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CLINICAL SCIENCE: CONCISE COMMUNICATION

Multidrug-resistant tuberculosis at an HIV testing center in Haiti

Joseph, Patricea; Severe, Patricea; Ferdinand, Severineb; Goh, Kye Sengb; Sola, Christopheb; Haas, David Wc; Johnson, Warren Dd; Rastogi, Nalinb; Pape, Jean Wa,d; Fitzgerald, Daniel Wd

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doi: 10.1097/01.aids.0000206505.09159.9a
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Abstract

Introduction

Tuberculosis is the major opportunistic infection of HIV/AIDS in developing countries [1,2]. Between 5 and 10% percent of patients presenting for HIV testing in developing countries have active pulmonary tuberculosis [3–5]. Several reports have suggested that HIV-infected individuals may be at increased risk for multidrug-resistant (MDR) tuberculosis [6–10]. High rates of pulmonary MDR-tuberculosis at HIV testing centers in devoloping countries would pose a serious public health threat. In response to the burgeoning HIV epidemic, many developing countries are rapidly expanding the number of HIV voluntary counseling and testing (VCT) centers, and people living in these countries are being encouraged to seek HIV testing at these centers [11–13]. In countries where MDR-tuberculosis is prevalent, VCT centers may attract individuals with active MDR-tuberculosis and individuals with AIDS who are at great risk of developing active tuberculosis if exposed to it. Transmission of M. tuberculosis at VCT centers could thus fuel the spread of MDR-tuberculosis.

We conducted a study at an HIV testing center in Port-au-Prince Haiti to determine the rates and risk factors for MDR-tuberculosis. The annual incidence of M. tuberculosis infection in Haiti is approximately 300 per 100 000 population, which ranks among the highest in the world [14]. Haiti also has a generalized HIV epidemic with approximately 5% of urban adults being HIV infected [15].

Methods

The study was conducted at the HIV testing center of the Haitian Study Group of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) in Port-au-Prince, Haiti. The GHESKIO Center provides free HIV voluntary counseling and testing with integrated primary care services to a poor urban population [16].

Based on a previous report from our center showing high rates of tuberculosis in patients presenting with cough [4], all patients who come to GHESKIO for HIV testing are asked at their first visit if they have a cough [17,18]. Patients who have had a cough for 5 days or longer are screened for active tuberculosis by medical history and physical, chest radiography, and sputum smear for acid fast bacilli (AFB). Suspected tuberculosis is defined as the presence of symptoms and a chest radiograph highly suggestive of tuberculosis. Confirmed tuberculosis is defined as the presence of symptoms and a positive sputum AFB smear. Primary tuberculosis is defined as disease in a patient who reports no past tuberculosis treatment. Recurrent tuberculosis is defined as disease in a patient who reports past tuberculosis treatment. Patients diagnosed with suspected or confirmed tuberculosis are immediately started on anti-mycobacterial treatment on-site following international guidelines [19].

For the current study, all patients aged at least 18 years, with suspected or confirmed tuberculosis between January 2000 and December 2002 were invited to enroll. All participants gave their written consent. Study participants answered an epidemiological questionnaire, had a medical history and physical examination, and were asked to provide sputum for Mycobacterium tuberculosis culture. The culture was performed in Lowenstein–Jensen media after sodium hydroxide digestion, decontamination and concentration.

Drug susceptibility testing was performed by the standard proportionate technique. Isolates were tested for susceptibility to the four first-line anti-tuberculosis drugs: isoniazid, rifampin, streptomycin, and ethambutol. Multidrug-resistant M. tuberculosis was defined by resistance to both isoniazid and rifampin. Primary drug resistance was defined as drug resistance in patients with primary tuberculosis. All drug-resistant isolates were further analyzed at the Pasteur Institute of Guadeloupe to confirm that they were members of the M. tuberculosis complex.

Statistical analysis was performed using SPSS (version 11.5; Chicago, Illinois, USA). All tests were two tailed and P values < 0.05 were considered statistically significant. Comparison of proportions was determined using the chi-squared test. Fisher's exact test was used when cell values were less than five. Comparison of means was done by the Student's t-test and comparison of medians by the Mann–Whitney test.

The study protocol and consent form were approved by the institutional review boards of GHESKIO in Port-au-Prince, Haiti and the Weill Medical College of Cornell University in New York, USA.

Results

Between January 2000 and December 2002, 28 261 patients ≥ 18 years of age came to the GHESKIO Center for HIV testing. Of these, 3708 (13%) reported having cough for at least 5 days and were screened for tuberculosis on the day of arrival to the clinic. Among the 3708 with cough, 925 (25%) were diagnosed with suspected or confirmed tuberculosis.

Of these 925 patients, 330 (36%) had positive sputum culture for M. tuberculosis upon which drug susceptibility testing was performed. The characteristics of these 330 patients are shown in Table 1.

Table 1
Table 1:
Characteristics of 330 patients with positive sputum cultures for M. tuberculosis.

Among the 330 patients, the numbers of isolates that were resistant to each drug were as follows: isoniazid 56 (17%), rifampin 36 (11%), ethambutol 33 (10%), and streptomycin 13 (4%). Twenty six patients (8%) had MDR-tuberculosis. The rates of drug resistance were higher among patients with recurrent tuberculosis than in patients with primary disease (Table 2).

Table 2
Table 2:
Drug resistance among patients with primary and recurrent tuberculosis.

Co-infection with HIV was associated with primary MDR-tuberculosis but not with recurrent MDR-tuberculosis. In patients with primary tuberculosis, 11 (10%) of 115 HIV-infected patients had MDR-tuberculosis compared with five (3%) of 166 HIV-negative patients, (risk ratio, 3.2; 95% confidence interval, 1.1–8.9; P = 0.0331). Among patients with recurrent tuberculosis, none of 16 HIV-infected patients had MDR-tuberculosis compared with 10 (30%) of 33 HIV-negative patients, (P = 0.0197). No other baseline characteristic was associated with primary or recurrent drug resistance.

Discussion

This report documents a high rate of pulmonary tuberculosis and multidrug-resistant disease in individuals seeking HIV testing in Port-au-Prince, Haiti. Patients with HIV co-infection were more likely to have primary MDR-tuberculosis than HIV negative patients.

Previous reports from our group and others have demonstrated that 5–10% of patients presenting for HIV testing in developing countries have active pulmonary tuberculosis [3–5]. The current study expands upon these earlier observations by documenting a high rate of MDR-tuberculosis among patients presenting for HIV testing. Eight percent of all tuberculosis cases diagnosed at this testing center and 6% with primary disease had a multidrug-resistant M. tuberculosis. Epidemiologists define sites with a greater than 5% rate of primary MDR-tuberculosis as ‘hot zones’ where transmission to the general population is likely [20].

The potential risk to patients and medical staff is considerable. On a busy day at GHESKIO, 250 individuals present for HIV counseling and testing. Based on the present data, an estimated 5–10% of these 250 patients would have active pulmonary tuberculosis, of whom 8% would have MDR disease. Thus, on a busy day one or two patients with pulmonary MDR-tuberculosis would sit in our crowded waiting room unless an intervention is introduced to prevent this from happening.

Rates of primary MDR-tuberculosis were higher in HIV-infected patients than in HIV-negative patients. Patients with HIV/AIDS probably frequent health care facilities more often than HIV-negative patients and may therefore be at greater risk for nosocomial acquisition of MDR-tuberculosis. Patients with untreated HIV infection are susceptible to new M. tuberculosis infection, even after completing anti-tuberculous therapy, and HIV-infected patients are at great risk of progressing to active tuberculosis following infection [21–24]. In contrast, rates of recurrent MDR-tuberculosis were higher in HIV-negative than in HIV-infected patients. Recurrent MDR-tuberculosis generally results from repeated courses of unsuccessful anti-tuberculous therapy [25]. We speculate that HIV-infected individuals with high mortality rates are unlikely to survive repeated rounds of unsuccessful anti-tuberculous therapy.

A limitation of this study is that we cannot compare resistance rates at this VCT center with national rates in Haiti, as there is no recent national drug-resistance data. Studies conducted in 1982, 1990, and 1994 showed that the rates of primary MDR-tuberculosis during those years were less than 1% [26–28]. This study was limited to a single site. Similar studies are needed at other VCT centers and in other health care settings in Haiti to determine the full impact of the HIV epidemic on the emergence of MDR-tuberculosis.

We have implemented measures to prevent tuberculosis transmission at our VCT center. These measures include improved ventilation, the creation of outdoor seating, and implementation of rapid on-site tuberculosis screening for all patients with cough [29]. High rates of MDR-tuberculosis reinforce the necessity of such measures to prevent nosocomial transmission at VCT centers.

Acknowledgements

The authors thank Maryse Thimotee, Patricia de Mateis, Edna Eyma, and Marie Marcelle Mabou for assistance with laboratory assays, Ismène Plancher for assistance with patient care and counseling, and Marc Enold Orelus for assistance with data management.

Sponsorship: The project was supported in part by grants AI64021, AI54999 and AI58257 from the National Institute of Allergy and Infectious Diseases and TW006896, TW006901, TW 00018, and TW00002 from the Fogarty International Center of the United States National Institutes of Health and the VIH PAL/ANRS (AC12)-PED grant from the Agence Nationale de Recherches sur le SIDA (ANRS) Paris, France.

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Keywords:

HIV; multidrug-resistant tuberculosis; Haiti

© 2006 Lippincott Williams & Wilkins, Inc.