Opportunistic infections in AIDS

Retno Wahyuningsih
Department of Parasitology Indonesia Christian University Faculty of Medicine

Opportunistic infection: def

infection caused by organism that in normal immuno-competent host does not caused disease, but in immuno - compromised host causes severe infection

HIV infection

Damage of immune system (AIDS phase) fails to overcome infections: immunocompromised. In AIDS the deficit of immune system is complex but in some extents presented by the decrease of CD4 count in the circulation

Repentigny et al. CMR 2004; 17: 729-59

Immuno-compromised host

Characterized by opportunistic infections Opportunistic infections:

parasites Virus bacteria fungus

Parasitic infections in immunocompromised host

Reactivation of old/dormant lesion

e.g. toxoplasmosis

Non pathogen parasites becomes pathogen

e.g. isosporiasis

Parasites that cause OI

Helminth Protozoa

S. stercoralis

Toxoplasma gondii Cryptosporidium sp. Isospora sp. Blastocystis hominis Cyclospora cayetanensis Microsporidia

Toxoplasma gondii

Toxoplamosis, a serious often fatal infection in immunodeficient patients Mode of infection: ingestion of raw or undercooked meat contaminated water/ contaminated food, ingestion of oocyst, trans-placental, Organ transplantation laboratory accident. Occur in immunosuppresed invidual, e.g. AIDS.

Toxoplasma gondii
Definitive host is cat asymptomatic in immunocompetent host reactivate in immunocompromised host Antibody against toxoplasma is prevalent world wide but clinical toxoplasmosis is less common until the pandemic of AIDS One of the commonest opportunistic infections in AIDS.

Tachyzoit Rapidly dividing/transmitted form

http://scienceblogs.com/afarensis/upload/2006/08/ToxoplasmaSB-a.jpg

Bradizoit/cyst in muscle Slowly dividing/persist in tissue reactivated

Signs and symptoms

pregnant woman: parasites may disseminate to the offspring AIDS: commonest clinical presentation is cerebral infection, 95% is reactivation of latent infections as the result of progressive loss of cellular immune cells CD4<0.1x109/L sub acute acute confusional state with or without neurological defect Clinical manifestations: cranial nerve disturbances, seizures etc. (brain tumor) Jakarta: commonest cerebral disorder in AIDS

diagnosis

Laboratory test:

Clinical symptoms esp. cerebral involvement (not specific) Imaging: tumors with enhancing lesion (with contrast) exjuvantibus

demonstration of the parasite in clinical materials (LCS-rare) Serology to detect antibody, IgG & IgM PCR: LCS, blood

Treatment

1st line therapy: combination of Pyrimethamine (50-75mg/day) and sulphadiazine 4-6g/day sulphadiazine induced rashes and fever are often happen in AIDS. Lifelong maintenance therapy to prevent relapse since the drugs unable to destroy cyst. Folic acid to counteract pyrimethamine on the marrow suppression Antibiotics: clyndamycin, spiramycin, clarithromycin, roxithromycin and azythromycin (active against both form).

Prevention
Proper

attention to hygiene Avoid eat raw meat cook meat (heating to 65C kills the organisms) Avoid cat feces, use gloves when cleaning cat litters and use disinfectants

Strongyloides stercoralis

strongyloidiasis

tropical & subtropical regions Man to man transmission female parasitic, rhabditiform & filariform larvae in the intestine filariform larvae: creeping eruption
Rarely found in AIDS, for the students only nice to know

Strongyloides stercoralis
Autoinfection :
- rhabditiform becomes filariform larvae in the intestine/perianal skin - filariform larvae penetrates the intestinal mucosa or perianal skin and continue its life cycle as the adult worm and cause chronic strongyloidiasis - in immunocompromised host Hyperinfection: large amount of rh filari

Strongyloides stercoralis
Major risk factors: steroid therapy, HTLV-1 infection, transplantation, hematology malignancy additional risk factors: DM, malnutrition, CRF, chronic alcohol consumption AIDS is rare risk factor

S. stercoralis
Diagnosis
rhabditiform larvae - fresh stool - duodenal aspiration - culture of specimen

filariform larvae and and free living adults in culture

Closed mouth part and end of tail

SS: Treatment & prevention

Albendazole 400 mg bid 7 days or

DOC: Ivermectine 200g/kg daily 1-2 days for immunocompetent host (not available) Take care of risk factors.

Intestinal protozoa

Similarities among Intestinal Spore-Forming Protozoa

PATHOGENESIS OF DIARRHEA
1.

Infection inflammatory infiltrate crypt hyperplasia and blunt of the villi abnormalities in absorption, secretion and motility Non ulcerative and non invasive ( except Microsporidia and Cryptosporidia) Pathology relates to the number of organisms

2.

3.

Similarities among Intestinal Spore-Forming Protozoa

DIAGNOSIS 1. Light Microscopic stool examination 2. Use of proper stains : - modified of acid fast staining: Cryptosporidium, Cyclospora, Isospora - chromotrope : Microsporidia 3. Fluorescent microscope : Cyclospora, Isospora

Cryptosporidium parvum

Host : man, animal MOI: ingestion of mature oocyst Pathology: living in alimentary tract system esp. jejunum and also in pancreas the surface of epithelial cells is its habitat and it able producing toxins

C. parvum: clinical symptoms

animal: cause diarrhea, self limiting but sometimes fatal. human:

immuno-competent: asymptomatic and self limiting immunocompromized: - chronic diarrhea, - malnutrition - fatal in untreated case; acuteprofuse diarrhea (12-17x/day fatal)

C. parvum: diagnosis
- Demonstration of oocyst in stool (Ziehl Nielsen staining - antibody detection (ELISA, IFA)

Direct stool exam.

Ziehl Nielsen staining

treatment

epidemiology

Strengthening the immune system by giving HAART Antibiotics: paromomycin 2535mg/kgbw, for one month Nitaxozamide

water borne disease

animal and man as reservoir host travelers diarrhea

Cyclospora cayetanensis
Host: man MOI infection is ingestion of mature oocyst. Pathology: living intracellular in jejunum enterocyte.
symptoms Could be asymptomatic diarrhea and other gastrointestinal disturbances fever malaise

C.cayetanensis
Diagnosis oocyst in stool (ZN stain), seen as partially acid fast structure easily infected by mature oocyst:

Treatment trimethoprim 160 mg + sulfamethoxasole twice daily for 7 days Epidemiology: travelers diarrhea

laboratory personnel people who take care patients

C. cayetanensis

Blastocystis hominis
symptoms

Host: man esp. immunocompromized host and animals. MOI: ingestion of cyst in contaminated drinking water/food.

asymptomatic GIT: - diarrhea - dysentry - nausea - constipation etc. infection associated with: - ulcerous colitis, - terminal ileitis, - enteritis.

B. hominis:
diagnosis finding vacuolar forms in stool Treatment metronidazole 3 x 750mg/dayfor 10 days
Epidemiology Travelers diarrhea

Stool prep.: B. hominis

Coccidia : Isospora
I. belli & I. hominis

Size: 20-30 um Mature oocyst with 4 sporozoites in 2 sporocysts

MOI : ingestion of oocyst or sporocyst Clinical symptom: asymptomatic/ GIT complaints and self limiting in immunocompetent host

MORPHOLOGY
Isospora - Size : 20-30 um - Mature oocyst with 4 sporozoites in 2 sporocysts
Microsporidia - Size : 1-2 um - Hard to differentiate from bacteria & debris

Isospora belli

Can cause severe disease esp. in AIDS patients:

fever malaise persistent diarrhea death

Diagnosis: finding oocyst in stool

management

Cotrimoxazole 2X2 tab, 2 weeks

Followed by maintenance 1X2 tab

Check stool post treatment

Prevention for intestinal protozoa

Wash hand properly Food handler hygiene Properly cooked dishes Water treatment resistant against chlorine filtration is suggested

Opportunistic infection caused by fungus/ Mycotic infection

Mycoses in AIDS
major fungal infection are: C. albicans (mostly) responsible for mucosal
infections candidosis P. jiroveci cause infection in the lung & other organ PCP Cr. neoformans the most frequent cause of meningitis cryptococcosis H. capsulatum, is dimorphic fungus that cause infection in untreated HIV infected patients who lives in endemic area histoplasmosis

Candidosis
Oropharygeal candidosis (OPC) most common fungal infection in AIDS occurs when CD4 count ca. 200-400 cells/L clinical classifications: - pseudomembranous
- erythematous - angular cheilitis.

predictive for progression & onset of AIDS decreased with the introduction of HAART, remain problem in poor resources country

Repentigny et al. CMR 2004; 17: 729-59

OPC
complicated by esophageal candidosis (EC) CD4 count <200 cells/L. limited food consumption which threaten the general health. EC could be independent.

Repentigny et al. CMR 2004; 17: 729-59

Management: diagnosis
OPC

DD/ hairy leucoplakia Laboratory test (oral swab): fungal element

EC

clinical, radiology and laboratory, but laboratory sample must be taken by endoscope

Coogan et al., Bull WHO 2005, 83: 700-6

Management: therapy
Good

oral hygiene is important

Topical

antifungal for 2 weeks nystatin Amphoterin B lozenges fluconazole (DOI)

Oral:

Cryptococcosis
Cr.yptococcus AIDS: Risk

: inhalation of spore

the most common clinical manifestations is meningitis

factors: CD4 < 50-100 cells/L in Jakarta ca, 33%

Prevalence:

Casadeval 2003; Dupont et al 2003; data Lab Parasitology FKUI

Cryptococcosis

Meningitis: subacute, seldom acute with fever and head ache as the most common symptoms More symptoms will manifest with time Altered mental status and fever is suggestive for meningoencephalitis Dissemination to other organ is possible including skin

Casadeval 2003; Dupont et al 2003. Wahyuningsih et al

diagnosis

Culture on SDA

Direct examination india ink:

CSF from AIDS patient with meningitis encapsulated yeast

Serology: detect GXM antigen

Picture: R. Wahyuningsih, Dept. Parasitol FKUI

Therapy:

Amphotericin B + 5FC first line of therapy for cryptococcal meningitis Continued by the application of fluconazole In the management of cryptococcosis the CSF investigation is mandatory LP is mandatory in meningitis In cryptococcosis outside CNS, the aim is to prevent CNS cryptococcosis by giving antifungal tretament

Saag et al CID 30:710-8

histoplasmosis

Caused by H. capsulatum, a thermally dimorphic fungi, endemic mycosis, true pathogenic In nature: saprophytic mould; produces microconidia.

Environment: avian dropping and bat guano

Infection: inhalation of microconidia & causes primary histoplasmosis in the lung which in immunocompetent host is self limiting with calcification.

Histoplasmosis in AIDS: pathogenesis

From

lung disseminates throughout the body via RES mostly reactivation of old lesion fever, weight loss, fatigue, pneumonia, sweats, skin lesion
Cited from Kauffman, Clin Mycol 2003

Diagnosis

Biopsy: direct exams giemsa stain Intracellular yeast (arrow)

Culture on SDA: Whitish filamentous colony at room temperature, grow slowly, 3-4 weeks

Therapy:

1st line therapy is amphotericin B then continued by itraconazole

Critical point in therapy is low absorption of itraconazole and its interaction with many agents esp. with anti TB. To increase the bioavailability of itraconazole it must be taken with high fat meal or acidic beverage e.g. classic coca cola or pepsi cola

Cited from: Como & Dismukes Clin Mycol 2003

Pneumocystis Pneumonia (PCP)

P. jiroveci : no ergosterol as wall component Not cultivated in vitro life cycle has not been fully elucidated. CD4 200 cells/L MOI: inhalation? Symptoms: fever, non productive cough, dyspnea, substernal chest tightness and shortness of breath

Cited from Decker & Masur Clin Mycol 2003

Diagnosis & its constrain

Not cultivable no media available Found organism in clinical materials Gold standard is GMS the most relevance clinical materials is BAL which needs bronchoscopy induced sputum is simple, sensitive and noninvasive Monoclonal AB - immunofluoresence

PCP: diagnosis

Based on clinical symptoms (non specific) Chest radiograph: diffuse, symetrical insterstitial markings. CT scan ground glass appearance
Laboratory: demonstration of the organism in clinical materials

PCP dengan pewarnaan Giemsa

PCP: treatment

1st line: TMP-SMX

2nd

TMP: 15-20 mg/kg/day SMX 75-100 mg/kg/day i.v/p.o

line

Dapsone 100 mg/day (p.o.)- TMP 15-20 mg/kg/day, (p.o/i.v) Atovaquone 750 mg (p.o.) tid Pentamidine isethionate (i.v.) 4 mg/kg/day, max 300 mg/day