon. It highlights the limits of using morphological criteria to differentiate some tsetse species. Molecular tools based on the polymorphism of ITS1 of tsetse flies can differentiate tsetse species through a simple PCR before downstream analyses or vector control planning., (© 2024 The Authors. Medical and Veterinary Entomology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.)

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21-47% and 2-19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0-6%, 3-10%, and 6-20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Although studies on African Trypanosomiases revealed a variety of trypanosome species in the blood of various animal taxa, animal reservoirs of Trypanosoma brucei gambiense and anatomical niches such as skin have been overlooked in most epidemiological settings. This study aims to update epidemiological data on trypanosome infections in animals from human African trypanosomiasis (HAT) foci of Cameroon. Blood and skin snips were collected from 291 domestic and wild animals. DNA was extracted from blood and skin snips and molecular approaches were used to identify different trypanosomes species. Immunohistochemical analyses were used to confirm trypanosome infections in skin snips. PCR revealed 137 animals (47.1%) with at least one trypanosome species in the blood and/or in the skin. Of these 137 animals, 90 (65.7%) and 32 (23.4%) had trypanosome infections respectively in the blood and skin. Fifteen (10.9%) animals had trypanosome infections in both blood and skin snip. Animals from the Campo HAT focus (55.0%) were significantly (X2 = 17.6; P< 0.0001) more infected than those (29.7%) from Bipindi. Trypanosomes of the subgenus Trypanozoon were present in 27.8% of animals while T. vivax, T. congolense forest type and savannah type were detected in 16.5%, 10.3% and 1.4% of animals respectively. Trypanosoma b. gambiense infections were detected in the blood of 7.6% (22/291) of animals. No T. b. gambiense infection was detected in skin. This study highlights the presence of several trypanosome species in the blood and skin of various wild and domestic animals. Skin appeared as an anatomical reservoir for trypanosomes in animals. Despite methodological limitations, pigs, sheep, goats and wild animals were confirmed as potential reservoirs of T. b. gambiense. These animal reservoirs must be considered for the designing of control strategies that will lead to sustainable elimination of HAT., Competing Interests: The authors have declared that they have no competing interests., (Copyright: © 2023 Magang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Monitoring and assessment of control strategies for African trypanosomoses' elimination require not only updating data on trypanosome infections, but also to have an overview on the molecular profiles of trypanocides resistance in different epidemiological settings. This study was designed to determine, in animals from six tsetse-infested areas of Cameroon, the prevalence of trypanosome infections as well as the diminazene aceturate (DA) and isometamidium chloride (ISM) sensitivity/resistance molecular profiles of these trypanosomes. From 2016 to 2019, blood was collected in pigs, dogs, sheep, goats and cattle from six tsetse infested areas of Cameroon. DNA was extracted from blood and trypanosome species were identified by PCR. The sensitivity/resistance molecular profiles of trypanosomes to DA and ISM were investigated using PCR-RFLP. From 1343 blood samples collected, Trypanosoma vivax, Trypanosoma congolense forest and savannah, Trypanosoma theileri and trypanosomes of the sub-genus Trypanozoon were identified. The overall prevalence of trypanosome infections was 18.7%. These prevalence vary between trypanosome species, animal taxa, within and between sampling sites. Trypanosoma theileri was the predominant species with an infection rate of 12.1%. Trypanosomes showing resistant molecular profiles for ISM and DA were identified in animals from Tibati (2.7% for ISM and 65.6% for DA) and Kontcha (0.3% for ISM and 6.2% for DA). No trypanosome carrying resistant molecular profile for any of the two trypanocides was detected in animals from Fontem, Campo, Bipindi and Touboro. Mixed molecular profiles of sensitive/resistant trypanosomes were detected in animals from Tibati and Kontcha. Results of this study highlighted the presence of various trypanosome species as well as parasites carrying sensitive/resistant molecular profiles for DA and ISM in animals of tsetse infested areas of Cameroon. They indicate that the control strategies must be adapted according to epidemiological settings. The diversity of trypanosomes indicates that AAT remains a serious threat for animal breeding and animal health in these tsetse infested areas., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Inflammation is undoubtedly a hallmark of cancer development. Its maintenance within tumors and the consequences on disease aggressiveness are insufficiently understood., Methods: Data of 27 tumor entities (about 5000 samples) were downloaded from the TCGA and GEO databases. Multi-omic analyses were performed on these and in-house data to investigate molecular determinants of tumor aggressiveness. Using molecular loss-of-function data, the mechanistic underpinnings of inflammation-induced tumor aggressiveness were addressed. Patient specimens and in vivo disease models were subsequently used to validate findings., Results: There was significant association between somatic copy number alterations (sCNAs) and tumor aggressiveness. SOX2 amplification was the most important feature among novel and known aggressiveness-associated alterations. Mechanistically, SOX2 regulates a group of genes, in particular the AP1 transcription factor FOSL2, to sustain pro-inflammatory signaling pathways, such as IL6-JAK-STAT3, TNFA and IL17. FOSL2 was found overexpressed in tumor sections of specifically aggressive cancers. In consequence, prolonged inflammation induces immunosuppression and activates cytidine deamination and thus DNA damage as evidenced by related mutational signatures in aggressive tumors. The DNA damage affects tumor suppressor genes such as TP53, which is the most mutated gene in aggressive tumors compared to less aggressive ones (38% vs 14%), thereby releasing cell cycle control. These results were confirmed by analyzing tissues from various tumor types and in vivo studies., Conclusion: Our data demonstrate the implication of SOX2 in promoting DNA damage and genome instability by sustaining inflammation via FOSL2/IL6, resulting in tumor aggressiveness., (© 2023. The Author(s).)

Preventive chemotherapy (PC) that remains the main control strategy recommended by the World Health Organization to achieve the elimination of soil-transmitted helminth (STH) infections as a public health problem must be strengthened by identifying the remaining transmission hot-spots for the deployment of appropriate control measures. This study was designed to assess the prevalence and infections intensities of soil-transmitted helminths and perform micro scale mapping in order to identify transmission hot-spots for targeted control operations. Stool samples were collected from 1775 children in ten primary schools of eight sub-districts of Makenene in Cameroon. Kato Katz technique was used to process and examine stool samples to detect the eggs of soil-transmitted nematodes. The prevalence of soil-transmitted helminth species as well as the infection intensities was compared. Data visualizations in forms of maps were made using Quantum geographic information system (QGIS) software. The overall prevalence of soil-transmitted helminth infections was 4.8% with a 95% confidence interval (CI) of 3.8-5.9%: 3.0% (95% CI 2.2-3.9) for Ascaris lumbricoides, 1.4% (95% CI 0.9-2.0) for Trichuris trichiura and 0.8% (95% CI 0.5-1.4) for hookworms. The prevalence of soil-transmitted helminth species differ significantly between schools and sub-districts. The intensity of infections was light (2.4%, 1.1% and 0.8%), moderate (0.4%, 0.1% and 0.1%) and heavy (0.2%, 0.2% and 0%) for A. lumbricoides, T. trichiura and hookworm respectively. The mean intensity of infections was 7255 EPG for A. lumbricoides, 2900 EPG for T. trichiura and 298 EPG for hookworm. Between schools, significant difference was recorded in the means of infection intensities of T. Trichiura and hookworms but not for A. lumbricoides. This difference was also significant for T. Trichiura when comparison were between sex. No significant difference were recorded when the comparison were between age. Fine mapping revealed that children harbouring heavy infections were clustered in the same sub-districts; highlighting the presence of high endemicity sub-districts and hot-spots for the transmission of different soil-transmitted helminth species. This study showed a diversity in the prevalence and transmission of different soil-transmitted helminth species. It also hightlighted the need for micro scale mapping to enable the localisation of high endemicity sub-districts and transmission hot-spot sites where targeted control operations must be deployed to achieve STH elimination., (© 2022. The Author(s).)

Background: Approximately 25% of the risk of Schistosoma mansoni is associated with host genetic variation. We will test 24 candidate genes, mainly in the T h 2 and T h 17 pathways, for association with S. mansoni infection intensity in four African countries, using family based and case-control approaches. Methods: Children aged 5-15 years will be recruited in S. mansoni endemic areas of Ivory Coast, Cameroon, Uganda and the Democratic Republic of Congo (DRC). We will use family based (study 1) and case-control (study 2) designs. Study 1 will take place in Ivory Coast, Cameroon, Uganda and the DRC. We aim to recruit 100 high worm burden families from each country except Uganda, where a previous study recruited at least 40 families. For phenotyping, cases will be defined as the 20% of children in each community with heaviest worm burdens as measured by the circulating cathodic antigen (CCA) assay. Study 2 will take place in Uganda. We will recruit 500 children in a highly endemic community. For phenotyping, cases will be defined as the 20% of children with heaviest worm burdens as measured by the CAA assay, while controls will be the 20% of infected children with the lightest worm burdens. Deoxyribonucleic acid (DNA) will be genotyped on the Illumina H3Africa SNP (single nucleotide polymorphisms) chip and genotypes will be converted to sets of haplotypes that span the gene region for analysis. We have selected 24 genes for genotyping that are mainly in the Th2 and Th17 pathways and that have variants that have been demonstrated to be or could be associated with Schistosoma infection intensity.   Analysis: In the family-based design, we will identify SNP haplotypes disproportionately transmitted to children with high worm burden. Case-control analysis will detect overrepresentation of haplotypes in extreme phenotypes with correction for relatedness by using whole genome principal components., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Nyangiri OA et al.)

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10 -3 ). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans., (© 2021. The Author(s).)

African animal trypanosomiases (AAT) remain the major constraint for livestock production, agriculture and food security in Africa. Although several control measures have been developed to fight AAT, the use of trypanocides remains the main strategy in most affected poor and rural communities. However, several studies have highlighted drug-resistant-trypanosome infections in many African countries, though this phenomenon is still not well described. This study aims to detect trypanosome species and the molecular profiles of drug-resistant-trypanosomes in naturally infected domestic animals of Yoko in the centre region of southern Cameroon. Therefore, in October 2017, 348 animals were blood sampled. The level of packed cell volume (PCV) was evaluated in each animal and trypanosome infections were investigated with the capillary tube centrifugation technique (CTC). Thereafter, DNA was extracted from blood samples and different trypanosome species were identified by PCR. The resistant/sensitive molecular profiles of trypanosomes for diminazene aceturate (DA) and isometamidium chloride (ISM) were investigated by PCR-RFLP. About 18.4% (64/348) of animals analyzed by PCR were found with trypanosome infections including Trypanosoma vivax, Trypanosoma brucei s.l. and Trypanosoma congolense forest and savannah. Trypanosoma congolense savannah was the predominant species with an infection rate of 15.2%. Between villages, significant (p˂0.0001) differences were found in the overall trypanosome infection rates. No molecular profile for ISM resistant-trypanosomes was identified. Conversely, about 88.9% (40/45) of T. congolense positive samples have shown molecular profiles of DA-resistant strains while the remaining 11.1% (5/45) showed mixed molecular profiles of resistant/sensitive strains. Results showed that the molecular profiles of DA-resistant strains of T. congolense in domestic animals of Yoko were widespread. This data needs to be confirmed by testing in vivo the drug susceptibilities of the trypanosome strains herein detected. In conclusion, appropriate future control measures are required. In addition to the intensification of vector control, ISM is advised for the treatment of animals infected by trypanosomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

African animal trypanosomiases are caused by trypanosomes cyclically or mechanically transmitted by tsetse and other biting flies. Although molecular tools have been developed to identify drug-resistant trypanosomes in mammals, little or no investigation on drug-resistance has been undertaken on trypanosomes harbored by tsetse flies. Moreover, no data on mechanical vectors of African trypanosomes is available in most endemic areas of Cameroon. This study was designed to update our knowledge on the cyclical and mechanical vectors of African trypanosomes, and using molecular tools to identify different trypanosome species as well as diminazene aceturate resistant trypanosomes in tsetse flies trapped at Yoko in the Centre region of Cameroon. For this study, traps were used to catch tsetse and mechanical vectors of African trypanosomes. The flies trapped were counted and identified by sex and species. DNA was extracted from tsetse and species-specific primers were used to identify different trypanosome species. PCR-RFLP was used to detect diminazene aceturate resistant strains of Trypanosoma congolense . In all, 454 flies comprising 168 (37%) Tabanus spp. , 71 (15.6%) Stomoxys spp. and 215 (47.4%) tsetse fly ( i.e. 107 (49.8%) Glossina fusca congolensis , 71 (33%) Glossina fusca fusca and 37 (17.2%) Glossina palpalis palpalis ) were trapped. Trypanosome infections were identified in 12.6% (27/215) of tsetse flies: 13 in G. f. congolensis , 6 in G. p. palpalis and 5 in G. f. fusca . From 24 T. congolense positive samples, PCR-RFLP was successful on 37.5% of the samples. Four samples (16.2%) harbored T. congolense strains that were resistant to diminazene aceturate while the remaining samples had drug-sensitive strains. These results show for the first time the applicability of molecular tools for the identification of drug-resistant trypanosomes in tsetse. They revealed the existence of diminazene aceturate resistant strains of T. congolense in the tsetse-infested area of Yoko in the Centre region of Cameroon. Detection of drug-resistant trypanosomes in tsetse may enable scientists to map with accuracy specific areas where these parasites are transmitted. With such mapping, control strategies against African trypanosomiases could be improved by adapting control measures according to drug resistance distribution., Competing Interests: The authors declare that they have no competing interests. The funding agencies played no role in the design or implementation of the study, the analysis or interpretation of the data, or the preparation and submission of the manuscript., (© 2020 Published by Elsevier Ltd on behalf of World Federation of Parasitologists.)

The cattle tick Rhipicephalus microplus is the most important arthropod vector of livestock diseases globally. Since its introduction in West Africa a decade ago, it has been reported in Ivory Coast, Benin, Togo, Mali, Burkina Faso and Nigeria with potentially far-reaching adverse impacts on the livestock sector in the region. Cameroon is located on a major route for transboundary cattle trade between Central and West Africa and it is therefore at risk from R. microplus invasion. This study investigated the occurrence of R. microplus in Cameroon, the genetic polymorphism of the tick and population structure of isolates from different regions of the country to provide data that underpin the design of future vector control programs. A cross-sectional survey was conducted in which ticks were collected from cattle at 54 sites across the five Agroecological zones (AEZs) within Cameroon. Tick identity (sex and species) was assigned using taxonomic keys. Species identity was confirmed through amplification and sequencing of the mitochondrial COI and 16S rRNA genes. A total of 7091 ticks were collected out of which 1112 (15.6%) were morphologically identified as R. microplus. The presence of R. microplus was confirmed in 4 out of 5 agroecological zones. Only two haplotypes were identified by both COI and 16S rRNA genes, indicating a very low divergence in the genetic structure of the R. microplus population in Cameroon. 16S rRNA sequence analysis revealed a new haplotype specific to Cameroon. Phylogenetic trees revealed that all isolates of R. microplus from Cameroon were grouped into the previously described Africa/Americas clade. Application of a niche modelling algorithm to R. microplus distribution in Cameroon predicted that suitable habitat for the tick extended into southern Nigeria. This study demonstrated for the first time the presence of R. microplus in Cameroon. Genetic diversity tests indicate that the tick has not evolved significantly since the initial introduction to West Africa. We suggest further longitudinal studies to better define the spatial and temporal expansion of the range of the tick and the drivers of this spread., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Human papilloma virus (HPV) infection is an etiological factor for cervical cancer development and Chlamydia trachomatis (Ct) is considered as a cofactor. Understanding the dynamics of HPV and Ct infection could help to explain the incidence of early onset of cervical cancer (CC) observed in Cameroon. Lower vaginal swabs and sera from sexually active women were analyzed for HPV and Ct infection in association with risk factors. Questionnaires were used to document patients' lifestyle and risk factors. A total of 206 women participated in the study average 28.1±8years (16-50 years). HPV prevalence was 23.3% with subtypes 16 and 18 at respectively 2.9% and 1%. Ct infection totalised 40.8%, of which 23.8% were HPV- Ct co-infections. HPV infection was inversely associated with age (p=0.028). We found a positive association between Ct infection and the number of sex partners (p=0.012) and a negative association with parity (p=0.032). There was no significant association between HPV and Ct infections. High rates of HPV and Ct infections could be an indicator of cervical cancer risk in the near future. There is therefore an urgent need for sensitization as well as implementation of appropriate preventive measures., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH)., Methodology: A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test., Results: Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204-0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness., Conclusion: The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP.

Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II) and without (stage I) brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II), 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested) showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

The tsetse fly, Glossina palpalis is a vector of the trypanosome that causes sleeping sickness in humans and nagana in cattle along with associated human health problems and massive economic losses. The insect is also known to carry a number of symbionts such as Sodalis, Wigglesworthia, Wolbachia whose effects on the physiology of the insect have been studied in depth. However, effects of other bacterial flora on the physiology of the host and vector competence have received little attention. Epidemiological studies on tsetse fly populations from different geographic sites revealed the presence of a variety of bacteria in the midgut. The most common of the flora belong to the genera Entrobacter (most common), Enterococcus, and Acinetobacter. It was a little surprising to find such diversity in the tsetse midgut since the insect is monophagous consuming vertebrate blood only. Diversity of bacteria is normally associated with polyphagous insects. In contrast to the symbionts, the role of resident midgut bacterial flora on the physiology of the fly and vector competence remains to be elucidated. With regard, Sodalis glossinidius, our data showed that flies harbouring this symbiont have three times greater probability of being infected by trypanosomes than flies without the symbiont. The data delineated in these studies under score the need to carry out detailed investigations on the role of resident bacteria on the physiology of the fly and vector competence., (Copyright © 2013 International Atomic Energy Agency. Published by Elsevier Inc. All rights reserved.)

To characterize the potential transmission sites of sleeping sickness in Kinshasa, two entomologic surveys were carried out during the dry and the rainy seasons in rural and periurban areas of Kinshasa in 2005. About 610 pyramidal traps were set up, and 897 Glossina fuscipes quanzensis were captured. Environmental and biologic factors were reported, and relationships between these factors were evaluated using logistic regression and multiple correspondence analysis. The biologic factors (the presence of tsetse flies, human blood meals, and teneral flies) were progressively accumulated at each capture site to permit the characterization of the sleeping sickness transmission risk. The dry season was found to be a more favorable period for the disease transmission than the rainy season. Moreover, the landscapes characterized by the presence of argillaceous soils, raised ground cover with forest residues and rivers, were identified as types of environments with greater risk of sleeping sickness transmission. Pig breeding appeared as an important factor increasing the disease transmission. If vector control is continuously performed along rivers segments at high risk, the transmission of sleeping sickness in rural and periurban areas of Kinshasa will considerably decrease.