Effect on clinical outcome of breast feeding during acute diarrhoea.

The effects of oral rehydration fluid alone and of oral rehydration fluid plus breast feeding on the course and outcome of acute diarrhoea were assessed in two groups of 26 children aged under 2 years. Children who continued to be breast fed during treatment with oral rehydration solutions passed significantly fewer diarrhoeal stools. They also passed, on average, a smaller volume of diarrhoeal stools and recovered from diarrhoea sooner after the start of treatment. Their requirement for oral rehydration fluid was significantly reduced. Breast feeding exerts a beneficial effect on the course and outcome of acute diarrhoea by reducing the number and volume of diarrhoeal stools.     

Randomised double blind trial of single dose doxycycline for treating cholera in adults.

OBJECTIVE--To compare the efficacy of a single dose of doxycycline (200 or 300 mg) with the standard multiple doses of tetracycline in patients with cholera. DESIGN--Randomised double blind controlled trial. Patients were given a single 200 mg dose of doxycycline, a single 300 mg dose of doxycycline, or multiple doses of tetracycline (500 mg, six hourly intervals). SETTING--Hospital in Bangladesh treating diarrhoea. PATIENTS--261 Patients aged over 15 admitted to the hospital with severe dehydration due to acute watery diarrhoea associated with Vibrio cholerae. All vibrios isolated from the stools and rectal swabs of patients, including those patients with prolonged excretion of vibrios, were sensitive to tetracycline. The stools of all patients at admission were negative for shigella and salmonella. INTERVENTIONS--All patients received rapid intravenous acetate solution for the first four hours after admission to hospital. They were then entered in the study and randomised. Oral rehydration was started immediately after the intravenous treatment. If signs of severe dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until dehydration was fully corrected. MAIN OUTCOME MEASURES--Stool output in first 24 hours and till diarrhoea stopped, total intake of oral rehydration fluid, duration of diarrhoea, and excretion of vibrio after receiving antibiotic treatment. RESULTS--The median stool outputs during the first 24 hours (275 ml/kg body weight) and till diarrhoea stopped (296 ml/kg body weight) were significantly higher in patients receiving 200 mg doxycycline as a single dose than in patients receiving either standard tetracycline (242 ml/kg body weight and 254 ml/kg body weight) or 300 mg doxycycline (226 ml/kg body weight and 255 ml/kg body weight). Similarly, median consumption of oral rehydration solution (18.45 l) was significantly higher in patients receiving 200 mg doxycycline than in patients receiving either 300 mg doxycycline (16.10 l) or standard tetracycline (14.80 l). Almost equal numbers of patients in each group required unscheduled intravenous acetate solution to correct dehydration during antibiotic treatment. Patients treated with doxycycline (low or high dose), however, had more prolonged excretion of bacteria. CONCLUSIONS--A single 300 mg dose of doxycycline is as effective as the standard multiple dose tetracycline treatment for cholera in terms of stool output, duration of diarrhoea, vomiting, and requirement for oral rehydration solution.     

Albendazole chemotherapy for treatment of diarrhoea in patients with AIDS in Zambia: a randomised double blind controlled trial.

OBJECTIVE--To determine the value of short course, high dose albendazole chemotherapy in the treatment of persistent diarrhoea related to HIV in unselected patients in urban Zambia. DESIGN--A randomised double blind placebo controlled trial of albendazole 800 mg twice daily for two weeks. Patients were monitored intensively for one month and followed for up to six months. SETTING--Home care. AIDS services in Lusaka and Ndola. PATIENTS--174 HIV seropositive patients with persistent diarrhoea (defined as loose but not bloody stools three or more times a day for three weeks or longer). No investigations were undertaken except HIV testing after counselling. MAIN OUTCOME MEASURES--Proportion of time periods during which diarrhoea was experienced after completion of treatment; proportion of patients with full remission after completion of treatment; mortality. RESULTS--The patients taking albendazole had diarrhoea on 29% fewer days than those taking placebo (P < 0.0001) in the two weeks after treatment. The benefit of albendazole was maintained over six months. In patients with a Karnofsky score of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital) diarrhoea was reduced by 50%. Remission was obtained in 26% of all patients who received albendazole (P = 0.004 against 9% receiving placebo), and this difference was maintained over six months (log rank test, P = 0.003). Albendazole had no effect on mortality. Minimal adverse effects were noted. CONCLUSIONS--For HIV infected Zambians with diarrhoea of more than three weeks'' duration albendazole offers substantial relief from symptoms and may be used empirically, without prior investigation.     

Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity.

OBJECTIVE--To assess the impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhoea. DESIGN--Double blind randomised placebo controlled field trial. SETTING--An urban slum area in New Delhi, India. SUBJECTS--900 children aged 12-60 months attending a local health facility for acute diarrhoea of less than seven days'' duration randomly allocated to receive vitamin A 200,000 IU or placebo. MAIN OUTCOME MEASURES--Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance. RESULTS--The incidence (relative risk 1.07; 95% confidence interval 0.92 to 1.26) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups. Among children aged 23 months or less there was a significant reduction in the incidence of measles (relative risk 0.06; 95% confidence interval 0.01 to 0.48). The incidence of diarrhoea was also similar (relative risk 0.95; 0.86 to 1.05) in the two groups. There was a 36% reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months. CONCLUSIONS--Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea.     

Risk factors for persistent diarrhoea.

With a systematically sampled population of children aged under 5 attending this centre for diarrhoeal disease research during 1983-5 a retrospective analysis of persistent diarrhoea (defined as greater than 14 days'' duration) was performed to identify the possible risk factors for this syndrome. Of the 4155 children included in the analysis, 410 (10%) gave a history of persistent diarrhoea. A comparison with children with acute diarrhoea matched for age showed that 11 factors were correlated with persistent diarrhoea, and strongly associated factors were stools with blood or mucus, or both, lower respiratory tract infection, malnutrition, vitamin A deficiency, and antibiotic use before presentation. The peak age was 2 years, and there was no sex difference. Deaths occurred more often in the group with persistent diarrhoea. Although Shigella spp, Campylobacter jejuni, and Giardia lamblia were frequently identified, their rates of isolation were not significantly higher among patients with persistent diarrhoea. No seasonal variation was observed in the rates of persistent diarrhoea. Although the introduction of family food to the diet was associated with higher rates, this factor was difficult to separate from the age dependent risks.     

Comparative Trial of Tetracycline,Chloramphenicol, and Trimethoprim Sulphamethoxazole in Eradication of Vibrio cholera El Tor

A comparison of tetracycline, chloramphenicol, and trimethoprim/sulphamethoxazole showed that all hasten the eradication of Vibrio cholerae from the stools of patients with cholera.A four-day period of tetracycline or trimethoprim/ sulphamethoxazole was adequate for eradicating V. cholerae from the stools of all patients, but three days, as suggested by the W.H.O. Expert Committee, was not. Four days of chloramphenicol therapy was sufficient for most patients, but a minority required up to seven days'' therapy.Purging produced reappearance of V. cholerae in the stools of one-eighth of the patients who had had three successive daily negative stool cultures; such patients are a potential danger to the population.     

Comparison of Side-effects of Tetracycline and Tetracycline Plus Nystatin

In a multicentre, double-blind, controlled trial of tetracycline plus nystatin (Mysteclin) and tetracycline, 111 patients with respiratory infections received one or other drug for a period of 10 days.The incidence of gastrointestinal symptoms was high in both groups before treatment began, and somewhat higher in the Mysteclin group than in the tetracycline group. After 10 days'' treatment 50% of the patients in the Mysteclin group had symptoms, a mean of 1.44 each, compared with 34% of the patients in the tetracycline group, with a mean of 1.47 symptoms each; the difference between the two groups is not significant (P>0.05). The incidence of Candida albicans in the stools at 10 days in the Mysteclin group (9.1%) was significantly lower than that in the tetracycline group (37.1%), but this was not reflected in any reduction in the frequency of gastrointestinal symptoms.     

Controlled Comparison of Tetracycline and Furazolidone in Cholera

A controlled comparison of furazolidone and tetracycline in the treatment of cholera indicates that, in either dosage used, furazolidone reduced total stool volume by 50% and duration of diarrhoea by 40%. These results are comparable to those achieved with tetracycline, which was given in presently recommended dosage. Both furazolidone and tetracycline significantly reduced the rate of stool output within 18 to 24 hours of starting antibiotic treatment. Furazolidone was significantly less effective than tetracycline in rapidly and consistently terminating vibrio excretion. One convalescent carrier of cholera vibrios was identified among control patients; none was identified among patients treated with either tetracycline or furazolidone. All Vibrio cholerae strains tested were sensitive to tetracycline and furazolidone, but larger concentrations of the latter were required to achieve inhibition of growth. It is concluded that tetracycline remains the antibiotic of choice in cholera but that furazolidone would be a useful adjunct to cholera therapy when tetracycline is unobtainable or if strains of V. cholerae with clinically significant resistance to tetracycline should be encountered.     

Experimental Diarrhoea in Human Volunteers Following Oral Administration of Clostridium perfringens Enterotoxin

Peroral administration of purified enterotoxin to human volunteers provoked diarrhoea and abdominal pain, symptoms identical with those encountered in outbreaks of Clostridium perfringens food poisoning. Eight milligrams of enterotoxin caused diarrhoea in one of two volunteers. All of five subjects given 10 and 12 mg of purified enterotoxin or crude enterotoxin developed the classical symptoms of this food poisoning. Passive haemagglutination anti-enterotoxin titres in serum increased in only 5 of 9 volunteers after exposure to enterotoxin. As such levels of anti-enterotoxin can be detected in normal serum samples, titration of anti-enterotoxin may be of little use in diagnosing Cl. perfringens food poisoning. Enterotoxin was detected in all diarrhoeal faecal specimens, and the enterotoxin level varied from 0·2–16 μg/g. Detection of enterotoxin in diarrhoeal faeces may be the most reliable procedure in diagnosing outbreaks of Cl. perfringens food poisoning.     

Evaluation of the efficacy of a low-passage bovine rotavirus (strain WC3) vaccine in children in Central Africa

The safety and efficacy of a WC3 rotavirus vaccine was evaluated in a double-blind placebo-controlled trial involving 472 children in Bangui (Central African Republic). Each child received two doses of either placebo (235 children) or vaccine (237 children) at a 1-month interval, the first dose being given at 3 months of age. During the follow-up survey 9 months after the first dose, 117 rotavirus diarrhoeas were observed, 59 in the placebo group, 58 in the vaccinated group. The only positive effect of the vaccine was a significantly higher proportion of mild rotavirus diarrhoeal episodes in the vaccinated group than in the placebo group. Of the children in the vaccinated group, 60% had a positive immune response to WC3 rotavirus when tested by plaque reduction seroneutralization.     

Cholestyramine in treatment of postvagotomy diarrhoea--double-blind controlled trial.

A double-blind controlled trial was performed to assess the effectiveness of cholestyramine in treating severe continuous postvagotomy diarrhoea. Each patient and a clinician assessed the results, and those treated with cholestyramine showed a considerable improvement over those given placebo. There were no significant side effects or changes in laboratory values in the cholestyramine group. Although the numbers were too small for statistical analysis, these results suggest that cholestyramine may be of value in the management of some patients with severe continuous postvagotomy diarrhoea who are unresponsive to other forms of treatment.     

Value of stool examination in patients with diarrhoea.

Findings of stool examinations in 1593 patients with diarrhoea due to a single enteric pathogen--enterotoxigenic Escherichia coli rotavirus, Shigella, Campylobacter jejuni, Vibrio cholerae 0:1, Entamoeba histolytica, or Giardia lamblia--were reviewed to determine how well they predicted the agent associated with the diarrhoea. Specimens were examined visually for blood and mucus, tested for pH, and examined under a microscope for the presence of red and white blood cells, parasites, and stool fat. Although visible blood was more common in specimens from patients infected with Shigella (51%) and Ent histolytica (39%) than in those from patients infected with other agents (6%; p less than 0.01), patients infected with Shigella were most likely to have numerous faecal leucocytes (greater than 50/high power field: 39% v 8% of all patients and 7% of patients infected with Ent histolytica, p less than 0.01 in both cases). Patients infected with enterotoxigenic E coli, rotavirus, V cholerae 0:1, or C jejuni had loose stools with fewer red or white cells. Patients infected with rotavirus and C jejuni were more likely to have acid stools with 3 to 4+ fat, but these findings were related to young age and breast feeding. Stool examination is most useful in establishing a diagnosis of dysentery and in helping to distinguish between patients infected with Shigella and Ent histolytica; it is of limited usefulness in discriminating between pathogens causing watery diarrhoea.     

Remission of diarrhoea due to cryptosporidiosis in an immunodeficient child treated with hyperimmune bovine colostrum.

A boy aged 6 months who presented with poor weight gain, diarrhoea, and infection with Pneumocystis carinii was found to have congenital hypogammaglobulinaemia, which did not improve despite monthly treatment with intravenous gammaglobulin. At the age of 3 years and 2 months he developed severe vomiting and diarrhoea due to cryptosporidiosis, which failed to respond to conventional treatment. Infusion of hyperimmune bovine colostrum produced against parasite antigen, given by nasogastric tube, was started after symptoms had persisted for three weeks. His vomiting and diarrhoea resolved within five days of treatment, and oocysts were no longer seen in the stools after eight days. Later, however, he developed a rare complication, and oocysts were found in the common bile duct. Hyperimmune bovine colostrum may be useful in the treatment of many patients with immunodeficiency disorders.     

Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea.

The efficacy of vancomycin in pseudomembranous colitis was assessed in a prospective randomised controlled trial. Forty-four patients with postoperative diarrhoea were allocated to five days'' treatment with either 125 mg vancomycin six-hourly or a placebo. Sixteen patients had high titres of the neutralised faecal toxin characteristic of pseudomembranous colitis; nine received vancomycin and seven placebo. At the end of treatment faecal toxins were present in one patient given vancomycin compared with five of the controls. Vancomycin caused the disappearance of Clostridum difficile from the stool in all except one patient, whereas toxicogenic strains of Cl difficile persisted in all but one of the controls. Histological evidence of psuedomembranous colitis had disappeared by the end of treatment in six out of seven patients given vancomycin compared with only one out of seven patients given vancomycin compared with only one out of five patients given placebo. In patients with faecal toxins bowel habit had returned to normal in seven of the vancomycin group compared with only one of the controls, but there was no significant difference in clinical response among patients without faecaal toxins. The results suggest that vancomycin eliminates toxin-producing Cl difficile from the colon and is associated with rapid clinical and histological improvement in patients with pseudomembranous colitis.     

Five-year winter chemoprophylaxis for chronic bronchitis

Seventy-nine patients with chronic bronchitis were randomly allotted to four treatment regimens—placebo throughout the winter months for five years; tetracycline for the first two winters and placebo for the next three; placebo for the first two winters and tetracycline for the next three; and tetracycline for five winters. In addition all groups recevied a five-day course of tetracycline for any acute exacerbation. There was a significant reduction in the number of exacerbations among the more susceptible patients—that is, those who suffered more than one exacerbation each winter. Though the average decline in F.E.V.₁ over the five-year period was less in the treated groups this was not statistically significant. There was no significant difference between the groups in respect of lung volumes, diffusing capacity, and blood gases.     

Studies on Calf Diarrhoea in Mozambique: Prevalence of Bacterial Pathogens

The prevalence of diarrhoea in calves was investigated in 8 dairy farms in Mozambique at 4 occasions during 2 consecutive years. A total of 1241 calves up to 6 months of age were reared in the farms, and 63 (5%) of them had signs of diarrhoea. Two farms had an overall higher prevalence (13% and 21%) of diarrhoea. Faecal samples were collected from all diarrhoeal calves (n = 63) and from 330 healthy calves and analysed for Salmonella species, Campylobacter jejuni and enterotoxigenic Escherichia coli (ETEC). Salmonella spp. was isolated in only 2% of all calves. Campylobacter was isolated in 11% of all calves, irrespective of health condition, and was more frequent (25%) in one of the 2 diarrhoeal farms (p = 0.001). 80% of the isolates were identified as C. jejuni. No ETEC strains were detected among the 55 tested strains from diarrhoeal calves, but 22/55 (40%) strains from diarrhoeal calves and 14/88 (16%) strains from healthy calves carried the K99 adhesin (p = 0.001). 6,757 E. coli isolates were typed with a biochemical fingerprinting method (the PhenePlate?) giving the same E. coli diversity in healthy and diarrhoeal calves. Thus it was concluded: i) the overall prevalence of diarrhoea was low, but 2 farms had a higher prevalence that could be due to an outbreak situation, ii) Salmonella did not seem to be associated with diarrhoea, iii) Campylobacter jejuni was common at one of the 2 diarrhoeal farms and iv) ETEC strains were not found, but K99 antigen was more prevalent in E. coli strains from diarrhoeal calves than from healthy, as well as more prevalent in one diarrhoeal farm.     

Campylobacter colitis.

Eleven consecutive patients with diarrhoea from whose stools campylobacter were isolated were investigated by sigmoidoscopy and rectal biopsy. Eight had definite proctitis, and in seven biopsy specimens were abnormal with histological changes ranging from non-specific colitis to gross colitis with goblet-cell depletion and crypt-abscess formation. Nine of the patients passed blood in their stools, and in all but one abdominal pain was a feature of the illness. Severe campylobacter colitis may be clinically, sigmoidoscopically, and histologically difficult to differentiate from ulcerative colitis and is a differential diagnosis in acute colitis.     

Multi-gene amplification: simultaneous detection of three virulence genes in diarrhoeal stool

Enterotoxigenic Escherichia coli (ETEC) and Shigella account for a substantial proportion of acute diarrhoeal illnesses among Third-World children. Rapid detection of these infectious agents in faeces followed by the prompt implementation of public health measures could help reduce their spread during the early phase of epidemics. Towards this end, three pairs of synthetic oligonucleotide primers were prepared and shown to hybridize specifically to the genes encoding the heat-stable (ST) and the heat-labile (LT) enterotoxins of ETEC and to invasion-associated loci (ial) of the large Shigella virulence plasmid. When the three primer pairs were used together in the polymerase chain reaction (PCR), the three corresponding genetic loci could be simultaneously amplified using DNA extracted directly from stool; the amplified products were readily detected by ST-, LT- and ial-specific, alkaline phosphatase-labelled oligonucleotide probes (AP probes). The performance of this system was evaluated in a Mayan community in southeastern Mexico, where diarrhoeal illnesses are a common cause of childhood morbidity and mortality. Using only simple and inexpensive laboratory equipment, multigene amplification with these primers and probes led to the identification of ETEC and/or Shigella in the stools of 20 out of 71 children with diarrhoea; the procedure could be completed in seven hours and was more sensitive than conventional diagnostic tests or DNA probes used without amplification.     

Association of antecedent malnutrition with persistent diarrhoea: a case-control study.

To determine the effect of nutritional state on persistent diarrhoea a case-control study was carried out on 756 children followed up prospectively for 18 months. Children who developed persistent diarrhoea were compared with population controls and controls with acute diarrhoea. The mean weight for age in the children with persistent diarrhoea (69.9%) was significantly lower than that in the population controls (77.0%) and the diarrhoeal controls (76.2%). Weight for age of less than or equal to 70% was associated with persistent diarrhoea in both case-control analyses (population controls, matched odds ratio 3.25; diarrhoeal controls, matched odds ratio 2.46). The corrected odds (multiple logistic regression) in the two analyses were 3.2 (95% confidence interval 1.3 to 8.1) and 3.4 (1.2 to 9.1). Weight for age of less than or equal to 70% increases the risk of persistent diarrhoea. In an underweight child there is a higher risk of diarrhoea becoming persistent. Prevention of malnutrition and intensive management of acute diarrhoea in malnourished children should help reduce the risk of the diarrhoea persisting.     

Therapeutic Agents in Acne Vulgaris: I. Tetracycline

A total of 120 consecutive patients with pustular and cystic acne vulgaris were selected for study. Patients were assigned a placebo and a tetracycline medication in a random method. Of the 53 patients who were given tetracycline, 45 showed some response, which was fair in 19 and excellent in 26. Of the 55 patients who received placebo, 24 showed no response while 31 showed some improvement. No side effects were reported. The difference in response between the two groups is statistically significant. It is concluded that administration of 250 mg. tetracycline four times daily, even for periods as short as two weeks, enhances the likelihood of improvement of cystic or pustular acne vulgaris.