Week 10 - Protozoan part 2

Acanthamoeba

• It usually causes infection in immunocompromised patients.

• It is a free-living amoeba that causes inflammation of the brain substance and its meningeal coverings (meningoencephalitis)

• Found widely in soil, contaminated freshwater lakes, and other water environment

• It is able to survive in cold water

• Infective stage is the cyst; wjile pathogenic stage is the trophozoite

Aspiration or nasal inhalation

Direct invasion in the eye

Swimming in contaminated water

Contact lenses

Contaminated tap water

Inhalation from dust with cyst

acanthamoeba can be acquired through:

life cycle of Acanthamoeba

Granulomatous amoebic encephalitis

• Infections among immunocompromised individuals

• Parasite produces ___ and brain abscesses

• Symptoms develop slowly and may include: headache, seizures, stiff neck, nausea and vomiting

• The brain lesions may contain both the trophozoites and the cysts

• In rare instances. it may spread in the kidneys, pancreas, prostate, and uterus

Keratitis (acanthamoeba)

• Infection of the cornea of the eye

• Symptoms include severe eye pain, and vision problems. Loss of vision may occure due to perforation of the cornea.

cerebrospinal fluid

finding both acanthamoeba trophozoites and cysts in the ___ as well as brain tissue and corneal scrapings.

Calcofluor white

a stain usually used to demonstrate fungi, may be used to demonstrate the acanthamoeba in corneal scraping specimens

Fluorescent microscopy of corneal scrapings

Pentamidine

Ketoconazole

Flucytosine

medicines for infections by acanthamoeba

Topical miconazole

Chlrhexidine

Itraconazole

Rifampicin

Propamidine

medicine for eye and skin involvement against acanthamoeba

Propamidine

medine with a best success record for acanthamoeba

Prevented through adequate boiling of water

Regular disinfection of contact lenses is also advised

Contact lens wearers are also advised to avoid using homemade non-sterile saline solutions

prevention and control for acanthamoeba

Naegleria

• Classified as a free-living protozoan

• Found worldwide in soil and contaminated water environment

• Can survive in thermal spring water

• Known pathogen worldwide is Naegleria fowleri, which is the only amoeba with 3 identified morphologic forms - trophozoites, flagellate, and cyst forms

• The trophozoite: exhibits amoeboid motility, “slug-like'.

• Flagellate Form: pear-shaped; equipped with 2 flagella that is responsible for the parasite’s jerky or spinning movement.

• Cyst: non-motile form

  >The amoeboid trophozoite form is however the only form that is known to exist in humans

Life Cycle of Naeglaria fowleri

Epidemiology and Pathogenesis of Naeglaria

• Usually acquired transnasally when swimming in contaminated

• Parasite penetrates the nasal mucosa and cribriform plate, enters the central nervous system, and produces a rapidly fatal meningitis and encephalitis (primary amoebic meningoencephalitis)

• Unlike Acanthamoeba, the parsite produces infection in otherwise healthy individuals, usually children.'

• In some instances, the parasite may be acquired trhough inhalation of dust containing the parasite

• The entire life cycle of the parasite (amoeboid trophozoites > Flagellate trophozoite > amoeboid trophozoites > cyst form) occures entirely in the external environment.

Asymptomatic infection (Naegleria)

The most common clinical preentation in patients with colonization of the nasal passages.

Primary Amoebic Meningoencephalitis (PAM)

• The result of colonization of the brain by the amoeboid trophozoites leading to rapid tissue destruction

  • Symptoms: sore throat, nausea, vomiting, fever and headache. May eventually develop meningeal irritation (e,g, Kernig’s sign), as well as alterations in their senses of smell and taste.

  • If untreated, patients may die within one week after onset of symptoms.

Kernig’s sign

Cerebrospinal fluid

finding of the amoeboid trophozoites (Naeglaria) in the __

Amphotericin B

• Treatment of choice of Naeglaria is ___ in combination with miconazole and rifampicin

• But treatment is ineefective because of its rapidly fatal course. However, some patients have been shown to recover from infection due to early detection and initiation of treatment.

Prevention of contamination of water sources

Adequate chlorination of swimming pools and hot tubs

Prevention and Control (Naeglaria)

Hemoflagellates Leishmania spp.

• Life cycle of the parasite involves a vector, the female sandly of the Phlebotomus and Lutzomyia genera

  • They are the obligate intracellular parasites. It has 3 morphologic forms: amastigote, promastigote, and epimastigote.

  • The infective stage is promastigote

  • The pathogenic stage and diagnostic form is amastigote.

Life Cycle of

Hemoflagellates Leishmania spp.

Epidemiology and Pathogenesis

• Has a worldwide distribution. Natural reservoirs include rodents, ant eaters, dogs, and cats.

• In endemic areas, the parasite may be transmitted in human-vector-human cycle.

• 3 major strains of Leishmania:

  1. Leishmania dinivani (visceral leishmaniasis)

  2. Leishmania tropica (cutaneous leishmaniasis); and

  3. Leishmania braziliensis (mucocutaneous leishmaniasis).

1. Leishmania dinivani

2. Leishmania tropica

3. Leishmania braziliensis

3 major strains of Leishmania

Leishmania donovani Complex

• Is the causative agent visceral leishmaniasis (also known as kala-azar or dumdum fever)

• The complex consists of:

  1. L. donovani chagasi

  2. L. donovani donovani

  3. L. donovani infantum

• The promastigote is injected into the human host through bite of the sandfly. After entry into the host, it loses its flagella, is engulfed by macrophages, and transforms into amastigotes

• The organs of the reticuloendothelial system (liver, spleen and bone marrow) are the most severly affected

L. donovani chagasi

L. donovani donovani

L. donovani infantum

Leishmania donovani Complex consist of

L. donovani chagasi

is mainly seen in Central America (mainly Mexico, West Indies, and South America) and is transmitted by the Lutzomiya sandfly

L. donovani donovani

found in parts of Africa and Asia (Thailand, India, China, Burma, and East Pakistan) and is transmitted by the Phlebotomus sandfly

L. donovani infantum

also transmitted by Phlebotomus sandfly and is found mainly in Mediterranean Europe, Near East and Africa.

2 weeks to 18 months

After incubation period of ____ , the disease beings with intermittent fever, weakness and weight loss

Skin changes in visceral leishmaniasis

Montenegaro skin test

Screening test for Hemoflagellates Leishmania spp. is called ___. This test is similar to the tuberculin skin test for the diagnosis of tuberculosis

• It is used as screening for large population at risk but not used for diagnosis

• Definitive diagnosis is done by demonstration of the amstigote from Giemsa stained slides of specimen from blood, bone marrow, lymph nodes, and biopsies of infected areas.

• Culture of blood, bone marrow, and other tisues may also be done, which will show the promastigote forms.

• Serologic tests are now available such as indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assay (ELISA), or direct agglutination test (DAT).

Liposomal amphotericin B (Ambisome)

drug of choice for Hemoflagellates Leishmania spp is _____

Sodium stibogluconate

the medicine for Hemoflagellates Leishmania spp is ____ jas also been found to be effective but the development of resistance may occur.

gamma interferon in combination with pentavalent antimony

other patients with leishmaniasis have shown favourable response to__

Control of the vector population is important in the prevention of infection

The use of repellents, protective clothing, and installation of screens may be helpful

Prompt treatment of infected humans is essential to help halt the spread of the disease

Prevention and Control of Hemoflagellates Leishmania spp

Leishmania braziliensis Complex

• Is the causative agent of mucocutaneous leishmaniasis which involves skin, cartilage, and mucous membranes

• Infection with it occurs most commonly in Brazil and Central America, primarily in construction and forestry workers

• The complex consist of:

  1. L. panamensis (Panama and Colombia)

  2. L. peruviana (Peruvian Andes

  3. L. guyanensis (The Guianas, parts of Brazil and Venezuela

• Infection is transmitted by sandflys (Lutzomyia and Psychodopigus) through skin bite.

• The promastigotes invade the reticuloendothelial cells where they transform into amastigotes (diagnostic stage)

• Reproduction of the amastigotes result in tissue destruction. The amastigotes are taken up by the vector during a blood meal and are transformed into promastigotes.

Mucocutaneous Leishmaniasis

• also called espundia, begins with a papule at the site of insect bite, then forms metastatic lesions, usually at the mucocutaneous junction of the nose and mouth

  • Disfiguring granulomatous, ulcerating lesions destroy the nasal cartilage (tapur nose) but not the adjacent bone.

  • Death can occur from secondary infections.

Laboratory Diagnosis of mucocutaneous leishmaniasis

Sodium stibogluconate

most widely used treatment for mucocutaneous leishmaniasis is ____, although resistnace has been shown to develop

Liposmal Amphotericin B

Oral antifugal drugs (Fluconazole, ketoconazole, and itraconazole)

Alternative drugs for mucocutaneous leishmaniasis are:

The most important preventive measure is the control of the insect vector

Measures should be undertaken to protect individuals from sandfly bites using netting, window screens, protective clothing, and insect repellents

Prompt treatment can also help prevent spread of the disease

Prevention and Control for Leishmania braziliensis Complex

Leishmania tropic complex

The complex consists of:

L. tropica

L. aethiopica

L. major

These are the causative agents of what is referred to as Old World cutaneous leishmaniasis

• The life cycle of it is similar to what of L. braziliensis. All three members of the complez are transmitted by the Phlebotomus sandfly and primarily attacks the human lymphoid tissue of the skin

Old World Cutaneous Leishmaniasis

• Is also known as Oriental sore, and Baghdad or Delhi boil.

• It is characterized by one or several pus-containing ulcers that may heal spontaneously

• Initial lesion: small, pruritic red papule at the bite site.

• In patients with allergy and hypersensitivity responses, spontaneous healing does not occure.

  >Thick skin plaques with multiple nodules may develop especially on the limbs and face.

Laboratory Diagnosis for Leishmania tropic complex

• Microscopic examination of Giemsa-stained slides of fluid aspirated from beneath the ulcer bed is the usual diagnostic procedure of choice. Reveals the typical amastigotes.

• Culture of specimen will show the promastigote form

• Serologic tests are also available

Treatment for Leishmania tropic complex

• The drug of choice is sodium stibogluconate

• Steroids with application of heat to the infected lesions may be used.

• Other alternative drugs are meglumine antimonite, pentamidine, and oral ketoconazole

• Paromomycin ointment may be helpful in the healing of the ulcers

Prevention and Control for L. tropica

• Preventive measures same with forms of leishmaniasis

• However, unlike the other leishmania, a vaccine has been developed against it which is currently undergoing clinical trials.

Trypanosoma spp.

• Are also hemoflaggellates like Leishmania. The major difference between the two lies in their diagnostic stages, which is the amastigote for Leishmania and the trypomastigotigot for the trypanosome

• The trypomastigotes are curved, assuming the shape of letters C, S, or U.

• The trypomastigotes are visible in the peripheral blood

Trypanosoma cruzi

• Primarily found in South and Central America

• Transmitted by the bite of the reduviid or triatomid bud (Triatoma or “cone-nose” bug).

• It is transferred to a human host when feces of the bug containing the infective trypomastigotes is deposited near the bite site.

• The feces are then introduced into the bite site when the host scratches the bite area.

• Other routes of transmission include blood transfusion, sexuak intercourse, transplacental transmission, and through the mucous membranes, when the bite is near the eye or mouth.

• Humans and animals (domestic cats and dogs, and wild species such as armadillo, raccoon, and rat) serve as resevoir hosts.

Life cycle of Trypanosoma cruzi

Chagas Disease (American Trypanosomiasis)

• The acute phase begins with a nodule (chagoma) near the bite size; also with unilateral swelling of the eyelid with conjuctivitis (Romana’s sign)

  • The eyelid swelling may be due to the bug feces being accidentally rubbed into the eye

  • This is accompanied by fever, chills, malaise, myalgia, and fatigue.

  • Patients may recover or may enter the chronic phase.

• Chronic Phase: Hepatosplenomegaly, enlargement of lymph nodes (lymphadenopathy), and myocarditis with cardia arrhythmia characterize the chronic phase of Chagas disease.

  • Cardiac muscle is the most frequently and most severly affected tissue

  • Loss of tone of the colon and esophagus due to destruction of the Auerbach’s plexus may lead to abnormal dilatation of these organs, called megacolon and megaesophagus; respectively

  • CNS involvement may also be seen in the form of meningoencephalitis and cysts

  • Death may occur due to cardia failure and arrhythmias

Laboratory Diagnosis of Trypanosoma cruzi

benznidazole

nifurtimox

Drug of choice for Trypanosoma cruzi are ___ but these are less effective during the chronic phase of the disease

Allopurinol

Ketoconazole

Alternative agents for Trypamosoma cruzi are ___

Protection from the bite of the reduviid bug, improvement of housing conditions, and insect control

Education regarding the disease and its transmission is also helpful

prevention and control for trypamosoma cruzi

trypanosoma brucei gambiens and Trypanosoma brucei rhode

• Two species are similar in morphology and life cycle

• Involce the tsetse fly (Glossina) as the vector

• Resevoir

  • Humans: for T. brucei gambiense;

  • Domestic animals (especially cattle) and wild animals serve as the resevoir for T. brucie rhodesiense

• The infective and pathogenic stage is the trypomastigote

• T. gambiense infection: (West African or Gambian Sleeping Sickness) is chronic while;

• T. rhodesiense infection: (East African or Rhodesian Sleeping Sickness) is more rapidly;

• The disease is endemic in sub-Saharan African is the natural habitat of the tsetse fly. T. gambiense causes disease along the water courses in West Africa while T. rhodesiense causes disease mostly in the arid regions of East Africa.

Life Cycle of trypanosoma brucei gambiens and Trypanosoma brucei rhode

African Sleeping Sickness

• The initial lesion is an indurated ulcer called thancre at the site of the insect bite

• Intermitten weekly fever and lymphadenopathy then develop.

  • Enlargement of the posterior cervical lymph nodes (Winterbottom’s sign) is commonly seen

  • Other manifestations: red rash accompanied by pruritus, localized edema, and a delayed pain sensation (Kerandel sign)

• The encephalitis is characterized by headache, insomia, and mood changes

  • muscle tremors, slurred speech, and apathy follow, progressing to somnolence (sleeping sickness) and coma

• Untreated disease is fatal

Laboratory Diagnosis of trypanosoma brucei gambiens and Trypanosoma brucei rhode

melarsoprol

suramin

pentamidine

eflornithine

• medicines for trypanosoma brucei gambiens and Trypanosoma brucei rhode are ___

• The choice of drug will depend on whether the patient is pregnant or not, the age of the patient, and the stage of the disease.

Involve protection against bite of the fly

Use netting and protective clothing are recommended

Use of fly traps and insecticides may be helpful

Clearing forest around the villages are also helpful measures

Prevention and Control of trypanosoma brucei gambiens and Trypanosoma brucei rhode

Plasmodium spp.

• Malaria is the caused by five plasmodia species: Plasmodium vivax, Plasmodium malrie, PLasmodium ovale, Plasmodium knowlesi, and Plasmodium falciparum

• The vector and definitive host is the female Anopheles mosquito.

• The sexual cycle (sporogony) occurs primarily in mosquitos; and the asexual cycle (schizogony) occurs in humans (intermediate hosts)

• Occurs worldwide, primarily in tropical and subtropical areas, especially in Asia, Africa, and Central and South America

Malaria Life Cycle

Exoerythrocytic phase

• The infective stage is the sporozoite from the saliva of the biting mosquito, which is taken up by the live cells

• Multiplication of sporozoites into merozoites occur during this stage

• P. vivax and P. ovale produce a latent form (called hypnozoite or sleeping form) in the liver which is the cause of the relapse or recrudescence seen in vivax and ovale malaria

Erythrocytic phase

Merozoites (pathogenic stage) are re relesed from liver cells and infect the red blood cells

• The parasites life cycle now enters this phase. These merozoites multiply and are eventually released to infect other red blood cells

• The periodic release of merozoites causes the typical recurrent symptoms seen in malaria patients

• Some merozoites then develop into microgametacytes (male gametocytes) and macrogametocytes (female gametocytes)

• The gametocyte-containing red blood cells are ingested by the mosquito during feeding.

• Sexual reproduction then ensues

female mosquito vector

Main mode of transmission of malaria

black water fever

the dark color of the patient’s urine is due to kidney damage giving rise to the term

P. falciparum

causes malignant tertian malaria since it causes severe infection which is potentially life-threatening due to extensive brain (cerebral malaria) and kidney damage

Tertian Malaria

48 hours malaria

Quartan malaria

72 hours

Toxoplasma gondii

defenitive host: domestic cat or other felines

intermediate host: humans and other mammals

Epidemiology and Pathogenesis of

Toxoplasma gondii

Toxoplasmosis (Infection in immunocompetent individuals)

• Usually asymptomatic

• Acute infection may manifest non-specific symptoms such as chills, fever, headache, and fatigue'

• Thia may be accompanied by inflammation of lymph nodes (lymphadenitis)

• Chronic infection may manifest with lymphadenitis, hepatitis, myocarditis, and encephalomyelitis

• Chlorioretinitis leading to blindness may also occure

Toxoplasmosis (Congenital Infection)

• Occurs in infants born to mothers who were infected during pregnancy

  • Infection during the first trimester of pregnanacy may result to miscarriage, stillbirth, or severe infection (encephalitis, microcephaly, hydrocephalus, mental retardation, and pneumonia).

  • If the infant acquires during the last trimester, symptoms may not develop until months to years after delivery

  • The most common manifestation is chorioretinitis with or without blindness

Toxoplasmosis (infection in immunocompromised hosts)

• Usually manifest with neurologic symptoms similar to patients with encephalopathy, meningoencephalitis, or brain tumors.

• Reactivation of latent toxoplasma infection is common. Other sites of infection include the lungs, eye, and testes

Toxoplasmosis (Laboratory Diagnosis)

Pyrimethamine plus sulfadiazine

treatment for toxoplasmosis

• THe most effective preventive measure is through adequate cooking of meat

• Pregnant women should refrain from eating undercooked meat and should avoid contact with cats and refrain from handling litter boxes.

• Cats should not be fed raw meat

prevention and control of Toxoplasma gondii