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Journal of Clinical Microbiology, April 2001, p. 1571-1576, Vol. 39, No. 4
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.4.1571-1576.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Quantitation of Bacteria in Bone Marrow from Patients with Typhoid Fever: Relationship between Counts and Clinical Features

John Wain,1,2,* Phan Van Be Bay,3 Ha Vinh,4 Nguyen M. Duong,4 To Song Diep,4 Amanda L. Walsh,1,2 Christopher M. Parry,1,2 Robert P. Hasserjian,5 Vo Anh Ho,3 Tran T. Hien,4 Jeremy Farrar,1,2 Nicholas J. White,1,2 and Nicholas P. J. Day1,2

Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases,1 and Centre for Tropical Diseases,4 Ho Chi Minh City, and Dong Thap Provincial Hospital, Cao Lanh, Dong Thap,3 Vietnam, Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, John Radcliffe Hospital, Oxford,2 and Department of Histopathology, Imperial College School of Medicine, Hammersmith Campus, London, W12 0NN,5 United Kingdom

Received 29 August 2000/Returned for modification 11 December 2000/Accepted 30 January 2001

Enteric fever is the only bacterial infection of humans for which bone marrow examination is routinely recommended. A prospective study of the concentrations of bacteria in the bone marrow and their relationship to clinical features was conducted with 120 Vietnamese patients with suspected enteric fever, of whom 89 had confirmed typhoid fever. Ninety-three percent of the Salmonella enterica serovar Typhi samples isolated were resistant to ampicillin, chloramphenicol, and co-trimoxazole. For 81 patients with uncomplicated typhoid and satisfactory bone marrow aspirates, the number of serovar Typhi CFU in bone marrow aspirates was a median value of 9 (interquartile range [IQR], 1 to 85; range, 0.1 to 1,580) compared to 0.3 (IQR, 0.1 to 10; range, 0.1 to 399) CFU/ml in simultaneously sampled blood. The ratio of individual blood counts to bone marrow counts was 10 (IQR, 2.3 to 97.5). The number of bacteria in blood but not bone marrow was correlated inversely with the duration of preceding fever. Thus, with increasing duration of illness the ratio of bone marrow-to-blood bacterial concentrations increased; the median ratio was 4.8 (IQR, 1 to 27.5) during the first week compared with 158 (IQR, 60 to 397) during the third week. After lysing the host cells, the median ratio of viable bone marrow to blood increased, reflecting the higher concentration of intracellular serovar Typhi in the bone marrow. Effective antibiotic pretreatment had a significantly greater effect in reducing blood counts compared to bone marrow counts (P < 0.001). Thus, bacteria in the bone marrow of typhoid patients are less affected by antibiotic treatment than bacteria in the blood. The numbers of bacteria in bone marrow correlated negatively with the white blood cell (R = -0.3, P = 0.006) and platelet counts (R = -0.32, P = 0.01) and positively with fever clearance time after treatment (R = 0.4, P < 0.001). The bacterial load in bone marrow therefore may reflect the clinical course of the infection, and high levels may suppress neutrophil proliferation.

* Corresponding author. Present address: Department of Infectious Diseases and Microbiology, Imperial College Medical School, Norfolk Place, London, W2 1PG, United Kingdom. Phone: 020-7594-3715. Fax: 020-7262-6299. E-mail: j.wain{at}ic.ac.uk.

Journal of Clinical Microbiology, April 2001, p. 1571-1576, Vol. 39, No. 4
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.4.1571-1576.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.