Question 13- Design a program to eradicate sleeping sickness as a human disease, based on your understanding of the parasite’s lifecycle.

Question 13- Design a program to eradicate sleeping sickness as a human disease, based on your understanding of the parasite’s lifecycle.

By Gillary Cuartas

References:

Refer to Figure 51.2 Schaechter(4th ed)-Mechanisms of microbial disease or Module 7 page 4. Read pages 501-502 textbook - optional since most condensed here.

http://www.who.int/mediacentre/factsheets/fs259/en/

http://www.who.int/trypanosomiasis_african/vector_control/en/print.html

http://tc.iaea.org/tcweb/publications/factsheets/tsetse.pdf#search=%22SIT%20for%20tsetse%22



Human African Trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. The parasites concerned are protozoa belonging to the Trypanosoma Genus includingTrypanosoma brucei gambiense (T.b.g.) and Trypanosoma brucei rhodesiense (T.b.r.). They are transmitted to humans by saliva of tsetse fly (Glossina Genus) bites which have acquired their infection from human beings or from animals harbouring the human pathogenic parasites.

Tsetse flies are found in Sub-Saharan Africa, mainly found in vegetation by rivers and lakes, in gallery-forests and in vast stretches of wooded savannah.

Human African Trypanosomiasis takes two forms, depending on the parasite involved:

Trypanosoma brucei gambiense (T.b.g.) is found in west and central Africa accounts for< 90% of reported cases of sleeping sickness and causes a chronic infection. A person can beinfected for months or even years without major signs or symptoms of the disease. When symptoms do emerge, the patient is often already in an advanced disease stage when the central nervous system is affected.

Trypanosoma brucei rhodesiense (T.b.r.) is found in eastern and southern Africa. <10% of reported cases and causes an acute infection. First signs and symptoms are observed after a few months or weeks. The disease develops rapidly and invades the central nervous system



INFECTION AND SYMPTOMS

First stage: (haemolymphatic phase) fever, headaches, joint pains and itching. Multiplication in subcutaneous tissues.

Second stage (neurological phase) parasite crosses the blood-brain barrier and invades the CNS. signs and symptoms usually appear at this stage include: confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, hence the name ”sleeping sickness”, also occurs at this stage.

During the months or years of chronic bloodstream infection, patients undergo bouts of parasitemia, (flucuations in the no. of trypanosomes in the blood), due to antigenic variation. Hence, human starts to combat disease, trypanosomes go down, then changes surface glycoprotein, host must develop new defences. (SEE Figure 52-10 below)

Without treatment, sleeping sickness is fatal. The process can take years with T.b. gambiense.



DISEASE MANAGEMENT

Disease management is performed in three steps:

Screening for potential infection. This involves the use of serological tests and/or checking for clinical signs - generally swollen cervical glands.

Diagnosis shows whether the parasite is present.

Staging to determine the state of progression of the disease entails examination of cerebro-spinal fluid obtained by lumbar puncture and is used to determine the course of treatment.

Diagnosis must be made as early as possible and before the neurological stage in order to avoid complicated, difficult and risky treatment procedures.

Screening of asymptomatic high risk groups in Africa as means of prevention is costly and time consuming.

TREATMENT (different for each stage of the disease, stages previously discussed)

First stage treatments (effective, less costly, easy to administer)

Pentamidine: for first stage of T.b. gambiense sleeping sickness. Well tolerated

Suramin: for the first stage of T.b. rhodesiense. Can make allergic rxns.



Second stage treatments (drugs cross blood brain barrier, complicated to administer, more toxic)

Melarsoprol: arsenic derivative can cause (encephalopathic syndrome) which can be fatal (3% to 10%). Resistance a problem in Africa.

Eflornithine: effective against T.b. gambiense. Strict and difficult reginmen

Life Cycle

(1)The tsetse fly vector inoculates infectious trypomastigotes under the skin when it bites humans or other mammals. Once inside the new host(2), the parasite replicates in the bloodstream by binary fission as a trypomastigote (3). The rate of movement of trypomastigotes from the bloodstream and lymph nodes to the CNS is when illness goes from a systemic (hemolymphatic) infection to an encephalitis. (4) Circulating trypomastigotes taken up again by tsetse flies that bite host complete the cycle. (5). Within the tsetse fly the parasites replicate in the gastrointestinal tract and transform into epimastigotes The dashed line below stage 4 indicates that natural transmission does not occur in countries such as the United States where the tsetse fly vector is not present.

SEE FIGURE 51-2 TEXTBOOK FOR THE LIFECYLE PICTURE

(In case you dont know the textbook is available online with pictures see your front cover for details)

For a more detailed lifecycle go to http://web.capetown.gov.za/eDocuments/Diseases_-_African_Sleeping_Sickness_-_Life_Cycle_952005204730_245.pdf



In your answer include a bit of knowledge described above and suggest interventions based on your knowledge of the lifecycle.



FIGURE 51-2 Idealized (model) parasite life cycle and points of intervention. The human stages of the life cycle are located in the top half of the diagram. The extrahuman stages (in animate or inanimate reservoirs) are in the lower half. When the parasite reaches the infective stage, it invades the human host, matures, replicates, and ultimately completes the life cycle by producing infective forms. The infective forms are taken up by a vector or released into the environment. Control measures interfere with the replication or survival of the extrahuman stages of the parasite. They reduce the incidence of infection by reducing the number of infective stages to which humans are exposed. Immunization (vaccination) prevents symptomatic infection by inhibiting or killing the parasite as it enters (or replicates within) the human host. Chemoprophylaxis is used to inhibit parasite replication and thus prevent symptomatic infection. Neither immunization nor chemoprophylaxis prevents the initial entry of the parasite. Drug treatment is used to prevent death or severe morbidity in persons with established infections.

Some suggestions/considerations:



Eradicating trypanosomiasis is hard cos can affect humans, antelopes, bovine cattle, camels, horses, sheep, goats, and pigs. These diseases are caused by several different trypanosome species which may also survive in wild animals such as crocodiles and monitor lizards. So to eradicate it as a human disease you must also eliminate potential reservoirs of infection- all those pigs, cattle, etc which are needed for livestock, transport etc. TOO HARD!



Vaccination-may be problem due to antigenic variation of trypanosomes. can prevent replication of trypanosomes effectively halting transmisission from occurring via insect bite.



Wearning protective clothing in areas where tse tse fly commonly found

Sub-Saharan africaà vegetation by rivers and lakes, in gallery-forests and in vast stretches of wooded savannah. Perhaps also when around potentially infected animals.

Surveillance of high populations of tse tse fly – compulsory to use insecticides and supply must be free.

Large scale campaign to supply people with RID or other insecticides that can be applied to the skin or themselves and animals they own or are in contact with. Consideration to whether the animal will be toxic to eat after the application of the insecticide is important.

Continued research into the genetics of the tse tse fly will also be key in developing better modes of eradicating the tse tse fly and eradicating sleeping sickness.



Current vector control measures include:

Current vector control interventions involve the use of insecticides either through sequential aerosol spraying technique (SAT); ground spraying; insecticide-treated targets or insecticide-treated animals – live baits; the use of traps, and the sterile insect technique (SIT).

1.SAT,- clear large areas of tsetse in a relatively short time, is quite expensive and requires substantial economic and infrastructure support. Recent advances in aircraft guidance systems have considerably increased the accuracy and the efficiency of insecticide delivery as shown in recent control operations in the Okavango delta in Botswana and Namibia. Aerial spraying is scheduled to be undertaken in Angola and Zambia in 2007. The main limitation of aerial spraying as with other methods is the re-invasion pressure if the area is not isolated.



2. Pour-ons (application of insecticides to backs of cattle on which tsetse feed) or selective spraying on legs and belly where flies go selectively to bite are another effective means of vector control saving funds and minimizing the distribution of pesticide in the environment.

3. Odor baited traps and screen impregnated with insecticide and appropriate attractive colours have been used in many countries to effectively suppress tsetse population by 99%. cheaper than ground and aerial spraying but communities and governments cannot deploy them on sustainable bases, as they are labor and management intensive.

Importance of large scale implementation since re-invasion is a major issue.

4. The Sterile Insect Technique (SIT) -females mate only once in their lifetime, thus any mating with a sterile male will prevent females from giving birth to any offspring. SIT consists in rearing a large numbers of laboratory male tsetse flies which are irradiated and subsequently released in the wild to compete with wild (naturally occurring) males so that females inseminated by them produce no off-spring. The technique has been effectively used for eradication of tsetse (G. Austeni) from Unguja island in Zanzibar. Costly, logistics problems, presence of other species need to rear lots of flies.

5.1 Genomics of tsetse symbiotic bacteria are of interest since in the absence of their gut flora; tsetse flies are severely impaired in their longevity and reproduction. Two bacteria have been implicated in modifying vector competence of their host (Sodalis golssinidius and Wigglesworthia glossinidia). A third symbiont, Wolbachia can confer mating sterility. Such transgenic refractory flies could be released into natural populations to replace their susceptible counterparts and hence reduce disease transmission. They could also be immediately used in SIT release programmes and reduce the cost of the projects and the increase the efficacy of their application in HumanAfricanTrypanosomiasis endemic areas.

5. 2 Knowledge of olfactory genes may result in development of more potent attractants and repellents.

TIPS ON DESIGNING YOUR PROGRAM-

Talk about life cycle in your answer at which points in the life cycle the strategies in your program will target.

The use of several methods in an integrated disease and vector management package is generally recommended.

An integrated pest management approach is preferable because it exploits all the weaknesses in fly behavior and enables synergies of the methods that increase the intensity of the control effort. Since reinvasion of cleared areas from adjacent un-controlled areas is a major problem due to the mobility of the flies and absence of natural barriers, an area–wide pest management approach should be undertaken. therefore eradication is very difficult but a huge reduction in incidence can be acheived with an effective program.