fungal and parasitic diseases .on.04 07-2014

FUNGAL AND PARASITIC DISEASES

• Fungi are eukaryotes with cell walls that give them their shape. Fungal cells can grow as multicellular filaments called moulds or as single cells or chains of cells called yeast.

• Most yeasts reproduce by budding. Some

yeasts, such as Candida albicans, can produce buds that fail to detach and become elongated, producing a chain of elongated yeast cells called pseudo hyphae.

1.Superficial And Cutaneous Mycoses, which are common and limited to the very superficial or keratinized layers of skin, hair, and nails;

2. Subcutaneous Mycoses, which involve the skin, subcutaneous tissues, and lymphatics and rarely disseminate systemically;

3. Endemic Mycoses, which are caused by dimorphic fungi that can produce serious systemic illness in healthy individuals; and

4. Opportunistic Mycoses, which can cause life-threatening systemic diseases in individuals who are immunosuppressed or who carry implanted prosthetic devices or vascular catheters.

1. Candidiasis• Residing normally in the skin, mouth, gastrointestinal

tract, and vagina, • DIABETICS AND BURN PATIENTS are particularly

susceptible to superficial candidiasis. In individuals with indwelling intravenous lines or catheters, or undergoing peritoneal dialysis,

• Severe disseminated candidiasis most commonly occurs in patients who are neutropenic due to Leukemia, Chemotherapy, Or Bone Marrow Transplantation, and may cause shock and DIC.

Macroscopic and Microscopic appearance of Candida

Pseudohypal structures in Candida

The morphology of Candida infections. A, Severe candidiasis of the distal oesophagus. B, Silver stain of oesophageal candidiasis reveals the dense mat of Candida.C, Characteristic pseudo hyphae and blast conidia (budding yeast) of Candida

OPPORTUNISTIC INFECTION BY CANDIDA ALBICANS IN AN AIDS PATIENT

• Most commonly candidiasis takes the form of a superficial infection on mucosal surfaces of the oral cavity (thrush).

• This form of Candidiasis Is Seen In Newborns, debilitated people, children receiving oral steroids for asthma, and following a course of broad-spectrum antibiotics that destroy competing normal bacterial flora.

• The other major risk group includes HIV-positive patients; people with oral thrush for no obvious reason should be evaluated for HIV infection.

• CANDIDA ESOPHAGITIS is commonly seen in AIDS patients and in those with hematolymphoid malignancies.

• These patients present with dysphagia (painful swallowing) and retrosternal pain; endoscopy demonstrates white plaques and pseudo membranes resembling oral thrush on the oesophageal mucosa.

• CANDIDA VAGINITIS is a common form of vaginal infection in women, especially those who are diabetic, pregnant, or on oral contraceptive pills. It is usually associated with intense itching and a thick, curdlike discharge.

• CUTANEOUS CANDIDIASIS can present in many different forms, including infection of the nail proper ("onychomycosis"), nail folds ("paronychia"), hair follicles ("folliculitis"), moist, intertriginous skin such as armpits or webs of the fingers and toes ("intertrigo"), and penile skin ("balanitis"). "Diaper rash" is a cutaneous candidial infection seen in the perineum of infants, in the region of contact with wet diapers

• Invasive candidiasis is caused by blood-borne dissemination of organisms to various tissues or organs.

• Common patterns include (1) renal abscesses, (2) myocardial abscesses and endocarditis, (3) brain micro abscesses and meningitis,

• (4) endophthalmitis (virtually any eye structure can be involved), and (5) hepatic abscesses.

• People with acute leukemias who are profoundly neutropenic after chemotherapy are particularly prone to developing systemic disease.

• Candida endocarditis is the most common fungal endocarditis, usually occurring in the setting of prosthetic heart valves or in intravenous drug abusers.

Cryptococcosis• Cryptococcus neoformans grows as an

encapsulated yeast that causes meningoencephalitis in otherwise healthy individuals but more frequently presents as an opportunistic infection in people with AIDS, leukemia, lymphoma, systemic lupus erythematosus, or sarcoidosis, as well as in transplant recipients.

• Many of these patients receive high-dose corticosteroids, a major risk factor for Cryptococcus infection.

• Cryptococcus neoformans is present in the soil and in bird (particularly pigeon) droppings and infects people when it is inhaled.

• Several virulence factors • (1) a polysaccharide capsule, (2) melanin

production, and (3) enzymes.

• Morphology.• Cryptococcus has yeast but not pseudohyphal or hyphal

forms. The 5- to 10-μm Cryptococci yeast has a highly characteristic thick gelatinous capsule.

• Capsular polysaccharide stains intense red with periodic acid-Schiff and mucicarmine in tissues and can be detected with antibody-coated beads in an agglutination assay.

• India ink preparations create a negative image, visualizing the thick capsule as a clear halo within a dark background.

• Although the lung is the primary site of infection, pulmonary involvement is usually mild and asymptomatic, even while the fungus is spreading to the CNS.

• The major lesions caused by C. neoformans are in the CNS, involving the meninges, cortical gray matter, and basal nuclei. The host response to Cryptococci is extremely variable.

• In immunosuppressed people, organisms may evoke virtually no inflammatory reaction, so gelatinous masses of fungi grow in the meninges or expand the perivascular Virchow-Robin spaces within the gray matter, producing the so-called soap-bubble lesions .In severely immunosuppressed persons,

• C. neoformans may disseminate widely to the skin, liver, spleen, adrenals, and bones.

• In no immunosuppressed people or in those with protracted disease, the fungi induce a chronic granulomatous reaction composed of macrophages, lymphocytes, and foreign body-type giant cells. Suppuration also may occur, as well as a rare granulomatous arteritis of the circle of Willis.

Pigeons and Red river gum tress harbors the Cryptococcus in nature

Life cycle of C.neofromans

• Can manifest with involvement of ,Skin, mucosa,organs,Bones,and as Disseminated

form.

Can mimic like Tuberculosis,

CRYPTOCOCCUS

MICROABSCESSES

Laboratory Diagnosis.

• CSF Microscopic observation under India Ink preparation

• Direct microscopy - Gram staining• Cultures on Sabouraud dextrose agar,• Serological tests for detection of Capsular antigen• CSF findings mimic like Tuberculosis• IN CSF - latex test for detection of Antigen• Blood cultures,• ELISA

Aspergillosis

• Aspergillus is a ubiquitous mold that causes allergies (allergic bronchopulmonary aspergillosis) in otherwise healthy people and serious sinusitis, pneumonia, and invasive disease in immunocompromised individuals.

• The major conditions that predispose to Aspergillus infection are neutropenia and corticosteroids.

• Aspergillus fumigatus is the most common species to cause disease, and it produces severe invasive infections in immunocompromised individuals

B, Histologic sections from this case, stained with Gomori methenamine-silver stain, show septate hyphae with acute-angle branching, features consistent with Aspergillus. Occasionally, Aspergillus may demonstrate fruiting bodies (inset)

Fungal spores enters through respiratory tract

• Morphology. • Colonizing aspergillosis (aspergilloma) usually implies

growth of the fungus in pulmonary cavities with minimal or no invasion of the tissues (the nose also is often colonized).

• The cavities are usually the result of prior tuberculosis, bronchiectasis, old infarcts, or abscesses. Proliferating masses of hyphae form brownish "fungal balls" lying free within the cavities.

• The surrounding inflammatory reaction may be sparse, or there may be chronic inflammation and fibrosis. People with aspergillomas usually have recurrent hemoptysis.

Important Clinical Manifestations

• Rhino cerebral Zygomycosis associate with Diabetes mellitus, leukemia, or lymphomas

• Causes extensive Cellulitis, and tissue destruction.

Mucormycosis

• Cellulitis causes extensive tissue destruction.

• Spread from Nasal mucosa to turbinate bone,paranasal sinuses ,orbit, and Brain

• Rapdily fatal if untreated

Laboratory Diagnosis

• Histopathology more reliable than culturing

• A certain Diagnosis needs Biopsy

• Nasal discharges Sputum, rarely contain many fungal elements

• DERMATOPHYTES(SUPERFICIAL) (“TINEA”), epidermophyton, trichophyton, microsporum

• DEEP FUNGI (GRANULOMAS)–HISTOPLASMOSIS–BLASTOMYCOSIS–COCCIDIOMYCOSIS

Parasitology

• Study of eukaryotic parasites, protozoa and helminthes

• Cause 20% of all infectious diseases• Less prevalent in industrialized countries• Increasingly common in AIDS patients

Parasitic Infections• PROTOZOA

• Protozoa are unicellular, eukaryotic organisms. • The parasitic protozoa are transmitted by

insects or by the fecal-oral route and, in humans, mainly reside in the blood or intestine .

• Most of these infections are diagnosed by microscopic examination of blood smears or lesions.

An Intestinal Ciliate: Balantidium coli

• An occupant of the intestines of domestic animals such as pigs and cattle

• Acquired by ingesting cyst-containing food or water

• Trophozoite erodes intestine and elicits intestinal symptoms

• Healthy humans resistant• Rarely penetrates intestine or enters blood

Leishmania species

• Leishmaniasis• Endemic to equatorial regions• Promastigotes are injected with sand fly

bite– convert to amastigote and multiply– if macrophage is fixed the infection is

localized– systemic if macrophage migrates

• L. major

Entamoeba histolytica

• Amebiasis• Alternates between a large trophozoite• Motile by means of pseudopods and a smaller

nonmotile cyst• Humans are the primary hosts• Ingested• Carried by 10% of world population

Entamoeba histolytica• Cysts swallowed and travel to small intestine– alkaline pH and digestive juices stimulate cysts to release 4

trophozoites• Trophozoites attach, multiply, actively move about and feed• Asymptomatic in 90% of patients• Ameba may secrete enzymes that dissolve tissues and

penetrate deeper layers of the mucosa• Causing dysentery, abdominal pain, fever, diarrhea and weight

loss

Entamoeba histolytica

• Life-threatening manifestations are– Hemorrhage– Perforation– Appendicitis– Amebomas • Tumor-like growths

• May invade liver and lung• Severe forms of disease• result in 10% fatality rate

Giardia lamblia

• Giardiasis• Pathogenic flagellate• Cysts are small, compact, and

multinucleate• Reservoirs include beavers, cattle,

coyotes, cats, and humans• Cysts can survive for two months

in environment• Usually ingested with water and

food• 10 to 100 cysts

Giardia lamblia

• Cysts enter duodenum, germinate, travel to jejunum to feed and multiply

• Diagnosis difficult because organism is shed in feces intermittently

Trichomonads: Trichomonas species• Small, pear-shaped• 4 anterior flagella and an undulating membrane• Exist only in trophozoite form• 3 infect humans:– T. vaginalis– T. tenax– T. hominis

Trichomonas vaginalis

• Causes an STD called trichomoniasis• Reservoir is human urogenital tract• Strict parasite• 3 million cases yearly• Female symptoms

– foul-smelling, green-to-yellow discharge; vulvitis; cervicitis; urinary frequency and pain

• Male symptoms– urethritis, thin, milky discharge, occasionally prostate infection

Protozoal Diseases of the Blood and Nervous System

• The Plasmodium Parasite Infects the Blood– Malaria affects 300-500 million people

Four species of Plasmodium cause malaria • P. vivax• P. ovale• P. malariae• P. falciparum

Plasmodium:

• Malaria• Dominant protozoan disease• Obligate intracellular

sporozoan• Female Anopheles mosquito

is the primary vector– blood transfusions, mother

to fetus

Plasmodium

• Africans with sickle-cell anemia gene–Resistant!!!

Trypanosoma species and Trypanosomiasis

• Distinguished by their infective stage– trypomastigote • elongate, spindle-shaped cell with tapered ends, eel-

like motility

• 2 types of trypanosomiasis:– T. brucei • African sleeping sickness

– T. cruzi • Chagas disease

Trypanosoma brucei

• African Sleeping Sickness• Spread by tsetse flies– Biting of fly inoculates skin with trypomastigotes– Multiplies in blood and damages spleen, lymph

nodes and brain• Harbored by reservoir mammals• Two variants of disease caused by 2

subspecies:– T.b.gambiense – Gambian strain; West Africa– T.b. rhodesiense – Rhodesian strain; East Africa

Trypanosoma brucei• Chronic disease symptoms are

sleep disturbances, tremors, paralysis and coma.

• Blood, spinal fluid or lymph nodes

• Control involves eliminating tsetse fly

Trypanosoma cruzi

• Chagas disease• Endemic to Central and South America• Reduviid bug (kissing bug) is the vector

– Bug feces is inoculated into a cutaneous portal

• Local lesion, fever, and swelling of lymph nodes, spleen, and liver

• Heart muscle and large intestine harbor masses of amastigotes

• Chronic inflammation occurs in the organs (especially heart and brain)

• Tapeworms (Cestodes): • Cysticercosis and Hydatid Disease• Taenia solium and Echinococcus granulosus are

cestode parasites (tapeworms) that cause cysticercosis and hydatid infections, respectively.

• Both diseases are caused by larvae that develop after ingestion of tapeworm eggs.

• These tapeworms have a complex life cycle requiring two mammalian hosts: a definitive host, in which the worm reaches sexual maturity, and an intermediate host, in which the worm does not reach sexual maturity.

• Morphology.• Cysticerci may be found in any organ, but the more common

locations include the brain, muscles, skin, and heart. • Cerebral symptoms depend on the precise location of the

cysts, which may be intraparenchymal, attached to the arachnoid, or freely floating in the ventricular system.

• The cysts are ovoid and white to opalescent, often grape-sized, and contain an invaginated scolex with hooklets that are bathed in clear cyst fluid

• The cyst wall is more than 100 μm thick, is rich in glycoproteins, and evokes little host reaction when it is intact. When cysts degenerate, however, there is inflammation, followed by focal scarring, and calcifications, which may be visible by radiography.

• Trichinosis• Trichinella spiralis is a nematode parasite

that is acquired by ingestion of larvae in undercooked meat from infected animals (usually pigs, boars, or horses) that have themselves been infected by eating T. spiralis-infected rats or meat products.

• Still, trichinosis is widespread where undercooked meat is eaten.

Trichinellosis • Trichinella spiralis– T. spiralis lives in pig intestines and can

encyst in skeletal muscles– Transmission to humans occurs by eating

raw or poorly cooked pork– Symptoms include:

• pain• vomiting• nausea• constipation

– Larvae can migrate– to the tongue, eyes, and ribs

• Schistosomiasis• Schistosomiasis infects approximately 200 million

persons and kills over 100,000 individuals annually.• Most of the mortality comes from hepatic cirrhosis,

caused by Schist soma mansoni in Latin America, Africa, and the Middle East and Schistosoma japonicum and Schistosoma mekongi in East Asia.

• In addition, Schistosoma haematobium, found in Africa, causes haematuria and granulomatous disease of the bladder, resulting in chronic obstructive uropathy.

• In S. haematobium infection, inflammatory cystitis due to massive egg deposition and granulomas appear early, leading to mucosal erosions and haematuria .

• Later, the granulomas calcify and develop a "sandy" appearance, which, if severe, may line the wall of the bladder and cause a dense concentric rim (calcified bladder) on radiographic films.

• The most frequent complication of S. haematobium infection is inflammation and fibrosis of the ureteral walls, leading to obstruction, hydronephrosis, and chronic pyelonephritis.

• There is also an association between urinary schistosomiasis and squamous cell carcinoma of the bladder

• Lymphatic Filariasis• Lymphatic filariasis is transmitted by mosquitoes and is caused

by closely related nematodes, Wuchereria bancrofti and Brugia species (B. malayi or B. timori), which are responsible for 90% and 10%, respectively, of the 90 million infections worldwide.

• In endemic areas, which include parts of Latin America, sub-Saharan Africa, and Southeast Asia, filariasis causes a spectrum of diseases, including

• (1) Asymptomatic microfilaremia, • (2) recurrent lymphadenitis,• (3) chronic lymphadenitis with swelling of the

dependent limb or scrotum (elephantiasis), and• (4) tropical pulmonary eosinophilia.

• Onchocerca volvulus, a filarial nematode transmitted by black flies, affects millions of people in Africa, South America, and Yemen.

• O. volvulus remains the second most common preventable cause of blindness in sub-Saharan Africa (called "river blindness" because of its prevalence near some rivers).

• It is estimated that there are half a million people who are blind due to onchocerciasis.