Management of aids pneumonia

Br. J. Dis.

Chest

(1985) 79, 105

Topical Reuiew

MANAGEMENT A. L. POZNIAK, Medical

Unit,

OF AIDS

C. R. SWINBURN The Middlesex

Hospital,

PNEUMONIA

AND Mortimer

N. MCI. JOHNSON Street,

London

WI

Introduction There have been over 100 reported cases of the acquired immune deficiency syndrome (AIDS) in the UK (up to the end of November 1984), with an estimated case doubling time of 6 months (Ebbesen et al. 1983). Many more hundreds of cases may be reasonably anticipated within the next few years. At present the rise in the number of new cases is exponential (McEvoy 1984). To date most AIDS patients have presented to the departments of genitourinary medicine in central London which have large homosexual clienteles. More recently cases have begun to be referred or have presented directly to other departments especially those of respiratory medicine. The respiratory physician will be expected to play a prime role as he not only has to diagnose AIDS but also has to give advice on the management of the pneumonic illnesses which are frequent, often fatal and usually of an opportunistic nature. As new cases continue to present, more and more hospitals will meet their first case and have to deal with the problems both clinical and administrative that we have experienced over the last 18 months. We are therefore writing this brief outline giving some practical guidelines which we have developed. Recently a little has become known about the transmission and infectivity of AIDS. A retrovirus, the human T-cell lymphotropic virus III (HTLV-III) initially described in France (Barre-Sinoussi et al. 1983) as lymphadenopathy associated virus (LAV) has been strongly implicated in the pathogenesis of AIDS.,HTLV-III has been isolated from the blood, lymph nodes, saliva and semen of AIDS patients (Broder & Gallo 1984). The virus has a selective cytopathic effect upon activated OKT4+ (helper/inducer) lymphocytes (Seligmann et al. 1984) thus precipitating the cellular immune deficiency which leads to the breakdown of the normal pulmonary host defence mechanisms. Antibodies to this virus have been detected in serum from AIDS patients (97% positive) (Cheingsong-Popov et al. 1984). In this study no heterosexuals or unselected blood donors had antibody to HTLV-III. Who is at Risk? Certain groups are most susceptible to AIDS. Homosexuals, almost exclusively male, bisexuals, haemophiliacs (who have received commercial factor VIII Correspondence Street, London

to: Dr N. MCI. Johnson, Wl.

The Medical

Unit,

The Middlesex

Hospital,

Mortimer

106

A. L. Pozniak, C. R. Swinburn and N. MCI. Johnson

concentrate), Haitians, intravenous drug abusers constitute 95% of AIDS cases; sexual partners of AIDS patients and children born to mothers with AIDS constitute the other 5% (Adler & Weller 1984). Black Africans have been reported to have AIDS (Clumeck et al. 1983) and in Central Africa 12.4% of 250 Zairian medical outpatients were definitely HTLV-III antibody positive, and 12% had borderline levels suggesting a high prevalence of HTLV-III infection in the environment (Biggar et al. 1984). Surprisingly none of the Zairian patients with Kaposi’s sarcoma were anti-HTLV-III positive. How

may they be Clinically

Recognized?

Homosexuals may deny their sexual orientation and it is important in suspected cases to find any previous notes especially from departments of genitourinary medicine which are often kept separately from the other hospital notes. A past history of anal warts, syphilis, gonorrhoea, herpes genitalis or hepatitis B infection is common. Although many homosexuals with AIDS are promiscuous there have been many cases where there has only been one or two homosexual partners. Originally it was thought that contact with partners from the USA or visits to North America were necessary to develop AIDS but we have not found this to be the case. Although it may be easy to identify some homosexuals by their mannerisms and dress this is not infallible and in reality they come from all walks of life. Being single, having artistic professions, and exclusively male friends visiting whilst in hospital, are only clues to sexual behaviour, not diagnostic signs. It is now essential in taking a history from all male patients with vague respiratory symptoms to ask directly about their sexual orientation. HTLV-III

Antibody

Test

A laboratory test measuring serum antibodies to HTLV-III has recently become available in a limited number of centres in the UK either by membrane immunofluorescence or by competitive radioimmunoassay (Cheingsong-Popov et al. (1984). The value of this test so far is in identifying patients in a high-risk group, but it is not diagnostic of AIDS - however 100% of our patients with AIDS have had this antibody present. The value of a positive test lies in being able to identify how the patient should be nursed, how specimens from him should be treated in the laboratory and how other equipment should be sterilized. How many patients with a positive test go on to develop AIDS and die is unknown but is estimated at l-10% (G azzard et al. 1984). A negative test is of value in that it makes the diagnosis unlikely although recently virus has been isolated from anti-HTLV-III negative cases. Pulmonary Pulmonary Complications opportunistic pneumonias tree or lung parenchyma.

Complications

of AIDS

consist either of one of the established AIDS-related or of Kaposi’s sarcoma involving the tracheobronchial The major opportunistic infections of the lung in AIDS

Management of AIDS

Pneumonia

107

are Pneumocystis carinii (85%), cytomegalovirus (17%) and Mycobacterium avium intracellulare (17%) (N a t ional Heart and Lung Institute Workshop 1984). Many patients have a combination of more than one organism. Kaposi’s sarcoma of the lung occurs in 8%. If any of the above pulmonary infections is found in a suspected case a diagnosis of AIDS can be confidently made. Although not diagnostic of AIDS itself, other non-opportunistic infections such as Mycobacterium tuberculosis (common in Haitians), Legionella pneumophila, pyogenic bacteria and fungi also occasionally occur in patients with established AIDS. It is well to remember that homosexuals (whether HTLV-III antibody positive or not) who do not have AIDS can have tuberculosis or life-threatening pyogenic pneumonia and obviously should not have intensive treatment withheld. Pneumonia in a homosexual does not necessarily mean AIDS. Clinical

Presentation

The patients infected with the multiflagellate protozoan Pneumocystis carinii usually have a more prolonged clinical prodrome prior to presentation than those with pyogenic pneumonia. Dry cough and insidious breathlessness have usually been present for an average of 3 weeks (Engelberg et al. 1984; Swinburn et al. 198513); whereas malaise and weight loss are usually present several months before presentation. Physical signs are usually limited to low body weight, increased respiratory rate and occasionally bilateral diffuse crackles. It is important to note that chest examination can be normal. Associated oropharyngeal candidiasis, generalized lymphadenopathy or the typical skin lesions of Kaposi’s sarcoma may also be noted, but again are not always present. Investigations Any high risk patient presenting with fever, cough and dyspnoea should have a chest radiograph. If there is a focal abnormality it is likely that this is a non-opportunistic bacterial infection. Routine sputum tests such as Gram, Ziehl-Neelsen or auramine stains should be performed as well as sputum and blood cultures. Further investigation may or may not be necessary depending on response to conventional antibiotic therapy. If the chest radiograph shows bilateral diffuse alveolar or interstitial shadowing the likely diagnosis is one of Pneumocystis carinii pneumonia (PCP) . If the chest radiograph is normal PCP may nevertheless be present. In this case, if the patient is symptomatic, in particular breathless, additional tests of lung function should be performed to confirm or refute pulmonary involvement. Like the Americans we have found the Paop to be a most useful test (National Heart and Lung Institute Workshop 1984; Swinburn et al. 198513). We have shown hypoxaemia with an increased alveolar-arterial gradient in all our patients with PCP and have confined ourselves to this single test. Others have used the carbon monoxide transfer factor coefficient (Kco) (National Heart and Lung

108

A. L. Potniak,

C. R. S&burn

and N. MCI. Johnson

Institute Workshop 1984) and found it to be decreased to <70% of predicted in PCP. In a series from the USA (National Heart and Lung Institute Workshop 1984) gallium scans were positive in 96 of 98 (98%) patients with PCP but were also positive in 23 of 49 (46%) of those without PCP and so lacks specificity. Thus if these three tests are normal pulmonary infection is unlikely. If one or more are abnormal then diagnostic fibreoptic bronchoscopy may be indicated. The disadvantage of gallium scanning is the time involved (48-72 hours), the high false positive rate and the need for injections which increase the risk of staff exposure. The disadvantage with the other two is again the risk of staff exposure and also contamination of equipment with saliva, sputum or blood. Admission

and Care in Hospital

Precautions should be taken if persons are thought to have opportunistic infections that are not associated with other known underlying immunosuppressive disease or therapy. They should also be taken in patients with Kaposi’s sarcoma, persistent generalized lymphadenopathy, unexplained weight loss and/or prolonged fever in patients who belong to groups with an apparent increased risk of AIDS (Special Report 1983). As the infectivity of AIDS is unknown at present we treat all cases as highly infectious, similar to hepatitis B antigen positive cases. The patients are put into a side ward and the infection control officer notified. All secretions and excretions have to be specially packed and disposed of. Cutlery and plates are specially marked for the use of that patient only. Blood should only be taken by qualified medical staff and every effort taken to avoid needlestick incidents. If needlestick incidents occur they are immediately reported and the staff followed up in a special clinic by the occupational health physician who will check their HTLV-III antibody status as well as monitor their general health. The outcome of this group is unknown. It is known, however, that HTLV-III seroconversion is possible from such incidents (Tedder 1984). Fibreoptic

Bronchoscopy

and Lung

Biopsies

There are two reasons for lung biopsies by the transbronchial, percutaneous or open route in patients with suspected AIDS: first, to make a firm diagnosis of an opportunistic infection and thus ‘diagnose’ AIDS according to Centre for Disease Control criteria; second, to identify the specific infecting organism and to help therapeutic decisions. Fibreoptic bronchoscopy in an AIDS risk patient is a major logistical challenge. The transbronchial biopsy (TBB) is performed preferably with radiographic control with as few people present as possible. The bronchoscopist wears hat, gloves, masks, non-absorbent gowns, overshoes and goggles. The goggles are worn to prevent conjunctival contamination from secretions emitted from the suction channel. Unfortunately goggles significantly impair the view through a fibreoptic instrument. Pathological specimens are placed in sealed double bags and clearly labelled as

Management of AIDS

Pneumonia

109

high risk for AIDS - with request forms taped to the outside of the bags. The laboratory must be made aware in advance of the nature of the specimens and must have appropriate facilities to handle category 3 material. In practice this means that a doctor personally delivers the samples to the doctor in charge of the particular laboratory. Tubings, gowns and all other disposables are specially bagged and incinerated. Contaminated surfaces are washed down with 1: 10 dilution of 5.25% sodium hypochlorite solution. After use the bronchoscope is washed with soap and water including brushing the lumen. It is then rinsed with distilled water and immersed for 10 hours in 2% glutaraldehyde (older fibreoptic bronchoscopes are not fully immersible unlike newer models). It is then dried and checked for any visible dirt and sent off for ethylene oxide sterilization. This cycle can take up to 4 days and tends to blister the sheath of the bronchoscope. Neither the new nor old fibreoptic bronchoscopes are guaranteed against this process. After return the bronchoscope should ideally not be used for 7 days to allow for any ethylene oxide fumes to disperse. In practice this leads to difficulties if more than one AIDS risk patient presents simultaneously. Recent reports that alcohol and heat are effective in killing HTLV-III are encouraging (Tedder 1984) and may decrease the time for the sterilization process or alter the recommended sterilization procedure from the one we use which was developed before the virus was isolated. We have set aside a fibreoptic bronchoscope and biopsy forceps exclusively for use in patients with known or suspected AIDS. In hospitals where no separate fibreoptic bronchoscope can be set aside for AIDS patients a TBB through a rigid bronchoscope followed by autoclaving of equipment should be considered. Fibreoptic bronchoscopy has been shown to be a highly effective procedure for diagnosing pulmonary complications of AIDS (Coleman et al. 1983; National Heart and Lung Institute Workshop 1984); 95% of 368 cases of PCP were successfully diagnosed in the USA using it. In our experience to date eight out of nine patients suspected of PCP were positively diagnosed using libreoptic bronchoscopy. Investigation was withheld on the other case because of severe thrombocytopenia. Several different laboratory techniques can be used in the diagnosis of PCP. Fixed tissue specimens and touch imprints from TBB have a 95% positive yield for suspected PCP (National Heart and Lung Institute Workshop 1984). We use a ground TBB specimen and stain it rapidly (1 hour) for Pneumocystis with silver methanamine. Bronchoalveolar lavage (BAL) has proven particularly useful in the diagnosis of cytomegalovirus and Mycobacterium avium intracellulare infections although it has not been so successful in our hands for PCP. Elsewhere 79-85% success rates have been achieved (National Heart and Lung Institute Workshop 1984; Stover et al. 1984). Organisms in the BAL may be multiple and it is often difficult to decide which are responsible for the respiratory illness. Organisms found in one patient from bronchoalveolar lavage of the right upper lobe were Streptococcus pneumoniae, Staphylococcus pyogenes Group G, Bacteroides spp., Mycobacterium xenopii, Proteus spp. and cytomegalovirus (Swinburn et al. 1985a). Higher yields may be achieved when a combination of BAL and TBB is used (National Heart and Lung Institute Workshop 1984). Brush biopsy has also been

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A. L. Potniak,

C. R. Swinburn and N. MCI. Johnson

used with success (National Heart and Lung Institute Workshop 1984). We have not found formalin-fixed sections as useful as silver staining of ground specimens. If no organisms are found on fibreoptic bronchoscopy and the diagnosis is still required, an open lung biopsy, percutaneous or drill biopsy may be performed, again with a risk to personnel involved. Risks

of Technique

We have felt that it is best to concentrate on the single technique of TBB even though this carries with it the theoretical danger of haematological transmission of AIDS to the operator. Wearing full protection we hope to have reduced the risk to a minimum. BAL may also be performed without any great diagnostic benefit over TBB although French workers have had good results with this technique alone (Caubarrere et al. 1983) but it does tend to increase coughing and spillage of secretions. Drill biopsy would generate an aerosol mist of blood. We have used percutaneous biopsy successfully but have not yet needed open lung biopsy and all the problems this might raise in the operating theatre. The risk of nosocomial infection appears to be low. None of nine gastroenterological endoscopists and one bronchoscopist with multiple exposure to biopsy specimens and secretions from patients with AIDS was seropositive for HTLV-III (Hirsch et al. 1985). Therapy

Pyogenic pneumonias are treated along the usual lines. PCP is treated with 21 days intravenous co-trimoxazole (given in the dose of 20 mg trimethoprim per kg daily in three divided doses). It is difficult to give this in less than 2 litres of intravenous fluid daily. In the USA 88/107 patients survived an initial episode of PCP after this therapy alone (National Heart and Lung Institute Workshop 1984). Complications are usually fever, thrombocytopenia and skin rashes, which often occur about 9 days after commencement of therapy and usually disappear on drug withdrawal (‘Gaffe et al. 1983). Initially daily platelet counts are needed. Studies are underway using folinic acid up to 30 mg daily either to treat or prevent thrombocytopenia. Alternatively if patients are given oral therapy-3.84 g twice daily of co-trimoxazole-the blood levels of the trimethoprim component can be monitored and kept at 5 pug/ml or higher. The alternative therapy is with pentamidine which is given in a dose of 4 mg/day intramuscularly. Its major side effect is renal toxicity which usually recovers on drug withdrawal. Abnormal liver function tests, hypocalcaemia, hypoglycaemia and local reactions at infection sites are also found (Hughes et al. 1978). Daily urea and electrolytes, blood sugar and creatinine are needed. In the USA, 78/185 patients who had to stop co-trimoxazole therapy fell into. two groups: 33137 who were given pentamidine because of the lack of response to co-trimoxazole died whereas the 41 who switched to pentamidine because of co-trimoxazole toxicity all survived the pneumonic episode (National Heart and Lung Institute Workshop 1984).

Management

Treatment

of Other

of AIDS Pneumonia Opportunistic

111

Organisms

In Mycobacterium auium intracellulare infection conventional multiple drug antituberculous regimens have been tried with little success. Clofazamine or ansamycin have been suggested as the best drugs to use but there is as yet little information about them. The prognosis is very poor. There is no effective therapy for are treated with amphotericin B cytomegalovirus infection. Fungal pneumonias but again the outlook is poor. Herpes simplex pneumonia has been effectively treated in some cases, with intravenous acyclovir. Prophylaxis

Against

PCP

Treatment pies after

for PCP does not always eradicate the protozoa as repeat bronchoscoclinical ‘cure’ with co-trimoxazole and pentamidine may still show Pneumocystis carinii present in the TBB (Rosen et al. 1983). It is not known whether complete eradication of PCP will improve recurrence rates. To prevent the recurrence of PCP low dose prophylaxis with either co-trimaxozole (two tablets twice daily) or fansidar (one tablet weekly) has been advocated and initially appears to be useful (Gottlieb et al. 1984). The optimal dosage schedule is unknown. Thrombocytopenia or marrow aplasia may still occur and careful follow-up of patients treated with prophylaxis is required. Respiratory

Failure

If there is failure to respond to the therapy outlined above type I hypoxic respiratory failure ensues. The conventional therapy for this is artificial ventilation within an intensive care unit. In one series in the USA only 14% of such patients survived one such episode and were discharged from the ITU (National Heart and Lung Institute Workshop 1984). Again contamination of ventilators is are needed. a problem and b arrier nursing and full protective precautions Disposable circuits and equipment should wherever possible be used so that they can be incinerated. We have found the majority of needlestick accidents occur in ITU because of the number of invasive procedures undertaken there.

Prognosis The median cumulative survival in AIDS patients with PCP alone is 35 weeks (Rivin et al. 1984). Paradoxically patients with both Kaposi’s sarcoma and PCP have a median cumulative survival of 61 weeks. Those with Kaposi’s sarcoma alone survive a median time of 125 weeks. No patient with documented AIDS and opportunistic infections has lived for more than 2 years from diagnosis. We are only treating the complications of the immune deficiency. The minimum stay in hospital for patients treated with i.v. co-trimoxazole is 3 weeks, although in reality the inpatient care is usually for much longer. The average stay for AIDS patients with PCP treated in our hospital was 4 weeks per episode. Patients go

112

A. L. Pozniak, C. R. Swinburn and N. MCI. Johnson

home after therapy but can and do present with further pulmonary problems or die at home. Staff working with AIDS patients have an understandable fear of catching the disease and irrational fear can cloud sensibility. Education of nursing staff in all aspects of AIDS especially nursing care is vital to prevent undue anxiety. Nursing staff need to be kept informed about the disease as they have the most contact with the patient and secretions. Morale can flag when AIDS patients have been in hospital for weeks and a feeling of hopelessness can easily prevail in staff and patients. Patients need continuous support, most know AIDS is eventually fatal. Relatives also require care and consideration as the community attach a stigma to AIDS akin to that of leprosy. Acute hospitals are dealing with the terminal care of most AIDS patients, although some are leaving hospital to go home to relatives or friends for their last days. Hospice care or community nursing may be especially- needed if the projected figures are reached. Unlike tuberculosis AIDS is not yet a notifiable disease, although all cases are being monitored by Centres for Disease Control in the UK and USA. A suggestion has been made to nurse all AIDS patients in hospitals for infectious diseases. These patients often have other organs involved such as the brain and the gut which may require facilities beyond the scope of infectious disease units, such as bronchoscopy, gastroendoscopy, computerized tomography or radioisotope scanners. They will rapidly overfill with AIDS cases if the projected figures are reached. Recent DHSS .guidelines are available which suggest that post-mortem examination should not be performed on AIDS cases. The Future The hope for the future is that a cure will be found for AIDS. In the long term a vaccine for those at high risk may be found. Meanwhile other treatments have been advocated such as alpha and gamma interferon, interleukin 2, thymic factors, bone marrow transplants and lymphocyte transfusions. The most promising may be the drug suramin used in African trypanosomiasis which has been shown to protect OKT+ (helper/inducer) T-cells from the cytopathic effect of HTLV-III in vitro as well as blocking the infectivity and replication of the virus in neoplastic T-cell clones (Broder & Gallo 1984). Respiratory physicians will see more and more AIDS as the numbers escalate. There will be the added problem of confidently reassuring homosexuals who do not have AIDS and who are anxious about respiratory symptoms. We hope that this personalized account will help physicians in the practical diagnosis and management of AIDS cases. We are now asking ourselves whether it is justified to treat AIDS patients with suspected PCP on clinical grounds only, as we often do with other pneumonias, to minimize the risk to staff and contamination of equipment. Some may feel that this question can be answered already.

Management of AIDS

Pneumonia

113

References Adler, M. W. & Weller, I. V. D. (1984) AIDS - sense not fear. Br. med. J. 288, 1177-l 178. Barre-Sinoussi, F., Chermann, J. C., Rey, F. et al. (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk from the Acquired Immune Deficiency Syndrome (AIDS). Science 220, 868-870. Biggar, R. J., Melbye, M., Kestems, L. et al. (1984) Kaposi’s sarcoma in Zaire is not associated with HTLV-III infection. New Engl. J. Med. 311, 1051-1052. Broder, S. & Gallo, R. (1984) A pathogenic retrovirus (HTLV-III) linked to AIDS. New Engl. J. Med. 311, 1292-1297. Caubarrere, I., Sors, H. & Even, P. (1983) D’la g nosis of pneumocystis pneumonia. New Engl. J. Med. 298, 741. Cheingsong-Popov, R., Weiss, R. A., Dalgleish, A. et al. (1984) Prevalence of antibody to human T-lymphotropic virus type III in AIDS and AIDS-risk patients in Britain. Lancet 2, 47711-80. Clumeck, nT., Mascart-Lemone, F., DeMaubeuge, J., Brenez, D. & Marcellis, L. (1983) Acquired immune deficiency syndrome in Black Africans. Lancet 2, 642. Coleman, D. L., Dobek, P. M., Lute, J. M., Golden, J. A. & Murray, J. F. (1983) Pneumocytis pneumonia and other opportunistic lung infections in patients with Acquired Immunodeficiency Syndrome: utility of iibreoptic bronchoscopy. Am. Rev. resp. Dis. 127, 8. Ebbesen, P., Biggar, R. J. & Melbye, M. (1983) AIDS in Europe. Br. med. J. 287, 1324-1326. Engelberg, L. A., Lerner, C. W. & Tapper, M. L. (1984) Clinical features of pneumocystis pneumonia in the Acquired Immune Deficiency Syndrome. Am. Rev. resp. Dis. 130, 689-694. Gazzard, B. G., Shanson, D. C., Farthing, C. et al. (1984) Clinical findings and serological evidence of HTLV-III infection in homosexual contacts of patients with AIDS and persistent generalised lymphadenopathy in London. Lancet 2, 48&483. Gottlieb, M. S., Knight, S., Mitsuyasu, R., Weisman, J., Roth, M. & Young, L. S. (1984) Prophylaxis of Pneumocystis carinii infection in AIDS with pyrimethamine-sulfadoxine. Lancet 2, 398-399. Hirsch, M. S., Wonnser, G. P., Schooley, R. T. et al. (1985) Risk of nosocomial infection with human T-cell lymphotropic virus III (HTLV-III). New Engl. J. Med. 312> l-4. Hughes, W. T., Feldman, S.: Chaudhary, S. C., Ossi, M. J., Cox, F. & Sanyal, S. K. (1978) Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J. Pediat. 92, 285-29 1. Jaffe, H. S., Abrams, D. I., Arin, Ann A. J., Lewis, B. J. & Golden, J, A. (1983) Complications of co-trimoxazole in treatment of AIDS-associated Pneumocystis carinii pneumonia in homosexual men. Lancet 2, 1109-1-l 1 I. McEvoy, M. B. (1984) Personal communication, December 1984. National Heart and Lung Institute workshop (1984) P u 1monary complications of the Acquired Immune Deficiency Syndrome. Neze,Engl. J. Med. 310, 1682-1688. Rivin, B. E., Munroe, J. M., Hubschman, B. P. & Thomas, P. A. (1984) AIDS outcome: first follow-up. New Engl. J. Med. 311, 857. Rosen, S. J., Teirstein, A. S., Chuang, M. T. & Brown, L. (1983) Response to therapy of Pneumocystis carinii pneumonia in patients with Acquired lmmune Deficiency Syndrome. Chest 84, 347. Seligmann, M., Chess, L., Fahey, J. L. et al. (1984) AIDS - an immunologic re-evaluation. Nete, Engl. J. Med. 311, 1287-1292. Special report (1983) Infection control guidelines for patients with AIDS. New Engl. J. Med. 309, 740-744. Stover, D. E., White, D. A., Romano, P. A. & Gellene, R. A. (1984) Diagnosis of pulmonary disease in Acquired Immune Deficiency Syndrome (AIDS): role of bronchoscopy and bronchoalveolar lavage. Am. Rev. resp. Dis. 130, 659-662. Swinburn, C. R., Pozniak, A. L., Banks, R. A., Teal, A. J. & Johnson, X. MCI. (1985a) Early experience and difficulties with bronchoalveolar and transbronchial biopsy in the diagnosis of AIDS associated pneumonia in the U.K. Thorax (in press).

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Swinburn,

C. R., Pozniak, A. L., Flint, K. C. & Johnson, N. MCI. (1985b) Pneumonia (in press). R. (1984) Personal communication, November, 1984.

in AIDS.

Thorax

Tedder,

Appendix Summary of the Criteria for the Diagnosis of AIDS used by the Centers for Disease Control, A,tlanta, for Epidemiological Surveillance

For the limited purposes of epidemiological AIDS as a person who has had: 1. A reliably underlying 2. No known of reduced

surveillance,

CDC defines a case of

diagnosed disease that is at least moderately indicative of an cellular immune deficiency, but who, at the same time, has had: underlying cause of cellular immune deficiency nor any other cause resistance reported to be associated with that disease.

With regard to 1, diseases at least moderately immune deficiency are:

indicative

of underlying

cellular

(a) protozoa1 or helminthic; Pneumocystis carinii pneumonia, intestinal cryptosporidosis, or widespread strongyloidosis or toxoplasmosis. (b) fungal; oesophageal candidiasis or widespread aspergillosis or cryptococcosis. (c) bacterial; disseminated infection by ‘atypical’ mycobacteria. (d) viral; widespread herpes simplex or cytomegalovirus infection, or progressive multifocal leucoencephalopathy. (e) cancer; Kaposi’s sarcoma (under the age of 60 years), or lymphoma limited to the brain. With regard to 2, known causes of reduced resistance include widespread malignancy and therapy with corticosteroids or other immunosuppressive or cytotoxic drugs.