Hour of onset of cholera and diarrhoea.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D R Nalin.
Explore the source record for details and available documents.
Purified cholera toxoid is antigenic when given enterally and orally. Purified toxoid fails to provide protection against experimental challenge. Clinical cholera confers formidable protection against homologous or heterologous rechallenge. Failure to culture vibrios from intestinal fluid or stool of re-challenge volunteers suggests that the predominant immune mechanism is antibacterial rather than antitoxic.
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.
Enterotoxigenic Escherichia coli strains represent the most frequent etiological agent of travelers diarrhea. Challenge studies with several of these strains were undertaken in volunteers to evaluate the mechanisms of disease-induced immunity. Seventeen students and other community volunteers were given 10(6) or 10(8) organisms of E. coli B7A (O148:H28), which produces heat-labile and heat-stable enterotoxins. Ten individuals developed diarrheal illness closely resembling natural travelers diarrhea; of these ten, rises in titer of serum antitoxin and anti-O antibody occurred in eight (80%). Eight of the volunteers who developed diarrhea in the first test agreed to undergo rechallenge 9 weeks later with 10(8) B7A organisms. Only one of these eight "veterans" developed diarrhea versus seven of twelve controls given the same challenge (P = 0.05). Despite clinical protection, all "veterans" excreted B7A after rechallenge. Four controls who developed diarrhea during the homologous B7A rechallenge test were rechallenged 9 weeks later with 10(9) organisms of E. coli strain E2528-C1 (O25:H-), which produces only heat-labile enterotoxin and possesses a different O, H, and pili antigen composition than B7A. Three of four "veterans" and two of six controls developed comparable diarrhea. These studies demonstrate that prior disease due to enterotoxigenic E. coli confers homologous immunity against subsequent challenge, and the operative mechanism apparently is not bactericidal and is not mediated by serum anti-O antibodies. Heterologous protection was not conferred where the only common antigen was heat-labile enterotoxin, indicating that serum infection-derived antitoxin to heat-labile enterotoxin also is not protective.
Incubation of Vibrio cholerae of O-group serotype 1 with chitin particles resulted in adsorption of vibrios onto chitin; chitin-adsorbed V. cholerae survived exposure to acid better than nonadsorbed vibrios. V. cholerae multiplied in dialyzed chitin suspended in 4.2% NaCl, suggesting that adherence to ingested chitin of crustacea might be of epidemiological significance by providing a substrate for vibrio multiplication as well as protection from gastric acid during stomach transit.
To explore the relationship between neuraminidase immunity and the degree of attenuatíon of live influenza A virus vaccines, a comparative evaluation of three Victoria/75-ts-1[E] (Vic/75-ts-1[E]) recombinant viruses in serum hemagglutination-inhibiting-negative (titer, </=1:8) adult volunteers was performed. These three ts-1[E] viruses had a similar restriction of replication at 38 degrees C in vitro, and each possessed the two attenuating genes of the ts-1[E] donor strain (13). However, Vic/75-ts-1[E] recombinants 81 and 113 possessed both Vic/75 hemagglutinin (H3(75)) and Vic/75 neuraminidase (N2(75)), whereas Vic/75-ts-1[E] recombinant 67 had Vic/75 hemagglutinin but the N2(65) neuraminidase. Vic/75-ts-1[E] recombinant 67 was significantly more attenuated than Vic/75-ts-1[E] recombinants 81 and 113 in that fewer local and systemic signs and symptoms of illness were observed in those volunteers who received clone 67. These findings were consistent with our previous observations which suggested that the following two factors contribute to the attenuation of ts-1[E] vaccine strains in adults: (i) the attenuating effect of the two ts-1[E] genes and (ii) the neuraminidase immunity of the host. Vic/75-ts-1[E] recombinant clone 67 vaccinees developed an immunological response to the H3(75) hemagglutinin in the absence of a response to the N2(75) neuraminidase. To assess the role that anti-hemagglutinin immunity induced by an attenuated live virus vaccine plays in resistance to influenza A virus, vaccinees who received recombinant 67 were challenged with Vic/75 wild-type virus, and their responses were compared with those of Vic/75-ts-1[E] vaccinees who received recombinant 81 or 113. Each of the three groups of ts-1[E] vaccinees was significantly protected against illness induced by wild-type virus infection, although resistance was not complete. However, the clone 67 vaccinees were protected less against infection. The infection-permissive resistance induced by clone 67 resembled that previously described for inactivated neuraminidase-specific vaccines. These results suggested that a ts-1[E] recombinant that possessed the hemagglutinin of a new pandemic variant, the neuraminidase of the preceding subtype, and the two ts-1[E] ts genes would be satisfactorily attenuated for children and adults with neuraminidase immunity and could induce resistance to illness caused by the new pandemic wild-type influenza A virus.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Fasting and postprandial stomach acid production were low in 16 of 37 Bangalees convalescing from cholera or non-vibrio cholera. Gastric juice of hypochlorhydric patients did not kill cholera vibrios in vitro, whereas that from normochlorhydric patients rapidly killed vibrios in concentrations up to 10(10)/ml. To determine whether hypoacidity resulted from cholera or was a common predisposing factor, basal and betazole-hydrochloride-stimulated acid production were measured before and after cholera in a second group of patients consisting of American volunteers participating in a vaccine development programme. Cholera did not alter the stomach acid secretion of American volunteers, but low precholera basal acid production predispose to severe cholera. The results indicate that hypochlorhydria observed in convalescent Bangalee cholera patients is not caused by cholera, and must therefore have preceded it. Idiopathic tropical hypochlorhydria may be a major factor accounting for the high incidence of diarrhoea due to acid-sensitive pathogens in developing countries.
In 90 volunteers participating in a vaccine-development programme consumption of beer more than 3 days a week was linked with high stomach acid output, and smoking of cannabis greater than 2 days a week was linked with low acid output. In 92 volunteers challenged with Vibrio cholerae or enterotoxigenic Escherichia coli, heavy use of cannabis was associated with more voluminous diarrhoea. Cannabis use may be an important factor predisposing to severe diarrhoea.
In a randomised double-blind trial, 51 5--10% dehydrated infants were rehydrated with oral electrolyte solutions containing sucrose or glucose. Most infants in both groups were successfully rehydrated, but the sucrose solution produced a slower correction of electrolyte abnormalities and a higher percentage of patients who needed more than 24 h of therapy. Where there is adequate knowledge of the oral therapy method sucrose can substitute for glucose in many cases; where there is a choice glucose is recommended.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Three enteropathogenic Escherichia coli (E.P.E.C.) strains (O127:K63:H6, O128:K67:H2, and O142:K86:H6) isolated from outbreaks of infantile diarrhoea and one strain from the "normal" colonic flora (E. coli HS) of a healthy adult were fed in doses of 10(6), 10(8), and 10(10) organisms in NaHCO3 to adult volunteers. The strains, which had been stored for 7--9 years, gave negative results in sensitive tests for heat-labile (L.T.) enterotoxin (Y-1 adrenal-cell test), heat-stable (S.T.) enterotoxin (infant mouse assay), invasiveness (guineapig eye test), and gross fluid accumulation (infant rabbit assay). Two strains (O142 and O127) caused diarrhoea. L.T. or S.T. enterotoxins were not found in E. coli stool isolates from individuals with diarrhoea and no one had a rise in L.T. antitoxin titre; the findings suggest that L.T. and S.T. enterotoxins were not involved in pathogenesis of the diarrhoea. Non-invasive E.P.E.C. strains probably induce diarrhoea by a mechanism (presumably an enterotoxin) distinct from L.T. or S.T. enterotoxins.
Culture superantes of Escherichia coli from diarrhoea patients were tested in dog jejunal loops for thermostable (ST) and thermolabile (LT) enterotoxins. Pre-treatment with choleragenoid blocked LT but not ST. Glucose was found to reduce fluid accumulation induced by both types of enterotoxin. The findings confirm and extend previous evidence of similarities between cholera toxin and E. coli LT and differences between it and E. coli ST.
The heat-stable enterotoxin (ST) of Escherichia coli can be detected by infant mouse or dog intestinal loop tests. These tests differ in that the dog assay uses concentrated culture supernatants and is based on measurements of net intestinal absorption, whereas the mouse test uses unconcentrated supernatants and depends on gross fluid accumulation. To compare the relative sensitivities of these assays, culture supernatants of randomly selected E. coli isolates from 34 Bangalee diarrhea patients were tested for ST in dog loops and infant mice. Supernatants were also tested for heat-labile enterotoxin (LT) in dog loops, Y-1 adrenal cells, and Chinese hamster ovary cells. E. coli supernatants that produced positive responses for both ST and LT in the dog loop assay (ST+/LT+) also produced positive responses when tested for ST in infant mice and for LT in cell lines. Supernatants of strains negative for ST and LT in dog loop (ST-/LT) were also negative in other assays. Of 10 strains positive for just ST in the dog loop test (ST+/LT-), only 5 were ST positive in the standard infant mouse test. Supernatants of the other five strains (dog loop positive, mouse test negative) were then concentrated 100-fold and retested in mice. Three of these five gave consistently positive results after concentration, and two were only intermittently positive. Concentrated supernatants of negative control strains (ST-/LT-) were all negative in mice. The dog assay detects more strains producing ST than the infant mouse test. The infant mouse test, which detects only gross fluid accumulation, failed to detect approximately half of the 10 strains which produced ST alone (ST+/LT-; P = 0.025). Concentrating supernatants for the mouse assay increases sensitivity for detection of ST, but certain E. coli strains produce a variety of ST to which infant mice do not respond.
In many developing countries and ablution with surface water is a daily habit. This water is heavily contaminated with microbes, raising the possibility that and contamination may lead to immune responses. This hypothesis was experimentally tested in 21 dogs by anal or rectal application of Vibrio cholerae suspension V. cholerae was recovered from rectal swab cultures for a mean of one day after rectal contamination and 2.5 days after anal application (P less than .02). Significant increases occurred in the geometric mean titer of serum vibriocidal antibody; this suggests the need for study of the possible role of anal ablution in maintaining serum vibriocidal antibody levels in endemic cholera areas.