Livestock, pathogens, vectors, and their environment: a causal inference-based approach to estimating the pathway-specific effect of livestock on human African trypanosomiasis risk

Livestock are important reservoirs for many diseases, and investigation of such zoonoses has long been the focus of One Health research. However, the effects of livestock on human and environmental health extend well beyond direct disease transmission. In this retrospective ecological cohort study we use pre-existing data and methods derived from causal inference and spatial epidemiology to estimate three hypothesized mechanisms by which livestock can come to bear on human African trypanosomiasis (HAT) risk: the reservoir effect, by which infected cattle and pigs are a source of infection to humans; the zooprophylactic effect, by which preference for livestock hosts exhibited by the tsetse fly vector of HAT means that their presence protects humans from infection; and the environmental change effect, by which livestock keeping activities modify the environment in such a way that habitat suitability for tsetse flies, and in turn human infection risk, is reduced. We conducted this study in four high burden countries: at the point level in Uganda, Malawi, and Democratic Republic of Congo (DRC), and at the county-level in South Sudan. Our results indicate cattle and pigs play an important reservoir role for the rhodesiense form (rHAT) in Uganda, however zooprophylaxis outweighs this effect for rHAT in Malawi. For the gambiense form (gHAT) we found evidence that pigs may be a competent reservoir, however dominance of the reservoir versus zooprophylactic pathway for cattle varied across countries. We did not find compelling evidence of an environmental change effect.

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Tsetse Flies (Glossina) as Vectors of Human African Trypanosomiasis: A Review

BioMed Research International ◽

10.1155/2016/6201350 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 18

Author(s):

Florence Njeri Wamwiri ◽

Robert Emojong Changasi

Keyword(s):

Disease Transmission ◽

Human African Trypanosomiasis ◽

Tsetse Fly ◽

Public Health Issue ◽

Tsetse Flies ◽

African Trypanosomiasis ◽

Land Use Patterns ◽

Transmission Cycle ◽

Use Patterns ◽

Abundance And Distribution

Human African Trypanosomiasis (HAT) transmitted by the tsetse fly continues to be a public health issue, despite more than a century of research. There are two types of the disease, the chronicgambienseand the acuterhodesiense-HAT. Fly abundance and distribution have been affected by changes in land-use patterns and climate. However, disease transmission still continues. Here, we review some aspects of HAT ecoepidemiology in the context of altered infestation patterns and maintenance of the transmission cycle as well as emerging options in disease and vector control.

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African Trypanosomiasis Dynamics: Modelling the Effects of Treatment, Education, and Vector Trapping

International Journal of Mathematics and Mathematical Sciences ◽

10.1155/2020/3690472 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Yustina A. Liana ◽

Nyimvua Shaban ◽

Goodluck Mlay ◽

Anitha Phibert

Keyword(s):

Disease Transmission ◽

Deterministic Model ◽

Reproduction Number ◽

Public Health Education ◽

Tsetse Fly ◽

Control Measures ◽

Effective Control ◽

Tsetse Flies ◽

Model Parameters ◽

African Trypanosomiasis

African trypanosomiasis is a vector-borne disease that is mainly transmitted by infected tsetse flies. A deterministic model of tsetse fly vector, human, and cattle hosts is formulated and analyzed to gain insights into the disease dynamics. The roles of public health education, treatment, and tsetse fly traps are studied. The effective reproduction number, a threshold used to determine whether the disease persists or dies out in the population, is determined. The sensitivity analysis of the model parameters is performed to determine their relationship with the effective reproduction number. The results show that the tsetse fly biting rate is the most sensitive parameter to the effective reproduction number. Furthermore, the model’s numerical simulation shows that a combination of all three interventions has the most significant impact on the control of African trypanosomiasis. Thus, we recommend that these control measures be put concurrently in endemic areas for effective control of the disease transmission.

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Potential impacts of climate change on geographical distribution of three primary vectors of African Trypanosomiasis in Tanzania’s Maasai Steppe: G. m. morsitans, G. pallidipes and G. swynnertoni

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009081 ◽

2021 ◽

Vol 15 (2) ◽

pp. e0009081

Author(s):

Happiness Jackson Nnko ◽

Paul Simon Gwakisa ◽

Anibariki Ngonyoka ◽

Calvin Sindato ◽

Anna Bond Estes

Keyword(s):

Public Health ◽

Climate Change ◽

Ecological Niche Modeling ◽

Tsetse Fly ◽

Tsetse Flies ◽

African Trypanosomiasis ◽

Modeling Tools ◽

Distribution Maps ◽

Current Climate ◽

Maasai Steppe

In the Maasai Steppe, public health and economy are threatened by African Trypanosomiasis, a debilitating and fatal disease to livestock (African Animal Trypanosomiasis -AAT) and humans (Human African Trypanosomiasis—HAT), if not treated. The tsetse fly is the primary vector for both HAT and AAT and climate is an important predictor of their occurrence and the parasites they carry. While understanding tsetse fly distribution is essential for informing vector and disease control strategies, existing distribution maps are old and were based on coarse spatial resolution data, consequently, inaccurately representing vector and disease dynamics necessary to design and implement fit-for-purpose mitigation strategies. Also, the assertion that climate change is altering tsetse fly distribution in Tanzania lacks empirical evidence. Despite tsetse flies posing public health risks and economic hardship, no study has modelled their distributions at a scale needed for local planning. This study used MaxEnt species distribution modelling (SDM) and ecological niche modeling tools to predict potential distribution of three tsetse fly species in Tanzania’s Maasai Steppe from current climate information, and project their distributions to midcentury climatic conditions under representative concentration pathways (RCP) 4.5 scenarios. Current climate results predicted that G. m. morsitans, G. pallidipes and G swynnertoni cover 19,225 km2, 7,113 km2 and 32,335 km2 and future prediction indicated that by the year 2050, the habitable area may decrease by up to 23.13%, 12.9% and 22.8% of current habitable area, respectively. This information can serve as a useful predictor of potential HAT and AAT hotspots and inform surveillance strategies. Distribution maps generated by this study can be useful in guiding tsetse fly control managers, and health, livestock and wildlife officers when setting surveys and surveillance programs. The maps can also inform protected area managers of potential encroachment into the protected areas (PAs) due to shrinkage of tsetse fly habitats outside PAs.

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Human African trypanosomiasis

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.070810_update_001 ◽

2010 ◽

pp. 1119-1127

Author(s):

August Stich

Keyword(s):

West Africa ◽

East Africa ◽

Trypanosoma Brucei ◽

Human African Trypanosomiasis ◽

Protozoan Parasite ◽

Sleeping Sickness ◽

Tsetse Flies ◽

African Trypanosomiasis ◽

Tropical Africa

Human African trypanosomiasis (HAT, sleeping sickness) is caused by two subspecies of the protozoan parasite Trypanosoma brucei: T. b. rhodesiense is prevalent in East Africa among many wild and domestic mammals; T. b. gambiense causes an anthroponosis in Central and West Africa. The disease is restricted to tropical Africa where it is transmitted by the bite of infected tsetse flies (...

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Human African trypanosomiasis

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0169 ◽

2020 ◽

pp. 1451-1459

Author(s):

Reto Brun ◽

Johannes Blum

Keyword(s):

Trypanosoma Brucei ◽

Human African Trypanosomiasis ◽

Specific Treatment ◽

Protozoan Parasite ◽

Control Measures ◽

Tsetse Flies ◽

African Trypanosomiasis ◽

Control Programmes ◽

The 1960S ◽

Stage 1

Human African trypanosomiasis (sleeping sickness) is caused by subspecies of the protozoan parasite Trypanosoma brucei. The disease is restricted to tropical Africa where it is transmitted by the bite of infected tsetse flies (Glossina spp.). Control programmes in the 1960s were very effective, but subsequent relaxation of control measures led to recurrence of epidemic proportions in the 1980s and 1990s. Control is now being regained. Untreated human African trypanosomiasis is almost invariably fatal. Specific treatment depends on the trypanosome subspecies and the stage of the disease. Drugs used for stage 1 include pentamidine and suramin, and for stage 2 include melarsoprol, eflornithine, and nifurtimox, but regimens are not standardized, and treatment is difficult and dangerous; all of the drugs used have many side effects, some potentially lethal.

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In silico analysis of proteins and microRNAs related to human African trypanosomiasis in tsetse fly

Computational Biology and Chemistry ◽

10.1016/j.compbiolchem.2020.107347 ◽

2020 ◽

Vol 88 ◽

pp. 107347

Author(s):

Zhiyuan Yang ◽

Mingqiang Wang ◽

Xi Zeng ◽

Angel Tsz-Yau Wan ◽

Stephen Kwok-Wing Tsui

Keyword(s):

In Silico ◽

Human African Trypanosomiasis ◽

In Silico Analysis ◽

Tsetse Fly ◽

African Trypanosomiasis ◽

Silico Analysis

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PO 8421 LITERATURE REVIEW OF BIOMARKERS FOR HUMAN AFRICAN TRYPANOSOMIASIS POST-TREATMENT FOLLOW-UP

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.92 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A35.3-A36

Author(s):

Lukusa Ngay ◽

Veerle Lejon ◽

Mumba Ngoyi

Keyword(s):

Treatment Failure ◽

Human African Trypanosomiasis ◽

Post Treatment ◽

Immunoglobulin M ◽

Sub Saharan Africa ◽

Tsetse Flies ◽

African Trypanosomiasis ◽

Cell Counts ◽

Specificity And Sensitivity

IntroductionHuman African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and rhodesiense and is transmitted to humans by tsetse flies in sub-Saharan Africa. To detect cure or treatment failure, patients are followed up after treatment integrating the use of biomarkers in blood or cerebrospinal fluid (CSF).MethodsA systematic review of the literature according to the PRISMA Statement for Reporting Systematic Reviews was done, focusing on biological markers for HAT post-treatment follow-up. Articles were retrieved from PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) by using keywords: Human African Trypanosomiasis, Biomarkers, Follow up, Post treatment.ResultsA panel of biomarkers is used to detect relapses or to confirm recovery. For post-treatment follow-up, an examination of the CSF is performed. White blood cell counts in CSF with a defined cut-off value have been proven to be the most accurate to assess the treatment outcome. The intrathecal immunoglobulin M synthesis is a specific and sensitive parameter for the detection of CNS involvement in cases of HAT caused by T. brucei gambiense. The decrease of trypanosome-specific antibodies concentrations in CSF could be a good parameter for definite cure. High CSF IL-10 levels during treatment follow-up indicate recurring CNS inflammation and treatment failure. An increase of Neopterin in CSF and the presence of trypanosome spliced leader RNA in the blood have a high potential as predictors for treatment failure but need further validation.ConclusionNew biomarkers for post-treatment follow-up in HAT should 1) have high diagnostic specificity and sensitivity; 2) be applicable in field conditions; 3) preferentially be performed on blood and thus avoid the painful lumbar puncture during post-treatment control visits; and 4) shorten the follow-up period.

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A Tale of Three Species: Adaptation ofSodalis glossinidiusto Tsetse Biology,WigglesworthiaMetabolism, and Host Diet

mBio ◽

10.1128/mbio.02106-18 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 8

Author(s):

Rebecca J. Hall ◽

Lindsey A. Flanagan ◽

Michael J. Bottery ◽

Vicki Springthorpe ◽

Stephen Thorpe ◽

...

Keyword(s):

Trypanosoma Brucei ◽

Human African Trypanosomiasis ◽

Strong Dependence ◽

Tsetse Fly ◽

Disease Spread ◽

Growth Media ◽

Insect Vector ◽

African Trypanosomiasis ◽

Content Type ◽

Sodalis Glossinidius

ABSTRACTThe tsetse fly is the insect vector for theTrypanosoma bruceiparasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium,Sodalis glossinidius. The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model ofS. glossinidiusmetabolism. The model enabled the design and experimental verification of a defined medium that supportsS. glossinidiusgrowthex vivo. This has been used subsequently to analyzein vitroaspects ofS. glossinidiusmetabolism, revealing multiple unique adaptations of the symbiont to its environment. Continued dependence on a sugar, and the importance of the chitin monomerN-acetyl-d-glucosamine as a carbon and energy source, suggests adaptation to host-derived molecules. Adaptation to the amino acid-rich blood diet is revealed by a strong dependence onl-glutamate as a source of carbon and nitrogen and by the ability to rescue a predictedl-arginine auxotrophy. Finally, the selective loss of thiamine biosynthesis, a vitamin provided to the host by the primary symbiontWigglesworthia glossinidia, reveals an intersymbiont dependence. The reductive evolution ofS. glossinidiusto exploit environmentally derived metabolites has resulted in multiple weaknesses in the metabolic network. These weaknesses may become targets for reagents that inhibitS. glossinidiusgrowth and aid the reduction of trypanosomal transmission.IMPORTANCEHuman African trypanosomiasis is caused by theTrypanosoma bruceiparasite. The tsetse fly vector is of interest for its potential to prevent disease spread, as it is essential forT. bruceilife cycle progression and transmission. The tsetse’s mutualistic endosymbiontSodalis glossinidiushas a link to trypanosome establishment, providing a disease control target. Here, we describe a new, experimentally verified model ofS. glossinidiusmetabolism. This model has enabled the development of a defined growth medium that was used successfully to test aspects ofS. glossinidiusmetabolism. We presentS. glossinidiusas uniquely adapted to life in the tsetse, through its reliance on the blood diet and host-derived sugars. Additionally,S. glossinidiushas adapted to the tsetse’s obligate symbiontWigglesworthia glossinidiaby scavenging a vitamin it produces for the insect. This work highlights the use of metabolic modeling to design defined growth media for symbiotic bacteria and may provide novel inhibitory targets to block trypanosome transmission.

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The Flipside of Eradicating a Disease; Human African Trypanosomiasis in a Woman in Rural Democratic Republic of Congo: A Case Report

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed4040142 ◽

2019 ◽

Vol 4 (4) ◽

pp. 142 ◽

Cited By ~ 2

Author(s):

Junior Mudji ◽

Jonathan Benhamou ◽

Erick Mwamba-Miaka ◽

Christian Burri ◽

Johannes Blum

Keyword(s):

Case Report ◽

Sleep Disorder ◽

Human African Trypanosomiasis ◽

Democratic Republic Of Congo ◽

Disease Diagnosis ◽

Tsetse Flies ◽

Test Results ◽

African Trypanosomiasis ◽

Laboratory Test Results ◽

Two Phases

Human African Trypanosomiasis (HAT) is a neglected disease caused by the protozoan parasites Trypanosoma brucei and transmitted by tsetse flies that progresses in two phases. Symptoms in the first phase include fever, headaches, pruritus, lymphadenopathy, and in certain cases, hepato- and splenomegaly. Neurological disorders such as sleep disorder, aggressive behavior, logorrhea, psychotic reactions, and mood changes are signs of the second stage of the disease. Diagnosis follows complex algorithms, including serological testing and microscopy. Our case report illustrates the course of events of a 41-year old woman with sleep disorder, among other neurological symptoms, whose diagnosis was made seven months after the onset of symptoms. The patient had consulted two different hospitals in Kinshasa and was on the verge of being discharged from a third due to negative laboratory test results. This case report highlights the challenges that may arise when a disease is on the verge of eradication.

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Tsetse blood-meal sources, endosymbionts and trypanosome-associations in the Maasai Mara National Reserve, a wildlife-human-livestock interface

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008267 ◽

2021 ◽

Vol 15 (1) ◽

pp. e0008267

Author(s):

Edward Edmond Makhulu ◽

Jandouwe Villinger ◽

Vincent Owino Adunga ◽

Maamun M. Jeneby ◽

Edwin Murungi Kimathi ◽

...

Keyword(s):

Blood Meal ◽

Glossina Pallidipes ◽

Tsetse Fly ◽

Tsetse Flies ◽

African Buffalo ◽

African Trypanosomiasis ◽

African Trypanosomes ◽

Sodalis Glossinidius ◽

Vertebrate Hosts ◽

Blood Meals

African trypanosomiasis (AT) is a neglected disease of both humans and animals caused by Trypanosoma parasites, which are transmitted by obligate hematophagous tsetse flies (Glossina spp.). Knowledge on tsetse fly vertebrate hosts and the influence of tsetse endosymbionts on trypanosome presence, especially in wildlife-human-livestock interfaces, is limited. We identified tsetse species, their blood-meal sources, and correlations between endosymbionts and trypanosome presence in tsetse flies from the trypanosome-endemic Maasai Mara National Reserve (MMNR) in Kenya. Among 1167 tsetse flies (1136 Glossina pallidipes, 31 Glossina swynnertoni) collected from 10 sampling sites, 28 (2.4%) were positive by PCR for trypanosome DNA, most (17/28) being of Trypanosoma vivax species. Blood-meal analyses based on high-resolution melting analysis of vertebrate cytochrome c oxidase 1 and cytochrome b gene PCR products (n = 354) identified humans as the most common vertebrate host (37%), followed by hippopotamus (29.1%), African buffalo (26.3%), elephant (3.39%), and giraffe (0.84%). Flies positive for trypanosome DNA had fed on hippopotamus and buffalo. Tsetse flies were more likely to be positive for trypanosomes if they had the Sodalis glossinidius endosymbiont (P = 0.0002). These findings point to complex interactions of tsetse flies with trypanosomes, endosymbionts, and diverse vertebrate hosts in wildlife ecosystems such as in the MMNR, which should be considered in control programs. These interactions may contribute to the maintenance of tsetse populations and/or persistent circulation of African trypanosomes. Although the African buffalo is a key reservoir of AT, the higher proportion of hippopotamus blood-meals in flies with trypanosome DNA indicates that other wildlife species may be important in AT transmission. No trypanosomes associated with human disease were identified, but the high proportion of human blood-meals identified are indicative of human African trypanosomiasis risk. Our results add to existing data suggesting that Sodalis endosymbionts are associated with increased trypanosome presence in tsetse flies.

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