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Prevention of lung infections associated with human immunodeficiency virus infection.

Current evidence indicates that the length of survival for patients with the acquired immunodeficiency syndrome (AIDS) is increasing, thereby affording a greater opportunity for strategies designed to prevent the infectious diseases that mark the syndrome. Because these infections may occur at different stages of immunosuppression caused by the human immunodeficiency virus (HIV), effective application of preventive measures depends not only on detection of HIV infection but also on the use of staging indicators. The diseases that serve to define AIDS, such as Pneumocystis carinii pneumonia, tend to occur late in the course of HIV infection and often when the T helper lymphocyte (CD4+ cells) count is less than 0.2 x 10(9)/l. Other infections, such as tuberculosis and pyogenic bacterial pneumonia, may develop at any point after HIV infection has occurred. Given this relation between the degree of immunosuppression and the occurrence of particular pulmonary infections, different preventive interventions should be applied at different times. It is now known that the incidence of several of the pulmonary infections that are common in patients with HIV infection can be reduced by prophylactic measures. Pneumocystis pneumonia is decreased in frequency by any one of several prophylactic agents, the best established being pentamidine administered as an inhaled aerosol. The role of isoniazid in the chemoprophylaxis of tuberculosis in patients not infected with HIV is well established. Although there is little evidence of benefit so far from isoniazid in HIV infected patients with a positive tuberculin skin test response, it is logical to assume that there could be some effect. The use of pneumococcal polysaccharide vaccine may also be of some benefit in reducing the frequency of pneumococcal pneumonia in patients with AIDS. In addition to these specific measures, the antiretroviral agent zidovudine decreases both the frequency and the severity of opportunist infections, at least during the first few months of treatment. A comprehensive strategy for prevention of HIV associated lung infection first requires detection of HIV seropositivity, staging the immunosuppression by the CD4+ cell count, and determining whether tuberculous infection is present by a tuberculin skin test. All seropositive individuals should be given pneumococcal vaccine and those with evidence of tuberculosis infection should be treated with isoniazid for one year. Zidovudine should probably be started when CD4+ cell counts are in the range 0.4-0.5 x 10(9)/l and prophylaxis against pneumocystis infection when CD4+ cell counts are in the range 0.2-0.3 x 10(9)/l.

Acquired Immunodeficiency Syndrome↗

Protective effect of Staphylococcus chromogenes infection against Staphylococcus aureus infection in the lactating bovine mammary gland.

The susceptibility of uninfected or Staphylococcus chromogenes-infected quarters to challenge with Staphylococcus aureus was measured. Seventeen S. chromogenes-infected quarters were challenged by infusion of S. aureus into the teat sinus; 47% (8 of 17) became infected and all 18 uninfected quarters challenged similarly with S. aureus became infected. No differences in daily milk yield were seen between uninfected quarters and S. chromogenes-infected quarters prior to S. aureus infusion. Postinfusion, milk yield for S. aureus-infected, S. chromogenes-infected, and S. chromogenes- and S. aureus-infected quarters differed. Somatic cell counts were elevated in S. chromogenes-infected quarters compared with uninfected quarters prior to S. aureus infusion. Somatic cell counts were not different between S. aureus- and S. chromogenes- and S. aureus-infected quarters postinfusion, but were different for S. chromogenes-infected quarters. Chloride concentrations in S. chromogenes- and S. aureus-infected quarters were different from either S. aureus-infected or S. chromogenes-infected quarters. Staphylococcus aureus colony forming units in quarters with preexisting S. chromogenes infections were lower than S. aureus colony-forming units in previously uninfected quarters. Possible protective mechanisms induced by S. chromogenes against superinfection by S. aureus are discussed.

Animals↗

Effect of naturally occurring coagulase-negative staphylococci infections on new infections by mastitis pathogens in the bovine.

Microbiological data from 1123 uninfected quarters and 216 quarters with preexisting coagulase-negative staphylococci infections were analyzed to determine the influence of infection status on subsequent new infection rate. Overall, prevalence of new infections in uninfected quarters was approximately two times that in quarters already harboring a coagulase-negative Staphylococcus infection. New infections by coagulase-negative staphylococci were greater in uninfected quarters than in quarters with preexisting coagulase-negative staphylococci infections. However, no differences were observed between uninfected and infected quarters in number of new infections by major pathogens (Staphylococcus aureus, streptococci, and coliforms). No differences were observed in uninfected or coagulase-negative Staphylococcus-infected quarters in infections with minor pathogens compared with major pathogens. The influence of individual coagulase-negative Staphylococcus species on new infections was also analyzed. However, numbers of existing infections by Staphylococcus species other than Staphylococcus chromogenes were limited. Therefore, the protective capacity of each coagulase-negative Staphylococcus species was difficult to assess. Overall, a significant restriction of bacterial invasion was observed in quarters with a preexisting infection. These results suggest that quarters harboring a coagulase-negative Staphylococcus infection suppress colonization of the mammary gland by mastitis-causing pathogens.

Animals↗

Severe lower respiratory tract infections associated with human parainfluenza viruses 1-3 in children infected and noninfected with HIV type 1.

The aim of this study was to compare the clinical course of severe lower respiratory tract infections associated with human parainfluenza virus types 1-3 (HPIV 1-3) in hospitalised children infected with the human immunodeficiency virus type 1 (HIV-1) versus that in hospitalised children not infected with HIV-1. Children were enrolled prospectively as part of a broader study that evaluated the aetiology of lower respiratory tract infections in HIV-1-infected and -noninfected children from March 1997 through March 1999. HPIV types 1-3 were isolated from nasopharyngeal aspirate samples that were analysed using immunofluorescein monoclonal antibody assays. Thirty percent (24 of 80) of the children from whom HPIV was isolated were infected with HIV-1. Sixty-six percent (47 of 62) and 22% (14 of 62) of the HPIV isolates that were typed were subtypes 3 and 1, respectively. The clinical presentation of severe lower respiratory tract infection was similar in both HIV-1-infected and -noninfected children, except that the former were less likely to have wheezing (4.2% vs. 28.6%, P=0.01). Furthermore, the duration of hospitalisation was longer in HIV-1-infected children than in HIV-1-noninfected children (median 11.5 days [range 1-15 days] vs. median 7.5 days [range 1-22 days]; P=0.02), and mortality was higher (5 of 24 [20.8%] infected children vs. 0 of 56 noninfected children; P=0.001). Importantly, four of five (80%) of the HIV-1-infected children who died had other concurrent illnesses or predisposing factors for severe HPIV-associated disease. HPIV-associated lower respiratory tract infection causes greater morbidity and mortality in HIV-1-infected children than in HIV-1-noninfected children; however, this may be due to other concurrent illnesses in HIV-1-infected children.

Child, Preschool↗

Status of infection surveillance and control programs in the United States, 1992-1996. Association for Professionals in Infection Control and Epidemiology, Inc.

BACKGROUND: Nosocomial infections have been recognized as a source of morbidity and mortality throughout the world for several decades. In the United States, an estimated 2.1 million nosocomial infections occur annually in acute care hospitals alone. Infection surveillance and control programs (ISCPs) play a vital role in addressing this problem, but no national studies have described the status and composition of these programs since the 1970s. METHODS: In January 1997, a voluntary survey was sent by mail to members of the Association for Professionals in Infection Control and Epidemiology, Inc. Only one response per facility was requested. The survey asked for information for the years 1992 to 1996 (study period), and questions pertained to characteristics of the health care facility in which the respondent worked, characteristics of the ISCP and its personnel, and the overall level of administration support for infection control activities. RESULTS: Completed questionnaires were received from personnel at 187 health care facilities located in 40 states and the District of Columbia. The majority (76.5%) of responding facilities were nongovernment owned, and 57.2% were classified as general acute care facilities. The number of licensed beds at these facilities remained stable throughout the study period, but all other measures of facility size and activity (eg, number of patient days and number of nurses) decreased by as much as 28.9%. In 1992, ISCPs were most likely to be organizationally located in the Nursing Department, but by 1996, many had been transferred to departments of Medical Records, Quality Assurance, or Risk Management. Throughout the course of the study period, the number of facilities performing surveillance for health care-associated infections in outpatient settings increased by 44.0%, from 100 to 144. In 1996, only 47.6% of facilities had a hospital epidemiologist (HE), and HEs devoted a median of 15% or less of their time to infection control activities. For the most part, HEs were trained in infectious diseases, and few had certification in infection control. Infection control professionals (ICPs) were much more common than were HEs (ICPs were reported at 97.9% of respondents' facilities in 1996), and they spent the majority (80% in 1996) of their time on infection control activities. During the course of the study period, increasing numbers of facilities had ICPs who had certification in infection control. Furthermore, most respondents did not report a change over time in the level of administration support for infection control activities. CONCLUSIONS: Health care delivery has changed dramatically during the past 20 years. This study presents an updated description of ISCPs in the United States. Our results illustrate several changing parameters, such as departmental shifts and increased outpatient surveillance, that reflect adjustments in health care priorities during the study period. As the transformation of the health care system continues, continued evaluation of the status of ISCPs on a national level will be necessary. Diligent monitoring, proactive measures, and collaboration between infection control organizations and government agencies will be vital for the prevention and control of health care-associated infections in the future.

Ambulatory Care↗

Infected urine as a risk factor for postprostatectomy wound infection.

OBJECTIVE: To study the relation of preoperative infected urine and postprostatectomy wound infection in patients with and without indwelling bladder catheters. DESIGN: Patients undergoing prostatectomy were evaluated for the presence of infected urine prior to prostatectomy and postoperative wound infection. They were further divided into patients with indwelling urinary catheter and catheter-free patients. All had received antibiotic prophylaxis. PATIENTS: One hundred fifty consecutive patients undergoing open prostatectomy--mean age was 67 years; 100 patients with an indwelling catheter for a mean period of 50 days; 50 catheter-free patients. RESULTS: Wound infection was found in 19 of 81 (23.5%) and in 6 of 69 (8.7%) patients with infected and sterile urine, respectively (p = .028). In patients with indwelling catheters prior to operation, wound infection was 22.4% when urine was infected and 8.3% when it was not. In patients without catheters, infected urine was associated with 40% of wound infections, as compared with 8.9% of wound infections in patients with sterile urine. Organisms obtained from infected wound and urine were identical in 84% of cases. These results were obtained despite antibiotic prophylaxis. CONCLUSIONS: Wound infection has been demonstrated to be a postprostatectomy complication directly related to the presence of urinary infection at surgery; thus, elective prostatectomy should be deferred until urine becomes sterile.

Aged↗

Invasive pneumococcal infections in children infected with HIV are not associated with splenic dysfunction.

OBJECTIVES: Children infected with HIV-1 are more likely to acquire infections associated with the encapsulated bacterial pathogens of childhood than their non-HIV-infected peers. The goal of the current study was to determine what proportion of community-acquired, invasive pneumococcal disease in HIV-infected children could be attributed to splenic dysfunction, as measured by enumerating the number of pocked red blood cells (RBCs) in peripheral blood. METHODS: Splenic reticuloendothelial function was assessed semiquantitatively by examining the morphology of the RBCs of 84 children born to HIV-infected mothers using phase interference microscopy. Surveillance of medical records, and a review of the Yale-New Haven Hospital Clinical Microbiology computerized database, revealed that all of the bacterial cultures of blood and cerebrospinal fluid from these patients were positive. RESULTS: Of the 84 children assessed, 70 were infected with HIV (median age 66 months) and 14 were uninfected seroreverters (controls). Sixty-one of the 70 HIV-infected children met the CDC criteria for moderate or severe immunodeficiency and/or moderate or severe symptomatic conditions. Seventeen of the 70 HIV-infected children experienced 23 invasive bacterial infections. Streptococcus pneumoniae was responsible for all 23 infections. The median age at the time of first infection among these 17 subjects was 20 months (range, 10-58 months). There were no episodes of invasive bacterial infections in the remaining 53 HIV-infected children nor among the 14 controls. All 84 children studied, including those with invasive pneumococcal disease, had normal proportions (i.e., < 2%) of pocked erythrocytes in peripheral blood. CONCLUSION: Splenic dysfunction, as measured by the pocked RBC count, does not account for the increased occurrence of invasive pneumococcal disease found in children infected with HIV.

AIDS-Related Opportunistic Infections↗

Clinical infections in the noninstitutionalized geriatric age group: methods utilized and incidence of infections. The Pittsburgh Good Health Study.

Because noninstitutionalized senior citizens comprise over 95% of the population 65 years of age and older, their health needs are a major concern. Data regarding infections in this population including the epidemiology, morbidity, and mortality are lacking. The authors recruited a study population of 417 free-living persons, all 65 years of age or older, from two neighborhoods in Pittsburgh, Pennsylvania. After the collection of self-reported baseline information from these persons, they were monitored for all clinical infections for 2 years, beginning July 1986 and through June 1988, using clinic visits, hospitalizations, or phone calls when needed. The baseline information showed the study population of 417 persons to be comparable with a neighborhood comparison group and with established populations for epidemiologic studies of the elderly in three other states. The 24 months of infection surveillance yielded 494 diagnosed infections in 224 or 54% of the subjects. Respiratory infections were most frequent with 259 or 52% of the total, followed by genitourinary infections with 24%, skin infections with 18%, gastrointestinal infections with 4%, and other types of infection with 2%. By comparing 22 self-reported baseline conditions with the occurrence of infection, 10 historic factors were univariately significant for infection. Of these 10 factors, only history of a lung problem (relative risk = 1.7, 95% confidence interval (CI) 1.1-2.9) and history of difficulty controlling urination (relative risk = 2.7, 95% CI 1.3-4.9) were statistically significant in multivariate analysis. To our knowledge, this study represents the first prospective data on infections in the noninstitutionalized elderly. The data demonstrate the wide variety of infections that occurred in this population and suggest that persons with a history of any one of several medical problems were possibly at greater risk for infection.

Aged↗

Respiratory virus infections in children with cancer or HIV infection.

Most studies focusing on respiratory infections in immunocompromised children have been addressed to bacterial etiology. However, respiratory virus infections in this population can also lead to severe disease. The objective of this study is to evaluate the clinical significance of respiratory virus infections in children with cancer or human immunodeficiency virus (HIV) infection. Retrospective study conducted in a teaching hospital in Madrid. Medical records from children <or=14 years diagnosed with cancer or with HIV infection were reviewed. We analyzed demographic characteristics, clinical syndromes associated with the infection, need for hospitalization, treatment prescribed, and outcome. Fifty-three respiratory viral infections were identified: 26 (20%) in 129 HIV-infected children and 27 (12%) in 218 children with cancer. Twenty (38%) of the respiratory infections were nosocomial. Causal viruses were: respiratory syncytial virus, 43%; influenza A, 26%; adenovirus, 13%; parainfluenza virus, 13%; and influenza B, 4%. Thirty-three children were hospitalized: 14 (54%) with HIV infection and 19 (70%) receiving anticancer chemotherapy. Pneumonia occurred in 11 (34%) of the 33 hospitalized children. Four (21%) of the 19 hospitalized children with cancer, but none of the HIV-infected children, were admitted to the Pediatric Intensive Care Unit (P=0.096). Two children with cancer died. Common respiratory virus infections in children with cancer or HIV infection have a relevant morbidity. The fact that 40% of these infections are hospital-acquired emphasizes the need for isolation and preventive measures.

Adolescent↗

Intravenous immune globulin for the prevention of infections in children with symptomatic human immunodeficiency virus infection.

Infection with human immunodeficiency virus (HIV) causes a progressive immunodeficiency, often manifested in adults by the development of infections with relatively rare, opportunistic organisms. However, in HIV-infected children, recurrent serious infections with common encapsulated bacteria, as well as recurrent minor bacterial and viral infections, may be early and frequent manifestations of HIV disease. The use of i.v. immune globulin (IVIG) has been shown to prevent infections in patients with primary immunodeficiency and in uncontrolled studies of HIV-infected children. This article reviews the problem of and immunologic predisposition for recurrent infections in pediatric HIV infection and reports on the use of IVIG for prophylaxis. Updated analysis from the National Institute of Child Health and Human Development IVIG Clinical Trial, a multicenter, double-blind, placebo-controlled trial of the safety and efficacy of IVIG for the prevention of infections in children with symptomatic HIV infection, is presented. Between March 1988 and January 1991, 376 children with clinical or immunologic evidence of HIV disease who were randomized to receive IVIG or albumin placebo were enrolled in this trial. In children with an entry CD4+ count of 200/mm3 or higher, IVIG significantly increased the time free from serious bacterial infections and significantly decreased the rates of minor bacterial infections and viral infections.

AIDS-Related Opportunistic Infections↗

Infectious pancreatic necrosis virus infection in Atlantic salmon Salmo salar post-smolts affects the outcome of secondary infections with infectious salmon anaemia virus or Vibrio salmonicida.

Infectious pancreatic necrosis (IPN) virus (IPNV) infection in Atlantic salmon Salmo salar L. post-smolts and its influence on the outcome of secondary infections with infectious salmon anaemia (ISA) virus (ISAV) or Vibrio salmonicida were studied. The infections with ISAV or V salmonicida were performed both in a period of acute IPN and in the following IPNV carrier stage, 3 and 6 to 8 wk after experimental IPNV challenge, respectively. An IPNV carrier condition at low virus titre did not influence the mortality rates after secondary infections. Neither the ISAV infection nor the V. salmonicida infection in experimentally induced IPNV carriers resulted in mortalities different from those observed after challenge of IPNV-free fish. At higher IPNV titres in Atlantic salmon with acute IPN, the outcome of secondary infections was quite different from that observed in IPNV-free fish and in IPNV carriers. In 2 different experiments significantly more fish died when fish with acute IPN were infected with V salmonicida than when fish were infected with V salmonicida alone. Mortality also started earlier in the double-infected group than in the group challenged with V. salmonicida alone, 3 to 4 and 8 d after V salmonicida infection, respectively. Similar results were observed independent of whether mortalities due to IPN alone were registered in the experiments. When Atlantic salmon with acute IPN were infected with ISAV, significantly fewer fish died than when fish were infected with ISAV alone. The ongoing IPNV infection seemed to provide some protection against development of ISA.

Animals↗

Herpes virus infection of RPE and MDCK cells: polarity of infection.

Our objective was to determine quantitatively whether herpes simplex virus infects preferentially the apical or basolateral surfaces of two well-differentiated cell types, human retinal pigment epithelial cell and Madin-Darby canine kidney epithelial cells. Secondarily, we sought to localise the mannose 6-phosphate/insulin-like growth factor II receptor, a putative receptor for herpes simplex virus, in the membrane domains of the retinal pigment epithelial cells. Although it has been suggested that receptors utilized by the herpesviruses are heterogeneously distributed on epithelial cells, no quantitative evidence of preferential polarized uptake of wild-type herpes simplex virus into an epithelial cell has yet appeared. Moreover, no evidence has appeared of the distribution of mannose-6-phosphate/insulin-like growth factor II receptor in human retinal pigment epithelial cells. We hypothesized that the preferred pole of uptake and infection by HSV would correlate with the distribution of the receptor. Understanding the preferred site of entry in these cells may shed light on the mechanism of pathological infection and spread of this and related viruses, such as cytomegalovirus, in acute retinal necrosis and herpetic encephalitis. The efficiency of viral infection was assayed two ways. First, using permeable filters on which the monolayer of polarized epithelial cells was grown, we compared the number of foci of infected cells that resulted from an apical infection with that resulting from application of virus to the underside of the filter from which the virus could reach the basolateral surface of the cells. Second, we compared the number of infected cell foci that resulted from an apical infection to the number formed following infection at both the apical and basolateral surfaces of the cells. Both surfaces were exposed to virus following disruption of the tight junctions between cells with a Ca2+ chelator. After the efficiency of infection was normalized for relative surface areas, we found that both cell types were equally infectable with the F strain of the virus. However, there was a difference in the degree of polarized uptake of virus by the two cell types. Virus infected the basolateral surface of the retinal cells only about 6.5 times as effectively as it infected the apical surface of those cells, whereas virus infected the basolateral surface of the kidney epithelial cells about 435 times as effectively as it infected the apical surface of the same cells. These data suggest that herpes simplex virus can efficiently enter either the apical or basolateral surface of retinal pigment epithelial cells, unlike its more polarized preference for the basolateral surface of the kidney epithelial cell type. The mannose 6-phosphate/insulin-like growth factor II receptor was present in human retinal pigment epithelial cells, as determined by Western blotting. Surface biotinylation experiments revealed the presence of the receptor in both the apical and basolateral membranes of the retinal epithelial cells. Our evidence is consistent with the hypothesis that the virus may utilize the mannose 6-phosphate/insulin-like growth factor II receptor to facilitate entry.

Animals↗

Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection.

A mouse-adapted strain of Ebola Zaire virus produces a fatal infection when BALB/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. To identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to Ebola virus in mice infected ip (10 PFU/mouse), or sc (100 PFU/mouse) and sc "immune" mice rechallenged ip (10(6) PFU/mouse) at several time points postinfection (pi). Ebola viral antigens were detected in the serum, liver, spleen, and kidneys of ip-infected mice by day 2 pi, increasing up to day 6. Sc-infected mice and immune mice rechallenged ip had no detectable viral antigens until day 6 pi, when low levels of viral antigens were detected in the livers of sc-infected mice only. TNF-alpha and MCP-1 were detected earlier and at significantly higher levels in the serum and tissues of ip-infected mice than in sc-infected or immune mice challenged ip. In contrast, high levels of IFN-alpha and IFN-gamma were found in tissues within 2 days after challenge in sc-infected and immune mice but not in ip-infected mice. Mice became resistant to ip challenge within 48 h of sc infection, coinciding with the rise in tissue IFN-alpha levels. In this model of Ebola virus infection, the nonlethal sc route of infection is associated with an attenuated inflammatory response and early production of antiviral cytokines, particularly IFN-alpha, as compared with lethal ip infection.

Animals↗

Infection, immunity and the development of local skin reactions in rabbits infected with cyclically-transmitted stocks of Trypanosoma congolense.

The development of local skin reactions following bites by tsetse flies (Glossina morsitans) infected with Trypanosoma congolense was observed in normal rabbits, in rabbits with concurrent infections with T. congolense and in rabbits challenged after immunization by infection and treatment. Local reactions developed in normal rabbits within seven days of fly bite and were resolved by approximately 19 days after infection. In rabbits with concurrent infections no typical local reactions developed when they were bitten by infected tsetse flies. By allowing a single infected fly to bite a rabbit sequentially it was established that suppression of reaction development to homologous secondary challenge occurred within three to eight days of primary infection. Suppression of reaction development also occurred in infected rabbits challenged with an antigenically heterologous trypanosome stock within 14 to 18 days of primary infection, suggesting that reaction suppression is not associated with the specific immune response. It was also found that no neutralizing antibodies had developed against the parasites used for secondary infection by 28 days post-challenge. Rabbits were immunized by allowing an infected tsetse fly to feed on a rabbit and seven days later, when local reactions had appeared, treating it with homidium chloride. All rabbits challenged within 75 days of immunization by a tsetse fly infected with a homologous trypanosome stock resisted re-infection and some animals were immune up to 300 days after treatment. In most of the immunized animals specific neutralizing antibody activity against homologous parasites was low, suggesting that local expression of immunity in the skin might be more important in resistance to cyclically transmitted infections than serum antibodies. No local reactions developed on immune rabbits challenged with a homologous trypanosome stock but immunized rabbits challenged with heterologous trypanosome stocks developed typical local reactions.

Animals↗

Infection of tick cells and bovine erythrocytes with one genotype of the intracellular ehrlichia Anaplasma marginale excludes infection with other genotypes.

Anaplasma marginale, a tick-borne rickettsial pathogen of cattle, is endemic in several areas of the United States. Many geographic isolates of A. marginale that occur in the United States are characterized by the major surface protein 1a, which varies in sequence and molecular weight due to different numbers of tandem repeats of 28 or 29 amino acids. Recent studies (G. H. Palmer, F. R. Rurangirwa, and T. F. McElwain, J. Clin. Microbiol. 39:631-635, 2001) of an A. marginale-infected herd of cattle in an area of endemicity demonstrated that multiple msp1alpha genotypes were present but that only one genotype was found per individual bovine. These findings suggested that infection of cattle with other genotypes was excluded. The present study was undertaken to confirm the phenomenon of infection exclusion of A. marginale genotypes in infected bovine erythrocytes and cultured tick cells. Two tick-transmissible isolates of A. marginale, one from Virginia and one from Oklahoma, were used for these studies. In two separate trials, cattle inoculated with equal doses of the two isolates developed infection with only one genotype. Tick cell cultures inoculated with equal doses of the two isolates became infected with only the Virginia isolate of A. marginale. When cultures were inoculated with different ratios of the Oklahoma and Virginia isolates of A. marginale, the isolate inoculated in the higher ratio became established and excluded infection with the other. When cultures with established infections of one isolate were subsequently infected with the other, only the established isolate was detected. We documented infection exclusion during initial infection in cell culture by labeling each isolate with a different fluorescent dye. After 2 days in culture, only a single isolate was detected per cell by fluorescence microscopy. Finally, when Anaplasma ovis infections were established in cultures that were subsequently inoculated with the Virginia or Oklahoma isolate of A. marginale, A. marginale infection was excluded. These studies confirm that infection exclusion occurs with A. marginale in bovine erythrocytes and tick cells, resulting in the establishment of only one genotype, and appears to be the first report of infection exclusion for Anaplasma and Ehrlichia species.

Anaplasma↗

Early stage of establishment of persistent Sendai virus infection: unstable dynamic phase and then selection of viruses which are tightly cell associated, temperature sensitive, and capable of establishing persistent infection.

We obtained 157 cloned cell lines persistently infected with Sendai virus; these cell lines were generated independently of each other. Infectious viruses could be isolated from 123 of these cloned cell lines by inoculation of culture fluids or infected cells into embryonated eggs. The majority of the viruses carried by cells persistently infected with viruses showed high cytotoxicity and did not have the ability to establish persistent infection. The association of carried virus with cells became stronger and virus isolation correspondingly became more difficult as cells persistently infected with virus were subcultured. Viruses derived from virus-infected cells eventually acquired the ability to establish persistent infection, although the ways in which the viruses acquired this ability varied. The viruses also acquired temperature sensitivity as persistently infected cells were subcultured. First, the hemagglutinin-neuraminidase and M proteins acquired temperature sensitivity, and then the polymerase(s) did so. The M proteins were localized in the nuclei of cells infected with cloned viruses that had the ability to establish persistent infection. Cells infected with viruses capable of establishing persistent infection showed no or slight staining by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling. Specific amino acid substitutions accumulated in the M protein and the L protein as virus-infected cells were subcultured. This study shows that there is an unstable dynamic phase at an early stage of the establishment of persistent Sendai virus infection (steady state), and then viruses capable of establishing persistent infection are selected.

Animals↗

Treatment of co-infection with bancroftian filariasis and onchocerciasis: a safety and efficacy study of albendazole with ivermectin compared to treatment of single infection with bancroftian filariasis.

BACKGROUND: In order to use a combination of ivermectin and albendazole for the elimination of lymphatic filariasis, it is important to assess the potential risk of increased adverse events in individuals infected with both lymphatic filariasis and onchocerciasis. We compared the safety and efficacy of albendazole (400 mg) in combination with ivermectin (150 micrograms/kg), for the treatment of co-infections of Wuchereria bancrofti and Onchocerca volvulus with single infection of W. bancrofti. METHODS: The safety study on co-infections was a crossover, double blind design, while for the single infection of bancroftian filariasis an open design comparing two treatments was used. For co-infection, one group was allocated a single dose of ivermectin (150 micrograms/kg) plus albendazole (400 mg) (Group A). The other group received placebo (Group B). Five days later the treatment regime was reversed, with the Group A receiving placebo and Group B receiving treatment. For the single bancroftian filariasis infection, one group received a single dose of albendazole (400 mg) plus ivermectin (150 microg/kg) (Group C) while the other group received a single dose of albendazole (400 mg) alone (Group D). Blood and skin specimens were collected on admission day, day 0, and on days 2, 3, and 7 to assess drug safety and efficacy. Thereafter, blood and skin specimens were collected during the 12 months follow up for the assessment of drug efficacy. Study individuals were clinically monitored every six hours during the first 48 hours following treatment, and routine clinical examinations were performed during the hospitalisation period and follow-up. RESULTS: In individuals co-infected with bancroftian filariasis and onchocerciasis, treatment with ivermectin and albendazole was safe and tolerable. Physiological indices showed no differences between groups with co-infection (W. bancrofti and O. volvulus) or single infection (W. bancrofti). The frequency of adverse events in co-infected individuals was 63% (5/8, Group A, albendazole + ivermectin) and 57% (4/7, Group B, placebo) and of mild or moderate intensity. In single W. bancrofti infection the frequency of adverse events was 50% (6/12, Group C, albendazole + ivermectin) and 38% (5/13, Group D, albendazole) and of a similar intensity to those experienced with co-infection. There were no differences in adverse events between treatment groups. There was no significant difference in the reduction of microfilaraemia following treatment with albendazole and ivermectin in groups with single or co-infection. CONCLUSION: Our findings suggest that ivermectin plus albendazole is a safe and tolerable treatment for co-infection of bancroftian filariasis and onchocerciasis.

Journal Article↗

Specific anti-Toxoplasma antibodies in relation to infection and reinfection using different infective stages.

The possibility of rat re-infection with different Toxoplasma gondii stages was studied in this work. Two groups of rats were infected with either intra-peritoneal injection of 1000 trophozoites of virulent Toxoplasma strain or 1000 oocysts through oral routes. IgA, IgM and IgG were detected 15, 30, 60 and 120 days post infections. IgA and IgM appeared as early as 15 days post infection but declined afterwards. IgA antibody response was more prominent with oocyst infection and IgM was more prominent with tachyzoite infection with insignificant statistical difference. On the other hand, IgG started to increase 60 days post infection, then increased gradually till the end of the experiment (120 days). The primary orally infected rats were either re-infected orally with oocysts or intra-peritoneal trophozoites and re-examined after 15 and 120 days for the same immunological parameters. Those rats which primary infected with intra-peritoneal trophozoites were re-examined after oral infection with oocysts or injection of trophozoites intra-peritoneal. The level of IgA and IgM in one rat of group A and 2 rats of group B were significantly increased and this occurred in presence of anti-Toxoplasma IgG from the primary infection. In this study, the rats were lab-bred so, the factors affect the immune system could be under control, also strain variability was excluded as the infection was only by one strain, and as the IgG level was high, these rats were presumed to be immune from the primary infection. So, the rats which became positive after challenge most probably re-infected.

Animals↗