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Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome.

BACKGROUND: The relationship between gestational age at time of maternal cytomegalovirus (CMV) infection and outcome of fetal infection is not well defined because the timing of maternal infection is usually not known. OBJECTIVE: To determine whether congenital cytomegalovirus (CMV) infection following primary maternal infection during the first trimester of pregnancy is more likely to lead to central nervous system (CNS) sequelae than fetal infection due to maternal infection later in pregnancy. STUDY DESIGN: Using serum collected during pregnancy from mothers of newborns with congenital CMV infection, maternal infection was categorized as first trimester (<13 weeks) or later based on dates and results of IgG and IgM assays for CMV antibody. Outcome of congenital CMV infection was assessed by longitudinal fotlow-up of the infected cohort. RESULTS: Sensorineural hearing loss was found in 8/34 (24%) of children in the first trimester group, compared with 1/40 (2.5%) in the later infection group (P=0.01, relative risk, 9.6). Considering any CNS sequela (hearing loss, mental retardation, cerebral palsy, seizures, chorioretinitis) 11/34 (32%) first trimester cases were affected compared with 6/40 (15%) in the later infection group (P=0.07, relative risk 2.2). None of the later group had more than one sequela, compared with 4 (12%) of the first trimester group (P=0.04). CONCLUSIONS: Children with congenital CMV infection following first trimester maternal infection are more likely to have CNS sequelae, especially sensorineural hearing loss, than are those whose mothers were infected later in pregnancy. However, some degree of CNS impairment can follow even late gestational infection.

Antibodies, Viral↗

Age at primary infection with Salmonella enterica serovar Typhimurium in the chicken influences persistence of infection and subsequent immunity to re-challenge.

Salmonella enterica remains one of the most important food-borne pathogens of humans and is often acquired through consumption of infected poultry meat or eggs. Control of Salmonella infections in chicken is therefore an important public health issue. Infection with S. enterica serovar Typhimurium results in a persistent enteric infection without clinical disease in chickens of more than 3 days of age, and represents a source for contamination of carcass at slaughter and entry into the human food chain. Data presented indicate a profound effect of age at initial exposure on the persistence of infection and a lesser effect on the development of effective immunity to re-challenge. The percentage of birds positive for Salmonella was high until 8-9 weeks of age, regardless of the age at which the birds were infected (1, 3 or 6 weeks). The birds infected at 3 and 6 weeks of age produced a more rapid and higher antibody response (IgY and IgA) than those infected at 1 week of age, but in all cases infection persisted for a considerable period despite the presence of high antibody levels. Following a re-challenge infection with S. Typhimurium, all three previously-infected groups had fewer bacteria in the gut, spleen and liver compared with age-matched birds receiving a parallel primary infection. However, the birds primary infected at 3 and 6 weeks of age cleared infection more rapidly than those infected at a younger age. Interestingly older-primed birds had higher specific T lymphocyte proliferative responses and specific circulating levels of IgY antibody at time of re-challenge. Although birds initially infected at 1 week of age and those that were previously uninfected produced a stronger antibody response following re-challenge, they were slower to clear Salmonella from the gut than the older-primed groups which expressed a stronger T lymphocyte response. The data presented indicate that clearance of Salmonella from the gut is age-dependent and we propose that this relates to the increased competence of the enteric T cell response. The findings that Salmonella persists beyond 8-9 weeks, irrespective of age at exposure, has implications for the broiler sector and indicates the need to remain Salmonella free throughout the rearing period. Moreover, the re-challenge data demonstrates that infection at a young age is less effective in producing protective immunity than in older chickens. This feature of the development of protective immunity needs to be considered when developing vaccines for the broiler sector of the poultry industry.

Age Factors↗

Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection.

We studied the incidence of primary and recurrent cytomegalovirus infection in 3712 pregnant women--2698 of middle to high income and 1014 of low income--to determine whether there were differences in the effects on the fetus. In the higher-income group, 1203 women (45 per cent) did not have antibodies to cytomegalovirus and were therefore susceptible to primary infection, as compared with 179 women (18 per cent) of low income. Congenital infection occurred more often (1.6 vs. 0.6 per cent) in infants in the low-income group. In this group it was associated with recurrent maternal infection more often (in 82 per cent) than with primary maternal infection, whereas in the upper-income group, it was associated with primary maternal infection in half the cases. Altogether, there were 32 cases of congenital cytomegalovirus infection - 16 in each group. Whereas primary maternal infection resulted in fetal infection in only half the cases, it was more likely to ge associated with clinically apparent disease than was recurrent infection. When these cases were combined with 28 cases of congenital infection retrospectively identified at other prenatal clinics, five of 33 infected infants born after primary maternal infection had clinically apparent disease, as compared with none of 27 born after recurrent maternal infection. We conclude that congenital cytomegalovirus infection resulting from primary maternal infection is more likely to be serious than that resulting from recurrent infection, and is more likely to occur in upper socioeconomic groups.

Adult↗

Ultrasound markers of fetal infection, Part 2: Bacterial, parasitic, and fungal infections.

Up to 1% of all pregnancies have clinically overt intra-amniotic bacterial infections, and an even larger percentage of pregnant women may be affected by silent infections. Although most pregnant women with overt intra-amniotic bacterial infection have experienced prolonged rupture of membranes (PROM), symptomatic and most silent nonviral intra-amniotic infections may occur with intact membranes. The etiology of intra-amniotic infection after PROM is almost always polymicrobial and consists of genital tract pathogens, such as group B streptococci, Chlamydia trachomatis, Neisseria gonorrhoeae, mycoplasmas, aerobic Gram-negative bacilli, such as the coliforms, and facultative and anaerobic endogenous organisms, such as peptococci, peptostreptococci, and Bacteroides species. These organisms gain access to the uterine cavity by the ascending route. Organisms such as Treponema pallidum, Listeria monocytogenes, Toxoplasma gondii, trypanosomes, and plasmodia are capable of gaining access to the amniotic cavity by transplacental hematogenous spread, and cause devastating fetal infections. Symptomatic intra-amniotic infection is usually a diagnosis of exclusion. Diagnostic criteria based on both clinical and laboratory findings lack sensitivity and are nonspecific. It is difficult to obtain uncontaminated intra-amniotic samples, especially when there is PROM. The problem is even greater with silent infections. In most cases, fetal infection is suspected after an unexplained and unexpected adverse outcome. Maternal morbidity is increased with intra-amniotic infection; although maternal mortality is extremely rare in developed countries, this is not the case in societies where pregnant women have limited or no access to medical care. Although infected women who are treated early and aggressively with wide-spectrum antibiotics do well, more than 10% of these women develop bacteremia and up to half of them will require cesarean delivery because of poor uterine contractions and arrest of labor. The overwhelming majority of term neonates exposed to intrauterine infection after PROM do well, but up to 30% of these neonates require treatment of neonatal pneumonia or bacteremia. Outcomes for preterm neonates or for neonates who experienced silent fetal infections are more severe. Morbidity and mortality rates in these cases are high, and survivors may have long-term devastating sequelae. The ability to identify ultrasound markers of fetal infection will help clinicians identify etiologic agents with greater accuracy and correlate these infections with specific antepartum and postpartum syndromes. The recognition of markers of intrauterine infection will also reduce unexpected adverse outcomes that result from undiagnosed fetal infections.

Bacterial Infections↗

Neonatal predictors of infection status and early death among 332 infants at risk of HIV-1 infection monitored prospectively from birth. New York City Perinatal HIV Transmission Collaborative Study Group.

BACKGROUND AND METHODS: Differences in newborn outcome measures for human immunodeficiency virus (HIV)-1-infected and HIV-1-exposed but uninfected infants have been found in several studies, but not in others. Eighty-four infected and 248 uninfected children born to HIV-1-seropositive mothers followed prospectively in a multicenter, perinatal HIV-1 transmission cohort study were compared for differences in maternal demographics, health status, and newborn outcome measures, including delivery complications, physical examination findings, neonatal complications, and laboratory results. RESULTS: Mothers of HIV-1-infected infants were more likely than those of uninfected infants to have acquired immunodeficiency syndrome (AIDS) diagnosed through 2 weeks postpartum (21% vs 11%, P = .04); the transmission rate for the 38 women with AIDs was 37% compared with 22% for the 245 women without AIDS. Two of 27 (7%) women receiving zidovudine during pregnancy had infected infants compared with 73 (27%) of 275 women who did not receive zidovudine (P = .033). Mean gestational age was significantly lower among HIV-1-infected (37 weeks) than among uninfected infants (38 weeks; P < .001). Infected infants had significantly higher rates of prematurity (gestational age less than 37 weeks) (33% vs 19%, P = .01) and extreme prematurity (gestational age less than 34 weeks) (18% vs 6%, P = .001) than uninfected infants. Infection was associated with lower birth weight (2533 g vs 2862 g, P < .001) and smaller head circumference (32.0 cm vs 33.1 cm, P = .001). HIV-1-infected infants were significantly more likely to be small for gestational age (26% vs 16%, P = .04) and low birth weight (less than 2500 g) (45% vs 29%, P = .006) than infants who were uninfected. Twenty-two (26%) HIV-1-infected children died during a median follow-up of 27.6 months (range 1.9 to 98.3 months). Prematurity was predictive of survival: by Kaplan-Meier, an estimated 55% (95% confidence interval, 31% to 72%) of preterm infected children survived to 24 months compared with 84% (95% confidence interval, 70% to 92%) of full-term infected children (P = .005). CONCLUSION: Infants born to women with AIDS are at higher risk for HIV-1 infection than are infants born to HIV-1-infected women with AIDS not yet diagnosed. Women receiving zidovudine appear less likely to transmit HIV-1 to their infants. Significantly higher rates of prematurity and intrauterine growth retardation were found among HIV-1-infected infants than among those in the uninfected, HIV-1-exposed control group. Prematurity was associated with shortened survival in HIV-1-infected infants. Measures of intrauterine growth and gestation appear to be important predictors of HIV-1 infection status for seropositive infants and of prognosis for the infected infant.

Acquired Immunodeficiency Syndrome↗

Prophylactic intravenous immunoglobulin in HIV-infected children with CD4+ counts of 0.20 x 10(9)/L or more. Effect on viral, opportunistic, and bacterial infections. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: To evaluate the efficacy of intravenous immunoglobulin (IVIG) for prevention of viral, opportunistic, and minor bacterial infections in children infected with human immunodeficiency virus (HIV). DESIGN: Randomized, double-blind, placebo-controlled, outpatient clinical trial comparing subjects treated with 400 mg of IVIG per kilogram of body weight every 28 days with those given albumin placebo. SETTING: Twenty-eight clinical centers in mainland United States and Puerto Rico. PATIENTS: Three hundred seventy-six children infected with human immunodeficiency virus with clinical or immunologic evidence of HIV disease, 313 of whom had entry CD4+ counts of at least 0.20 x 10(9)/L (greater than or equal to 200/mm3). MAIN OUTCOME MEASURES: The incidence of laboratory-proven and clinically diagnosed viral, opportunistic, and bacterial infections. MAIN RESULTS: Viral infections and minor bacterial infections contributed more frequently to morbidity in children with entry CD4+ counts of at least 0.20 x 10(9)/L (together over five times as frequent) than did serious bacterial infection, the primary outcome measure of the trial. Opportunistic infections occurred at a similar rate as laboratory-proven serious bacterial infections. In this group of children, IVIG was significantly associated with a decrease in the rate of viral infections and minor bacterial infections per 100 patient-years (36.0 vs 54.0 episodes of viral infection per 100 patient-years, IVIG vs placebo, P = .01; and 115.1 vs 159.7 episodes of minor bacterial infection per 100 patient-years, IVIG vs placebo, P = .02), as well as a decrease in the rate of serious bacterial infections per 100 patient-years (26.4 vs 48.2 episodes per 100 patient-years; P = .002). There was no apparent difference in the rate of opportunistic infections between treatment arms. CONCLUSIONS: Beneficial effect of IVIG was seen across multiple infectious outcome measures, with reductions in serious and minor viral and bacterial infections observed in children with entry CD4+ counts of at least 0.20 x 10(9)/L.

Bacterial Infections↗

[Immunologic findings in HIV infected children with bacterial infections].

BACKGROUND: Bacterial infections are a major cause of illness in HIV-infected children. HIV-infected children with severe dysfunction of cellular and humoral immunity are particularly vulnerable. METHODS AND PATIENTS: We conducted a retrospective study to analyse the incidence and spectrum of bacterial infections in HIV-infected children compared to HIV-exposed but not infected controls related to their immunological status. Data collected during 1985 to May 1993 were evaluated considering 333 HIV-infected and 81 controls. RESULTS: During observation time 359 episodes (29% of the visits) of purulent rhinitis were diagnosed in HIV-infected children compared to the controls (53 episodes/8%); p = 0.0001. Comparable results were seen in otitis media. 178 episodes/14% were found in HIV-infected children and 66 episodes/10% in the controls (p = 0.001). 53 episodes/5% of bacterial pneumonia were represented in HIV-infected versus 11 episodes/2% in controls (p = 0.001). The increase of lymphocyte immune defect correlated to an increase of bacterial infections. This alterations were particularly observed in HIV-infected children with bacterial pneumonia. Severe dysfunction of cellular immunity was found in children with recurrent pneumonia compared to children with only one episode of bacterial pneumonia. The proliferate response of peripheral blood lymphocyte to pokeweed mitogen (13,351 cpm versus 3080 cpm); p = 0.009 and Concanavalin A (12,607 cpm versus 2470 cpm); p = 0.01 was significantly reduced in both groups, although the defect was much more pronounced in the group with the recurrent pneumonia. CONCLUSIONS: Our observations results showed that bacterial respiratory tract infections occurred significantly more frequently in HIV-infected children compared to an age related control group. Not only the occurrence of opportunity infections but also severe bacterial infections especially recurrent pneumonia are associated with a defect in cell-mediated immunity.

AIDS-Related Opportunistic Infections↗

Infections in HIV-infected travelers: risks and prevention.

OBJECTIVE: To review risks for infection and to outline strategies to protect the health of travelers infected with human immunodeficiency virus (HIV). DATA SOURCES: Original reports and summaries of the geographic distribution and frequency of infections as well as of special risks these infections impose on HIV-infected persons. The recommendations incorporate guidelines published by the Centers for Disease Control (CDC) and the World Health Organization. STUDY SELECTION: Sources containing the most recent, pertinent information. DATA SYNTHESIS: Infections of the gastrointestinal tract are common in all travelers to developing countries and are likely to be more frequent, severe, and difficult to treat in HIV-infected persons. Prominent among the respiratory tract infections that pose special risks to HIV-infected travelers are influenza, measles, and fungal infections with geographically focal distributions. The most common vector-borne infection, malaria, appears to present relatively little, if any, incremental risk to the HIV-infected traveler. Persons with HIV infection respond less vigorously to vaccines and have a higher frequency of adverse reactions to antimicrobial agents. Nevertheless, immunizations and chemoprophylaxis can reduce the risk for many travel-related infections. Additionally, there are protective measures that travelers can take to minimize exposure to pathogens. CONCLUSIONS: By understanding the risks for disease in different destinations, assessing patients' HIV status, counseling patients about travel plans and personal protective measures, appropriately using vaccines and chemoprophylaxis, as well as instituting early treatment of infection, physicians can help HIV-infected patients to preserve their health during travel.

Gastrointestinal Diseases↗

Impact of hepatitis G virus co-infection on the course of hepatitis C virus infection before and after liver transplantation.

BACKGROUND/AIMS: Hepatitis G virus (HGV), a new RNA virus that is parenterally transmitted, has frequently been found in patients with chronic hepatitis C (HCV) infection but its role in chronic liver disease is unknown. The purpose of this study was to determine the prevalence of HGV infection in transplantation patients infected with hepatitis C and to assess the impact of HGV co-infection on the course of HCV infection after liver transplantation. METHODS: Eighty-nine liver transplantation recipients with persistent hepatitis C viremia detected by polymerase chain reaction (PCR) were evaluated. Serum samples were tested before and after liver transplantation for HGV RNA by two different PCR methods: LC assay (Abbott Laboratories) and an RT-PCR procedure which we developed using the silica gel technique for extraction of the HGV RNA. E2 antibodies were detected before orthotopic liver transplantation by an EIA-test. HCV RNA was quantified by branched DNA assay, and HCV genotype was determined. A mean of nine liver biopsy specimens were examined for each patient and the severity of the lesions was compared in HCV-positive patients with or without HGV co-infection. RESULTS: The concordance between the two HGV RNA detection methods was excellent and the reproducibility of our RT-PCR procedure was confirmed. The prevalence of pretransplantation and posttransplantation HGV infection was 11% and 19%, respectively. Pretransplantation HGV infection was positively correlated with posttransplantation HGV infection (p<0.001). Before transplantation the E2 antibodies seroprevalence was 34%. Seven patients became HGV RNA positive after transplantation, but all of them were negative for E2 antibodies. Among the patients who remained RNA negative after liver transplantation, 40% were positive for E2 antibodies (p=0.04). Pretransplantation clinical features (except AST mean value) were not different in patients with HCV and HGV co-infection and those with HCV only. After a mean follow-up of 34 months (range: 6 to 70), 67/89 (75%) patients developed histological features of recurrent hepatitis but the frequency of the occurrence of graft hepatitis was not different between HGV/HCV co-infected patients and those with HCV alone (p=0.89). The mean interval from orthotopic liver transplantation to recurrence was 12.2 months (range: 3-63), which was not different for HVG/HVC-co-infected patients and HCV-infected patients. The histological severity of posttransplantation liver disease, and the graft and patient survival were not different for patients with and without HGV co-infection. CONCLUSIONS: Our results suggest the general persistence of HGV infection after liver transplantation, but HGV co-infection did not appear to influence the posttransplantation course of HCV infection. Before transplantation the prevalence of E2 antibodies was 34%, and our data clearly indicate that E2 antibodies were protective against HGV infection.

Adult↗

A comparison of re-infection rates with Schistosoma haematobium following chemotherapy in areas with high and low levels of infection.

Two groups of children (6-15 years) from a Schistosoma haematobium endemic area were followed for 9 months after praziquantel treatment. Seventy-three children came from an area of high infection while 67 children came from an area of low infection. Pre-treatment infection prevalence in the high infection area (76.6%) was significantly higher than that in low infection area (36.3%). Levels of anti-SEA immunoglobulin (Ig)A and IgM were significantly higher and levels of IgG3 significantly lower in children from the low infection area. Nine months after treatment, infection prevalence was significantly higher in the high infection area (29.0%) (where re-infection rates were higher) than in the low infection area (12.9%). Children from the high infection area were six times more likely to get re-infected than those from the low infection area, while younger children were 30 times more likely to get re-infected than older children. These results are discussed in relation to differences in transmission and the development of acquired immunity. Pre-treatment levels of IgM and the difference between IgE and IgG4 were positively associated with re-infection in the high infection area. These results are discussed in relation to the interpretation of simple correlations between infection and some antibody levels and the inference of causal relationships between observed epidemiological and immunological patterns.

Adolescent↗

Responses of Fasciola hepatica infected sheep to various infection levels.

The response to Fasciola hepatica was studied in sheep infected with 5, 30, 150 metacercariae. The animals were necropsied 12 weeks post-infection (p-i) for counting and measuring flukes. Cellular and humoral responses were detected by peripheral eosinophil count, peripheral blood lymphocyte proliferation with excretory-secretory products (FhESP) and ELISA. All sheep were infected at necropsy except one sheep which was infected with 5 metacercariae. Mean parasitic intensities were 40%, 44% and 27% of the infection dose in sheep infected with 5, 30, 150 metacercariae respectively. FhESP-specific lymphocyte responses of the 3 infected groups were significantly enhanced in weeks 3 and 4 p-i (p < 0.05). The kinetics of the specific humoral response were similar for the 3 infected groups but the antibody level was significantly lower in animals infected with 5 metacercariae than in the 2 other infected groups from week 5 p-i to week 12 p-i (p < 0.05). Peripheral eosinophil count was significantly enhanced (p < 0.05) in infected groups. The numbers of peripheral eosinophils were significantly different between the 3 infected groups in week 3, 4 and 6 p-i and were related to infection level. These results confirm that sheep are highly susceptible to F. hepatica infection, even when infection pressure is very low. Peripheral eosinophilia was dependent of the infection level. The immune response was similar in sheep infected with various numbers of flukes.

Animals↗

Reasons for the absence of a history of recurrent genital infections in mothers of neonates infected with herpes simplex virus.

Thirty-one cases of neonatal herpes simplex (HSV) infection were evaluated to determine how often mothers of infected infants lacked a history of recurrent genital infections and the reasons for its absence. A history of recurrent genital infections was elicited from eight (26%) of the mothers. Nine (29%) of the mothers had primary infections; three of these were oral and six were genital. The mother was not the source of infection in three (9.6%) cases. In eleven (35%) cases, the mother had antibody to HSV but did not have a history or findings of primary or recurrent infection. Two of these mothers had positive cervical or vaginal cultures, but neither had genital lesions typical of HSV in the perinatal period. Two mothers had recurrent HSV infections documented later. The source of the HSV infection remained uncertain in 23% of cases including two in which only the father had a history of recurrent genital infection. When mothers with primary infections in the perinatal period were excluded, the HSV neutralization titers of the mothers of infected infants were similar to the titers of the mothers with recurrent genital infections whose infants were not infected. In contrast, the infected infants had titers fourfold lower than their mother's titer as well as fourfold lower than the 16 infants exposed to HSV who remained uninfected. This discrepancy suggests that the mothers may have had a rise in titer late in pregnancy or that placental transport of antibody was limited. Although 26% of the mothers of infected infants had recurrent genital infections, only three (9.6%) had an easily elicitable history.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Incidence of opportunistic and other infections in HIV-infected children in the HAART era.

CONTEXT: Combination anti-retroviral therapy or highly active antiretroviral therapy (HAART) has resulted in a dramatic decline in the incidence of opportunistic and other infections in human immunodeficiency virus (HIV)-infected adults and children. OBJECTIVES: To estimate the incidence of 29 targeted opportunistic and other infections occurring in the era of HAART-between January 1, 2001, and December 31, 2004-in HIV-infected infants, children, and adolescents followed up in Pediatric AIDS Clinical Trials Group (PACTG) 219C; to compare incidence rates in the HAART era to those of the pre-HAART era; and to test for linear trends over time in the HAART era. DESIGN, SETTING, AND PARTICIPANTS: Ongoing, multicenter, prospective cohort study designed to examine long-term outcomes in HIV-infected children. The study population included 2767 children enrolled between September 15, 2000, and December 31, 2004, with information entered in the database up to August 1, 2005, when data analysis was conducted. The pre-HAART era comparison population included 3331 children enrolled in 13 PACTG protocols from October 1988 to August 1998. MAIN OUTCOME MEASURES: First occurrence of each of the 29 targeted infections. RESULTS: Seventy-five percent of the children were enrolled in 2000 and 2001, 90% acquired HIV perinatally, 52% were girls, and 59% were black. The median age was 8.2 years (range, 6-13 years). The median duration of follow-up was 3.4 years. Overall, 553 first episodes of a specific infection occurred among 395 (14%) of the study participants. The number of events for the 4 most common first-time infections and their incidence rates (IRs) per 100 person-years were 123 bacterial pneumonia (IR, 2.15; 95% confidence interval [CI], 1.79-2.56), 77 herpes zoster (IR, 1.11; 95% CI, 0.88-1.39), 57 dermatophyte infections (IR, 0.88; 0.67-1.14), and 52 oral candidiasis (IR, 0.93; 95% CI, 0.70-1.22). Incidence rates of first bacteremia, Pneumocystis jeroveci pneumonia, disseminated Mycobacterium avium complex, lymphoid interstitial pneumonitis, systemic fungal infection, cytomegalovirus retinitis, and tuberculosis were all less than 0.50 per 100 person-years. There were no statistically significant linear trends in incidence for any of the 29 infections over the 4 calendar years. However, infection rates were significantly lower than those reported in the PACTG in the pre-HAART era. The pre-HAART IRs were as follows: for bacterial pneumonia, IR, 11.1; 95% CI, 10.3-12.0; bacteremia, IR, 3.3; 95% CI, 2.9-3.8; herpes zoster, IR, 2.9; 95% CI, 2.6-3.3; disseminated M avium complex, IR, 1.8; 95% CI, 1.5-2.1; P jeroveci, IR, 1.3; 95% CI, 1.1-1.6; oral candidiasis, IR, 1.2; 95% CI, 1.0-1.5; cytomegalovirus retinitis, IR, 0.5; 95% CI, 0.3-0.6; and tuberculosis, IR, 0.2; 95% CI, 0.1-0.4. CONCLUSIONS: Opportunistic infections and other related infections are uncommon in children in the HAART era, and infection rates continue to be lower than those reported in the pre-HAART era. Continued surveillance is important to assess the long-term effect of HAART on the occurrence of opportunistic and other related infections in children.

AIDS-Related Opportunistic Infections↗

The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee.

OBJECTIVE: To determine the prevalence of intensive care unit (ICU)-acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. DESIGN: A 1-day point-prevalence study. SETTING: Intensive care units in 17 countries in Western Europe, excluding coronary care units and pediatric and special care infant units. PATIENTS: All patients (> 10 years of age) occupying an ICU bed over a 24-hour period. A total of 1417 ICUs provided 10 038 patient case reports. MAIN OUTCOME MEASURES: Rates of ICU-acquired infection, prescription of antimicrobials, resistance patterns of microbiological isolates, and potential risk factors for ICU-acquired infection and death. RESULTS: A total of 4501 patients (44.8%) were infected, and 2064 (20.6%) had ICU-acquired infection. Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary tract infection (17.6%), and bloodstream infection (12%) were the most frequent types of ICU infection reported. Most frequently reported micro-organisms were Enterobacteriaceae (34.4%), Staphylococcus aureus (30.1%;[60% resistant to methicillin], Pseudomonas aeruginosa (28.7%), coagulase-negative staphylococci (19.1%), and fungi (17.1%). Seven risk factors for ICU-acquired infection were identified: increasing length of ICU stay (> 48 hours), mechanical ventilation, diagnosis of trauma, central venous, pulmonary artery, and urinary catheterization, and stress ulcer prophylaxis. ICU-acquired pneumonia (odds ratio [OR], 1.91; 95% confidence interval[Cl], 1.6 to 2.29), clinical sepsis (OR, 3.50; 95% Cl, 1.71 to 7.18), and bloodstream infection (OR, 1.73; 95% Cl, 1.25 to 2.41) increased the risk of ICU death. CONCLUSIONS: ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. The potential effects on outcome emphasize the importance of specific measures for infection control in critically ill patients.

APACHE↗

Nosocomial infections among neonates in high-risk nurseries in the United States. National Nosocomial Infections Surveillance System.

BACKGROUND: Nosocomial infections result in considerable morbidity and mortality among neonates in high-risk nurseries (HRNs). PURPOSE: To examine the epidemiology of nosocomial infections among neonates in level III HRNs. METHODS: Data were collected from 99 hospitals with HRNs participating in the National Nosocomial Infections Surveillance system, which uses standard surveillance protocols and nosocomial infection site definitions. The data included information on maternal acquisition of and risk factors for infection, such as device exposure, birth weight category (< or = 1000, 1001 through 1500, 1501 through 2500, and > 2500 g), mortality, and the relationship of the nosocomial infection to death. RESULTS: From October 1986 through September 1994, these hospitals submitted data on 13 179 nosocomial infections. The bloodstream was the most frequent site of nosocomial infection in all birth weight groups. Nosocomial pneumonia was the second most common infection site, followed by the gastrointestinal and eye, ear, nose, and throat sites. The most common nosocomial pathogens among all neonates were coagulase-negative staphylococci, Staphylococcus aureus, enterococci, Enterobacter sp, and Escherichia coli. Group B streptococci were associated with 46% of bloodstream infections that were maternally acquired; coagulase-negative staphylococci were associated with 58% of bloodstream infections that were not maternally acquired, most of which (88%) were associated with umbilical or central intravenous catheters. CONCLUSIONS: Bloodstream infections, the most frequent nosocomial infections in all birth weight groups, should be a major focus of surveillance and prevention efforts in HRNs. For bloodstream infections, stratification of surveillance data by maternal acquisition will help focus prevention efforts for group B streptococci outside the HRN. Within the nursery, bloodstream infection surveillance should focus on umbilical or central intravenous catheter use, a major risk factor for infection.

Bacterial Infections↗

EPIDEMIOLOGY AND PATHOGENESIS OF STAPHYLOCOCCAL INFECTION. I. AN EXPERIMENTALLY INDUCED ATTENUATED STAPHYLOCOCCAL INFECTION IN GUINEA PIGS AND ITS MODIFICATION BY TETRACYCLINE.

An aerosol-induced staphylococcal infection of previously non-infected guinea pigs is described. Investigations concerning the dynamics of this infection indicate that: 1. An infection ("carrier state") could be established predictably in every animal exposed to the aerosol inoculum. 2. Infection was limited to the upper respiratory tract and occurred without apparent systemic dissemination. 3. Cross-infection between infected and non-infected animals did not occur. 4. The initially established infection persisted in detectable form for 6 days or less in the majority of exposed animals. 5. Tetracycline administration prior to and following aerosol infection with tetracycline-resistant strains significantly prolonged the duration of the carrier state. 6. When tetracycline-resistant strains were employed, the infection could be recalled predictably by means of tetracycline administration. 7. Infection initiated with a tetracycline-susceptible strain could not be recalled by tetracycline administration. 8. The mechanism(s) of action of tetracycline in recalling the attenuated infection is (are) unknown. It (they) may not be wholly attributable to ecological changes alone, at least as these are usually considered. The indigenous microflora diminished and changed as a result of tetracycline administration, and no growth-enhancing effect of the antimicrobial of the infection strains was detectable in vitro. 9. The experimental model described lends itself well to the study of attenuated staphylococcal infection in guinea pigs, and to more general studies of staphylococcal epidemiology and pathogenesis.

Aerosols↗

Effect of natural infection with minor pathogens on susceptibility to natural infection with major pathogens in the bovine mammary gland.

OBJECTIVE: To evaluate the effect of natural udder infection with minor pathogens on subsequent natural infection with major pathogens. SAMPLE POPULATION: 7 dairy herds with low bulk milk somatic cell count. PROCEDURE: During a 20-month prospective study, milk samples were collected from diary cows at regular intervals and from quarters with clinical signs of mastitis. Incidence of intramammary infection was calculated in uninfected quarters and in quarters infected with minor pathogens. A within-cow, matched case-control analysis was used to evaluate the effect of minor pathogens on subsequent infection with major pathogens. RESULTS: Quarters infected with minor pathogens had higher somatic cell count than did uninfected quarters. In quarters infected with Corynebacterium bovis, the rate of infection with major pathogens was lower, whereas in quarters infected with coagulase-negative Micrococcaceae, the rate of infection with major pathogens was higher than that in uninfected quarters. From the within-cow comparison, it appeared that, in quarters infected with minor pathogens, infection with major pathogens was significantly lower than that in comparable control quarters not infected with minor pathogens. CONCLUSIONS: Minor pathogens have a protective effect against infection with major pathogens. The protective effect of C bovis against subsequent infection with major pathogens appears to be greater than the effect of coagulase-negative Micrococcaceae.

Animals↗

Histological and microbiological findings in non-infected and infected revision arthroplasty tissues. The OSIRIS Collaborative Study Group. Oxford Skeletal Infection Research and Intervention Service.

An assessment of clinical and laboratory findings is generally required to distinguish between septic and aseptic loosening of a hip implant. In order to evaluate the diagnostic utility of histological and microbiological investigative techniques to differentiate between these two conditions, we analysed their results in 617 patients with hip implant loosening. Histology and microbiology study confirmed the clinical diagnosis of septic loosening in approximately 98% and 89%. respectively. The clinical diagnosis of aseptic loosening was confirmed by histology in 99% of cases. In all but 2 of 81 cases of septic loosening, in which an organism was isolated on microbiological culture, the histological diagnosis of septic loosening was made on the basis of the degree of the acute inflammatory infiltrate (i.e. the presence of 1 or more neutrophil polymorphs per high power field (x 400) on average after examination of at least 10 high power fields) in periprosthetic tissues. In 10 patients for whom there was a strong clinical suspicion of septic loosening but no organisms were isolated on microbiological culture, the histological findings, using the above criteria, were in keeping with the clinical diagnosis of septic loosening. As almost 11% of cases of septic loosening would not have been diagnosed by microbiological investigation alone, our findings indicate that histological examination of periprosthetic tissues should form part of the investigative protocol to distinguish between aseptic and septic loosening.

Adult↗