Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine.

Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder.     

人类免疫缺陷病毒与深部真菌感染

人类免疫缺陷病毒（HIV）感染的发病率与致死率很高,已成为人类健康的一大威胁,其中约50％的HIV感染者最终因侵袭性真菌病而死亡。高效抗反转录病毒治疗（HAART）的应用大大降低了 HIV感染者深部真菌病的发生率。因此,深入研究HIV与深部真菌病的关系,对预防、诊断和治疗HIV感染者深部真菌病具有十分重要的意义。本文归纳了HIV感染者深部真菌病的流行病学调查、诊断与治疗进展,有助于临床医师预防和诊治HIV感染者深部真菌病,也为将来新型抗真菌药物的研发提供了思路和方向。     

Immunopathogenesis of hepatitis B virus infection

Hepatitis B virus (HBV) infection is a non-cytopathic hepatotropic virus that can lead to severe liver disease including acute hepatitis, cirrhosis and hepatocellular carcinoma. Successful clearance of the virus as well as the establishment of liver disease is largely driven by a complex interaction between the virus and the host immune response. In this review, the immunological events, including both the innate and adaptive immune response are discussed in the setting of both acute and chronic HBV infection and liver disease.     

Dynamics of hepatitis B virus infection

Mathematical models of the dynamics of HIV and hepatitis C virus infection have proven to be of great utility in understanding pathogenesis and designing better treatments. Here, we review the state of the art in modeling and interpreting data obtained from hepatitis B virus infected patients treated with antiviral agents.     

Failure to deliver hepatitis B vaccine: confessions from a genitourinary medicine clinic.

OBJECTIVE--To audit hepatitis B immunisation of homosexual or bisexual men in a genitourinary medicine clinic. DESIGN--Retrospective case note review of all homosexual and bisexual men presenting to a genitourinary clinic as new patients during 12 months in 1988 and follow up review of notes to May 1990. SETTING--One department of genitourinary medicine, Middlesex Hospital. PATIENTS--758 homosexual or bisexual men, of whom 207 started a course of hepatitis B vaccine in 1988. Case notes were unavailable for one patient. MAIN OUTCOME MEASURES--The proportion of patients screened for hepatitis B virus markers, the proportion of susceptible patients immunised, the proportion completing the vaccine course, and the proportion rendered immune. RESULTS--25 men had been previously tested for hepatitis markers; of the 732 not previously tested, 440 (60.1%) were screened for hepatitis B markers. 207 (69%) of the 300 patients without hepatitis B serological markers started the vaccine course, and 141 (68%) completed it, with 75 (84%) of the 89 tested after immunisation being immune. An estimated 24% of susceptible new patients were rendered immune as a result of the immunisation policy. Patients who presented with a further episode of a sexually transmitted disease were more likely to have been screened (25% v 12%, p less than 0.0001) and immunised (31% v 18% p = 0.02); those known or found to be positive for HIV antibody were more likely to have been screened (23% v 14%, p = 0.047) but less likely to have been immunised (6% v 17%, p = 0.004). CONCLUSIONS--The major failure was that in not screening; failure to immunise patients found to be susceptible and failure of compliance with the vaccine course contributed. Non-response to the vaccine was of minor importance. Improvements in vaccine delivery are required. IMPLICATIONS--Other providers should be encouraged to review their performance.     

Human immunodeficiency virus seroconversion and evolution of the hepatitis C virus quasispecies

When chronic hepatitis C virus (HCV) infections are complicated by acquisition of human immunodeficiency virus (HIV), liver disease appears to accelerate and serum levels of HCV RNA may rise. We hypothesized that HIV might affect the HCV quasispecies by decreasing both complexity (if HIV-induced immunosuppression lessens pressure for selecting HCV substitutions) and the ratio of nonsynonymous (d(N)) to synonymous (d(S)) substitutions, because d(N) may be lower (if there is less selective pressure). To test this hypothesis, we studied the evolution of HCV sequences in 10 persons with chronic HCV infection who seroconverted to HIV and, over the next 3 years, had slow or rapid progression of HIV-associated disease. From each subject, four serum specimens were selected with reference to HIV seroconversion: (i) more than 2 years prior, (ii) less than 2 years prior, (iii) less than 2 years after, and (iv) more than 2 years after. The HCV quasispecies in these specimens was characterized by generating clones containing 1 kb of cDNA that spanned the E1 gene and the E2 hypervariable region 1 (HVR1), followed by analysis of clonal frequencies (via electrophoretic migration) and nucleotide sequences. We examined 1,320 cDNA clones (33 per time point) and 287 sequences (median of 7 per time point). We observed a trend toward lower d(N)/d(S) after HIV seroconversion in 7 of 10 subjects and lower d(N)/d(S) in those with rapid HIV disease progression. However, the magnitude of these differences was small. These results are consistent with the hypothesis that HIV infection alters the HCV quasispecies, but the number of subjects and observation time may be too low to characterize the full effect.     

Detection of hepatitis B virus infection markers at a collective

The occurrence of serological markers of hepatitis B virus infection among the members of a newly formed community (370 persons) was determined. The markers were detected with the use of highly sensitive methods for the detection of HBsAg, anti-HBs, HBeAg, anti-HBc, IgM anti-HBc. At the time of the formation of this community HBsAg, anti-HBs and anti-HBc were detected, respectively, in 4%, 11% and 31.3% and 6 months later, in 8.4%, 9.5% and 46.4% of persons. The presence of a considerable number of inapparent forms of hepatitis B and differences in the degree of the involvement of individual groups in this community into the epidemic process have been shown.     

Prevalence of hepatitis B virus infection in pregnant women in the Montreal area.

From January 1982 to June 1984, 30,315 serum specimens from pregnant women at nine hospitals in the Montreal area were screened for hepatitis B surface antigen (HBsAg). Of the specimens 103, from 98 women, were positive, a prevalence rate of 3.4 per 1000. The ethnic origin of the 98 women and the number who were also positive for e antigen (HBeAg) were as follows: French-Canadian, 29 (3 HBeAg-positive); Asian, 28 (14); Haitian, 32 (0); other, 7 (0); and unknown, 2 (0). The prevalence rates of HBsAg positivity according to ethnic origin at one of the hospitals were 73.9 in Asians, 33.1 in Haitians, 0.9 in French Canadians and 8.0 in women of other extraction. If the prevalence rate found in this study is true for the 95 000 live births that occur yearly in the province of Quebec, there are an estimated 323 infants at risk for hepatitis B virus (HBV) infection each year in the province. Screening programs for detecting HBV carriage in pregnant women should be instituted, since recent studies have shown combined active-passive immunization to be effective in preventing perinatal transmission of HBV infection.     

Human immunodeficiency virus infection in cells of myeloid-monocytic lineage

We established persistent infection with a strain of human immunodeficiency virus type 1, HTLV-IIIB, in a promyelomonocytic cell line, ML-1 (CD4 antigen nearly negative and CD4 mRNA negative), and a promonocytic cell line, THP-1 (CD4 antigen positive). Different reaction of giant cell formation was found after co-cultivation of infected and uninfected cells of ML-1, HL-60, THP-1 and U-937 cell lines with uninfected and infected MOLT4 (a T-lymphoma cell line).     

Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection.

OBJECTIVE--To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN--Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING--Four major medical centres in the United States. PATIENTS--12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES--In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS--Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS--Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.     

Human leukocyte antigen B58 supertype and human immunodeficiency virus type 1 infection in native Africans

Human leukocyte antigen (HLA) class I alleles can be grouped into supertypes according to their shared peptide binding properties. We examined alleles of the HLA-B58 supertype (B58s) in treatment-na?ve human immunodeficiency virus type 1 (HIV-1)-seropositive Africans (423 Zambians and 202 Rwandans). HLA-B and HLA-C alleles were resolved to four digits by a combination of molecular methods, and their respective associations with outcomes of HIV-1 infection were analyzed by statistical procedures appropriate for continuous or categorical data. The effects of the individual alleles on natural HIV-1 infection were heterogeneous. In HIV-1 subtype C-infected Zambians, the mean viral load (VL) was lower among B*5703 (P = 0.01) or B*5703-Cw*18 (P < 0.001) haplotype carriers and higher among B*5802 (P = 0.02) or B*5802-Cw*0602 (P = 0.03) carriers. The B*5801-Cw*03 haplotype showed an association with low VL (P = 0.05), whereas B*5801 as a whole did not. Rwandans with HIV-1 subtype A infection showed associations of B*5703 and B*5802 with slow (P = 0.06) and rapid (P = 0.003) disease progression, respectively. In neither population were B*1516-B*1517 alleles associated with more favorable responses. Overall, B58s alleles, individually or as part of an HLA-B-HLA-C haplotype, appeared to have a distinctive impact on HIV-1 infection among native Africans. As presently defined, B58s alleles cannot be considered uniformly protective against HIV/AIDS in every population.     

The earliest steps in hepatitis B virus infection

The early steps in hepatitis B virus (HBV) infection, a human hepadnavirus, initiates from cell attachment followed by entry and delivery of the genetic information to the nucleus. Despite the fact that these steps determine the virus-related pathogenesis, their molecular basis is poorly understood. Cumulative data suggest that this process can be divided to cell attachment, endocytosis, membrane fusion and post-fusion consecutive steps. These steps are likely to be regulated by the viral envelope proteins and by the cellular membrane, receptors and extracellular matrix. In the absence of animal model for HBV, the duck hepadnavirus DHBV turned out to be a fruitful animal model. Therefore data concerning the early, post-attachment steps in hepadnaviral entry are largely based on studies performed with DHBV in primary duck liver hepatocytes. These studies are now starting to illuminate the mechanisms of hepadnavirus route of cell entry and to provide some new insights on the molecular basis of the strict species specificity of hepadnavirus infection.     

The earliest steps in hepatitis B virus infection

The early steps in hepatitis B virus (HBV) infection, a human hepadnavirus, initiates from cell attachment followed by entry and delivery of the genetic information to the nucleus. Despite the fact that these steps determine the virus-related pathogenesis, their molecular basis is poorly understood. Cumulative data suggest that this process can be divided to cell attachment, endocytosis, membrane fusion and post-fusion consecutive steps. These steps are likely to be regulated by the viral envelope proteins and by the cellular membrane, receptors and extracellular matrix. In the absence of animal model for HBV, the duck hepadnavirus DHBV turned out to be a fruitful animal model. Therefore data concerning the early, post-attachment steps in hepadnaviral entry are largely based on studies performed with DHBV in primary duck liver hepatocytes. These studies are now starting to illuminate the mechanisms of hepadnavirus route of cell entry and to provide some new insights on the molecular basis of the strict species specificity of hepadnavirus infection.     

Modeling the mechanisms of acute hepatitis B virus infection

Mathematical models have been used to understand the factors that govern infectious disease progression in viral infections. Here we focus on hepatitis B virus (HBV) dynamics during the acute stages of the infection and analyze the immune mechanisms responsible for viral clearance. We start by presenting the basic model used to interpret HBV therapy studies conducted in chronically infected patients. We then introduce additional models to study acute infection where immune responses presumably play an important role in determining whether the infection will be cleared or become chronic. We add complexity incrementally and explain each step of the modeling process. Finally, we validate the model against experimental data to determine how well it represents the biological system and, consequently, how useful are its predictions. In particular, we find that a cell-mediated immune response plays an important role in controlling the virus after the peak in viral load.