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Infective endocarditis in northeastern Thailand.

Serologic testing of patients with blood culture-negative endocarditis has identified Coxiella burnetii, the causative agent of Q fever, and Bartonella spp. as noteworthy causes of infective endocarditits (IE) in resource-limited countries (1-4). Many cases of IE that were not diagnosed by standard blood culture were caused by zoonotic bacteria (5). Prospective, systematic descriptions of the etiology and characteristics of IE in Southeast Asia are lacking. We therefore collected detailed clinical, laboratory, and epidemiologic information for patients with confirmed IE in Khon Kaen, Thailand, and conducted specialized testing methods in addition to standard blood cultures to facilitate assessment for zoonotic and nonzoonotic bacteria as the cause of IE.

The Study

During January 25, 2010-July 19, 2012, patients were prospectively enrolled in this study at 2 tertiary care referral hospitals located on the campus of the medical school of Khon Kaen University. Srinagarind Hospital is a 777-bed general hospital, and the Queen Sirikit Heart Center of the Northeast is a 200-bed specialized cardiac center in which [approximately equal to] 10 heart valve replacement surgeries are performed each month. Patients with suspected IE are referred from much of northeastern Thailand, a region of [approximately equal to] 21 million persons.

Transthoracic echocardiography was performed for patients suspected of having IE; consenting patients [greater than or equal to] 16 years of age who met modified Duke criteria for endocarditis were enrolled in this study. Underlying cardiac conditions were assessed by cardiologists on the basis of patients' medical records, history, physical examination, and echocardiographic findings. At admission to a hospital, 3 separate blood samples for culture were obtained in <90 minutes. Blood was inoculated into aerobic medium (BD BACTEC Plus Aerobic/F Medium; Becton Dickinson, Franklin Lakes, NJ, USA), and cultures were processed by using an automated system (BD Bactec Fx series; Becton Dickinson). Pathogens were identified to species level whenever possible, but some blood culture isolates were defined only to the genus level (e.g., viridans group streptococci). One month after admission, a convalescent-phase serum specimen was obtained from each study patient and these patients were evaluated by a cardiologist.

Acute- and convalescent-phase serum specimens were tested for C. burnetii and Legionella pneumophila by indirect immunofluorescence assay (IFA) as described (5). Phase 1 IgG reciprocal titers >800 for C. burnetii and total antibody reciprocal titers [greater than or equal to] 256 for L. pneumophila on either serum specimen were defined as positive (5). IFA IgG reciprocal titers of [greater than or equal to] 800 to Bartonella quintana and Bartonella henselae were deemed positive. Specific antibodies to Brucella melitensis and Mycoplasma pneumoniae were detected with a commercial immunoenzymatic antibody test (Brucella antibody and Platellia M. pneumoniae IgM kits, respectively; Bio-Rad, Marnes-la-Coquette, France). Reciprocal titers [greater than or equal to] 200 were considered positive. DNA was extracted from surgically excised heart valves by using the QIAamp DNA FFPE Tissue Kit (QIAGEN, Courtaboeuf, France) as described by the manufacturer. Previously described broad spectrum PCR primers and amplification and sequencing conditions (4) were used to detect all bacteria (16S rRNA); all fungi (18S rRNA); Staphylococcus aureus, mitis and gallolyticus group streptococci, Enterococcus faecalis and E. faecium, Mycoplasma hominis, C. burnetii, Bartonella spp., and Tropheryma whipplei.

Table 1 describes characteristics of the 132 enrolled patients: the median age was 47 years (range 16-85) and 68.9% were male. Most of the study patients lived in rural areas, most had a history of animal contact, and most were farmers of rice or vegetables. All study patients had definite IE as determined by using modified Duke criteria. Patients had high fever and were severely ill at admission; more than half had congestive heart failure (Table 1). Underlying cardiac pathologic changes were identified in 96 (72.7%) study patients (Table 1); rheumatic heart disease (RHD) was the most common condition, as has been found in other resource-limited countries (1,2,6,7). RHD was identified in 37 (28.0%) of the 132 patients overall; the 37 represented 38.5% of the 96 patients with identified underlying cardiac pathologic changes. IE was detected on prosthetic heart valves in 12 (9.9%) of the study patients, including 2 patients whose blood cultures grew coagulase-negative staphylococci.

Of the 132 study patients, 100 (75.8%) underwent surgery. Such management reflects current international guidelines for complicated IE, which emphasize identifying high-risk patients, transferring them to a specialized medical-surgical center, and performing early valvular surgery (8). Within 1 month, 11 (8.3%) of the 132 patients died and 6 were still hospitalized; 5 died after discharge. Four additional patients are known to have died after leaving the study, but we did not systematically assess survival beyond the 1-month follow-up examination. The case-fatality proportion calculated on the basis of known deaths was 11.4%, but the possibility of additional fatalities cannot be excluded. The mortality rate was 18.8% for patients who did not undergo surgery and 9.0% for those who did.

A pathogen was identified for 60 (45.5%) cases (Table 2). The etiologic agent was identified for 7 (21.9%) of 32 nonsurgical cases, 5 by blood culture and 2 by IFA, compared with 53 (53.0%) of the 100 study patients who underwent surgery (Fisher exact test, p = 0.02). Among patients who underwent surgery, diagnosis was made by PCR of heart valve tissue for 29, by blood culture for 11, and by >1 method for the remaining 13; no discrepancies between results from different diagnostic modalities were found. Many (80.3%) patients had been referred from other hospitals for management of IE and were already being treated for that illness. We confirmed that 77 (58.3%) patients had received antibacterial drugs during the week before admission. We suppose that the low diagnostic yield was associated with antibacterial drug use, but more detailed information is needed to determine the accuracy of this supposition.

Among the 60 cases of IE for which a causative pathogen was identified, 15 (25.0%) were attributed to zoonotic bacteria (Table 2): C. burnetti (5 cases), B. henselae (4 cases), Streptococcus suis (4 cases), Erysipelothrix rhusiopathiae (1 case), and Campylobacter fetus (1 case). B. quintana causes [approximately equal to] 75% of Bartonella IE cases worldwide (9) but was not found in this study. Verification that C. burnetti (10), Bartonella spp. (11), E. rhusiopathiae, and C. fetus cause IE in Thailand highlight the noteworthiness of emerging zoonotic pathogens in this region. The identification of Q fever IE stimulated efforts by public health authorities of Thailand to characterize Q fever prevalence and transmission nationwide.

Streptococci generally cause the majority of infections of native heart valves (12), and 90.1% of patients in this study had native valve involvement. Viridans streptococci, including S. suis, accounted for 43.3% of cases of known etiology (Table 2) and included 3 species of streptococci not previously reported to cause IE in Thailand (S. gallolyticus, S. difficilis, and S. sinensis). In Thailand, as elsewhere, health care-associated IE and IE among intravenous drug users is often caused by S. aureus (13,14). None of the patients in this study were known to be intravenous drug users, and few had health care-associated infections; 5 (8.3%) of 60 cases were caused by S. aureus.


Zoonotic bacteria were detected by specialized testing of 11.4% of IE patients in northeastern Thailand, but an etiology could not be determined for more than half (54.5%) of the patients. Infections with viridans streptococci predominated among cases of known etiology, and RHD was the most common underlying pathologic change. To increase diagnostic yield, we recommend intensification of efforts to obtain blood cultures in the absence of antimicrobial drugs and increase of laboratory capacity to test for zoonotic bacteria (15).

This work was supported by the Global Disease Detection Program and the Division of Vector Borne Infectious Diseases at the Centers for Disease Control and Prevention, USA and the Mediterranee Infection Foundation, Marseille, France.



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(2.) Benslimani A, Fenollar F, Lepidi H, Raoult D. Bacterial zoonoses and infective endocarditis, Algeria. Emerg Infect Dis. 2005;11:216-24.

(3.) Lamas CC, Ramos RG, Lopes GQ, Santos MS, Golebiovski WF, Weksler C, et al. Bartonella and Coxiella infective endocarditis in Brazil: molecular evidence from excised valves from a cardiac surgery referral center in Rio de Janeiro, Brazil, 1998 to 2009. Int J Infect Dis. 2013;17:e65-6.

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(7.) Nunes MCP, Gelape CL, Ferrari TAB. Profile of infective endocarditis at a tertiary care center in Brazil during a seven-year period. Int J Infect Dis. 2010;14:e394-8.

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(11.) Pachirat O, Kosoy M, Bai Y, Prathai S, Puapairoj A, Zeidner N, et al. The first reported case of Bartonella endocarditis in Thailand. Infectious Disease Reports. 2011;3:44-5.

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Dr Watt is a tropical medicine consultant at the International Emerging Infectious Diseases program in the Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration. He is principal investigator of a project that seeks to define the causes and risk factors of infective endocarditis in Thailand. His main research interests are zoonotic infections and interactions between HIV-1 and tropical diseases of public health importance.

Author affiliations: Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand (G. Watt, H.C. Baggett, S.A. Maloney, S. Bhengsri, S. Thamthitiwat, W. Sukwicha, T. Whistler); Khon Kaen University Faculty of Medicine, Khon Kaen, Thailand (O. Pachirat, V. Lulitanond, A. Paupairoj, N. Ud-Ai); Aix Marseille Universite, Marseille, France (D. Raoult, P.-E. Fournier); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (H.C. Baggett, S.A. Maloney, T. Whistler); and Centers for Disease Control and Prevention, Fort Collins, Colorado, USA (M. Kosoy)

Address for correspondence: George Watt, DTM&H; IEIP, DDC 7 Building, 3rd Floor; Ministry of Public Health, Soi 4, Nonthaburi 11000, Thailand; email
Table 1. Characteristics of 132 patients with infective
endocarditis, Khon Kaen, Thailand, January 2010-July 2012

                                                       No. patients
Characteristic                                            (%) *

  Median age, y (range)                                 47 (16-85)
  Male sex                                              91 (68.9)
  Live in rural area                                    111 (84.1)
    Poultry farmer                                      74 (56.1)
    Livestock farmer                                    39 (29.6)
    Rice farmer                                         59 (44.7)
    Vegetable farmer                                    28 (21.2)
    Housewife                                            9 (6.8)
Animal contact
  Own pets                                              92 (69.7)
  Own livestock                                         46 (34.9)
  Own poultry                                           89 (67.4)
Underlying cardiac pathologic changes
  Identified underlying cardiac condition               96 (72.7)
  Rheumatic heart disease                               37 (28.0)
  Mitral valve prolapse                                 19 (14.4)
  Prosthetic heart valve                                 13 (9.9)
  Congenital heart disease                               11 (8.3)
  Degenerative valve disease                             9 (6.8)
  Other cardiac conditions                               4 (3.0)
Clinical findings
  Type of heart valves involved
    Native                                              120 (91.1)
    Prosthetic                                           12 (9.9)
  Heart valves involved overall, n = 132
    Aortic                                              62 (47.0)
    Mitral                                              52 (39.4)
    Tricuspid                                            2 (0.2)
    Aortic and mitral                                    10 (7.6)
    Mitral and pulmonary                                 1 (0.01)
    Aortic and tricuspid                                 1 (0.01)
    Mitral and tricuspid                                 1 (0.01)
    Aortic, mitral, and tricuspid                        1 (0.01)
  Heart valves involved in patients with
      underlying rheumatic heart disease, n = 37
    Aortic                                              21 (56.8)
    Mitral                                              10 (27.0)
    Mitral and aortic                                    5 (13.5)
    Mitral, aortic, and tricuspid                        1 (2.7)
  Days of fever before admission, median (range)        21 (0-270)

Patients receiving antibacterial drugs during           77 (58.3)
  week before admission
Mean [+ or -] SD maximum temperature during          38.3[degrees]C.
  first 24 h after admission                             [+ or -]
Congestive heart failure at admission ([dagger])        64 (48.5)

* Data indicate no. (%) patients with specified characteristic
unless otherwise indicated.

([dagger]) Diagnosis was made by a cardiologist.

Table 2. Bacterial species identified in 60 patients with
infective endocarditis, Khon Kaen, Thailand, January
2010-July 2012 *

Disease type, organisms                      No. (%) cases

Zoonoses                                        15 (25)
  Coxiella burnetti ([dagger])                     5
  Bartonella henselae ([dagger])                   4
  Streptococcus suis                               4
  Erysipelothrix rhusiopathiae ([dagger])          1
  Campylobacter fetus ([dagger])                   1

Nonzoonoses                                     45 (75)
  Enterococcus faecalis                            6
  Enterococcus spp.                                4
  Staphylococcus aureus                            5
  Coagulase-negative Staphylococcus sp.            2
  Viridans streptococci                            5
  Streptococcus agalactiae                         4
  Streptococcus anginosus                          4
  Streptococcus gordonii                           2
  Streptococcus gallolyticus ([dagger])            2
  Streptococcus mitis                              2
  Streptococcus dysgalactiae                       1
  Streptococcus oralis                             1
  Streptococcus difficilis ([dagger])              1
  Streptococcus pneumonia                          1
  Streptococcus sinensis ([dagger])                1
  Streptococcus spp.                               1
  Corynebacterium diptheriae                       1

* No pathogenic agents were identified for 72 (54.6%)
of 132 patients.

([dagger]) Not previously reported to cause infective
endocarditis in Thailand.
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Article Details
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Title Annotation:DISPATCHES
Author:Watt, George; Pachirat, Orathai; Baggett, Henry C.; Maloney, Susan A.; Lulitanond, Viraphong; Raoult
Publication:Emerging Infectious Diseases
Article Type:Report
Geographic Code:9THAI
Date:Mar 1, 2014
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