Trypanosoma evansi, the agent of “surra,” is a salivarian trypanosome, originating from Africa. It is thought to derive from Trypanosoma brucei by deletion of the maxicircle kinetoplastic DNA (genetic material required for cyclical development in tsetse flies). It is mostly mechanically transmitted by tabanids and stomoxes, initially to camels, in sub-Saharan area. The disease spread from North Africa towards the Middle East, Turkey, India, up to 53° North in Russia, across all South-East Asia, down to Indonesia and the Philippines, and it was also introduced by the conquistadores into Latin America. It can affect a very large range of domestic and wild hosts including camelids, equines, cattle, buffaloes, sheep, goats, pigs, dogs and other carnivores, deer, gazelles, and elephants. It found a new large range of wild and domestic hosts in Latin America, including reservoirs (capybaras) and biological vectors (vampire bats). Surra is a major disease in camels, equines, and dogs, in which it can often be fatal in the absence of treatment, and exhibits nonspecific clinical signs (anaemia, loss of weight, abortion, and death), which are variable from one host and one place to another; however, its immunosuppressive effects interfering with intercurrent diseases or vaccination campaigns might be its most significant and questionable aspect.

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Trypanosoma evansi and Surra: A Review and Perspectives on Origin, History, Distribution, Taxonomy, Morphology, Hosts, and Pathogenic Effects

This review discusses the challenges of chemotherapy for human African trypanosomiasis (HAT). The few drugs registered for use against the disease are unsatisfactory for a number of reasons. HAT has two stages. In stage 1 the parasites proliferate in the haemolymphatic system. In stage 2 they invade the central nervous system and brain provoking progressive neurological dysfunction leading to symptoms that include the disrupted sleep wake patterns that give HAT its more common name of sleeping sickness. Targeting drugs to the central nervous system offers many challenges. However, it is the cost of drug development for diseases like HAT, that afflict exclusively people of the world's poorest populations, that has been the principal barrier to new drug development and has led to them becoming neglected. Here we review drugs currently registered for HAT, and also discuss the few compounds progressing through clinical trials. Finally we report on new initiatives that might allow progress to be made in developing new and satisfactory drugs for this terrible disease.

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Human African trypanosomiasis: pharmacological re-engagement with a neglected disease

Drugs and drug resistance in African trypanosomiasis.

Most cells have the inherent capacity to shift their reliance on glycolysis relative to oxidative metabolism, and studies in model systems have shown that targeting such shifts may be useful in treating or preventing a variety of diseases ranging from cancer to ischemic injury. However, we currently have a limited number of mechanistically distinct classes of drugs that alter the relative activities of these two pathways. We screen for such compounds by scoring the ability of >3,500 small molecules to selectively impair growth and viability of human fibroblasts in media containing either galactose or glucose as the sole sugar source. We identify several clinically used drugs never linked to energy metabolism, including the antiemetic meclizine, which attenuates mitochondrial respiration through a mechanism distinct from that of canonical inhibitors. We further show that meclizine pretreatment confers cardioprotection and neuroprotection against ischemia-reperfusion injury in murine models. Nutrient-sensitized screening may provide a useful framework for understanding gene function and drug action within the context of energy metabolism.

/pdf/nutrient-sensitized-screening-for-drugs-that-shift-energy-4l2u4bnv87.pdf

Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis

Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.

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The animal trypanosomiases and their chemotherapy: a review.

Comparison of antibody- and antigen-detection enzyme immunoassays for the diagnosis of Trypanosoma evansi infections in camels

Homidium bromide as a chemoprophylactic for cattle trypanosomiasis in Kenya

Preliminary efficacy trial of Cymelarsan, a novel trypanocide, in camels naturally infected with Trypanosoma evansi in Kenya.

Results Prevalence of tungiasis was 57% (218/385; 95% CI=51.7%-61.6%). Itching (89.1%) was the most common associated symptom, followed by pain upon pressure (67.3%), sleep disturbance (58.2%) and walking difficulties (53%). In multivariate logistic regression analysis the following independent factors were identified to be associated with tungiasis: living in houses with an earthen floors (adjusted OR=3.84; 95%IC: 2.09-7.06), walking barefooted (OR=3.28; 1.78-6.04), having a common resting place outside the house (OR=2.36; 1.01-5.51) and presence of rats on the compound (OR=1.69; 1.03-2.75).

/pdf/tungiasis-jigger-infestation-in-rural-kenya-an-emerging-1awa84pcc8.pdf

Tungiasis (jigger infestation) in Rural Kenya, an emerging infectious disease

The Mau Forest situated in western Kenya is is the largest remaining near continuous block of indigenous forest in East Africa. It is a biodiversity haven with a wide range of fauna and flora some of which are endangered. The Mau is important as a water tower feeding rivers and lakes thus supporting livelihoods of millions of people in Kenya and the region. Over the last 20 years an estimated 2000 Km2 of forest was destroyed in the Mau resulting in environmental, social and economic loss. As a major water tower, the impact of this loss is evident lowered water levels in the rivers that emanate from this forest and increased temperatures. In addition are economic losses in agriculture, tourism and energy sectors that affect the livelihoods of people not just in areas adjacent to the Mau but also in neighbouring countires. The unobstructed destruction of the Mau forest continues to deprive the country of a national heritage and is of regional and global concern. Attempts to rehabilitate the Mau have had limited success and they require multidisciplinary local and international support.

https://eujournal.org/index.php/esj/article/download/6471/6211

M. W. Mutugi

Papers

Comparison of antibody- and antigen-detection enzyme immunoassays for the diagnosis of Trypanosoma evansi infections in camels

Homidium bromide as a chemoprophylactic for cattle trypanosomiasis in Kenya

Preliminary efficacy trial of Cymelarsan, a novel trypanocide, in camels naturally infected with Trypanosoma evansi in Kenya.

Tungiasis (jigger infestation) in Rural Kenya, an emerging infectious disease

Biodiversity, local resource, national heritage, regional concern, and global impact: the case of mau forest, kenya