The infectiousness of tuberculosis patients coinfected with HIV.
BACKGROUND
The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.


RESULTS
All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour.


CONCLUSIONS
A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.
Escombe
A Roderick
AR
Department of Infectious Diseases and Immunity, Imperial College London, United Kingdom. rod.escombe@imperial.ac.uk
Moore
David A J
DA
Gilman
Robert H
RH
Pan
William
W
Navincopa
Marcos
M
Ticona
Eduardo
E
Martínez
Carlos
C
Caviedes
Luz
L
Sheen
Patricia
P
Gonzalez
Armando
A
Noakes
Catherine J
CJ
Friedland
Jon S
JS
Evans
Carlton A
CA
D000328:Adult; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D015658:HIV Infections / Q000382:microbiology* / Q000635:transmission / Q000821:virology*; D006801:Humans; D008297:Male; D013183:Sputum / Q000382:microbiology / Q000821:virology; D014376:Tuberculosis / Q000382:microbiology* / Q000635:transmission / Q000821:virology*
PLoS Med. 2006 Oct;3(10):e384
17020405
Int J Tuberc Lung Dis. 2005 Oct;9(10):1147-54
16229227
Clin Infect Dis. 2007 May 15;44(10):1349-57
17443474
J Clin Microbiol. 1997 Apr;35(4):907-14
9157152
Clin Infect Dis. 2007 May 15;44(10):1358-60
17443475
JAMA. 2000 May 17;283(19):2537-45
10815117
Am J Respir Crit Care Med. 2004 Mar 1;169(5):604-9
14656754
Tubercle. 1976 Dec;57(4):275-99
827837
Int J Tuberc Lung Dis. 2001 Apr;5(4):321-8
11334250
PLoS Med. 2007 Feb;4(2):e68
17326709
Int J Tuberc Lung Dis. 2003 Nov;7(11):1015-26
14598959
N Engl J Med. 1994 Jun 16;330(24):1710-6
7993412
J Infect Dis. 2003 Dec 15;188(12):1878-84
14673768
Lancet. 2006 Nov 4;368(9547):1575-80
17084757
Am J Epidemiol. 2001 Nov 15;154(10):934-43
11700248
Am J Respir Crit Care Med. 2003 May 15;167(10):1348-54
12519740
Am Rev Respir Dis. 1990 Sep;142(3):505-7
2389901
Br J Dis Chest. 1984 Oct;78(4):317-29
6487525
Am Rev Respir Dis. 1989 May;139(5):1286-94
2653151
J Clin Microbiol. 2002 May;40(5):1873-4
11980982
Am Rev Respir Dis. 1991 Aug;144(2):302-6
1907115
Bull Int Union Tuberc Lung Dis. 1991 Jun-Sep;66(2-3):103-6
1756290
J Infect Dis. 1999 Sep;180(3):726-36
10438361
J Infect Dis. 2007 Aug 15;196 Suppl 1:S108-13
17624819
Am Rev Respir Dis. 1969 Jan;99(1):109-11
5762102
Am Rev Respir Dis. 1962 Apr;85:511-25
14492300
Am Rev Respir Dis. 1982 May;125(5):559-62
7081816
Am J Respir Crit Care Med. 1999 Jul;160(1):203-10
10390401
Respir Res. 2006 Jul 17;7:99
16846493
Am Rev Respir Dis. 1960 Sep;82:358-69
13835667
Am Rev Respir Dis. 1979 Apr;119(4):603-9
443630
Infect Immun. 1992 Nov;60(11):4762-7
1398986
Medicina (B Aires). 2002;62(3):221-5
12150003
Am Rev Respir Dis. 1985 Jul;132(1):125-32
3925826
Am J Epidemiol. 1995 Jul 1;142(1):3-14
7785671
J Clin Microbiol. 2000 Mar;38(3):1203-8
10699023
Lancet. 1999 Feb 6;353(9151):444-9
9989714
Clin Infect Dis. 2001 Dec 1;33(11):1922-30
11692305
Arch Intern Med. 2000 Mar 13;160(5):630-6
10724048