- Email: [email protected]
Pseudomonas pseudomallei: danger in the paddy fields
TR.ANS.KTIONS OF THE ROYAL SOCIETYOF TROPICALMEDICINE AND HYGIENE (1591) 85, l-3
Leading Article Pseudomonas
pseudomallei:
danger
in the paddy fields
D. A. B. Dance Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, Keppel Street, London, WCIE 7HT, UK ‘Whitmore’s diScSlSe’, ‘morphia injector’8 septicaemia’, ‘the great mimicker’ and ‘Vietnamese timebomb’ are some of the more colourful names which have been given to melioidosis since it was lirst described inBurma by WHITMORE& KRISHNASWAMI (1912). Pzz&monus pseudmllei has caused outbreaks of infection amongst animals in such diverse settings as a Hong Kong dolphinarium and zoos in Paris (GALIMAND & DODIN, 1982). It received considerable attention as a cause of illness amongst French and American soldiers in Vietnam (HOWE et al., 1971), and at one stage was considered as a potential agent for bacteriological warfare (LEVI, 1960). Until relatively recently, however, melioidosis was usually regarded as a rare and esoteric tropical disease, found only in south-east Asia and northern Australia. The provision of modern microbiological facilities in rural areasof Thailand has unearthed large numbers of both mild and life-threatening P. pseudomallei infections (CHAOWAGULet al., 1989: LEELARASAMEE& BOVORNKITTI, 1989), suggesting that melioidosis may be greatly under-diagnosed where laboratory facilities are less well developed. In addition to south-east Asia, sporadic cases have been diagnosed in the Indian subcontinent, central Africa and central and south America (LEELARASAMEE& BOVORNKI-~TI,1989). The factors which influence the local incidence of clinical melioidosis are poorly understood, and the true worldwide distribution and incidence of the disease are therefore unknown. Melioidosis is a strikingly seasonal disease, with annroximatelv 80% of cases in north-east Thailand presenting during the rainy season from June to November (CHAOWAGUL et al.. 1989: DANCE et al.. 1989a). These infections are *presumably recently acquired, since P. pseuahallei is an environmental saprophyte, and is most easily isolated from soil and water during the rainy season (LEELARASAMEE & BOVORNKITTI, 1989). In Thailand, most patients are rice-farmers, who are thought to contract infection through cuts and abrasions sustained whilst working in flooded rice-paddy (CHAOWAGLJL et al., 1989; LEELARASAME~ & -B~VORNKITTI, 1989). Ex: perimental animals can be infected by inhalation and ingestion of P. pseuahmalZei,but the importance of these routes in naturallv acauired infection is uncertain. Iatrogenic infections &e occasionally reported (IENKINS et al.. 1990). but human-human transmisBon has been reported only once (MCCORMICK et al., 1975), which questions the value of the barriernursing and chemoprophylaxis of contacts that are sometimes recommended (SHEPPARD et al., 1990). Infection
is seen in all
outnumber females 3:2.
age groups,
whilst
males
Relatively little is known about the pathogenesis of P. pseudomalleiinfection. Although melioidosis may affect apparently healthy individuals, the disease behaves predominantly as an opportunistic infection in man. 70% of patients with septicaemic melioidosis in Thailand have underlying diseases;most commonly diabetes mellitus or chronic renal failure (CHAOWA&IL et al., 1989; LEELARASAMEE & BOV~RNKITTI, 1989). A wide range of immunopathology is associated with both these conditions, and the precise deficits which render an individual susceptible to melioidosis are unknown. It is likely that cellmediated immunity plays an important role in control of P. ~seudomallei infection, so the snread of the acquired immune deficiency syndrome in endemic areasmay unmask many further casesof melioidosis. P. pseudomallei uossessesseveral possible virulence factors, although the importance of each in the nathoaenesis of natural melioidosis is obscure. These mclu& endotoxin, a heat-labile exotoxin, and several potentially tissue-damaging digestive enzymes (LEELARASAMEE & BOVORNKITTI, 1989). There is increasing evidence that intracellular survival of P. pseudomallei plays an important role in the disease, particularly in the long latent periods and relapses after treatment which gave rise to the term ‘timebomb disease’ (PRUKSACHARTWTHI et al.. 1990). The clinical s&3xrum of P. pseudomalleiinfections is extremely wide, and it is perhaps something of a historical accident that these various clinical pictures are grouped together under the name melioidosis, whereas there is no equivalent name for P. aerugitwsu infections, for example. There is also much overlap between sub-types of the disease?with the result that no entirely satisfactory classilicatlon has been devised. The usual outcome of contact between man and environmental P. pseudomalleiappears to be asymptomatic seroconversion, or perhaps trivial infections which are not brought to medical attention (CHAOWAGUL et al., 1989; LEELARASAMEE & BOVORNKITTI, 1989). In some studies, serological evidence of past infection has been present in as many as 47% of normal individuals (KHUPULSUP & PETCHCLAI, 1986), and in rural rice-farming communities the prevalence may be still higher. At the other end of the spectrum, approximately 60% of melioidosis cases seen in Ubon Ratchatani had positive blood cultures (WHITE & DANCE, 1988). Most of these patients presented with the picture of Gram-negative septicaemia, with evidence of multi-system failure and widespread metastatic infection, particularly in the lungs, liver and spleen (CHAOWAGUL et al., 1989). The remaining 40% had localized infections, most commonly a cavitating pneumonia often confused
with tuberculosis. Skin and soft-tissue infections, liver or splenic abscesses,suppurative parotitis in children and lymphadenitis are other common manifestations (DANCE et al., 1989a; LEELARASAMEE & BOVORNKITTI, 1989). The clinical diagnosis of melioidosis is fraught with difficulty because of the broad spectrum and nonspecific nature of clinical manifestations. Within an endemic area, the diagnosis should be considered in all patients with communitv-acquired septicaernia, par&ularly in the presenceofmuiti-nodula; pneumoi nia and hvnerelvcaemia or uraemia. The identification of Gram-Gega3;e rods in pus, sputum or urine may also help, although the classical ‘safety-pin’ bipolarity is not always seen. P. pseuakmalki is easy to grow and identify (DANCE et al., 1989c), although the use of selective media will increase the yield from sites with a normal flora (WUTHIEKANUN et al., 1990). The indirect haemagglutination test is most wideiy used for serodiagnosis of melioidosis, but lacks specificity in populations regularly exposed to the organism in the environment KHAOWAGUL et al.. 1989X Tests for the detection of‘specific immunoilobulih M antibodies to P. pseudomallei show greater specificity for the detection of active disease. and enzvme-linked immunosorbent assaysfor this purpose h&e recently been described (ASHDOWN et al., 1989; KUNAKORNet al., 1990). What is urgently needed is a rapid test to assist with therapeutic decisions in life-threatening infections, for example to detect P. pseudomallei antigens or nucleic acids directly in clinical specimens. Such assaysare under development, but await validation in clinical use (WONGRATANACHEEWIN et al., 1990). Resuscitation, intensive care and surgical drainage of abscessesare all of paramount importance in the management of patients with melioidosis. Antibiotic therapy has, until recently, been based on anecdotal regimens which have not been assessedprospectively. P. pseudomallei is intrinsically resistant to many antimicrobials, including the aminoglycosides and early p-lactams, and is thus totally unresponsive to the empirical regimens used to treat community-acquired septicaemia in many tropical regions (DANCE et al.; 1989b). The third generation cephalosporin ceftazidime has recently been shown to halve the mortality of acute, severemelioidosis, and is now the treatment of choice (WHITE et 91:) 1989), although several other agents possesspromlsmg in v~rroactivity and warrant further assessment.Many problems remain, however. The cost of ceftazidime and other new p-lactams may preclude their widespread use in melioidosis-endemic zones. The optimum duration of treatment, and appropriate oral agents for ‘maintenance’ therapy and treatment of mild infections, remain to be defined. Chloramphenicol, tetracyclines, co-trimoxazole and amoxycillin/clavulanic acid are all currently used for this purpose, but in north-east Thailand -relapse of infection has been seen in up to 30% of survivors of severe melioidosis, despite heatrnent for at least 2 months (and longer in patients with persisting abscesses or osteomyelitis: W. Chaowagul et al., unpublished data). The emergence of resistance in P. pseudotnallei during treatment has been a further problem with both ‘conventional’ agents and the newer drugs alike (DANCE et al., 1989b). The past decade has seen a great resurgence of
interest in ‘Whitmore’s disease’, accelerated by the recognition of its importance as a public health problem in north-east Thailand. Whether this is an isolated quirk produced by a combination of ecological, sociological and medical phenomena, or a reflection of the true prevalence of the diseaseelsewhere, remains to be determined. Many other fascinating questions are posed by melioidosis and P. pseudomab lei, and with the armamentarium of techniques at our &sposal in the 199Os,many answers should be rapidly forthcoming. Acknowledgements
My work on melioidosis was part of the WellcomeMahidol University, Oxford Tropical Medicine Research Programme,fundedby the WeIIcomeTrust of GreatBritain. References
Ashdown, L. R., Johnson, R. W., Koehler, J. M. & Cooney,C. A. (1989).Enzyme-linkedimmunosorbent assay for the diagnosis of clinical and subclinical melioidosis.3ournalof Infectious Diseases, 160, 25L260. Chaowagul,W., White, N. J., Dance,D. A. B., Wattanagoon,Y., Naigowit, P., Davis,T. M. ET,Looareesuwan, S. & Pitakwatchara,N. (1989). Mehoidosis: a major causeof community-acquiredsepticemiain northeastern Thailand. Journal of Infectious Diseases, 159, 890-899. Dance, D. A. B., Davis, T. M. E., Wattanagoon,Y., Chaowagul, W., Saiphan, P., Looareesuwan, S., Wuthiekanun, V. & White, N. J. (1989a). Acute suppurativeparotitiscausedby PseudomonaspseudomaUei in children.Journal of Infectious Diseases, 159,654-660. Dance, D. A. B., Wuthiekanun, V. Chaowagul,W. & White, N. J. (1989b).The antimicrobialsusceptibilityof Pseudomonas pseudomullei. Emergenceof resistancein vitro and during treatment. Journal of Antimicrobial Chemotherapy, 24, 295-309.
Dance,D. A. B., Wuthiekanun,V., Naigowit, P. & White, N. J. (1989~).Identificationof PseudmMnas pseudomaller in clinical practice:useof simplescreeningtestsand API 20NE. Journal of Clinical Pathology, 42, 645-648.
Galimand, M. & Dodin, A. (1982). Le point sur la m(lioidose dans le monde. Bulletin de la Soctiti de Pathologie Ewotique, 75, 375-383.
Howe, C., Sampath, A. & Spotnitz, M. (1971). The PseudomalJeigroup: a review. Joumul of Infectious Diseases, 124, 598606.
Jenkins,D. R., Lewis, A. M. & Strachan,C. J. L. (1990). Imported melioidosis in a British native. JournuZof Infection,
21, 221-222.
Khupulsup, K. & Petchclai, B. (1986). Application of indirect haemagglutination test and indirect fluorescent antibody test for IgM antibody for diagnosis of melioidosis in Thailand. American Joumal of Tropical Medicine and Hygiene, 35, 366-369. Kunakorn, M., Boonma, P., Khupulsup, K. & Petchclai, B. (1990). Enzyme-linked immunosorbent assay for immvo#obulin M specific antibody for the diagnosis of F2$ydosis. Journal of Clinical Microbiology, 28, 1249Leelaraskee, A. & Bovomkitti, S. (1989). Melioidosis: review and update. Reviews of Infectious Diseases, 11, 413-425. Levi, M. I. (1960). Current studies of melioidosis and certain tasks for scientific investigation. Zhurnal Mikrobiologii, Epidemiologii i Zmmunobiologii, 31, 133-139. McCormick. J. B., Sexton, D. J., McMurray, J. G., Carey, E., Hayes, P. & Feldman, R. A. (1975). Human-tohuman transmission of Pseudomonas pseudomallei. Annals of Internal Medicine, 83, 512-513. Pruksachartvuthi, S., Aswapokee, N. & Thankerngpol, K. (1990). Survival of Fseudom~s pspdo@lei in human I;:qagocytes. Journal of Medical Mxrobtology, 31, 109-
3 Sheppard, M. J., Marriott, R. M. & Brown, T. J. (1990). Long latency pneumonia: a case of melioidosis. Journul of Infection, 20, 8%84. White, N. J. & Dance, D. A. B. (1988). Clinical and laboratory studies of malaria and mehoidosis. Transactims of theRoyal Societyof Tropical Medicine and Hygiene, 82, 15-20. White, N. J., Dance, D. A. B., Chaowagul, W., Wattanagoon, Y., Wuthiekanun, V. & Pitakwatchara, N. (1989). Halving of mortality of severe melioidosis by ceftazidime. Lancet, ii? 697-700. Whirmore, A. & Knshnaswami, C. S. (1912). An account of
1 Announcement
ROYAL
the discovery of a hitherto undescribed infective disease occurring among the population of Rangoon. Indian Medical Gazette, 47, 262-267. Wongratanacheewin, S., Tattawasart, U. & Lulitanond, V. (1990). An avidin-biotin enzyme-linked tiPuntn&t assay for the detection of Pseudaumcrs antigens. Transactionsof the Rwal So&@ of Tropical Medicine and Hygiene, 84, 429A30. Wuthiekanun, V., Dance, D. A. B., Wattanagoon, Y., Supputtamongkol, Y., Chaowagu!, W. & White, N. J. (1990). The use of selective me& for the isolation of Pseudmnaac pseudoma& in clinical practice. $nmal of Medical Microbiology, 33, 121-126.
1
SOCIETY
OF TROPICAL
MEDICINE
AND
HYGIENE
The Transactions of the Royal Society of Tropical Medicine and Hygiene is issued bi-monthly (six parts per year) and publishes not only papers presented at Society meetings and symposia but also papers and correspondence submitted from all over the world on every aspect of tropical medicine and health. Supplements on specialist topics are published from time to time. The Transactions is available to Libraries and non-Fellows at an annual subscription dispatched by Accelerated Surface Post at no extra charge.
of f%.
It is
The annual subscription to Fellows is E40. Applications for Fellowship must be made on the correct form, obtainable from the address below. Rate for bmtu $de students f25. Further
information
from: The Honorary Secretaries, Royal Society of Tropical Medicine Manson House, 26 Portland Place, London WIN 4EY
and Hygiene,
Leading Article Pseudomonas
pseudomallei:
danger
in the paddy fields
D. A. B. Dance Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, Keppel Street, London, WCIE 7HT, UK ‘Whitmore’s diScSlSe’, ‘morphia injector’8 septicaemia’, ‘the great mimicker’ and ‘Vietnamese timebomb’ are some of the more colourful names which have been given to melioidosis since it was lirst described inBurma by WHITMORE& KRISHNASWAMI (1912). Pzz&monus pseudmllei has caused outbreaks of infection amongst animals in such diverse settings as a Hong Kong dolphinarium and zoos in Paris (GALIMAND & DODIN, 1982). It received considerable attention as a cause of illness amongst French and American soldiers in Vietnam (HOWE et al., 1971), and at one stage was considered as a potential agent for bacteriological warfare (LEVI, 1960). Until relatively recently, however, melioidosis was usually regarded as a rare and esoteric tropical disease, found only in south-east Asia and northern Australia. The provision of modern microbiological facilities in rural areasof Thailand has unearthed large numbers of both mild and life-threatening P. pseudomallei infections (CHAOWAGULet al., 1989: LEELARASAMEE& BOVORNKITTI, 1989), suggesting that melioidosis may be greatly under-diagnosed where laboratory facilities are less well developed. In addition to south-east Asia, sporadic cases have been diagnosed in the Indian subcontinent, central Africa and central and south America (LEELARASAMEE& BOVORNKI-~TI,1989). The factors which influence the local incidence of clinical melioidosis are poorly understood, and the true worldwide distribution and incidence of the disease are therefore unknown. Melioidosis is a strikingly seasonal disease, with annroximatelv 80% of cases in north-east Thailand presenting during the rainy season from June to November (CHAOWAGUL et al.. 1989: DANCE et al.. 1989a). These infections are *presumably recently acquired, since P. pseuahallei is an environmental saprophyte, and is most easily isolated from soil and water during the rainy season (LEELARASAMEE & BOVORNKITTI, 1989). In Thailand, most patients are rice-farmers, who are thought to contract infection through cuts and abrasions sustained whilst working in flooded rice-paddy (CHAOWAGLJL et al., 1989; LEELARASAME~ & -B~VORNKITTI, 1989). Ex: perimental animals can be infected by inhalation and ingestion of P. pseuahmalZei,but the importance of these routes in naturallv acauired infection is uncertain. Iatrogenic infections &e occasionally reported (IENKINS et al.. 1990). but human-human transmisBon has been reported only once (MCCORMICK et al., 1975), which questions the value of the barriernursing and chemoprophylaxis of contacts that are sometimes recommended (SHEPPARD et al., 1990). Infection
is seen in all
outnumber females 3:2.
age groups,
whilst
males
Relatively little is known about the pathogenesis of P. pseudomalleiinfection. Although melioidosis may affect apparently healthy individuals, the disease behaves predominantly as an opportunistic infection in man. 70% of patients with septicaemic melioidosis in Thailand have underlying diseases;most commonly diabetes mellitus or chronic renal failure (CHAOWA&IL et al., 1989; LEELARASAMEE & BOV~RNKITTI, 1989). A wide range of immunopathology is associated with both these conditions, and the precise deficits which render an individual susceptible to melioidosis are unknown. It is likely that cellmediated immunity plays an important role in control of P. ~seudomallei infection, so the snread of the acquired immune deficiency syndrome in endemic areasmay unmask many further casesof melioidosis. P. pseudomallei uossessesseveral possible virulence factors, although the importance of each in the nathoaenesis of natural melioidosis is obscure. These mclu& endotoxin, a heat-labile exotoxin, and several potentially tissue-damaging digestive enzymes (LEELARASAMEE & BOVORNKITTI, 1989). There is increasing evidence that intracellular survival of P. pseudomallei plays an important role in the disease, particularly in the long latent periods and relapses after treatment which gave rise to the term ‘timebomb disease’ (PRUKSACHARTWTHI et al.. 1990). The clinical s&3xrum of P. pseudomalleiinfections is extremely wide, and it is perhaps something of a historical accident that these various clinical pictures are grouped together under the name melioidosis, whereas there is no equivalent name for P. aerugitwsu infections, for example. There is also much overlap between sub-types of the disease?with the result that no entirely satisfactory classilicatlon has been devised. The usual outcome of contact between man and environmental P. pseudomalleiappears to be asymptomatic seroconversion, or perhaps trivial infections which are not brought to medical attention (CHAOWAGUL et al., 1989; LEELARASAMEE & BOVORNKITTI, 1989). In some studies, serological evidence of past infection has been present in as many as 47% of normal individuals (KHUPULSUP & PETCHCLAI, 1986), and in rural rice-farming communities the prevalence may be still higher. At the other end of the spectrum, approximately 60% of melioidosis cases seen in Ubon Ratchatani had positive blood cultures (WHITE & DANCE, 1988). Most of these patients presented with the picture of Gram-negative septicaemia, with evidence of multi-system failure and widespread metastatic infection, particularly in the lungs, liver and spleen (CHAOWAGUL et al., 1989). The remaining 40% had localized infections, most commonly a cavitating pneumonia often confused
with tuberculosis. Skin and soft-tissue infections, liver or splenic abscesses,suppurative parotitis in children and lymphadenitis are other common manifestations (DANCE et al., 1989a; LEELARASAMEE & BOVORNKITTI, 1989). The clinical diagnosis of melioidosis is fraught with difficulty because of the broad spectrum and nonspecific nature of clinical manifestations. Within an endemic area, the diagnosis should be considered in all patients with communitv-acquired septicaernia, par&ularly in the presenceofmuiti-nodula; pneumoi nia and hvnerelvcaemia or uraemia. The identification of Gram-Gega3;e rods in pus, sputum or urine may also help, although the classical ‘safety-pin’ bipolarity is not always seen. P. pseuakmalki is easy to grow and identify (DANCE et al., 1989c), although the use of selective media will increase the yield from sites with a normal flora (WUTHIEKANUN et al., 1990). The indirect haemagglutination test is most wideiy used for serodiagnosis of melioidosis, but lacks specificity in populations regularly exposed to the organism in the environment KHAOWAGUL et al.. 1989X Tests for the detection of‘specific immunoilobulih M antibodies to P. pseudomallei show greater specificity for the detection of active disease. and enzvme-linked immunosorbent assaysfor this purpose h&e recently been described (ASHDOWN et al., 1989; KUNAKORNet al., 1990). What is urgently needed is a rapid test to assist with therapeutic decisions in life-threatening infections, for example to detect P. pseudomallei antigens or nucleic acids directly in clinical specimens. Such assaysare under development, but await validation in clinical use (WONGRATANACHEEWIN et al., 1990). Resuscitation, intensive care and surgical drainage of abscessesare all of paramount importance in the management of patients with melioidosis. Antibiotic therapy has, until recently, been based on anecdotal regimens which have not been assessedprospectively. P. pseudomallei is intrinsically resistant to many antimicrobials, including the aminoglycosides and early p-lactams, and is thus totally unresponsive to the empirical regimens used to treat community-acquired septicaemia in many tropical regions (DANCE et al.; 1989b). The third generation cephalosporin ceftazidime has recently been shown to halve the mortality of acute, severemelioidosis, and is now the treatment of choice (WHITE et 91:) 1989), although several other agents possesspromlsmg in v~rroactivity and warrant further assessment.Many problems remain, however. The cost of ceftazidime and other new p-lactams may preclude their widespread use in melioidosis-endemic zones. The optimum duration of treatment, and appropriate oral agents for ‘maintenance’ therapy and treatment of mild infections, remain to be defined. Chloramphenicol, tetracyclines, co-trimoxazole and amoxycillin/clavulanic acid are all currently used for this purpose, but in north-east Thailand -relapse of infection has been seen in up to 30% of survivors of severe melioidosis, despite heatrnent for at least 2 months (and longer in patients with persisting abscesses or osteomyelitis: W. Chaowagul et al., unpublished data). The emergence of resistance in P. pseudotnallei during treatment has been a further problem with both ‘conventional’ agents and the newer drugs alike (DANCE et al., 1989b). The past decade has seen a great resurgence of
interest in ‘Whitmore’s disease’, accelerated by the recognition of its importance as a public health problem in north-east Thailand. Whether this is an isolated quirk produced by a combination of ecological, sociological and medical phenomena, or a reflection of the true prevalence of the diseaseelsewhere, remains to be determined. Many other fascinating questions are posed by melioidosis and P. pseudomab lei, and with the armamentarium of techniques at our &sposal in the 199Os,many answers should be rapidly forthcoming. Acknowledgements
My work on melioidosis was part of the WellcomeMahidol University, Oxford Tropical Medicine Research Programme,fundedby the WeIIcomeTrust of GreatBritain. References
Ashdown, L. R., Johnson, R. W., Koehler, J. M. & Cooney,C. A. (1989).Enzyme-linkedimmunosorbent assay for the diagnosis of clinical and subclinical melioidosis.3ournalof Infectious Diseases, 160, 25L260. Chaowagul,W., White, N. J., Dance,D. A. B., Wattanagoon,Y., Naigowit, P., Davis,T. M. ET,Looareesuwan, S. & Pitakwatchara,N. (1989). Mehoidosis: a major causeof community-acquiredsepticemiain northeastern Thailand. Journal of Infectious Diseases, 159, 890-899. Dance, D. A. B., Davis, T. M. E., Wattanagoon,Y., Chaowagul, W., Saiphan, P., Looareesuwan, S., Wuthiekanun, V. & White, N. J. (1989a). Acute suppurativeparotitiscausedby PseudomonaspseudomaUei in children.Journal of Infectious Diseases, 159,654-660. Dance, D. A. B., Wuthiekanun, V. Chaowagul,W. & White, N. J. (1989b).The antimicrobialsusceptibilityof Pseudomonas pseudomullei. Emergenceof resistancein vitro and during treatment. Journal of Antimicrobial Chemotherapy, 24, 295-309.
Dance,D. A. B., Wuthiekanun,V., Naigowit, P. & White, N. J. (1989~).Identificationof PseudmMnas pseudomaller in clinical practice:useof simplescreeningtestsand API 20NE. Journal of Clinical Pathology, 42, 645-648.
Galimand, M. & Dodin, A. (1982). Le point sur la m(lioidose dans le monde. Bulletin de la Soctiti de Pathologie Ewotique, 75, 375-383.
Howe, C., Sampath, A. & Spotnitz, M. (1971). The PseudomalJeigroup: a review. Joumul of Infectious Diseases, 124, 598606.
Jenkins,D. R., Lewis, A. M. & Strachan,C. J. L. (1990). Imported melioidosis in a British native. JournuZof Infection,
21, 221-222.
Khupulsup, K. & Petchclai, B. (1986). Application of indirect haemagglutination test and indirect fluorescent antibody test for IgM antibody for diagnosis of melioidosis in Thailand. American Joumal of Tropical Medicine and Hygiene, 35, 366-369. Kunakorn, M., Boonma, P., Khupulsup, K. & Petchclai, B. (1990). Enzyme-linked immunosorbent assay for immvo#obulin M specific antibody for the diagnosis of F2$ydosis. Journal of Clinical Microbiology, 28, 1249Leelaraskee, A. & Bovomkitti, S. (1989). Melioidosis: review and update. Reviews of Infectious Diseases, 11, 413-425. Levi, M. I. (1960). Current studies of melioidosis and certain tasks for scientific investigation. Zhurnal Mikrobiologii, Epidemiologii i Zmmunobiologii, 31, 133-139. McCormick. J. B., Sexton, D. J., McMurray, J. G., Carey, E., Hayes, P. & Feldman, R. A. (1975). Human-tohuman transmission of Pseudomonas pseudomallei. Annals of Internal Medicine, 83, 512-513. Pruksachartvuthi, S., Aswapokee, N. & Thankerngpol, K. (1990). Survival of Fseudom~s pspdo@lei in human I;:qagocytes. Journal of Medical Mxrobtology, 31, 109-
3 Sheppard, M. J., Marriott, R. M. & Brown, T. J. (1990). Long latency pneumonia: a case of melioidosis. Journul of Infection, 20, 8%84. White, N. J. & Dance, D. A. B. (1988). Clinical and laboratory studies of malaria and mehoidosis. Transactims of theRoyal Societyof Tropical Medicine and Hygiene, 82, 15-20. White, N. J., Dance, D. A. B., Chaowagul, W., Wattanagoon, Y., Wuthiekanun, V. & Pitakwatchara, N. (1989). Halving of mortality of severe melioidosis by ceftazidime. Lancet, ii? 697-700. Whirmore, A. & Knshnaswami, C. S. (1912). An account of
1 Announcement
ROYAL
the discovery of a hitherto undescribed infective disease occurring among the population of Rangoon. Indian Medical Gazette, 47, 262-267. Wongratanacheewin, S., Tattawasart, U. & Lulitanond, V. (1990). An avidin-biotin enzyme-linked tiPuntn&t assay for the detection of Pseudaumcrs antigens. Transactionsof the Rwal So&@ of Tropical Medicine and Hygiene, 84, 429A30. Wuthiekanun, V., Dance, D. A. B., Wattanagoon, Y., Supputtamongkol, Y., Chaowagu!, W. & White, N. J. (1990). The use of selective me& for the isolation of Pseudmnaac pseudoma& in clinical practice. $nmal of Medical Microbiology, 33, 121-126.
1
SOCIETY
OF TROPICAL
MEDICINE
AND
HYGIENE
The Transactions of the Royal Society of Tropical Medicine and Hygiene is issued bi-monthly (six parts per year) and publishes not only papers presented at Society meetings and symposia but also papers and correspondence submitted from all over the world on every aspect of tropical medicine and health. Supplements on specialist topics are published from time to time. The Transactions is available to Libraries and non-Fellows at an annual subscription dispatched by Accelerated Surface Post at no extra charge.
of f%.
It is
The annual subscription to Fellows is E40. Applications for Fellowship must be made on the correct form, obtainable from the address below. Rate for bmtu $de students f25. Further
information
from: The Honorary Secretaries, Royal Society of Tropical Medicine Manson House, 26 Portland Place, London WIN 4EY
and Hygiene,