African Sleeping Sickness

The bite of an infected tsetse fly yields a regional difference in disease type — the uncommon but more fulminant Trypanosome rhodesiense of east Africa, to the far more common yet rather more indolent gambiense strain of west Africa. There is also an American variant, known as Chagas disease, this time spread through the excrement of an infected Reduviid bug. The respective trypanosomes can infect almost all mammalian types, and recent evidence has implicated a hitherto unrecognised parasite sexual reproduction stage.

American Trypanosomiasis: a disease of central and south America

Carte_maladie_Chagas

Trypanosoma_cruzi_LifeCycle

Life-cycle of T. cruzi

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Vector: Reduviid bug are colloquially known as “Kissing” or “Assassin” bugs.

African Trypanosomiasis: a disease of Sub-Saharan Africa

  • T. brucei rhodesiense substrain is found in East Africa — Malawi, Zambia, Uganda, and Tanzania — and causes 2% of all trypanosomiasis cases.
  • T. brucei gambiense substrain accounts for 98% of sleeping sickness and is found in central and western African countries of the DRC, Congo, Angola, Sudan, Chad and the Central African Republic

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There are 23 different species of Glossina, found within three broad habitat types: forest; riverine; and savannah. They are mostly active during the day time.

tsetseblood

Vector: a post-prandial tsetse

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East Africa vs. Central / West Africa

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VIRULENCE FACTORS

Antigenic variation

Changes in the variable surface glycoprotein (VSG) coat, through transcriptional switches and DNA rearrangements à impairs antibody-mediated clearing mechanisms. The organism can quickly switch between hundreds of these VSG genes, each time forcing the immune system to respond to the parasite anew.

research_pasteur_fr_group-brice-rotureau-e1438855726647_Trypanosoma brucei procyclic form from tsetse midgut observed by SEM

Parasite: Trypanosoma

“A specialised morphology with most nutrient uptake occurring in the privileged location of the flagellar pocket”

Flagellum

Self-propagation allows access to different tissues, including the ability to cross the blood brain barrier. The flagellum is also involved in host cell attachment, particularly important for vector colonisation.

Trypanosomes

The kinetoplast drives the flagellum.

Clinical

The features are characterised by two distinct stages, the evolution of which occurs rather more quickly in rhodesiense infection (than that by the gambiense species):

  • Peripheral circulation — headache, fever, joint aches and stiffness, enlarged lymph nodes +/- enlarged sore at the bite site within 1-2 weeks of infection.

Inoculation chancre: Wikimedia Commons; Clerinx et al (2012);

  • Central nervous system — involvement occurs within weeks (cf. 1-2 years for gambiense) leading to relatively rapid progression to coma and death within several months.
  • Disturbed sleep-cycle, often inverted
  • Personality changes and confusion
  • Partial paralysis and disorders of balance
  • Seizures, somnolence, coma, multi-system organ failure and death

Untreated, rhodesiense is uniformly fatal in a matter of months and gambiense in a matter of years. Diagnosed and treated within the first stage, the mortality rate drops to 6%.

DIAGNOSIS

  1. Screening physical examination and serology
  2. Confirming parasite presence and subspecies
  3. Staging (to determine treatment options and as a general prognostic guide) requires lumbar puncture

[A number of individual organisms are examined systematically to confirm size and appearances (monomorphic vs. polymorphic), presence of a free flagellum, kinetoplast size and position, degree of development of undulating membrane, shape of especially the posterior part (blunt vs. pointed). This will help identify the subspecies of infection if there is a mixed (polymorphic) infection of more than one specie. Classification under light microscopy, as can be imagined, is requisite to a good quality stained preparation with adequate numbers of organisms.]

Particularly in central/west Africa, where the disease has a long incubation period, regular population screening allows for early detection and reduced transmission. These are, however, labour and resource intensive procedures in regions of little infrastructure.

TREATMENT

Management will depend on type and stage of disease. Early detection (peripheral circulation stage) allows for simpler, less toxic, treatment and a much higher chance of cure:

  • Pentamidine for gambiense infection — usually well tolerated but can cause hypoglycaemia, hypotension, and nephrotoxicity
  • Suramin for rhodesiense infection — has more significant side effects including neuropathy, fatigue, anaemia, rash, and hyperglycaemia.

Treating central nervous system infection is more problematic:

  • Melarsoprol, an arsenic derivative, is used to treat both forms and can cause seizures, loss of consciousness, and a potentially fatal encephalopathy (in 5-10%)

Recent reports of Melarsoprol-resistance in central Africa have renewed interest in eflornithine for gambiense infection, a less severe form of treatment than Melarsoprol but requiring a long and difficult treatment regimen. Nifurtimox, a drug used in American trypanosomiasis, has been used in conjunction with eflornithine to treat gambiense.

PREVENTION

No chemoprophylaxis is available for control of infection, so that prevention is aimed at controlling the vector.

Host Immune Response

Triggering of the alternative complement pathway will lead to parasite lysis but only if the parasite is not coated by VSG, which is almost never the case for brucei sp.

APPENDIX  — HISTORICAL

A Scottish bacteriologist identified and named T. brucei as the aetiological agent of nagana disease. Some of these parasites have been spread by humans from Africa to other continents. For example, T. vivax had been introduced to the Americas, by the importation of West African cattle in the eighteenth and nineteenth centuries, and it is likely that T. evansi had already “escaped” from Africa far earlier by animal movements (in particular camels) between Africa and Asia.

REFERENCES
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