The principal causes of liver failure in an AIDS patient are: infections (tuberculosis, atypical mycobacteria, CMV, hepatitis B and C), septicaemia, cryptosporidia cholangitis, extrapulmonary pneumocystosis), drugs (anti-TB medication, paracetamol overdose, antiviral medication), alcohol. Pancreatitis can be induced by medication, such as Hivid® and Videx®.

Fever can, among other things, be due to tuberculosis or opportunistic infections. Investigations in an AIDS patient with fever should be aimed at detecting treatable causes. Malaria is not an opportunistic infection, but can also occur in HIV patients. Recurrent Salmonella septicaemia is frequent. The reason is that Salmonella bacteria are facultative intracellular pathogens. They are normally eradicated by T-cell-activated macrophages. This mechanism is deficient in AIDS patients. A “functional hypogammaglobulinaemia” exists despite the polyclonal B-cell stimulation and the accompanying hypergammaglobulinaemia. There is an increased risk of infections with encapsulated bacteria (e.g. pneumococci), but also with Branhamella, Haemophilus and Staphylococcus. Infections with Mycoplasma and Legionella are not more frequent in seropositive persons. “Drug fever” occurs more frequently in seropositive than in seronegative persons.

Pneumocystis carinii was originally described in 1909 by Carlos Chagas. He thought it was a cystic form of Trypanosoma cruzi. In 1910 Antonio Carini observed similar cysts in rats with experimental trypanosomiasis, but thought that it was a new, unknown organism. He sent material to his colleague Laveran for further investigation. In 1912 Laveran’s student Delanoe described similar cysts in lungs of Trypanosoma-free sewer rats. He gave the organism the name Pneumocystis carinii. The taxonomic classification is debatable, though on the basis of DNA analysis it is at present regarded as an unusual fungus. It is a microscopic organism that frequently causes inflammation of the lungs in severe immunosuppressed individuals. Disseminated infections can occur, e.g. with retinal lesions and foci in spleen and kidneys (frequently calcified). It is not easy to confirm the diagnosis via microscopic investigation, as this has a limited sensitivity. The pathogenic organism is best shown via bronchoscopy and broncho-alveolar lavage, though it can also be found in sputum induced in a non-invasive manner. The latter however requires availability of a special aerosol appliance to create a very fine spray of 3% saline solution. The technique is less sensitive. The organism can be shown with Giemsa staining and is recognizable as small, fine blue spots (the capsule is not stained with Giemsa). Gomori methenamine silver staining, which also stains the capsule, is better.

Several neurological complications can occur in AIDS patients. These can be subdivided into diseases induced by HIV itself, by opportunistic diseases or by medication.

HIV itself affects the brain. Glia cells are infected. HIV causes progressive behavioural, short-term memory and concentration disorders. These develop over the course of several months into presenile dementia with retention of consciousness. Aphasia, alexia and agraphia are usually absent (in contrast to Alzheimer’s disease), though motor abnormalities frequently occur, with unstable gait and a feeling of weakness in the legs. The tendon reflexes are increased. The patient becomes forgetful, can concentrate only with difficulty, quickly loses the thread of a conversation or has to read a text repeatedly in order to understand it. He/she becomes clumsy, suffers from tremor, his/her handwriting becomes blurred (coordination problems) and the sense of balance can become somewhat disturbed, especially when the patient quickly turns his/her head. Awareness of the disease is retained for quite a long time and the patient can describe the symptoms well. Apathy occurs later and the patient becomes mentally retarded. The cerebrospinal fluid often contains a large number of cells, an increased protein level and a discretely reduced glucose level. Agitation, confusion, hallucinations and psychosis can occur. Pyramidal symptoms such as spasticity, hyperreflexia, clonus and the presence of Babinski's sign can occur late. Incontinence also occurs late.

One of the most feared consequences of HIV is AIDS-related dementia. The same genetic mutation (epsilon-4 mutation of apolipoprotein E) that increases the risk for Alzheimer's dementia in HIV negative elderly persons may place HIV positive persons at higher risk for AIDS-related dementia (AIDS dementia complex) and peripheral neuropathy. Larger trials are needed to confirm these results.

Toxoplasma gondii was first described by Nicolle in 1909 in a North African rodent, Ctenodactylus gondii. The pathogen derives its species name from this. It is a unicellular parasite that is very widespread in nature and can infect many animal species. It is localised and replicates in practically all nucleated cells. The parasite has 3 principal forms: (1) banana-shaped trophozoites (hence the generic name “toxon” = bow) which reproduce asexually in nucleated cells, (2) intracellular dormant cysts with bradyzoites. In the cells the parasite forms cysts that are held in check by the immune system. The parasite thus remains present in the body, especially in muscle cells and in the brain, throughout the animal’s life. (3) oocysts that are the result of the parasite’s sexual cycle in the intestine of the cat. These oocysts can survive in the outside world for several months. If tissue cysts are present the parasite can become active again due to diminished activity of the immune system.

People are infected primarily via cat faeces or by eating contaminated and insufficiently cooked meat. In adults with an intact immune system Toxoplasma usually causes few problems, apart from occasional lymph node swelling and/or hepatitis. Reactivated parasites can attack the brain and retina in immunodepressed persons. Headache, neurological problems, blindness and focal cerebral lesions can occur. Such focal lesions can lead to epileptic fits. A favourable clinical response to anti-toxoplasmosis therapy is suggestive of cerebral toxoplasmosis (a good clinical response usually occurs within 2 weeks). Cerebral biopsy and PCR (Polymerase chain reaction) can be performed if there is doubt about the diagnosis. Toxoplamosis is an infection that can be prevented by prophylactic therapy. Cerebral localisations of lymphomas as well as tuberculomas can resemble cerebral toxoplasmosis.

Various abnormalities are of course possible, but these can be roughly divided schematically into:

Cryptococcosis is a cosmopolitan infectious disease caused by a yeast, Cryptococcus neoformans. There are two varieties: C. neoformans var. neoformans and C. neoformans var. gattii. These differ in their geographical distribution, ecology and biochemical characteristics. The antigenic specificity of the polysaccharide capsule determines four serotypes: A, B, C and D. Serotypes A and D are found worldwide in bird droppings (avian excreta), especially of pigeons. Serotypes B and C are geographically associated with certain Eucalyptus trees. C. n. neoformans occurs worldwide, whereas C. n. gattii is restricted to the tropics and subtropics. In Australia Eucalyptus camadulensis trees form the natural habitat for the var. gattii. The typical vegetative form of C. neoformans is a yeast with a diameter of 2.5 to 10 µm. The organism can also reproduce sexually. As it is a basidiomycete (Filobasidiella neoformans) it forms sexual spores: “basidiospores”. [Basidiospore: Gr: “basidon”: small base and “sporon”: seed. This indicates the morphology: a club-shaped cell with the haploid spores at the far end.] Infection can probably occur as a result of inhalation of either dehydrated yeast form or basidiospores. Cryptococcus neoformans primarily causes a chronic meningitis. Systemic infections, inflammation of the lungs and cutaneous lesions also occur as a result of these yeasts. The demonstration of cryptococcal meningitis in a patient is at present considered proof of HIV infection and AIDS.

The clinical picture can be very atypical. Mild fever, headache, confusion and emaciation can be found in patients with cryptococcal meningitis. Neck stiffness is present in less than half of infected persons. Photophobia occurs in 25%. Confusion and coma occur later. Focal signs are seldom observed. Blindness can occur (possibly due to concomitant arachnoiditis), although this is less frequent in HIV patients than in immunocompetent individuals with cryptococcal meningitis. The diagnosis of a cryptococcal meningitis is made by centrifuging a few ml of cerebrospinal fluid and mixing the sediment with an equal quantity of East Indian ink. The yeasts are recognized quite easily as round organisms with a thick capsule. The saccharide capsule can be detected via an antigen detection test (latex agglutination test for serum, cerebrospinal fluid and urine). The encapsulated organism can likewise be detected in tissue biopsies.

Progressive multifocal leukoencephalopathy (PML) is a demyelinising disease caused by infection with a papova virus, the JC virus. The family of the Papovaviridae is divided into two genera: Papilloma virus (e.g. wart virus) and Polyoma virus (including JC virus, BK virus and the SV40 virus). The name papova is derived from papilloma, polyoma and vacuolating agent. They are small double-stranded DNA viruses that are potentially oncogenic. The infection preferentially destroys the oligodendrocytes, leading to demyelinisation since the myelin sheath around axons in the central nervous system is formed by concentric folds of the cytoplasma membrane of the oligodendrocytes (analogous to the Schwann cells in the peripheral nervous system). The disease was first described in 1958 by Aström. By injection into experimental animals the virus can induce a number of brain tumours (gliomas, meningomas, neuroblastomas, medulloblastomas). JC virus undergoes intranuclear replication in the astrocytes and oligodendrocytes, as well as in other cells (the virus can be found in epithelial cells in urine, liver, spleen, lymph nodes and lungs). Infections with this virus are frequent but nearly always remain without further consequences. However, in severe immunosuppresion (CLL, Hodgkin’s disease, sarcoidosis, SLE, AIDS) a neurological syndrome can occur. Selective destruction of myelin takes place, but the axons are spared. There is little inflammation (in contrast to multiple sclerosis, where there is an inflammatory lymphocytic infiltrate). Multiple distinct foci of myelin destruction are observed in brain tissue obtained via stereotactic biopsy. The foci become confluent after a while. The lesions are asymmetrical without any preferred localisation, although lesions rarely occur in the spinal cord. The oligodendrocytes exhibit intranuclear viral inclusions. Giant astrocytes with pleomorphic, hyperchromatic nuclei strongly reminiscent of glioblastomas also occur. The clinical evolution is rapid, with an average course of disease of 2 to 4 months. Remission seldom occurs. Mono- or hemiparesis, speech disorders, mental deterioration with progression to dementia and death are the rule. Transverse myelopathy is rare. There is no fever. Headache and fits or convulsions are exceptional. The differential diagnosis includes other opportunistic infections (mycobacteria, fungi, Toxoplasma, cytomegalovirus), syphilis, cerebral lymphoma, endocarditis with embolism, HIV encephalopathy and multiple sclerosis. The EEG is usually diffusely disturbed and aspecifically slow. The cerebrospinal fluid is normal, though the virus can be detected in the fluid by PCR. CT brain scans and, even better, MRI scans show the subcortical lesions in the white matter. There is no mass effect and no staining of the lesions with contrast medium. As regards treatment, the results with various medications have hitherto been disappointing. Regression of the lesions has sometimes been seen under treatment with “HAART”.

Dark brown (on black skin) or purplish plaques and nodules (on white skin) on the skin or reddish-purple elevations in the mouth indicate Kaposi's sarcoma. This is a cancer that can affect any part of the body (lung, intestine, eye etc.) in AIDS patients, in contrast to the so called endemic Kaposi in Africa, which develops slowly and usually causes lesions only on the feet and legs. [Note: The disease was first described in 1872 by Moritz Kaposi, a Hungarian dermatologist. The disease is encountered principally in persons from Eastern Europe and the Mediterranean basin]. Kaposi's sarcoma thus occurs less frequently in Southeast Asia than in Africa. Since Kaposi's sarcoma occurs much more frequently in homosexual men than in patients infected with HIV via blood, an infectious cause was suspected. Kaposi's sarcoma also occurs more frequently in HIV-negative transplant patients. Immunosuppression appears to be needed for expression of the agent. A new herpes virus genome (KSHV [Kaposi's Sarcoma Herpes-like Virus] or HHV-8 [human herpes virus 8]) was found in the DNA of Kaposi's sarcoma cells and certain lymphomas. This virus apparently has a causal role in these cancers (and also in a variant of Castleman’s disease, a lymphoproliferative disease of B-cells). The virus is found in sperm, though much higher concentrations occur in saliva. This virus is also suspected of playing a role in pulmonary hypertension, but more research is needed.