Novel HIV-1 Recombinant Identified in a Foreign Heterosexual Resident in Japan: Relatedness to Recently Reported CRF69_01B, Detected Primarily among Japanese Men Who Have Sex with Men.

We report here an HIV-1 recombinant composed of CRF01_AE and subtype B, with a total of eight recombination breakpoints in the gag-pol and vpr-tat regions. This recombinant was identified from a Myanmarese heterosexual male in Japan and showed the chimera structure identical to recently reported CRF69_01B, detected primarily among men who have sex with men in Japan.

Investigation of emtricitabine-associated skin pigmentation and safety in HIV-1-infected Japanese patients.

Emtricitabine (FTC) has been reported to cause skin pigmentation (SP), and the incidence of SP associated with FTC varied with ethnicity, with a higher rate in African-American patients (8%). We assessed the incidence of SP in Japanese HIV-1-infected patients receiving combination antiretroviral therapy (cART) with FTC for a period of 48 weeks and confirmed new findings of FTC-associated SP, including pathological characteristics. This was a multicenter, prospective, longitudinal non-randomized study. We evaluated the appearance of SP at 48 weeks as the primary endpoint in 155 Japanese patients, and secondary endpoints included the characteristics of the SP (location, color tone, size, and progression). Six cases (3.9%) of SP occurred at a median of 124 days (range: 7-259 days) within 48 weeks. The SP looked like an isolated dark spot, 1-2 mm in diameter, mainly on the hands and/or feet. The severity of all the SPs was mild. Each SP had disappeared or faded at a median of 112 days (range: 28-315 days) with continued FTC. FTC-associated SP was considered to be lentigo simplex by dermatoscopy and pathological appearance. In summary, the incidence of FTC-associated SP in Japanese patients was 3.9%, and was comparable to the previously reported incidence in Asian patients (4%). FTC-associated SP was not associated with any clinically significant symptoms and has little clinical significance.

Intracellular efavirenz levels in peripheral blood mononuclear cells from human immunodeficiency virus-infected individuals.

We describe a novel method for isolating plasma-free peripheral blood mononuclear cells retaining intracellular efavirenz. Quantification of efavirenz in 13 human immunodeficiency virus-infected patients by liquid chromatography-tandem mass spectrometry showed a higher correlation of intracellular levels with unbound plasma levels (accumulation ratio, 1,190) than with total plasma levels.

[A case of disseminated candidiasis as an initial presentation of AIDS].

A 44-year-old woman referred for skin eruptions and an altered mental status was confirmed to have HIV infection on Western Blot analysis. Her CD4+ T cell count was 15/microl. On admission, she appeared quite ill with respiratory distress. Chest X-ray showed bilateral patchy infiltration and pleural effusions. She was treated with cefotaxime, pentamidine, and antituberculosis drugs, but her condition worsened and dopamine was initiated. Intensive treatment failed, and she died the following day. An autopsy showed purplish papules on her face and trunk and multiple white nodules in her liver, spleen and lungs. Culture was positive for Candida Albicans, yielding a diagnosis and of disseminated candidiasis. It is rare for HIV patients to be diagnosed with disseminated candidiasis, since the pathogenesis usually requires disruption of the mucosal barrier. The defense mechanism against disseminated candidiasis is mainly neutrophils and macrophages, and its dysfunction is not a primary characteristic of HIV infection. To the best of our knowledge, this is the first report in Japan of a HIV patient to have disseminated candidiasis.

[Voriconazole as an effective therapy against pulmonary aspergillosis in a man with immunodeficiency virus-infection: a case report].

A 45-year-old homosexual man with pneumocystis pneumonia and esophageal candidiasis tested positive in ELISA and Western blot analysis for HIV-1. His CD4+ T cell count was 43/microL and his HIV-RNA load was 250,000 copies/mL. He was treated with Trimetoprim-Sulfamethoxazole, Prednisolone and Fluconazole. Valganciclovir was added to treat CMV retinitis. During the clinical course, 21 days after admission, the patient presented with a temperature of 39 degrees C and blood analysis showed neutropenia. Cefepime and G-CSF were initiated, but new consolidation was observed in the upper left lobe in chest radiography. He underwent bronchoscopy and lavage culture was positive for Aspergillus fumigatus. Serum testing of galactomannan was also positive and pulmonary aspergillosis was diagnosed. The patient was initially treated with Micafungin but switched to Voriconazole when clinical symptoms worsened. An eventual clinical response was observed and pulmonary aspergillosis was controlled. Unfortunately, he died of sepsis due to MRSA 2 months later. Pulmonary aspergillosis is a devastating complication with poor prognosis in patients with HIV infection. Amphotericin-B has been the mainstay of pulmonary aspergillosis treatment, but reports indicate mortality exceeding 80%. Use of Voriconazole, a relatively new antifungal agent, may lower mortality with fewer adverse effects than conventional antifungal therapy.

Clinical features of 62 imported cases of dengue fever in Japan.

To describe the clinical features of dengue cases in Japan, a retrospective study was conducted on 62 laboratory-confirmed Japanese dengue cases presented to Tokyo Metropolitan Komagome Hospital between 1985 and 2000. Age distribution was from 18 to 62 years old (mean, 31.5 years). All cases were imported from abroad and diagnosed as dengue fever. Clinical manifestations included fever (100%), headache (90%), and skin rash (82%). Laboratory examinations revealed leukocytopenia (71%), thrombocytopenia (57%), elevated levels of serum aspartate aminotransferase (78%), and lactate dehydrogenase (71%). Antibody responses were consistent with that of secondary flavivirus infection in 60% of cases. Severity of symptoms in patients with primary dengue antibody response and those with secondary flavivirus antibody responses didn't show statistical significance. Dengue virus infection should be taken into consideration in the differential diagnosis of febrile patients who recently entered Japan from tropical or subtropical countries.

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

A female patient with malarial nephropathy.

Malaria remains one of the world's major health problems, particularly in developing tropical countries. Imported malaria is reportedly increasing in Western countries. Acute renal failure (ARF) is the most common cause of death in severe malaria. We report the case of a 63-year-old female patient with a history of travel to a rural area in South Africa who was in coma and had a high fever on admission. Thirty percent of her erythrocytes were infected with Plasmodium falciparum. She had cerebral malaria, malarial nephropathy, anemia, hepatic dysfunction, and disseminated intravenous coagulation (DIC). Quinine and artesunate treatment decreased the number of parasites in the blood. To manage renal failure, hemodialysis was performed for 11 days. A relationship between ARF and hepatic dysfunction was suggested. This relationship is an indication of the clinical course of the disease. In this article, we discuss the mechanism underlying the development of malarial nephropathy and its management, particularly the usefulness of hemodialysis.

Differential prevalence of HIV type 1 subtype B and CRF01_AE among different sexual transmission groups in Tokyo, Japan, as revealed by subtype-specific PCR.

We determined the subtype of HIV-1 in 89 infected individuals attending three reference hospitals located in the Tokyo metropolitan area of Japan. Subtyping was performed with subtype-specific polymerase chain re-action (PCR) distinguishing subtype A, B, C, and CRF01_AE and/or phylogenetic analysis of HIV-1 env C2V3C3 sequences. Subtype-specific PCR provided unequivocal results in 97% of samples. Sixty-five subjects were infected with subtype B, 16 with CRFO1_AE, 4 with subtype A, 1 with CRF02_AG, and 3 with subtype C. Among 31 Japanese individuals infected through heterosexual contact, 13 were infected with subtype Band 12 with CRFO1_AE. All of the 41 Japanese men infected through homosexual contact harbored subtype B. These results indicate that subtype B is exclusively predominant in a homosexually transmitted group, whereas subtype B and CRFO1_AE are evenly predominant in a heterosexually transmitted group.

[Cyclosporiasis: four case reports with a review of the literature].

Four patients infected with Cyclospora cayetanensis who sought medical care at the Tokyo Metropolitan Komagome Hospital are herein presented. All were Japanese males, and their ages ranged from 22 to 50 years of age. One patient, who was HIV-positive with a CD4+ lymphocyte count of 141/microliter, demonstrated no AIDS-defining illness. This patient acquired HIV in some Southeast Asian country/countries through heterosexual contact. This patient presented with watery diarrhea with a frequency of up to 18 times a day for more than two months. The other three cases were not considered to be debilitated hosts. Diarrhea occurring from one to ten times a day continued for 6 to 26 days in all of these three patients. The presumed origin of the infection was considered to be Southeast Asian countries and the season of onset of diarrhea was March to July in all four cases. Treatment with a sulfamethoxazole/trimethoprim compound was performed for both the HIV-infected patient and the other non-debilitated patient. Both symptomatic and parasitologic improvements were quickly observed in these patients. A prospective study was performed using fecal specimens from the diarrheal patients to identify the presence of C. cayetanensis during the period from 1996 to 2001. Protozoa-positive specimens were found in 3 of 410 (0.7%) specimens from patients who had traveled overseas, is one of 148 (0.7%) for HIV-infected (the C. cayetanensis-positive patient also acquired the protozoa in Southeast Asia), and in none of 513 (0%) patients who developed diarrhea in Japan. In summary, C. cayetanensis infection is rare in Japan and most patients infected with this pathogen tend to be overseas travelers and HIV-infected individuals at present.