By Raghda El-Sayed Farag Asisst prof. tropical medicine OPPORTUNISTIC INFECTIONS IN IMMUNOCOMPROMISED PATIENTS.

By Raghda El-Sayed FaragAsisst prof. tropical medicine

OPPORTUNISTIC INFECTIONS

IN IMMUNOCOMPROMISED PATIENTS

objectives Know the immune system defense function Define opportunistic infections &

Immunocompromised person Discuss Common infection in

Immunocompromised person

Immune systeme &Defense Against Disease

If these barriers are penetrated,the body responds with

If the innate immune response is insufficient,the body responds with

Adaptive(specific) Immune Responsecell-mediated immunity, humoral immunity

Nonspecific External Barriersskin, mucous membranes

Innate Immune Responsephagocytic and natural killer cells,

inflammation, fever

First line of defense

Non-specific defenses are designed to prevent infections by viruses and bacteria. These include:

Intact skin Mucus and Cilia Phagocytes

Role of skin

Intact skin cells making it hard for invading bacteria to enter and colonize.

Sweat and oils contain anti-microbial chemicals, including some antibiotics.

Role of mucus and cilia

Mucus contains lysozymes, enzymes that destroy bacterial cell walls.

The normal flow of mucus washes bacteria and viruses.

Cilia in the respiratory tract move mucus out to keep bacteria and viruses out.

Role of phagocytes

Phagocytes are several types of white blood cells (including macrophages and neutrophils) that seek and destroy invaders.

Phagocytes are attracted by an inflammatory response of damaged cells.

Specific defenses

Specific defenses are those that give us immunity to certain diseases.

In specific defenses, the immune system forms a chemical “memory” of the invading microbe. If the microbe is encountered again, the body reacts so quickly that few or no symptoms are felt.

Major players

The major players in the immune system include:

Macrophage T cells (helper, cytotoxic, memory) B cells (plasma, memory) Antibodies

Antigen recognition

Cells of the immune system are “trained” to recognize “self” proteins vs. “not self” proteins.

If an antigen (“not self”) protein is encountered by a macrophage, it will bring the protein to a helper T-cell for identification.

If the helper T-cell recognizes the protein as “not self,” it will launch an immune response.

Helper T cells

Helper T-cells have receptors for recognizing antigens. If they are presented with an antigen, they release cytokines to stimulate B-cell division.

The helper T-cell is the key cell to signal an immune response.

If helper T-cells are disabled, as they are in people with AIDS, the immune system will not respond.

B cells

B-cells differentiate into either plasma cells or memory B-cells.

- Plasma cells rapidly produce antibodies.

- Memory cells retain the “memory” of the invader and remain ready to divide rapidly if an invasion occurs again.

Clonal Selection

“Killer” T cells

While B-cells divide and differentiate, so do T-cells.

Some T-cells become cytotoxic, or “killer” T-cells. These T-cells seek out and destroy any antigens in the system, and destroy microbes “tagged” by antibodies.

Some cytotoxic T-cells can recognize and destroy cancer cells.

DEFINITION: Immunocompromised :

Denoting an individual with deficient immunologic mechanisms either because of an immunodeficiency disorder or because the system has been rendered so by immunosuppressive agents.

Medical Dictionary for the Health Professions and Nursing © Farlex 2012

Opportunistic infection:

An infection by a microorganism that normally does not cause disease but becomes pathogenic when the body's immune system is impaired and unable to fight off infection, as in AIDS and certain other diseases.

Suspicion of immunodeficiency disorder:

• Chronic or recurrent infections.• Infection caused by opportunistic or unusual pathogens.• Failure to respond as expected to standard treatment for infectious

process. • Unusual complications to a usual infection.• Family history of primary immunodeficiency.

CAUSES OF IMMUNODEFICIENCY

Genetic Physiology Acquired Chronic diseases Medications (Iatrogenic) Hematology

SOME EXAMPLES OF THE OPPORTUNISTIC INFECTIONS

FUNGAL INFECTIONSPneumocystis jiroveci

pneumonia (PCP) Candidiasis CryptococcosisAspergillosis

BACTERIAL INFECTIONSTuberculosis Mycobacterium avium

complex (MAC) infectionsMycosis Legionnaire’s disease

PARASITIC INFECTIONSToxoplasmosisCryptosporidiosisIsospridiamStrongyloides Stercolalis

VIRAL INFECTIONS Herpes simplex virus

infection (HSV) Cytomegalovirus virus CMVVaricella Zoster VirusAdenovirus

Oral candidiasis

herpes simplex virus infection

Varicella zoster infection

Mycosis : ulcers on leg

EXAMPLES OF OPPORTUNISTIC INFECTIONS ACCORDING TO TYPES OF IMMUNOCOMPROMISED INDIVIDUAL

PHYSIOLOGY ASPECTS

FETAL AND NEONATAL

Bacterial : E. coli, Chlamydia sp., M. pneumoniae, K. pneumoniae, Staphylococci sp., M. tuberculosis, streptococci

Virus : Herpes simplex (HSV), HIV, CMV, and varicella zoster virus (VZV)

Fungi : Candida albicans & Pneumocystis jiroveci

MALNUTRITION

Infectious diarrhea, pneumonia, TB, measles, malaria, salmonellosis

Malnutrition is a significant immunocompromising condition worldwide. Those affected are less able than others to tolerate infection.

GENETICALLY

HEMOGLOBINOPATHY Def.: a kind of genetic defect that results in abnormal

structure of one of the globin chains of the haemoglobin molecule

Common infectious agents are encapsulated organisms, particularly Streptococcus pneumoniae. 

Others like Salmonella sp., E coli, H. influenzae, K pneumoniae, and Neisseria sp.

TRISOMY 21Trisomy 21 and other

genetic disorders are linked to otitis media and upper respiratory infections, as well as to infections with Candida.

ACQUIRED

AIDS

AIDS (Acquired Immune Deficiency Syndrome) is caused by an infection by the HIV (Human Immunodeficiency Virus), which attacks and destroys T-helper cells.

Some drugs can slow down HIV reproduction, but no cure exists yet. Prevention is still the best “cure.”

Common infections associated AIDS

Bacterial: Mycobacterium avium-intracellulare complex ,S pneumoniae, S aureus, M.tuberculosis, Salmonella

Viral: CMV, HCV, VZV, HSV, human papilloma virus Fungal: Pneumocystis carnii, Cryptococcus

neoformans, Candida species

Parasitic: Toxoplasma gondii, C parvum

LEUKEMIA OR LYMPHOMA

infections with Staphylococci sp., P aeruginosa, enteric organisms, fungi, H influenzae, mycobacteria, and viruses.

MEDICAL CONDITIONS

Hepatic complications (LCF): Enteric organisms, enterococci, streptococci, S aureus.

Metabolic complications (DM): S aureus infection, candidiasis, mucormycosis

Pregnancy complications:-- S agalactiae- Candida sp.- Listeria sp.- hep. E virus

Renal complications(CRF): - S aureus - S pneumoniae - E coli - enterococci- S viridans

HEMATOLOGY

B-CELL DEFECTSB-cell defects predispose patients

to:- Frequent pulmonary and respiratory tract infections Infections with non-enveloped viruses, parvovirus B19,

and rotavirus. Also at risk for infections with S pneumoniae; S aureus;

Pseudomonas aeruginosa; M pneumoniae; Giardia lamblia; Salmonella & Shigella 

T-CELL DEFECTS

Predispose to infections with Candida, Mycobacterium avium-intracellulare complex, herpes viruses.

COMBINED B- AND T-CELL DEFECTS Patients often present with failure to thrive, thrush. Bacterial e.g. S pneumoniae, P aeruginosa, Legionella

pneumophila, L monocytogenes, Mycobacterium species Fungi

Virus e.g. VZV, HSV, CMV, Epstein-Barr virus (EBV)

PHAGOCYTE DEFICIENCY 

predisposes patients to infections with:

 S aureus, Nocardia sp., P aeruginosa, Serratia sp., streptococci, enteric organisms, and Candida, Aspergillus

COMPLEMENT DEFICIENCIES

Cryptosporidia,  meningococcal infections, respiratory viruses, frequent respiratory tract infections in infancy and childhood.

invasive aspergillosis in immunocompromised patients.

bancroftian filariasis. neonatal gram-negative sepsis

Ficolin-3 (H-ficolin) deficiency : Recurrent infections, bronchiectasis, neonatal gram-positive sepsis

Deficiency C1q, C1r, C1rs, C4, C2, C3, or C5-9 : Recurrent sino-pulmonary infections, S pneumoniae, H influenzae, Neisseria sp.

Deficiency of factor D, factor P, factor I, factor H, or properdin : Meningococcal infections

IATROGENIC

ORGAN TRANSPLANT

Toxoplasma sp. (heart or heart-lung transplant)

Adenovirus (after renal transplant) Candida (early post-transplantation

period), aspergillosis, cryptococcosis,

other molds, endemic fungi. Nocardia, Listeria, mycobacteria, other

bacteria (early post-transplant)

STEM CELL TRANSPLANT

Aerobic gram-negative rods, staphylococci sp., streptococci, C difficile

Candida, Aspergillus, Molds, T gondii Respiratory and enteric viruses

TREATMENTS AND MEDICATIONS MAY INTERFERE DIRECTLY WITH IMMUNE FUNCTION

Corticosteroid therapy : S aureus, S pneumoniae, Legionella sp., Listeria sp.

Inhaled corticosteroid : thrush and community-acquired pneumonia (CAP)

Drugs that decrease gastric acidity: Salmonella sp. , V. cholerae

Inhibitors of TNF: TB, HSV encephalitis, histoplasmosis, Listeria infection, and severe falciparum malaria.

CONCLUSION

Most patients usually died from infections rather than original disorder.

Managing opportunistic infections is the MOST IMPORTANT part in the treatment of immuno-deficient patients.

As a preventive measure, one must prevent these patients from getting exposed and getting the disease.