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Internal Medicine

African trypanosomiasis “Sleeping sickness”

Introduction

African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals caused by protozoa Trypanosoma brucei usually transmitted by the bite of an infected tsetse fly, most common in rural areas.


History

370px-davidbruce
In 1903, David Bruce recognized the tsetse fly as the arthropod vector. | Dietmar Steverding. The history of African trypanosomiasis. Parasites & Vectors 2008, 1:3doi:10.1186/1756-3305-1-3, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=4306063
640px-sleeping_sickness_commission_photos_wellcome_l0049107
The British-led Sleeping Sickness Commission collecting tsetse flies, Uganda and Nyasaland, 1908-1913 | https://wellcomeimages.org/indexplus/obf_images/93/03/6e46e31e21246bffa07c83c28852.jpgGallery: https://wellcomeimages.org/indexplus/image/L0049107.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36129080

Epidemiology

640px-african_trypanosomiasis_deaths_2002-svg
Deaths per 100,000 population due to African trypanosomiasis by country in 2002. | Richard Wheeler (Zephyris) – data from WHO mortality and health data and statistics, Public Domain, https://commons.wikimedia.org/w/index.php?curid=6006242

Transmission

  • Vector transmission (M/C)
  • Other forms:
    • Mother-to-child infection
    • Laboratories: accidental infections
    • Blood transfusion
    • Sexual contact

Life cycle:

afrtryp_lifecycle
The life cycle of the Trypanosoma brucei parasites. | CDC: Јованвб – en:File:AfrTryp LifeCycle.gif, Public Domain, https://commons.wikimedia.org/w/index.php?curid=34652932
  • Two types that infect humans:
    • Trypanosoma brucei gambiense (TbG) (98% cases)
    • Trypanosoma brucei rhodesiense (TbR)

Vector:

  • Tsetse fly (painful bite)
640px-tsetse-bkf-2
Tsetse (tzetze) and also known as tik-tik flies, are large biting flies that inhabit much of tropical Africa. The tsetse are obligate parasites that live by feeding on the blood of vertebrate animals. Tsetse have been extensively studied because of their role in transmitting disease. They have a prominent economic impact in sub-Saharan Africa as the biological vectors of trypanosomes, which cause human sleeping sickness and animal trypanosomiasis. | International Atomic Energy Agency, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=42087829

Clinical features

First stage “hemolymphatic phase”

  • Fever, headaches, joint pains, and itching
    • Fever is intermittent, with attacks lasting from a day to a week, separated by intervals of a few days to a month or longer
  • Invasion of the circulatory and lymphatic systems by the parasites:
    • Lymphadenopathy
    • Winterbottom’s sign (Tell-tale swollen lymph nodes along the back of the neck)
  • Chancre (red sore) develops at the location of the tsetse fly bite
  • If untreated, the disease overcomes the host’s defenses and can cause more extensive damage:
    • Anaemia, endocrine, cardiac, and kidney dysfunctions

Second phase “neurological phase”

Begins when the parasite invades the central nervous system by passing through the blood-brain barrier (BBB)

Damage caused in the neurological phase is irreversible

  • Disruption of the sleep cycle (leading symptom, leading to the name ‘sleeping sickness‘)
    • Disorganized and fragmented 24-hour rhythm of the sleep-wake cycle (eg. daytime sleep episodes and nighttime periods of wakefulness)
  • Other neurological symptoms:
    • Confusion, tremor, general muscle weakness, hemiparesis, and paralysis of a limb
    • Parkinson-like movements
      • Due to non-specific movement disorders and speech disorders
  • Psychiatric symptoms (can sometimes dominate the clinical diagnosis):
    • Irritability, psychotic reactions, aggressive behaviour, or apathy

Untreated infections:

  • Progressive mental deterioration leading to coma
  • Systemic organ failure and death (within months)

Diagnosis

Investigations

Detection of trypanosomes:

  • Samples for study:
    • Chancre fluid, lymph node aspirates, blood, bone marrow, and CSF (during neurological stage)
  • Preparation of samples:
    • Wet preparation (can be used to look for the motile trypanosomes)
    • Fixed (dried) smear (stained using Giemsa’s or Field’s technique and examined under a microscope)
  • Concentration of samples (prior to microscopic examination):
    • Blood samples:
      • Centrifugation followed by examination of the buffy coat
      • Mini anion-exchange/centrifugation
      • Quantitative buffy coat (QBC) technique
    • Other samples:
      • Centrifugation followed by examination of the sediment

Serological tests:

  • Dried blood:
    • Micro-CATT
  • Whole blood samples:
    • wb-CATT
    • wb-LATEX

Management

First stage

  • T. b. gambienseIV/IM pentamidine
  • T. b. rhodesienseIV suramin

Second stage

  • T. b. gambiense:
    • First-line treatment regimens:
      • Nifurtimox + eflornithine, or
      • Nifurtimox-eflornithine combination treatment (NECT), or
      • Eflornithine (alone)
  • IV melarsoprol
    • T. b. rhodesiense (1st-line)
    • T. b. gambiense (2nd-line)

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