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David A Sack

Publications and source records attributed to David A Sack.

At least 19 recordsLinked to original sources
PubMed2005

Self-limiting nature of seasonal cholera epidemics: Role of host-mediated amplification of phage.

Phage predation of Vibrio cholerae has recently been reported to be a factor that influences seasonal epidemics of cholera in Bangladesh. To understand more about this phenomenon, we studied the dynamics of the V. cholerae-phage interaction during a recent epidemic in Dhaka. Because the outbreak strain causing this epidemic was resistant to multiple antibiotics, including streptomycin, we used a selective medium containing streptomycin to monitor accurately the abundance of this strain in the environment. The changing prevalence in the environment of the epidemic V. cholerae O1 strain and a particular lytic cholera phage (JSF4) to which it was sensitive was measured every 48-72 h for 17 weeks. We also monitored the incidence of phage excretion in stools of 387 cholera patients during the epidemic. The peak of the epidemic was preceded by high V. cholerae prevalence in the environment and was followed by high JSF4 phage levels as the epidemic ended. The buildup to the phage peak in the environment coincided with increasing excretion of the same phage in the stools of cholera patients. These results suggest that patients toward the end of the epidemic ingested both JSF4 phage and the outbreak V. cholerae strain. Host-mediated phage amplification during the cholera epidemic likely contributed to increased environmental phage abundance, decreased load of environmental V. cholerae and, hence, the collapse of the epidemic. Thus, in vivo phage amplification in patients and subsequent phage predation in the environment may explain the self-limiting nature of seasonal cholera epidemics in Bangladesh.

Bacteriophages↗
PubMed2005

Typing of human rotaviruses: nucleotide mismatches between the VP7 gene and primer are associated with genotyping failure.

BACKGROUND: Rotavirus genotyping is performed by using reverse transcription PCR with type-specific-primers. Because the high rotavirus mutation rate generates an extensive genomic variation, different G-type-specific primer sets are applied in different geographical locations. In Bangladesh, a significant proportion (36.9%) of the rotavirus strains isolated in 2002 could not be G-typed using the routinely used primer set. To investigate the reason why the strains were untypeable, nucleotide sequencing of the VP7 genes was performed. RESULTS: Four nucleotide substitutions at the G1 primer-binding site of the VP7 gene of Bangladeshi G1 rotaviruses rendered a major proportion of circulating strains untypeable using the routine primer set. Using an alternative primer set, we could identify G1 rotaviruses as the most prevalent genotype (44.8%), followed by G9 (21.7%), G2 (15.0%) and G4 (13.8%). CONCLUSION: Because of the natural variation in the rotaviral gene sequences, close monitoring of rotavirus genotyping methods is important.

Antigens, Viral↗
PubMed2005

Antidiarrheal effects of L-histidine-supplemented rice-based oral rehydration solution in the treatment of male adults with severe cholera in Bangladesh: a double-blind, randomized trial.

BACKGROUND: Because of the antisecretory potential of L-histidine in the intestinal tract, its antidiarrheal effects were determined in cholera. METHODS: In a double-blind trial of 126 adult male patients with cholera, L-histidine (2.5 g/L) was mixed with a rice-based oral rehydration solution (ORS) and administered to 62 patients; 64 patients received the same ORS without L-histidine. All patients received ciprofloxacin at a dosage of 500 mg every 12 h for 72 h. Fluid output (of stool, urine, and vomit) and intake (of ORS, water, and intravenous fluid) were determined every 8 h for 72 h. RESULTS: Administration of ORS with L-histidine significantly (P<.05) reduced the frequency of stool output during 32-64 h after initiation of ORS treatment, compared with that in patients given ORS without L-histidine ([all data are means+/-SD] 32-48 h, 11.5+/-6.9 mL/kg vs. 18.8+/-16.0 mL/kg; 40-48 h, 6.7+/-4.4 mL/kg vs. 11.5+/-9.7 mL/kg; and 56-64 h, 6.3+/-5.8 mL/kg vs. 7.8+/-4.1 mL/kg). An overall reduction of 22% in the volume of stool was observed in patients given ORS without L-histidine. The amount of required unscheduled intravenous fluid was lower in patients given ORS with L-histidine, compared with that in patients given ORS without L-histidine (0-24 h, 82.5+/-44.4 mL/kg vs. 158.6+/-72.2 mL/kg [P<.01]; and 24-48 h, 41.6+/-40.4 mL/kg vs. 52.5+/-22.1 mL/kg [P>.05]). Administration of ORS with L-histidine also significantly reduced (P<.05) the intake of ORS and the duration of illness. No adverse effects were observed in these patients. CONCLUSIONS: L-histidine reduces the weight of stool and the frequency of stool output in cholera and could be a useful and safe adjunct treatment that will increase the success rate of ORS and antibiotic therapy in cholera.

Adult↗
PubMed2005

Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages.

The relationship among (i) the local incidence of cholera, (ii) the prevalence in the aquatic environment of Vibrio cholerae, and (iii) bacterial viruses that attack potentially virulent O1 and O139 serogroup strains of this organism (cholera phages) was studied in Dhaka, Bangladesh. Over nearly a 3-year period, we found that significantly more environmental water samples contained either a phage or a phage-susceptible V. cholerae strain than both (P < 0.00001). The number of cholera patients varied seasonally during this period and frequently coincided with the presence of pathogenic V. cholerae strains in water samples that otherwise lacked detectable cholera phages. Interepidemic periods were characterized by water samples containing cholera phages but no viable bacteria. Our data support the conclusion that cholera phages can influence cholera seasonality and may also play a role in emergence of new V. cholerae pandemic serogroups or clones.

Bacteriophages↗
PubMed2005

Isolation and characterization of provisional serovar Shigella boydii E16553 from diarrhoeal patients in Bangladesh.

In previous studies with strains of the Shigella dysenteriae provisional serovars E22383 and E23507 from diarrhoeal stools from patients in Bangladesh, two strains of Shigella species were identified as Shigella boydii provisional serovar E16553 by a reference laboratory. Further tests with an antiserum to an international type strain of the provisional serovar E16553 identified an additional 15 isolates. None of the isolates reacted with antisera to the established Shigella serovars or any other provisional serovars reported so far and all showed biochemical reactions typical of S. boydii. All of the isolates harboured the 140 MDa invasion plasmid, had the ipaH gene and produced keratoconjunctivitis in the guinea pig eye. All isolates were susceptible to ampicillin, sulfamethoxazole-trimethoprim, nalidixic acid, ciprofloxacin and mecillinam but eight strains were resistant to tetracycline. A single PFGE type (type A) was shown for all 17 clinical isolates, indicating a common source of origin. The pulsotype of the Bangladeshi isolates was closely related to that of a Japanese strain but was different from that of the type strain. On the basis of these biochemical, serological and virulence markers, and diverse geographical origin, it is recommended that the provisional status of serovar E16553 be changed and that it be included in the international serotyping classification scheme as S. boydii 19.

Animals↗
PubMed2005

Genomic relatedness of the new Matlab variants of Vibrio cholerae O1 to the classical and El Tor biotypes as determined by pulsed-field gel electrophoresis.

The genomes of the recently described Matlab variants of Vibrio cholerae O1 that are hybrids between classical and El Tor biotypes were compared with those of El Tor and classical biotypes by the use of pulsed-field gel electrophoresis. Dendrograms constructed using the unweighted-pair group method using average linkages generated from NotI restriction patterns of whole-chromosomal DNA grouped these strains into two major clusters that were found to be similar but not identical to those of either of the biotypes. Strains that clustered with the classical biotype appear to have been derived from the classical strains, which are thought to be extinct.

Bacterial Typing Techniques↗
PubMed2005

Pandemic serovars (O3:K6 and O4:K68) of Vibrio parahaemolyticus associated with diarrhea in Mozambique: spread of the pandemic into the African continent.

Forty-two episodes of Vibrio parahaemolyticus infections were detected in Beira, Mozambique, from January to May 2004. The majority of the isolates (81%) belonged to the pandemic serovars (O3:K6 and O4:K68) of V. parahaemolyticus. The pandemic serovars were positive by group-specific PCR (GS-PCR) and a PCR specific for open reading frame ORF8 (ORF8-PCR), which are molecular markers of the pandemic clone, and were positive for tdh but negative for trh. The remaining 19% of the strains also possessed the tdh gene but were GS-PCR and ORF8-PCR negative and did not belong to the pandemic serovars. Patients with V. parahaemolyticus infection were older (mean age, 27 years) than patients infected by other diarrheal agents (mean age, 21 years). Ten percent of diarrhea patients from whom no V. parahaemolyticus was cultured were severely dehydrated, but none of the V. parahaemolyticus cases were severely dehydrated. This is the first report of the isolation of pandemic strains of V. parahaemolyticus in sub-Saharan Africa and clearly indicates that the pandemic of V. parahaemolyticus has spread into the African continent.

Adult↗
PubMed2004

Genetic relatedness of ciprofloxacin-resistant Shigella dysenteriae type 1 strains isolated in south Asia.

OBJECTIVES: The aim of the present study was to determine the clonal relationships of ciprofloxacin-resistant Shigella dysenteriae type 1 strains isolated from south Asia, and S. dysenteriae 1 strains associated with epidemics in 1978, 1984 and 1994. METHODS: The antimicrobial susceptibilities were examined by NCCLS methods. Molecular epidemiological characterization was performed by plasmid profiling, pulsed-field gel electrophoresis (PFGE) and mutation analysis of the quinolone resistance-determining region (QRDR) of gyrA by sequencing. RESULTS: Plasmid patterns of the current ciprofloxacin-resistant strains from India, Nepal and Bangladesh were very similar to those of the 1978, 1984 and 1994 epidemic isolates of S. dysenteriae 1, except for the presence of a new plasmid of approximately 2.6 MDa, which was found in one recent ciprofloxacin-resistant strain isolated in Bangladesh. PFGE analysis showed that the ciprofloxacin-resistant strains isolated in Bangladesh, India and Nepal belonged to a PFGE type (type A), which was possibly related to that of the 1984 and 1994 clone of S. dysenteriae 1, but different from 1978 epidemic strains. The current ciprofloxacin-resistant strains belong to five subtypes (A3-A7), all of which were found in India, but in Bangladesh and Nepal, only A3 existed. Mutation analysis of the QRDR of gyrA revealed that amino acid substitutions at positions 83 and 87 of ciprofloxacin-resistant strains isolated in Bangladesh were similar to those of the strains isolated in Nepal, but different (at position 87) from ciprofloxacin-resistant strains isolated in India. CONCLUSIONS: PFGE and mutation analysis of gyrA showed differences between the current ciprofloxacin-resistant S. dysenteriae 1 strains isolated in south Asia and those associated with epidemics in 1978, 1984 and 1994.

Amino Acid Substitution↗
PubMed2004

Genetic diversity and virulence potential of environmental Vibrio cholerae population in a cholera-endemic area.

To understand the evolutionary events and possible selection mechanisms involved in the emergence of pathogenic Vibrio cholerae, we analyzed diverse strains of V. cholerae isolated from environmental waters in Bangladesh by direct enrichment in the intestines of adult rabbits and by conventional laboratory culture. Strains isolated by conventional culture were mostly (99.2%) negative for the major virulence gene clusters encoding toxin-coregulated pilus (TCP) and cholera toxin (CT) and were nonpathogenic in animal models. In contrast, all strains selected in rabbits were competent for colonizing infant mice, and 56.8% of these strains carried genes encoding TCP alone or both TCP and CT. Ribotypes of toxigenic O1 and O139 strains from the environment were similar to pandemic strains, whereas ribotypes of non-O1 non-O139 strains and TCP(-) nontoxigenic O1 strains diverged widely from the seventh pandemic O1 and the O139 strains. Results of this study suggest that (i) the environmental V. cholerae population in a cholera-endemic area is highly heterogeneous, (ii) selection in the mammalian intestine can cause enrichment of environmental strains with virulence potential, (iii) pathogenicity of V. cholerae involves more virulence genes than currently appreciated, and (iv) most environmental V. cholerae strains are unlikely to attain a pandemic potential by acquisition of TCP and CT genes alone. Because most of the recorded cholera pandemics originated in the Ganges Delta region, this ecological setting presumably favors extensive genetic exchange among V. cholerae strains and thus promotes the rare, multiple-gene transfer events needed to assemble the critical combination of genes required for pandemic spread.

Animals↗
PubMed2004

Cholera.

Intestinal infection with Vibrio cholerae results in the loss of large volumes of watery stool, leading to severe and rapidly progressing dehydration and shock. Without adequate and appropriate rehydration therapy, severe cholera kills about half of affected individuals. Cholera toxin, a potent stimulator of adenylate cyclase, causes the intestine to secrete watery fluid rich in sodium, bicarbonate, and potassium, in volumes far exceeding the intestinal absorptive capacity. Cholera has spread from the Indian subcontinent where it is endemic to involve nearly the whole world seven times during the past 185 years. V cholerae serogroup O1, biotype El Tor, has moved from Asia to cause pandemic disease in Africa and South America during the past 35 years. A new serogroup, O139, appeared in south Asia in 1992, has become endemic there, and threatens to start the next pandemic. Research on case management of cholera led to the development of rehydration therapy for dehydrating diarrhoea in general, including the proper use of intravenous and oral rehydration solutions. Appropriate case management has reduced deaths from diarrhoeal disease by an estimated 3 million per year compared with 20 years ago. Vaccination was thought to have no role for cholera, but new oral vaccines are showing great promise.

Africa↗
PubMed2004

Enteroaggregative Escherichia coli diarrhea in travelers: response to rifaximin therapy.

BACKGROUND AND AIMS: We have recently shown that enteroaggregative Escherichia coli (EAEC) strains commonly cause travelers' diarrhea. The study was designed to determine whether U.S. travelers with EAEC diarrhea responded to rifaximin therapy. METHODS: In a multicenter placebo-controlled clinical trial of travelers' diarrhea without non-EAEC pathogens we evaluated 2 doses of rifaximin. EAEC was sought in stool samples in enrolled subjects by HEp-2 cell assay. Response to rifaximin (both groups combined) and placebo were evaluated in EAEC-positive and EAEC-negative patient groups. RESULTS: Compared with placebo, rifaximin shortened the postenrollment illness in travelers with EAEC diarrhea (median, 22 vs. 72 hours; P = 0.03). In subjects with EAEC-negative diarrhea, the median duration of post-treatment diarrhea was shorter with rifaximin (33 hours) than with placebo (52 hours), but this difference was not significantly different (P = 0.14). CONCLUSIONS: Improvement of EAEC-mediated diarrhea with antibiotic treatment supports the pathogenicity of this organism in travelers to developing countries. The study provides information on the value of the poorly absorbed drug rifaximin in therapy of travelers' diarrhea.

Anti-Infective Agents↗
PubMed2004

Diarrhoea in elderly people: aetiology, and clinical characteristics.

We examined the characteristics of elderly people attending the Dhaka Hospital of ICDDR,B. The hospital has a diarrhoeal disease surveillance system that enrols a 2% systematic sample of all patients visiting the hospital. We reviewed data of all patients enrolled into the surveillance system (n = 13,782) over the period 1996-2001 to identify patients aged 60 y and above for inclusion into the current study (4% of all surveillance patients; n = 478). V. cholerae O1 was the most common enteric pathogen isolated from faecal culture of the patients (20%), followed by ETEC (13%), Shigella (11%), V. cholerae O139 (10%), Campylobacter jejuni (5%), Salmonella (3%), EPEC (2%), rotavirus (4%), and E. histolytica (2%). The isolation rate of V. cholerae O139 and Shigella was higher among the elderly compared to adults (15-59 y of age, 10% vs 6%, and 11% vs 7% respectively; p < 0.05 for both comparisons). Compared to 15-59-y-olds, a significantly higher proportion of the elderly had visible blood in stools (8% vs 5%), required short-stay ward admission (86% vs 82%) or referral (1% vs < 1%) to a health facility. Early initiation of oral or i.v. rehydration therapy, prompt referral, and immediate clinical diagnosis for assessment of the need for antibiotic therapy might be beneficial for the elderly.

Adolescent↗
PubMed2004

Use of antibodies in lymphocyte secretions for detection of subclinical tuberculosis infection in asymptomatic contacts.

We have previously demonstrated that Mycobacterium bovis BCG-specific immunoglobulin G antibodies in lymphocyte secretions (ALS) can be employed as a marker for active tuberculosis (TB). We aimed to determine whether the ALS method allows detection of subclinical TB infection in asymptomatic individuals. A prospective study of family contacts (FCs) of patients with active TB and healthy controls was performed. Thirteen of 42 FCs had high ALS responses, including 6 FCs who subsequently developed active TB. No correlation was observed between the tuberculin skin test and the ALS responses in the FCs (r = 0.1, P = 0.23). Among patients with active TB, BCG-specific ALS responses steadily declined from the time of diagnosis through 6 months following antimycobacterial chemotherapy (P = 0.001). The ALS assay enabled detection of infection in exposed symptom-free contacts, who are at greater risk for developing active TB. The method may also allow discrimination between effective treatment of active infection and suboptimal response to therapy.

Antibodies, Bacterial↗
PubMed2004

Pandemic strains of O3:K6 Vibrio parahaemolyticus in the aquatic environment of Bangladesh.

A total of 1500 environmental strains of Vibrio parahaemolyticus, isolated from the aquatic environment of Bangladesh, were screened for the presence of a major V. parahaemolyticus virulence factor, the thermostable direct haemolysin (tdh) gene, by the colony blot hybridization method using a digoxigenin-labeled tdh gene probe. Of 1500 strains, 5 carried the tdh sequence, which was further confirmed by PCR using primers specific for the tdh gene. Examination by PCR confirmed that the 5 strains were V. parahaemolyticus and lacked the thermostable direct haemolysin-related haemolysin (trh) gene, the alternative major virulence gene known to be absent in pandemic strains. All 5 strains gave positive Kanagawa phenomenon reaction with characteristic beta-haemolysis on Wagatsuma agar medium. Southern blot analysis of the HindIII-digested chromosomal DNA demonstrated, in all 5 strains, the presence of 2 tdh genes common to strains positive for Kanagawa phenomenon. However, the 5 strains were found to belong to 3 different serotypes (O3:K29, O4:K37, and O3:K6). The 2 with pandemic serotype O3:K6 gave positive results in group-specific PCR and ORF8 PCR assays, characteristics unique to the pandemic clone. Clonal variations among the 5 isolates were analyzed by comparing RAPD and ribotyping patterns. Results showed different patterns for the 3 serotypes, but the pattern was identical among the O3:K6 strains. This is the first report on the isolation of pandemic O3:K6 strains of V. parahaemolyticus from the aquatic environment of Bangladesh.

Bacterial Toxins↗