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Sexually transmitted infections in European HIV-infected women: incidence in relation to time from infection. European Study on the Natural History of HIV Infection in Women.

OBJECTIVES: To investigate the prevalence and incidence of sexually transmitted infections (STI) in HIV-infected women in relation to time from infection and sexual behaviour. DESIGN: The European study on the natural history of HIV infection in women is a prospective cohort study of 487 HIV-infected women with a known interval of seroconversion from 12 European countries. METHODS: Incidence was measured with person-time methods. Generalized estimating equations analysis was used to determine risk factors for STI. RESULTS: At entry, 15% of the women were diagnosed with at least one acute STI (chlamydial infection, trichomoniasis or gonorrhoea), 10% with at least one other STI (genital warts or genital ulcerations) and 13% with vaginal candidiasis. Although frequently diagnosed during follow-up, the occurrence of acute STI and vaginal candidiasis decreased, whereas the occurrence of other STI increased with ongoing time from HIV infection. Furthermore, women with a history of prostitution [relative risk (RR), 2.00; 95% confidence interval (95% CI), 1.20-3.33] and women with irregular condom use (RR, 7.74; 95% CI, 3.52-17.0) were at higher risk for an acute STI. CONCLUSIONS: Although STI diagnoses were frequent, the occurrence of acute STI declined with time from infection which might be explained by changed sexual behaviour over time. The occurrence of other STI increased with time from HIV infection, presumably due to reactivation as a result of immunosuppression.

Acute Disease↗

Review of case definitions for nosocomial infection--towards a consensus. Presentation by the Nosocomial Infection Surveillance Unit (NISU) to the Hospital Infection Liaison Group, subcommittee of the Federation of Infection Societies (FIS).

As part of the preparatory work for a national surveillance scheme, consensus was sought on the case definitions for nosocomial infection. We compare six sets of case definitions for nosocomial urinary tract infection, surgical wound infection, bloodstream infection and pneumonia, and highlight areas of agreement and variation. We hope this will stimulate discussion among those with expertise and interest in surveillance and so contribute to the development of nationally agreed case definitions.

Bacteremia↗

Nosocomial infections in a rural regional hospital in a developing country: infection rates by site, service, cost, and infection control practices.

OBJECTIVE: To assess the prevalence of nosocomial infections at a rural government hospital from 1992 to 1995. DESIGN: Retrospective review of data from 1992 to 1995 regarding rates of nosocomial infections, cost to government, and infection control practices. SETTING: 653-bed rural hospital providing primary and tertiary care. PATIENTS: Patients admitted to the hospital between 1992 and 1995 who were found with hospital-acquired infections during their stay. INTERVENTIONS: None. RESULTS: Over the 4-year period, 7,158 nosocomial infections were identified from 72,532 patients (10.0/100 admissions). High nosocomial infection rates were found on the intensive-care unit (67/100 admissions), urology (30/100 admissions), neurosurgery (29.5/100 admissions), and newborn nursery (28.4/100 admissions). Urinary tract infections (4.1/100 admissions) accounted for most nosocomial infections (42%), followed by postoperative wound infections (26.8%) with a rate of 2.6/100 admissions. Nosocomial pneumonias and bloodstream infections also were common with 13.2% and 8.0%, respectively. The highest rates occurred on the intensive-care unit for both pneumonia (26.4/100 admissions) and bloodstream infection (7.0/100 admissions). The cost to the government for nosocomial infections was estimated at US $697,000 annually (US $1=$6 Trinidad and Tobago). Poor infection control practices, inadequate handwashing facilities, lack of supplies, and nonexistent garbage cans on most wards were quite evident. CONCLUSIONS: Strict adherence to proper infection control practices, such as handwashing techniques, and improvement of facilities are crucial steps in preventing cross-infections in the hospital environment. Implementing these measures may substantially reduce the massive drain on the hospital budget in treating nosocomial infections. The saved revenue could go toward improvement of ward facilities and reduction of overcrowding, thus further reducing cross-infection.

Cross Infection↗

[Diagnosis and treatment of infections in a neonatal unit--viral infections, spirochete infections and toxoplasma infections].

Viral and protozoal infections are often suspected as causes of neonatal illness or congenital anomalies. The TORCH titer has traditionally been the foremost diagnostic tool in this context, but it is now becoming increasingly clear that this tool is inadequate, partly for conceptual reasons, but also because of the often uncritical way in which it is used. During a recent critical review of our routines and practices for diagnosis and treatment of neonatal infections we also revised our approach to the diagnosis and treatment of suspected pre- or perinatally acquired viral, spirochetal, and protozoal illnesses. The resulting guidelines, originally intended for our house staff, are presented here.

Humans↗

Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group.

BACKGROUND AND METHODS: Cytomegalovirus (CMV) has been implicated as a cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We assessed 440 infants (75 of whom were HIV-1-infected and 365 of whom were not) who had known CMV status and were born to HIV-1-infected women and who were followed prospectively. HIV-1 disease progression was defined as the presence of class C symptoms (according to the criteria of the Centers for Disease Control and Prevention [CDC]) or CD4 counts of less than 750 cells per cubic millimeter by 1 year of age and less than 500 cells per cubic millimeter by 18 months of age. RESULTS: At birth the frequency of CMV infection was similar in the HIV-1-infected and HIV-1-uninfected infants (4.3 percent and 4.5 percent, respectively), but the HIV-1-infected infants had a higher rate of CMV infection at six months of age (39.9 percent vs. 15.3 percent, P=0.001) and continued to have a higher rate of CMV infection through four years of age (P=0.04). By 18 months of age, the infants with both infections had higher rates of HIV-1 disease progression (70.0 percent vs. 30.4 percent, P=0.001), CDC class C symptoms or death (52.5 percent vs. 21.7 percent, P=0.008), and impaired brain growth or progressive motor deficits (35.6 percent vs. 8.7 percent, P=0.005) than infants infected only with HIV-1. In a Cox regression analysis, CMV infection was associated with an increased risk of HIV-1 disease progression (relative risk, 2.59; 95 percent confidence interval, 1.13 to 5.95). Among children infected with HIV-1 alone, but not among those infected with both viruses, children with rapid progression of HIV-1 disease had higher mean levels of HIV-1 RNA than those with slower or no progression of disease. CONCLUSIONS: HIV-1-infected infants who acquire CMV infection in the first 18 months of life have a significantly higher rate of disease progression and central nervous system disease than those infected with HIV-1 alone.

Acquired Immunodeficiency Syndrome↗

Cryptosporidium parvum infection in experimentally infected mice: infection dynamics and effect of immunosuppression.

The effect of mouse strain, age, sex, and the size of infective dose on the susceptibility to infection with the coccidium Cryptosporidium parvum Tyzzer, 1912 was determined using several murine models. Mice were infected with C. parvum oocysts originally of cervine origin, maintained by repeat passage in calves. All mice in the experimental groups proved susceptible to infection, though this resulted asymptomatic in all cases. C. parvum infection in BALB/c and Porton mice exhibited some variation. BALB/c mice demonstrated a longer prepatent period than Porton mice. They also produced a greater oocyst output over the patent period, though the differences were not statistically significant. Differences were observed between mice infected at either 3 or 4 weeks of age. Prepatent period was shorter in those mice infected at 3 weeks of age, reaching 100% infection rate by day 7 post-inoculation. The patent period was longer in younger mice showing that age at time of infection can modify the oocyst shedding profile. However, no sex related differences in the course of infection were observed. The effect of different infective doses of oocysts was analysed. The three doses used (10(4), 10(5), 10(6)) proved infective for all mice, there were no statistical differences in either prepatent or patent periods, or in the oocyst shedding profiles. Experimental cryptosporidiosis was also induced in cyclophosphamide-immunosuppressed mice. Cyclophosphamide was orally administered by stomach tube at a dose of 50 mg/kg/day starting 10 days before the intragastric inoculation of 10(6) oocysts of C. parvum per mouse and continuing until the end of the experiment. Immunosuppressed mice had a shorter prepatent period, remained infected longer and shed more oocysts than immunocompetent mice. Immunosuppression produced high mortality rates; during the course of the experiment 44% of immunosuppressed-infected and 30% of immunosuppressed-uninfected mice died. There were no deaths in the untreated groups. Differences in the clinical course of the infection were also observed between immunosuppressed and immunocompetent mice; however, some mice recovered without immunosuppression withdrawal.

Age Factors↗

Opportunistic infections and retrovirus-induced immunodeficiency: studies of acute and chronic infections with Toxoplasma gondii in mice infected with LP-BM5 murine leukemia viruses.

Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-gamma) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with reduced proliferation and impaired production of IFN-gamma in response to stimulation with soluble T. gondii antigens or to concanavalin A. Continuing resistance to lethal reactivation in the remaining mice was shown to require CD8+ T cells and expression of IFN-gamma. In addition, it was found that chronic infection with T. gondii altered the course of MAIDS by inhibiting the progression of splenomegaly and immunodeficiency and reducing the expression of both the helper and etiologic defective viruses. These results support previous studies which indicate that infection with T. gondii is controlled by synergistic interactions between CD4+ and CD8+ T cells, the functions of which are progressively impaired during the course of MAIDS.

Acute Disease↗

Coxiella burnetii infection in subjects with HIV infection and HIV infection in patients with Q fever.

The objective of the study was to determine whether HIV infection favors the acquisition of Coxiella burnetii infection or increases the frequency of symptomatic Coxiella infections. A total of 754 subjects were tested for Coxiella antibodies: 596 intravenous drug users (IVDUs) (306 HIV-infected IVDUs matched by aged and sex with 291 non-HIV-infected IVDUs), and 157 healthy puerperal women matched to the IVDU women. A total of 520 patients with Q fever were tested for HIV antibodies. The seroprevalence of Coxiella antibodies was similar in the 2 groups of IVDUs (19.3% of HIV + IVDUs vs 22.9% of HIV - IVDUs). Likewise, there was no difference in the prevalence of Coxiella antibodies in the groups of IVDU women and healthy women. Of the 520 subjects with acute Q fever, diagnosed between 1987 and 1992, only 4 (0.77%) had HIV infection. The proportions of HIV-infected subjects in the population of patients, with Q fever, of 20-39 years of age (the age of maximum incidence of both HIV and Coxiella infection in our region), coincided with the estimated proportions of HIV subjects in the respective general populations of the province. In conclusion, infection by Coxiella burnetii was not more frequent among HIV-infected subjects. It is not likely that Coxiella infection produces symptomatic infections more often in HIV-infected subjects.

Adolescent↗

High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIV infection.

Two hundred eleven HIV-seropositive patients with AIDS, AIDS-related complex, or a CD4+ cell count less than 200 x 10(6) were examined for the presence of hepatitis B virus markers during the course of their HIV infection (median follow-up of 18 months; range of 1 to 107 months). Anti-HBs was detected initially in 138 patients (65%). Sixteen patients (8%) were HBsAg positive at entry. Fourteen had chronic HBV infection of whom 12 initially were positive for HBeAg and HBV DNA; 11 remained positive during follow-up, whereas one seroconverted to anti-HBe and lost HBV DNA. Two patients with chronic HBV infection were initially negative for HBeAg and HBV DNA: one later had reactivated HBV replication and one cleared HBeAg following onset of hepatitis D infection. The last two HBsAg-positive patients had resolving acute HBV infection. Six of the 57 patients who initially were negative for HBV markers acquired HBV infection during follow-up. Four of these six patients developed chronic infection whereas two patients had acute subclinical resolving hepatitis. In addition, four patients became HBsAg positive with their last serum samples, possibly indicating reactivation of HBV infection following progressive immunological and clinical deterioration. None of the patients developed clinical symptoms that could be ascribed to HBV infection, and transaminase elevations were only sporadically recorded. It is concluded that acquisition of HBV infections is not infrequent in HIV-seropositive patients with immune deficiency. Furthermore, the course of both previously established chronic HBV infection and newly acquired HBV infection is modified in such patients, whereas reactivation of past HBV infection seems to be a rare event.

Adult↗

Antibiotics versus placebo for prevention of postoperative infection after appendicectomy.

BACKGROUND: Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. The cause of appendicitis is unclear and the mechanism of pathogenesis continues to be debated. Despite improved asepsis and surgical techniques, postoperative complications, such as wound infection and intraabdominal abscess, still account for a significant morbidity. Several studies implicate that postoperative infections are reduced by administration of antimicrobial regimes. OBJECTIVES: The objective of this review is to compare the use of antibiotics with placebo or no treatment in patients undergoing appendectomy. Will these patients benefit from antimicrobial prophylaxis? The outcomes are described according to the nature of the appendix, as either simple appendicitis (including the non-infectious stage) and complicated appendicitis. This review do not attempt to compare the effect of different regimens, a clinical question that is addressed in another review undertaken by this Group (CCCG). SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register (Cochrane Library 2000 issue 4), Medline (January 1966 to September 2000), Embase and the Cochrane Colorectal Cancer Group specialised register (September 2000). In addition we manually searched the reference lists of the primary identified trials. SELECTION CRITERIA: Randomised Controlled Trials (RCT) and Controlled Clinical Trials (CCT) in which any antibiotic regime were compared to placebo in patients suspected of having appendicitis undergoing appendectomy were evaluated. Both studies on children and adults were reviewed. The outcome measures of the studies were either wound infection, intraabdominal abscess, length of stay in hospital or mortality. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed, recorded and cross-checked by to reviewers. MAIN RESULTS: Forty-four studies including 9298 patients were included in this review. The overall result is that use of antibiotics is superior to placebo for the outcome wound infection and intraabdominal abscess, with no apparent difference in the nature of the removed appendix. Studies exclusively on children and studies examining topical application reported results in favour to the above although the results were not significant. REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis is effective in the prevention of postoperative complications in appendectomised patients, whether the administration are given pre-, per- and post-operatively and could be considered for routine in emergency appendectomies.

Abdominal Abscess↗

Tissue sites of persistent infection and active replication of equine infectious anemia virus during acute disease and asymptomatic infection in experimentally infected equids.

Equine infectious anemia virus (EIAV) infection of horses is characterized by recurring cycles of disease and viremia that typically progress to an inapparent infection in which clinical symptoms are absent as host immune responses maintain control of virus replication indefinitely. The dynamics of EIAV viremia and its association with disease cycles have been well characterized, but there has been to date no comprehensive quantitative analyses of the specific tissue sites of EIAV infection and replication in experimentally infected equids during acute disease episodes and during asymptomatic infections in long-term inapparent carriers. To characterize the in vivo site(s) of viral infection and replication, we developed a quantitative competitive PCR assay capable of detecting 10 copies of viral DNA and a quantitative competitive reverse transcription-PCR assay with a sensitivity of about 30 copies of viral singly spliced mRNA. Animals were experimentally infected with one of two reference viruses: the animal-passaged field isolate designated EIAV(Wyo) and the virulent cell-adapted strain designated EIAV(PV). Tissues and blood cells were isolated during the initial acute disease or from asymptomatic animals and analyzed for viral DNA and RNA levels by the respective quantitative assays. The results of these experiments demonstrated that the appearance of clinical symptoms in experimentally infected equids coincided with rapid widespread seeding of viral infection and replication in a variety of tissues. During acute disease, the predominant cellular site of viral infection and replication was the spleen, which typically accounted for over 90% of the cellular viral burden. In asymptomatic animals, viral DNA and RNA persisted in virtually all tissues tested, but at extremely low levels, a finding indicative of tight but incomplete immune control of EIAV replication. During all disease states, peripheral blood mononuclear cells (PBMC) were found to harbor less than 1% of the cellular viral burden. These quantitative studies demonstrate that tissues, rather than PBMC, constitute the predominant sites of virus replication during acute disease in infected equids and serve as resilient reservoirs of virus infection, even in the presence of highly effective immune responses that maintain a stringent control of virus replication in long-term inapparent carriers. Thus, these observations with EIAV, a predominantly macrophage-tropic lentivirus, highlight the role of tissues in sequestering lentiviral infections from host immune surveillance.

Animals↗

Interactions between HIV-infected monocytes and the extracellular matrix: increased capacity of HIV-infected monocytes to adhere to and spread on extracellular matrix associated with changes in extent of virus replication and cytopathic effects in infected cells.

Monocytes express cell surface receptors for extracellular matrix (ECM) proteins of basement membranes. These receptors are engaged during extravasation of cells through capillary endothelium into tissue. The number of human immunodeficiency virus (HIV)-infected monocytes that adhered to ECM over 2 h was threefold higher than that of uninfected control cells. This difference was ECM specific and was not observed with a bovine serum albumin substrate. Enhanced adhesion to ECM was evident in monocytes by 4 days after HIV infection and increased through 10 days. Monocytes exposed to a T cell-tropic HIV strain that binds to but does not replicate in monocytes showed no changes in adherence to ECM. Thus, productive infection of monocytes by HIV induces a significant increase in the capacity of these cells to interact with ECM. Enhanced adhesion of HIV-infected monocytes to ECM was associated with increased spreading: at 12 h, sixfold more HIV-infected monocytes were spread on ECM than were uninfected control cells. Cell processes of HIV-infected monocytes formed a complex network on ECM: many of these cells expressed HIV proteins as detected by indirect immunofluorescence. HIV-associated cytopathic effects and levels of virion-associated reverse transcriptase activity depended on the substrate to which monocytes were attached. Virus replication and cytopathic effects in monocytes adhered to ECM, fibronectin, or plastic alone were comparable. In contrast, HIV-infected monocytes attached to laminin showed a significant increase in virus replication and in extent of cytopathic effects through 2 weeks after infection. The lowest levels of HIV replication and cytopathic effects were in monocytes attached to collagen IV. Interactions between monocytes and ECM profoundly affect the manner in which these cells control HIV infection: HIV infection changes the capacity of infected monocytes to attach and spread on ECM; attachment to ECM alters the extent of virus replication in infected cells.

Cell Adhesion↗

Infection of CD8+ T lymphocytes with HIV. Requirement for interaction with infected CD4+ cells and induction of infectious virus from chronically infected CD8+ cells.

In this study, we have investigated the basic requirements for HIV-1 infection of CD8+ lymphocytes in vitro. Unfractionated PBL obtained from healthy HIV-1 seronegative donors were activated with PHA and infected in vitro with HIV-1LAV. Based on immunofluorescent labeling, the vast majority of cells (85 to 97%) surviving peak virus replication belonged to the CD8+ subset and only a small percentage (0.5 to 1.5%) were CD4+. Amplification of HIV-1 proviral sequences by polymerase chain reaction performed on the sorted surviving CD8+ cells demonstrated that CD8+ cells harbored HIV-1 proviral DNA. In addition, stimulation of these HIV-1-infected, CD8(+)-sorted cells either with PHA or anti-CD2 mAb resulted in induction of virus replication, as measured by reverse transcriptase activity. Electron microscopic analysis of CD8+ cells chronically infected with HIV-1 and stimulated with PHA showed typical virions budding from, and associated with, the surface of cells immunolabeled with gold beads directed toward the CD8 molecule. Infection of CD8+ cells with HIV-1 occurred only when CD4+ cells were present in the PHA-activated lymphocyte population exposed to HIV-1 at the beginning of the culture or when sorted CD8+CD4- lymphocytes were cocultured with autologous sorted CD8-CD4+ cells that had been previously infected with HIV-1. Coculture of these cells with PHA-blasts and incubation of their supernatants with a CD4+ cell line showed that these chronically infected CD8+ cells could spread HIV-1 infection to uninfected CD4+ cells after stimulation with PHA or anti-CD2 mAb. Therefore, these results suggest that the minimal requirement for in vitro infection of CD3+CD8+CD4- lymphocytes is the presence of infected CD4+ cells and that infected CD8+ T lymphocytes can further spread the infection to CD4+ cells.

Antigens, CD↗

Infective and anti-infective properties of breastmilk from HIV-1-infected women.

Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly by cell-to-cell contact. We postulated that transmission of HIV-1 through breastmilk could be favoured by the presence of infected cells, by deficiency of anti-infective substances in breastmilk, or both factors. 215 HIV-1-infected women were enrolled at delivery in Kigali, Rwanda; milk samples were collected 15 days, 6 months, and 18 months post partum. HIV-1 IgG, secretory IgA, and IgM were assayed by western blot, for the latter two after removal of IgG with protein G. In the 15-day and 6-month samples, we sought viral genome in milk cells by a double polymerase chain reaction with three sets of primers (gag, pol, and env). HIV-1 infection in the offspring was defined according to serological and clinical criteria. At 15 days, 6 months, and 18 months post partum, HIV-1 specific IgG was detected in 95%, 98%, and 97% of breastmilk samples, IgA in 23%, 28%, and 41%, and IgM in 66%, 78%, and 41%. In children who survived longer than 18 months, the probability of infection was associated with lack of persistence of IgM and IgA in their mothers' milk (adjusted chi 2 for trend, p = 0.01 for IgM and p = 0.05 for IgA). The presence of HIV-1-infected cells in the milk 15 days post partum was strongly predictive of HIV-1 infection in the child, by both univariate (p < 0.05) and multivariate analysis (p = 0.01). The combination of HIV-1-infected cells in breastmilk and a defective IgM response was the strongest predictor of infection. HIV-1 infection in breastfed children born to infected mothers is associated with the presence of integrated viral DNA in the mothers' milk cells. IgM and IgA anti-HIV-1 in breastmilk may protect against postnatal transmission of the virus.

Analysis of Variance↗

Multicenter surveillance study for nosocomial infections in major hospitals in Korea. Nosocomial Infection Surveillance Committee of the Korean Society for Nosocomial Infection Control.

BACKGROUND: The goals of a surveillance for nosocomial infections (NIs) are to observe the magnitude and characteristics of NIs and to plan and evaluate policies and guidelines of infection control. This study was designed to determine the rate and distribution of NIs and their causative pathogens in Korean hospitals. METHODS: Prospective surveillance was performed at 15 acute care hospitals with more than 500 beds during a 3-month period from June to August 1996. The case-finding methods were laboratory-based surveillance for patients in the general wards and a direct review of medical charts done regularly for all the patients in the intensive care units. RESULTS: A total of 3162 NIs were found among 85,547 discharged patients, with an overall nosocomial infection rate of 3.70 per 100 patients discharged. Urinary tract infections constituted 30.3% of all NIs. Other infections were pneumonias, 17.2%, surgical site infections, 15.5%, and primary bloodstream infections, 14.5%. The infection rate was the highest in neurosurgery (14.21), followed by neurology (8. 62) and ontology services (6.70). The infection rate in intensive care units was higher than it was in the general wards (10.74 vs 2. 57, P =.001). The commonly isolated organisms were Staphylococcus aureus (17.2%), Pseudomonas aeruginosa (13.8%), and Escherichia coli (12.3%). CONCLUSIONS: This first multicenter surveillance study provided extensive information on the current status and trends of NIs in major hospitals in Korea. The results may contribute to the evaluation of infection control programs and the development of effective strategies in these hospitals.

Contact Tracing↗

Massive mammary gland infection and pregnancy-dependent mammary tumor development in mice infected neonatally with mouse mammary tumor virus (SW) but not in mice infected as adults, despite a dramatic local response.

Mouse mammary tumor virus (MMTV) (SW) caused a high incidence (65%) of pregnancy-dependent adenocarcinomas in BALB/c(SW) mice infected as newborns by suckling their mothers' milk. These tumors were type B adenocarcinomas which developed early, at about 1 year of age. Uninfected breeding females and those infected at an age of 8 weeks by injection of virus had the same low incidence of malignant tumors (13%), and the tumors developed later (at approx. 23-24 months). The low incidence of tumors in adult-infected mice was correlated with partial infection of the mammary glands, and delayed transmission of MMTV(SW) to the offspring. Although the virus was rapidly disseminated in both types of infection, the responses of neonatally infected and adult-infected mice to MMTV(SW) infection and viral superantigen (vSAG) presentation were different. Activation by and presentation of the vSAG was impaired in mice infected neonatally, and tolerance induction by clonal deletion was delayed. Local activation was dramatic in mice infected as adults and clonal deletion followed rapidly. Although interaction between B and T cells is needed for completion of the virus life cycle and viral amplification, the strong local immune response to MMTV(SW) in adult-infected mice limits mammary gland infection, and protects them against mammary tumor development.

Adenocarcinoma↗

Schistosoma japonicum infection in the pig: the effect of a patent primary infection on a challenge infection.

The response of pigs to a challenge infection of Schistosoma japonicum following a primary infection was assessed using parasitological parameters and eosinophil counts. Twenty-five Danish Landrace/Yorkshire/Duroc crossbred pigs were divided into four groups. Group A (n = 10) received a primary infection, group B (n = 5) received both a primary and challenge infection, group C (n = 5) received a challenge control infection and group D (n = 5) received no infection serving as helminth-free controls. A dose of 850 cercariae was administered by intramuscular injection at the primary infection (week 0) and challenge infection (week 12). The pigs were perfused at week 21, except for half of the group A pigs which were slaughtered at week 12. Challenge infection did not result in higher worm burdens or tissue egg counts in group B than group A at week 21 and mature/immature worm ratios were similar for the two groups. In addition, no increases in faecal egg counts or eosinophil counts were observed in group B after challenge infection. The results indicate that pigs are able to mount a very rapid and effective response to reinfection with S. japonicum following a patent primary infection resulting in prevention of establishment of challenge infection schistosomes. An anti-worm effect appears to be the main feature of this regulatory host response.

Animals↗

Failure to spread bovine virus diarrhoea virus infection from primarily infected calves despite concurrent infection with bovine coronavirus.

Previous reports on the spread of bovine virus diarrhoea virus (BVDV) from animals primarily infected with the agent are contradictory. In this study, the possibility of transmission of BVDV from calves simultaneously subjected to acute BVDV and bovine coronavirus (BCV) infection was investigated. Ten calves were inoculated intranasally with BVDV Type 1. Each of the 10 calves was then randomly allocated to one of two groups. In each group there were four additional calves, resulting in five infected and four susceptible calves per group. Virulent BCV was actively introduced in one of the groups by means of a transmitter calf. Two calves, susceptible to both BVDV and BCV, were kept in a separate group, as controls. All ten calves actively inoculated with BVDV became infected as shown by seroconversions, and six of them also shed the virus in nasal secretions. However, none of the other eight calves in the two groups (four in each) seroconverted to this agent. In contrast, it proved impossible to prevent the spread of BCV infection between the experimental groups and consequently all 20 study calves became infected with the virus. Following infection, BCV was detected in nasal secretions and in faeces of the calves and, after three weeks in the study, all had seroconverted to this virus. All calves, including the controls, showed at least one of the following clinical signs during days 3-15 after the trial started: fever (> or =40 degrees C), depressed general condition, diarrhoea, and cough. The study showed that BVDV primarily infected cattle, even when co-infected with an enteric and respiratory pathogen, are inefficient transmitters of BVDV. This finding supports the principle of the Scandinavian BVDV control programmes that elimination of BVDV infection from cattle populations can be achieved by identifying and removing persistently infected (PI) animals, i.e. that long-term circulation of the virus without the presence of PI animals is highly unlikely.

Acute Disease↗