Short report: disease severity and outcome of melioidosis in HIV coinfected individuals.
ABSTRACT This study examined whether coinfection with HIV and Burkholderia pseudomallei leads to altered disease severity or outcome associated with melioidosis. Coinfection was detected in only 8 of 524 (1.5%) adults with melioidosis in northeast Thailand. Clinical presentation and acute outcome were similar in HIV-positive and HIV-negative patients.
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ABSTRACT: Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei. Individuals with subclinical melioidosis have no apparent clinical signs or symptoms, and are identified only by positive serology. The present study is the first to investigate cell-mediated immune (CMI) responses following in vitro stimulation with B. pseudomallei antigens in peripheral blood mononuclear cells (PBMC), collected under field conditions in Papua New Guinea (PNG) from individuals with exposure to B. pseudomallei (n = 13). While five had a clinical history of melioidosis (C(+)), the remaining individuals (n = 8) were seropositive, yet healthy with no clinical history of melioidosis (S(+)/C(-)). Proliferation and IFN-gamma production were significantly greater in lymphocyte cultures from S(+)/C(-) individuals compared to C(+) individuals (P < 0.001 and P < 0.05, respectively). These findings demonstrate that compared to C(+) patients, individuals with subclinical melioidosis have a stronger CMI response to B. pseudomallei antigens in vitro. Such a response may be essential for protection against disease progression.Clinical Immunology 11/2004; 113(1):22-8. · 3.77 Impact Factor
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ABSTRACT: A preliminary survey was conducted for the prevalence of HIV infections in pulmonary tuberculosis and melioidosis patients in Ubon Ratchathani province, in Thailand, the second largest province in population which supplies labors to Bangkok metropolis. In this province, tuberculosis is prevalent in a higher rate than in most other provinces and melioidosis is endemic. Four HIV-seropositives were found in a total of 551 suspected and culture-positive cases of pulmonary tuberculosis, while no HIV-seropositive was found in 121 melioidosis patients. In view of the rapidly expanding HIV-infections in Thailand, a strict watch will be needed on the future epidemiological status of HIV-infection in tuberculous patient.Japanese journal of medical science & biology 01/1992; 45(5-6):247-53.
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ABSTRACT: Melioidosis is a bacterial infection caused by Burkholderia pseudomallei. The aim of this study was to determine whether a cell-mediated adaptive immune response against B. pseudomallei developed in patients who had recovered from melioidosis. Lymphocyte proliferation assays were done on peripheral blood mononuclear cells from patients (n=13) and control subjects (n=10) to determine the lymphocyte response to B. pseudomallei antigens. Production of interferon-gamma and interleukin-10 was also determined. Activation of T cell subsets was assessed by fluorescence-activated cell sorter analysis, using antibodies to CD4, CD8, and CD69 antigens. Lymphocyte proliferation and interferon-gamma production in response to B. pseudomallei antigens were significantly higher (P<.001 for both) in patients than in control subjects. There was also an increase in the percentage of activated CD4+ (P<.004) and activated CD8+ T cells (P<.035) in cell cultures from patients. The development of such a cell-mediated immune response in patients may be essential for their survival.The Journal of Infectious Diseases 07/2002; 186(2):286-9. · 5.85 Impact Factor
SHORT REPORT: DISEASE SEVERITY AND OUTCOME OF MELIOIDOSIS IN HIV
WIRONGRONG CHIERAKUL,* VANAPORN WUTHIEKANUN, WIPADA CHAOWAGUL, PREMJIT AMORNCHAI,
ALLEN C. CHENG, NICHOLAS J. WHITE, NICHOLAS P. J. DAY, AND SHARON J. PEACOCK
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Medical Department, Sappasithiprasong Hospital, Ubon
Ratchathani, Thailand; Menzies School of Health Research, Charles Darwin University, Darwin, and The Geelong Hospital, Barwon
Health, Geelong Australia; Center for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine,
University of Oxford, Churchill Hospital, Oxford, United Kingdom
severity or outcome associated with melioidosis. Coinfection was detected in only 8 of 524 (1.5%) adults with melioidosis
in northeast Thailand. Clinical presentation and acute outcome were similar in HIV-positive and HIV-negative patients.
This study examined whether coinfection with HIV and Burkholderia pseudomallei leads to altered disease
Melioidosis, an infection caused by the bacterium
Burkholderia pseudomallei, is a major cause of community-
acquired septicemia in northeast Thailand. A wide spectrum
of disease presentations is recognized; septicemia is clinically
similar to that caused by other major pathogens, whereas
subacute and chronic disease may mimic tuberculosis clini-
cally.1There may be prolonged latency between presumed
exposure and disease, and recurrence after apparent cure is
relatively common. Given the clinical features, the intracel-
lular survival of B. pseudomallei, and the lack of protective
humoral immunity, it has been suggested that cell-mediated
immunity may be important in controlling infection with B.
pseudomallei.2,3However, in contrast with the well-described
association between HIV and tuberculosis, the proportion of
patients with melioidosis who are coinfected with HIV is low
and not significantly different to that in apparently healthy
blood donors.4,5In this case series, we describe the clinical
manifestations of patients with melioidosis coinfected with
A retrospective study was performed of patients presenting
to Sappasithiprasong Hospital, Ubon Ratchathani, northeast
Thailand, between 1995 and 2001 with culture-proven melioi-
dosis. These patients had been prospectively recruited by our
study team through active ward surveillance as part of screen-
ing for inclusion into treatment trials. Data were recorded
prospectively and admission sera taken in all cases. The pa-
tients were followed-up long-term by one of the coauthors
(Wipada Chaowagul). Before HIV testing, a clinical database
containing a subset of clinical information minus patient hos-
pital or other identifying numbers was created and linked to
an anonymous serum sample bank. Seven patients were
known to be HIV-positive on presentation with melioidosis,
none of whom had a recorded history of an AIDS defining
illness. Ethical approval for this study was obtained from the
Faculty of Tropical Medicine, Mahidol University, and the
Oxford Tropical Research Ethics Committee.
HIV serology testing was performed according to the
World Health Organization guidelines. All serum samples
were evaluated using a screening test (Serodia-HIV1/2 kit,
Fujirebio, Tokyo, Japan). A negative result was interpreted as
negative. A positive result was confirmed using a second test
(Determine HIV-1/2 kit, Abbott Laboratories, Illinois). Dis-
cordant results were repeated in parallel. For these repeat
samples, two negatives were classified as negative, two posi-
tives as positive, and discrepant results as indeterminate.
A total of 524 patients were evaluated. Of these, 15 were
positive for HIV on the screening test, but only 8 were posi-
tive for HIV by the second test. All indeterminate test
samples were negative on both tests when retested in parallel.
Thus, 8 of 524 patients (1.5%) were considered to be infected
with HIV. Clinical details for patients who tested as HIV-
positive are shown in Table 1. Bacteremia was present on
admission in 5 of 8 (63%) coinfected patients, compared with
291 of 561 (52%) patients who were HIV-negative (P ?
0.73). The total number of body sites culture positive for B.
pseudomallei was not different in the two groups (P ? 0.96).
No patients were known to have tuberculosis. The duration of
hospital stay was shorter for coinfected patients; admission
ranged from 1 to 35 days (median, IQR 8 [2 to 9.5] days) for
coinfected patients compared with 0 to 324 days (median,
IQR 14 [7 to 22] days) for HIV-negative patients (P ? 0.047).
There was no significant difference between the two groups in
mortality (1 of 8 [13%] HIV-positive patients versus 150 of
516 [29%] HIV-negative patients) or recurrent disease (1 of 8
[13%] HIV-positive patients versus 50 of 516 [10%] HIV-
Our finding of a low prevalence of HIV infection in pa-
tients with melioidosis is consistent with a previous small
study in Ubon Ratchathani, where no cases of HIV were
found in 121 patients with melioidosis in 1992.4Additionally,
we did not observe a rise in melioidosis rates at our institution
coincident with the rise of HIV prevalence in the province, in
contrast to rates of other HIV-associated pathogens such as
nontyphoidal Salmonella spp.5These figures are similar to
those in Darwin, Australia, where only one patient with HIV/
AIDS has been noted in 419 melioidosis patients between
1989 and 2005 (Currie BJ, personal communication). The rea-
sons for the lack of interaction between HIV and melioidosis,
and indeed the specific immunologic responses that may be
protective against B. pseudomallei generally, are poorly un-
There are several limitations to this study. The number of
HIV-positive patients was small. We do not have CD4 count
data for the HIV-positive patients; lymphocyte counts were
not used as a surrogate as these are likely to be affected by
acute illness and are not reliable. Information regarding stage
of HIV infection is limited by the anonymous nature of the
database, although the 7 patients already known to be HIV-
positive did not have advanced disease.
* Address correspondence to Wirongrong Chierakul, Department of
Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol
University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand. E-mail:
Am. J. Trop. Med. Hyg., 73(6), 2005, pp. 1165–1166
Copyright © 2005 by The American Society of Tropical Medicine and Hygiene
A specific cell-mediated response against B. pseudomallei
antigens has been noted in immunocompetent survivors of
melioidosis when compared with healthy controls and asymp-
tomatic seropositive patients,2,3suggesting that cell-mediated
immunity may be important in determining resistance to and
the outcome of melioidosis. However, in contrast to diabetes,
thalassemia, and renal disease, HIV infection does not appear
to be a major risk factor for melioidosis. We conclude that
HIV infection does not influence the presentation or outcome
of disease due to B. pseudomallei.
Received July 20, 2005. Accepted for publication August 3, 2005.
Acknowledgments: We are grateful for the assistance of staff at the
Sappasithiprasong Hospital and to Dr. Stuart Blacksell.
Financial support: S.J.P. is supported by a Wellcome Trust Career
Development Award in Clinical Tropical Medicine. This study was a
part of the Wellcome Trust-Mahidol University-Oxford Tropical
Medicine Research Programme funded by the Wellcome Trust.
Authors’ addresses: Wirongrong Chierakul, Vanaporn Wuthiekanun,
and Premjit Amornchai, Faculty of Tropical Medicine, Mahidol Uni-
versity, 420/6 Rajvithi Road, Bangkok, Thailand 10400. Wipada
Chaowagul, Medical Department, Sappasithiprasong Hospital, Sap-
pasith Road, Muang District, Ubon Ratchathani, Thailand. Allen C.
Cheng, Menzies School of Health Research, Charles Darwin Univer-
sity, Darwin, Australia, and The Geelong Hospital, Barwon Health,
Geelong, Australia. Nicholas J. White, Nicholas P. J. Day, and
Sharon J. Peacock, Faculty of Tropical Medicine, Mahidol University,
420/6 Rajvithi Road, Bangkok, Thailand 10400, and Center for Clini-
cal Vaccinology and Tropical Medicine, Nuffield Department of
Clinical Medicine, University of Oxford, Churchill Hospital, Oxford
OX3 7LJ, United Kingdom.
Reprint requests: Dr. Wirongrong Chierakul, Department of Clinical
Tropical Medicine, Faculty of Tropical Medicine, Mahidol Univer-
sity, 420/6 Rajvithi Road, Bangkok, 10400, Thailand. Telephone: 66-
2-354-1395, Fax: 66-2-354-9169, E-mail: firstname.lastname@example.org.
1. White NJ, 2003. Melioidosis. Lancet 361: 1715–1722.
2. Barnes JL, Warner J, Melrose W, Durrheim D, Speare R, Reeder
JC, Ketheesan N, 2004. Adaptive immunity in melioidosis: a
possible role for T cells in determining outcome of infection
with Burkholderia pseudomallei. J Infect Dis 113: 22–28.
3. Ketheesan N, Barnes JL, Ulett GC, VanGessel HJ, Norton RE,
Hirst RG, LaBrooy JT, 2002. Demonstration of a cell-
mediated immune response in melioidosis. J Infect Dis 186:
4. Kanai K, Kurata T, Akksilp S, Auwanit W, Chaowagul V,
Naigowit P, 1992. A preliminary survey for human immuno-
deficient virus (HIV) infections in tuberculosis and melioidosis
patients in Ubon Ratchathani, Thailand. Jpn J Med Sci Biol 45:
5. Chierakul W, Rajanuwong A, Wuthiekanun V, Teerawattanasook
N, Gasiprong M, Simpson A, Chaowagul W, White NJ, 2004.
The changing pattern of bloodstream infections associated
with the rise in HIV prevalence in northeastern Thailand.
Trans R Soc Trop Med Hyg 98: 678–686.
Clinical details for patients coinfected with HIV and B. pseudomallei
Known risk factors
for melioidosis*Blood cultureSite(s) of infectionOutcome
Splenic and liver abscesses
No clinical focus
Lymph node and superficial
Pneumonia, throat swab
Multiple liver abscesses
Multiple splenic abscesses
5 26/male LaborerNone PositiveDied
Survived acute episode,
* Diabetes mellitus, renal impairment, thalassemia, steroid use, or malignancy.
CHIERAKUL AND OTHERS