and Pallav Gupta2
(1)
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
(2)
Department of Histopathology, Sir Ganga Ram Hospital, New Delhi, India
During the last few decades, certain clinical and therapeutic developments, such as the HIV/AIDS pandemic, advances in organ transplantation, cancer chemoradiotherapy, prolonged use of steroids, and other immunosuppressants for various autoimmune diseases while prolonging patient survival, have also created major aberrations in host defense mechanisms, thereby increasing the vulnerability of these patients to a variety of opportunistic infections.
Further, the increasing use of certain therapeutic procedures and interventions like prolonged use of central lines, IV canulae, indwelling catheters, shunts, postoperative states, peritoneal and hemodialysis, postinfective states, and many other debilitating disease states and other clinical conditions such as diabetes mellitus, major organ compromises like chronic kidney diseases (CKD), chronic liver diseases (CLD), and chronic lung diseases also lead to altered immune responses, therefore, predisposing the patients to infections with opportunistic pathogens. The patients at extremes of age such as neonates and infants due to immature immune system and the elderly due to abrasions in immune responses are also at risk of contracting various opportunistic infections. Therefore, due to unusual clinical presentation and lack of early detection, often these infections, and not the primary illness, significantly contribute to the associated morbidity and mortality in such patients.
Immunocompromised states lead to impairment of natural/specific immunity causing increased risk to infections by a variety of microorganisms, which can broadly be classified into three categories.
- 1.
“True pathogens” possess virulence to overcome natural host resistance.
- 2.
“Sometime pathogens” are normal colonizers of mucocutaneous surfaces and cause clinical disease only when introduced into the tissues following a breach in the integrity of the mucocutaneous barrier; once introduced, these organisms possess sufficient virulence to cause lethal infections.
- 3.
“Nonpathogens” are the organisms generally susceptible to natural body resistance supplemented by specific immunity. However, they can cause disease in individuals with impaired immunity.
The term opportunistic infection(s) is used either for invasive infection(s) due to “nonpathogens” (Pneumocystis carinii, Aspergillus fumigatus, etc.) or to denote infection(s) due to “true” or “sometime pathogens” which are of a type or severity rarely encountered in an immunocompetent host. Hepatosplenic candidiasis in leukemic patients and disseminated herpes infection or recurrent salmonellosis in AIDS are some examples of such infections.
Factors Influencing Host Defense Mechanisms
Various factors may be responsible for lowering of natural/specific host resistance. The extremes of age predispose to opportunistic infections by virtue of immature immune system in neonates and infants and impaired repair mechanisms in elderly. Disease states like diabetes mellitus, chronic liver disease, chronic renal failure, malignancies, malnutrition, and also as yet undetermined genetic factors also predispose to opportunistic infections. Major aberrations of innate/acquired immunity in common clinical practice are due to:
- 1.
Granulocytopenia: As the granulocyte count falls below 500/μl, the frequency of infections tend to increase. Infection is also more likely to occur with rapidly falling counts than in the setting of stable granulocytopenia as observed in conditions like aplastic anemia or benign idiopathic neutropenia. Granulocytopenia is frequently observed after the administration of chemotherapy and/or radiations. Organ transplant recipients may also experience myelosuppression while receiving cyclophosphamide or azathioprine. Defects in immune functions are further enhanced by the addition of steroids. In the presence of granulocytopenia, normal colonizers of the mucosa invade and establish infection. E. coli, K. pneumoniae, and P. aeruginosa are the most common Gram-negative pathogens encountered in granulocytopenic patients, while S. aureus and coagulase-negative staphylococci are important Gram-positive coccal pathogens. The use of broad-spectrum antibiotics further provides an opportunity for overgrowth by yeast and filamentous fungi, such as Candida species, Torulopsis glabrata, and Aspergillus.
- 2.
Cellular immune dysfunction: Patients with lymphoma, HIV/AIDS, etc., have an inherent abnormality in cellular immune functions. Similar alterations may also develop as a result of drug reactions, radiation therapy, or immunosuppression associated with organ transplantation. Relatively few organisms cause infection in these settings, most being intracellular pathogens. Bacterial infections encountered in these patients include Listeria monocytogenes, Salmonella, typical and atypical Mycobacteria, and Legionella pneumophila. Viruses like varicella zoster, CMV, EBV, and respiratory syncytial virus (RSV) and fungi like, Cryptococcus, Histoplasma, and Coccidioides are also important pathogens in this group of patients. It is important to emphasize that in many patients, the illness is caused by reactivation of a latent or dormant infection. Infections by protozoan parasites such as Toxoplasma gondii, Cryptosporidium, and Microspora and helminths such as Strongyloides stercoralis are also not uncommon in these patients.
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