Inverse relationship between the titre of TT virus DNA and the CD4 cell count in patients infected with HIV.

OBJECTIVES: To investigate the prevalence and relative titre of TT virus (TTV) DNA, and to examine the relationship between the extent of TTV viraemia and the immune status among 144 patients with HIV infection; 178 age- and sex-matched healthy individuals were also studied. METHODS: TTV DNA was detected quantitatively by two distinct polymerase chain reaction (PCR) methods [untranslated region (UTR) and N22]. UTR PCR detects all TTV genotypes, and N22 PCR can primarily detect four major TTV genotypes (1-4). RESULTS: Using UTR PCR and N22 PCR, respectively, TTV DNA was detected significantly more frequently in HIV-infected patients than in controls (99 versus 91%, P < 0.001; 56 versus 27%, P < 0.0001), and the relative titre (10N/ml) was significantly higher in HIV-infected patients [4.5 +/- 1.2 (mean +/- SD) versus 3.1 +/- 0.9, P < 0.0001; 2.6 +/- 1.5 versus 1.5 +/- 0.9, P < 0.0001]. Age, sex, co-infection with hepatitis B or C virus, and risk factors for HIV transmission did not appear to be significant factors associated with the titre of TTV viraemia. However, the titre of TTV DNA was significantly higher in HIV-infected patients with AIDS (P < 0.0001), those with low CD4 T cell count (P < 0.0001), or those with high HIV viral loads (P = 0.0047). CONCLUSION: TTV is highly prevalent and high-titred in HIV-infected patients. The TTV viral load may reflect the degree of immune status of these immunocompromised hosts.

Quantitative and qualitative abnormalities in HIV-1-specific T cells.

OBJECTIVE: To assess the characteristics of CD4 and CD8 T cells specific for HIV-1 and cytomegalovirus (CMV) antigens in untreated and treated HIV-1-infected patients. METHODS: Antigen-specific T cell frequencies were determined by flow cytometric detection of antigen-induced intracellular cytokines. RESULTS: In untreated patients, HIV-1-specific CD4 T cell counts in peripheral blood were less than one tenth of CMV-specific CD4 T cell counts, while the number of specific CD8 T cells was approximately the same for both HIV-1 and CMV. In patients treated with highly active antiretroviral therapy (HAART) for less than 1.5 years, HIV-1-specific CD4 and CD8T cell counts were significantly lower than those in untreated patients. Perforin expression in HIV-1-specific CD8 T cells was significantly lower than that in CMV-specific CD8 T cells. CONCLUSION: These data indicate that HIV-1-specific T cells in HIV-1-infected patients have quantitative and qualitative abnormalities.

A case of hepatocellular carcinoma in HIV-infected patient.

Persistent human immunodeficiency virus (HIV) infection induces an immuno-suppressive state and therefore malignant tumors are a very common complication. Hepatocellular carcinoma is very rare, however, because it is associated with chronic liver disease by the persistent infection of hepatitis B or C virus (HBV or HCV). We reported a case of HCC with HIV infection who had no evidence of HBV or HCV infection, and that had a rapid growth and active pulmonary metastases. Pathological findings of the resected liver showed moderately differentiated HCC and no chronic liver disease. Despite efforts to find potential HBV integration in tumor and non-tumor tissue, none was observed. To our knowledge, this is the first report of HCC in HIV-infected patient with no evidence of hepatitis virus infection.

[A case of perinatal transmission of human immunodeficiency virus--diagnosis of HIV infection by culture and PCR].

A child born from a mother with HIV infection was reported. We have followed the patient from 3 month old of age. Her HIV antibody disappeared at 7 month by EIA, and at 10 month by WR. But we confirmed her HIV infection by PCR and HIV culture, repeatedly at those times, PCR and HIV culture are thought to be necessary for sero-negative infants born from mothers positive for HIV antibody.

[Varicella in adulthood: clinical features, severity scores, source of infection and complications].

Varicella has been thought to be one of the representative infectious disease in childhood, but recently we are under the impression that adults contracting varicella are increasing in number. On the other hand, they say that varicella generally causes a serious illness in adult patients. So we investigated signs and symptoms of varicella, source of infection, occupations of adult patients, except those who were immunologically compromised, by means of medical records, to know the characteristics of varicella in adulthood. According to the varicella severity score proposed by Nagai et al., varicella in the hospitalized adult patient was found to be much severer than that in children. The most remarkable symptoms, were high fever and sore throat, and these were the main reason of hospitalization in most of our patients. Although severity scores were very high in admitted adult patients with varicella, their clinical courses were not serious, and most of them recovered with only supportive therapy. These patients rarely suffered from complications, like pneumonia. If adult patients with varicella hospitalized in the early stage and received supportive care, they could recover without any complications. In most cases of adult varicella the source of infection was unknown. In the case of married persons, however, many of them were infected through their child. When adults contract varicella, not only the patients themselves suffer from high fever and sore throat, but also they act as the source of infection, if they are medical care workers. Furthermore, in public, the contraction of varicella results a socioeconomic loss from suspension of business caused by the illness. Prophylaxis with varicella vaccine, therefore, should be considered, when there are people who have never contracted varicella, whether or not they are medical staff.

[Two cases of typhoid fever with reduced susceptibility to fluoroquinolones].

Two separate febrile Indian patients who reside in Japan and had recently returned from their country were diagnosed as suffering from typhoid fever. Fluoroquinolone therapy was clinically ineffective and the addition of a third-generation cephalosporin was required in each case. Each strain of Salmonella Typhi was resistant to nalidixic acid in vitro and also showed higher minimal inhibitory concentration to other quinolones than usual susceptible strains. Similar cases of typhoid fever responding poorly to quinolone treatment have been observed in the Indian subcontinent, south-east Asia and central Asia since the early 1990s, and potential spread by travelers into Japan is of serious concern. Although quinolones still remain the drugs of choice for treatment of typhoid fever, physicians should be aware of the possibility and implications of clinical treatment failure.

[Basic and clinical studies of fleroxacin on infectious enteritis. Research Group of AM-833 on infectious enteritis].

A clinical study was conducted on fleroxacin (FLRX) in 143 patients and carriers with infectious enteritis (shigellosis, Salmonella enteritis, Campylobacter enteritis, pathogenic Escherichia coli enteritis, Vibrio parahaemolyticus enteritis, cholera, multiple bacterial infections, pathogen-negative enteritis). Furthermore, its antibacterial activity against clinical isolates, fecal concentration and effect on fecal microflora were conducted. FLRX was administered orally in doses of 200 mg once a day (200 mg group) or 300 mg once a day (300 mg group) for 3 days to cholera, for 7 days to Salmonella enteritis and for 5 days to the other infectious enteritis. The clinical efficacy rates were 100% in both the 200 mg and 300 mg groups. The bacteriological efficacy rates were 100% against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and V. cholerae O1, and 63.6% against Campylobacter spp. in the 200 mg group. The rates of the 300 mg group were 93.3% against Shigella spp., and 100% against Campylobacter spp. and pathogenic E. coli. As adverse effects, skin rash was observed in 1 case each in both groups (1.1%, 2.1%). Abnormal laboratory findings consisted of 1 case of increased eosinophils and 1 case of elevated GOT and GPT levels in the 200 mg group (2.8%), and 1 case of elevated GPT in the 300 mg group (2.9%). The clinical usefulness rates were 92.9% and 93.3% in the 200 mg and 300 mg groups, respectively. Antibacterial activity was somewhat inferior to that fo ciprofloxacin and equal to or better than that of norfloxacin, demonstrating MIC90 values against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and Campylobacter spp. of 0.1, 0.2, 0.1, 0.2 and 0.78 micrograms/ml, respectively. Peak fecal concentrations of the drug were 49.0 micrograms/g and 274.4 micrograms/g in the 200 mg group, and 43.3 micrograms/g and below the detection limit (5.0 micrograms/g) in the 300 mg group. With respect to fecal microflora (4 cases), a decrease in Enterobacteriaceae was observed in 3 cases during dosing. But this change showed a tendency to recover after completion of dosing. No effects were observed on anaerobic bacteria.

[Cryptosporidium diarrhea developing in two Japanese adults--one in AIDS and the other in a normal host. Research Group for Infectious Enteric Diseases, Japan].

Case I: A middle-age homosexual male developed AIDS with Pneumocystis carinii pneumonia (PCP) and esophageal candidiasis in 1986 during his stay in an European country about five months prior to transfer to Tokyo Metropolitan Komagome Hospital, Tokyo, in 1987. He was also diagnosed as having cryptosporidiosis presenting with mild diarrhea a month following the diagnosis of PCP. Diarrhea was successfully treated with spiramycin. On transfer to Tokyo Metropolitan Komagome Hospital, he was febrile but had no diarrhea. Serum HIV and TPHA were positive and his blood lymphocyte subset T4a was markedly decreased. On the 13th day after transfer to the hospital, watery diarrhea appeared. Cryptosporidium oocysts were detected from the feces taken on the 17th hospital day. The patient died of Escherichia coli septicemia on the 38th hospital day. Autopsy finding yielded Cryptosporidium infection widely spread over the stomach, ileum, bile and pancreatic ducts. Case II: A 31-year-old previously healthy female presented with abrupt onset of mucous stool five times daily. Mucous passage continued on the subsequent days despite administration of loperamide, and the passage increased to 20 times daily with mucous to watery diarrhea associated with mild abdominal cramps and nausea on the 4th day after onset of illness. On the 6th day of illness, she visited Tokyo Metropolitan Komagome Hospital. She denied close contact with pet animals or contact with any person presenting diarrhea. She had no recent history of travelling anywhere outside Tokyo. On examination she was an apparently healthy woman except for a slightly distended abdomen with localized tenderness in the right upper quadrant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical study of prulifloxacin on infectious enteritis. Japan Research Committee of Prulifloxacin, Research Group on Infectious Enteritis].

Prulifloxacin (PUFX), a new quinolone antimicrobial agent, was administered to a total of 122 patients and carriers to investigate its clinical efficacy, safety and usefulness in infectious enteritis (bacillary dysentery, enteritis caused by Salmonella spp. and enteropathogenic E. coli, cholera and so on). In addition, the minimum inhibitory concentration (MIC) of UFX (active compound) was determined against each clinical isolate, and compared with that of ciprofloxacin (CPFX), ofloxacin (OFLX), tosufloxacin (TFLX) and nalidixic acid (NA). The correlation between the concentration of UFX in feces and the change of the fecal microflora were also investigated when PUFX was administered to the patients with acute infectious enteritis. A daily dose of 400 mg of PUFX was administered orally in two divided doses (morning and evening) for 5 days, with the exception of 7 days administration against salmonella enteritis and 3 days administration against cholera. 84 cases were adapted for evaluating the usefulness. The clinical efficacy was 100% in all the enteritis except salmonella enteritis, in which it was 88.9% (8/9 cases). On the bacteriological efficacy, the elimination rate was 100% in all isolates except Salmonella spp., in which it was 75.0% (12/16 cases). As for the adverse effect, uriticaria in moderate degree was observed in 1 (0.9%) of 109 cases. Abnormal changes in laboratory findings were seen in 3 (3.0%) of 100 cases, consisting of 1 with eosinophilia and 2 with elevated S-GPT, although they were all slight in degree. The usefulness rate was 65.5% (55/84 cases) for "very useful" and 95.2% (80/84 cases) for "very useful" and "useful". MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae, was 0.025, 0.05, 0.025 and 0.05 microgram/ml, respectively. These values were the same as those of CPFX and TFLX, and superior to OFLX and NA. UFX concentrations in feces followed by administration of PUFX in 3 cases with acute infectious enteritis were higher than that of MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae. The changes of the fecal microflora, which influence the efficacy and safety of PUFX, were not observed.

[Basic and clinical studies of pazufloxacin on infectious enteritis research group of T-3761 on infectious enteritis].

A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.

[Causes of death (1983-1997) in patients infected with human immunodeficiency virus by contaminated blood coagulation factor products: report of the clinical study group on prevention and treatments of HIV infection].

Our group conducted a national survey of patients who had died of acquired immunodeficiency syndrome (AIDS) after being infected with human immunodeficiency virus type 1 (HIV-1) by contaminated blood coagulation factor products. A total of 1446 hospitals, clinics, and other health-care institutions throughout Japan were enrolled in the study, which was supported by the Japanese government Ministry of Health and Welfare with a health sciences grant for research on HIV/AIDS. Of the 1434 registered patients who had been infected with HIV-1 by contaminated blood coagulation factor products, 493 (34%) had died as of Oct. 30, 1997. Most were hemophiliacs. The average CD4+ cell count was 25/microliter for the 398 who died of complications from AIDS, compared to an average of 158/microliter for those who died of other causes. Pneumocystis carinii pneumonia, cytomegalovirus infection, and atypical mycobacterial disease were the main causes of death in patients with AIDS. The annual death rate for AIDS patients in Japan dropped dramatically in 1997, 1 year later than a similar trend observed in the United States. The introduction and widespread adoption of new and effective drugs and treatment regimens for HIV-1 and opportunistic infections will be essential life-saving measures.