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.

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.

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.

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.

[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.

Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children.

To determine incidence of invasive Haemophilus influenzae type b (Hib) disease in a defined population of Jeonbuk Province, Korea, children <5 years were evaluated in prospective, population-based surveillance of invasive bacterial diseases using standardized methods for patient referral, clinical evaluation and laboratory testing (optimized culture, latex agglutination, polymerase chain reaction). Vaccine utilization was assessed with vaccination histories of patients in surveillance, monthly data on Hib vaccine distribution and a coverage survey of clinic patients in study population. From September 1999 to December 2001, 2176 children were evaluated for possible meningitis, 1541 had no cerebrospinal fluid (CSF) findings of meningitis, 605 had CSF abnormalities (suspected bacterial meningitis) but no pathogen identified; six patients had probable Hib meningitis and eight had confirmed Hib meningitis. The annual suspected bacterial meningitis incidence was 258.4/100,000 <5 years and the probable/confirmed Hib meningitis incidence was 6.0/100,000 <5 years. Pneumococcal meningitis incidence was 2.1/100,000 <5 years and Group B streptococcal meningitis incidence was 0.17/1000 live births. A total of 69,589 Hib vaccine doses were distributed during the study. Hib vaccine coverage was negligible initially but increased to 16% (complete Hib immunization) and 27% (partial immunization) in final months of study. Suspected bacterial meningitis incidence was high but proven invasive Hib meningitis incidence was low. Hib was leading cause of bacterial meningitis yet bacterial pathogens were identified in only 4% of abnormal CSF. These findings may reflect truly low incidence, presumptive antibiotic treatment, partial Hib immunization, or incomplete clinical evaluations. Given the apparent Hib meningitis burden in Jeonbuk Province, additional studies to describe other invasive Hib syndromes, Hib-associated mortality and disability, and economic impact of Hib disease will be useful to guide public health decisions regarding routine Hib vaccine introduction.

[Rotavirus surveillance data from Kunming Children's Hospital, 1998 - 2001].

OBJECTIVE: To study the epidemiological status on rotavirus diarrhea in Kunming to improve the rotavirus vaccine immunization program. METHODS: A hospital-based sentinel surveillance program for rotavirus was set up among children less than 5 years old with acute diarrhea in Kunming Children's Hospital. Clinical information and fecal specimens were collected and rotavirus were detected by polyacrylamide gel electrophoresis (PAGE) and/or enzyme linked immunosorbent assay (ELISA). Positive specimens were further serotyped or genotyped by ELISA and/or RT-PCR. RESULTS: During the three years of surveillance, 466 specimens were collected. Rotavirus were detected on 246 (52.8%) specimens. 97% of the rotavirus diarrhea cases occurred among children less than 2 years old. There was a peak of admissions for rotavirus diarrhea cases between October and December which accounted for 48% of all the rotavirus hospitalizations each year. Among 204 specimens with G serotyping, the predominant strain was serotype G1 (47.5%) followed by G2 (17.6%), G3 (15.7%), G9 (4.9%) and G4 (1.0%). Mixed infection (2.5%) were rare and 22 specimens (10.8%) remained non-typeable. P genotyping showed P[4], P[8] and P[6] were the most common strains, accounting for 29.3%, 27.6% and 13.8% respectively. P[4]G2 was the most common strain which accounted for 34.1% (14/41) followed by P[8]G1 (29.3%) and P[6]G9 (12.2%). Another 7 uncommon P-G combinations were also identified. CONCLUSION: Rotavirus was the major cause of acute diarrhea in Kunming. An effective rotavirus vaccine for prevention and control of rotavirus diarrhea should be developed.

[Epidemiologic surveillance for bacterial meningitis in 140 000 children under 5 years of age in Nanning district, Guangxi province].

OBJECTIVE: To characterize the incidence, epidemiologic features, etiologic agents and sequelae of bacterial meningitis in children under 5 years of age in Nanning, Guangxi. METHODS: A population-based surveillance was conducted to evaluate children with signs and symptoms of meningitis. All hospitals, township health centers and village clinics in the surveillance area were structured to participate in the case referral and evaluation. Cerebrospinal fluid (CSF) and blood specimens were obtained and processed using standardized microbiologic methods. RESULTS: During the 26-month surveillance period, among the children under 5 years old, a total of 1272 cases who met the screening criteria of meningitis were studied. 265 of 1272 cases were identified as clinically diagnosed meningitis, with an incidence rate of 86.36 per 100 000 population. The annual incidence rate under the 38 cases of confirmed bacterial meningitis appeared to be 12.38/100 000. Staphylococcus species accounted for the largest proportion of laboratory-confirmed bacterial meningitis, followed by E. coli and S. pneumoniae. The highest attack rate occurred in neonates < 1 month, followed by children aged 1 - 12 months in the confirmed patients. Meningitis caused by Sp and Hi mainly occurred in children aged 1 - 12 months. All cases of meningitis due to Hi and Sp were children aged 1 - 24 months. 13.16% and 0.00% of the cases survived with complications and sequelae, and the case-fatality rate was 18.42%. 40 bacterial isolates were identified from 1193 blood cultures and 23 from 1211 cerebrospinal fluid samples, but no Neisseria meningitidis was found. CONCLUSION: Meningitis due to Hi was first confirmed in Guangxi with the incidence of 0.98 per 100 000 population. The annual incidence rate of confirmed bacterial meningitis was 12.38 per 100 000, which was considered an important public health problem in children. Staphylococci was the predominant pathogen in confirmed bacterial meningitis.

[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.

[Epidemiological study of rotavirus diarrhea in Beijing, China - a hospital-based surveillance from 1998 - 2001].

OBJECTIVE: To provide information on epidemiology of rotavirus infection in Beijing, China. METHODS: An ongoing hospital-based surveillance was conducted among children < 5yr old with acute diarrhea according to WHO generic protocol (CID-98). During a 3-year study (Apr. 1998 to Mar. 2001), a total of 484 stool samples were collected from 1 457 patients, including 275 samples from 1 048 outpatients and 209 samples from 409 inpatients. RESULTS: The overall detection rate of rotavirus infection was 25.4%. Rotavirus was responsible for 27.3% of diarrhea inpatients on a yearly base, and 46.2% during rotavirus season. Two peaks of diarrhea were observed each year, one in the summer (June-Sep.) due to bacterial dysentery (16.7%) and another in fall winter (Oct.-Dec.) due to rotavirus infection (23.0%). The detection rate on rotavirus was the highest in age group of 6 - 11 months (38.2%), followed by 1 - 2 years old (28.5%). Ninety six point eight percentage of children were infected under 3 years of age. The number of deaths, possibly caused by rotavirus diarrhea were accounted for 40% of all diarrhea deaths and 11.1% of the total deaths. Serotyping of 123 rotavirus isolates showed that serotype G1 (55.3%) was predominant, followed by G2 (26.8%), G3 (9.8%), G4 (0.8%), and 10 isolates (8.1%) remained non-typeable. Mixed infections (0.8%) seemed to be rare. CONCLUSION: Rotavirus diarrhea was an important infectious disease among children in Beijing. Safe and effective rotavirus vaccines for the prevention of severe diarrheas and the reduction of treatment costs are of significant importance to China.

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.

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.

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.

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.

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.

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.