niazid chemoprophylaxis due to resis- References Extensively
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1. Kavanaugh A. Health economics: impli- Drug-Resistant
niazid among M. kansasii isolates is
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common (7,8), and this microorgan- 2. Wallis RS, Broder MS, Wong JY, Hanson
ME, Beenhouwer DO. Granulomatous
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infectious diseases associated with tumor
amide (9). This pattern of resistance is necrosis factor antagonists. Clin Infect
To the Editor: India is contrib-
a serious obstacle for the use of these Dis. 2004;38:1261–5. uting nearly one third of the world’s
drugs in monotherapy or when com- 3. Gardam MA, Keystone EC, Menzies R, tuberculosis (TB) cases and has the
bined with rifampin in the prevention Manners S, Skamene E, Long R, et al. highest rate of new TB cases (1).
Anti-tumor necrosis factor agents and tu-
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Prevalence of multidrug-resistant TB
(10). clinical management. Lancet Infect Dis. (MDR TB) cases is on the rise in India,
The source of the infection in this 2003;3:148–55. and proportions of new cases of MDR
patient is unknown. In a large series 4. Pfyffer GE, Brown-Elliott BA, Wallace TB have been observed to vary from
RJ. Mycobacterium: general character-
of infectious diseases associated with istics, isolation, and staining procedures.
1.1% to 5.3% in most of the reported
inﬂiximab therapy, nontuberculous In: Murray PR, Baron EJ, Jorgensen JH, studies. The proportion of previously
mycobacteria were isolated in 9% of Pfaller MA, Yolken RH, editors. Manual treated patients with MDR TB varied
the patients who had mycobacterial of clinical microbiology. 8th ed. Washing- from 8% to 67% (2). Although these
ton: ASM Press; 2003;532–59.
diseases (2). As in our patient, these 5. Carmona L, Gómez-Reino JJ, Rodríguez
studies have been conducted in differ-
infections developed shortly after ini- V, Montero D, Pascual E, Mola EM, et ent parts of India, they indicate an in-
tiation of treatment with inﬂiximab, al. Effectiveness of recommendations to creasing trend of MDR TB cases.
which suggests that reactivation of a prevent reactivation of latent tuberculosis MDR TB cases threaten the ef-
infection in patients treated with tumor ne-
latent infection is the most probable crosis factor antagonists. Arthritis Rheum.
fectiveness of chemotherapy for both
origin of the disease. Although a mild- 2005;52:1766–72. treatment and control of TB and re-
ly positive tuberculin skin test result 6. van der Klooster JM, Bosman RJ, Ou- quire the use of second-line drugs that
can be observed in patients infected demans-van Straaten HM, van der Spoel are more expensive, toxic, and less
JI, Wester JP, Zandstra DF. Disseminated
with atypical mycobacteria, the strong tuberculosis, pulmonary aspergillosis and
effective than ﬁrst-line anti-TB drugs
reaction seen in this patient suggests cutaneous herpes simplex infection in a (3). The Green Light Committee es-
a latent infection with M. tuberculosis patient with inﬂiximab and methotrexate. tablished by the Stop TB partners (4),
(10). We could speculate on the possi- Intensive Care Med. 2003;29:2327–9. which ensures the proper use of sec-
7. Alcaide F, Calatayud L, Santia M, Mar-
bility of a double infection with M. tu- tín R. Comparative in vitro activities of
ond-line drugs to prevent increasing
berculosis (contracted through house- linezolid, telithromycin, clarithromycin, drug resistance in MDR TB cases in
hold contacts with his father) and M. levoﬂoxacin, moxiﬂoxacin and four con- resource-limited countries, encoun-
kansasii through environmental expo- ventional drugs against Mycobacterium tered resistance to these drugs. This
kansasii. Antimicrob Agents Chemother.
sure. In this scenario, isoniazid che- 2004;48:4562–5.
led to the emergence of new termi-
moprophylaxis could have prevented 8. Shitrit D, Baum GL, Priess R, Lavy A, Shi- nology in relation to drug-resistant
the former but not the latter. trit AB, Raz M, et al. Pulmonary Mycobac- TB, i.e., extensively drug-resistant
In summary, failure of isoniazid terium kansasii infection in Israel, 1999– TB (XDR TB). XDR TB is deﬁned
2004: clinical features, drug susceptibility,
chemoprophylaxis can be anticipated and outcome. Chest. 2006;129:771–6.
as TB caused by a Mycobacterium tu-
in patients who initiate treatment with 9. Sun Z, Zhang Y. Reduced pyrazinamidase berculosis strain that is resistant to at
inﬂiximab and who have latent in- activity and the natural resistance of My- least rifampin and isoniazid among the
fections due to M. kansasii. Despite cobacterium kansasii to the antituberculo- ﬁrst-line anti-TB drugs (MDR TB) in
sis drug pyrazinamide. Antimicrob Agents
routine antituberculous chemopro- Chemother. 1999;43:537–42.
addition to resistance to any ﬂuoroqui-
phylaxis, patients receiving inﬂiximab 10. American Thoracic Society and Centers nolones and at least 1 of 3 injectable
therapy should be carefully evaluated for Disease Control. Targeted tuberculin second-line drugs (5). A recent report
for lung infection caused by atypical testing and treatment of latent tuberculo- describes the current prevalence of
sis infection. Am J Respir Crit Care Med.
XDR TB worldwide (6). Although In-
dia has high annual risk for TB cases
Manuel L. Fernández-Guerrero,* Address for correspondence: Manuel L. and increasing prevalence of MDR TB
Jaime Esteban,* Fernández-Guerrero, Department of Internal cases, XDR TB has not yet been de-
Carlos Acebes,* Medicine, Fundación Jiménez Díaz, Avda, scribed in India.
and Miguel Górgolas* Reyes Católicos, 2, 28040 Madrid, Spain; email: From December 2000 through
*University of Madrid, Madrid, Spain
email@example.com December 2002, 68 MDR TB isolates
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 9, September 2007 1429
were obtained from sputum samples reomycin), were classiﬁed as XDR of drugs were used in drug susceptibil-
from pulmonary TB patients, referred TB. A total of 5 (7.4%) of 68 MDR ity testing, and the sample size is also
to Department of Microbiology, King TB strains met criteria for XDR TB. not statistically adequate. A communi-
George’s Medical University, Luc- XDR TB isolates were usually resis- ty-based, multicenter study, which in-
know Uttar Pradesh, India, for culture tant to almost all 4 ﬁrst-line and sec- cludes all parts of the country and uses
and sensitivity testing. Drug suscepti- ond-line anti-TB drugs tested (Table). the full spectrum of drugs, is needed to
bility testing for ﬁrst-line drugs was Global data on XDR TB are limited; describe the true prevalence of XDR
performed by 1% proportion method however, a recent article reported that TB in India.
against streptomycin (4 μg/mL), iso- the problem of XDR TB is worldwide
niazid (0.2 μg/mL), rifampin (40 μg/ and includes a prevalence of 6.6% Rajesh Mondal* and Amita Jain*
mL), and ethambutol (2 μg/mL) (7). XDR TB cases in the studied countries *King George’s Medical University, Luc-
The susceptibility of MDR TB isolates (6). The Republic of Korea reports the know, India
against second-line drugs was done by maximum numbers of such cases,
the absolute concentration method with 200 (15.4%) of 1,298 XDR TB References
(MIC) for oﬂoxacin (0.5–16 μg/mL) strains tested from MDR TB patients
1. World Health Organization. Global tuber-
and kanamycin (2–64 μg/mL) and by included in the study. On December 1, culosis control: surveillance, planning, ﬁ-
1% proportional sensitivity method 2006, World AIDS Day, South Africa nancing: Geneva: the Organization; 2005.
for ethionamide (40 μg/mL), p-amino reported >300 cases of XDR TB (9). WHO /HTM/TB/2005.349.
2. Prasad R. Current MDR status. Indian J
salicylic acid (0.5 μg/ml), clarithro- Here, we report, to our knowl-
mycin (2 μg/mL), and capreomycin edge, the ﬁrst XDR TB cases in India 3. Prammananan T, Arjatankool W, Chaip-
(40 μg/mL). Resistance to oﬂoxacin, and the emergence of XDR TB in set- rasert A, Tingtoy N, Leechawengwong M,
kanamycin, and ethionamide was de- tings like India, where adequate moni- Aswapokee N, Leelaramasae A, Dhirapu-
tra C. Second-line drug susceptibilities of
termined by a cut-off of MIC >8 μg/ toring of treatment regimens for MDR
Thai multidrug-resistant Mycobacterium
mL, >64 μg/mL, and >128 μg/mL, TB in TB control programs is difﬁcult tuberculosis isolates. Int J Tuberc Lung
respectively (8). All drugs were pro- to implement due to a huge population Dis. 2005;9:216–9.
cured from Sigma (St. Louis, MO, and the high annual risk of acquiring 4. Gupta R, Cegielski JP, Espinal MA,
Henkens M, Kim JY, Lambregets-Van
USA), and quality control for drug TB is of great concern. A limitation to
Weezenbeek CS, et al. Increasing trans-
susceptibility test was provided by the accurate detection of XDR TB is those parency for health—introducing the Green
Tuberculosis Research Center, Chen- existing tests for resistance to second- Light Committee. Trop Med Int Health.
nai, India. line drugs is not yet standardized and is 2002;7:970–6.
5. World Health Organization. Global tu-
Among 68 MDR strains, 21 were less reproducible than results for ﬁrst-
berculosis control: WHO report. Geneva:
from patients who had never been line drugs (10). Access to management the Organization; 2006. WHO/HTM/
previously treated, and 47 were from and treatment of MDR TB cases with TB/2006.362.
patients whose medical history was second-line drugs, standardized meth- 6. Shah NS, Wright A, Bai GH, Barerra L,
Boulahbal F, Casabona N, et al. World-
positive for anti-tubercular treatment ods, improved diagnostics, and qual-
wide emergence of extensively drug-re-
in the past, for at least 4 weeks. All ity assurance for susceptibility testing sistant tuberculosis. Emerg Infect Dis.
MDR TB isolates were tested for are needed to ensure reliable testing 2007;13:380–7.
susceptibility to second-line drugs, and the design of appropriate drug 7. Canetti G, Fox W, Khomenko A, Mahler
HT, Menon NK, Mitchison DA, et al.
and high resistance to these drugs regimens.
Advances in techniques of testing myco-
was found. MDR strains, which were Our study has some limitations, bacterial drug sensitivity and the use of
further resistant to oﬂoxacin, and to however. The data are not representa- sensitivity testes in tuberculosis control
at least 1 of 2 injectable second-line tive of the whole community and are programmes. Bull World Health Organ.
drugs tested (i.e., kanamycin or cap- limited to 1 hospital. Limited numbers
8. World Health Organization. Guidelines
for drug susceptibility testing for second
Table. Resistance pattern of XDR TB isolates*
line anti-tuberculosis drugs for DOTS
Strain no. Resistant to first-line drugs Resistant to second-line drugs plus. Geneva: the Organization. WHO/
RM 55 S, H, R, E K, O, CAP, CLA, PAS, ETH CDS/TB/2001.288.
RM 490 S, H, R, E K, O, CAP, CLA, PAS, ETH 9. Singh JA, Upshur R, Padayatchi N. XDR
RM 552 S, H, R, E K, O, CAP, CLA, PAS, ETH TB in South Africa: no time for denial or
RM 585† S, H, R, E K, O, CLA, PAS, ETH complacency. PLoS Med. 2007;4:e50.
RM 789 S, H, R, E K, O, CAP, CLA, PAS, ETH 10. Kim SJ. Is second line anti-tuberculo-
*n = 5; XDR TB, extensively drug-resistant tuberculosis; S, streptomycin; H, isoniazid; R, rifampin; sis drug susceptibility testing reliable?
E, ethambutol; K, kanamycin; O, ofloxacin; CAP, capreomycin; CLA, clarithromycin; PAS, p–amino [letter]. Int J Tuberc Lung Dis. 2004;8:
salicylic acid; ETH, ethionamide. 1157–8.
†Sensitive to capreomycin.
1430 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 9, September 2007
Address for correspondence: Amita Jain, Post our study, the prevelance of infection perniciosus, 93 (19.06%) Ph. ariasi,
Graduate Department of Microbiology, King in domestic dogs was 18.4% (51/277), and 3 (0.61%) Ph. sergenti. Phleboto-
George’s Medical University, Lucknow 226003 and the prevelance in stray dogs was mine density ranged from 0.08 to 7.70
UP, India; email: firstname.lastname@example.org 21.6% (21/97), with no statistical dif- specimens/CDC trap/night. Ph. ariasi
ference (p = 0.48, signiﬁcance level was found infected, reﬂecting an over-
95%). These results support the im- all infection rate of 1.22 % (1/82).
portance of the role of stray dogs in In Portugal, Ph. ariasi and Ph.
parasite transmission in Lisbon but perniciosus are the proven vectors of
differ from the 7.8% seroprevalence L. infantum (8). Although phleboto-
found in Madrid, where 1,803 stray mine infection was proven in Lisbon,
Stray Dogs and dogs were studied over a 10-year pe-
riod (3). However, the sample size and
it was low when compared with the
canine infection rate, highlighting
Leishmaniasis in duration of both studies are different. the need for a more extensive vecto-
Urban Areas, In other urban areas of large European rial study in these areas. From 2002
Portugal cities and Brazil, the existence of a
high canine seroprevalence has shown
through 2006, 20 new cases of kala-
azar in immunocompromised patients
To the Editor: In southern Eu- an urbanization of the parasitosis (4,5). (16 children and 4 adults) were diag-
rope, zoonotic visceral leishmaniasis This is associated with an increase in nosed in our laboratory. In spite of
caused by Leishmania infantum used 1-family homes with gardens in the the number of new cases being higher
to be considered a rural disease, but peripheries of cities. Dogs are com- in immunocompromised persons,
it is becoming more prevalent in ur- monly kept in these gardens, which namely, HIV-infected patients, gener-
ban areas. Outbreaks in urban/periur- can provide good habitats for sandﬂies. ally only the cases of immunocompe-
ban settings are associated with the On the other hand, the development tent persons reﬂect natural zoonotic
urbanization of natural zoonotic foci of suburban areas can also lead to an transmission. Immunocompromised
(1). The presence of a high number of increase of solid waste and deﬁcient patients can also experience the reac-
stray dogs in urban/periurban settle- sanitary conditions, thus attracting tivation of an old latent infection or be
ments may contribute to the spread infected stray dogs. The difference in infected by zoonotic transmission or
and increase of new infections. percentage of domestic dogs (39.21%) by anthroponotic transmission with-
A canine survey was performed and stray dogs (28.57%) that appeared out a vector. Despite some studies that
twice a month from December 1, healthy, although infected, was not have shown a direct relationship be-
2002, through December 31, 2003. A statistically signiﬁcant (p = 0.39). The tween the prevalence of leishmaniasis
total of 374 dogs from urban areas of percentage of apparently healthy dogs in canine and human populations, ca-
Lisbon were screened for leishmani- was lower than expected, as different nine leishmaniasis is much more prev-
asis. Owners voluntarily brought 277 studies have shown that more than half alent and more widely distributed than
domestic dogs; 97 stray dogs were of the seropositive dogs are asymp- visceral leishmaniasis, and it does not
from public shelters. Indirect ﬂuores- tomatic (3,6). Moreover, stray dogs strongly correlate with the prevalence
cent assay was used for detection of are more likely to experience deﬁcient in humans (6). Moreover, Ph. ariasi
anti-Leishmania antibodies using a health and nutritional conditions, and and Ph. perniciosus are known to be
cut-off of 1/64, and popliteal lymph we thus expected larger differences preferentially zoophilic.
node aspirates for Novy, Nicolle, and between the 2 groups of animals. Of In domestic dogs, if the owner
MacNeal cultures were tested (2). note, asymptomatic infected dogs can takes preventive measures, the infec-
A high overall prevalence (19.2%) be a source of infection to the vectors, tion risk may be reduced. Stray dogs,
of canine leishmaniasis was found, although symptomatic dogs are more however, are an easier target for infec-
despite use of conventional tests only. effective reservoirs (6). tion and sandﬂy biting due to precari-
The infection rate would probably have Along with the canine survey, ous physical conditions and outdoor
been higher had more sensitive tech- from June through September a to- living habits that make canine leish-
niques, such as molecular tools, been tal of 488 sandﬂies were collected maniasis control much more difﬁcult.
used. During the 1980s, Abranches et from 99 biotopes selected from the In conclusion, sanitary conditions
al. (2) performed a similar seroepide- studied areas where canine or human and animal health must be improved to
miologic survey and found a preva- cases have been diagnosed. The vec- prevent the transmission risk of leish-
lence rate of 5.5%. tors were morphologically identiﬁed maniasis by this group of animals. The
Our results show an increase of ca- by standard entomologic keys (7) as absence of surveillance or preventative
nine leishmaniasis cases in Lisbon. In follows: 392 (80.33%) Phlebotomus measures and equilibrium rupture in
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 9, September 2007 1431