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International Journal of Infectious... Oct 2018East African trypanosomiasis is an uncommon, potentially lethal disease if not diagnosed and treated in a timely manner. South Africa, as a centre for emergency medical...
BACKGROUND
East African trypanosomiasis is an uncommon, potentially lethal disease if not diagnosed and treated in a timely manner. South Africa, as a centre for emergency medical evacuations from much of sub-Saharan Africa, receives a high proportion of these patients, mostly tourists and expatriate residents.
METHODS
The cases of East African trypanosomiasis patients evacuated to South Africa, for whom diagnostic and clinical management advice was provided over the years 2004-2018, were reviewed, using the authors' own records and those of collaborating clinicians.
RESULTS
Twenty-one cases were identified. These originated in Zambia, Malawi, Zimbabwe, Tanzania, and Uganda. Nineteen cases (90%) had stage 1 (haemolymphatic) disease; one of these patients had fatal myocarditis. Of the two patients with stage 2 (meningoencephalitic) disease, one died of melarsoprol encephalopathy. Common problems were delayed diagnosis, erroneous assessment of severity, and limited access to treatment.
CONCLUSIONS
The key to early diagnosis is recognition of the triad of geographic exposure, tsetse fly bites, and trypanosomal chancre, plus good microscopy. Elements for successful management are rapid access to specific drug treatment, skilled intensive care, and good laboratory facilities. Clinical experience and the local stock of antitrypanosomal drugs from the World Health Organization have improved the chance of a successful outcome in the management of East African trypanosomiasis in South Africa; the survival rate over the period was 90.5%.
Topics: Adult; Aged; Animals; Antiprotozoal Agents; Female; Humans; Male; Middle Aged; South Africa; Trypanosoma; Trypanosomiasis, African
PubMed: 30153486
DOI: 10.1016/j.ijid.2018.08.012 -
International Journal of Molecular... Jan 2021African Animal Trypanosomiasis (AAT) is transmitted by the tsetse fly which carries pathogenic trypanosomes in its saliva, thus causing debilitating infection to...
African Animal Trypanosomiasis (AAT) is transmitted by the tsetse fly which carries pathogenic trypanosomes in its saliva, thus causing debilitating infection to livestock health. As the disease advances, a multistage progression process is observed based on the progressive clinical signs displayed in the host's body. Investigation of genes expressed with regular monotonic patterns (known as Monotonically Expressed Genes (MEGs)) and of their master regulators can provide important clue for the understanding of the molecular mechanisms underlying the AAT disease. For this purpose, we analysed MEGs for three tissues (liver, spleen and lymph node) of two cattle breeds, namely trypanosusceptible Boran and trypanotolerant N'Dama. Our analysis revealed cattle breed-specific master regulators which are highly related to distinguish the genetic programs in both cattle breeds. Especially the master regulators and found in this study, seem to influence the immune responses strongly, thereby susceptibility and trypanotolerance of Boran and N'Dama respectively. Furthermore, our pathway analysis also bolsters the crucial roles of these master regulators. Taken together, our findings provide novel insights into breed-specific master regulators which orchestrate the regulatory cascades influencing the level of trypanotolerance in cattle breeds and thus could be promising drug targets for future therapeutic interventions.
Topics: Animals; Cattle; Host-Pathogen Interactions; Humans; Immunity, Innate; Liver; Organ Specificity; Proto-Oncogene Proteins c-myc; Spleen; Trypanosoma; Trypanosomiasis, African; Tsetse Flies
PubMed: 33429951
DOI: 10.3390/ijms22020562 -
Bulletin of the World Health... Aug 2023Having caused devastating epidemics during the 20th century, the incidence of life-threatening human African trypanosomiasis has fallen to historically low levels as a...
Having caused devastating epidemics during the 20th century, the incidence of life-threatening human African trypanosomiasis has fallen to historically low levels as a result of sustained and coordinated efforts over the past 20 years. Humans are the main reservoir of one of the two pathogenic trypanosome subspecies, , found in western and central Africa. The expected advent of a safe and easy-to-use treatment to be given to seropositive but microscopically unconfirmed individuals would lead to further depletion; in the meantime, the presence of infection in the community must be monitored to allow the control strategy to be adapted and the elimination status to be assessed. The World Health Organization has therefore developed a target product profile that describes the optimal and minimal characteristics of an individual laboratory-based test to assess infection in low-prevalence settings. Development of the target product profile involved the formation of a Neglected Tropical Diseases Diagnostics Technical Advisory Group and a subgroup on human African trypanosomiasis diagnostic innovation needs, and an analysis of the available products and development pipeline. According to the product profile, the test should ideally: (i) require a minimally invasive or non-invasive specimen, collectable at peripheral facilities by minimally trained health workers; (ii) demonstrate good sensitivity and high specificity; (iii) have a stability of samples allowing transfer to reference laboratories preferably without cold chain; (iv) be stable over a wide range of environmental conditions for more than 2 years; and (v) after marketing, be available at low cost for at least 7 years.
Topics: Animals; Humans; Trypanosoma brucei gambiense; Trypanosomiasis, African; Prevalence; Incidence
PubMed: 37529025
DOI: 10.2471/BLT.23.290176 -
Revista Da Sociedade Brasileira de... 2019
Topics: Humans; Neglected Diseases; Nitroimidazoles; Trypanocidal Agents; Trypanosomiasis, African
PubMed: 31596351
DOI: 10.1590/0037-8682-0176-2019 -
PLoS Neglected Tropical Diseases Feb 2018Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense...
BACKGROUND
Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT.
METHODOLOGY AND RESULTS
We included 238 and 202 participants from the Busoga Tbr and Northwest Uganda Tbg endemic areas respectively. Single Nucleotide Polymorphism (SNP) genotype data were analysed in the CGAS. The study was powered to find odds ratios > 2 but association testing of the SNPs with HAT yielded no positive associations i.e. none significant after correction for multiple testing. However there was strong evidence for no association with Tbr HAT and APOL1 G2 of the size previously reported in the Kabermaido district of Uganda.
CONCLUSIONS/SIGNIFICANCE
A recent study in the Soroti and Kaberamaido focus in Central Uganda found that the APOL1 G2 allele was strongly associated with protection against Tbr HAT (odds ratio = 0.2, 95% CI: 0.07 to 0.48, p = 0.0001). However, in our study no effect of G2 on Tbr HAT was found, despite being well powered to find a similar sized effect (OR = 0.9281, 95% CI: 0.482 to 1.788, p = 0.8035). It is possible that the G2 allele is protective from Tbr in the Soroti/Kabermaido focus but not in the Iganga district of Busoga, which differ in ethnicity and infection history. Mechanisms underlying HAT infection outcome and virulence are complex and might differ between populations, and likely involve several host, parasite or even environmental factors.
Topics: Adult; Alleles; Apolipoprotein L1; Black People; Case-Control Studies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Kidney Diseases; Male; Middle Aged; Polymorphism, Single Nucleotide; Trypanosoma brucei rhodesiense; Trypanosomiasis, African; Uganda
PubMed: 29470556
DOI: 10.1371/journal.pntd.0006300 -
British Medical Journal May 1976
Topics: Humans; Insect Control; Pentamidine; Trypanosomiasis, African; Tsetse Flies
PubMed: 1268670
DOI: No ID Found -
Parasites & Vectors Nov 2017Serological tests for gambiense human African trypanosomiasis (gHAT) detect antibodies to antigens on the cell surface of bloodstream trypanosomes. As trypanosomes that...
BACKGROUND
Serological tests for gambiense human African trypanosomiasis (gHAT) detect antibodies to antigens on the cell surface of bloodstream trypanosomes. As trypanosomes that cause animal African trypanosomiasis (AAT) also express related antigens, we have evaluated two rapid diagnostic tests (RDTs) on cattle in trypanosomiasis endemic and non-endemic regions, to determine whether gHAT serological tests could also be used to screen for AAT.
METHODS
Two RDTs, 1G RDT, made with native antigens, and p2G RDT, made with recombinant antigens, were tested on 121 cattle in a trypanosomiasis-free region, and on 312 cattle from a rhodesiense HAT and AAT endemic region. A subset of samples from the endemic region were also tested with two immune trypanolysis (TL) tests. The sensitivity of the tests was estimated by evaluating the result of the RDT on samples that were positive by both microscopy and internal transcribed spacer (ITS) PCR, whilst specificity was the result of the RDT on samples that were negative by ITS PCR and microscopy, and others from the non-endemic region.
RESULTS
The specificity of the p2G RDT on cattle from the non-endemic region was 97.5% (95% CI: 93.0-99.2%), compared to only 57.9% (95% CI: 48.9-66.3%) for 1G RDT. The specificities of 1G RDT, p2G RDT and TL on endemic control cattle were 14.6% (95% CI: 9.7-21.5%), 22.6% (95% CI: 16.4-30.3%) and 68.3% (95% CI: 59.6-75.9%), respectively. The sensitivities of the tests on trypanosome positive samples were 85.1% (95% CI: 79.1-89.7%), 89.1% (95% CI: 83.7-93.0%) and 59.3% (95% CI: 51.8-66.4%), respectively. Among the same samples, 51.7% were positive by both TL and the 1G RDT.
CONCLUSIONS
These serological tests detect cross-reacting antibodies in cattle. The p2G RDT based on recombinant antigens had a high specificity in a non-endemic region, while the 1G RDT had a lower specificity, suggesting cross-reactivity with other pathogens.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Cattle; Cattle Diseases; Cross Reactions; Humans; Polymerase Chain Reaction; Sensitivity and Specificity; Serologic Tests; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 29100526
DOI: 10.1186/s13071-017-2487-8 -
Parasites & Vectors Mar 2022African animal trypanosomosis (AAT), transmitted by tsetse flies, is arguably the main disease constraint to integrated crop-livestock agriculture in sub-Saharan Africa,...
BACKGROUND
African animal trypanosomosis (AAT), transmitted by tsetse flies, is arguably the main disease constraint to integrated crop-livestock agriculture in sub-Saharan Africa, and African heads of state and governments adopted a resolution to rid the continent of this scourge. In order to sustainably reduce or eliminate the burden of AAT, a progressive and evidence-based approach is needed, which must hinge on harmonized, spatially explicit information on the occurrence of AAT and its vectors.
METHODS
A digital repository was assembled, containing tsetse and AAT data collected in Burkina Faso between 1990 and 2019. Data were collected either in the framework of control activities or for research purposes. Data were systematically verified, harmonized, georeferenced and integrated into a database (PostgreSQL). Entomological data on tsetse were mapped at the level of individual monitoring traps. When this was not possible, mapping was done at the level of site or location. Epidemiological data on AAT were mapped at the level of location or village.
RESULTS
Entomological data showed the presence of four tsetse species in Burkina Faso. Glossina tachinoides, present from the eastern to the western part of the country, was the most widespread and abundant species (56.35% of the catches). Glossina palpalis gambiensis was the second most abundant species (35.56%), and it was mainly found in the west. Glossina morsitans submorsitans was found at lower densities (6.51%), with a patchy distribution in the southern parts of the country. A single cluster of G. medicorum was detected (less than 0.25%), located in the south-west. Unidentified tsetse flies accounted for 1.33%. For the AAT component, data for 54,948 animal blood samples were assembled from 218 geographic locations. The samples were tested with a variety of diagnostic methods. AAT was found in all surveyed departments, including the tsetse-free areas in the north. Trypanosoma vivax and T. congolense infections were the dominant ones, with a prevalence of 5.19 ± 18.97% and 6.11 ± 21.56%, respectively. Trypanosoma brucei infections were detected at a much lower rate (0.00 ± 0.10%).
CONCLUSIONS
The atlas provides a synoptic view of the available information on tsetse and AAT distribution in Burkina Faso. Data are very scanty for most of the tsetse-free areas in the northern part of the country. Despite this limitation, this study generated a robust tool for targeting future surveillance and control activities. The development of the atlas also strengthened the collaboration between the different institutions involved in tsetse and AAT research and control in Burkina Faso, which will be crucial for future updates and the sustainability of the initiative.
Topics: Animals; Burkina Faso; Insect Vectors; Trypanosoma; Trypanosomiasis, African; Tsetse Flies
PubMed: 35246216
DOI: 10.1186/s13071-021-05131-4 -
PLoS Neglected Tropical Diseases Apr 2023Gambiense human African trypanosomiasis (gHAT) is a deadly vector-borne, neglected tropical disease found in West and Central Africa targeted for elimination of...
Gambiense human African trypanosomiasis (gHAT) is a deadly vector-borne, neglected tropical disease found in West and Central Africa targeted for elimination of transmission (EoT) by 2030. The recent pandemic has illustrated how it can be important to quantify the impact that unplanned disruption to programme activities may have in achieving EoT. We used a previously developed model of gHAT fitted to data from the Democratic Republic of the Congo, the country with the highest global case burden, to explore how interruptions to intervention activities, due to e.g. COVID-19, Ebola or political instability, could impact progress towards EoT and gHAT burden. We simulated transmission and reporting dynamics in 38 regions within Kwilu, Mai Ndombe and Kwango provinces under six interruption scenarios lasting for nine or twenty-one months. Included in the interruption scenarios are the cessation of active screening in all scenarios and a reduction in passive detection rates and a delay or suspension of vector control deployments in some scenarios. Our results indicate that, even under the most extreme 21-month interruption scenario, EoT is not predicted to be delayed by more than one additional year compared to the length of the interruption. If existing vector control deployments continue, we predict no delay in achieving EoT even when both active and passive screening activities are interrupted. If passive screening remains as functional as in 2019, we expect a marginal negative impact on transmission, however this depends on the strength of passive screening in each health zone. We predict a pronounced increase in additional gHAT disease burden (morbidity and mortality) in many health zones if both active and passive screening were interrupted compared to the interruption of active screening alone. The ability to continue existing vector control during medical activity interruption is also predicted to avert a moderate proportion of disease burden.
Topics: Animals; Humans; Trypanosomiasis, African; Trypanosoma brucei gambiense; Democratic Republic of the Congo; COVID-19
PubMed: 37115809
DOI: 10.1371/journal.pntd.0011299 -
Open Biology Nov 2019African trypanosomes escape the mammalian immune response by antigenic variation-the periodic exchange of one surface coat protein, in the variant surface glycoprotein... (Review)
Review
African trypanosomes escape the mammalian immune response by antigenic variation-the periodic exchange of one surface coat protein, in the variant surface glycoprotein (VSG), for an immunologically distinct one. transcription is monoallelic, with only one being expressed at a time from a specialized locus, known as an expression site. switching is a predominantly recombination-driven process that allows sequences to be recombined into the active expression site either replacing the currently active or generating a 'new' by segmental gene conversion. In this review, we describe what is known about the factors that influence this process, focusing specifically on DNA repair and recombination.
Topics: Animals; Antigenic Variation; DNA Repair; Gene Conversion; Humans; Recombination, Genetic; Trypanosoma brucei brucei; Trypanosomiasis, African; Variant Surface Glycoproteins, Trypanosoma
PubMed: 31718509
DOI: 10.1098/rsob.190182