A cluster of transfusion-associated babesiosis in extremely low birthweight premature infants.

Babesiosis is a parasitic infection of the red blood cells most often acquired by a tick bite. As it has also been known to be transmitted vertically and via transfusion, neonates have occasionally been reported with the infection. Here, we report a series of three premature neonates who acquired babesiosis via blood transfusion from a single donor, one of whom had difficulty clearing the infection and required multiple antimicrobials.

Fifth (human parvovirus) and sixth (herpesvirus 6) diseases.

Fifth (erythema infectiosum) and sixth (roseola infantum) diseases are common rash illnesses of childhood that have long been recognized in clinical medicine. The discovery of the viruses that cause these illnesses has revealed relationships with other syndromes. Primary infection with the agent of erythema infectiosum, human parvovirus B19, is associated with transient aplastic crisis in hemolytic anemia, arthropathy in adults, chronic anemia in immunocompromised patients, and nonimmune fetal hydrops in pregnant women. The only documented illness associated with primary infection with human herpesvirus 6 is roseola or exanthema subitum in young children. However, reactivated infections in adults and immunocompromised patients may be associated with serious illness such as encephalitis/encephalopathy, and bone marrow suppression leading to transplant failure or graft-versus-host disease. Diagnostic studies for both viruses have been limited, although reliable serologic tests for human parvovirus B19 have recently become available. Diagnosis of human herpesvirus 6 remains problematic, because current tests cannot differentiate primary from reactivated disease. This is more of an issue for the putative relationship of these viruses to more chronic conditions, such as rheumatologic disease for human parvovirus B19 and multiple sclerosis for human herpesvirus 6. The relationship between the viruses and these conditions remains controversial, and better diagnostic tests and further information on viral pathogenesis for both viruses are required in order to make a reliable judgment in this regard.

Human parvovirus B19 infection in infancy associated with acute and chronic lymphocytic myocarditis and high cytokine levels: report of 3 cases and review.

Human parvovirus B19 infection is occasionally associated with acute lymphocytic myocarditis (ALM). Three infants with B19 virus-associated ALM were followed up clinically, histologically, and immunovirologically. Each infant had B19 virus DNA in the blood or B19 virus-specific IgM antibodies. Two infants with postnatal infection recovered after immunosuppressive therapy. The third infant with possible prenatal infection developed chronic persistent myocarditis associated with persistent B19 virus DNA in the blood. All 3 infants had increased levels of interferon-gamma, tumor necrosis factor-alpha, and interleukins -6 and -8. Four newborns with congenital B19 virus infection and 4 infants and children who had postnatally acquired B19 virus infection without myocarditis all had normal levels of these cytokines. These observations suggest that B19 virus infection in infancy causes ALM in some infants and children.

Serologic and virologic evidence for frequent intrauterine transmission of human parvovirus B19 with a primary maternal infection during pregnancy.

OBJECTIVE: To define the intrauterine viral transmission rate during primary maternal parvovirus B19 infection and identify factors that may influence this rate. METHODS: Forty-three pregnant women at two medical centers were identified with a primary B19 infection and followed to delivery. At delivery maternal and infant (umbilical cord) blood was obtained for B19 serologic and virologic PCR testing. RESULTS: All of the women delivered healthy infants at term and none was hydropic. Overall 22 (51%) of the 43 infants had some evidence of a congenital B19 infection. B19-specific IgM was detected in 11 infants at delivery, B19 IgA was detected in 10 and B19 DNA was detectable by PCR in 11 infants. One infant was negative at birth but became positive for IgM, IgA and PCR at 6 weeks of age. No association was found between the likelihood of intrauterine infection and: maternal age; symptomatic maternal infection; method of delivery; maternal IgG titer at delivery; maternal IgG avidity at delivery; or maternal viremia at delivery. Intrauterine infection was associated with maternal IgM positivity at delivery; this association may have been a result of maternal infection occurring later in gestation. CONCLUSION: Although the incidence of intrauterine hydrops and fetal demise after maternal infection is low, there is a high rate of intrauterine viral infection that occurs throughout gestation and yields newborns who, although infected in utero, are asymptomatic at birth.

Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms.

OBJECTIVE: To assess the risk of maternal parvovirus B19 infection from exposure to various sources and the fetal morbidity of those infections. METHODS: We obtained demographic and occupational information about pregnant women exposed to sources of B19 and about the nature and duration of the exposures. We performed serologic testing 10-14 days after exposure using an indirect capture enzyme-linked immunosorbent assay. Women with immunoglobulin (Ig) M were examined with weekly ultrasound until 12 weeks after exposure, and the outcome of the pregnancy was ascertained from interviews with patients and their obstetricians. Logistic regression analysis was used to determine risk factors for maternal immunity and infection by B19. RESULTS: Of 618 pregnant women exposed, 307 (49.7%) were immune to B19, 259 remained susceptible after exposure, and 52 (16.7% of all susceptibles) contracted B19 infection. None of the 52 fetuses of infected women developed nonimmune hydrops, and there were no fetal deaths attributable to B19 in this group. The relative risk of maternal B19 infection was 2.8 if the source was a related child living in the household (95% confidence interval 1.7, 4.6; P < .001). No significant differences were found for maternal B19 infection in eight categories of maternal occupation. Maternal symptoms of polyarthralgia (46%), fever (19%), and nonspecific rash (38%) were significantly more common (P < .001) in IgM-positive patients than in noninfected women (4.1%, 2.8%, and 5.7%, respectively). Only 17 (33%) of the IgM-positive women were entirely asymptomatic. CONCLUSION: The risk of maternal B19 infection in pregnancy could not be predicted by a gravida's occupation, but it was significantly higher when the source of exposure was her own child. The fetal risk of nonimmune hydrops after maternal B19 infection must be very low. As a consequence, exclusion of pregnant women from the workplace during endemic periods with seasonal clusters of cases is not justified. Weekly fetal ultrasound evaluation in these cases carries a low yield.

Parvovirus B19 infection in patients with hemophilia.

BACKGROUND: The long-term consequences of parvovirus B19 infection in transfusion recipients are not known, and thus the value of B19 screening of blood donors remains unresolved. Hemophiliacs, at risk for B19 through their chronic exposure to clotting factor concentrates, have frequent, close medical follow-up and thereby constitute an ideal group in which to study the hematologic sequelae of B19 infection. STUDY DESIGN AND METHODS: An enzyme-linked immunosorbent assay was used to detect B19 IgG and IgM and the polymerase chain reaction was used to detect B19 DNA in frozen, stored plasma samples, obtained between 1987 and 1994, from 136 subjects with hemophilia, including 71 who were human immunodeficiency virus (HIV)-positive and 65 who were HIV-negative. Then the results of the tests were compared with clinical hematological data and blood product usage data. RESULTS: B19 seroprevalence in the hemophilic cohort was 81.6 percent (111/136), including 74.6 percent (53/71) of HIV-positive and 89.2 percent (58/65) of HIV-negative hemophiliacs. It was not affected by age, type or severity of hemophilia, HIV status, CD4 number, or yearly blood product usage. Only 1 (0.7%) of the 136 samples was positive for B19 IgM and none was positive in polymerase chain reaction for B19 DNA. After adjusting for HIV status, there were no differences between B19-positive and B19-negative hemophiliacs in hematologic values, CD4 counts, or blood product use. CONCLUSION: Although B19 IgG seroprevalence in this hemophilic cohort is high and indicative of past B19 infection, there is no detectable B19 viral activity or any associated long-term clinical or hematologic sequelae.

Intrauterine parvovirus B19 infection may cause an asymptomatic or recurrent postnatal infection.

Although infection with parvovirus B19 (B19) during pregnancy may cause fetal demise, the true incidence of intrauterine infection is unknown. For 19 women with serologically confirmed B19 infections between 4 and 38 weeks of gestation, we performed follow-up examinations of their infants. Serial sonograms of the 19 fetuses showed that none developed hydrops. All 19 women delivered healthy term infants. Cord sera of four infants were tested for IgM to B19 and three were positive. Between 3 and 21 months of age, all 19 infants had normal physical examinations, developmental evaluations and hematocrits; and 16 lacked IgG to B19. One infant who was IgM-positive to B19 at birth was IgM-positive at age 7 months when he also had an IgG titer to B19 of 1:500,000 (mother's concurrent titer, 1:10,000), and had B19 DNA in serum detected by polymerase chain reaction. The other two infants who were IgM-positive at birth were IgM- and IgG-negative by 11 and 16 months of age. These results suggest that intrauterine B19 infection may be frequent and occasionally cause an asymptomatic postnatal infection.

Risk of human parvovirus B19 infections among school and hospital employees during endemic periods.

Because human parvovirus B19 (B19) infections are common in children, and maternal infection of pregnant women may cause fetal death, risk factors for B19 infections for hospital and school employees were identified during an endemic period. By serologic testing, 2730 employees of 135 schools in three school systems and 751 employees of a hospital were monitored. Of these, 60% were initially seropositive. After adjusting for age, race, and gender, risk factors for seropositivity were contact with children 5-18 years old at home (odds ratio [OR] = 1.2), at work (OR = 1.2), and employment in elementary schools in school system 2 (OR = 1.4). Over 42 months, 1 of 198 susceptible hospital employees seroconverted versus 62 of 927 school employees. Four factors associated with seroconversion were employment at elementary schools in system 2, contact with children 5-11 years old at home or with children 5-18 years old at work, and age < 30 years. Those in daily contact with school-age children had a fivefold increased annual occupational risk for B19 infection.

Aplastic crisis.

Red blood cell aplasia in pediatric patients who have chronic hemolysis is associated most frequently with B19 infection. Although this entity is usually recognized easily, other red cell hypoplastic anemias, such as TEC and Diamond-Blackfan anemia, must be considered as part of the differential diagnosis. Although usually a transient event, an aplastic crisis has the potential for significant morbidity. The patient usually can be supported through the episode without incident with the judicious use of erythrocyte transfusions. The recognition of the infectious nature of the event is important for an understanding of the clinical manifestation, course of illness, and need for isolation. Several questions remain unanswered regarding the pathogenesis and treatment of this disorder. Could the use of intravenous gamma-globulin prove effective in treating select cases of B19-induced red cell aplasia? Are there effective measures to prevent B19 infection in children at risk for significant morbidity from such infection? There is interest in development of a vaccine to B19, and children with hereditary hemolytic anemias represent a potential target group for its use. Are there other viruses that cause red cell aplasia, especially in the case of TEC? It is hoped that current research will provide the answers for more effective treatment and possible prevention of these aplastic crises.

Manifestations and treatment of human parvovirus B19 infection in immunocompromised patients.

We diagnosed infections from human parvovirus B19 in three patients by using dot-blot hybridization and a polymerase chain reaction to detect B19 DNA and using an enzyme immunoassay to detect IgG and IgM to B19. For 5 months a 5-year-old boy with acute lymphoblastic leukemia in remission had anemia without reticulocytes or bone marrow erythrocyte precursors. His serum lacked IgG and IgM to B19 but contained B19 DNA. He received gamma globulin intravenously (0.4 gm/kg/day for 5 days); his viremia promptly cleared and reticulocytosis developed. A 14-year-old boy with acute lymphoblastic leukemia in remission had fever, rash, neutropenia (less than 300 leukocytes/mm3), and a hemophagocytic syndrome lasting 3 weeks. His serum contained IgM to B19 and B19 DNA. Without therapy, IgG to B19 developed; although low levels of B19 DNA persisted, the leukocyte count returned to normal. In a 19-year-old patient with systemic lupus erythematosus and hemolytic anemia, an aplastic crisis lasted 2 weeks. Her serum lacked IgG and IgM to B19 but contained B19 DNA. Without therapy, IgG and IgM to B19 appeared, viremia diminished, and reticulocytosis occurred. These patients illustrate the varied manifestations of chronic B19 infections, the importance of DNA detection for diagnosis, and the possible efficacy of gamma globulin therapy.

Detection of human parvovirus B19 DNA by using the polymerase chain reaction.

The polymerase chain reaction (PCR) was investigated for detecting human parvovirus B19 (B19) DNA in sera. Three pairs of oligonucleotides were evaluated as primers. The best oligonucleotide pair spanned 699 nucleotides, including the region common to VP1 and VP2. After PCR amplification of B19 DNA in serum, a 699-nucleotide DNA fragment was detected on agarose gels. This DNA fragment was B19 DNA, because after Southern transfer it hybridized to a 19-nucleotide internal probe and contained a single PstI cleavage site. Dot blot hybridization with a radiolabeled cloned portion of the B19 genome as a probe was compared with PCR. PCR was 10(4) times more sensitive than dot blot hybridization and, with an internal radiolabeled probe, 10(7) times more sensitive than dot blot hybridization. Of 29 serum specimens from 18 patients with proven B19 infections, 24 were PCR positive. None of 20 serum samples from uninfected controls were positive. Of 22 serum samples positive for immunoglobulin M to B19, PCR detected B19 DNA in 17. Seven serum samples lacking immunoglobulin M were PCR positive. PCR detected B19 DNA in urine, amniotic fluid, pleural fluid, ascites, and leukocyte extracts. PCR is a rapid and simple method for diagnosing infections with human parvovirus B19 but must be combined with serologic tests for immunoglobulin M to B19, especially when testing only a single serum sample.

Human parvovirus B19 infections in women of childbearing age and within families.

Human parvovirus B19 (B19) crosses the placenta causing fetal death. We used an indirect capture enzyme immunoassay to measure IgG to B19 in sera of 845 subjects from 2 groups. The first group included 405 women (mean age, 30 years) composed of 85 pediatric nurses and 130 other female hospital employees, 122 women employed caring for preschool children and 68 mothers of preschool children enrolled in day care. Twenty-eight percent of all these women were seropositive. Seropositivity was unrelated to occupational group. Four of 235 women observed between 1983 and 1987 for a mean of 435 days/woman acquired B19 infections (an annual seroconversion rate of 1.5%). We investigated intrafamilial associations of B19 infection in a second group of 440 subjects from 111 families. Seropositivity of parents was not associated with seropositivity of their children. Seropositivity of one spouse was not associated with seropositivity of the cospouse. However, of 47 seropositive older siblings, 32 (68%) of their younger siblings were seropositive, compared to 20 (18%) seropositive younger siblings of 112 seronegative older siblings (P less than 0.001). B19 infections increased with age from 19% for those younger than 10 years to 67% for those older than 49 years. For all ages females had a higher rate (51%) of B19 infection than males (38%). These data suggest that children may be more susceptible to B19 than adults and B19 infections occur infrequently among women younger than 40 years of age. However, during local outbreaks the B19 infection rate for susceptible pregnant women remains unknown.

Early treatment of Campylobacter jejuni enteritis.

The bacteriologic and clinical effects of early antibiotic treatment of Campylobacter jejuni enteritis were studied. Erythromycin rapidly eliminated C. jejuni from stools, whereas trimethoprim-sulfamethoxazole did not. Despite its bacteriologic effectiveness, erythromycin did not reduce the duration or severity of diarrhea, abdominal pain, or other symptoms.

Failure to thrive due to obstructive sleep apnea.

The clinical features of two children with failure to thrive due to obstructive sleep apnea are presented. Both patients had subnormal growth velocities for height and weight for many months before diagnosis; both were underweight for height. Relief of their airway obstruction by adenotonsillectomy was promptly followed by catch-up growth and subsequent normal growth velocities. Obstructive sleep apnea should be considered in the differential diagnosis of failure to thrive in children.

Human physiological response and adaption to ammonia.

Other than anecdoted observations, there are no published reports on the physiological effects of ammonia at concentrations normally encountered industrially or information on whether inurement develops after repeated exposure. Six unacclimated male and female volunteers were exposed six hours per day over a six week period to concentrations of 25, 50, and 100 ppm ammonia in an industrial environment, under strict medical surveillance. Inurement to eye, nose, and throat irritation was demonstrated after two to three weeks in addition to short-term subjective adaption. There were no significant differences between subjects or controls on common biological indicators, in physical examinations, or in performance of normal job duties. After acclimation, continuous exposure to 100 ppm, with occasional excursions to 200 ppm, is easily tolerated and has no observed effect on general health.