Rotavirus gastroenteritis in Finland: burden of disease and epidemiological features.

The burden of disease attributable to childhood rotavirus infection in Finland was assessed from data on hospital admissions for acute gastroenteritis and from reported virological diagnoses of rotavirus from 1985 to 1995. The mean number of hospitalizations (3584 annually in children under 5 y of age) corresponded to approximately 5.6% of the birth cohort. Rotavirus was estimated to be responsible for 54% of cases; accordingly, 3% of all children in Finland are hospitalized for rotavirus diarrhoea. The monthly distribution of hospitalizations for acute diarrhoea showed a similar pattern as monthly diagnoses of rotavirus, with a long epidemic period starting as early as November or December and lasting until June or even July. The prevalent rotavirus G-type throughout the study period was G1, which was detected in over 60% of the cases; however, in the season 1988-89 G4 was the prominent type. Improved case management has led to a shorter duration of hospital stay (3.3 d in 1985 vs. 2.3 d in 1995), but otherwise these was no significant trend for rotavirus gastroenteritis over the years. These findings underscore the need to control rotavirus gastroenteritis with a specific intervention, notably rotavirus vaccination.

Management of acute diarrhoea with low osmolarity oral rehydration solutions and Lactobacillus strain GG.

Two hypotonic oral rehydration solutions with osmolarities of 224 mosmol/l (Na+ 60 mmol/l, glucose 84 mmol/l) and 204 mosmol/l (Na+ 60 mmol/l, glucose 64 mmol/l), respectively, and oral treatment with Lactobacillus GG were evaluated in a double blind trial in children aged 6-36 months hospitalised for acute diarrhoea. Early administration of Lactobacillus GG at the start of oral rehydration resulted in the shortest duration of diarrhoea, best weight gain, and fastest correction of acidosis. A reduced osmolarity oral rehydration solution (224 mosmol/l) combined with early administration of Lactobacillus GG is an effective treatment for acute diarrhoea in young children; further reduction of osmolarity may not be beneficial.

Community-based survey of paediatric diarrhoeal morbidity and home treatment practices in Finland.

To determine total diarrhoeal morbidity and current home case management practices, a recall study was conducted among 345 mothers whose 406 children under 5 y of age had had diarrhoea in the past 4 months. The seasonally adjusted annual diarrhoea incidence rate was 0.48 episodes/child/y. For home treatment, increased amounts of fluid were given in 93% and oral rehydration solution (ORS) in 37% of cases. However, when given, ORS was diluted with other fluids in 41% of cases. More than half (55%) of the children received increased or normal amounts of food during the diarrhoeal episode, but 7% of the children were kept fasting for at least 1 d. Use of antidiarrhoeal drugs was minimal (0.7%), but products containing lactic acid bacteria were given in 44% of cases. Case management practice in cases of diarrhoea at home have much improved during the last 20 y, but are still not optimal.

Randomised double blind study of hypotonic oral rehydration solution in diarrhoea.

A hypotonic (osmolality 224 mmol/l, sodium 60 mmol/l) oral rehydration solution (ORS) was compared with an isotonic high glucose ORS (osmolality 304 mmol/l, sodium 60 mmol/l) in children with acute diarrhoea in a randomised double blind study. The stool output and hence the mean consumption of ORS for maintenance hydration was less (p = 0.036) in patients receiving hypotonic (69 ml/kg) than isotonic (97 ml/kg) ORS. Hypotonic ORS was more effective in patients with rotavirus positive than with rotavirus negative diarrhoea.

Randomised double blind trial of hypotonic oral rehydration solutions with and without citrate.

Hypotonic oral rehydration salts solutions (ORS) have been proved to be better than isotonic solutions with respect to water absorption. To establish whether a base precursor is essential in the composition of a hypotonic ORS with improved absorption properties, a randomised double blind clinical trial was conducted comparing two formulas of hypotonic ORS, each with an osmolality of 224 mmol/l, with or without citrate, in a group of 107 children admitted to hospital with acute diarrhoea. The two solutions were effective in the correction of dehydration and there was no difference between the treatments in the duration of diarrhoea. The patients receiving the hypotonic ORS with citrate consumed less of the solution, however, and their metabolic acidosis was corrected earlier. It is concluded that citrate is clinically advantageous in a hypotonic ORS, but a hypotonic formula without a base precursor is also effective.

Clinical experience with a hypotonic oral rehydration solution in acute diarrhoea.

A hypotonic oral rehydration salts (ORS) solution with total osmolality of 224 mosmol/l was compared in an open clinical trial with an isotonic (osmolality 304 mosmol/l) ORS solution for the treatment of dehydration due to acute diarrhoea. Both ORS solutions had the same electrolyte composition with a Na+ concentration of 60 mmol/l. Children given the hypotonic ORS solution (n = 103) passed significantly fewer diarrhoeal stools, and their diarrhoea and hospital stay were shorter than those of children given the isotonic ORS solution (n = 135). We conclude that hypotonic ORS ("light" ORS) has clinical advantages over the standard ORS currently used in Finland.

A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children.

To determine the effect of a human Lactobacillus strain (Lactobacillus casei sp strain GG, Gefilac) on recovery from acute diarrhea (82% rotavirus), 71 well-nourished children between 4 and 45 months of age were studied. After oral rehydration, the patients randomly received either Lactobacillus GG-fermented milk product, 125 g (10(10-11) colony-forming units) twice daily (group 1); Lactobacillus GG freeze-dried powder, one dose (10(10-11) colony-forming units) twice daily (group 2); or a placebo, a pasteurized yogurt (group 3) 125 g twice daily; each diet was given for 5 days, in addition to normal full diet otherwise free of fermented dairy products. The mean (SD) duration of diarrhea after commencing the therapy was significantly shorter in group 1 (1.4 [0.8] days) and in group 2 (1.4 [0.8] days) than in group 3 (2.4 [1.1] days); F = 8.70, P less than 0.001. After rehydration, each dietary group maintained a positive weight trend. The urinary lactulose-mannitol recovery ratios (means [95% confidence intervals]) on admission were 0.09 (0.03, 0.24) in group 1, 0.12 (0.07, 0.22) in group 2, and 0.08 (0.04, 0.18) in group 3; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation. The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea. It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea.

Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age.

Live attenuated oral rhesus Rotavirus candidate vaccine (strain MMU 18006 [lot RRV-1]) was evaluated for immunogenicity, safety, and clinical protection in a double-blind, placebo-controlled trial involving 200 infants aged 2 to 5 months when vaccinated. Vaccine-induced fourfold or greater rise of Rotavirus antibodies was seen in 62% of the infants. Febrile reactions of short duration on days 3 and/or 4 after vaccination occurred in 26% of the vaccine recipients. The clinical follow-up covered two Rotavirus seasons, in which serotypes 1 and 4 were prevalent. There were 16 cases of confirmed Rotavirus diarrhea in the placebo-treated group and 10 in the vaccine-treated group; from this a vaccine protection rate of 38% was derived. Clinical severity of Rotavirus diarrhea was assessed by a score; 13 cases in the placebo-treated group and 5 in the vaccine-treated group were regarded as severe or moderately severe, giving a vaccine protection rate of 67%. The rhesus Rotavirus vaccine induces partial protection against heterotypic Rotavirus disease, but the level of protection achieved with the present vaccine dose in this age group appears to be insufficient for a general Rotavirus vaccination.

Immunogenicity and safety of a low passage level bovine rotavirus candidate vaccine RIT 4256 in human adults and young infants.

A candidate rotavirus vaccine RIT 4256, derived from Nebraska calf diarrhea virus by 21 tissue culture passages, was tested in humans and compared with the RIT 4237 vaccine derived from the same stem virus by 147 tissue culture passages. The low passage strain RIT 4256 was first tested in adult volunteers for immunogenicity and safety: a serological response was seen in 9/18 (50%) vaccinees; three subjects had a mild fever reaction attributable to the vaccine. In 6 month old children the RIT 4256 vaccine elicited a serological response in 12 of the 21 (57%) seronegative recipients; two children had a possible fever reaction from the vaccination. In newborn infants a serological response following vaccination was detected in 19/41 (46%) of the recipients of the RIT 4256 and in 19/40 (48%) of the RIT 4237 vaccine; none of the newborn infants had any reaction from either vaccine. It is concluded that the low passage strain RIT 4256 is not more immunogenic than the high passage vaccine RIT 4237 in humans. The vaccines do not differ in clinical reactogenicity for man.

Clinical trials of rotavirus vaccines.

The clinical efficacy of candidate rotavirus vaccines has been tested in Tampere, Finland, over four winter and spring rotavirus epidemic seasons in 1983-1986. Testing against natural challenge has demonstrated that heterologous oral rotavirus vaccines induce cross-protection to human rotavirus diarrhoea. The trials have also given insight into mechanisms of protection in human rotavirus diarrhoea. After the oral vaccination of infants aged six to 12 months the highly attenuated bovine rotavirus strain RIT 4237, titre 10(8) per dose, probably 'takes' in most vaccinees, producing a symptomless intestinal infection with a low virus excretion rate and an antibody response in over 80% of the initially seronegative subjects. Upon natural challenge such vaccination gives no protection against human rotavirus infection but gives 50-60% protection against any clinically detectable rotavirus-associated illness and 80-90% protection against severe rotavirus diarrhoea, regardless of the infecting human rotavirus serotype. The less attenuated rhesus monkey rotavirus RRV-1, titre 10(5)-10(6) per dose, is more infectious in humans, and virus multiplication in the intestine results in excretion of vaccine virus in the stools and some clinical symptoms, mainly fever, 3-4 days after vaccination. The degree of protection against human rotavirus diarrhoea appears similar to that induced by bovine rotavirus vaccine.