Spectrum of Opportunistic Infections and Malignancies in Patients with Human Immunodeficiency Virus Infection in South Korea

Clinical Infectious Diseases, Dec 1999

To determine the frequency and types of major opportunistic diseases in patients with HIV infection in South Korea, we reviewed the medical records of 173 HIV-infected patients. The patients were seen from 1985 to 1998 at a referral hospital for AIDS in South Korea. Most patients (85%) were male, and 107 (62%) were infected by heterosexual contacts. CD4+ lymphocyte counts at presentation were <200/µL in 27% of the patients. Tuberculosis was the most frequent opportunistic infection (25% of patients), followed by candidiasis (21%), herpes zoster (20%), Pneumocystis carinii pneumonia (10%), cytomegalovirus disease (9.8%). There were no cases of toxoplasmosis. Kaposi's sarcoma developed in 3 patients (1.7%), and non-Hodgkin's lymphoma, in 2 (1.2%). Eleven patients (6.4%) developed peripheral neuropathy, and 8 (4.6%) had HIV encephalopathy. Tuberculosis was the single most important HIV-related infection in South Korean patients.

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Spectrum of Opportunistic Infections and Malignancies in Patients with Human Immunodeficiency Virus Infection in South Korea

Myoung-don Oh 0 2 Sang Won Park 0 2 Hong Bin Kim 0 2 Ui Seok Kim 0 2 Nam Joong Kim 0 2 Hee Jung Choi 0 2 Dong Hyeon Shin 0 2 Joo Shil Lee 0 1 Kangwon Choe () 0 2 0 Patients. We reviewed the medical records of 173 HIV-infected patients seen from May 1985 to April 1998 at the Seoul National University Hospital, a 1600-bed university-affiliated teaching hos- 1 Center for AIDS Research, National Institute of Health , Seoul, South Korea 2 Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine To determine the frequency and types of major opportunistic diseases in patients with HIV infection in South Korea, we reviewed the medical records of 173 HIV-infected patients. The patients were seen from 1985 to 1998 at a referral hospital for AIDS in South Korea. Most patients (85%) were male, and 107 (62%) were infected by heterosexual contacts. CD4+ lymphocyte counts at presentation were !200/mL in 27% of the patients. Tuberculosis was the most frequent opportunistic infection (25% of patients), followed by candidiasis (21%), herpes zoster (20%), Pneumocystis carinii pneumonia (10%), cytomegalovirus disease (9.8%). There were no cases of toxoplasmosis. Kaposi's sarcoma developed in 3 patients (1.7%), and nonHodgkin's lymphoma, in 2 (1.2%). Eleven patients (6.4%) developed peripheral neuropathy, and 8 (4.6%) had HIV encephalopathy. Tuberculosis was the single most important HIVrelated infection in South Korean patients. - pital and a referral center for patients with HIV infection or AIDS in South Korea. The patients were referred because their CD41 lymphocyte counts were !500/mL or because they developed symptoms presumed to be due to HIV infection. Heterosexual transmission of HIV was presumed if the patients sex partner was known to have HIV infection or the patient had multiple sexual contacts with prostitutes. Homosexual transmission of HIV was presumed only if the patient admitted having sex with men. Patients with CD41 lymphocyte counts !200/mL received trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia. Prophylactic treatments for tuberculosis and other opportunistic infections were not given. Bacille Calmette-Guerin (BCG) vaccine has been recommended for universal childhood immunization since 1960 in South Korea. In South Korea, zidovudine has been available since 1991, didanosine since 1996, and other antiretroviral drugs, including lamivudine and indinavir, since 1997. Patients were treated with zidovudine when they had CD41 lymphocyte counts !500/mL or when they had symptomatic AIDS-related diseases. Of the 173 patients included in this study, 72 were prescribed zidovudine; 72, didanosine; and 9, triple-drug therapy including a protease inhibitor. Diagnoses of opportunistic diseases. Ziehl-Neelsen staining and culture were routinely performed when tuberculosis was suspected. Induced sputum specimens were obtained, and Diff-Quick staining was used to identify P. carinii. Diarrheal stools were sent to a special parasitology laboratory, where modified procedures for acid-fast staining of stool concentrates were employed. For the diagnosis of cytomegalovirus (CMV) retinitis, an ophthalmologist examined patients at regular intervals. Diagnoses of other CMV diseases were made by histological findings. Cases of tuberculosis were classified as definite, probable, or possible: definite if culture for Mycobacterium tuberculosis was positive; probable if clinical symptoms and signs consistent with tuberculosis were present and a stain was positive for acid-fast bacilli or there were histological findings consistent with tuberculosis; possible if clinical and radiological signs consistent with tuberculosis were present and there was improvement with standard antituberculous therapy [4]. The other opportunistic diseases, including P. carinii pneumonia, were diagnosed according to criteria suggested by the Centers for Disease Control and Prevention [5]; AIDSdefining diseases were also diagnosed according to the 1993 case definition of AIDS by the Centers for Disease Control and Prevention, but criteria for CD4 cell counts were not used. Results Patient characteristics. Of the 173 patients, 85% were male, 90% were aged 2049 years, and 93% were infected by sexual contact (table 1). Duration of follow-up ranged from 1 month to 107 months; one-third of the patients were followed up for !6 months. The annual number of patients, including those who were hospitalized, is shown in figure 1. Opportunistic infections. The frequency of opportunistic infections among the 173 patients is shown in table 2. Herpes zoster was by far the most frequent initial opportunistic infection. Herpes zoster developed in 35 patients (20%), and recurred in 8 (23%) of them. Seventeen patients (9.8%) had CMV diseases: retinitis, 14 patients; esophagitis, 4; gastroenteritis, 2; and disseminated disease, 1. Tuberculosis was the most frequent opportunistic infection, developing in 44 patients (25%). The diagnosis of tuberculosis was definite for 18, probable for 10, and possible for 16 of these cases. Of the 8 patients with CD41 lymphocyte counts >200/ mL, 2 (25%) had extrapulmonary tuberculosis, and 6 (75%) had pulmonary tuberculosis. Of the 32 patients with CD41 lymphocyte count !200/mL, 24 (75%) had extrapulmonary tuberculosis, and 8 (25%) had pulmonary tuberculosis. Multidrugresistant M. tuberculosis was isolated from 1 patient. Three patients died; 1 had an infection due to multidrug-resistant M. tuberculosis and 2 had presented with advanced tuberculosis. All other patients responded well to standard antituberculosis agents. P. carinii pneumonia developed in 18 patients (10%); definite diagnoses were made in 10 cases, and presumptive diagnoses were made in 8. None of these patients were receiving prophylactic treatment for P. carinii pneumonia, because either their HIV infection status was unknown or they were lost to followup. Most of the patients with P. carinii pneumonia were in the advanced stages of AIDS (median CD41 lymphocyte count, 16/mL). Cryptosporidium and Isospora belli were the pathogens most frequently isolated from patients with diarrhea. Nontyphi Salmonella and Shigella species were not isolated when stool cultures were performed. Amebic liver abscess developed in 3 patients. Four percent of the patients had serological tests positive for Toxoplasma. CD41 lymphocyte counts at the time of diagnosis of each opportunistic infection are shown in figure 2. Malignancies. Kaposis sarcoma developed in 3 patients Table 1. Baseline characteristics of 173 South Korean patients with HIV infection. No. (%) of patients (1.7%), including 1 with disseminated sarcoma involving the stomach, lung, and thyroid gland. Two of the patients were bisexual men, and 1 was a female prostitute. Non-Hodgkins lymphoma developed in 2 patients (1.2%) patients: 1 with primary CNS lymphoma and 1 with tongue lymphoma. Other malignancies included squamous cell lung cancer (1 patient), bladder cancer (1), and pancreatic cancer (1). Neurological diseases. Eleven patients (6.4%) developed peripheral neuropathy. Of the 11 patients, 2 were prescribed zidovudine and didanosine, 6 zidovudine only, and 3 didanosine only. Eight patients (4.6%) had HIV encephalopathy. Neurological infections were rare. Only 3 patients developed cryptococcal meningitis. There were no patients with tuberculous or bacterial meningitis, nor any with cerebral toxoplasmosis. Hypersensitivity reactions to drugs. Of the 46 patients who were prescribed trimethoprim-sulfamethoxazole for prophylaxis for or treatment of P. carinii pneumonia, none developed hypersensitivity reactions. Of the 44 patients with tuberculosis who were treated with antituberculosis drugs, only 1 developed a hypersensitivity skin rash due to rifampin. First AIDS-defining diseases. Of the 173 patients, 61 developed AIDS-defining diseases. The first AIDS-defining diseases were tuberculosis in 39 patients (64%), esophageal candidiasis in 6 (10%), P. carinii pneumonia in 6 (10%), HIV encephalopathy in 3 (5%), CMV disease in 3 (5%), isospora infection in 2 (3%), cryptococcal meningitis in 1 (2%), and cryptosporidiosis in 1 (2%). Causes of death. Twenty-four patients (14%) died. Causes of death were as follows: pneumonia, 7 patients; disseminated tuberculosis, 3; cryptococcal meningitis, 2; disseminated CMV disease, 1; lung cancer, 1; bacterial peritonitis, 1; liver cirrhosis, 1; unknown, 4; and suicide, 4. Condition Viral NOTE. CMV, cytomegalovirus; PML, progressive multifocal leukoencephalopathy. No. (%) of patients Discussion Since the first case of AIDS in South Korea was reported in 1985, the number of patients with HIV infection has been increasing every year (figure 1). The total number of cases of HIV infection officially reported as of September 1998 was 844 [3]. The prevalence of HIV infection in South Korea has been estimated to be 0.01% (presumed total number of HIV-infected individuals, 3100) [6]. Our data show that the number of symptomatic patients, especially those admitted to our hospital, has been increasing since the mid-1990s. This epidemiological trend reflects the fact that the AIDS epidemic did not begin until the late 1980s in South Korea. The major mode of transmission of HIV was heterosexual contacts, accounting for 62% of the cases. Because homosexuality is culturally unacceptable in South Korean, many homosexuals will not disclose their sexual preferences. Therefore, the rate of heterosexual transmission might be overestimated in this study. Tuberculosis was the single most prevalent disease in HIVinfected patients in this study. Tuberculosis developed in 25% of the patients and accounted for 64% of the first AIDS-defining diseases. These findings are not unexpected given the fact that tuberculosis is one of the most prevalent infectious diseases in South Korea. A recent nationwide survey showed that the prevalence of tuberculosis among people aged 029 years was 15.5% and the prevalence of radiologically active tuberculosis was 1.0% [7]. In countries with high rates of M. tuberculosis infection, particularly in Africa, the number of cases of tuberculosis has increased since the AIDS epidemic began [8]. In contrast, the prevalence of tuberculosis in South Korea has decreased even after HIV infection was introduced in our population. This occurrence could be attributed to the fact that the number of patients with HIV infection is too small to influence the incidence of tuberculosis. The manifestation of tuberculosis in our patients varied according to CD41 lymphocyte counts. For patients with early HIV infection, radiographic findings resembled those seen for patients with reactivation tuberculosis. However, most patients with advanced HIV infection had disseminated tuberculosis, and lymphadenopathy was also common. These findings are consistent with those of previous studies [911]. Of note is the fact that there was only 1 case of infection due to multidrug-resistant M. tuberculosis in South Korean patients with AIDS. The recent nationwide survey [7] revealed that the overall prevalence of drug-resistant M. tuberculosis was 9.9%; the prevalence of resistance to >2 drugs was 6.1%, and the prevalence of resistance to >3 drugs was 4.6%. The fact that iv drug abusers, one of the major groups not compliant with antituberculous treatment, have not been found among South Korean HIV-infected individuals may explain why infection due to multidrug-resistant M. tuberculosis is rare in South Korea. P. carinii pneumonia developed in 10% of our patients. Trimethoprim-sulfamethoxazole was prescribed to all the patients with CD41 lymphocyte counts !200/mL as primary prophylaxis for P. carinii pneumonia. One of the major drawbacks of trimethoprim-sulfamethoxazole prophylaxis is an increased frequency of hypersensitivity reactions in HIV-infected individuals. The frequency of hypersensitivity reactions has been reported to be as high as 25% [12]. However, in our study there were no cases of hypersensitivity reaction due to trimethoprimsulfamethoxazole. Walmsley et al. [13] suggested that genetically determined pathways of metabolism and detoxification of sulfonamides might be involved in the pathogenesis of these reactions, and that patients whose acetylator status is slow have an increased risk for hypersensitivity reactions [14]. To explain the low incidence of hypersensitivity reactions to trimethoprimsulfamethoxazole, further investigation is warranted to elucidate whether the acetylator status of Koreans is fast. Three of our patients had amebic liver abscess; 2 were homosexual. In South Korea, the prevalence of amebic infections has been decreasing rapidly [15]. At our hospital, we have only seen 4 patients with amebic liver abscess since 1995. Among these patients, 3 were HIV-infected. It is of note that 2 of them were found to be HIV-positive after amebic liver abscess was diagnosed. In countries with low prevalences of amebic infestation, amebic liver abscess may be regarded as an opportunistic infection in immunocompromised patients. No patients had toxoplasmosis. The prevalence of Toxoplasma gondii antibodies among our HIV-infected patients was 4%. Most Koreans do not own pets, nor do they come into close contact with dogs or cats (which may be the reason for the low prevalence of toxoplasmosis in South Korea). In contrast, in the United States, where 10%40% of adults with AIDS are latently infected, one-third of these patients will develop toxoplasmic encephalitis. In Africa, Europe, and Latin America, where the incidence of latent infection is much higher, the number of patients with AIDS who develop toxoplasmosis is 3 times greater than that in the United States [16]. Our study is limited by the relatively small number (173) of patients, which accounts for 20% of all cases of HIV infection reported in South Korea. A population-based, prospective study on opportunistic diseases in patients with HIV infection or AIDS is being launched by the Korean AIDS Research Group. References


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Myoung-don Oh, Sang Won Park, Hong Bin Kim, Ui Seok Kim, Nam Joong Kim, Hee Jung Choi, Dong Hyeon Shin, Joo Shil Lee, Kangwon Choe. Spectrum of Opportunistic Infections and Malignancies in Patients with Human Immunodeficiency Virus Infection in South Korea, Clinical Infectious Diseases, 1999, 1524-1528, DOI: 10.1086/313516