- Email: [email protected]
FUNGAEMIA
323
and permit the identification of different malaria isolates of this parasite. Finally, the recombinant DNA technique, applied for the first time to malaria parasites, has identified repetitive DNA sequences from the genome of two isolates of P falciparum, and the genes for ribosomal RNA of P yoelii and P falciparum; moreover, sequences homologous to the acting gene have been identified in fragments of plasmodial DNA cloned to prokaryotic carriers. Field research, as defined by the Programme, aims at the improvement of methods of malaria control in different environmental and socioeconomic conditions. Progress has been achieved in the reduction of sources of mosquito breeding, but the most substantial contribution has been in the world-wide assessment and monitoring of resistance to antimalarials; soon reliable computerised information on this point will be available from many endemic malarious areas. Last year the World Health Organisation released its Seventh General Programme of Work for the period 1984-89.6It chose the year 1989 as a target for all countries with an established health care system to reduce their annual malaria morbidity to less than 1% of the population, and to mount a strong attack on malaria mortality in children and pregnant women. This is an ambitious aim, in view of gloomy reports from the World Bank.Nevertheless the activity and drive of the Tropical Diseases Research Programme justifies much hope for progress in the fight against malaria and other tropical infections.
of P
falciparum
FUNGAEMIA A TYPICAL general hospital might expect between one and five per cent of all positive blood cultures to yield fungi, depending on the type of specialist units served.8,9 In the United Kingdom, disseminated fungal disease is most likely to arise in patients whose host defences are compromised by underlying disease (eg, aplastic anaemia or neoplasia) or by cytotoxic and immunosuppressive chemotherapy. Other risk factors include the excessive use of broad-spectrum
antibiotics, high-dose corticosteroids, indwelling
venous
catheters (as used for parenteral nutrition), and prosthetic devices: fungal infection is particularly serious when associated with peritoneal dialysis catheters and prosthetic heart valves. Candida species are the most frequent isolates, and the importance of candidaemia depends on the clinical setting; if the fungaemia is only transient, full-scale antifungal chemotherapy will not be required.10 The matter is further complicated by the fact that positive blood cultures are reported in only 40-50% of cases of disseminated candidiasis II or candida endocarditis,r2 and serological tests, whether for antibody or for antigen, can be difficult to interpret. 13 It has been suggested that non-albicans
candidaemia carries a better prognosis than infection with C albicans,14,15 although the evidence for this is not compelling. In three large reviews of fungaemia, yeasts (predominantly Candida species) were the group most commonly implicated.14,16 Other fungi which may cause generalised disease are only rarely isolated from the blood. Blood cultures
positive in acute disseminated histoplasmosisl7 but rarely so in coccidioidomycosis or blastomycosis, even though the infection may be widely disseminated.18,19 Similarly, blood cultures were positive in only 3 of 40 patients with aspergillus endocarditis,20 and in none of 125patients in may be are
studies of disseminated aspergillosis. 21,22 Cryptococcus neoformans is recovered from blood cultures in 15-35% of cases of cryptococcal meningitis23,24 and even occasionally in patients without apparent meningeal involvement. Isolation of C neoformans from the blood is generally thought to indicate a poor prognosis. Diamond and Bennett24 reported on 111 patients with cryptococcal meningitis and identified cryptococcaemia as one of the factors associated with a fatal outcome. None of their 40 patients with positive blood cultures was cured by amphotericin B alone. More recently, Perfect et al,25 working in an area of unusually high incidence of the disease, have described their experience of 15 patients with cryptococcaemia seen over seven years. All save 1 patient were immunocompromised; 12 were receiving corticosteroids and one other patient had Cushing’s syndrome. 9 of the 15 survived the initial infection and 4 (29%) were still alive after one year. All of the 9 initial survivors received the now standard combined regimen of amphotericin B and flucytosine;26 conversely, only 3 patients died having received this therapy. Perfect and co-workers judge that none of the deaths was attributable to uncontrolled cryptococcal infection. Serodiagnosis is much more useful in cryptococcal infection than in candidiasis: the latex agglutination test for cryptococcal antigen in serum, performed in 7 patients, was positive in all at a titre of 1 in 256 or greater. Cryptococcosis is uncommon, but in disseminated infection the outlook can be improved by early diagnosis and treatment. The latex test is simple, rapid, sensitive, and specific and it can be used (with the proper controls) to detect antigen in both cerebrospinal fluid and blood.13 All laboratories serving high-risk populations should consider the benefits of performing this test on site. two
,
6. World Health Organisation. Seventh general programme of
work (1984-1989). WHO,
1983
7 World Bank. Health sector policy paper. Washington, DC: World Bank, 1980. 8 Lewis JF, Alexander JJ. Blood cultures m bacteremia. South Med J 1982; 75: 147-50. 9 Michel MF, Priem CC Positive blood cultures in a university hospital in the Netherlands. Infection 1981; 9: 283-89 10. Cohen J. Antifungal chemotherapy. Lancet 1982; ii: 532-37. 11 Luria DB, Stiff DP, Bennett B. Disseminated moniliasis in the adult. Medicine 1962; 41: 307-37. 12 Harford CG. Postoperative fungal endocarditis. Fungemia, embolism and therapy. Arch Intern Med 1974; 134: 116-20. 13. Richardson MD, Warnock DW. Serological tests in the diagnosis and prognosis of fungal infection in the compromised host. In: Warnock DW, Richardson MD, eds. Fungal infection in the compromised patient. Chichester: John Wiley, 1982: 229-50
JJ, Watanakunakorn C. Hospital-acquired fungemia. Its natural course and clinical significance. Am J Med 1979; 67: 51-58. 15. Meunier-Carpentier F, Kiehn TE, Armstrong D. Fungemia in the 14 Klein
Immunocompromised Host. Changing patterns, antigenemia, high mortality. AmJ Med 1981; 71: 363-70. 16. Young RC, Bennett JE, Geelhoed GW, Levine AS. Fungemia with compromised host resistance. Ann Intern Med 1974; 80: 605-12. 17. Sarosi GA, Davies SF. Clinical manifestations and management of histoplasmosis in the compromised patient. In: Warnock DW, Richardson MD, eds. Fungal infection in the compromised patient. Chichester: John Wiley, 1982: 187-98. 18. Bouza E, Dreyer JS, Hewitt WL, Meyer RD. Coccidioidal meningitis. Medicine 1981; 60: 139-72. 19. Witorsch P, Utz JP. North American blastomycosis: a study of 40 patients. Medicine 1968; 47: 169-200. 20. Kammer RB, Utz JP. Asperigillus species endocarditis. The new face of a not so rare disease. Am J Med 1974; 56: 506-21. 21. Young RC, Bennett JE, Vogel CL, Carbone PP, deVita VT. Aspergillosis. The spectrum of disease in 98 patients. Medicine 1970; 49: 147-73. 22. Fisher BD, Armstrong D, Yu B; Gold JW. Invasive aspergillosis. Progress in early diagnosis and treatment. Am J Med 1981; 71: 571-77. 23. Butler WT, Alling DW, Spickard A, UtzJP. Diagnostic and prognostic value of clinical and laboratory findings in cryptococcal meningitis. A follow-up study of forty patients. N Engl J Med 1964; 270; 59-67. 24. Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med 1974; 80: 176-81. 25. Perfect JR, Durack DT, Gallis HA. Cryptococcemia. Medicine 1983; 62: 98-109. 26. Bennett JE, Dismukes WE, Duma RJ et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 1979; 301 126-31.
and permit the identification of different malaria isolates of this parasite. Finally, the recombinant DNA technique, applied for the first time to malaria parasites, has identified repetitive DNA sequences from the genome of two isolates of P falciparum, and the genes for ribosomal RNA of P yoelii and P falciparum; moreover, sequences homologous to the acting gene have been identified in fragments of plasmodial DNA cloned to prokaryotic carriers. Field research, as defined by the Programme, aims at the improvement of methods of malaria control in different environmental and socioeconomic conditions. Progress has been achieved in the reduction of sources of mosquito breeding, but the most substantial contribution has been in the world-wide assessment and monitoring of resistance to antimalarials; soon reliable computerised information on this point will be available from many endemic malarious areas. Last year the World Health Organisation released its Seventh General Programme of Work for the period 1984-89.6It chose the year 1989 as a target for all countries with an established health care system to reduce their annual malaria morbidity to less than 1% of the population, and to mount a strong attack on malaria mortality in children and pregnant women. This is an ambitious aim, in view of gloomy reports from the World Bank.Nevertheless the activity and drive of the Tropical Diseases Research Programme justifies much hope for progress in the fight against malaria and other tropical infections.
of P
falciparum
FUNGAEMIA A TYPICAL general hospital might expect between one and five per cent of all positive blood cultures to yield fungi, depending on the type of specialist units served.8,9 In the United Kingdom, disseminated fungal disease is most likely to arise in patients whose host defences are compromised by underlying disease (eg, aplastic anaemia or neoplasia) or by cytotoxic and immunosuppressive chemotherapy. Other risk factors include the excessive use of broad-spectrum
antibiotics, high-dose corticosteroids, indwelling
venous
catheters (as used for parenteral nutrition), and prosthetic devices: fungal infection is particularly serious when associated with peritoneal dialysis catheters and prosthetic heart valves. Candida species are the most frequent isolates, and the importance of candidaemia depends on the clinical setting; if the fungaemia is only transient, full-scale antifungal chemotherapy will not be required.10 The matter is further complicated by the fact that positive blood cultures are reported in only 40-50% of cases of disseminated candidiasis II or candida endocarditis,r2 and serological tests, whether for antibody or for antigen, can be difficult to interpret. 13 It has been suggested that non-albicans
candidaemia carries a better prognosis than infection with C albicans,14,15 although the evidence for this is not compelling. In three large reviews of fungaemia, yeasts (predominantly Candida species) were the group most commonly implicated.14,16 Other fungi which may cause generalised disease are only rarely isolated from the blood. Blood cultures
positive in acute disseminated histoplasmosisl7 but rarely so in coccidioidomycosis or blastomycosis, even though the infection may be widely disseminated.18,19 Similarly, blood cultures were positive in only 3 of 40 patients with aspergillus endocarditis,20 and in none of 125patients in may be are
studies of disseminated aspergillosis. 21,22 Cryptococcus neoformans is recovered from blood cultures in 15-35% of cases of cryptococcal meningitis23,24 and even occasionally in patients without apparent meningeal involvement. Isolation of C neoformans from the blood is generally thought to indicate a poor prognosis. Diamond and Bennett24 reported on 111 patients with cryptococcal meningitis and identified cryptococcaemia as one of the factors associated with a fatal outcome. None of their 40 patients with positive blood cultures was cured by amphotericin B alone. More recently, Perfect et al,25 working in an area of unusually high incidence of the disease, have described their experience of 15 patients with cryptococcaemia seen over seven years. All save 1 patient were immunocompromised; 12 were receiving corticosteroids and one other patient had Cushing’s syndrome. 9 of the 15 survived the initial infection and 4 (29%) were still alive after one year. All of the 9 initial survivors received the now standard combined regimen of amphotericin B and flucytosine;26 conversely, only 3 patients died having received this therapy. Perfect and co-workers judge that none of the deaths was attributable to uncontrolled cryptococcal infection. Serodiagnosis is much more useful in cryptococcal infection than in candidiasis: the latex agglutination test for cryptococcal antigen in serum, performed in 7 patients, was positive in all at a titre of 1 in 256 or greater. Cryptococcosis is uncommon, but in disseminated infection the outlook can be improved by early diagnosis and treatment. The latex test is simple, rapid, sensitive, and specific and it can be used (with the proper controls) to detect antigen in both cerebrospinal fluid and blood.13 All laboratories serving high-risk populations should consider the benefits of performing this test on site. two
,
6. World Health Organisation. Seventh general programme of
work (1984-1989). WHO,
1983
7 World Bank. Health sector policy paper. Washington, DC: World Bank, 1980. 8 Lewis JF, Alexander JJ. Blood cultures m bacteremia. South Med J 1982; 75: 147-50. 9 Michel MF, Priem CC Positive blood cultures in a university hospital in the Netherlands. Infection 1981; 9: 283-89 10. Cohen J. Antifungal chemotherapy. Lancet 1982; ii: 532-37. 11 Luria DB, Stiff DP, Bennett B. Disseminated moniliasis in the adult. Medicine 1962; 41: 307-37. 12 Harford CG. Postoperative fungal endocarditis. Fungemia, embolism and therapy. Arch Intern Med 1974; 134: 116-20. 13. Richardson MD, Warnock DW. Serological tests in the diagnosis and prognosis of fungal infection in the compromised host. In: Warnock DW, Richardson MD, eds. Fungal infection in the compromised patient. Chichester: John Wiley, 1982: 229-50
JJ, Watanakunakorn C. Hospital-acquired fungemia. Its natural course and clinical significance. Am J Med 1979; 67: 51-58. 15. Meunier-Carpentier F, Kiehn TE, Armstrong D. Fungemia in the 14 Klein
Immunocompromised Host. Changing patterns, antigenemia, high mortality. AmJ Med 1981; 71: 363-70. 16. Young RC, Bennett JE, Geelhoed GW, Levine AS. Fungemia with compromised host resistance. Ann Intern Med 1974; 80: 605-12. 17. Sarosi GA, Davies SF. Clinical manifestations and management of histoplasmosis in the compromised patient. In: Warnock DW, Richardson MD, eds. Fungal infection in the compromised patient. Chichester: John Wiley, 1982: 187-98. 18. Bouza E, Dreyer JS, Hewitt WL, Meyer RD. Coccidioidal meningitis. Medicine 1981; 60: 139-72. 19. Witorsch P, Utz JP. North American blastomycosis: a study of 40 patients. Medicine 1968; 47: 169-200. 20. Kammer RB, Utz JP. Asperigillus species endocarditis. The new face of a not so rare disease. Am J Med 1974; 56: 506-21. 21. Young RC, Bennett JE, Vogel CL, Carbone PP, deVita VT. Aspergillosis. The spectrum of disease in 98 patients. Medicine 1970; 49: 147-73. 22. Fisher BD, Armstrong D, Yu B; Gold JW. Invasive aspergillosis. Progress in early diagnosis and treatment. Am J Med 1981; 71: 571-77. 23. Butler WT, Alling DW, Spickard A, UtzJP. Diagnostic and prognostic value of clinical and laboratory findings in cryptococcal meningitis. A follow-up study of forty patients. N Engl J Med 1964; 270; 59-67. 24. Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med 1974; 80: 176-81. 25. Perfect JR, Durack DT, Gallis HA. Cryptococcemia. Medicine 1983; 62: 98-109. 26. Bennett JE, Dismukes WE, Duma RJ et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 1979; 301 126-31.