1. Trypanosoma brucei causes African sleeping sickness Paul R Earl Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo León San Nicolás, NL 66541, Mexico

2. In the present warming trend, the destruction of our forests by multinational as well as national loggers is causing the world to become drier. An added notorious threat is primitive or nomadic farming. These farmers, whether in Mexico, Brazil or Kenya whose activities are supported by the World Bank, clear the land for crops and for cattle. Many nations kill trees under the banner of agriculture. Then it follows that the epidemiology changes as the environment is so changed.

3. This terrible business of landclearing with consequently reduced transmission of the protozoan flagellate: Trypanosoma brucei in this case is partly due to human overpopulation. The vectors are tsetse flies that live in wooded areas. Landclearing has been called “agronomic prevention” that consists of methodically clearing undergrowth from villages, watersources, paths and bridges to destroy its natural habitat. Soon only protected national parks in Africa may have trypanosomes and tsetses.
The point may be that as forests dwindle, the ecology so changes to accomodate more people. When international spraying campaigns against tsetses are added, African trypanosomiasis may be eradicated. This is good news! The bad news is increasing hunger via land-destructive overpopulation.

4. The eradication of malaria and other tropical diseases around the world with emphasis on Afroasia should include sleeping sickness. A special spraying campaign is needed for the elimination of the tsetse from the national parks like Kruger. Things were better in 1965, but DDT was much abandoned by then. Such difficult refuges as this famous park and world treasure have to be cleaned out of flies on a priority basis if eradication is to succeed. Vector control is the keynote. But also, very few effective genetic investigations of tsetse flies are ongoing. Here we advocate vector control on the worst area first basis.
Highly endemic countries, where prevalence is moderate are Cameroon, Central African Republic, Chad, Congo, Côte d'Ivoire, Guinea, Mozambique, Uganda and United Republic of Tanzania.
There have been 3 major epidemics, one between 1896 and 1906, mostly in Uganda and the Congo, one in 1920 in several African countries, and one that began in 1970 and is still in progress. The disease had practically disappeared between 1960 and After the DDT success, screening and effective surveillance were relaxed, and the disease has reappeared in endemics over the last 30 years. International DDT spraying from aircraft will do nicely.
Vectors like mosquitoes are now being treated transgen-ically so that they do not transmit some given disease. However, it is still too early to announce success in this fascinating area.

5. We have, in Africa, a most complex ecology involving increasing rural populations. Is our goal to raise the standard of living by reducing the disease burden? Is tsetse elimination important for the cattle industry as well as for human health? Is clearing woods a wise path to take to reduce tsetse flies, or is landclearing wanton destruction. The cropper wants grain to feed his family, and this much is possible by clearing land. Then the consequence is a larger unskilled rural population.
The industrialized sophisticate likely cannot understand the rural philosophy. For instance, people living without money! Then who will reduce the health risks of rural countries around the world? African disease vectors are entwined in other matters ranging from civil wars to AIDS.
Two most important links are
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See also Leishmaniasis and Chagas disease.

6. The parasite exists as 2 morphologically identical subspecies: Trypanosoma brucei rhodesiense (East African or Rhodesian African trypanosomiasis) and T. brucei gambiense (West African or Gambian African trypanosomiasis), and T. b. brucei can be added, although it is much like T. b. rhodesiense. Human blood contains a factor that lyses animal trypanosomes. Human-invasive parasites are transmitted to human hosts by bites of infected tsetse flies (Glossina species), which are found only in Africa.
The reservoirs of infection for these vectors are exclusively human in West African trypanosomiasis, but zoonotic in East Africa with animal reservoirs such game ruminants and domestic cattle. The African animal “tryps” are: 1/ T. congolense of cattle, 2/ T. vivax of cattle, 3/ T. evans of camels and horses, and 4/ T. equiperdum of horses.

7. T. b. brucei
Diagram of a tsetse fly

8. Glossina pallidipes

9. Tsetse flies. G. morsitans is the most important vector in East Africa and G. fuscipes (previously known as G. palpalis) in West Africa G. morsitans is found in savanna and woodland areas, whereas G. fuscipes is found in gallery forests along rivers and lakes. Having painful bites, tsetses will follow moving objects, be attracted by the odors like acetone and phenol and will bite through thin clothing.

10. Mother and son arranging a tsetse trap. Note the heavy vegetation.
Mobile electric nets are very effective for monitoring tsetses. Cloth nets like the one illustrated are also effective, especially with attractants like acetone in a bottle with a slow evaporating wick. Most traps have insecticides in them.
Mother and son arranging a tsetse trap. Note the heavy vegetation.

11. Dead tsetses from a trap impregnated with DDT
Tsetses were eliminated from the island of Zanzibar by releasing sterile males. What is missing for eradication? Determination. Political will to finance is lacking, and political strive is an added obstacle. Of course, the real problem is rural poverty. Note that infected flies usually occur at 1/1,000 flies.
Many other different techniques are also PARTIALLY EFFECTIVE against tsetses like pouron pyrethroids for cattle, BUT they do not control epidemics or give hope of eradication. All techniques require disciplined cooperation through ALL social levels and over vast distances..
Dead tsetses from a trap impregnated with DDT

12. Life cycle. Many changes occur in the morphology and physiology including of cource antigenicity during the life cycle which is rather simple having human hosts, tsetse vectors and many mammal hosts or reservoirs.

13. As illustrated, metacyclic trypomastigotes (MT) in the saliva of the tsetse fly infect the bloodstream of the mammalian host as long slender (LS) forms, exhibiting a trypomastigote morphology. In addition to the LS forms, intermediate and short stumpy (SS) forms are also found in the blood. The bloodstream trypomastigote differentiates into a procyclic trypomastigote (PT) within the gut of the tsetse. After reaching the salivary glands, the procyclic trypomastigotes transform into epimastigotes (E) and attach to epithelial cells via their flagella. Metacyclic trypomastigotes (MT) in the salivary glands are transferred to the bloodstream of the mammalian host and multiply by longitudinal binary fission (LSs).
T. brucei rhodesiense lives in East Africa, and another subspecies T. b. gambiense lives in West Africa. The organisms are long and slender, 30 x 3.5 microns. Each has a nucleus (N), kinetoplast (K), undulating membrane (UM) and long flagellum (F).

14. Symptoms of sleeping sickness
Symptoms of sleeping sickness. Infection leads to malaise, lassitude and irregular fevers. Early symptoms include fever and enlarged lymph glands and spleen, that are more severe and acute in T.b. rhodesiense infections. Early signs are followed by a range of symptoms. Within 1-2 weeks after the bite, a dusky red nodule which can reach 6 cm in size develops and lasts about 2 weeks. This primary chancer may be painful and is located often on the legs.

15. Woman in a stage of lethargy
Symptoms include headache, anemia, joint pains and swollen tissues. Advanced signs include neurological and endocrine disorders. As the parasites invade the central nervous system (CNS), mental deterioration begins, leading to coma and death. T.b. rhodesiense infection is usually acute, causing severe symptoms and death within a few days or weeks. T.b. gambiense infections tend to progress more slowly over several years and are less severe.
Woman in a stage of lethargy

16. The parasites escape the initial host defense mechanisms by extensive antigenic variation of parasite surface glycoproteins (VSG). This evasion of the humoral immune responses contributes to parasite virulence. During the parasitemia, most pathologic changes occur in the hematologic, lymphatic, cardiac and the CNS. Immune-mediated reactions against antigens on red blood cells, cardiac and brain tissue can result in hemolysis, anemia, pancarditis and meningoencephalitis.

17. Lumbar puncture to see if tryps are in the CNS
A hypersensitivity reaction causes skin problems, including persistent urticaria, pruritus and facial edema. An increase in lymphocytes in the spleen and lymph nodes can lead to fibrosis. Monocytes, macrophages and plasma cells infiltrate blood vessels, causing and increased vascular permeability.
Lumbar puncture to see if tryps are in the CNS

18. Treatment. If the disease is diagnosed early, the chances of cure are good. Success in the second neurological phase depends on having a drug that can cross the blood-brain barrier to reach the parasite. Four drugs have been used until now.

19. First phase treatments: 1/ Suramine, discovered in 1921, is used in treatment of the initial phase of T. b. rhodesiense. There are certain undesirable effects, especially indigestion. 2/ Pentamidine, discovered in 1941, is used in treatment of the initial phase of T. b. gambiense sleeping sickness. In spite of some undesirable effects, it is well tolerated by patients. Aventis dropped pentamidine. Future production is problematic.

20. Second phase treatments: 3/ Melarsoprol, discovered in 1949, is the only drug available on the market to treat the advanced stage of sleeping sickness, no matter which parasite is the cause. It is the last of the arsenicals. The undesired effects are drastic; they include reactive encephalopathy allergic nature that is often fatal. Survivors suffer serious neurological sequelae. Furthermore, there is considerable resistance to melarsoprol / Eflornithine, registered in 1990, is the alternative to melarsoprol. It is effective only against T.b. gambiense. Production ceased in 1999 and Aventis gave the licence to WHO, which has undertaken several initiatives to seek a new source of production.

21. Antigenic variation and genetics
Antigenic variation and genetics How do tryps evade the immune response? Trypanosomes are covered with a surface coat of a monomolecular layer of a glycoprotein called variable surface glycoprotein (VSG). This protein is being changed every 5-7 days, resulting in a new variable antigen type (VAT). Immunoglobulins directed against these VSGs recognize the trypanosome binding of antibodies that will lead to cell lysis by complement and the demise of these tryps.
A few change their VSG that thereby is not recognized by current antibodies. This population multiplies unlimitedly and expands until antibodies will be produced against this new variant so that the system is then induced to repeat.

22. At least 100 different VATs that have been identified in T
At least 100 different VATs that have been identified in T. equiperdum at least 1000 different genes that are present in the genome of T. brucei. Trypanosomes have a very high capacity for homologous recombination. Different members of the VSG gene family may recombine to form new variants. Cytologically unseen recombination here is by the polymerase chain reaction, and meiosis is INFERRED by flow cytometery DNA content so that due circumspection is called for.
When a host is infected with a single cloned trypanosome there is a partially ordered sequence of VAT's, yet every new VAT can be totally different from the previous one without any crossreactivity. In general, the VSGs that appear in an infection can be divided in early, medium and late VSGs as they have a slight tendency to appear in order.

23. There are 3 size classes of chromosomes: a) minichromosomes of 50–150 kilobases (kb) containing repeat sequences and basic copies of VSG genes, b) the intermediate chromosomes of 200–900 kb containing VSG expression sites and c) 11 megabase chromosomes of 1-6 Mb thought to contain all housekeeping genes. The megabase chromosomes are said to be diploid and inherited in Mendelian fashion. Nevertheless. meiosis which must contain a reduction division is not evinced, thus discussion of sex and evolution in tryps might be premature.

24. Haploid + haploid chromosomes immediately reduced is zygotic meiosis
Haploid + haploid chromosomes immediately reduced is zygotic meiosis. HAPLOID means one set (1n) of chromosomes as in ferns and thousands of protozoa and metazoa. Diploid (2n) reduced to the haploid state (1n) is gametic meiosis in which the 2 haploid gametes fuse (fertilize) to create or restore the diploid set of chromosomes. The role of the DNA kinetoplast and more cytology in trypanosomes is only partially explained today.
However, peptide nucleic acid (PNA) combined with fluorescence in situ hybridization (FISH) probes have supported these daring endeavors. Many inadequate studies by PCR methodology are fragile by simple faults like very small sample sizes and not entirely trustworthy, because some of these proof-free authors are grasping at straws. Each technique may have its own little set of assumptions. Regardless, we do indeed have faith in FISH!

25. PLEASE BE CAREFUL ABOUT WHAT IS MEANT BY MEIOSIS
PLEASE BE CAREFUL ABOUT WHAT IS MEANT BY MEIOSIS. WHEN THE WORD RECOMBINATION ENTERS, CROSSINGOVER HAD OCCURRED (?). WHERE IS THE EVIDENCE FOR THIS LIKE CHIASMATA? MEIOSIS CONTAINS A REDUCTION OF THE CHROMOSOME SET WHICH CAN HAPPEN BEFORE (GAMETIC) OR AFTER (ZYGOTIC) FERTILIZATION. THE SEXUAL DRAMA THAT MAY WELL TAKE PLACE IN THE TSETSE GUT IS UNKNOWN. THE SYSTEM OF DNA MINICIRCLES IN KINETOPLASTS IS UNIQUE.

26. Tomorrow more credible cytogenetic data will be presented on chromosomes, and perhaps transgenic tsetse flies incompetent of parasite transmission will have been created. More, susceptible and refractory families of flies are already known. These and other sophistications that—somehow—are related to making vaccines are not necessary for vector control. The grant money flows into genetics and vaccines as if these disease problems required more new advanced technology. Vector control, including release of sterile male tsetses, is proven.
Then, what is the problem of the eradication of African trypanosomiasis? It is rural poverty, no priority to kill the vector or lack of functional governmental structure.
Political cooperation among countries is needed in order to weld the Determination that will eliminate MANY tropical diseases by perhaps 2025.