Trypanosomiasis; symptom, transmission, treatment and prevention

18/09/2022

Tsetse flies are the cyclical vectors of trypanosomes, the causative agents of ‘sleeping sickness’ or human African trypanosomosis (HAT) in humans and ‘nagana’ or African animal trypanosomosis (AAT) in livestock in Sub-saharan Africa. Many consider HAT as one of the major neglected tropical diseases and AAT as the single greatest health constraint to increased livestock production. This review provides some background information on the taxonomy of tsetse flies, their unique way of reproduction (adenotrophic viviparity) making the adult stage the only one easily accessable for control, and how their ecological affinities, their distribution and population dynamics influence and dictate control efforts. The paper likewise reviews four control tactics (sequential aerosol technique, stationary attractive devices, live bait technique and the sterile insect technique) that are currently accepted as friendly to the environment, and describes their limitations and advantages and how they can best be put to practise in an IPM context. The paper discusses the different strategies for tsetse control i.e. localised versus area-wide and focusses thereafter on the principles of area-wide integrated pest management (AW-IPM) and the phased-conditional approach with the tsetse project in Senegal as a recent example. We argue that sustainable tsetse-free zones can be created on Africa mainland provided certain managerial and technical prerequisites are in place.

18/09/2022

Across sub-Saharan Africa, a variety of Trypanosoma spp transmitted by tsetse flies (Glossina spp) cause human and animal trypanosomiases. There are >10,000 cases/year of Human African Trypanosomiasis (HAT) with an estimated burden of ∼1.3 million Disability Adjusted Life Years (DALYs) and economic losses in excess of $1 billion due to human and animal trypanosomiasis While interventions can be directed against the vector or the parasite, emphasis has usually been on the use of drugs to treat the disease both in humans and in livestock.
While the importance of treating cases, especially human ones, cannot be overstated, several advances in our understanding of tsetse biology and ecology, and improvements in the cost-effectiveness of tsetse control, have revived interest in that approach to disease management. First, the use of satellite navigation as an aid to nocturnal aerial spraying, spraying much larger areas than previously, and protecting the sprayed areas with odor-baited targets, has provided impressive results, such as the eradication of G. m. centralis from Botswana Second, the demonstration of the importance of odor for host location in some species of tsetse provided a means of attracting them to insecticide-treated targets and, by killing the flies, provided control of cattle and human trypanosomiasis Third, the particularly low reproductive rate in tsetse made it possible to use as few as four such targets per square kilometer to eliminate isolated populations of G. pallidipes Austen and two sub-species of G. morsitans The method is cheaper than aerial spraying and more environmentally friendly than insecticidal ground spraying, game destruction or habitat clearance . Issues of cost, logistics, government commitment, and theft of materials have meant, however, that the approach has not been used in large-scale control programs except in Zimbabwe and in the Western Province of Zambia
Part of the reason for this limited use stems from the fact that, simultaneously with the development of insecticide-treated target technology, it was realized that tsetse control could be achieved equally effectively by applying insecticide to the very livestock - generally cattle - off which the tsetse were feeding. This approach has been used very successfully in areas where tsetse feed predominantly on cattle, though it would be less effective in areas where – as in large parts of Zimbabwe and Tanzania – the predominant food source for the tsetse are wild mammals.
Whereas insecticide-treated cattle (ITC) can be used in operations aimed at eliminating tsetse populations, animal trypanosomiasis can also be reduced to low levels even where tsetse populations persist . It is, of course, relief from cattle disease – rather than issues of tsetse fly control versus eradication – which most interests stockholders in tsetse areas and which can be used to interest the stockholder in becoming actively involved in tsetse and trypanosomiasis control. Recent advances in our understanding of the feeding behavior of tsetse on cattle have led to even cheaper methods of tsetse control where the insecticide is applied to the body regions and/or individual animals on which most tsetse feed. This restricted application of pyrethroids is comparable in its cost and simplicity to the widespread use of trypanocides by farmers to prevent or cure trypanosomiasis in their livestock
There are several possible reasons why these advances in affordable, low-technology tsetse control have not, as yet, played a significant role in efforts against HAT. First, there is an imperative to find and treat infected humans and livestock and this approach is thus the foundation of all efforts against the disease. Second, the odor-baited devices used so effectively in efforts against animal trypanosomiasis are less effective against the important vectors of HAT. This poor efficacy is probably related, in part, to the distinctions between the host relationships of the various tsetse species. The important vectors of animal trypanosomiasis, i.e., the Morsitans-group tsetse, feed almost exclusively on mammals (e.g. warthog, kudu, buffalo and cattle) which they locate largely by odor, whereas the Palpalis-group species, which are the main vectors of HAT, are less responsive to odors and include reptiles and birds in their diet. For instance, between 50 and 90% of meals taken by Glossina fuscipes fuscipes are from monitor lizard which themselves do not support all the trypanosome species infective to mammals
In this paper, we investigate the theoretical effects of two different approaches to trypanosomiasis control, both of which have already been shown to be of interest to small-scale stockholders in resource-limited settings. First we consider the effect of treating animals with trypanocides, which prevent the disease without having any insecticidal effect. Second, we consider the use of the ITC method, which has no direct trypanocidal effect but which increases mortality in the vectors. We limit our study to the situation typical of eastern and southern Africa, where Trypanosoma vivax, T. congolense and T. brucei rhodesiense occur in livestock and wildlife - and where the last-named parasite also causes “Rhodesian” sleeping sickness in humans

18/09/2022

Prevention & Control
There is no vaccine or drug for prophylaxis against African trypanosomiasis. Preventive measures are aimed at minimizing contact with tsetse flies. Local residents in endemic countries are usually aware of the areas that are heavily infested and may be able to provide advice about places to avoid. Other helpful measures include:
Wear long-sleeved shirts and pants of medium-weight material in neutral colors that blend with the background environment. Tsetse flies are attracted to bright or dark colors, and they can bite through lightweight clothing.
Inspect vehicles before entering. The flies are attracted to the motion and dust from moving vehicles.
Avoid bushes. The tsetse fly is less active during the hottest part of the day but will bite if disturbed.
Use insect repellent. Permethrin-impregnated clothing and insect repellent have not been proved to be particularly effective against tsetse flies, but they will prevent other insect bites that can cause illness.

18/09/2022

American trypanosomiasis, commonly known as Chagas disease, is caused by the flagellate protozoan parasite Trypanosoma cruzi. An estimated eight million people infected with T. cruzi currently reside in the endemic regions of Latin America. However, as the disease has now been imported into many non-endemic countries outside of Latin America, it has become a global health issue. We reviewed the transmission patterns and current status of disease spread pertaining to American trypanosomiasis at the global level, as well as recent advances in research. Based on an analysis of the gaps in American trypanosomiasis control, we put forward future research priorities that must be implemented to stop the global spread of the disease.

18/09/2022

Treatment
The type of treatment depends on the form of the disease and the disease stage. The earlier the disease is identified, the better the prospect of a cure. The assessment of treatment outcome requires follow up of the patient up to 24 months and entails clinical assessment and laboratory exams of body fluids including in some cases, cerebrospinal fluid obtained by lumbar puncture, as parasites may remain viable for long periods and reproduce the disease months after treatment.
Treatment success in the second stage depends on drugs that cross the blood-brain barrier to reach the parasite.
New treatment guidelines for gambiense human African trypanosmiasis were issued by WHO in 2019. In total six different drugs are used for the treatment of sleeping sickness. These drugs are donated to WHO by manufacturers and distributed free of charge to disease endemic countries.
Drugs used in the treatment of first stage:
Pentamidine: discovered in 1940, used for the treatment of the first stage of T. b. gambiense sleeping sickness. Despite non-negligible undesirable effects, it is in general well tolerated by patients.
Suramin: discovered in 1920, used for the treatment of the first stage of T. b. rhodesiense. It provokes certain undesirable effects, including nephrotoxicity and allergic reactions.
Drugs used in the treatment of second stage:
Melarsoprol: discovered in 1949, it is used for the treatment of both gambiense and rhodesiense infections. It is derived from arsenic and has many undesirable side effects, the most dramatic of which is reactive encephalopathy (encephalopathic syndrome) which can be fatal (3% to 10%). It is currently recommended as first-line treatment for the rhodesiense form, but rarely used in the gambiense form.
Eflornithine: much less toxic than melarsoprol, registered in 1990 is only effective against T.b. gambiense. It is generally used in combination with nifurtimox (as part of the Nifurtimox-eflornithine combination therapy, NECT) but can be used also as monotherapy. The regimen is complex and cumbersome to apply.
Nifurtimox: The Nifurtimox-eflornithine combination therapy, NECT, was introduced in 2009. It simplifies the use of eflornithine by reducing the duration of treatment and the number of IV perfusions, but unfortunately it has not been studied for T.b. rhodesiense. Nifurtimox is registered for the treatment of American trypanosomiasis but not for human African trypanosomiasis. Both drugs are provided free of charge by WHO to endemic countries with a kit containing all the material needed for its administration.
Drugs used in the treatment of both stages:
Fexinidazole is an oral treatment for gambiense human African trypanosomiasis It was included in 2019 in the WHO Essential medicines list and WHO human African Trypanosomiasis treatment guidelines. This molecule is indicated as first line for first stage and non-severe second stage. It should be administered for 10 days within 30 minutes after a solid meal and under supervision of trained medical staff. Currently a clinical trial for its use in rhodesiense HAT is ongoing.

18/09/2022

Disease management: diagnosis
Disease management is made in 3 steps:
Screening for potential infection. This involves using serological tests (only available for T. b.gambiense) and checking for clinical signs - especially swollen cervical lymph nodes.
Diagnosing by establishing whether the parasite is present in body fluids.
Staging to determine the state of disease progression. This entails clinical examination and in some cases analysis of the cerebrospinal fluid obtained by lumbar puncture.
Diagnosis must be made as early as possible to avoid progressing to the neurological stage in order to elude complicated and risky treatment procedures
The long, relatively asymptomatic first stage of T. b. gambiense sleeping sickness is one of the reasons why an exhaustive, active screening of the population at risk is recommended, to identify patients at an early stage and reduce transmission by removing their status of reservoir. Exhaustive screening requires a major investment in human and material resources. In Africa such resources are often scarce, particularly in remote areas where the disease is mostly found. As a result, some infected individuals may die before they can ever be diagnosed and treated.

18/09/2022

Infection and symptoms
The disease is mostly transmitted through the bite of an infected tsetse fly but there are other ways in which people are infected:
Mother-to-child infection: the trypanosome can cross the placenta and infect the fetus.
Mechanical transmission through other blood-sucking insects is possible, however, it is difficult to assess its epidemiological impact.
Accidental infections have occurred in laboratories due to pricks with contaminated needles.
Transmission of the parasite through s*xual contact has been reported.
In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph. This is also called haemo-lymphatic stage, which entails bouts of fever, headaches, enlarged lymph nodes, joint pains and itching
In the second stage the parasites cross the blood-brain barrier to infect the central nervous system. This is known as the neurological or meningo-encephalic stage. In general this is when more obvious signs and symptoms of the disease appear: changes of behaviour, confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is an important feature. Without treatment, sleeping sickness is considered fatal although cases of healthy carriers have been reported.

18/09/2022

Major human epidemics
There have been several epidemics in Africa over the last century:
one between 1896 and 1906, mostly in Uganda and the Congo Basin;
one in 1920 in a number of African countries; and
the most recent epidemic started in 1970 and lasted until the late 1990s.
The 1920 epidemic was controlled thanks to mobile teams which carried out the screening of millions of people at risk. By the mid-1960s, the disease was under control with less than 5000 cases reported in the whole continent. After this success, surveillance was relaxed, and the disease reappeared, reaching epidemic proportions in several regions by 1970. The efforts of WHO, national control programmes, bilateral cooperation and nongovernmental organizations (NGOs) during the 1990s and early 21st century reversed the curve.
Since the number of new human African trypanosomiasis cases reported between 2000 and 2012 dropped significantly as a result of international coordinated efforts, the WHO neglected tropical diseases road map targeted its elimination as a public health problem by 2020 and interruption of transmission (zero cases) for 2030.

18/09/2022

Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. It is caused by infection with protozoan parasites belonging to the genus Trypanosoma. They are transmitted to humans by tsetse fly ( Glossina genus) bites which have acquired their infection from human beings or from animals harbouring human pathogenic parasites.
Tsetse flies are found just in sub-Saharan Africa though only certain species transmit the disease. For reasons that are so far unexplained, in many regions where tsetse flies are found, sleeping sickness is not. Rural populations living in regions where transmission occurs and which depend on agriculture, fishing, animal husbandry or hunting are the most exposed to the tsetse fly and therefore to the disease. The disease develops in areas ranging from a single village to an entire region. Within an infected area, the intensity of the disease can vary from one village to the next.

18/09/2022

African trypanosomiasis is caused by parasites of genus Trypanosoma and transmitted by infected tsetse flies and is endemic in 36 sub-Saharan African countries where there are tsetse flies that transmit the disease. Without treatment, the disease is considered fatal.
The people most exposed to the tsetse fly and to the disease live in rural areas and depend on agriculture, fishing, animal husbandry or hunting.
Human African trypanosomiasis takes 2 forms, depending on the subspecies of the parasite involved: Trypanosoma brucei gambiense accounts for more than 95% of reported cases.
Sustained control efforts have reduced the number of new cases. In 2009 the number reported dropped below 10 000 for the first time in 50 years, and in 2019 there were with 992 and 663 cases reported in 2019 and 2020 cases recorded respectively.
Diagnosis and treatment of the disease is complex and requires specifically skilled staff.

19/08/2022

Vectors are living organisms that can transmit infectious pathogens between humans, or from animals to humans. Many of these vectors are bloodsucking insects, which ingest disease-producing microorganisms during a blood meal from an infected host (human or animal) and later transmit it into a new host, after the pathogen has replicated. Often, once a vector becomes infectious, they are capable of transmitting the pathogen for the rest of their life during each subsequent bite/blood meal.
Vector-borne diseases
Vector-borne diseases are human illnesses caused by parasites, viruses and bacteria that are transmitted by vectors. Every year there are more than 700,000 deaths from diseases such as malaria, dengue, schistosomiasis, human African trypanosomiasis, leishmaniasis, Chagas disease, yellow fever, Japanese encephalitis and onchocerciasis.
The burden of these diseases is highest in tropical and subtropical areas, and they disproportionately affect the poorest populations. Since 2014, major outbreaks of dengue, malaria, chikungunya, yellow fever and Zika have afflicted populations, claimed lives, and overwhelmed health systems in many countries. Other diseases such as Chikungunya, leishmaniasis and lymphatic filariasis cause chronic suffering, life-long morbidity, disability and occasional stigmatisation.
Distribution of vector-borne diseases is determined by a complex set of demographic, environmental and social factors. Global travel and trade, unplanned urbanization

19/08/2022

Vector-borne diseases account for more than 17% of all infectious diseases, causing more than 700 000 deaths annually. They can be caused by either parasites, bacteria or viruses.
Malaria is a parasitic infection transmitted by Anopheline mosquitoes. It causes an estimated 219 million cases globally, and results in more than 400,000 deaths every year. Most of the deaths occur in children under the age of 5 years.
Dengue is the most prevalent viral infection transmitted by Aedes mosquitoes. More than 3.9 billion people in over 129 countries are at risk of contracting dengue, with an estimated 96 million symptomatic cases and an estimated 40,000 deaths every year.
Other viral diseases transmitted by vectors include chikungunya fever, Zika virus fever, yellow fever, West Nile fever, Japanese encephalitis (all transmitted by mosquitoes), tick-borne encephalitis (transmitted by ticks).
Many of vector-borne diseases are preventable, through protective measures, and community mobilisation.

19/08/2022

A vector is a living organism that transmits an infectious agent from an infected animal to a human or another animal. Vectors are frequently arthropods, such as mosquitoes, ticks, flies, fleas and lice.
Vectors can transmit infectious diseases either actively or passively:
Biological vectors, such as mosquitoes and ticks may carry pathogens that can multiply within their bodies and be delivered to new hosts, usually by biting.
Mechanical vectors, such as flies can pick up infectious agents on the outside of their bodies and transmit them through physical contact.
Diseases transmitted by vectors are called vector-borne diseases. Many vector-borne diseases are zoonotic diseases, i.e. diseases that can be transmitted directly or indirectly between animals and humans. These include for example Lyme disease, tick-borne encephalitis, West Nile virus, Leishmaniosis and Crimean-Congo haemorrhagic fever.
Many vector-borne diseases are considered as emerging infectious diseases in the European Union:
a disease that appears in a population for the first time, or
that may have existed previously but is rapidly increasing in incidence or geographic range.
Some vectors are able to move considerable distances. This may affect the transmission ranges of vector-borne zoonotic diseases. Vectors can be introduced to new geographic areas for example by:
travel of humans and international trade;
animal movement, for instance of livestock;
migratory birds;
changing agricultural practices;
or the wind.
Other factors may play a role in their establishment and persistence in new areas, including climatic conditions.
EFSA's role
EFSA and its Panel on Animal Health and Welfare provide independent scientific advice and scientific assistance on human health and animal health-related aspects of vector-borne zoonotic diseases. EFSA monitors and analyses the situation on zoonoses, zoonotic micro-organisms, antimicrobial resistance, microbiological contaminants and food-borne outbreaks across Europe.
EFSA works with European Centre for Disease Prevention and Control (ECDC), sharing information on present and future projects on vectors and vector-borne zoonotic diseases.
Based on data collected by the EU Member States, EFSA and ECDC produce annual European Union summary reports on vector-borne zoonoses in animals and food-borne outbreaks caused by these micro-organisms.
Disease Profiles
EFSA has produced interactive disease profiles that provide user-friendly and evidence-based information on vector-borne diseases. The disease profiles are updated through seven living systematic reviews covering: 1) Geographic Distribution; 2) Experimental Infections; 3) Vaccination Efficacy; 4) Pathogen Survival; 5) Diagnostic Test Accuracy 6) Vector Control and 7) Treatment Efficacy. When sufficient studies are found and reviewed, a meta-analysis is carried out automatically on the extracted data and the results are visualised in the disease profiles. In addition, links to other risk assessments on the diseases carried out by EFSA are provided.

26/05/2022

05/02/2022

Zero malaria starts with me”
On World Malaria Day 2020, WHO joins the RBM Partnership to End Malaria in promoting “Zero malaria starts with me”, a grassroots campaign that aims to keep malaria high on the political agenda, mobilize additional resources, and empower communities to take ownership of malaria prevention and care.

We know that through country leadership and collective action, we can radically reduce suffering and death from malaria. Between 2000 and 2014, the number of malaria-related deaths fell by 40% worldwide, from an estimated 743 000 to 446 000.

But in recent years, progress has ground to a standstill. According to WHO's World malaria report 2019, there were no global gains in reducing new infections over the period 2014 to 2018. And nearly as many people died from malaria in 2018 as the year before.

In the Western Pacific Region, eighty percent of the malaria cases were reported in Papua New Guinea (80%); when taken together with Cambodia and Solomon Islands, the three countries comprise 98% of the estimated cases. There were roughly 250 reported deaths in the region due to malaria. Still, five out of the 10 malaria endemic countries in the region are on target to achieve more than a 40% reduction in case incidence by 2021.

Urgent action is needed to get back on track, and ownership of the challenge lies in the hands of countries most affected by malaria. The “Zero malaria” campaign engages all members of society: political leaders who control government policy decisions and budgets; private sector companies that will benefit from a malaria-free workforce; and communities affected by malaria, whose buy-in and ownership of malaria control interventions is critical to success. Join us in our shared effort to get to zero malaria.