Extensively Drug-Resistant Mycobacterium tuberculosis, India

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					                                                                                                                              LETTERS


niazid chemoprophylaxis due to resis-       References                                              Extensively
tance of the infecting organism.
     Decreased susceptibility to iso-
                                             1. Kavanaugh A. Health economics: impli-              Drug-Resistant
niazid among M. kansasii isolates is
                                                cations for novel antirheumatic therapies.
                                                Ann Rheum Dis. 2005;64(Suppl 4):S65–9.             Mycobacterium
common (7,8), and this microorgan-           2. Wallis RS, Broder MS, Wong JY, Hanson
                                                ME, Beenhouwer DO. Granulomatous
                                                                                                 tuberculosis, India
ism is naturally resistant to pyrazin-
                                                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-
of lung disease caused by M. kansasii           berculosis risk: mechanisms of action and
                                                                                                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.
mycobacteria.                                   2000;161:S221–47.
                                                                                                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
                                            mlfernandez@fjd.es                                  December 2002, 68 MDR TB isolates

                          Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 9, September 2007                          1429
LETTERS


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-
                                                                                                              Tuberc. 2005;52:121–31.
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.
                                                                                                              1969;41:21–43.
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
                                                                                                                         LETTERS


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: amita602002@yahoo.com        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