Brassica sprouts exposed to microplastics: Effects on phytochemical constituents.

Microplastics (MPs) can affect plant biomass, tissue composition, and root traits. However, the effects of MPs on the synthesis of secondary metabolites and on the accumulation of bioactive compounds remain poorly studied. The objective of this work was to analyze accumulation of bioactive compounds in broccoli and radish sprouts grown hydroponically in a substrate containing seven different toxic amounts (from very low to extremely high) of low-density polyethylene (PE). Radish was more severely affected by microplastic pollution than broccoli. The effect on the phytochemical composition was statistically significant in both species compared to control. In this aspect, glucosinolate (GSL) content was negatively affected by MPs decreasing from 182 to 124 mg 100 g-1 at medium doses of MPs in broccoli, whereas these compounds drastically decreased from 253 to 151 mg 100 g-1 at the same doses in radish. Anthocyanin content significantly increased until medium doses of MPs ranging from 6.28 to 11.44 mg 100 g-1 in broccoli whereas in radish was from 2.44 to approximately 4 mg 100 g-1. In addition, other morphological and physiological parameter were considered. The analysis of malondialdehyde (MDA) showed significant effects on broccoli and radish in all the MP treatments. The results revealed that high loads of MPs in the substrate affect growth parameters, lipid peroxidation rate estimated by MDA, and phytochemicals of broccoli and radish sprouts, with differences in response to MPs pollution and intensity between species.

Safety and immunogenicity of a hexavalent DTwP-IPV-HB-PRP∼T vaccine versus separate DTwP-HB-PRP∼T and IPV vaccines in healthy infants in India.

Background: Multivalent vaccines containing whole-cell pertussis (wP) antigens combined with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens allow the provision of a high-quality, affordable DTwP-IPV-HB-PRP∼T vaccine. Methods: Phase I/II, randomized, active-controlled, open-label study in healthy toddlers (Cohort I) and infants (Cohort II). Toddlers in Cohort I who had completed primary series D, T, P, HB, Hib, and polio vaccination received a booster dose of DTwP-IPV-HB-PRP∼T (N = 30) or DTwP-HB-PRP∼T + IPV (N = 15) vaccines at 15-18 months of age. After satisfactory review of safety data in Cohort I, infants in Cohort II received DTwP-IPV-HB-PRP∼T (N = 100) or DTwP-HB-PRP∼T + IPV (N = 50) at 6-8, 10-12, and 14-16 weeks of age. All infants in Cohort II had received previous oral polio and HB vaccines per country recommendations. Results: Booster and primary series vaccinations were well tolerated with no clinically significant differences between vaccine groups. Most adverse events were mild and resolved spontaneously; there were no vaccine-related serious adverse events and no deaths. In both vaccine groups, anti-D, anti-T, anti-HB, anti-Hib, and anti-polio 1, 2, and 3 seroprotection was 100% post-booster and post-primary series. For the pertussis antigens, booster response rate was > 86% in both groups. For the primary series, vaccine response rate was slightly higher for DTwP-IPV-HB-PRP∼T than DTwP-HB-PRP∼T + IPV for anti-PT (80.2% and 70.8%) and anti-FHA (81.3% and 68.8%), slightly lower for anti-PRN (72.5% and 81.3%), and similar in each group for anti-FIM (95.6% and 97.9%). Conclusions: This study demonstrated a good safety and immunogenicity profile of the hexavalent DTwP-IPV-HB-PRP∼T vaccine for infant primary series vaccination at 6-8, 10-12, and 14-16 weeks of age and booster vaccination at 15-18 months of age and supported progression to the next development phase.

Antibody persistence following administration of a hexavalent DTwP-IPV-HB-PRP∼T vaccine versus separate DTwP-HB-PRP∼T and IPV vaccines at 12-24 months of age and safety and immunogenicity of a booster dose of DTwP-IPV-HB-PRP∼T in healthy infants in India.

Background: The combination of whole-cell pertussis (wP) antigens with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens provides a high-quality DTwP-IPV-HB-PRP∼T vaccine. This study evaluated a DTwP-IPV-HB-PRP∼T booster coadministered with measles, mumps, and rubella (MMR) vaccine. Methods: Phase II, open-label, randomized study. Healthy toddlers who had previously completed a DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV primary vaccination series received a DTwP-IPV-HB-PRP∼T booster vaccine at 12-24 months of age. All participants had also received 1 or 2 doses of measles-containing vaccine between primary vaccination and enrolment (N = 100 and N = 6, respectively). Those who had received 1 prior measles-containing vaccine received an MMR dose either concomitantly (N = 50) or 28 days after (N = 50) the DTwP-IPV-HB-PRP∼T booster. Immunogenicity was evaluated using validated assays and safety by parental reports. Results: Pre-booster vaccination, 100.0% participants showed antibody persistence after DTwP-IPV-HB-PRP∼T or DTwP-HB-PRP∼T and IPV for anti-T (≥0.01 IU/mL), anti-Hib (≥0.15 µg/mL), and anti-polio 3 (≥8 1/dil) and at least 95.8% of participants for anti-D (≥0.01 IU/mL), anti-HB (≥10 mIU/mL), and anti-polio 1 and 2 (≥8 1/dil). For the pertussis antigens, pre-booster antibody persistence (≥2 EU/mL) ranged from 88.6 to 88.7% (anti-PT), 91.4-98.6% (anti-FHA), 69.0-74.3% (anti-PRN), and 97.1-97.2% (anti-FIM). For the booster response, seroprotection based on either the primary series or measles-containing vaccination regimen was 100.0% for anti-D and anti-T (≥0.01 IU/mL and ≥0.10 IU/mL), anti-HB (≥10 mIU/mL and ≥100 mIU/mL), anti-Hib (≥0.15 µg/mL and ≥1 µg/mL) and anti-polio 1, 2, and 3 (≥8 1/dil), and for the pertussis antigens booster response ranged from 88.6 to 91.8% (anti-PT), 91.1-95.9% (anti-FHA), 88.6-93.9% (anti-PRN), and 95.9-98.6% (anti-FIM). There were no safety concerns in any group. Conclusions: This study showed good antibody persistence of the DTwP-IPV-HB-PRP∼T vaccine and good immunogenicity and safety of a booster dose given with MMR in the second year of life.Clinical Trials Registry India Number: CTRI/2018/04/013375.

Lot-to-lot consistency of a hexavalent DTwP-IPV-HB-PRP∼T vaccine and non-inferiority to separate DTwP-HB-PRP∼T and IPV antigen-matching vaccines at 6-8, 10-12, and 14-16 weeks of age co-administered with oral rotavirus vaccine in healthy infants in India: A multi-center, randomized, controlled study.

Background: Combination vaccines reduce the number of pediatric injections but must be as safe, immunogenic, and effective as each of the individual vaccines given separately. Additionally, consistency in manufacturing lots is essential for WHO prequalification. This study aimed to establish the lot-to-lot consistency of a fully liquid, hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b (PRP-T) (DTwP-IPV-HB-PRP∼T) vaccine and to demonstrate non-inferiority to licensed DTwP-HB-PRP∼T and IPV vaccines. Methods: A Phase III, randomized, active-controlled, and open-label study was conducted at multiple centers across India. Healthy infants who had received a birth dose of oral poliovirus vaccine and hepatitis B vaccine received one of three lots of DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV vaccines at 6-8, 10-12, and 14-16 weeks of age. Oral rotavirus vaccine was co-administered at 6-8 weeks of age and 10-12/14-16 weeks of age. DTwP-IPV-HB-PRP∼T lot-to-lot consistency and non-inferiority (pooled DTwP-IPV-HB-PRP∼T) versus DTwP-HB-PRP∼T and IPV post-third dose were assessed using seroprotection rates (anti-D, anti-T, anti-HBs, anti-PRP, anti-polio 1, 2, 3) and adjusted geometric mean concentrations (anti-PT, anti-FIM). Safety was assessed by parental reports. Results: Lot-to-lot consistency was demonstrated for DTwP-IPV-HB-PRP∼T and non-inferiority versus DTwP-HB-PRP∼T and IPV was confirmed with 95% CIs for seroprotection rate differences and adjusted geometric mean concentration ratios within pre-defined clinical margins. Pooled seroprotection rate was ≥ 99.7% for anti-D ≥ 0.01 IU/mL, anti-T ≥ 0.01 IU/mL, anti-HBs ≥ 10 mIU/mL, anti-PRP ≥ 0.15 µg/mL, and anti-polio 1, 2, and 3 ≥ 8 (1/dil) and vaccine response rate was 83.9% for anti-PT and 97.7% for anti-FIM. There were no safety concerns. Conclusions: Immunogenicity of three lots of the fully liquid DTwP-IPV-HB-PRP∼T vaccine was consistent and non-inferior to licensed comparators following vaccination at 6-8, 10-12, and 14-16 weeks of age. There were no safety concerns and no evidence of any effect of co-administration with rotavirus vaccine.

[Orthotopic liver transplantation. Experience in the University Hospital of Monterrey, N.L]. / Trasplante hepático ortotpico. Experiencia en el Hospital Universitario de Monterrey, N.L.

INTRODUCTION: Several programs of organ and tissues transplantation have been developed for over a decade at the University Hospital. OBJECTIVE: To describe long term complications and survival in the liver transplant program at the University Hospital, UANL. MATERIAL AND METHODS: The long term complications and survival were analyzed in the liver transplant program at the University Hospital Dr. José Eleuterio González in the period between 1991 and 2011. RESULTS: Ninety six liver transplants were performed during this period, four of them received one re-transplant and one patient received 2 retransplants. Most common long term complications were metabolic 62%, bony 31% and infectious 28%. Median survival was 78 months. CONCLUSIONS: Liver transplant program at the University Hospital UANL has grown, being the most active in the state of Nuevo Leon, with 1-, 5- and 10-years survival of 66.1, 53.3 and 46.2%, respectively.

Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America.

OBJECTIVE: Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. METHODS: The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. RESULTS: Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. CONCLUSIONS: The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.

Shigella enterotoxin 1: an enterotoxin of Shigella flexneri 2a active in rabbit small intestine in vivo and in vitro.

Culture filtrates of Shigella flexneri 2a strain M4243 grown in iron-depleted medium, caused significant fluid accumulation in rabbit ileal loops. Also, when tested in Ussing chambers, a greater rise in potential difference and short circuit current was seen with such filtrates compared with the medium control. Analogous filtrates from two M4243 derivatives lacking the 140-MD invasiveness plasmid (either M4243avir or BS103) retained 60-65% of the wild-type enterotoxic activity. Ultrafiltration and gel exclusion size fractionation of M4243 filtrate revealed that the activity was approximately 60 kD. SDS-PAGE performed on this fraction showed 18 bands, 5 of which reacted with human convalescent sera. Genes encoding this enterotoxin, named ShET1 for Shigella enterotoxin 1, were cloned from the S. flexneri 2a chromosome, and two separate open reading frames of 534 and 186 bp were sequenced. These observations suggest that S. flexneri 2a elaborates two distinct enterotoxins: ShET1, encoded by genes located on the chromosome, and ShET2, encoded by a gene on the 140-MD invasiveness plasmid. ShET1, which is composed of two distinct subunits and is elaborated in vivo, where it elicits an immune response, may be important in the pathogenesis of diarrheal illness due to S. flexneri 2a.

Comparative genomics of insect juvenile hormone biosynthesis.

The biosynthesis of insect juvenile hormone (JH) and its neuroendocrine control are attractive targets for chemical control of insect pests and vectors of disease. To facilitate the molecular study of JH biosynthesis, we analyzed ESTs from the glands producing JH, the corpora allata (CA) in the cockroach Diploptera punctata, an insect long used as a physiological model species and compared them with ESTs from the CA of the mosquitoes Aedes aegypti and Anopheles albimanus. The predicted genes were analyzed according to their probable functions with the Gene Ontology classification, and compared to Drosophila and Anopheles gambiae genes. A large number of reciprocal matches in the cDNA libraries of cockroach and mosquito CA were found. These matches defined known and suspected enzymes of the JH biosynthetic pathway, but also several proteins associated with signal transduction that might play a role in the modulation of JH synthesis by neuropeptides. The identification in both cockroach and mosquito CA of homologs of the small ligand binding proteins from insects, Takeout/JH binding protein and retinol-binding protein highlights a hitherto unsuspected complexity of metabolite trafficking, perhaps JH precursor trafficking, in these endocrine glands. Furthermore, many reciprocal matches for genes of unknown function may provide a fertile ground for an in-depth study of allatal-specific cell physiology. ESTs are deposited in GenBank under the accession numbers DV 017592-DV 018447 (Diploptera punctata); DR 746432-DV 747949 (Aedes aegypti); and DR 747950-DR 748310 (Anopheles albimanus).

Linear shock wave therapy in the treatment of erectile dysfunction.

INTRODUCTION: Linear Shock Wave Therapy (LSWT) is a new noninvasive therapy that uses low-intensity shock waves to induce local angiogenesis promising modality in the treatment of erectile dysfunction (ED). OBJECTIVE: To evaluate the effectiveness of LSWT in men with vasculogenic erectile dysfunction (ED), in a Tertiary Care Center. MATERIAL AND METHODS: Included 15 men aged 45-70 years, sexually active with mild and moderate vascular ED evaluated with the International Index of Erectile Function (IIEF). The study was conducted in three stage: screening, treatment and results. Treatment stage: 4 weekly sessions LSWT (RENOVA ®) 5000 waves (.09mJ/mm(2)). Erectile function was assessed with IIEFF-EF, SEP (Sexual Encounter Profile) and GAQ (Global Assessment Questions) at one and six months after treatment. RESULTS: The rate of success was 80% (12/15). Patients with mild ED (6/15) 40% and moderate ED (9/15) 60%. We found a positive association between IIEF-Basal (average 14.23 pts) and IIEF at one month and six months after therapy (19.69 pts) a difference of 5.46 pts. (P<.013). CONCLUSIONS: The feasibility and tolerability of this treatment, and rehabilitation potential features, make it this an attractive new treatment option for patients with ED.

cDNA cloning and pattern of expression of an adult, female-specific chymotrypsin from Aedes aegypti midgut.

A cDNA for a midgut chymotrypsin, induced by a blood meal, has been cloned and sequenced from the mosquito Aedes aegypti. The 938 base sequence codes for a 268 amino acid protein, which contains an 18-residue signal peptide and a seven-residue activation peptide. The deduced amino acid sequence contains several features typical of chymotrypsin proteases, including the catalytic triad of serine proteases and the residues that determine the chymotrypsin substrate specificity pocket. The chymotrypsin mRNA, absent in larvae, pupae, males and newly emerged females, reaches detectable levels within 24 h post-emergence and attains a maximum level 3-7 days after emergence. Translation of the chymotrypsin mRNA is induced by feeding a protein meal, and there is a dramatic increase in midgut chymotrypsin enzymatic activity after feeding. Chymotrypsin activity remained high during protein digestion, but chymotrypsin protein levels and enzymatic activity were almost undetectable once digestion was completed, 48 h after feeding.

Dietary control of late trypsin gene transcription in Aedes aegypti.

In Aedes aegypti the levels of midgut trypsin activity after feeding are directly proportional to the protein concentration in the meal. The mechanisms of this up-regulatory event were investigated by analyzing the expression of the late trypsin gene under different dietary conditions. Transcription of the gene was dependent on both the quality and quantity of protein in the meal. As measured by Northern blot analysis, the levels of late trypsin gene expression increased up to 100-fold 24 h after feeding on gamma-globulin, hemoglobin or albumin (100 mg/ml). In contrast, gelatin, histone, amino acids, saline or agarose were very poor inducers of transcription. The rates of late trypsin transcription induced during the first 24 h were directly proportional to the concentration of protein in the meal. These data further support the suggestion that the primary mechanism that regulates the synthesis of trypsin in the mosquito midgut is transcriptional regulation of the gene. This regulatory mechanism enables the midgut to maintain the appropriate balance between protease synthesis and the protein content of the meal.

Early trypsin activity is part of the signal transduction system that activates transcription of the late trypsin gene in the midgut of the mosquito, Aedes aegypti.

Trypsin activity during the first hours after feeding is essential to induce late trypsin gene expression. These results are consistent with the idea that free amino acids or other products released during digestion might be the initial signal for transcriptional activation of late trypsin. Besides early trypsin, some other factor(s) have to be translated for induction of late trypsin. This is the first case in which the proteolytic activity of a digestive enzyme is part of the signal transduction system which regulates expression of a second gene. The presence of two trypsins allows the mosquito to assess the quality of the meal and adjust the levels of late trypsin for a particular meal with remarkable flexibility.

Increase in the size of the amino acid pool is sufficient to activate translation of early trypsin mRNA in Aedes aegypti midgut.

Early trypsin is a female-specific protease present in the midgut of the yellow fever mosquito Aedes aegypti during the first 4-6 h after ingestion of a blood meal. Transcription of the early trypsin gene occurs after adult emergence under control of juvenile hormone, but the transcript remains untranslated before feeding. Early trypsin was in vitro translated using mRNA extracted from midguts of unfed and fed females, indicating that there are not structural features in the early trypsin mRNA that impede translation in vitro. Eight single protein meals exhibiting different molecular weights and amino acid composition, as well as ingestion of several amino acid mixtures of different complexity, had the ability to prompt early trypsin translation. In contrast, ingestion of saline, latex or midgut-filling sugars were unable to induce early trypsin mRNA translation. In addition intra-thoracic injection of an amino acid solution induced early trypsin translation, while injection of saline or albumin failed. In summary an increase in the size of the midgut amino acid pool by feeding or injection of an amino acid solution was sufficient to induce translation of early trypsin mRNA; 35S-labeled amino acids, fed with a protein meal, were incorporated into newly synthesized early trypsin; the first phase of trypsin synthesis is likely induced by an initial rapid increase in the concentration of amino acids in the midgut cells after ingestion of a blood meal.

Early trypsin, a female-specific midgut protease in Aedes aegypti: isolation, aminoterminal sequence determination, and cloning and sequencing of the gene.

Early trypsin is a female-specific protease present in the Aedes aegypti midgut during the first hours after ingestion of a blood meal. It plays an essential role in the transcriptional activation of the late trypsin form, the major midgut endoprotease involved in the blood meal digestion. Early trypsin is the most abundant midgut polypeptide isolated by benzamidine-sepharose affinity chromatography 3 h after feeding. The amino-terminal sequence of the early trypsin protein matches that of the 3a1 cDNA for a putative trypsinogen described by Kalhok et al. (Insect. Molec. Biol., 2, 71-79, 1993). The early trypsin cDNA was over expressed in Escherichia coli. Polyclonal antibodies generated against this recombinant protein were used to show that the enzyme was present in the midgut during the first 4 h after feeding. A 2.5 kb genomic clone of the early trypsin was isolated, mapped and subcloned. A 1.56 kb subclone, corresponding to 1303 bp of the upstream regulatory region and 265 bp of the coding region, was sequenced. The gene contains a 64 nucleotide intron which interrupts the codon for Val at position 18 of the protein. This Val is located toward the end of the putative signal sequence of the protein.

Identification of three allatostatins and their cDNA from the mosquito Aedes aegypti.

Three allatostatins have been isolated from the mosquito Aedes aegypti. These peptides have the following structures: Ser-Pro-Lys-Tyr-Asn-Phc-Gly-Leu-amide, Leu-Pro-His-Tyr-Asn-Phe-Gly-Leu-amide, and Arg-Val-Tyr-Asp-Phe-Gly-Leu-amide. A cDNA encoding these peptides was isolated from an abdominal ganglia cDNA library and sequenced. It was found to encode two additional allatostatins: Ala-Ser-Ala-Tyr-Arg-Tyr-His-Phe-Gly-Leu-amide and Leu-Pro-Asn-Arg-Tyr-Asn-Phe-Gly-Leu-amide. Northern analysis of whole mosquito mRNA revealed a single prepro-allatostatin message of around 3,000 bases. Identification of a partial prepro-allatostatin cDNA from a midgut cDNA library shows that the same gene is also expressed in the mosquito midgut.

Attenuated Salmonella as live oral vaccines against typhoid fever and as live vectors.

Attenuated Salmonella typhi vaccine strain CVD 908, which harbors deletion mutations in aroC and aroD, has been shown to be well-tolerated and highly immunogenic, eliciting impressive serum antibody, mucosal IgA and cell-mediated immune responses. A further derivative prepared by introducing a deletion in htrA (which encodes a heat-shock protein that also has activity as a serine protease in CVD 908 (Chatfield et al., unpublished data) resulted in CVD 908-htrA. In phase 1 clinical trials, CVD 908-htrA appears very attractive as a live oral vaccine candidate. Both CVD 908 and CVD 908-htrA are useful as live vector vaccines to deliver foreign antigens to the immune system. Conditions that enhance the expression and immunogenicity of foreign antigens carried by CVD 908 and CVD 908-htrA are being investigated.

Autogeny in three species of Triatominae: Rhodnius prolixus, Triatoma rubrovaria, and Triatoma infestans (Hemiptera: Reduviidae).

Autogeny, the capacity of a female to lay eggs without having ingested any blood meal in the adult stage, was studied in three species of Triatominae: Triatoma infestans, Triatoma rubrovaria, and Rhodnius prolixus. When nymphs of T. rubrovaria and R. prolixus were fed chicken blood, autogeny occurred frequently, even with only one meal. In T. infestans autogeny was frequent as well, but demanded at least two nymphal blood meals. Total number of autogenic eggs was positively correlated with the body weight of the adult female. We conclude, therefore, that autogeny is common in Triatominae.

Toxoplasma gondii maintenance in tissue culture: a new efficient method for culturing RH tachyzoites.

We describe here a new tissue culture method for prolonged laboratory maintenance of tachyzoites of the highly virulent RH strain of Toxoplasma gondii. Using a rapidly proliferating murine tumor cell line (YAC-1), the method described is easy to perform and is as or more efficient (both in terms of yield and cost) than other traditional methods for maintenance of the parasite. Furthermore, upon prolonged maintenance (greater than 160 days) in YAC-1 tissue culture, the pathogenicity of the parasite, as well as its capacity to elicit an immune response, are comparable to that of organisms maintained in mice. We conclude therefore, that the method described herein is a suitable alternative to the traditional method of maintenance of virulent RH strain T. gondii tachyzoites.

Vaccines to prevent bacterial enteric infections in children.

Considerable progress has been made in the last decade in developing vaccines against the most important bacterial enteric infections. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Newer generations of more sophisticated typhoid vaccines are undergoing clinical testing including recombinant attenuated S typhi strains and Vi polysaccharide-carrier protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated V cholerae 01 bacteria alone or in combination with the B subunit of cholera toxin, each conferred 50% to 53% protection over 3 years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated by children and adults in developing countries and highly immunogenic following administration of just a single oral dose; a large-scale field trial of the efficacy of this vaccine is underway. Several candidate vaccines against Shigella and enterotoxigenic E coli are in clinical trials.

A review of the current status of enteric vaccines.

Much progress has been made in developing vaccines against the most important enteric infections. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin, each conferred 50-53% protection over three years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated by children and adults in less developed countries and highly immunogenic following administration of just a single oral dose; a large-scale field trial of the efficacy of this vaccine is underway. In experimental challenge studies in volunteers, a single dose of CVD 103-HgR confers significant protection against challenge with wild-type V. cholerae O1 of either classical or El Tor biotype and either Inaba or Ogawa serotype. Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials. A multivalent rotavirus vaccine (rhesus reassortant vaccine) is undergoing extensive field testing in developed and less developed countries.

PIP: The development of safe, effective vaccines to prevent diseases due to rotavirus, enterotoxigenic Escherichia coli, enteropathogenic E. coli, Shigella, and Vibrio cholerae O1 would markedly reduce the burden of diarrheal diseases in Third World countries. This review concentrates on vaccines that have already been licensed, that have been evaluated in controlled trials of efficacy, or that have entered clinical trials to assess their safety and immunogenicity. Two new vaccines against typhoid fever have been licensed. Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines. Inactivated oral cholera vaccines consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin conferred 50-53% protection in a field trial in Bangladesh. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated and highly immunogenic after a single oral dose. In experimental challenge studies, a single dose of CVD 103-HgR conferred significant protection against challenge with wild-type V. cholerae O1. Several candidate vaccines against Shigella and enterotoxigenic E. coli are in clinical trials. Finally, a multivalent rotavirus vaccine (rhesus reassortant) is undergoing extensive field testing.