Biomedical subjects
Publications and source records attributed to R B Sack.
Isolation rates of Aeromonas hydrophila from stool samples of symptomatic and asymptomatic individuals were examined for several common enteric media. Sheep blood agar with 10 micrograms of ampicillin per ml, preceded by overnight enrichment in alkaline peptone water, yielded 2.6 times the number of isolates as the other media examined and is recommended for the isolation of A. hydrophila from humans.
The incidence of diarrhea, respiratory disease, and skin infections was prospectively determined after the introduction of a system which distributed unlimited quantities of high quality fresh water to each of the 150 housing units on Tupile, an island devoid of fresh water located off Panama's Caribbean coast and inhabited by 1,500 Cuna Indians. Tupile residents used 7.1 liters of water/person/day compared to the 2.3 usage rate of inhabitants on Achutupo, the control island. Despite ready availability of water in each household, Tupile residents continued to store water in contaminated vessels prior to use. Forty percent of stored water samples tested on Tupile and 45% on Achutupo were contaminated with E. coli organisms. There were 4.7 episodes/child year (E/Y) of acute diarrhea on Tupile compared with the 3.5 rate on Achutupo. The rotavirus infection rate on Tupile was 0.8 E/Y compared with 0.2 E/Y on Achutupo. Infection rates for Norwalk virus, respiratory syncytial virus and Coxsackie B 1-6 viruses were similar on both islands. Respiratory disease rates were high on both islands (2.2 E/Y on Tupile, 2.7 E/Y on Achutupo). Achutupo had much higher rates of impetigo and scabies (0.6 E/Y and 2.5 E/Y, respectively) than Tupile (0.2 E/Y and 1.4 E/Y). Provision of the water distribution system had a beneficial effect on the incidence of water-washed diseases (impetigo and scabies), but at best had no effect on diarrheal disease.
Oral rehydration solutions containing 50 to 90 mmol/L of sodium have recently been recommended for the treatment of diarrhea in both hospitalized and ambulatory children in the United States. Few data are available, however, from ambulatory US children. Therefore, we conducted a randomized double-blind study comparing the use of four different oral rehydration solutions with differing concentrations of sodium, glucose, and base. Ambulatory children less than 2 years of age with acute diarrhea (N = 140) were randomly chosen to receive solutions containing sodium at 90 (solution A), 50 (solution B), and 30 mmol/L (solutions C and D). All oral rehydration solutions contained 20 g/L of glucose except solution D which contained 50 g/L of glucose. Solution A contained bicarbonate as its base source whereas the other three contained citrate. All but three (98%) children were treated uneventfully according to the study protocol, and there were no differences among groups in measurements of clinical outcome. It was concluded that in ambulatory US children, oral rehydration solutions containing 90, 50, or 30 mmol/L of sodium can be used safely for the treatment of mild acute diarrhea and that citrate is as efficacious as bicarbonate in the correction of acidosis.
A controlled study was conducted comparing the standard method of treating hospitalized infants with acute diarrhea (limited starvation) with the initiation of "early feeding" using a soy-based, lactose-free formula in infants of an American Indian tribe 12 months of age or younger. Forty-three patients, randomly assigned to group A, were given a soy-based, lactose-free formula four hours after hospitalization, and 44 patients, randomly assigned to group B, received standard therapy (food was withheld for the first 48 hours of hospitalization). After the first 48 hours, the same soy-based, lactose-free formula was given to the group B patients. Fluid intake and output of stool, urine, and vomitus were measured until the diarrhea resolved. Overall, group A patients showed less mean stool output (121 +/- 129 (SD) mL/kg) than group B patients (299 +/- 319 mL/kg) (P less than .001). Furthermore, the duration of illness was significantly shorter in group A patients (54 +/- 28 hours v 93 +/- 56 hours) (P less than .001). It was concluded that soy-based, lactose-free formulas can be safely used during the acute phase of diarrheal illness in infants and that their use shortens the duration of illness and decreases stool output in comparison with standard therapy.
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The Escherichia coli flora of 23 Peace-Corps volunteers were monitored during the first six weeks of their stay in Morocco. Fifteen (65%) had a total of 21 diarrheal episodes, six of which were associated with enterotoxigenic Escherichia coli. Bioserotypes O25:K7:H42, O128:H-, O169:H- and O20H- were found. These or other characteristically enterotoxigenic Escherichia coli bioserotypes were not found in asymptomatic persons, except in one case. In general, the Escherichia coli flora not only changed after the volunteers arrived in Morocco but continued to change during the six weeks of investigation.
A randomized double-blind study to determine the efficacy of a three-week course of doxycycline (100 mg daily) in preventing travelers' diarrhea was performed in 1980 among 63 United States Peace Corps volunteers during their first five weeks in Thailand, an area where doxycycline-resistant enterotoxigenic Escherichia coli are known to be common. Eight (24%) of 33 volunteers taking placebo and 3 (10%) of 30 taking doxycycline developed travelers' diarrhea for a calculated protection of 59%, but this was not statistically significant (p = 0.12). Aeromonas hydrophila was isolated from 8 to 19 volunteers with either travelers' diarrhea or mild diarrhea in the placebo group, but from only 1 of 12 in the doxycycline group (p less than or equal to 0.05). Furthermore, doxycycline significantly prevented colonization of the gastrointestinal tract with A. hydrophila while it was being taken (p less than or equal to 0.01). Enterotoxigenic E. coli was isolated from only one volunteer with travelers' diarrhea in the placebo group and from none in the doxycycline group. Doxycycline prophylaxis of travelers' diarrhea in this geographic area, though not shown to be significantly protective, further supports the role of A. hydrophila as an enteric pathogen.
Daily doxycycline (DX), known to be effective prophylaxis against travelers' diarrhea (TD) in areas of the world where enterotoxigenic Escherichia coli (ETEC) are sensitive to the drug, has not been extensively studied in geographic areas where antibiotic resistance is common. Therefore we studied 44 U.S. Peace Corps Volunteers during their first 5 weeks in Honduras, which is such an area. During the first 3 weeks, volunteers took daily either 100 mg DX or placebo (PL) in a double-blind, randomized fashion. All 22 taking PL developed TD during the first 3 weeks, compared to 7 of 22 (32%) taking DX (P less than 0.001; 68% protection). ETEC were isolated from 39% of episodes of TD. From the PL group, ETEC from 7 of 13 stool samples (54%) were resistant to DX, whereas from the DX group, ETEC from 10 of 11 stool samples were resistant (P less than 0.05). TD that developed in persons taking DX was also found to be less severe, as judged by length of illness (P less than 0.01) and frequency of stools (P less than 0.05). This study demonstrates that DX 1) significantly prevents TD even in areas where antibiotic resistance is common, although it does not prevent TD caused by docycycline -resistant ETEC, and 2) significantly diminishes the severity of illness.
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Enterotoxigenic Escherichia coli (ETEC) isolates from 36 persons with acute traveler's diarrhea from whom no other pathogens were recovered were tested (after no more than three subcultures) for the presence of colonization factor antigens I and II (CFA/I and CFA/II) and type 1 somatic pili. CFA/I or CFA/II was identified in 7 of 10 strains with heat-labile and heat-stable enterotoxins (LT+/ST+), but in only 2 of 12 LT-/ST+ (P less than 0.05) and 0 of 14 LT+/ST- (P less than 0.02) strains. CFA pili were not found among 74 non-enterotoxigenic E. coli strains. Type 1 somatic pili were demonstrable in 42% of the 36 ETEC and in 49% of the 74 non-enterotoxigenic E. coli isolates. The nine ETEC isolates bearing a CFA were serially subcultured on 10 consecutive days and retested for CFA and toxin. After five subcultures only one strain had lost a CFA, but after 10 passages three strains were negative: two lost CFA/I and one lost CFA/II. The strain that lost CFA/II became negative for both LT and ST as well and was found to lack a 48- and a 60-megadalton plasmid. The two strains that lost CFA/I also became negative for ST, but plasmid analysis revealed no plasmid loss. Disappearance of the CFA/I phenotype without loss of a plasmid can be explained by phase variation, as exhibited by type 1 somatic pili, or by rearrangement of base sequences in the CFA/I plasmid genome. If purified pili vaccines are to provide broad-spectrum protection against ETEC diarrhea, the search must be intensified to identify the antigens responsible for adhesion to intestinal mucosa in the many ETEC strains that lack CFA/I and CFA/II.
The sera of patients with traveler's diarrhea were assayed for rotavirus-specific immunoglobulins in enzyme-linked immunosorbent and micro-neutralization assays. The antigenically related simian rotavirus SA-11 was used in both assays. Although similar titers of rotavirus-specific binding immunoglobulin G and A were observed in the sera of both symptomatic and asymptomatic subjects, clinical illness appeared to correlate with the failure to detect increased (greater than or equal to fourfold) titers of neutralizing antibodies in the post- as compared with the pretravel sera.
Oral rehydration solutions (ORS) containing 90 mmol/liter or 50 mmol/liter of sodium have been successfully used in the treatment of hospitalized well-nourished and undernourished children; however, few data are available on the use of these ORS in well-nourished ambulatory children with minimal dehydration. We therefore compared the safety and efficacy of both ORS with standard outpatient management in a controlled, randomized study among 93 well-nourished children aged 3 months to 2 years, with minimal dehydration secondary to acute diarrhea at an outpatient clinic in Panama. Patients in all three groups were hydrated successfully. However, patients in both ORS groups gained significantly (P less than 0.05) more weight at the 2-week follow-up compared to the control group. There were no complications due to the use of either ORS. No child developed hypernatremia nor hyponatremia during therapy. These studies indicate that both ORS (containing 90 or 50 mmol/liter of sodium) are effective and safe in hydrating well-nourished ambulatory children with minimal dehydration.
Antimicrobial therapy of travellers' diarrhoea with doxycycline or a combination of trimethoprim and sulphamethoxazole is effective only while the drugs are being taken. There is no evidence that sub-clinical infections or exposures leads to the development of immunity while the drugs are being taken. When the drugs are withdrawn, an increase in diarrhoea attack rate occurs in those persons who were previously taking the drug. Therefore, the drugs are only effective for short-term use and would not be indicated in persons travelling for long periods of time. Both drugs can be taken once a day, and are therefore convenient to use. There are adverse side effects with these drugs: the possibility of developing a skin rash with TMP-SMX or a photosensitivity reaction with doxycycline must be balanced against the protection afforded. Although both drugs have an effect on normal enteric flora there is no evidence to suggest that this renders the individual more susceptible to other enteric pathogens.
Although oral glucose-electrolyte solutions containing 90 mmol of sodium per liter have been widely used in the treatment of acute diarrhea among under-nourished children in the developing world, they have rarely been studied in well-nourished children. We therefore conducted a controlled randomized study among well-nourished children three months to two years who were hospitalized with acute diarrhea (52 in the United States, and 94 in Panama), to compare the efficacy of this solution with that of one containing 50 mmol of sodium per liter and with standard intravenous therapy. Oral rehydration with both solutions according to protocol was successful in 97 of 98 children (one required unscheduled intravenous therapy), and in 87 (89 per cent) no intravenous therapy was required. All of six children admitted with hypernatremia were successfully treated with oral therapy alone. We conclude that glucose-electrolyte oral solutions containing either 50 or 90 mmol of sodium per liter are effective and safe in the treatment of well-nourished children hospitalized with acute diarrhea, and that they may completely replace the intravenous fluids in the majority of such children.
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