EXCHANGE TRANSFUSION IN FALCIPARUM MALARIA

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Acceptance of emphysema, represented by irregular opacities, as part of the disease would encourage more emphasis on loss of function and less on rigid criteria. It would assist the work of the doctors of the pneumoconiosis medical panels who have to administer the system and would also mean that elderly miners with severe airways obstruction who do not fulfil the strict nodular radiological criteria for pneumoconiosis and who worked for many years underground would no longer be denied benefit. Some of these men are still alive, but they are a dying race in every sense of the word. The IIAC report concluded with the familiar call "more research

needed"-Bradford Hill

went

unheeded.

1. Pneumoconiosis and other prescribed respiratory diseases. NI 226. London: Department of Social Security, 1989. 2. Report of Industrial Injuries Advisory Council. London: HM Stationery Office, 1988. 3. International Labour Office. Radiological classification of radiographs of pneumoconiosis. Geneva: ILO, 1950; 1968; 1970; 1980. 4. Gilson JC, Hugh Jones P. Lung function in coalworkers’ pneumoconiosis. Med Res Council Spec Rep Ser 1955; 290. 5. Morgan WKC. Dust, disability and death. Am Rev Respir Dis 1986; 639: 641. 6. Soutar CA. Update on lung disease in coalminers. Br J Ind Med 1987; 44: 145-48. 7. Editorial. Should coalworkers be compensated for emphysema? Lancet 1983; i: 626-27. 8. Seaton A. Coal and the lung. Thorax 1983; 38: 241-43. 9. Ryder R, Lyons JP, Campbell H, Gough J. Emphysema in coal workers’ pheumoconiosis. Br Med J 1970; iii: 481-87. 10. Lyons JP, Ryder R, Campbell H, Gough J. Pulmonary disability in coalworkers’ pneumoconiosis. Br Med J 1972; i: 713-16. 11. Cockcroft A, Seal RME, Wagner JC, Lyons JP, Ryder R, Andersson N. Post-mortem study of emphysema in coalworkers and noncoalworkers. Lancet 1982; ii: 600-03. 12. Naeye RL. Types of fibrosis in coalworkers’ pneumoconiosis. Ann NY Acad Sci 1972; 200: 381-89. 13. Ruckley VA, Seaton A. Emphysema in coalworkers. Thorax 1981; 36: 716. 14. Jacobsen M. Smoking and disability in miners. Lancet 1980; ii: 740. 15. Reichel G, Ulmer WT. In: Research report on bronchitis and occupational dust exposure. Deutsche Forschungmeinschaft Boppard. Harold Boldt Verlag, 1986: 237-47. 16. Lyons JP, Ryder R, Seal RME, Wagner JC. Emphysema in smoking and non-smoking coalworkers with pneumoconiosis. Bull Eur Physiopathol Respir 1981; 17: 75-85. 17. Love RG, Miller BG, Longitudinal study of lung function in coalminers. Thorax 1982; 37: 103-07. 18. Attfield MD. Longitudinal decline in FEV in coalworkers in United States coalmines. Thorax 1985; 40: 132-37. 19. Hurley JF, Soutar CA. Can exposure to coal mine dust cause severe impairment to lung function? Br J Ind Med 1986; 43: 150-57. 20. Miller BG, Jacobson M. Dust exposure, pneumoconiosis and mortality of coalminers. Br J Ind Med 1985; 42: 723-33. 21. Rae S, Walker DD, Attfield MD. Chronic bronchitis and dust exposure in British coalminers. In: Walton WH, ed. Inhaled particles, vol III. Old Woking, Surrey: Unwin, 1971: 837-81. 22. Lyons JP, Ryder R, Campbell R, Clarke WG, Gough J. Significance of irregular opacities in the radiology of coalworkers’ pneumoconiosis. Br J Ind Med 1974; 31: 36-44. 23. Cockcroft A, Berry G, Cotes JE, Lyons JP. Shape of small opacities and lung function in coalworkers. Thorax 1982; 37: 765-69. 24. Cockcroft A, Wagner JC, Seal RME, Lyons JP, Campbell H. Irregular opacities in coalworkers’ pneumoconiosis—correlation with pulmonary function and pathology. Ann Occ Hyg 1982; 26: 767-87. 25. Cockcroft A, Lyons JP, Andersson N, Saunders MJ. Prevalence and relation to underground exposure of radiological irregular opacities in South Wales coalworkers with pneumoconiosis. Br Med J 1983; 40: 169-72. 26. Collins HPR, Dick JA, Bennett JG, et al. Irregularly shaped small shadows on chest radiographs, dust exposure and lung function in coalworkers’ pneumoconiosis. Br J Ind Med 1988; 43: 55.

A SURFEIT OF AUDIT? As Edward VII would have said, "We are all auditors nowadays"-but one can have too much of a good thing. Not yet, in the UK perhaps, where the related concepts of audit and accreditation in health-care provision are underdeveloped, but the omens are there. Last November, the Royal College of Pathologists published a report on its pilot study of accreditation, done in 24 laboratories in south Y orkshire.1 Deficiencies were found, though none was so serious that a rating worse than provisional approval was

justified. The criticisms were of laboratory organisation not technique-indeed all laboratories performed satisfactorily in that other type of audit known as external quality assessment. Nor would the defects have been picked up by the inspection schemes (yet another form of accreditation) for assessing training in medical and non-medical laboratory posts. The College, which on balance favours a professionled programme of five-yearly inspections, hopes that separate visitations to cover training can be avoided. A laboratory that is approved could still be wasteful, however; the aim is not to provide managers with an audit of the value-for-money variety, so that is something else again. Not all laboratory heads allowed the "provisional" label to be pinned on without protest. Some inspectors got things wrong; there may have been too much emphasis on dating reports; and another reasoned protest, mischievously borrowing the College’s own words, was that the lack of an integrated computer system does not inhibit "the execution of the right analysis on the right sample from the right patient". The standards, in other words, are organisational, just as they are in the King’s Fund Centre initiative.2 The centre’s document What is Accreditation? concedes that

organisational self-audit by health professions "cannot guarantee the quality of health care given, but is rather a measure of the hospital’s capability to provide a quality service". There has been no shortage of volunteers for the King’s Fund pilot scheme. Six NHS sites and two independent hospitals are taking part. The Royal College of Pathologists’ initiative has been well received too, on the whole. So there we have it: plenty of ideas and enthusiasm and a Government white-paper providing sympathetic ambience. Yet there is more to medicine than multiple audits, and one cannot run a clinical laboratory with one eye on the hospital car-park awaiting the next inspector’s limousine and one ear cocked for the district manager’s knock. 1.

2.

Royal College of Pathologists. Pilot study of laboratory accreditation. London: Royal College of Pathologists, 1989. (See J Clin Pathol 1990; 43: 89-91.) Millar B. Facing the challenge of accreditation. Health Serv J 1990; 100: 112.

EXCHANGE TRANSFUSION IN FALCIPARUM MALARIA The

physician, nurse, or village health worker who treats a patient with severe falciparum malaria arrives late in the course of rapidly evolving and ominous events. Coma, severe haemolytic anaemia, hypoglycaemia, lacticacidosis, non-cardiogenic pulmonary oedema, acute renal failure (mainly in adults), and complications such as aspiration pneumonia or gram-negative septicaemia, which commonly contribute to a fatal outcorne,l may already be present. In

325

tropics, the therapeutic options are often limited to administration of whatever antimalarial drugs happen to be available and nursing care. In the privileged context of a well-staffed intensive care unit, rate-controlled intravenous infusions of chloroquine, quinine, or quinidine2 (depending on the likely sensitivity of the infecting parasites) are started immediately. Seizures are treated promptly, high core are and intramuscular lowered, temperatures is to reduce the likelihood of given phenobarbitone convulsions. The blood concentration is glucose subsequent checked frequently and dextrose is administered to prevent hypoglycaemia. Fluid balance and haemodynamic status are monitored carefully as the physician treads warily between underhydration and overhydration.1 Acute renal failure is tackled promptly with early dialysis, and a constant watch is kept for septicaemia and pneumonia. Despite all these measures, the mortality of cerebral malaria remains about 20%.3 Isthere anything more that can be done? the

Between 1974 and 1988, there were eighteen published case-reports describing 25 patients with severe malaria and 2 with babesiosis who had been treated with antimalarial drugs and exchange blood transfusion. Most of the patients were travellers who had returned to their home countries, and all survived. Some of the responses were dramatic, but the true success rate is uncertain because we do not know how many unreported failures there were during the same period. Two groups have now reported prospective evaluations of exchange transfusion in severe falciparum malaria. Miller et al4 from the Centers for Disease Control recount the US collective experience between 1985 and 1987 during which 11 patients, 10 of whom had over 10% parasitaemia, were managed by exchange transfusion and either intravenous quinidine (9) or quinine (2). The treatment was well tolerated and parasite counts fell with predictable rapidity during the initial exchanges. 3 patients died. Saddler et al5 report interim results from Zimbabwe of a prospective randomised study: 4 patients received transfusions and all lived whereas 3 of 4 patients receiving antimalarial treatment only died. Collectively, these casereports and studies suggest that exchange transfusion benefits patients with severe malaria but the evidence is far from conclusive. The indications for exchange, the volume of blood that should be exchanged, and the procedures to be used are uncertain. Exchange transfusion is also expensive, labour intensive, and potentially dangerous. How might exchange transfusion work? The pathological features of severe Plasmodium falciparum infection are thought to result from the sequestration of red cells containing mature forms of the parasite in venules and capillaries of vital organs.6 There is no evidence that these sequestered parasitised erythrocytes are removed during exchange transfusion. So if it is not the cells, might the benefit accrue from removal of the cellular debris resulting from schizogony and "circulating toxic factors and harmful metabolites"1? Plasma exchange, which removes plasma but not cells, was successful in 1 case7-but so was automated cell exchange, which removes cells but not plasma.8 Whilst these uncertainties are a clear prescription for further study, including controlled trials, what should be advised meanwhile? Much depends on the skill of the nursing and medical staff and the availability of blood. Where there are good facilities, exchange transfusion is an option that should be considered for non-immune travellers with parasitaemia over 5% (depending on disease severity) and positively recommended for those with parasite

levels above 15%. The aim should be to reduce the level below 5%. But travellers comprise only a very small fraction of those with severe falciparum malaria worldwide. Most of the 0-5-25 million deaths each year occur in children who live in malarious areas of the tropics,9 where recourse to appropriate treatment is limited or absent. Patients fortunate enough to be managed in hospital are nursed on busy general wards where exchange blood transfusion would be inappropriate, impractical, and probably dangerous. Moreover, cross-matched blood free from hepatitis viruses, human immunodeficiency virus, treponemes, and parasites is much needed, expensive, and may be unobtainable at short notice. In these circumstances, the approach most likely to reduce the mortality of severe malaria is to make effective antimalarial drugs more widely available. It is now over ten years since the first reports appeared from China describing the safety and efficacy of a novel group of trioxane compounds in over 1000 patients with malaria, including 141 with cerebral malaria. In both China" and Burma,l1 the artemesinine (Qinghaosu) related drugs have proved consistently more rapidly acting than any other antimalarials, especially in severe falciparum malaria, with almost no reported toxicity-yet these drugs are still generally unavailable outside these countries. Why does it take so long to test and introduce potentially valuable new antimalarial drugs? Exchange transfusion cannot make inroads into this enormous annual death toll; the trioxanes

might. 1. World Health

Organisation Malaria Action Programme. Severe and complicated malaria. Trans R Soc Trop Med Hyg 1986; 80 (suppl):

1-50. 2. White NJ. Drug treatment and prevention of malaria. Eur J Clin Pharmacol 1988; 34: 1-14. 3. Warrell DA, Looareesuwan S, Warrell MJ, et al. Dexamethasone proves deleterious in cerebral malaria. A double blind trial in 100 comatose

patients. N Engl J Med 1982; 306: 313-19. 4. Miller KD, Greenberg AE, Campbell CC. Treatment of severe malaria in the United States with continuous infusion of quinidine gluconate and exchange transfusion. N Engl J Med 1989; 321: 65-70. 5. Saddler M, Barry M, Ternouth I, Emmanuel J. Treatment of severe malaria by exchange transfusion. N Engl J Med 1990; 322: 58. 6. White NJ. Pathophysiology. In: Strickland GT, ed. I. Malaria. Clin Trop Med Communic Dis 1986; 55-90. 7. Bambauer R, Jutzler GA. Falciparum malaria successfully treated with plasma exchange. Plasma Ther Transfus Technol 1984; 5: 343-47. 8. Files JC, Case CJ, Morison FS. Automated erythrocyte exchange in fulminant falciparum malaria. Ann Intern Med 1984; 100: 396-97. 9. Sturchler D. How much malaria is there worldwide? Parasitol Today 10.

11.

1989; 5: 39-40. Qinghaosu Antimalaria Coordinating Research Group. Antimalaria studies in Qinghaosu. Chinese Med J 1979; 92: 811-16. Shwe T, Myint PT, Htut Y, Myint W, Soe L. The effect of mefloquine-artemether compared with quinine on patients with complicated falciparum malaria. Trans R Soc Trop Med Hyg 1988; 82: 665-66.

THE NEWEST HUMAN HERPESVIRUS COMES INTO FOCUS The first report of a novel lymphotropic human herpesvirus indicated that the agent would grow only in freshly isolated human B cells-hence the appellation human B-lymphotropic virus (HBLV).1 The initial isolates came from six patients with lymphoproliferative disorders, and it was suggested that HBLV might have an aetiological role in such conditions.1,2