Pneumocystis pneumonia

Introduction 

-Pneumocystis pneumonia is caused by Pneumocystis jirovecii, previously known as Pneumocystis carinii 

-it was previously thought to be a protozoan, but now recognized as a fungus

-it is an extracellular pathogen 

-It has morphologically distinct forms: thin-walled trophozoites and thick-walled cysts 

-It is the most frequent serious complication of HIV infection in the United States

–it is the most common opportunistic infection among AIDS patients

-It is the most common identifiable cause of death in patients with AIDS

Symptoms & Signs 

-In the absence of immunosuppression, P. jiroveci does not cause disease

-It can cause disease in patients with immunocompromised conditions – AIDS, or organ transplantation, and chemotherapy 

– PCP is often the initial opportunistic infection that establishes the diagnosis of AIDS, often when the CD4+ T-lymphocyte count has fallen below 200 cells/mm3

-non-productive cough out of proportion to physical findings, fever, fatigue, weight loss, dyspnea, marked hypoxemia, and spontaneous pneumothorax

Diagnosis 

Diagnostic techniques: Routine sputum, induced sputum, transtracheal aspiration, Bronchoalveolar lavage, transbronchial biopsy, open lung biopsy, needle aspirate 

Histology: Alveoli filled with trophozoites, cysts, alveolar cells, monocytes, producing a distinctive foamy, honeycombed appearance 

Commonly used Stains: Giemsa, toluidine blue, methenamine silver, calcofluor white

Serology: measurement of 1-3 β-d-glucan levels, hypoxia, elevated LDH

Imaging: 

CXR: Diffuse, interstitial infiltration with classic “butterfly” pattern

CT Scan lung: bilateral patchy and ground-glass opacities and tree-in-bud nodular opacities

Treatment 

First-line therapeutic agent: Trimethoprim-sulfamethoxazole 

Other effective agents: Adjunctive corticosteroid therapy, Pentamidine, Clindamycin + Primaquine, dapsone, atovaquone 


Coccidioidomycosis

Introduction 

-Coccidioidomycosis is caused by dimorphic soil-dwelling fungi of the genus Coccidioides

-it is endemic in the arid regions of the southwestern United States, Central America, and South America

-Coccidioides grow in nature as a mold composed of barrel-shaped arthroconidia

-Infection occurs after inhalation of arthroconidia which will develop into large multinucleated spherical structures called spherules, which undergo division to release endospores 

Symptoms & Signs 

-Infection is usually self-limited in 60% of individuals 

-In the symptomatic, it takes the following clinical manifestations 

Valley fever, San Joaquin Valley fever, or desert rheumatism: the most common presentation; influenza-like or pneumonia like illness; fever, night sweats, profound fatigue, cough, headache, malaise, pleuritic chest pain, arthralgia, peripheral eosinophilia, hilar or mediastinal lymphadenopathy

Coccidioidal CNS disease: headache, fever, altered mental status, typically basilar meningitis, cranial nerve deficits 

Coccidioidal Skin Disease: most common form of disseminated disease, classic lesions seen on the nasolabial fold and sternoclavicular area, appears as papules, nodules, or verrucous plaques, ulcers, draining sinuses, abscesses, maculopapular rash (toxic erythema), erythema nodosum typically over the lower extremities, erythema multiforme, usually in a necklace distribution 

Coccidioidal joint disease: Joint pains and swellings often of the knees and ankles 

Diagnosis 

Microscopy: Large spherules containing endospores 

Culture: White to tan cottony colony formation, barrel-shaped arthroconidia
Serology: the mainstay of diagnosis, two serologic assays are used: The tube precipitin-reacting antigen detects IgM antibodies; The complement-fixing (CF) antigen detects IgG antibodies

Imaging: Patchy, nodular, lobar pulmonary infiltrates, hilar lymphadenopathy, mediastinal lymphadenopathy 

Treatment 

Mild disease: No treatment Severe disease: Amphotericin b, itraconazole, fluconazole, voriconazole, posaconazole


Histoplasmosis

Introduction 

Histoplasmosis is caused by Histoplasma capsulatum, an unencapsulated, dimorphic fungus, which has affinity to grow in soil containing bird or bat droppings 

-it is seen in Africa, India, Far East, the Ohio River and Mississippi River valleys in America, Canada 

-Histoplasmosis is the most prevalent endemic mycosis in North America

-mode of infection is usually the inhalation of mold microconidia 

Symptoms & Signs 

-Most patients are asymptomatic 

-In symptomatic, it takes the following forms which can overlap 

Acute Pulmonary Histoplasmosis: Fever, cough, chest pain, myalgias, arthralgias, arthritis, rash – toxic erythema, erythema multiforme, or erythema nodosum, pericarditis, mediastinitis; Chest radiographs usually show diffuse interstitial pattern 
Chronic Pulmonary Histoplasmosis: Upper lobe infiltrates, pulmonary consolidation and cavitation, closely resembling tuberculosis

Acute Progressive Disseminated Histoplasmosis: Dissemination to organs such as the liver, spleen, bone marrow, and lymphoreticular system; progressive weight loss, fever,anemia, hepatosplenomegaly; diffuse micronodular pulmonary infiltrates; common in AIDS patients

Chronic Progressive Disseminated Histoplasmosis: Oral or pharyngeal ulceration, hepatosplenomegaly, adrenal insufficiency (Addison disease) 

Cutaneous histoplasmosis: Guttate psoriasis-like papules, pustules, chronic ulcers, plaques, panniculitis 

Diagnosis 

Fungal culture (gold standard): identification of small, oval shaped, intracellular yeast-like cells of Histoplasma within macrophages in sputum, blood, bone marrow or biopsy specimens 

Serology: detection of antibodies to histoplasmin or the yeast cells; 

Urine: Histoplasmosis antigen testing 

Skin test: Histoplasmin skin test

Treatment 

Amphotericin B, Itraconazole, Voriconazole, Posaconazole, isavuconazole 


candidiasis

Introduction 

Candidiasis is a fungal infection caused by a yeast (a type of fungus) called Candida

-the most common species is Candida albicans

-Candida albicans can exist in both hyphal and yeast forms (dimorphism)

-It can form hyphae and pseudohyphae 

-Risk factors: use of oral antibiotics, use of steroids, immunodeficiency, diabetes, pregnancy, birth control pills, obesity and trauma 

Symptoms & Signs 

-It can appear in different manifestations: Cutaneous candidiasis, oral candidiasis, paronychia, onychomycosis, vulvovaginitis, balanitis, chronic mucocutaneous candidiasis, and disseminated candidiasis 

Morphology: Macules, beefy-red patches, plaques with satellite papules and pustules at the periphery 

Oral thrush: Whitish-curd-like pseudomembranous lesions over an erythematous base; it “wipes off” with the application of gauze 

Onychomycosis: Erythematous swelling of the nail folds 

Diagnosis 

Clinical features: Whitish, curd-like pseudomembranes

Potassium hydroxide (KOH) preparation: pseudohyphae and budding yeasts

-Candida albicans also shows true hyphae as germ tubes or chlamydospores

Other tests: Blood cultures, antigen and antibody testing, β-D-glucan tests 

Treatment 

Therapy for candidiasis includes three classes of medications:

1.Azoles: Ketoconazole, Fluconazole,miconazole, clotrimazole, itraconazole, posaconazole, isavuconazole, voriconazole

2.Echinocandins: Caspofungin, Anidulafungin, Micafungin 

3.Polyenes: Amphotericin B 

Mild disease: Nystatin or azoles 

Severe disease: Azoles or echinocandins or amphotericin B


Loiasis

Introduction 

Loiasis is a chronic filarial disease caused by infection with Loa loa (African eye worm) 

-the disease is found in the rainforests of West and Central Africa

-it is transmitted by the bite of the deer fly or mango fly called Chrysops 

-Infected larvae deposited by the bite of the deer fly crawl into the skin and develop into adults which migrate subcutaneously. Females produce microfilariae, which enter the blood 

-it is the adult worm rather than the microfilariae which produce clinical manifestations 

Symptoms & Signs 

Many infected persons are asymptomatic 

Skin: the characteristic finding of loiasis is the Calabar swelling, localized subcutaneous area of angioedema, erythema, pain and pruritis developing on the extremities due to migration of adult worms through subcutaneous tissues 

Eye: Adult worms crawling across the conjunctiva of the eye, scary but no loss of vision 

Blood: Peripheral eosinophilia, leukocytosis and elevated IgE levels 

Diagnosis 

Detection of microfilariae in the blood: peak circulation between 10 A.M and 2:00 P.M; so a daytime blood smear should be obtained 

Isolation of the adult worm from the eye or skin biopsy 

Treatment 

The treatment of choice is diethylcarbamazine

Worms in the eyes: surgical excision  


Onchocerciasis

Introduction

Onchocerciasis is a chronic parasitic disease caused by filarial nematode Onchocerca volvulus 

-it is transmitted by female blackflies near free-flowing rivers and streams 

-Most cases are in tropical Africa and Central America 

-Larvae deposited by the blackfly mature into adult worms in subcutaneous tissue and form skin nodules. Females produce microfilariae which migrate to the eyes and cause serious eye disorders. 

Symptoms & Signs 

Onchocerciasis is characterized by dermal, ocular and lymphatic manifestations

Dermal: Subcutaneous nodules over bony prominences (onchocercomata), intensely pruritic papular rash, skin atrophy, scaly dermatitis feeling like ‘lizard skin’ or ‘leopard skin’, loose pelvic skin described as ‘hanging groin’ 

Ocular: most serious manifestations of onchocerciasis; photophobia,   conjunctivitis, keratitis, uveitis, retinochoroiditis, iridocyclitis, optic atrophy, glaucoma, and blindness (river blindness) 

Lymphatic: Inguinal and femoral lymphadenopathy

Diagnosis 

Identification of microfilariae: in skin snips, in nodule biopsy or in the urine, but not in blood 

Eye: Slit-lamp examination revealing microfilariae in the eye 

Mazzotti test: Exacerbation of skin rash and pruritus after administration of diethylcarbamazine 

Other tests: PCR

Treatment 

-Ivermectin (drug of choice) kills microfilariae, not adult worms 

-Suramin kills adult worms 

Other agents: Moxidectin, doxycycline 


Lymphatic filariasis

Filarial infections are grouped into 3 categories of disease based on the location of disease: lymphatic, cutaneous, and body cavity

-Lymphatic filariasis is caused by three filarial nematodes: Wuchereria bancrofti (most common), Brugia malayi, and Brugia timori

-it is found mostly in South Asia and Africa 

-Humans are infected by the bites of infected mosquitoes

-Larvae move to the lymphatics and lymph nodes, where they mature into adult worms, which produce large numbers of microfilariae

Symptoms & Signs 

-Classical lesion: Lymphadenitis in the femoral area as a red, enlarged and tender lump spreading centrifugally down the lymphatic channels of the leg (centripetal spread in bacterial lymphangitis) 

-recurrent bouts of “filarial fevers” lasting 2 to 3 weeks

-High fever, transient local edema, lymphatic inflammation – Acute adenolymphangitis (ADL)

-Elephantiasis, thickening of the subcutaneous tissues, brawny edema

-Conjunctivitis, headache, photophobia, vertigo, scrotal pain, orchitis, epididymitis, elephantiasis of breasts, vulva 

Diagnosis 

Detection of microfilariae in peripheral blood, hydrocele fluid; Periodicity determines the best time for blood collection;  blood samples for Wuchereria and Brugia are only positive if drawn at night

Serology: Antigen assays, PCR 

High-frequency ultrasound: can show motile adult worms 

Treatment 

Effective agents: Diethylcarbamazine (Drug of choice), Albendazole, Doxycycline, ivermectin 

Diethylcarbamazine can cause hypersensitivity reaction with antigen liberation from dead microfilariae 


Anisakiasis

Introduction 

-Anisakiasis is a gastrointestinal parasitic disease caused by the larvae of the nematode, Anisakis simplex

-Transmission is due to ingestion of infective larvae from saltwater fish or squid that humans eat raw or undercooked sushi or sashimi or ceviche 

-it is most common in Japan

-Adult worms live in whales and dolphins 

Symptoms & Signs 

Acute infection can resemble appendicitis, and chronic infection can resemble gastrointestinal cancer

Severe epigastric or abdominal pain, nausea, vomiting, urticaria, angioedema, anaphylaxis 

Diagnosis 

Clinical: Acute abdomen after ingestion of raw fish 

Endoscopy: Direct visualization of larvae 

Biopsy: Eosinophilic granuloma with embedded larvae 

Treatment 

-No medical treatment is available 

-Surgical or endoscopic removal by extraction of the larvae 


Toxocariasis

Introduction 

Toxocariasis is due to human infection with Toxocara cati (an intestinal parasite of cats) or Toxocara canis (an intestinal parasite of dogs)

-Most commonly encountered among children 1 to 6 years of age 

-Transmission to humans by ingestion of eggs in soil, particularly in those with a history of pica

-Invading larvae migrate in human tissues and cannot mature to adult worms 

Symptoms & Signs 

A. Visceral larva migrans: it is due to disseminated systemic infection; It mostly affects the liver, lungs, heart, skeletal muscle and brain; eosinophilic granulomas surround parasite larvae

Pulmonary: Cough, wheezing, pulmonary infiltrates 

Abdominal: The most commonly affected organ is the liver; hepatomegaly, splenomegaly 

Heart: Myocarditis, pericarditis, cardiac arrhythmia

decreased visual acuity 

B. Ocular Larva Migrans

Unilateral posterior or peripheral inflammatory eye mass, granuloma formation, blurred vision, red eye, a whitish pupil due to loss of red reflex (leukocoria), unilateral strabismus

Diagnosis 

Labs: Leukocytosis with marked eosinophilia, anemia, and elevated liver function tests

Serology: ELISA, Western blot 

Liver biopsy: Demonstration of larva 

Treatment 

-It is usually a benign and self-limited illness 

-Severe disease: Albendazole, mebendazole, corticosteroids 


ANGIOSTRONGYLIASIS

Introduction 

Angiostrongyliasis is a parasitic disease caused by Angiostrongylus cantonensis and Angiostrongylus costaricensis

-They possess distinctive, coiled pattern due to their uterine tubes 

-Angiostrongylus cantonensis, the rat lungworm, is the most common cause of human eosinophilic meningitis

-it is transmitted between rats and mollusks (such as slugs or snails) in its natural life cycle

-Most cases of infection are diagnosed in Southeast Asia and the Pacific Basin,

-Humans acquire the Infection by ingesting raw or undercooked infected snails or slugs or foods contaminated by the slime of infected snails or slugs 

Symptoms & Signs 

Meningeal Angiostrongyliasis: Eosinophilic meningitis caused by Angiostrongylus cantonensis; headaches,nausea, vomiting, neck stiffness, cranial and extraocular nerve palsies, seizures, paralysis, lethargy 

Abdominal Angiostrongyliasis: caused by Angiostrongylus costaricensis; mimics appendicitis; nausea, vomiting, fever, abdominal pain  

Diagnosis 

Diagnosis is based on epidemiologic history, clinical features and labs 

Labs: Eosinophilia 

Epidemiologic history: History of travel to endemic regions, of eating snails and slugs 

Treatment 

There is no specific treatment for Angiostrongyliasis 


Trichinosis

Introduction

-Trichinosis is a parasitic disease caused by Trichinella spiralis and related species 

-it is the most common parasite of skeletal muscle

-it is spread by ingestion of undercooked meat, most commonly pork 

-Life cycle: Humans ingest undercooked meat containing encysted larvae, which mature into adults in the intestine. Female worms release larvae which enter blood and migrate to skeletal muscle or other organs, where they encyst

Symptoms & Signs 

-Most infections are asymptomatic

-Infection can be divided into two phases: 

Intestinal phase: fever, headache, chills, abdominal pain, nausea, vomiting, and diarrhea 

Muscular phase: Fever, facial edema, eyelid or periorbital edema, myalgia, weakness, maculopapular exanthem, subungual bleeding, conjunctivitis and subconjunctival hemorrhages, retinal hemorrhages, dry cough, dyspnea, dysphagia, painful movement of the eye muscles, involuntary movements, myocarditis, thromboembolic disease, and encephalitis

Diagnosis 

Labs: Eosinophilic leukocytosis, elevated serum muscle enzymes (creatine kinase, lactate dehydrogenase, aspartate aminotransferase), normal ESR 

-ELISA, serologic tests, muscle biopsy showing encysted larvae 

Treatment 

Albendazole is the drug of choice for trichinosis; Mebendazole 


Dracunculiasis

Introduction

-Dracunculiasis is caused by the nematode roundworm called Dracunculus medinensis, or Guinea worm.

-The Guinea worm is the largest tissue parasite of humans

-the disease is on the verge of being eradicated

-Humans are infected when they ingest water containing infective larvae from crustaceans like Cyclops 

Symptoms & Signs 

-Fever, periorbital edema, wheezing, urticaria, nausea, vomiting, diarrhea, dyspnea, blister formation, rupture of the blister with the worm emerging as a whitish filament in the center of a painful ulcer 

-Immersion in water relieves the pain

Diagnosis 

-identification of a typical skin ulcer with a protruding worm

Treatment 

-No drug is effective in treating dracunculiasis 

-Wet compresses, occlusive dressings

-Definitive treatment: Gradual extraction of the worm by sequentially rolling it over a small stick


Enterobiasis

Introduction

Enterobiasis is caused by a small intestinal parasite called Enterobius vermicularis 

-it is the most common intestinal nematode in the United States with highest prevalence in school-aged children 

-Transmission is by the fecal-oral route 

-Gravid female worms migrate nocturnally from the cecum to the perianal region to deposit large numbers of eggs 

Symptoms & Signs 

-Most individuals with pinworm infection are asymptomatic

-The most common symptom is perianal pruritis, which is most severe at night 

-Enuresis, restlessness, insomnia, perianal scratching, cellulitis, impetigo 

Diagnosis 

-Diagnosis can be made by “Scotch Tape” technique: Apply adhesive cellulose tape to the anal region and examine under thee microscope for ova 

-Eggs are football shaped with a thin outer shell

Treatment 

-The treatment of choice is albendazole

-Other effective agents: Mebendazole, Pyrantel pamoate 

-All family members may need treatment


Strongyloidiasis

Introduction

Strongyloidiasis is caused by S. stercoralis, a Nematode parasite

-Humans are the only hosts: It’s life cycle differs from that of most other helminths in that its entire life cycle may be completed within the human host 

-it is acquired by direct contact of skin with larvae or by ingestion of food contaminated with larvae 

-Life cycle: Filariform larvae (infectious) penetrate the skin, enter the blood, migrate to the lungs, move into alveoli, ascend up the trachea, swallowed, enter the colon, produce eggs which form rhabditiform larvae(non-infectious), which are passed in the feces

Autoinfection: Rhabditiform larvae can transform into filariform larvae in human host resulting in seeding of the perianal area with parasites; immunosuppression enhances risk of autoinfection  

-Of the common helminths, only  strongyloides may persist in the human host indefinitely

Symptoms & Signs 

Skin: A serpiginous urticarial rash in response to the migrating larvae; Generalized petechiae and reticular purpura of thee arms, legs, and abdomen with a characteristic thumbprint periumbilical distribution

Thumbprint sign: A unique pattern of periumbilical purpura resembling multiple thumbprints 

Larval currens: External autoinfection producing raised, red, serpiginous lesions over the buttocks, abdomen and back 

Pulmonary and intestinal manifestations can be like hookworm and Ascaris infections

Lungs: Cough, fever, eosinophilia

GI: Peptic-ulcer like pain, nausea, vomiting, diarrhea, constipation, malabsorption, weight loss

Hyperinfection: The most severe complication of Strongyloidiasis is hyperinfection

Immunodeficiency due to HIV,  human T-lymphotropic virus-1 (HTLV-1), has a stronger association with Strongyloides hyperinfection

Lung:  the most common extraintestinal manifestation of hyperinfection syndrome is pulmonary disease; Cough, wheezing, dyspnea, hemoptysis 

GI: Abdominal pain, diarrhea, ileus 

Other organs: liver, urinary tract, brain 

Diagnosis 

Larvae: Diagnosis depends on finding larvae, rather than eggs, in the stool

Serology: Serology via ELISA 

Labs: Eosinophilia 

Treatment 

Effective agents: Ivermectin (Drug of choice), Albendazole 


Hookworm disease

Introduction 

-Hookworm disease is caused by the Infection with the hookworms Ancylostoma duodenale and Necator americanus

-Adult hookworm possess two pairs of teeth in the buccal capsule 

-Male hookworm has a characteristic copulatory bursa 

-Infectious larvae present in soil penetrate the skin, enter bloodstream, reach the lungs, invade the alveoli, ascend the airways, are swallowed, reach the intestines, mature into adult worms, attach to the mucosa, and suck blood

Symptoms & Signs 

Most infected persons are asymptomatic

Skin: Initial skin infection by the larval penetration may cause a pruritic maculopapular rash (ground itch) and serpiginous tracks of subcutaneous migration (cutaneous larva migrans) 

Lungs: Pulmonary symptoms during larval migration through the lungs include fever, cough and wheezing 

Gastrointestinal: Abdominal pain, anorexia, nausea, vomiting, diarrhea, ascites 

Hematological: Hypochromic microcytic anemia, eosinophilia, hypoalbuminemia

Diagnosis 

Diagnosis is based on the identification of characteristic eggs in feces

Adult worms: Ancylostoma duodenale possesses four sharp tooth-like structures, whereas N americanus has dorsal and ventral cutting plates;  the males have a unique fan-shaped copulatory bursa

Labs: Microcytic anemia, occult blood in the stool, hypoalbuminemia, eosinophilia 

Treatment 

Effective agents: Albendazole, Mebendazole, Pyrantel pamoate 


Trichuriasis

Introduction

Trichuriasis is caused by whipworm Trichuris trichiura, a nematode parasite of the large intestine 

-Humans acquire the infection by eating foods contaminated with eggs. In the small intestine, the larvae hatch, mature and migrate to the colon 

– Unlike Ascaris, Trichuris does not have a migratory lung phase

-The adult worm has a ‘buggy whip’ appearance, hence the name whipworm 

Symptoms & Signs 

-Most infected persons are asymptomatic

-Abdominal pain, distention, cramps, nausea, vomiting, diarrhea, rectal prolapse, iron-deficiency anemia

Diagnosis 

-Diagnosis is based on finding the barrel-shaped or lemon-shaped eggs with a plug at each end 

-Adult worms may be seen in the prolapsed rectum

Treatment 

Effective agents: Albendazole, mebendazole, ivermectin, and oxantel pamoate