A nosocomial outbreak of Branhamella catarrhalis confirmed by restriction endonuclease analysis

An outbreak of respiratory illness due to Branhamella catarrhalis occurred in the intermediate care unit of a Veterans Administration hospital and involved patients and staff members. Four patients had pneumonia and four had bronchitis. Infected patients were placed in a cohort separated from noninfected patients and were treated. Pharyngeal culture was used to survey prevalence in staff and all other patients on the unit; three of 18 staff members and two of 19 asymptomatic patients were positive for B. catarrhalis. A case-control study showed that respiratory therapy, steroid use, and location within the unit were significant risk factors for B. catarrhalis infection or colonization. Strains from five patients and two staff members had identical bacterial restriction endonuclease digestion patterns with three different enzymes; these patterns were distinct from those of control strains. This study is the first to document an outbreak of B. catarrhalis infection confirmed with a typing system and thus establishes B. catarrhalis as a nosocomial pathogen.     

Virus-specific IgM antibodies in acute gastroenteritis due to a reovirus-like agent (rotavirus).

62 serum samples from 24 patients with rotavirus gastroenteritis were tested for IgM antibodies against a bovine rotavirus by an indirect fluorescent antibody technique. IgM antibodies were detected in one or more of the serum samples from all but one of the patients. IgM antibodies were not detected in samples obtained from 11 of the patients after the 5th week of illness. Absorption of sera for IgG with Staphylococcus aureus increased the sensitivity of the IgM antibody test. It is concluded that the presence of IgM antibodies against bovine rotavirus in a patient's serum, as measured by the present technique, does suggest a recent rotavirus infection. On the other hand, the lack of IgM antibodies in the serum of a child with acute gastroenteritis between the second and the 5th week of illness tends to exclude rotavirus as a cause of the disease.     

Oral administration of human rotavirus to volunteers: induction of illness and correlates of resistance

Four of 18 volunteers challenged orally with human rotavirus strain D (subgroup 2, serotype Wa) developed a diarrheal illness two to four days after inoculation. Viral shedding was detected in five of the 18 volunteers, whereas 12 (67%) developed serologic evidence of infection. Two volunteers who developed diarrheal illness after the initial inoculation were given the same inoculum 19 months later; neither developed diarrhea, although one developed constitutional and gastrointestinal symptoms. The presence of preinoculation serum immunofluorescent antibody to rotavirus strain D or high levels of neutralizing antibody to Wa or reassortant DS-1 human rotavirus correlated with resistance to diarrheal illness. Although prechallenge serum antibody correlated with resistance to diarrhea and/or shedding of rotavirus, the relationship of preexisting local neutralizing activity in intestinal fluid was less clear-cut.     

The immune response in primary asymptomatic and symptomatic rotavirus infection in newborn infants

Systemic and mucosal immune responses were determined using an enzyme-linked immunosorbent assay in 18 infants (7-86 days old) experiencing primary rotavirus infections over two winters. Fifteen infected infants were asymptomatic; 3 had diarrhea. Neutralization antibody (NA) was assayed in two asymptomatic infants who had a serotype 1 isolate identified. Seven asymptomatic infants had sera available for analysis; none had IgG, 1 had IgM, but 4 had IgA antibody responses. Neither tested infant had a serotype 1 NA rise. In the 3 symptomatic infants, 1 had IgG, 2 had IgM, and all had IgA serum antibody responses detected. Eleven (73%) of 15 asymptomatic and all symptomatic infants had a rotavirus-specific fecal antibody response. These findings identify IgA as an important antibody in primary rotavirus infection in very young infants. The predominance of this antibody in asymptomatic infants suggests that their responses (and protection on subsequent reexposure) may be primarily mucosal.     

Rotavirus infections in families. A clinical and virological study.

Among 25 family members of 8 children with acute rotavirus gastroenteritis (8 siblings and 17 adults) gastroenteritis was recorded in 9 (5 siblings and 4 adults), and minor symptoms in 8 (2 siblings and 6 adults). A rotavirus infection was diagnosed in 7 of the family members with gastroenteritis and was probably the cause of the disease in the remaining 2 in this group. Four of the 8 family members with minor symptoms were infected with rotavirus, whereas no infection was detected among the 8 family members without symptoms. Serological findings sugggested that infants and young children underwent a primary infection with rotavirus, whereas older children and adults probably were reinfected. Adults as well as children with rotavirus infection excreted virus and may have served as sources of infection.     

Estimating hospital admissions due to rotavirus gastroenteritis from hospital episode statistics

OBJECTIVES: To determine the proportion of hospital admissions, in children < 5 years old, coded for intestinal infectious disease or non-infectious gastroenteritis, using ICD-10 codes, that were due to rotavirus infection. To assess how many children admitted with rotavirus gastroenteritis were given the specific ICD-10 code (A080) for this disease. METHODS: Sixteen-month prospective, observational study of children < 5 years old, admitted to district general hospital with: acute gastroenteritis (> or =3 loose stools/day), proven rotavirus infection and those coded as intestinal infectious disease or non-infectious gastroenteritis. RESULTS: Four hundred and twenty children < 5 years old were admitted with acute gastroenteritis. Rotavirus was detected in 170 children's stools. Acute rotavirus gastroenteritis accounted for 81/397 (20%) children coded as having non-infectious gastroenteritis and 32/81 (40%) coded for intestinal infectious disease. Only 18 children were coded for rotavirus gastroenteritis. Potentially preventable rotavirus gastroenteritis occurred in 122 children; 78 coded as non-infectious gastroenteritis (20%) and 26 coded for intestinal infectious disease (34%). CONCLUSIONS: The proportion of children coded with diarrhoeal diseases and found to have rotavirus is less than previously estimated. Using the specific code for rotavirus infection to estimate hospital admissions would be a gross underestimate. Hospital episode statistics cannot reliably estimate the burden of disease due to rotavirus.     

Reovirus-like agent in acute epidemic gastroenteritis in Japanese infants: fecal shedding and serologic response.

The reovirus-like agent, sometimes referred to as duovirus or rotavirus, was visualized by electron microscopy in stool extracts from Japanese infants and young children with acute epidemic gastroenteritis. The virus particles measured 70 nm in diameter and had double-shelled capsids. One hundred ten (89%) of 124 patients with the gastroenteritis had such virus particles in stools obtained during the acute phase. The virus particles were excreted in the stools usually during the first eight days of illness. Agglutination of virus particles by antibody present in convalescent-phase sera was demonstrated by immune electron microscopy. Complement-fixing antibody was detected as early as day 3 of illness, and antibody titers peaked during the second and third weeks of the disease. The antibody appearing in the acute and early convalescent phases was sensitive to 2-mercaptoethanol. Antibody resistant to 2-mercaptoethanol was produced approximately 10 days after the onset of the symptoms. The serologic evidence suggests that a primary infection with the reovirus-like agent was responsible for the clinical attack of acute gastroenteritis.     

Serum antibody as a marker of protection against natural rotavirus infection and disease

To determine whether naturally acquired serum IgA and IgG antibodies were associated with protection against rotavirus infection and illness, a cohort of 200 Mexican infants was monitored weekly for rotavirus excretion and diarrhea from birth to age 2 years. Serum samples collected during the first week after birth and every 4 months were tested for anti-rotavirus IgA and IgG. Children with an IgA titer >1:800 had a lower risk of rotavirus infection (adjusted relative risk [aRR], 0.21; P<.001) and diarrhea (aRR, 0. 16; P=.01) and were protected completely against moderate-to-severe diarrhea. However, children with an IgG titer >1:6400 were protected against rotavirus infection (aRR, 0.51; P<.001) but not against rotavirus diarrhea. Protective antibody titers were achieved after 2 consecutive symptomatic or asymptomatic rotavirus infections. These findings indicate that serum anti-rotavirus antibody, especially IgA, was a marker of protection against rotavirus infection and moderate-to-severe diarrhea.     

Nosocomial transmission of delta hepatitis

A previously asymptomatic carrier of hepatitis B virus receiving chronic hemodialysis developed acute delta hepatitis. The patient regularly received dialysis treatments on the same machine as a parenteral drug abuser with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis whose serum was strongly positive for delta antibody. The drug abuser had a major bleeding episode that caused extensive environmental contamination 3 months before onset of illness in the index patient. No other patients receiving dialysis or staff members had evidence of delta infection. A surgeon previously infected with hepatitis B from the same parenteral drug abuser also had delta antibody. Testing for delta virus is indicated for both HBsAg-positive parenteral drug abusers and patients with hemophilia receiving chronic hemodialysis. All patients who are HBsAg- and delta-positive should receive dialysis separately from patients who are HBsAg-positive and delta-negative. Susceptible patients on dialysis and staff should receive hepatitis B vaccine to protect against both hepatitis B and delta virus infection.     

CEREBRAL DYSFUNCTION WITH EVIDENCE OF CEREBRAL HIV INFECTION AMONGST ASYMPTOMATIC HIV SEROPOSITIVE SUBJECTS

Twelve asymptomatic HIV seropositive subjects ages 21 to 40 years were examined for serologic evidence of cerebral HIV infection, for cerebral structural abnormalities, and for neuropsychologic evidence of cerebral dysfunction using standard methods. Eleven of the 12 had antibody to HIV in the cerebrospinal fluid (CSF). Nine subjects had oligoclonal immunoglobulins in the CSF, of whom five had some for which there were no corresponding serum oligoclonal immunoglobulins (‘unique’ oligoclonal immunoglobulins). Intracerebral synthesis of HIV specific antibodies was demonstrated for four subjects. Significant deficits of memory and frontal lobe function were found in five of the 12 subjects. Subjects who had oligoclonal immunoglobulins unique to the CSF all had significant neuropsychological abnormalities. No structural cerebral abnormalities were demonstrated using CT scanning for any subject tested. These results support other evidence that HIV is neurotropic and capable of directly inducing brain damage even in immunologically normal subjects. Tests of memory and frontal lobe function are frequently abnormal in patients with early HIV infection, and identify as abnormal a similar group of patients to immunological or biochemical tests which might indicate cerebral HIV infection.     

Group- and type-specific serologic response in infants and children with primary rotavirus infections and gastroenteritis caused by a strain of known serotype

Antibody response to group A rotavirus (RV), investigated in paired sera from 72 infants and young children with acute gastroenteritis caused by an RV infection, was diagnosed on the basis of a fourfold or greater rise in group A common RV IgG antibody titer. Virus-specific IgM was detected in sera from 64 patients showing seroconversion; these were considered primary infection. RV was detected in stools of 56 (77.8%) patients with serologic evidence of infection and 54 were considered primary infection isolates: 39, serotype 1; 11, serotype 4; and 2, serotype 2. Two could not be typed. Neutralizing antibody studies showed that in primary infections serotype 1 induced an antibody response to serotype 4 at least fourfold lower than the homotypic response; serotype 2 elicited antibody titers to serotypes 1 and 4 at least fourfold lower than homotypic titer; and serotype 4 infections produced a response to serotype 1 as high as the homotypic response. Of 12 patients with primary infection, virus was not typed in 2 or detected in 10; however, the infecting serotype was identified on the basis of distinct patterns of homotypic and heterotypic antibody response.     

A long-term survey of rotavirus infection in Japanese children with acute gastroenteritis.

Human rotavirus was detected by electron microscopic examination of the stools of 320 (63%) of 506 infants and young children hospitalized with acute gastroenteritis between December 1974 and March 1977. Serologic responses to infection with the rotavirus were revealed by the complement-fixation test in 130 (70%) of 185 patients examined. During the study period three epidemics of human rotavirus infection occurred during the winter months. The peak incidences occurred in January 1975 (88% of patients positive by serologic analysis or electron microscopy of stools), January 1976 (92%), and February 1977 (96%). Rotavirus was detected in the stools of 288 (79%) of 365 patients tested during the cooler months (December to March) and 35 (25%) of 141 during the rest of the year. In the summer (June to August), rotavirus infection occurred rarely. The frequency of human rotavirus infection was highest among patients aged six to 11 months. These results indicate that human rotavirus can be regarded as a major etiologic agent of acute gastroenteritis in infants and young children, of which wintertime epidemics are common in Japan.     

A reovirus-like agent (rotavirus) in gastroenteritis of children. Virus detection and serological studies.

A reovirus-like agent (rotavirus) was detected in 26 children (44%) when fecal specimens from 59 children with acute gastroenteritis were examined by electron microscopy. No rotavirus was detected in the feces of 49 children with other diseases. Sera from the acute and the convalescent phase from 40 children with acute gastroenteritis and from 18 other patients were examined for antibodies against a bovine rotavirus by an indirect fluorescent antibody test. 26 of the patients with gastroenteritis (65%) developed antibodies during their disease, whereas none of the other patients showed a rise in antibody titre. The specimens were submitted to the laboratory from hospitalized children during the period January 1973 through March 1975. Most of the cases of rotavirus gastroenteritis occurred during late autumn and early winter among children between 0.5 and 3 years of age. It is concluded that electron microscopy is a sensitive diagnostic technique during the acute phase of the disease, and that the serological test with bovine rotavirus antigen served as a useful diagnostic tool.     

Effects of antibody to rotavirus on protection of adults challenged with a human rotavirus

Effects of preinoculation rotavirus antibody titers on the probability of infection and illness were evaluated in adults challenged orally with different doses of a virulent human rotavirus (CJN strain). Preinoculation titers considered were serum neutralizing antibody, serum rotavirus IgA, serum rotavirus IgG, jejunal neutralizing antibody, jejunal rotavirus IgA, and stool rotavirus IgA. Doses of virus of either 9 x 10(1) or 9 x 10(3) focus-forming units were administered to 19 subjects each. Twenty-six were infected; 15 experienced illness. The probability of either outcome was unrelated to dose. Stool rotavirus IgA titers could not be correlated to either infection or illness, but the mean titers of the other five antibodies were significantly or nearly significantly lower in subjects infected or ill, when compared with those negative for either outcome. When analyzed by stepwise logistic regression, only serum rotavirus IgG remained significantly (P = .005) related to the probability of infection, and only jejunal neutralizing antibody remained significantly (P = .01) related to the probability of illness.     

Mutation Distribution in the NSP4 Protein in Rotaviruses Isolated from Mexican Children with Moderate to Severe Gastroenteritis

The NSP4 protein is a multifunctional protein that plays a role in the morphogenesis and pathogenesis of the rotavirus. Although NSP4 is considered an enterotoxin, the relationship between gastroenteritis severity and amino acid variations in NSP4 of the human rotavirus remains unclear. In this study, we analyzed the sequence diversity of NSP4 and the severity of gastroenteritis of children with moderate to severe gastroenteritis. The rotavirus-infected children were hospitalized before the rotavirus vaccine program in Mexico. All children had diarrhea within 1−4 days, 44 (88%) were vomiting and 35 (70%) had fevers. The severity analysis showed that 13 (26%) cases had mild gastroenteritis, 23 (46%) moderate gastroenteritis and 14 (28%) severe. NSP4 phylogenetic analysis showed three clusters within the genotype E1. Sequence analysis revealed similar mutations inside each cluster, and an uncommon variation in residue 144 was found in five of the Mexican NSP4 sequences. Most of the amino acid variations were located in the VP4 and VP6 binding site domains, with no relationship to different grades of gastroenteritis. This finding indicates that severe gastroenteritis caused by the rotavirus appears to be related to diverse viral or cellular factors instead of NSP4 activity as a unique pathogenic factor.     

Antibodies to parvovirus B19 non-structural protein are associated with chronic but not acute arthritis following B19 infection

OBJECTIVE: To determine the incidence and significance of antibodies to the parvovirus B19 non-structural (NS1) protein in B19-infected persons during acute infection and convalescence. METHODS: The B19 NS1 protein was expressed in SF9 cells using the baculovirus expression system and was used to prepare immunofluorescence slides. These were used in a fluorescent antibody test to determine anti-B19 NS1 IgG in a well-characterized cohort of 53 persons at the time of acute B19 infection and again after a follow-up period of 26-85 months. Results were examined for statistical significance by the use of Fisher's exact test. RESULTS: NS1 antibodies were detected in five of 32 persons with acute B19 infection (four with arthritis) and 10 of 53 persons with past B19 infection (six with chronic arthritis and two with chronic arthritis and chronic fatigue syndrome). Regarding the correlation of NS1 antibodies and arthritis, at the time of acute infection four of 24 persons with arthritis had NS1 antibodies detected compared with one of eight persons with any other symptoms (P: = 1). During convalescence, eight of 20 persons with chronic arthritis had NS1 antibodies compared with two of 33 with symptoms of any other category (all except one were asymptomatic) (P: = 0.007). All 10 patients with NS1 antibodies during convalescence had arthritis during acute infection, which persisted in eight persons until the time of follow-up. CONCLUSION: Antibodies to parvovirus B19 NS1 protein are associated with chronic but not with acute arthritis after B19 infection.     

Comparison of the number of Norovirus genome copies in patients and healthy persons

In viral gastroenteritis outbreaks occurred by Norovirus (NV), NV was detected not only from patients but also from healthy persons who have taken the same food, and also detected from healthy staff members working at community places such as hospital, school and nursing home. The number of fecal NV genome copies of patients, healthy persons and food handlers are examined by real-time PCR method, to investigate foodborne gastroenteritis and person to person transmission outbreaks. There is no significant difference on the number of NV genome copies in feces between patients, and NV-detected healthy persons. Those result indicate asymptomatic carrier of NV who were working as food handlers or staff members at community places will become an origin of food-borne gastroenteritis or person to person transmission outbreaks.     

Gastroenteritis in Auckland: An aetiological and clinical study

Faecal specimens from 60 patients (under six years old), most of whom were Maoris and Pacific Islanders admitted to Auckland Hospital with gastroenteritis during the months of June and July 1977, were examined for the presence of faecal viruses, bacterial pathogens and parasites. Faecal specimens from 18 non-diarrhoeal control patients were also examined, of which three contained rotavirus. Forty-three (72 per cent) gastroenteritis patients had rotavirus detectable in stools by electron microscopy or immune electron microscopy. Of the remainder, 17 patients were regarded as having non-rotavirus diarrhoea. Enterotoxigenic Esch. coli. was isolated from seven patients of whom six yielded stable toxin producers (ST+), four labile toxin producers (LT+) and two dual toxigenic strains (ST+/LT+). All ST+ isolates appeared to be of low enterotoxigenicity as indicated by low gut weight/carcass weight ratios in the infant mouse assay. Rotavirus was the commonest aetiological agent (72 per cent), bacterial pathogens (alone) accounted for only five per cent and no enteric pathogens were found in 15 per cent of cases. Non-agglutinable rotavirus, presumably a different serotype, was seen in both gastroenteritis and control patients. Rotavirus ‘satellite’ particles previously undescribed were demonstrated in a number of stool samples.     

Norovirus outbreaks in a teaching hospital: the role of infection control

In January 2004, 20 patients and 19 staff in one ward became ill in an outbreak of norovirus-related gastroenteritis over a 12-day period. The epidemic curve indicated person-to-person transmission. Infection control measures were instituted in consultation with the government health authorities. A prompt rigorous response may have prevented spread to other wards. In March 2004, 54 staff and 1 member of a patient's family became ill in an outbreak of gastroenteritis. The source of norovirus contamination was associated with food served at the hospital restaurant. Secondary infection was prevented because the outbreak was recognized early and staff members with gastroenteritis symptoms were asked to stay home. Immediate control measures, such as identification and announcement of the outbreak, isolation of symptomatic individuals from others, personal protection, helped control the infection.     

Effect of vaccination on serotype-specific antibody responses in infants administered WC3 bovine rotavirus before or after a natural rotavirus infection

In an evaluation of WC3 bovine rotavirus (serotype 6) vaccine in infants, some subjects experienced a natural serotype 1 rotavirus infection before vaccination and others after. Therefore, the effects of both WC3 and natural rotavirus strains as either primary or boosting immunogens on serotype-specific neutralizing antibody responses could be determined. After primary natural infection (symptomatic or asymptomatic), neutralizing antibody titers were highest to serotype 1 but were consistently high to serotype 3, and low titers (greater than or equal to 20) to serotypes 2 and 4 were often detected. Previous vaccination with WC3 had little effect on the magnitude of these responses. In contrast, subjects infected with serotype 1 strains before vaccination experienced large (average, 12-fold) rises in neutralizing antibody to human serotypes 1-4 when vaccinated with WC3. Thus, although WC3 and the natural strains are distinct serotypes, their epitopes were sufficiently similar that reinfection with WC3 could boost neutralizing antibody titers to human serotypes in subjects primed by a previous natural infection.