Persistent Carrier Research Articles

Nasal Carriage ofStaphylococcus intermediusin Humans in Contact with Dogs

study of staphylococci isolated from the anterior nares of 16 owners of dogs with atopic dermatitis and 13 veterinary practice staff in constant contact with dogs was conducted. There was one persistent nasal carrier and four transient nasal carriers of Staphylococcus intermedius. This carriage rate is higher than previously reported and presumably contributes to the presence of antibodies to S. intermedius in about 20 per cent of the normal population. Thus transfer of S. intermedius from dog to human is probably not uncommon.

Band tails and the insulator-metal transition in the persistent photoconductor Cd 1-xMn xTe:In

Persistent photoconductivity has been demonstrated in the dilute magnetic semiconductor Cd 1-xMn xTe:In and has been used to elucidate the shape of the band tail. It is further shown that the insulator-metal transition may be approached, in one sample, by controlling the persistent carrier density with illumination.

Alteration of neutrophil function in BCG-treated and non-treated swine after exposure to Salmonella typhimurium

Salmonella typhimurium infection in swine causes an enterocolitis followed by a persistent carrier state, but little is known about the mechanisms that allow this organism to colonize and persist in host tissues. Neutrophils provide a first line of defense against invading pathogens such as Salmonella typhimurium. The purpose of this study was to evaluate porcine neutrophil function after in vivo exposure to Salmonella and to determine if the immunomodulator, bacillus Calmette Guerin (BCG), exerts any effect on neutrophil function or on the colonization and persistence of S. typhimurium in the pig. Compared to negative controls, neutrophils from pigs exposed to S. typhimurium exhibited significantly decreased iodination, cytochrome-C reduction, antibody-dependent cell-mediated cytotoxicity, random migration, and chemotaxis ( P≤0.05). Neutrophil bactericidal activity against S. typhimurium was significantly enhanced. Most of the significant differences were noted in the first two days after exposure to Salmonella. Often the functional alterations were biphasic, peaking again 7–10 days after exposure. BCG alone significantly depressed random migration and cytochrome-C reduction in unstimulated neutrophils. The clinical course, colonization pattern, and persistence of Salmonella were similar between pigs receiving BCG and untreated pigs. These data suggest that S. typhimurium infection causes a depression in oxidative metabolism and motility, yet an increase in overall bactericidal activity against S. typhimurium in circulating porcine neutrophils. It also appears that BCG treatment, as reported here, does not enhance resistance of pigs to S. typhimurium colonization or reduce the number of persistent organisms in the porcine ileum.

The histopathology of the liver in older patients with hepatitis B virus surface antigenaemia

The histopathology of the liver and the detectability of intrahepatic hepatitis B virus (HBV) markers were studied in 34 autopsy cases in elderly patients (mean age 73.9 years, range 60-91 years) who had had a history of positive HBV surface antigenaemia prior to death. Seven of 14 persistent HBV carrier cases (group A) in which long-lasting HBV surface antigen (HBsAg) carriage in the sera had been confirmed by sequential assays, and 5 out of 15 HBV-infected people (group C, single assay) showed significant primary liver damages including chronic hepatitis, toxic hepatitis, liver cirrhosis and hepatocellular carcinoma. In 5 cases (group B), one of which was type B liver cirrhosis, HBsAg became negative and HBsAb appeared during the follow-up period (up to 33 months). Among confirmed HBV carriers, HBsAg and HBV core antigen were most frequently found in the liver of cirrhotic cases with and without hepatocellular carcinoma (5 of 6), whereas these were rarely detected in those with non-specific changes or slight hepatitic activity (1 of 7). All 5 cases in group B were negative for histological HBV-related antigens and the findings in group C were variously interpreted. Post-mortem cases of the aged HBV carriers who survived their mean life expectancy represent an important population in which to study the natural history of HBV carriers.

Replication of bovine viral diarrhoea virus in the bovine reproductive tract and excretion of virus in semen during acute and chronic infections.

Five mature bulls were studied during an acute transient infection with bovine viral diarrhoea virus (BVDV). The bulls had been infected experimentally by the intranasal instillation of blood and serum from a cow which was a persistent carrier of the virus. Infection was confirmed by the demonstration of a low titred viraemia in four of the five animals and by the seroconversion of all five. Semen samples were collected from each bull on four occasions between seven and 14 days after infection. The virus was isolated from the semen of three of the five bulls and from nine of 12 batches of semen from them. In contrast to other studies of the infection of semen, BVDV was isolated with similar efficiency from raw, unprocessed semen and from diluted, extended semen. The titres of virus in the semen ranged from 5 to 75 TCID50/ml. The infection did not appear to affect the quality of the semen. Shedding of virus continued after the end of the period of viraemia and appeared to be a consequence of the replication of the virus in the reproductive tract and its subsequent excretion in the seminal fluid. Virological studies of the reproductive tracts of these bulls suggested that the most productive sites of virus replication were the seminal vesicles and the prostate gland. Concurrent studies in a persistently infected bull supported these findings.

HORIZONTAL TRANSMISSION OF HEPATITIS B VIRUS

Meta-analysis of seroprevalence surveys shows that horizontal transmission of hepatitis B virus (ie, that occurring without apparent parenteral, sexual, or perinatal exposure) is common in areas endemic for the virus. It occurs especially in pre-adolescent children. In developed countries, where endemicity of hepatitis B virus is low, horizontal transmission (probably via saliva or open wounds) may occur in households with a persistent carrier, but it is less efficient a means of infection than is sexual or perinatal transmission. Horizontal transmission also seems possible in pre-school day-care centres in developed countries, despite the small numbers of carriers in such places.

Altered neurovirulence of temperature-sensitive vesicular stomatitis virus mutants in a murine model by inoculation of bombesin: A neuropeptide: I. Clinical, virological and pathological observations

Previous work in our laboratory has demonstrated that only certain temperature-sensitive (ts) mutants of vesicular stomatitis virus (VSV) appear capable of producing central nervous system (CNS) infection in a mouse model system. Considerable effort has been devoted to studies directed at unraveling the mechanisms underlying host virulence with these tsVSV mutants. With the previous demonstration that certain neuropeptides, capable of lowering body temperature, alter avirulent into virulent infection, we explored the role of one of these neuropeptides, bombesin, in CNS infection induced by normally avirulent tsG11 VSV, as well as certain tsVSV mutants derived from persistently infected (pi) carrier cultures. Our observations indicate that bombesin dramatically alters CNS infection with either tsG11 VSV as well as tsVSV mutants derived from persistent carrier cultures. When virus alone was inoculated intracerebrally, no sign of illness was observed and no animal died. When bombesin was injected along with normally avirulent tsG11 VSV, or glioma derived tsG31 VSV, 50% of mice died within 6–8 days after inoculation. Moreover, mice infected with virus and neuropeptide demonstrated striking pathological alterations in the CNS. These studies are in agreement with previously published results from others as well as our own laboratory and strongly suggest a direct correlation between CNS temperature and the capacity of certain tsVSV mutants to induce clinical and pathological disease.

Frequency and significance of concurrent hepatitis B surface antigen and antibody in acute and chronic hepatitis B

Of 228 consecutive hepatitis B surface antigen (HBsAg)-positive patients who had simultaneous hepatitis B surface antibody (anti-HBs) determinations, HBsAg and anti-HBs were found concurrently in 73 (32%). Concurrence was found with greater frequency in patients with chronic active hepatitis than in those with acute hepatitis (36 57 vs. 13 38, p < 0.02). Patients with chronic active hepatitis had concurrent markers more commonly than those with chronic persistent hepatitis or asymptomatic carrier state (36 57 vs. 24 133, p < 0.001). No major risk factors were identified. Hepatitis B e antigen was detected more frequently in patients with concurrence (68% vs. 42%, p < 0.01). Subtyping was possible in 30 patients with chronic infection, including 18 with chronic active hepatitis, 7 with chronic persistent hepatitis, and 5 with a carrier state. In 25 patients, HBsAg subtype ad was found with antibody to subdeterminant y and in four instances, HBsAg subtype ay was found with antibody to subdeterminant d. Only 1 patient had homotypic HBsAg and anti-HBs. Of 38 patients who had successive determinations, concurrence was constant in 29. In 9 others, anti-HBs was detected intermittently and the heterotypia of the recurrent antibody remained constant. Antibody to hepatitis δ-virus was not detected. We conclude that concurrent HBsAg and anti-HBs are found frequently in acute and chronic hepatitis B. The markers are commonly heterotypic in chronic disease. The presence of heterotypic markers is not associated with specific risk factors or δ-infection. Concurrence is associated with evidence of viral replication and features of active inflammation.

Serum antibodies to Epstein-Barr virus in patients with major depressive disorder.

To determine whether major depressive disorder might be associated with serologic evidence for a chronic active Epstein-Barr virus infection, viral-specific antibodies were measured in two separate groups of depressed patients (N=43) and in 46 appropriately matched healthy volunteers. No evidence that depression affects cellular immunity to the point that a persistent Epstein-Barr virus carrier state becomes activated was found. There was also no evidence that depression results from an unrecognized chronic active Epstein-Barr virus infection. The authors conclude that the routine clinical determination of expensive commercial Epstein-Barr virus antibody profiles is not indicated in most patients with major depressive disorder in the absence of other signs of chronic active Epstein-Barr viral infection.

Chemotherapy of East Coast fever. Treatment of infections induced by isolates of Theileria parva with halofuginone.

Cattle were infected with three isolates of Theileria parva and treated with halofuginone lactate during acute clinical disease. The health, weight gain and carrier state of the cattle were monitored for 15 months. Limited treatment rapidly reduced fever and parasitosis but parasite recrudescences occurred and 12 out of 21 treated cattle died. Persistent carrier states were identified with two T. p. parva isolate infections and a transient carrier state with T. p. lawrencei. Three cattle which died from a chronic wasting syndrome during the follow-up period showed exhaustion of lymph nodes but no Theileria macroschizonts were detected in any tissue.

Throughput Analysis for Persistent CSMA Systems

The channel throughput for a finite number of packet broadcasting users is analyzed for random access protocols, including slotted persistent carrier sense multiple access (CSMA) with and without collision detection and unslotted persistent CSMA with and without collision detection. We consider both <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</tex> - and 1-persistent CSMA. Our results can be extended to infinite population cases (by taking the proper limit), where they agree with the known throughput expressions when available.

SCREENING FOR HEPATITIS B VIRUS MARKERS IS NOT JUSTIFIED IN WEST AFRICAN TRANSFUSION CENTRES

62 severely anaemic Gambian children who were transfused with whole blood not screened for hepatitis B surface antigen (HBsAg) were followed for evidence of hepatitis B virus (HBV) infection over six months. 89% of donors and 44% of recipients before their transfusion had at least one HBV marker. Of the 54 recipient children surviving for the follow-up period, only 1 had a transient rise in liver enzymes. In 13 (37%) of 35 previously uninfected children HBV infection developed within twelve weeks of transfusion. Only 1 of these 13 children followed up at one year had become a persistent HBsAg carrier. The rate at which this cohort acquired persistent HBV infection or clinically important hepatitis was no greater than that in a cohort of similarly aged, non-transfused, children not admitted to hospital. In sub-Saharan Black Africa, where 15% of children have persistent HBV infection by the age of 10 years, HBV screening programmes in transfusion centres cannot at present be justified.

PREVENTION OF THE HBsAg CARRIER STATE IN NEWBORN INFANTS OF MOTHERS WHO ARE CHRONIC CARRIERS OF HBsAg AND HBeAg BY ADMINISTRATION OF HEPATITIS-B VACCINE AND HEPATITIS-B IMMUNOGLOBULIN: Double-blind Randomised Placebo-controlled study

Newborn infants of Chinese HBeAg-carrier mothers in Hong Kong were randomly assigned to one of four study groups. Group I was treated with 3 μg heat-inactivated hepatitis B (HB) vaccine at birth and at 1, 2, and 6 months thereafter, in conjunction with seven monthly HBIg injections; group II was treated according to the same vaccine schedule but received only one HBIg injection at birth; group III received only the vaccine, at months 0, 1, 2, and 6; and group IV received placebos for both vaccine and HBIg. The first set of injections was given within 1 h after birth. Comparisons were made in the 140 children who were at least six months old at the close of the trial (495 days). In all three treatment groups development of the persistent carrier state was significantly (p0·0001) less frequent than in controls (2·9%, 6·8%, and 21·0% versus 73·2%). Although vaccination alone was significantly less protective than vaccination plus multiple HBIg injections (p=0·03), the degree of protection was still remarkable. 12 months after the first set of injections 96-100% of the infants in the three treatment groups were anti-HBs positive; the geometric mean titres of anti-HBs in the three groups did not differ significantly. This indicates that even high doses of HBIg do not interfere with the anti-HBs response to the vaccine. Probable intra-uterine HB infections were observed in 3 infants. No serious side-effects were observed from the interventions, even in the babies with intra-uterine infections who had received HBIg and HB-vaccine at birth. To prevent development of the persistent HBsAg carrier state, and thereby the consequent chronic liver disease and/or primary carcinoma of the liver, HB vaccine and HBIg should be administered as soon as possible after birth to all newborn infants at risk of perinatal hepatitis B infection.

LONG-TERM FOLLOW-UP OF THE RATE OF PHARYNGEAL COLONIZATION WITH HAEMOPHILUS INFLUENZAE TYPE B (Hib) AT A CHRONIC-CARE FACILITY FOLLOWING PROPHYLAXIS WITH RIFAMPIN

Although rifampin is effective in eliminating pharyngeal carriage of Hib, there are few data about Hib colonization rates in treated groups long after administration of rifampin. After two children at a chronic-care facility for severely handicapped children had developed Hib meningitis, pharyngeal cultures using agar plates containing hyperimmune Hib antiserum revealed that 17 of the 97 children (18%) who resided there were colonized with Hib. A repeat survey 11 days after all carriers had been treated with rifampin showed that only 1 of these 97 children (1%) remained colonized with Hib. Six months later the rate of colonization rose significantly: 12 of the 85 available children (14%) were colonized with Hib(X2=11.69; P<0.001). Cultures were positive from 1 of 14 children in whom Hib colonization had previously been eradicated with rifampin. Potential sources for the reintroduction and transmission of Hib included visiting families, members of the staff, the one persistent carrier, and the newly admitted children (2 of 5 of whom were colonized with Hib). Although 6 months after prophylaxis with rifampin the prevalence of colonization with Hib was similar to that before rifampin was administered, no new cases of invasive Hib infections occurred at the facility during the ensuing 3 years. Because colonization with Hib is a dynamic process, reduction of the rate of colonization with Hib by chemoprophylaxis may only be transient, even in relatively closed populations.

Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines.

Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with the Edmonston strain of measles virus at a multiplicity of infection of 10(-6), and stable persistent infections were established. By immunofluorescence and electron microscopy, the vast majority of cells from both cell lines were expressing viral antigens and releasing virion-like particles. However, very little infectious virus could be detected at 37 degrees C, either by an infectious centers assay or by titration of supernates from persistently infected cultures. When cultures were shifted to 31 degrees C, the cells released a population of virus that was temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C revealed a highly heterogeneous population of temperature-sensitive mutants, differing in plating efficiency ratios, thermolability, and antigen production at the nonpermissive temperature. Factors such as interferon, defective interfering particles, and extracellular virus do not appear to be important in maintaining the persistent carrier state. These studies have important implications for persistent infections of lymphoid cells in vivo, and the slow neurological diseases associated with measles, subacute sclerosing panencephalitis, and multiple sclerosis.

Long-Term Persistent Vesicular Stomatitis Virus and Rabies Virus Infection of Cells In Vitro

BHK 21 carrier cells persistently infected with VSV Indiana for over 2 years have been shedding generally very low levels of mature infectious virus or mature T particles (averaging less than one-hundredth p.f.u./cell/day) yet most cells are producing virus antigens and are resistant to homologous superinfection. However, large amounts of biologically active T particle RNP can be recovered from cytoplasmic extracts of these carrier cells even at times when they are shedding no detectable infectious virus. This recovered cytoplasmic RNP replicates (with helper B virions) to produce mature T particles, interferes strongly after DEAE dextran-facilitated uptake and, together with B virions, allows the establishment of a persistent carrier state in exposed cells. No 'provirus' DNA copies of the VSV RNA genome are detectable (less than 1/40 copy/cell or I copy per 40 cells) in carrier cells after more than 2 years of persistent infection, and all transfection attempts have failed using DNA from these VSV carriers or DNA from carrier cells persistently infected with some other negative strand RNA viruses (measles, mumps, LCM, influenza, rabies). Infectious viruses shed after more than I year from carrier cells originally infected with wild-type B virions are small plaque mutants showing a slight temperature sensitivity. Cured cell populations can be obtained from the long term VSV carrier culture by cloning in the presence or absence of antiviral antibody.

Immunologic Mechanisms in the Pathogenesis of Virus-Induced Murine Leukemia

Abstract Thymocytes from preleukemic mice persistently infected with Moloney murine leukemia virus (MuLV-M-carriers) were vigorously autoaggressive toward normal syngeneic target cells; they exhibited a graded response to allogeneic cells, but they spared xenogeneic cells or syngeneic cells infected with MuLV-M or MuLV-G (Gross). Syngeneic target cells infected with nononcogenic lymphocytic choriomeningitis virus (LCMV), or transformed by the chemical carcinogen 3-methylcholanthrene were not similarly spared. This phenomenon, apparently induced by MuLV-M, is not associated with all persistent virus carrier states. Thymocytes from mice persistently infected with LCMV or with the lactic dehydrogenase virus (LDHV) failed to demonstrate an autoaggressive behavior. That transplantable lymphoma cells (derived from MuLV-M-carriers) were autoreactive in a pattern similar to thymocytes from preleukemic mice suggests a unique role for MuLV in the events leading from altered recognition of “self” to lymphoma.

Factors involved in the generation and replication of rhabdovirus defective T particles

Previous indications that cloned B virions might be genetically predisposed to generate a particular defective T particle are shown to be inaccurate. T particle generation was found to be a much more random process than was previously believed. We show that the previously observed generation of particular sizes of T particles by B virion pools is due to the random generation of T particles during preparation of first-passage pools of cloned B virions, and these breed true during the additional passages needed to produce visible quantities of T particles. It is also shown that different host cell lines selectively amplify different T particles, suggesting a strong role of host cell factors in T particle replication. Surprisingly, our line of HeLa cells did not generate or replicate detectable T particles of vesicular stomatitis virus (VSV) Indiana after either serial undiluted passage or direct addition of T particles, even though the added T particles strongly interfered with B virion replication. In contrast to VSV, rabies virus generates large amounts of T particles during the first passage of cloned B virions, and every rabies-infected baby hamster kidney-21 cell culture evolves into a persistent carrier state. We find that T particle RNA is biologically inactive although T particle nucleocapsid ribonucleoprotein replicates and interferes in cells coinfected with B virions. Efforts to study the mechanism of T particle generation by in vitro attempts to generate T particles or modify their size (using sheared ribonucleoprotein or chemical or UV mutagenesis) were unsuccessful. The kinetics of UV and nitrous acid inactivation of T particles indicate a smaller target size relative to B virions, even after correcting for lengths of RNA molecules. The intercalating dye proflavine does not photosensitize VSV B virions or T particles when present during replication, indicating that there is little or no RNA base pairing in the helical nucleocapsids of either.

Nursery outbreak of staphylococcal scalded skin syndrome. Rapid identification of the epidemic bacterial strain.

Within a seven-day period, three infants born at Harbor General Hospital were readmitted at ages 5 to 13 days with signs of the staphylococcal scalded skin syndrome (two with toxic epidermal necrolysis and one with bullous impetigo). From all three infants, isolates ofStaphylococcus aureusdemonstrated bacteriocin-like activity againstStaphylococcus502A. A nurse in the newborn area was found to be a persistent nasal carrier of aStaphylococcuswith bacteriocin-like activity. All strains with this activity were subsequently phage-typed as type 71. Because she was a possible source of the outbreak, the nurse-carrier was removed from the nursery and no subsequent cases occurred. The use of bacteriocin-like activity proved a simple and reliable marker of the epidemic staphylococcal strain in screening staphylococci from cases and carriers and in management of the outbreak.

GAMMA-GLOBULIN FOR HEPATITIS-VIRUS B PREVENTION OR EXTENSION ?

Inferential evidence is presented that attenuation of hepatitis-B-antigen (H.B. Ag)-positive hepatitis may favour the progression of acute to chronic liver disease and the development of a persistent H.B. Ag carrier state. These considerations may be relevant to the use of antibody to the hepatitisB antigen (anti-H.B. Ag) in the prophylaxis of hepatitis B. Based on preliminary encouraging results, controlled trials to test the efficacy of anti-H.B. Ag are being planned or are in progress. It is urged that these trials go beyond questions relevant to acute, overt hepatitis and specifically examine the possible induction of chronic liver disease and a persistent viral carrier state.