Heamoflagellates

• The family of trypanosomatidae contains only two genera that parasitize humans:

  • Genus Trypanosoma found either in circulating blood or intracellularly (in cardiac muscle) in African blood; American Blood and cardiac muscle
  • Genus Leishmania always intracellular, principally in the cell of the reticulo-endothelial system
• Hemoflagellates have up to eight life cycle stages which differ in the placement and origin of the flagellum:

  • Two stages may occur in vertebrate hosts: the amastigote and the trypomastigote
  • Three stages may occur in invertebrate hosts: the promastigote, paramastigote, and epimastigote
• A trypanosomatic cell has the kinetoplast, a unique organelle rich in DNA (kDNA)

  • Two types of DNA molecules are found in kinetoplast: maxicircles which encode important mitochondrial enzymes, and minicircles which function in RNA editing
  • The kinetoplast is reddish purple in Giemsa stain and darker than the nucleus, contrasting with the pale blue cytoplasm
• American Trypanosomiasis (Chagas Disease):

  • First described by Carlos Chagas in 1911
  • Leading cause of non-ischemic congestive heart failure worldwide, notably in Latin America where it is endemic
• Life Cycle of Trypanosoma cruzi:

  • Transmitted by the Reduviid (Triatomine) bug
  • Infection leads to local inflammatory reaction, chagoma formation, and spread to various organs including the heart, skeletal muscles, and nervous system
• Epidemiology of Chagas Disease:

  • Approximately 16-18 million people are infected worldwide
  • Disease is limited to the Western Hemisphere, prevalent in Mexico, Central America, and South America
  • Morbidity/mortality: acute phase mortality is 5%, with over 70,000 annual deaths; leading cause of congestive heart failure in Latin America
• Clinical Presentation of Chagas Disease:

  • Early phase is typically asymptomatic
  • Acute phase symptoms include flu-like illness with high temperature, chills, headache, irritability, tiredness, and more
• Symptoms of Chagas disease include a flulike illness with high temperature, chills, headache, irritability, tiredness, anorexia, malaise, myalgias, lymphadenopathy, and splenomegaly
• In chronic Chagas disease, the gastrointestinal system may be involved, leading to symptoms like dysphagia, regurgitation, hiccups, constipation, and abdominal pain
• Patients with colon affectation in Chagas disease may experience slow progressive constipation, with most patients with megacolon having a bowel movement every 10 days
• Clinical presentation of Chagas disease may include Romaña sign (if the bite is close to the eye), hepatosplenomegaly, meningoencephalitis more common in young infants, and cardiovascular abnormalities like cardiac enlargement, functional murmurs, and conduction blocks
• Laboratory studies for Chagas disease involve blood film CBC count, serologic tests like complement fixation (CF), indirect immunofluorescence (IFAT), enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR) to observe T. cruzi kinetoplast DNA, and Xenodiagnosis
• Investigations for Chagas disease include chest radiography, electrocardiography (ECG), echocardiography, cardiac MRI, fluoroscopic esophagrams, manometry revealing loss of peristalsis, and barium enema examination as the cornerstone for diagnosis
• Histologic findings in Chagas disease show lymphocytic, monocytic, and eosinophilic infiltration in the portal of entry lesion, and in the invaded heart, there is diffuse inflammation of the myocardium with dense foci of fibrosis and invasion of inflammatory cells
• Management of Chagas disease involves medical treatment with nifurtimox or benznidazole in the acute phase, surgical control by using insecticides to eliminate vector bugs from dwellings, improving the household environment, community participation strategies, and serologic screening in blood banks in endemic areas
• African Trypanosomiasis, also known as Sleeping Sickness, is caused by the flagellate protozoan Trypanosoma brucei, with two subspecies: T. b. rhodesiense (East African) and T. b. gambiense (West African)
• African Trypanosomiasis is transmitted by the bite of infected tsetse flies during daylight hours, with vertical transmission to unborn babies, blood transfusion, or sexual contact
• Tsetse flies, the vectors for African Trypanosomiasis, are large, biting flies that inhabit much of tropical Africa, and they are obligate parasites feeding on the blood of vertebrate animals

  [An obligate parasite or holoparasite is a parasitic organism that cannot complete its life-cycle without exploiting a suitable host]
• The life cycle of Trypanosoma brucei gambiense & T. b. rhodesiense involves transmission by tsetse flies and different stages of infection in humans
• Epidemiology of African Trypanosomiasis shows it affects 36 countries in sub-Saharan Africa, with a decrease in prevalence since 2000, and during epidemic periods, prevalence can reach 50% in certain regions
• Symptoms of African Trypanosomiasis include intermittent fevers, rash, lymphadenopathy, and variations in surface antigens allow the parasites to evade specific immunity
• Pathology and clinical picture of African Trypanosomiasis involve different stages like skin chancre, haematolymphatic stage with generalized lymphadenopathy and organ involvement, and central nervous system stage with meningoencephalitis
• Symptoms of African Trypanosomiasis progress from painful skin chancre to intermittent fever, malaise, myalgia, arthralgias, lymphadenopathy, and facial edema in some cases
• Symptoms of late or neurologic stage of African Trypanosomiasis include persistent headaches, daytime somnolence followed by nighttime insomnia, and behavioral changes
• Symptoms of stage 2 (late or neurologic stage) of trypanosomiasis include:

  • Persistent headaches refractory to analgesics
  • Daytime somnolence followed by nighttime insomnia
  • Behavioral changes, mood swings, and depression
  • Loss of appetite, wasting syndrome, and weight loss
  • Seizures in children (rarely in adults)
• Physical findings in stage 1 (early or hemolymphatic stage) of trypanosomiasis include:

  • Chancre at bite site
  • Skin lesions (trypanids) in light-skinned patients
  • Lymphadenopathy (axillary and inguinal more common in East African trypanosomiasis, cervical more common in West African form)
  • Fevers, tachycardia, edema, weight loss, and organomegaly, particularly splenomegaly in T. brucei gambiense
• Physical findings in stage 2 (late or neurologic stage) of trypanosomiasis include:

  • CNS manifestations like irritability, tremors, increased muscle rigidity, occasional ataxia, and hemiparesis
  • Kerandel sign (delayed pain on compression of soft tissue,Severe, delayed pain when soft tissues are compressed)
  • Behavioral changes consistent with mania or psychosis, speech disorders, psychosis, sensory disorders, and seizures
  • Stupor and coma (giving rise to the name sleeping sickness)
• Complications of late or neurologic stage of trypanosomiasis include:

  • Anemia and fatigue
  • Wasting syndrome
  • Aspiration pneumonia
  • Meningoencephalitis and seizures
  • Stupor or coma (sleeping sickness)
  • Perinatal death or abortion (after congenital infection), death
• Investigations for trypanosomiasis:

  • Blood: anemia, hypergammaglobulinemia[is an uncommon condition characterized by elevated levels of immunoglobulins in your blood], elevated ESR, thrombocytopenia, hypoalbuminemia
  • Blood Smear: unstained blood smear or a Giemsa-stained thick smear (more sensitive) for mobile trypanosomes
  • CSF: high total IgM, high CSF protein level
  • Serology: card agglutination test for trypanosomiasis (CATT) for West African trypanosomiasis
• Treatment for trypanosomiasis:

  • Melarsoprol for East African trypanosomiasis
  • Eflornithine for West African trypanosomiasis
  • Other drugs: Suramin, Pentamidine isethionate, Fexinidazole
• Leishmaniasis is a parasitic infection caused by kinetoplastid protozoans in the genera Leishmania and Endotrypanum, transmitted through the bite of sand flies
• Classification of Leishmaniasis:

  • Clinical disease: divided into 3 primary clinical forms - Cutaneous, Mucocutaneous, and Visceral
  • Geographic occurrence: Old World leishmaniasis (Africa, Asia, Middle East, Mediterranean, India) and New World leishmaniasis (Central and South America)
• Cutaneous leishmaniasis,(CL) is the most common form and causes skin lesions, mainly ulcers, on exposed parts of the body, It includes:

  • Localized cutaneous leishmaniasis
  • Diffuse (disseminated) cutaneous leishmaniasis
  • Leishmaniasis recidivans : a prolonged, relapsing form ofcutaneous leishmaniasisresembling tuberculosis of the skin that may persist for many years with a chronic and relapsing course.
  • Post-kala-azar dermal leishmaniasis
• Mucocutaneous leishmaniasis consists of the relentless destruction of the oropharynx and nose, resulting in extensive midfacial destruction, with optical and genital mucosal involvement in severe cases
• Visceral leishmaniasis (kala-azar) is a potentially lethal widespread systemic disease characterized by darkening of the skin, fever, weight loss, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia
• Diagnosis of Leishmaniasis includes:

  • Isolation, microscopy, and culturing of the parasite from infected tissue
  • Serologic detection of antibodies to recombinant K39 antigen
  • PCR, FBC count, coagulation studies, liver function tests, peripheral blood smear
  • Leishmanin (Montenegro) skin testing (LST)
• Treatment for Leishmaniasis:

  • Medical: Pentavalent antimony, Liposomal amphotericin B (AmBisome), Intramuscular pentamidine, orally administered ketoconazole, itraconazole, fluconazole, allopurinol, and dapsone, topical paromomycin
  • Control of local infection
• • These protozoans require hematin obtained from blood hemoglobin for aerobic respiration, hence they are called hemoflagellates
• the 5 stages out of 8. notice the flagellum and their postions

  
• Romaña sign, also known as the periorbital swelling syndrome, refers to periorbital swelling, palpebral edema and conjunctivitis seen 1-2 weeks following infection with Trypanosoma cruzi (causative agent in Chagas disease). basically a swelling all around the eye