Tetracycline in the treatment of severe cholera due to Vibrio cholerae O139 Bengal

Vibrio cholerae O139 synonym Bengal, recognized in 1993, is the second member in the list of about 200 serogroups of V. cholerae with epidemic and pandemic potential. Although replacement of fluids and electrolytes remains the cornerstone in the management of cholera, antimicrobial therapy can significantly shorten the duration of diarrhoea, and reduce stool volume and requirements ofrehydration fluids. The role of antimicrobial therapy on the natural course of the disease caused by this relatively new pathogen has not been systematically assessed. A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of tetracycline in the treatment of adults with severe cholera due to V. cholerae O139 Bengal. Forty-three adult males with severe cholera were randomly allocated to receive either 500 mg of tetracycline (n=21) or placebo (n=22) for three consecutive days. Demographic and clinical characteristics of these patients on admission were comparable. Tetracycline therapy was associated with significantly reduced total median (inter-quartile range) stool volume [216.48 (90.18-325.22) mL/kg vs 334.25 (215.12-537.64) mL/kg; p=0.001], higher rates of clinical cure (81% vs 27%; p<0.001), and shorter median (inter-quartile range) duration of diarrhoea [32 (24-48) hours vs 80 (48-104) hours; p<0.001]. The mean +/- (SD) requirement of intravenous fluid was not significantly different between the two groups [146.42 +/- 42.12 mL/kg vs 150.44 +/- 27.21 mL/kg; p=0.70]. The median (inter-quartile range) duration of faecal excretion of V. cholerae O139 was significantly shorter in the tetracycline group than the placebo group [1(1-2) day vs 5 (3-6) days; p<0.001]. The results of the study indicate that tetracycline therapy is clinically useful in the treatment of severe cholera due to V. cholerae O139 Bengal.     

Furazolidone in paediatric cholera

Tetracycline continues to be an effective antimicrobial agent in the clinical control of cholera but because of its high cost, relatively short shelf-life and recent reports of increased resistance of vibrios to tetracycline in vitro, alternative antimicrobial agents have been tested. Furazolidone, effective against cholera caused by the El Tor biotype in adults, was found to be as effective as tetracycline in reducing the volume and duration of diarrhoea in children with classical cholera and, given over a period of 7 days, only slightly less effective in reducing duration of vibrio excretion.     

Rice-ORS versus glucose-ORS in management of severe cholera due to Vibrio cholerae O139 Bengal: a randomized, controlled clinical trial

This study examined the comparative efficacies of rice-based oral rehydration solution (R-ORS) and glucose-based oral rehydration solution (G-ORS) in the management of severe cholera due to Vibrio cholerae O139 Bengal that causes epidemic cholera in many developing countries. Stool culture-proved adult male patients with severe cholera due to V. cholerae O139 Bengal were randomly assigned in a 1:1 ratio to receive either R-ORS or G-ORS after their initial rehydration with intravenous (i.v.) fluid and subsequently four hours of observation. They also received the usual hospital diet and tetracycline capsules (500 mg 6 hourly for three days) immediately after their enrollment in the study. The primary outcomes for observation were stool output during the first 24 hours after intervention and treatment failure as measured by the incidence of re-institution of i.v. fluid after initiation of trial therapy and duration of diarrhoea. Of 113 patients finally included in the study, 57 received R-ORS and 56 G-ORS. The admission characteristics of the two treatment groups were comparable. No significant differences in the first 24 hours of median (inter-quartile range) stool output [179 (67-206) g/kg in R-ORS group vs 193 (80-237) g/kg in G-ORS group; p = 0.52], incidences of unscheduled i.v. fluid requirement [21% (12/57) in R-ORS group vs 25% (14/56) in G-ORS group; p = 0.78], and median (inter-quartile range) duration of diarrhoea [32 (24-48) hours in R-ORS group vs 32 (24-56) hours in G-ORS group; p = 0.64] were observed. It is concluded that rice-based ORS is effective but not superior to standard glucose-based ORS in the management of adult males with severe cholera due to V. cholerae O139 Bengal.     

Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients

This study aims to evaluate the effect of hyperimmune immunoglobulin Y (IgY) against human rotavirus (HRV) among pediatric patients receiving standard supportive treatment for rotavirus-associated diarrhea mostly with an enteric non-cholera co-pathogen in a hospital setting. Two natural HRV reassortant clinical strains ATCC VR 2273 and ATCC VR 2274 were used as mixed immunizing antigens in poultry hens to generate anti-HRV IgY (Rotamix IgY). The Rotamix IgY was used in laboratory and clinical studies against control or placebo IgY. The control or placebo IgY was prepared using tissue culture medium from mock-infected MA104 cell line as antigen for poultry immunization. In vitro, Rotamix IgY exhibited multi-serotypic cross neutralization activities along with synergistic effects against major global serotypes G1, G2, G3, G4 and other human or animal rotavirus strains when compared with mono-specific IgY. Suckling mice (ICR strain) pre-treated orally once with Rotamix IgY and then challenged with rotavirus 3h later showed a significant dose-dependent reduction in frequency (p<0.05) and duration (p<0.05) of diarrhea compared to placebo IgY-treated mice. Out of 114 children aged between 3 and 14 months and with diarrhea upon admission in a Myanmar hospital, 54 dehydrated and rotavirus-positive children were randomized into Rotamix IgY group and placebo IgY group. Of these, only 52 children had complete data with n=26 children per study group. Ninety-two percent of patients in each of these groups were positive for co-infecting enteric non-cholera pathogen and all patients received standard supportive therapy for diarrhea. The patients were monitored for volume and duration of oral rehydration fluid (ORF) and intravenous fluid (IVF) intake, daily stool frequency and overall duration of diarrhea, and frequency and duration of rotavirus shedding. Compared to placebo IgY group, the Rotamix IgY group had statistically significant reduction in mean ORF intake (p=0.004), mean duration of intravenous fluid administration (p=0.03), mean duration of diarrhea from day of admission (p<0.01) and mean duration of rotavirus clearance from stool from day of admission (p=0.05). Overall, our novel approach using oral Rotamix IgY for rotavirus-infected children mostly with non-cholera enteric pathogen co-infection appears to be a promising, safe and effective adjunct to management of acute diarrhea in pediatric patients.     

Vibrio cholerae O139 Bengal: a descriptive study

A prospective study was conducted to determine the clinical and laboratory characteristics and the clinical course of cholera due to Vibrio cholerae O139 Bengal. The study subjects included 22 adult males with stool culture-proven V. cholerae O139. On enrollment, mean +/- SD concentrations (mmol/L) of serum sodium, potassium, chloride, and bicarbonate were 134 +/- 3, 4 +/- 1, 102 +/- 4, and 13 +/- 4 respectively, and stool sodium, potassium, chloride, and bicarbonate concentrations were 120 +/- 24, 18 +/- 6, 93 +/- 16, and 37 +/- 9 respectively. Seventeen patients (7.8%) had faecal leukocytes ranging from 11 to 50 per high-power field. All V. cholerae O139 isolates (100%) were susceptible to tetracycline, erythromycin, and ciprofloxacin, 92% to furazolidine, and only 5% to trimethoprim-sulphamethaxazole. The median (interquartile) volume of liquid stool during the first 24 hours was 9 (5-12) litre. The median (interquartile) volume of liquid stool and the amounts of intravenous and oral rehydration fluids required during the entire study period were 16 (9-24) litre, 9 (6-18) litre, and 14 (9-20) litre respectively. The median (interquartile) duration of diarrhoea was 80 (48-104) hours. The median (interquartile) duration of excretion of V. cholerae O139 in stool was 5 (3-6) days. Clinical and laboratory features, and case management of cholera due to V. cholerae O139 are very similar to conventional cholera due to V. cholerae O1.     

Optimal antibiotic therapy in cholera

Intravenous replacement of the diarrhoeal fluid and electrolyte losses to restore a physiological state of hydration is well established as the basis for successful management of cholera patients. The use of oral tetracycline as an adjunct in reducing the volume and duration of diarrhoea, as well as eradicating the vibrio from the gastrointestinal tract, has been proven beneficial. An optimal dose schedule has not been established previously, and clinical or bacteriological relapses have been generally reported. Chloramphenicol and sulfaguanidine have also been mentioned as adjuncts. The present report shows that 3 g or 4 g of tetracycline in one of 3 dose schedules were predictably efficacious. Chloramphenicol, while of benefit, was not as effective and sulfaguanidine was of little benefit compared with the tetracycline regimens.     

The use of oral replacement solutions in the treatment of choleraand other severe diarrhoeal disorders

Despite the progress that has been made in the treatment of cholera, mortality rates from this disease remain high in rural areas where intravenous fluids are not readily available. The authors have therefore conducted controlled studies into the efficacy of a simpler form of maintenance therapy—the administration of glucose-containing electrolyte solutions by mouth. The results obtained from the study of 51 adult patients (36 with cholera and 15 with severe non-cholera diarrhoea) indicate that oral fluids are adequate for maintenance therapy in cholera and severe diarrhoeal disease, and that there is no significant increase in the duration of diarrhoea or in the stool volume in patients receiving such therapy.     

Does an L-glutamine-containing,Glucose-free,Oral Rehydration Solution Reduce Stool Output and Time to Rehydrate in Children with Acute Diarrhoea? A Double-blind Randomized Clinical Trial

This study assessed whether an oral rehydration solution (ORS) in which glucose is replaced by L-glutamine (L-glutamine ORS) is more effective than the standard glucose-based rehydration solution recommended by the World Health Organization (WHO-ORS) in reducing the stool volume and time to rehydrate in acute diarrhoea. In a double-blind, randomized controlled trial in a Mexican hospital, 147 dehydrated children, aged 1-60 month(s), were assigned either to the WHO-ORS (74 children), or to the L-glutamine ORS (73 children) and followed until successful rehydration. There were no significant differences between the groups in stool output during the first four hours, time to successful rehydration, volume of ORS required for rehydration, urinary output, and vomiting. This was independent of rotavirus-associated infection. An L-glutamine-containing glucose-free ORS seems not to offer greater clinical benefit than the standard WHO-ORS in mildly-to-moderately-dehydrated children with acute non-cholera diarrhoea.     

Effect of massive doses of bacteriophage on excretion of vibrios, duration of diarrhoea and output of stools in acute cases of cholera

Each member of a group of 8 patients with acute cholera was treated with a mixture of four cholera bacteriophage preparations containing over 2 × 10¹² phage particles/ml. These massive doses were intended to kill immediately all vibrios in the intestine by ”lysis from without”. The numbers of Vibrio cholerae were drastically reduced rapidly. In 4 patients, V. cholerae was completely eliminated from the stools early in the treatment; the total stool volume and after-treatment of diarrhoea were reduced in comparison with a control group but were higher than in a group of patients treated with tetracycline. In the other 4 patients treated with phage, vibrios disappeard more slowly from the stools and there was no apparent clinical effect of the phage. In all the patients treated with phage, the duration of diarrhoea was longer than in patients in a control group who excreted vibrios for a similar length of time although the stool output was similar. This was interpreted as being due to the persistence of vibrios in foci of infection in the upper intestine.     

Prognostic indicators and risk factors for increased duration of acute diarrhoea and for persistent diarrhoea in children.

To identify the prognostic indicators and risk factors for increased duration of acute diarrhoea and for occurrence of persistent diarrhoea (i.e. acute episodes lasting longer than 14 days) in children under three years, a systematic sample (3690) of patients attending a large treatment centre in Bangladesh was analysed using multiple regression, logistic regression and stratified (Mantel-Haenszel) analysis. Significant prognostic indicators or risk factors for increase in duration of acute diarrhoea, after adjusting for confounders, include bloody or mucoid diarrhoea, concomitant signs of chest infection, presence of vitamin A deficiency signs, decreased weight for age, routine use of contaminated surface water, lack of breastfeeding and increasing age; presence of rotavirus or enterotoxigenic Escherichia coli or Vibrio cholerae 01 in stool had negative association. In logistic regression and stratified analysis these factors, except for lack of breastfeeding and age, were also found to be risk factors or prognostic indicators of persistent diarrhoea. Policy implications of these findings for programmes to reduce morbidity and mortality from persistent diarrhoea include development of effective vaccines against dysentery-causing Shigella, programmes to prevent vitamin A deficiency, protein energy malnutrition and acute respiratory infections in children, and long-term programmes to provide clean water for all day-to-day needs.     

The use of Ringer's lactate in the treatment of children with cholera and acute noncholera diarrhoea

Two regimens of fluid and electrolyte therapy were studied in children with severe cholera and noncholera diarrhoea. In one, lactated Ringer''s solution was the sole intravenous fluid, additional water, glucose, and potassium being given by mouth. In the other, three different intravenous solutions were employed to meet all fluid and electrolyte requirements. The response to therapy was satisfactory with each regimen. Because of prolonged stupor or vomiting about 15% of children treated by the first regimen were unable to ingest a sufficient quantity of glucose solution by mouth, and intravenous supplementation with a hypotonic glucose—saline solution was necessary. It is concluded that lactated Ringer''s solution is suitable as the sole intravenous solution for children with acute cholera and noncholera diarrhoea provided oral supplementation, as described, is possible. The study also provides useful observations on the means of evaluating fluid requirements in such children and specific guidelines for such therapy.     

Studies into the incidence of carriers of enteropathogenic E. coli.

Enteropathogenic Escherichia coli (EPEC) is frequently found in asymptomatic carriers. When checked over a period of two and a half months at fortnightly intervals, nine out of 20 children at a child care centre in Jamaica showed EPEC of three different serotypes in faecal smears. Four stool specimens were found to be positive in another 45 children, controlled routinely on admission to a district hospital in Jamica. None of either group had diarrhoea at the time of collection. These results confirm that serotypes should not be equated with pathogenicity. Also, current methods of detecting enterotoxin are too time-consuming and impractical for non-specialized laboratories. The place of antibiotics in EPEC diarrhoea is criticized. Initial control measures should centre on fluid and electrolyte replacement irrespective of the aetiology of the diarrhoea.     

Standard WHO-ORS versus reduced-osmolarity ORS in the management of cholera patients

The study compared the safety and efficacy of an oral rehydration salts (ORS) solution, containing 75 mmol/L of sodium and glucose each, with the standard World Health Organization (WHO)-ORS solution in the management of ongoing fluid losses, after initial intravenous rehydration to correct dehydration. The study was conducted among patients aged 12-60 years hospitalized with diarrhoea due to cholera. One hundred seventy-six patients who were hospitalized with acute diarrhoea and signs of severe dehydration were rehydrated intravenously and then randomly assigned to receive either standard ORS solution (311 mmol/L) or reduced-osmolarity ORS solution (245 mmol/L). Intakes and outputs were measured every six hours until the cessation of diarrhoea. During maintenance therapy, stool output, intake of ORS solution, duration of diarrhoea, and the need for unscheduled administration of intravenous fluids were similar in the two treatment groups. The type of ORS solution that the patients received did not affect the mean serum sodium concentration at 24 hours after randomization and the relative risk of development of hyponatraemia. However, patients treated with reduced-osmolarity ORS solution had a significantly lower volume of vomiting and significantly higher urine output than those treated with standard WHO-ORS solution. Reduced-osmolarity ORS solution was as efficacious as standard WHO-ORS solution in the management of cholera patients. The results indicate that reduced-osmolarity ORS solution is also as safe as standard WHO-ORS solution. However, because of the limited sample size in the study, the results will have to be confirmed in trials, involving a larger number of patients.     

Antibiotic therapy for Lyme disease in Maryland.

The recommended treatment of Lyme disease is evolving and important questions remain unanswered, such as (a) Are inexpensive oral regimens effective in curing acute illness and preventing arthritic, neurologic, and cardiac manifestations or are much more costly, and potentially toxic, intravenous antibiotics required? (b) Are relatively short 2- to 3-week courses of antibiotics sufficient or are prolonged regimens of a month, or more, better? This study reviews antibiotic therapy prescribed by Maryland physicians for the 283 cases reported in 1991 that meet the Centers for Disease Control and Prevention''s case definition for Lyme disease. The purpose of the review was to obtain baseline information on the antibiotics being used by physicians in practice to treat patients that they believe have Lyme disease. The most frequently prescribed antibiotics for either the 60 percent of patients presenting with erythema migrans or the 40 percent with arthritic, neurologic, or cardiac manifestations were oral doxycycline (47 percent), tetracycline (11 percent), and amoxicillin (13 percent). Seventy-one percent of therapeutic courses were for 2 to 3 weeks. Amoxicillin was used in two-thirds of children younger than 8 years. Sixty (21 percent) received intravenous therapy, of which ceftriaxone, with or without other antibiotics, was almost always (95 percent) used. Intravenous therapy was more frequently given to those with arthritic, neurologic, and cardiac manifestations than to those with erythema migrans (odds ratio = 3.7) and to those with these systemic symptoms along with erythema migrans than to those with erythema migrans alone (odds ratio = 3.8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Replacement of intravenous therapy by oral rehydration solution in a large treatment centre for diarrhoea with dehydration

Intravenous fluid therapy is particularly effective in reversing severe dehydration due to diarrhoea, but it can be replaced by oral rehydration, with the advantages of lower risks and costs, in the treatment of mild, moderate and some severe cases of dehydration. In this study, the efficacy of oral rehydration solution was compared with that of intravenous fluid in the treatment of moderate and some severe cases of dehydration due to diarrhoea in a treatment centre in Bangladesh during a period of 5 months in 1980 and the same months in 1981. The results of this study show that rehydration by oral rehydration solution (ORS) is as effective as intravenous fluid therapy. ORS can be used for the treatment of diarrhoeas in all age groups including young infants. The costs were reduced by 33% despite an increase in the duration of stay of some patients.     

Multidrug resistance and plasmid patterns of Escherichia coli O157 and other E. coli Isolated from diarrhoeal stools and surface waters from some selected sources in Zaria, Nigeria

We have assessed the prevalence of Escherichia coli O157 in diarrhoeal patients and surface waters from some selected sources in Zaria (Nigeria), evaluating the antibiotic susceptibility and plasmid profiles of 184 E. coli isolates, obtained from 228 water samples and 112 diarrhoeal stool specimens (collected from children aged <15 years), using standard methods. The detection rate of E. coli O157 in surface waters was 2.2% and its prevalence in children with diarrhoea was 5.4%. The most active antibiotics were gentamicin, chloramphenicol and fluoroquinolones. Seventy-nine (42.9%) of 184 E. coli isolates were resistant to four or more antibiotics. Multidrug resistance (MDR) was higher amongst aquatic isolates than the clinical isolates. Out of 35 MDR isolates (20 of which were O157 strains), 22 (62.9%) harboured plasmids all of which were no less than 2.1 kb in size. Amongst the 20 E. coli O157 strains, only seven (35.0%) contained multiple plasmids. An aquatic O157 isolate containing two plasmids was resistant to seven drugs, including ampicillin, cefuroxime, ciprofloxacin, cotrimoxazole, nalidixic acid, nitrofurantoin and tetracycline. Loss of plasmid correlated with loss of resistance to antibiotics in cured (mutant) strains selected in tetracycline (50 μg/mL)-nutrient agar plates. Our findings revealed that plasmids were prevalent in both the aquatic and clinical isolates, and suggest that the observed MDR is plasmid-mediated. The occurrence of plasmid-mediated multidrug resistant E. coli O157 in surface waters used as sources for drinking, recreation and fresh produce irrigation heightens public health concern.     

Helicobacter pylori is not a determinant factor of persistent diarrhoea or malnutrition in Peruvian children

To investigate the role of Helicobacter pylori in childhood diarrhoea, specific IgG antibodies to H. pylori (determined by an ELISA) were sought in 119 infants aged 3-36 months in Peru. Thirty one of the infants had acute diarrhoea (defined as lasting < 72 h and not present in the previous 3 weeks), 67 had persistent diarrhoea (lasting > or = 14 days with no more than 1 intervening diarrhoea-free day) and the remaining 21 had not had diarrhoea in the previous 3 weeks. The children with diarrhoea had been admitted to hospital in Lima for diarrhoea treatment, and the diarrhoea-free children for investigation of possible tuberculosis. Aspirates of duodenal contents and duplicate stool samples were investigated for the presence of bacterial overgrowth and of pathogenic bacteria, viruses and parasites. Anthropometric measurements were also made. There were no statistically significant differences between the prevalence rates of IgG against H. pylori in the children with acute diarrhoea, persistent diarrhoea and without diarrhoea (32%, 43% and 29%, respectively). In addition, H. pylori infection (as evidenced by specific antibodies) had no apparent influence on the presence of small-bowel overgrowth (in 20% of seropositive children compared with 18% of seronegative children) or of pathogens in the stool (in 53% of seropositive children compared with 49% of seronegative children) or on the occurrence of malnutrition in the groups of children considered as a whole. We conclude that H. pylori infection is not associated with acute or persistent diarrhoeal disease, small-bowel overgrowth, stool pathogens or malnutrition in Peruvian children.     

Characteristics of children hospitalized with severe dehydration and persistent diarrhoea in Bangladesh

The study analyzed data from a systematic sample of children, aged less than five years, who presented with persistent diarrhoea (diarrhoea of more than 14 days duration). It aims to differentiate (a) non-severe persistent diarrhoea (with no or mild dehydration) and (b) severe persistent diarrhoea (with moderate or severe dehydration), and to identify individual characteristics associated with severe persistent diarrhoea. In total, 7,505 patients, who represented a 4% systematic sample of the patient population, were seen during January 1993-December 1995. Of them, 297 (4%) presented with persistent diarrhoea. The male:female ratio was 2:1. Eighty-three percent of them had mild or no dehydration, and 17% had moderate or severe dehydration. Severe malnutrition of the study patients defined as weight-for-age z-score < -3, weight-for-length z-score < -3 and length-for-age z-score < -3 were 33.9%, 9.7%, and 22.7% respectively. Only 3% had oedematous malnutrition, and 11% had xerophthalmia. Factors independently associated with severe persistent diarrhoea by logistic regression analyses were: number of watery stool > 10 times during the last 24 hours prior to admission (OR, 10.0; CI, 1.2-87, p = 0.03), lower respiratory tract infection (OR, 111; CI, 4.2-2955, p = 0.004), and lack of mothers' education (OR, 7.8; CI, 1.4-41.9, p = 0.016) after controlling for confounders. Awareness and health education of mothers or caregivers and better case management during acute diarrhoeal episode might prevent the development of severe persistent diarrhoea in young children. In addition, children with severe persistent diarrhoea might need special attention to have adequate rehydration and control of extraintestinal infections, including respiratory tract infection.     

Occurrence of human astrovirus in S?o Paulo City, Brazil]

Human astrovirus was detected during a 13-month longitudinal study of the incidence of diarrhoea viruses among hospitalized children (less than 2 years of age) in a pediatric clinic of the city of S. Paulo (University Hospital). Serial fecal samples (intervals of 4 days) were collected from 146 children with and without acute diarrhoea at admission and during their stay in the hospital. Two (3%) of the 67 children with diarrhoea were positive at admission to the clinic by the highly sensitive ASTROVIRUS BIOTIN-AVIDIN ELISA, using CDC monoclonal antibodies (MAb SE7). All 79 children without diarrhoea (controls) were negative for astrovirus at admission. However, astrovirus was detected in 7 (4.8%) of the 146 hospitalized children during their stay in the clinic. Three of the positives shed astroviruses in 2 successive stool samples. All children positive for astrovirus were negative for rotavirus, adenovirus and bacterial and parasitic enteric agents. This is the first study of the detection of human astrovirus in Brazil. Astrovirus appears to be a significant cause of infantile gastroenteritis among young children in this country.     

The problem of emesis during oral glucose-electrolytes therapy given from the onset of severe cholera.

In an attempt to obviate the need for intravenous fluids by preventing dehydration, 57 adult volunteers who experienced induced clinical cholera during a vaccine development programme were treated from the onset of diarrhoea with oral glucose-electrolytes therapy. 44 individuals with mild to moderately profuse diarrhoea (less than 8 L. total volume) were maintained in normal water and electrolyte balance with oral therapy alone. 13 individuals with severe diarrhoea (greater than 8 L. total volume) could not be maintained in balance with oral therapy alone, due chiefly to emesis during the first day of illness. Emesis occurred in the absence of significant dehydration or acidosis. Since emesis precludes effective early oral therapy in severe cases, domiciliary oral therapy is unlikely to eliminate cholera mortality. Rural diarrhoea treatment centres using oral therapy with limited amounts of intravenous fluids when needed, could reduce case fatality from cholera and related diarrhoeas virtually to zero with least expense.