Dynamic gut microbiome changes following regional intestinal lymphatic obstruction in primates.

The pathogenesis of inflammatory bowel disease (IBD) has been linked with lymphostasis, but whether and how lymphatic obstruction might disturb the intestinal microbiome in the setting of Crohn's Disease (CD) is currently unknown. We employed a new model of CD in African Green monkeys, termed 'ATLAS' (African green monkey truncation of lymphatics with obstruction and sclerosis), to evaluate how gut lymphatic obstruction alters the intestinal microbiome at 7, 21 and 61 days. Remarkable changes in several microbial sub- groupings within the gut microbiome were observed at 7 days post-ATLAS compared to controls including increased abundance of Prevotellaceae and Bacteroidetes-Prevotella-Porphyromonas (BPP), which may contribute to disease activity in this model of gut injury. To the best of our knowledge, these findings represent the first report linking lymphatic structural/gut functional changes with alterations in the gut microbiome as they may relate to the pathophysiology of CD.

Chronic hepatitis B and C co-infection increased all-cause mortality in HAART-naive HIV patients in Northern Thailand.

A total of 755 highly active antiretroviral therapy (HAART)-naive HIV-infected patients were enrolled at a government hospital in Thailand from 1 June 2000 to 15 October 2002. Census dateo f survival was on 31 October 2004 or the date of HAART initiation. Of 700 (92.6%) patients with complete data, the prevalence of hepatitis B virus (HBV) surface antigen and anti-hepatitis C virus (HCV) antibody positivity was 11.9% and 3.3%, respectively. Eight (9.6%) HBV co-infected patients did not have anti-HBV core antibody (anti-HBcAb). During 1166.7 person-years of observation (pyo), 258 (36.9%) patients died [22.1/100 pyo, 95% confidence interval (CI) 16.7­27.8]. HBV and probably HCV co-infection was associated with a higher mortality with adjusted hazard ratios (aHRs) of 1.81 (95% CI 1.30­2.53) and 1.90 (95% CI0.98­3.69), respectively. Interestingly, HBV co-infection without anti-HBc Ab was strongly associated with death (aHR 6.34, 95% CI 3.99­10.3). The influence of hepatitis co-infection on the natural history of HAART-naive HIV patients requires greater attention.

Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam.

BACKGROUND: The association between environmental tobacco smoking (ETS) and childhood pneumonia has not been established in developed or developing countries. A study was conducted to assess the effect and impact of ETS exposure on pneumonia among children in central Vietnam. METHODS: A population-based large-scale cross-sectional survey was conducted covering all residents of 33 communes in Khanh Hoa Province, the central part of Vietnam. Information on demographics, socioeconomic status and house environment, including smoking status of each household member, was collected from householders. Hospital admissions for pneumonia among children aged <5 years in each household in the previous 12 months were recorded based on caregiver's report. RESULTS: A total of 353 525 individuals living in 75 828 households were identified in the study areas. Of these, 24 781 (7.0%) were aged <5 years. The prevalence of ETS was 70.5% and the period prevalence of hospital admissions for pneumonia was 2.6%. Multiple logistic regression analysis showed that exposure to ETS was independently associated with hospital admissions for pneumonia (adjusted odds ratio 1.55, 95% CI 1.25 to 1.92). The prevalence of tobacco smoking was higher among men than women (51.5% vs 1.5%). It is estimated that 28.7% of childhood pneumonia in this community is attributable to ETS. CONCLUSIONS: Children in Vietnam are exposed to substantial levels of ETS which results in 44 000 excess hospital admissions due to pneumonia each year among children aged <5 years.

Neurolymphatic biomarkers of brain endothelial inflammatory activation: Implications for multiple sclerosis diagnosis.

AIMS: Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults, and its diagnosis is often delayed due to the lack of diagnostic markers. Initiation of disease -modifying therapy in the early stages of MS is especially critical because currently available therapy mostly target relapsing-remitting MS, and is less effective as disease progresses into the more chronic form of secondary-progressive MS. Therefore, exploring specific and sensitive biomarkers will facilitate an expedited and more accurate diagnosis to allow currently available therapies to be more effective. MAIN METHODS: Western blotting was conducted to detect the expression of neurolymphatic proteins in human brain endothelial cells in culture. Additionally, using a cohort of 150 patients with relapsing remitting MS, 26 with secondary progressive MS, and 60 healthy control samples, neurolymphatic protein expression was detected in serum samples using dot blot analysis. KEY FINDINGS: Human brain microvascular endothelial cells express neurolymphatic markers. Neurolymphatic protein abundance increases with tumor necrosis factor (TNF)-α stimulation but decreases with interferon (IFN)- γ or combined (TNF + IFN) treatment. Circulating neurolymphatic protein levels is significantly lower in MS patients. Further, one of the markers, FOXC2, is associated with the clinical stages of MS, with significantly lower expression in secondary progressive MS compared to relapsing remitting MS. SIGNIFICANCE: Our findings describe brain endothelial expression of neurolymphatic proteins, which is altered under inflammatory stress, and provide a possibility of using a collective pool of circulating neurolymphatic proteins as a diagnostic and prognostic biomarker of MS.

The effect of ethanol on the passive Ca permeability of human red cell ghosts measured by means of arsenazo III.

Ethanol in the range of 0.76-2.40 M caused an immediate increase in the Ca permeability of the plasma membrane of resealed human red blood cell ghosts in which intracellular free Ca could be continuously monitored by means of the Ca chromophore arsenazo III. At a given concentration of ethanol, the Ca permeability increased markedly a few minutes following the mixing of the ghosts and the ethanol, and continued to increase over at least the next 30 min. Preincubating the ghosts in ethanol for 15, 60 and 120 min before measuring the rate of free Ca accumulation, progressively increased the effect of a given concentration of ethanol. These results indicate that the effect of a given concentration of ethanol is a complex function of concentration and exposure time. The effects of ethanol in this concentration range were completely reversible. The resealed ghosts used in these experiments were depleted of ATP to avoid interference from the Ca pump and all experiments were carried out with 150 mM KCl on both sides of the membrane to minimize changes in either the volume or membrane potential associated with activation of the Ca-dependent K channel.

Hospital-based surveillance of invasive pneumococcal disease and pneumonia in South Bangalore, India.

OBJECTIVE: To estimate the incidence of invasive pneumococcal disease and pneumonia, distribution of pneumococcal serotypes, and antibiotic susceptibility in children aged 28 days to <60 months. DESIGN: Hospital-based surveillance. SETTING: South Bangalore, India. PARTICIPANTS: 9950 children aged 28 days to <60 months with clinical suspicion of invasive pneumococcal disease or pneumonia. RESULTS: The estimated at-risk population included 224,966 children <5 years of age. Forty cases of invasive pneumococcal disease were identified. Estimated invasive pneumococcal disease incidence was 17.8/100,000 with incidence being highest among children aged 6 months to <12 months (49.9/100,000). Clinical pneumonia syndrome was the most frequent diagnosis (12.5/100,000). Pneumococcal serotypes included: 6A (n=6, 16.7%); 14 (n=5, 13.9%); 5 (n=4, 11.1%); 6B (n=4, 11.1%); 1, 18C, and 19A (n=3 each, 8.3%); 9V (n=2, 5.6%); and 3, 4, 10C, 18A, 18F, and 19F (n=1 each, 2.8%). Serotypes 6A, 14, 6B, 1, 18C, 19A, 9V, 4, 10C, and 18A showed antibiotic resistance. Clinical pneumonia incidence was 2109/100,000, with incidence being highest among children aged 28 days to <6 months (5033/100,000). Chest radiograph-confirmed pneumonia incidence was 1114/100,000, with incidence being highest among children aged 28 days to <6 months (2413/100,000). CONCLUSIONS: Invasive pneumococcal disease and pneumonia were found to be common causes of morbidity in young children living in South Bangalore, India.

Neonatal rotavirus infection in Bangladesh: strain characterization and risk factors for nosocomial infection.

BACKGROUND: Rotavirus (RV) diarrhea is an important cause of childhood morbidity and mortality in Bangladesh and is responsible for 24% of hospital admissions for diarrhea in children from 3 months to 2 years of age. However, the prevalence of neonatal RV infections and characteristics of RV strains infecting neonates have not been explored in Bangladesh. METHODS: We investigated neonates at six hospitals in Bangladesh to determine the prevalence of neonatal RV infection, to identify risk factors for infection and to characterize neonatal RV strains by reverse transcription-polymerase chain reaction. RESULTS: Of 381 neonates screened at 6 hospitals 61 of 146 infants (42%) at 2 hospitals in Dhaka were RV-positive. Of these 62% were detected within the first 5 days of life. We found an increased risk for neonatal RV infection among infants whose mothers reported no handwashing during care of the neonate (P = 0.03). Analysis of RV strains in enzyme-linked immunosorbent assay-positive specimens identified P[6]G4 and P[6]G1 genotypes to be most common; 7% (2 of 27) of strains were nontypable. A concurrent analysis of RV strains circulating in Bangladesh suggested that RV genotypes infecting neonates had a distinct P genotype, because most community strains were P-nontypable compared with neonatal strains, which carried the P[6] genotype. CONCLUSIONS: Hospitalized neonates in Dhaka have increased risk for infection with RV as early as the first week of life with strains having the unusual P[6] genotype. Our findings confirm studies in India showing that neonatal RV infection can be common and may occur with strains distinct from those circulating in the community. Neonatal RV infections could alter a child's response to the RV vaccine as well as the calculation of RV vaccine efficacy in these populations.

Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus.

OBJECTIVES: To examine trends in the hospitalizations of children for diarrheal disease in the U.S. and to provide estimates for the burden of disease associated with rotavirus diarrhea. METHODS: Data for diarrheal hospitalizations among U.S. children ages 1 month through 4 years were compiled from the National Hospital Discharge Survey for the years 1979 through 1992. Between 1979 and 1992, 12% of all hospitalizations of U.S. children 1 month through 4 years of age had an International Classification of Diseases code for diarrhea listed in one of the top three positions on the discharge diagnosis. RESULTS: The annual rate of diarrheal hospitalizations, 97 per 10 000 persons (average, 185 742 per year), did not change substantially during the 14-year study period and accounted annually for 724 394 inpatient days (3.9 days per hospitalization). For most diarrheal hospitalizations (75.9%) no causative agent was specified in the National Hospital Discharge Survey records; of the remaining 24.8%, viruses were most commonly reported (19.3%), followed by bacteria (5.1%) and parasites (0.7%). The proportion of hospitalizations associated with viral diarrheas rose from 13% to 27% during the 14-year study period, whereas the proportion of hospitalizations for noninfectious diarrhea declined from 79% to 60%. Every year the number of hospitalizations peaked from November through April, the "winter" months, among children ages 4 through 35 months; this peak began in the West during November and December and reached the Northeast by March. CONCLUSIONS: Diarrhea continues to be a common cause of hospitalization among children in the United States and the winter seasonality estimated to be caused in large part by rotavirus would be expected to decrease if rotavirus vaccines currently being developed were introduced. Our analysis of temporal trends in diarrheal hospitalizations provides a unique surrogate with which to estimate the disease burden associated with rotavirus diarrhea.

Visualizing geographic and temporal trends in rotavirus activity in the United States, 1991 to 1996. National Respiratory and Enteric Virus Surveillance System Collaborating Laboratories.

BACKGROUND: Rotavirus is the leading cause of severe pediatric gastroenteritis worldwide. A vaccine may soon be licensed for use in the United States to prevent this disease. To characterize US geographic and temporal trends in rotavirus activity, we made contour maps showing the timing of peak rotavirus activity. METHODS: From July, 1991, through June, 1996, 79 laboratories participating in the National Respiratory and Enteric Virus Surveillance System reported on a weekly basis the number of stool specimens that tested positive for rotavirus. The peak weeks in rotavirus detections from each laboratory were mapped using kriging, a modeling technique originally developed for geostatistics. RESULTS: During the 5-year period 118,716 fecal specimens were examined, of which 27,616 (23%) were positive for rotavirus. Timing of rotavirus activity varied by geographic location in a characteristic pattern in which peak activity occurred first in the Southwest from October through December and last in the Northeast in April or May. The Northwest exhibited considerable year-to-year variability (range, December to May) in the timing of peak activity, whereas the temporal pattern in the remainder of the contiguous 48 states was relatively constant. CONCLUSION: Kriging is a useful method for visualizing geographic and temporal trends in rotavirus activity in the United States. This analysis confirmed trends reported in previous years, and it also identified unexpected variability in the timing of peak rotavirus activity in the Northwest. The causes of the seasonal differences in rotavirus activity by region are unknown. Tracking of laboratory detections of rotavirus may provide an effective surveillance tool to assess the impact of a rotavirus vaccination campaign in the United States.

Anticipating rotavirus vaccines: hospital-based surveillance for rotavirus diarrhea and estimates of disease burden in Bangladesh.

OBJECTIVES: Rotavirus is the most common cause of severe diarrhea in children worldwide, and a vaccine may soon be licensed and available for use in immunization programs. To assess the need for a rotavirus vaccine in Bangladesh, we estimated the disease burden of rotavirus diarrhea from national vital statistics for births and diarrheal deaths, together with hospital surveillance data on the proportion of severe childhood diarrhea attributed to rotavirus. METHODS: From 1990 through 1993, hospital surveillance was conducted of a systematic, random 4% sample of >80,000 patients with diarrhea who sought care each year at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). RESULTS: Rotavirus was detected in 20% (1561 of 7709) of fecal specimens from children with diarrhea <5 years of age; 92% of all cases (1436) occurred in children <2 years of age, but only 3% (50) of cases occurred in infants <3 months of age. Children infected with rotavirus were more likely to have watery stools (P < 0.001), severe vomiting (P < 0.001) but less severe dehydration (P = 0.007) than children infected with other enteropathogens. CONCLUSIONS: We estimate that in this setting, where 18% of children die by age 5 and about 25% of these succumb to diarrhea, between 14,850 and 27,000 of the 3 million Bangladeshi children born in 1994 will die of rotavirus by the age of 5 years, equivalent to 1 rotavirus death per 111 to 203 children. The estimated burden of rotavirus diarrhea in Bangladesh is sufficiently great to warrant field testing of rotavirus vaccines for possible inclusion in the current immunization program.

Diarrheal mortality in US infants. Influence of birth weight on risk factors for death.

OBJECTIVES: To examine diarrhea-associated deaths among very low-birth-weight (VLBW) (< 1500 g) infants and low- and normal-birth-weight (LNBW) (> or = 1500 g) infants at birth and to identify specific interventions to prevent these deaths. DESIGN: Retrospective analyses of linked infant and birth death data on diarrhea of all causes compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, Ga. PATIENTS: Infants aged 27 days through 11 months who died with diarrhea. SETTING: United States, 1991. RESULTS: A majority (56%, n = 143) of the 257 diarrhea-associated deaths reported among US infants in 1991 occurred among VLBW infants. Compared with LNBW infants, VLBW infants had a 100-fold greater diarrheal mortality (269 deaths per 100,000 live births for VLBW infants vs 2.8 deaths per 100,000 live births for LNBW infants), died at a younger age, and more often died in the hospital. Diarrhea-associated deaths among VLBW infants were strongly associated with prematurity and a low 1-minute Apgar score whereas African American race, less maternal education, and a low 1-minute Apgar score were associated with increased diarrheal mortality among LNBW infants. CONCLUSIONS: Infants of VLBW are at an increased risk for diarrheal deaths and new efforts are required to understand and improve the diagnosis of and therapy for diarrhea among these infants. For LNBW infants, diarrheal deaths remain a social problem and efforts need to focus on improved education and home-based rehydration therapy for children whose mothers fit the high-risk profile and who may lack adequate access to health care.

[Relationship between severity of rotavirus diarrhea and serotype G and genotype].

OBJECTIVE: To learn the relationship between severity of rotavirus diarrhea and serotype G and genotype P. METHOD: The clinical information and fecal specimens of hospitalized children less than 5 years of age with acute diarrhea in four sentinel hospitals were collected from Aug 2001 to July 2003. Specimens were tested and typed for rotavirus. Each child with rotavirus infection was assessed for severity of diarrhea according to the 20-points scoring system of Vesikari. RESULTS: When combined with P[8], the severity scores for rotavirus diarrhea of P[8]G1 and P[8]G3 were 13 and 12 points, respectively, and the durations of diarrhea were 6 days and 5 days, respectively. The percentage of fever in patients with diarrhea caused by P[8]G1 was higher than that in those with diarrheas caused by P[8]G3 (97 percent vs. 73 percent). And the highest temperature in the cases with diarrheas caused by G1 and G3 was 39 degrees C and 38.6 degrees C, respectively. When combined with G3, the difference of diarrhea severity scores between P[4]G3 and P[8]G3 was not significant. But duration of diarrhea caused by P[4] was longer than that of diarrheas caused by P[8] (6.5 days vs. 5 days) and the maximum times of vomiting in P[8] cases was higher than in p[4] cases (4 times vs. 3 times per day). There was no significant difference in other clinical features between P[8] and P[4] infected cases. CONCLUSION: When combined with P[8], RV diarrhea caused by G1 was associated with higher severity scores than diarrhea caused by G3. When combined with G3, there was no significant difference in severity scores between P[4] and P[8] infected cases.

Incidence of bacterial meningitis in Asia using enhanced CSF testing: polymerase chain reaction, latex agglutination and culture.

To enhance the detection of bacterial meningitis in an East Asian surveillance study, we employed cerebrospinal fluid (CSF) bacterial culture, latex agglutination (LA) and polymerase chain reaction-enzyme immunoassay (PCR-EIA) testing for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). The sensitivity and specificity of CSF PCR-EIA testing was compared to LA and culture. A meningitis case was defined by one positive result for any of the three tests. The sensitivity of H. influenzae CSF PCR-EIA, LA, and culture was 100%, 40% and 57.5% respectively; and for Sp CSF PCR-EIA, LA and culture, the sensitivity was 100%, 58.3% and 66.7%, respectively. Hib and Sp specificity was 100% by each method. CSF PCR-EIA was more sensitive than culture or LA for the detection of Hib and Sp meningitis cases increasing their incidence by 74% and 50% compared to culture respectively. CSF PCR-EIA should be included for the detection of bacterial meningitis in surveillance studies.

Trends of diarrheal disease--associated mortality in US children, 1968 through 1991.

OBJECTIVES: To describe temporal patterns in mortality related to diarrheal disease in US children and to assess progress toward its prevention and control. DESIGN: Retrospective analyses of death certificate data on diarrhea of all causes compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, Ga. PATIENTS: Children aged 1 month through 4 years who died with diarrhea. SETTING: United States, 1968 through 1991. RESULTS: A total of 14 137 deaths associated with diarrhea among children were reported in the United States between 1968 and 1991. Of these, 78% occurred in infants (ie, aged 1 to 11 months); the median age at the time of death has declined from 5 to 1.5 months. Diarrheal disease mortality dropped by approximately 75% during the first 18 years of the study, but no decline has occurred since 1985. Infant mortality due to diarrhea (per 100 000 live births) averaged 12.8 and was found to be high for blacks (33.1) and for residents of the southern United States (18.5). The infant mortality due to diarrhea from 1986 through 1991 is 5.9. Peaks in winter deaths previously associated with rotavirus were prominent in the early years among infants aged 4 through 11 months. Such peaks have virtually disappeared since 1985. Diarrhea was the principal cause of death, as the leading associated diagnoses (electrolyte disorders [30%], cardiac arrest [16%], shock [8%], and nausea/vomiting [4%]) were commonly recognized complications of diarrhea. Since 1979, prematurity has emerged as a common associated diagnosis. CONCLUSIONS: Diarrheal deaths nationwide have declined 75% from 1968 to 1985 but stabilized since then at about 300 deaths per year. Because many of these deaths may still be preventable by early rehydration, future prevention efforts should be directed at educating health care providers about the continuing problem and recognition of the high-risk infant and at teaching mothers of such infants to begin rehydration early and to seek medical attention when their infant develops diarrhea.

Epidemiology of rotavirus diarrhoea in Africa: a review to assess the need for rotavirus immunization.

Rapid progress towards the development of rotavirus vaccines has prompted a reassessment of the disease burden of rotavirus diarrhoea in developing countries and the possible impact of these vaccines in reducing diarrhoeal morbidity and mortality among infants and young children. We examined the epidemiology and disease burden of rotavirus diarrhoea among hospitalized and clinic patients in African countries through a review of 43 published studies of the etiology of diarrhoea. The studies were carried out from 1975 through 1992, and only those in which a sample of more than 100 patients with diarrhoea were specifically screened for rotavirus by using an established diagnostic test were included. Rotavirus was detected in a median of 24% of children hospitalized for diarrhoea and in 23% who were treated as outpatients; 38% of the hospitalized patients with rotavirus were < 6 months and 81% were < 1 year of age. Rotavirus was detected year-round in nearly every country and generally exhibited distinct seasonal peaks during the dry months. In 5 countries where rotavirus strains had been G-typed, 74% of strains were of one of the four common serotypes (G1 to G4), G1 was the predominant serotype, and 26% were non-typeable. This cumulative experience from 15 African countries suggests that rotavirus is the most important cause of severe diarrhoea in African children and that most strains in circulation today belong to common G types that are included in reassortant vaccines. Wherever large numbers of cases of rotavirus diarrhoea occur early in infancy, immunization at birth may protect the children before their first symptomatic infection.

The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden.

The decision to develop rotavirus vaccines was predicated on the extensive burden of rotavirus disease among children worldwide. US reports on nationwide hospitalizations (1979-1992) and deaths (1968-1991) due to diarrhea and weekly reports of rotavirus infection by 74 laboratories were reviewed to estimate the burden of rotavirus disease, identify epidemiologic trends, and consider methods for evaluating an immunization program when a vaccine becomes available. From 1968 to 1985, diarrhea-related deaths among US children <5 years old declined from 1100 to 300/year. This decline was associated with the disappearance of winter peaks for diarrhea-related deaths previously associated with rotavirus infection among children 4-23 months old. From 1979 to 1992, however, hospitalizations for diarrhea averaged 186,000/year and retained their winter peaks, which have been linked to rotavirus infections. Each year an estimated 54,000-55,000 US children are hospitalized for diarrhea, but <40 die with rotavirus. A rotavirus vaccine program will require improved surveillance, including the timely collection of data from sentinel hospitals, in which a diagnosis of rotavirus can be established or ruled out for all children hospitalized for diarrhea.

A university outbreak of gastroenteritis due to a small round-structured virus. Application of molecular diagnostics to identify the etiologic agent and patterns of transmission.

An epidemiologic investigation of a gastroenteritis outbreak in December 1994 indicated that salad consumption during lunch was linked with illness on 2 days (5 December: odds ratio [OR]=3.1, 95% confidence interval [CI]=2.0-5.0; 6 December: OR=3.1, 95% CI=1.9-4.9). Single stool or vomitus specimens from ill students and staff (case-patients) were examined for bacterial and viral pathogens. Small round-structured viruses (SRSVs) were detected by electron microscopy in stool specimens from 9 of 19 case-patients and in vomitus specimens from 3 of 5 case-patients. By reverse transcription-polymerase chain reaction (RT-PCR), the SRSVs were shown to be G-2/P2-B type strain. The nucleotide sequences of RT-PCR products from vomitus and stool specimens of ill students were identical to stool specimens from the ill salad chef. These findings suggest that a single SRSV strain was the etiologic agent in the outbreak that was possibly transmitted to students through consumption of contaminated salad. Epidemiologic investigation in conjunction with molecular diagnostics may enable early identification of sources of infection and improve outbreak control.

Treatment of Bolivian hemorrhagic fever with intravenous ribavirin.

Bolivian hemorrhagic fever (BHF) is a potentially severe febrile illness caused by Machupo virus (family Arenaviridae). Initial symptoms include headache, fever, arthralgia, and myalgia. In the later stages of this illness, patients may develop hemorrhagic manifestations including subconjunctival hemorrhage, epistaxis, hematemesis, melena, and hematuria, as well as neurological signs including tremor, seizures, and coma. During the BHF epidemics of the 1960s, convalescent-phase immune plasma from survivors of BHF was administered to selected patients infected with Machupo virus. However, there is currently a paucity of survivors of BHF who can donate immune plasma, and there is no active program for collection and storage of BHF immune plasma; therefore, we had the opportunity to offer intravenous ribavirin to two of three patients with this potentially life-threatening infection. One patient with laboratory-confirmed Machupo virus infection who received ribavirin recovered without sequelae, as did a second patient with suspected BHF whose epidemiological and clinical features were similar to those of the first patient. This report describes the first use of intravenous ribavirin therapy for BHF in humans, and the results suggest the need for more extensive clinical studies to assess the usefulness of ribavirin for treating BHF.

An outbreak of typhoid fever, Xing-An County, People's Republic of China, 1999: estimation of the field effectiveness of Vi polysaccharide typhoid vaccine.

To evaluate the effectiveness of Vi polysaccharide vaccine (Vi vaccine) in preventing typhoid fever, an analysis was done of an outbreak of typhoid fever among students attending a middle school in the People's Republic of China, where Vi vaccine is licensed for use. Vi vaccine effectiveness was analyzed by using Cox proportional hazards modeling to account for the time-dependent nature of vaccination and illness status during the outbreak. Among 1260 students who had been immunized before the outbreak, receipt of Vi vaccine was associated with 73% (95% confidence interval [CI], 32%-89%) protection. Among the additional 441 students immunized during the outbreak, receipt of Vi vaccine was associated with 71% (95% CI, -9% to 92%) protection. These results provide the first evidence about the effectiveness of Vi vaccine when deployed routinely in a typhoid-endemic area and support the use of Vi vaccine as a public health tool to control typhoid fever.

[Surveillance finding on rotavirus in Changchun children's hospital during July 1998-June 2001].

OBJECTIVE: To establish baseline patterns of rotavirus diarrhea and to describe its epidemiologic features in Changchun city, prior to rotavirus vaccine immunization. METHODS: Hospital-based surveillance was conducted among children under 5 years old with acute diarrhea in Changchun Children's Hospital. Fecal samples were determined to identify rotavirus by PAGE and/or ELISA. G serotypes of rotavirus were identified by ELISA and/or nested RT-PCR. P genotyping were carried out by RT-PCR. All data were computerized and analysed by "Generic Manual on Rotavirus Surveillance" set by CDC in the USA. RESULTS: In total, 2 343 diarrhea cases were screened and 1 211 fecal samples were collected. Rotavirus was detected in 31.0% among outpatients and 52.9% in inpatients. During the peak of the season (November through March), 58.6% of diarrhea was caused by rotavirus among inpatients. 95.0% of rotavirus diarrhea cases occurred among children aged < 2 years. The predominant strain was serotype G1 (82.4%), followed by G2 (5.0%), G3 (3.3%), G4 (0.9%). P genotyping showed that P[8] and P[4] were the most common ones. Nine different P-G combinations were identified, four strains (P[8]G1, P[4]G2, P[8]G3, and P[8]G4) commonly seen worldwide accounted for 75.6% of the total. Taken together with uncommon strains, including the novel types P[4]G4 and P[8]G2, it highlights the extraordinary diversity of rotaviruses circulating in China. CONCLUSION: Rotavirus is the major cause of severe child diarrhea in Changchun. Developing a rotavirus vaccine for prevention of severe disease and reduction of treatment costs seemed to be necessary.