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Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections.

We evaluated the results of treatment for ninety-seven patients (106 infections in ninety-eight hips) who had had either an infection after a total hip arthroplasty or positive intraoperative cultures of specimens obtained during revision of a total hip arthroplasty for presumed aseptic loosening. The patients were managed according to various protocols on the basis of the clinical setting (positive intraoperative cultures, early postoperative infection, late chronic infection, or acute hematogenous infection). Aerobic gram-positive cocci accounted for 109 (74 per cent) of the 147 microbial isolates; gram-negative bacilli, for twenty-one (14 per cent); and anaerobes, for twelve (8 per cent). The white blood-cell count and erythrocyte sedimentation rate were elevated in association with seventeen (16 per cent) and sixty-seven (63 per cent) of the 106 infections, respectively. The mean duration of follow-up was 3.8 years (range, 0.3 to eleven years). A good result was noted after the initial treatment of twenty-eight (90 per cent) of the thirty-one infections that had been diagnosed on the basis of positive intraoperative cultures at the time of the revision, twenty-five (71 per cent) of the thirty-five early postoperative infections, twenty-nine (85 per cent) of the thirty-four late chronic infections, and three of the six acute hematogenous infections. Of the twenty++-one infections for which the initial therapy failed, twelve eventually were eradicated after additional treatment and the hip had a functional prosthesis at the time of follow-up. Of the ninety-seven infections that were treated successfully (there was a functional retained or exchange prosthesis in place at the time of the most recent follow-up and infection had not recurred at least two years after the discontinuation of antibiotic therapy), nine were associated with subsequent aseptic loosening of the prosthesis. The factors associated with recurrent infection were retained bone cement, the number of previous operations, potential immunocompromise, and early postoperative infection after arthroplasty without cement.

Acute Disease↗

Effect of Steinernema glaseri-infected host exudates on movement of conspecific infective juveniles.

The entomopathogenic nematode's decision to infect a host is paramount because once the decision is made it is irrevocable; nematodes that invade a host either develop and achieve reproductive success, or they die. Entomopathogenic nematodes that have a cruiser foraging behavior, such as Steinernema glaseri, follow host-associated cues to locate insects to infect. Most of the host finding and infection dynamics research has focused on the infective juvenile nematodes' responses to cues from live insects such as host-associated volatiles and host contact cues. Few studies focus on how previously infected hosts influence infective juvenile infection behaviors. We investigated how exudates from nematode-infected hosts affect the behavior of S. glaseri infective juveniles. We hypothesized that the infective juvenile's behavioral response to cadavers would change as the state of a nematode-infected host changes during pathogenesis. We examined the effect of exudates collected from infected hosts on infective juvenile locomotory behavior. We detected no effects on nematode repulsion or attraction from exudates produced within the first 48h post-infection. We observed repulsion from accumulated exudates during the 3-48, 3-72, 3-120, and 3-144h intervals. Repulsion from exudates was observed during the 48-66, 72-90, and 120-138h intervals in experiments evaluating daily exudate emissions. The repellent effect of infected host exudates may result in an infective juvenile discriminating between suitable and unsuitable hosts.

Animals↗

Hepatitis C superinfection in hepatitis C virus (HCV)-infected patients transplanted with an HCV-infected kidney.

Hepatitis C virus (HCV) genotypes, determined by polymerase chain reaction with type-specific primers, were studied in 5 already HCV-infected patients receiving kidneys from HCV-infected cadaver donors. Three patients were investigated retrospectively using stored pre- and posttransplantation sera and followed 18-28 months after transplantation. Two recipients with HCV genotype 2b infection had received kidneys from 1 genotype 3a-infected donor. In 1 recipient, HCV 2b was replaced by the donor's type; in the other recipient, a prolonged mixed infection of 3a and 2b occurred. Persistent alanine aminotransferase (ALT) elevation (3- to 5-fold) appeared in both patients. The third patient, also HCV 2b infected when transplanted with an HCV 3a-infected kidney, remained infected with HCV 2b only. Two patients, one with HCV genotype 1b and the other with genotype 3a, were followed prospectively with frequent bleeds (initially biweekly) and genotyping over 14 months after they had received kidneys from 1 HCV genotype 1a-infected donor. The HCV 1b-infected recipient remained infected with 1b only and had minimal biochemical signs of liver injury. In the other recipient, mixed infection of 3a and 1a appeared at week 3 and persisted for several weeks, until only genotype 1a could be detected. This patient had elevated ALT levels before transplantation. After onset of mixed infection, ALT levels increased further for several weeks, and returned to pretransplantation levels when only HCV 1a was found. HCV-infected kidneys transplanted into HCV-infected recipients gave 3 different virus patterns. Most patients benefitted in the short term, but some super-infected patients experienced increased liver damage.

Adult↗

Infectivity in extraneural tissues following intraocular scrapie infection.

Intraocular (i.o.) infection of mice with scrapie produces strain-specific targeting of replication and subsequent pathology within the visual system projection areas in the CNS, but also initiates an extraneural infection. Following i.o. infection with ME7 scrapie, infectivity was detected 24 h later in the Harderian gland, the superficial cervical lymph nodes (SCLNs) and the spleen, but not until 20 days in Peyer's patches and inguinal lymph nodes (ILNs). Persistent low levels of infectivity were found in the Harderian gland (which lies within the orbit), but the presence of PrP could not be confirmed by immunolabelling or Western blotting. SCLNs contained maximal amounts of infectivity by 20 days post-infection and remained at this level throughout the incubation period. ILNs reached a similar plateau at 60 days, as did Peyer's patches at 80 days and spleen at 100 days. Further investigation of the role of the spleen in pathogenesis showed that in contrast to ME7 scrapie, mice infected with 79A scrapie had high levels of infectivity in the spleen by 20 days post-infection, irrespective of the route of infection. In addition, the disease developed more rapidly following direct intrasplenic infection with ME7 scrapie than with intraperitoneal infection. Splenectomy at 7 days either before or after i.o. infection had no effect on the incubation period. These results indicate that the rate of replication of infectivity is both tissue and scrapie-strain dependent, and that extraneural spread of infection can occur via the lymphatic system.

Animals↗

Differential spirochetal infectivities to vector ticks of mice chronically infected by the agent of Lyme disease.

We determined whether the infectivity of the Lyme disease spirochete (Borrelia burgdorferi) to vector ticks varies with the duration of infection in laboratory mice. Thus, noninfected nymphal deer ticks were permitted to feed on two strains of early (2 months after infection) and late (8 months after infection) spirochete-infected mice. The attached ticks were removed from their hosts at specified time intervals and were thereafter examined for spirochetes by direct immunofluorescence microscopy. Spirochetes can be acquired by nymphal ticks as fast as 8 h after attachment. More than 80% of the attached ticks acquired spirochetal infection within 48 h after feeding on early spirochete-infected mice. In contrast, spirochetal infectivity to ticks was less than 50% after feeding on late spirochete-infected mice. The overall infectivity of spirochete-infected mice to ticks correlated with the duration of tick attachment. In addition, there was no adverse effect on the spirochetal infectivity to ticks by high levels of host antibody against spirochetes, and no obvious differences in infectivity to ticks was observed by the site of tick feeding. We conclude that the span of spirochetal infectivity to ticks varies with the duration of infection in mice and suggest that spirochetes may persist and may be evenly distributed in the skin of infected hosts, regardless of prominent host immunity.

Animals↗

Prenatal Schistosoma japonicum infection in piglets: effect of repeated exposure of the dams on treatment efficacy and susceptibility to challenge infections.

This study elucidated the fate of prenatal infections in piglets born by dams repeatedly infected before and during pregnancy with Schistosoma japonicum. Independent variables included repeated infections of the dams and treatment or challenge infection (or both) of the prenatally exposed piglets. Dependant variables were worm counts, fecal and tissue egg counts, weight gain, and gross pathological observations. Fifteen female piglets (the dams) were included, of which 6 received repeated infections with S. japonicum during 6 mo. All dams were inseminated and 10 wk pregnant; 12 of the dams were infected with S. japonicum, of which 6 had been repeatedly infected. Three dams remained uninfected. Eight weeks after delivery, the prenatally exposed piglets (the offspring) were grouped, and 6 of the 12 groups were treated with praziquantel. Four weeks after treatment, 5 groups of piglets were infected with S. japonicum. Groups of piglets were killed either 12 or 22 wk after delivery. Repeated infections of the dam did not prevent establishment of a congenital infection in the pig fetuses. Piglets born with a congenital infection were not resistant to a S. japonicum challenge infection given 12 wk after birth. Neither did praziquantel effectively cure the piglets nor did treatment of the prenatally infected piglets prevent establishment of a challenge infection given 4 wk after treatment. Results of the present study indicate that prenatal exposure, independently of the dam's infection status, may change the host response to challenge infections and treatment after birth.

Animals↗

A retrospective examination of sporozoite-induced and trophozoite-induced infections with Plasmodium ovale: development of parasitologic and clinical immunity during primary infection.

A retrospective analysis was made of clinical and parasitologic parameters in patients with induced Plasmodium ovale infection to document the initial clinical and parasitologic response and their subsequent development of clinical and parasitologic immunity, and to determine the effect of previous homologous and heterologous malaria on subsequent infection with this parasite. The prepatent periods were relatively uniform. Eight patients injected with sporozoites that had been stored frozen had a median prepatent period of 14 days (range = 14-20 days). Thirty-five patients infected via the bites of infected mosquitoes had a median prepatent period of 15 days (range = 12-18 days). In eight patients previously infected with P. vivax, the median prepatent period was 16 days. High-intensity fever (> or = 104 degrees F) was frequently seen, with instances of fever > or = 106 degrees F recorded on many occasions. Fever > 101 degrees F and > 104 degrees F occurred for much shorter periods of time than had been observed in patients infected with P. falciparum. Parasite counts > 10,000/microL were infrequent; in most patients, such parasite counts rarely lasted more than two or three days. Gametocytemia was generally of low density and lasted only a few days. The overall length of the clinical and parasitologic period was much shorter compared with that seen in patients infected with P. falciparum. Previous infection with P. ovale did not prevent reinfection, but resulted in reduced levels of parasitemia and fever. Previous infection with heterologous species of Plasmodium did not prevent infection; some reduction in the frequency and intensity of fever and parasite counts was evident. Previous infection with homologous or heterologous parasites failed to eliminate the production of infective gametocytes. A total of 462 lots of mosquitoes were fed on 67 patients with no previous history of infection. Of these feedings, 168 (36.4%) resulted in infection as determined by the presence of oocysts on the midguts of dissected mosquitoes. As shown, the infection rate increased with the density of gametocytes even though 48 (23.4%) of 205 lots of mosquitoes fed when no gametocytes were detected were infected.

Animals↗

Prediction of poorer prognosis by infection with antibiotic-resistant gram-positive cocci than by infection with antibiotic-sensitive strains.

HYPOTHESES: Surgical patients with antibiotic-resistant gram-positive coccal (GPC) infections have a poorer prognosis than those with antibiotic-sensitive GPC infections, and colonization with resistant GPC predisposes to the development of resistant GPC infections. DESIGN: All infections among surgical patients from December 1, 1996, to December 1, 1998, were followed up prospectively. Patients with antibiotic-sensitive and antibiotic-resistant GPC infections were compared. Cohorts were also subdivided on the basis of GPC species, colonization status, and immunosuppression. SETTING: The surgical wards and intensive care units of a tertiary care, university hospital. MAIN OUTCOME MEASURES: In-hospital mortality, inhospital mortality during antibiotic therapy, length of stay, and length of stay from the time of initiation of antibiotics to discharge. RESULTS: Antibiotic-resistant GPC infection compared ki4th antibiotic-sensitive GPC infection was associated with a higher mortality and previous colonization rate (25.8% and 31.0% vs 17.6% and 8.8%, respectively; P = .04 and P<.001, respectively) and a markedly longer length of stay (55.0 +/- 3.3 vs 31.0 +/- 2.0 days; P<.001). Length of stay and treatment to discharge times were longer after resistant Staphylococcus aureus infections than after resistant Staphylococcus epidermidis infections. The mortality and length of stay of patients with gentamicin-resistant or vancomycin-resistant enterococcal infections were equivalently higher than those with antibiotic-sensitive enterococcal infections. Transplant recipients with resistant enterococcal infection had the highest mortality (41.9%). CONCLUSIONS: Surgical patients who develop antibiotic-resistant GPC infections have a significantly higher mortality rate, longer length of stay, and longer treatment to discharge time than patients with antibiotic-sensitive GPC infections. Colonization with resistant GPC predisposes to resistant GPC infection. Gentamicin-resistant enterococcus appears to be as virulent as vancomycin-resistant enterococcus.

Drug Resistance, Microbial↗

High-energy, high-protein, oral, liquid, nutrition supplementation in patients with HIV infection: effect on weight status in relation to incidence of secondary infection.

OBJECTIVE: to evaluate the use of high-energy, high-protein, oral, liquid, nutrition supplementation and nutrition counseling on the weight status of patients infected with the human immunodeficiency virus (HIV) with and without secondary infections. DESIGN: Prospective, descriptive, intervention trial. Follow-up clinic visits were scheduled every 1 to 3 weeks for at least 6 weeks to monitor weight, gastrointestinal symptoms, number of supplements consumed, and incidence of secondary infections. SUBJECTS/SETTING: Community-based, HIV-infected patients, with and without an acquired immunodeficiency syndrome (AIDS) defining illness, who were receiving outpatient medical care at Deaconess Hospital. Twenty-two patients enrolled; however, 4 dropped out and 1 died, so 17 were eligible for evaluation. INTERVENTION: Dietary counseling consisted of recommendations to consume a high-protein diet (1.5 g/kg ideal body weight); select foods that minimize gastrointestinal complications; and take at least one high-energy, high-protein, oral, liquid, nutrition supplement daily. MAIN OUTCOME MEASURES: Energy intake from the supplements and weight change over time in relation to whether a secondary infection occurred. STATISTICAL ANALYSIS: Means, standard deviations, and frequency. RESULTS: At the time of entry to the study, the patients with preexisting weight loss (16 of 17) were 14+/-8% below their usual body weight. On average, patients consumed 11+/-4 supplements per week for 6+/-3 weeks. The majority (12 of 17) were able to gain or maintain weight. Overall weight change was 1.1+/-2.2 kg. Only 5 of 17 patients lost weight, 4 of whom developed a secondary infection during the study (ie, after enrollment in the study). All of those who developed a secondary infection were classified as having AIDS and had lower mean CD4 counts at baseline than those who did not develop a secondary infection. Although those who developed a secondary infection had a higher incidence of weight loss, their consumption of oral supplements per week was greater than that of those without a secondary infection. APPLICATIONS/CONCLUSIONS: In patients with HIV infection and in the early stages of AIDS without a secondary infection, weight gain and/or maintenance was achievable with a high-energy, high-protein, oral, liquid, nutrition supplement in conjunction with nutrition counseling. The majority of the patients who developed a secondary infection, however, lost weight despite the use of supplements and counseling. Use of a high-energy, high-protein, oral, liquid, nutrition supplement, with intact nutrients, should be the first-line nutrition treatment for malnourished, HIV-infected patients without secondary infections.

AIDS-Related Opportunistic Infections↗

Surgical site infections in patients undergoing major operations in a university hospital: using standardized infection ratio as a benchmarking tool.

BACKGROUND: Because patterns of infection acquired in patients undergoing operation are ever changing, it is an essential part of nosocomial infection surveillance programs to periodically document the epidemiologic features of infection in these patients. This study was conducted with the primary intention of describing the incidence and risk factors of the surgical site infection (SSI). METHODS: We performed a prospective study in patients undergoing certain major operations at a 750-bed university hospital in Thailand. The National Nosocomial Infection Surveillance (NNIS) system method and criteria were used for identifying and diagnosing infection. The infection rates were benchmarked with the NNIS report by means of indirect standardization and reported in terms of standardized infection ratio. Risk factors for SSI were evaluated using the multiple logistic regression model. RESULTS: From September 1998 to March 2000, the study included 4193 patients with 4437 major operations. The study identified 192 SSIs, 76 urinary catheter-related urinary tract infections, 26 central line-related bloodstream infections, and 39 instances of ventilator-associated pneumonia (VAP), yielding an infection rate of 4.3 SSIs/100 operations, 11.0 catheter-related urinary tract infections/1000 urinary catheter-days, 6.1 central line-related bloodstream infections/1000 central line-days, and 11.0 VAPs/1000 ventilator-days. When compared with data from NNIS, the standardized infection ratio of SSI, catheter-related urinary tract infection, central line-related bloodstream infection, and VAP were 2.3, 2.1, 1.1, and 0.8, respectively. The factors that significantly associated with SSI were duration of operation in minutes, American Society of Anesthesiologists (ASA) class, and degree of wound contamination. CONCLUSION: All of the infection rates identified, except VAP, were higher than the average NNIS rates. The risk factors for SSI were prolonged duration of operation, poor physical status according to ASA classification, and higher degree of wound contamination.

Adolescent↗

Mycobacterium avium infection in HIV-1-infected subjects increases monokine secretion and is associated with enhanced viral load and diminished immune response to viral antigens.

The complex interaction between HIV-1 infection and Mycobacterium avium was studied. Viral burden was assessed, as well as immune response to HIV-1 in the context of Myco. avium infections. We also examined serum cytokine levels and cytokine release by blood mononuclear cells in HIV-1-infected subjects, infected or not with Myco. avium. Undetectable serum levels of IL-1, tumour necrosis factor-alpha (TNF-alpha) and IL-6 were found in normal controls and in groups I, II and III of HIV-1-infected subjects. Moderate levels of TNF-alpha, IL-1 and IL-6 were found in the sera of group IV patients. When group IV was subdivided into subjects with and without Myco. avium infections, subjects with Myco, avium infections were shown to have higher serum levels of TNF-alpha, IL-1 beta and IL-6 than those with other infections. Blood mononuclear cells from controls and HIV subjects were stimulated with bacterial lipopolysaccharide, and cytokine levels assessed. Cells from group II patients were shown to secrete normal levels of TNF-alpha and IL-6, and lower levels of IL-1 beta; group III subjects released higher levels of IL-6. Patients in group IV had blood cells that released elevated levels of IL-6 and TNF-alpha, and lower levels of IL-1 beta. Group IV subjects with Myco. avium infections had blood cells that released higher levels of TNF-alpha, IL-6 and IL-1 than group IV subjects with other infections. Assessment of viral burden in cells of HIV-1-infected subjects revealed that Myco. avium-infected subjects had a higher level of virus burden and a lower level of lymphoproliferative response to an inactivated gp120-depleted HIV-1 antigen than AIDS subjects with other infections. These data suggest that Myco. avium infections in HIV-1-infected subjects hasten the progression of viral disease, enhance cytokine release and contribute to the anergy to viral antigens.

AIDS-Related Opportunistic Infections↗

Identification of directly infected cells in the bone marrow of neonatal moloney murine leukemia virus-infected mice by use of a moloney murine leukemia virus-based vector.

Early bone marrow infection of Moloney murine leukemia virus (M-MuLV)-infected mice was studied. Previous experiments indicated that early bone marrow infection is essential for the efficient development of T lymphoma. In order to identify the cellular pathway of infection in the bone marrow, infection of mice with a helper-free replication-defective M-MuLV-based retroviral vector was carried out. Such a vector will undergo only one round of infection, without spreading to other cells; thus, cells infected by the initially injected virus (directly infected cells) can be identified. For these experiments, the BAG vector that expresses bacterial beta-galactosidase was employed. Neonatal NIH/Swiss mice were inoculated intraperitoneally with ca. 10(6) infectious units of a BAG vector pseudotyped with M-MuLV proteins, and bone marrow cells were recovered 2 to 12 days postinfection. Single-cell suspensions were tested for infection by staining with X-Gal (5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside) or by immunofluorescence with an anti-beta-galactosidase antibody. Two sizes of infected cells were evident: large multinucleated cells and small nondescript (presumptively hematopoietic) cells. Secondary stains for lineage-specific markers indicated that the large cells were osteoclasts. Some of the small cells expressed nonspecific esterase, which placed them in the myeloid lineage, but they lacked markers for hematopoietic progenitors (mac-1, gr-1, sca-1, and CD34). These results provide evidence for primary M-MuLV infection of osteoclasts or osteoclast progenitors in the bone marrow, and they suggest that known hematopoietic progenitors are not primary targets for infection. However, the subsequent spread of infection to hematopoietic progenitors was indicated, since bone marrow from mice infected in parallel with replication-competent wild-type M-MuLV showed detectable infection in small cells positive for mac-1 or CD34, as well as in osteoclasts.

3T3 Cells↗

Effects of infection with Eimeria tenella upon Salmonella typhimurium infection in the gnotobiotic chicks. Scanning electron microscopic study.

The gnotobiotic chicks infected with Eimeria tenella received an oral inoculation of Salmonella typhimurium 4 or 8 days after E. tenella infection. Chicks were necropsied one day after the salmonella infection. In the experiments 1 and 2, there were two groups; birds infected with S. typhimurium alone and birds infected with a combination of E. tenella and S. typhimurium. The number of S. typhimurium in the cecal contents was significantly greater in the concurrent infections than S. typhimurium infection alone. The S. typhimurium counts in the cecal wall of gnotobiotic chickens killed 5 days after E. tenella infection were significantly greater than those of chickens infected with S. typhimurium alone. In the experiment 3, the scanning electron microscopic study was made on damage of cecal mucosa. There were four groups; uninfected birds as control, birds infected with E. tenella, birds infected with S. typhimurium and birds infected with a combination of E. tenella and S. typhimurium. No damage was observed on the cecal mucosa of both the control and the S. typhimurium infection alone. The concurrent infections caused greater damage on the cecal mucosa than did the E. tenella infection alone.

Animals↗

Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways.

Cells infected with two related retroviruses can generate heterozygous virions, which are the precursors of recombinant proviruses. Although many studies have focused on the frequencies and mechanisms of retroviral recombination, little is known about the dynamics of double infection. To examine this issue, viruses generated from two HIV-1 vectors containing different markers were mixed together, and were used to infect target cells. The numbers of cells expressing none, one, or both markers were measured and were used to calculate whether double infection occurred at frequencies expected from random infection events. We found that double infection occurred significantly more frequently than predicted from random distribution; increased rates of double infection were observed in both a T cell line and primary activated CD4(+) T cells. In addition to direct virus infection, we also examined the nature of cell-mediated HIV-1 double infection. Increased double infection was observed in all experiments regardless of whether a cell line or primary human dendritic cells were used for capture and transmission of HIV-1. Therefore, our results indicate that HIV-1 double infection occurs more frequently than it would at random in both direct and cell-mediated HIV-1 infections. To our knowledge, this is the first direct evidence of nonrandom double infection in HIV-1. Frequent double HIV-1 infections in infected individuals would allow the generation of recombinant viruses that could then affect their pathogenesis and evolution.

CD4-Positive T-Lymphocytes↗

Influence of human immunodeficiency virus type 1 infection on acute hepatitis A virus infection.

To assess the possible influence of human immunodeficiency virus type 1 (HIV-1) infection on the clinical course of acute hepatitis A virus (HAV) infection, 15 HIV-1-infected homosexual men and 15 non-HIV-infected age-matched subjects were compared. HAV load was higher in HIV-1-infected than in non-HIV-infected patients (P<.001). Duration of viremia in HIV-1-infected patients (median, 53 days) was significantly (P<.05) longer than in non-HIV-infected patients (median, 22 days). HIV-1-infected patients had lower elevations in alanine aminotransferase levels than did non-HIV-infected patients (P<.01) but had higher elevations in alkaline phosphatase levels than did non-HIV-infected patients (P<.001). Some HIV-1-infected patients still had HAV viremia when clinical symptoms had disappeared and alanine aminotransferase levels had returned to normal (60-90 days after the onset of symptoms). HIV-1 infection was associated with prolongation of HAV viremia, which might cause a long-lasting outbreak of HAV infection in HIV-1-infected homosexual men.

Acute Disease↗

Does hepatitis C virus co-infection accelerate clinical and immunological evolution of HIV-infected patients?

OBJECTIVE: To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. DESIGN: A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. METHODS: One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 x 10(6) cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Peto's tests) and multivariate methods (Cox's model). RESULTS: In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09-109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P < 0.02) for patients with an initial CD4 count above 600 x 10(6) cells/l. CONCLUSIONS: Clinical progression is more rapid in HIV-HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 x 10(6) cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.

Adult↗

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection.

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.

Adolescent↗

Effect of immunoglobulin G isotype on the infectivity of Chlamydia trachomatis in a mouse model of intravaginal infection.

It has been previously shown with an in vitro neutralization system that monoclonal antibodies (MAbs) to the major outer membrane protein (MOMP) of Chlamydia trachomatis, depending on the isotype of the MAb and the host cell used, can either neutralize or enhance the infectivity of this organism. MAbs to variable domain 4 (VD 4) of MOMP have been described that neutralize the infectivity of C. trachomatis when tested in a system in which either the host cell does not have detectable Fc gammaRIII receptors or complement is added to block the interaction of the MAb with the receptor. However, if Fc gammaRIII receptors are available, immunoglobulin G2b (IgG2b) MAbs to the VD 4 are able to enhance the infectivity of this pathogen. Two MAbs that recognize the sequence TLNPTIA in VD 4 of the MOMP but differ in isotype, E4 (IgG2b) and E21 (IgG1), were used to test whether in vivo the isotype of the MAb modulates the outcome of a vaginal infection in a murine model. A third MAb, CP33 (IgG2b), that recognizes the chlamydial lipopolysaccharide but does not neutralize infectivity of C. trachomatis, was also tested. Elementary bodies (EBs) of C. trachomatis, serovar E (BOUR), were pretreated with the three MAbs and were used to inoculate the vaginas of C3H/HeJ mice which had been pretreated with progesterone. Subsequently mice were monitored over a 5-week period with vaginal cultures. In the groups that were inoculated with EBs pretreated with MAbs directed to VD 4 of MOMP, there was a significant decrease (P < 0.05) in the number of mice infected. Only 30% of the mice were infected in the MAb E4-treated group, and 10% were infected in the MAb E21 group. This was in contrast to the groups inoculated with EBs pretreated with MAb CP33 and control untreated EBs, which resulted in 100 and 79% of the mice infected, respectively. Therefore, in this setting in which EBs were introduced in vivo coated with MAb, there was no enhancement of infection by IgG2b MAbs; rather, the results paralled the in vitro neutralization results, in which cells lacking Fc gammaRIII receptors were employed. Mice were also given the MAbs, as well as purified IgG as a control, by intraperitoneal injection before and after intravaginal inoculation with C. trachomatis. Despite relatively high levels of MAbs in serum and detectable levels of MAbs in the vagina at the time of infection, there was only modest protection in animals receiving MAb E21, with 60% of the mice infected in contrast to 90% of the mice receiving MAb E4, MAb CP33, and IgG. However, by the second week of infection compared to controls, there was a significant increase (P < 0.05) in the amount of chlamydiae recovered from the vaginas of mice that had received the two IgG2b MAbs, E4 and CP33. In summary, the presence of IgG2b MAbs directed to surface components of C. trachomatis at certain times during the course of infection may play a role in enhancing the infectivity of this pathogen.

Animals↗