Aetiology
Candidiasis is a mucocutaneous infection caused in most cases by Candida albicans, and occasionally by C glabrata, C tropicalis, and C krusei.[11]
Tuberculosis (TB) infection results from the inhalation of aerosolised particles (droplet nuclei) containing Mycobacterium tuberculosis.[12]
Non-tuberculous mycobacteria (NTM) organisms are ubiquitous in the environment. M avium complex (MAC) is the most common NTM to cause infection and includes several different species, most notably M avium and M intracellulare.[13] Since these are generally hard to distinguish microbiologically, they are also often referred to as M avium-intracellulare (MAI). Infection is typically acquired from inhalation, microaspiration, or ingestion of organisms.[14]
Cytomegalovirus, a member of the herpesvirus family, remains latent in the infected person, typically following primary infection during early childhood. Transmission can occur via multiple routes (e.g., close contact with infected body fluids or tissues, perinatally, or sexually, blood or tissue).[15][16][17]
Pneumocystis jirovecii pneumonia is one of the leading causes of illness and death in people with impaired immunity. The causative organism was long considered a protozoan but, in 2001, it was officially re-classified as a fungus and was re-named P jirovecii.[18]
Toxoplasmosis is caused by Toxoplasma gondii and can be transmitted either through ingestion of oocysts from under-cooked meat or contaminated vegetables, or through direct contact with cat faeces. Serological evidence of T gondii infection varies depending on geographic locale and population group. In people living with HIV (PLWH), most toxoplasmosis cases arise from re-activation of latent infection from a remote exposure.[19][20]
Cryptococcus neoformans is an encapsulated free-living fungus that can be isolated from soils and avian excreta. Infection with C neoformans may occur through inhalation of aerosolised organisms from environmental sources. Increased exposure to environmental sources of the organism or increased susceptibility due to impaired immunity predispose PLWH to cryptococcosis.[21][22]
Coccidioidomycosis is caused by the endemic dimorphic fungi Coccidioides immitis and C posadasii. It is primarily acquired through inhalation of airborne spores within the endemic areas of the southwestern US (particularly California and Arizona), northern Mexico, and limited areas of Central and South America. In rare cases, infection can occur as a result of cutaneous inoculation.[23] In the alkaline soils of the endemic area, the fungus grows as a saprobic mycelia, the hyphae of which form arthroconidia (spores). Natural forces such as wind or earthquakes, or disturbance of the soil by construction or other activities cause disruption of the hyphae and dispersion of the readily airborne arthroconidia.[24][25]
Pathophysiology
Impaired T-cell immunity and CD4-cell depletion as a consequence of uncontrolled HIV infection are the key pathophysiological elements in most opportunistic infections (OIs).[26] An impairment in the individual defence mechanisms and higher levels of plasma HIV RNA have been associated with increased rates of mucocutaneous candidiasis and colonisation with Candida.[27][28][29]
HIV infection is an independent risk factor for acquisition of tuberculosis (TB) and rapid progression to disease. Defects of cellular immunity and macrophage function have been demonstrated in people living with HIV and TB.[30]
Colonisation of the intestinal tract with MAC is believed to be the primary route of MAC infection in patients with AIDS, and precedes the development of bacteraemia and disseminated disease by several months.[31][32]
In patients with AIDS, progressive loss of cell-mediated immunity permits cytomegalovirus re-activation and replication to begin and results in tissue necrosis in association with non-specific inflammation.[33] Increasing evidence suggests that lung damage occurring during P jirovecii pneumonia is a result of the type and extent of the individual inflammatory response to P jirovecii rather than a result of direct damage by the organism.[34] Cellular immunity, mediated by T cells, macrophages, and activity of cytokines and tumour necrosis factor-alpha, is necessary for maintaining control of latent, chronic T gondii infection.[35][36]
The lungs are the initial site of almost all cryptococcal infections. Dry yeast cells or basidiospores are inhaled and deposited in the alveoli. Both innate and adaptive immune systems are involved in host response. Virulence factors include the polysaccharide capsule, melanin pigment production, ability to grow at well at 37°C (98.6°F), and extracellular enzymes.[37][38]
Innate and adaptive immune systems are generally involved in response to coccidioidomycosis.[39] Control of coccidioidomycosis is dependent on T cell-mediated responses. Although severe coccidioidomycosis can occur among immunocompetent individuals, the risk of disease is increased in PLWH with a CD4 count less than 250 cells/microlitre.[40]
Use of this content is subject to our disclaimer