RESUMO
Because concurrent infections with geohelminth parasites might impair the immune response to oral vaccines, we studied the vibriocidal antibody response to the oral cholera vaccine CVD 103-HgR in children infected with Ascaris lumbricoides and investigated the effect of albendazole pretreatment on the postvaccination response. Children with ascariasis were randomized to receive either 2 sequential doses of 400 mg of albendazole or placebo. After the second dose, CVD 103-HgR was given, and serum vibriocidal antibody levels were measured before and 10 days after vaccination. Postvaccination rates of seroconversion were greater in the treatment group that received albendazole (P=.06). Significantly greater rates of seroconversion and geometric mean titer were observed in the albendazole group in subjects with non-O ABO blood groups. A significant association was observed between vibriocidal seroconversion rates and treatment group, suggesting that A. lumbricoides infections impair the immune response to oral cholera vaccine, particularly in subjects of non-O blood groups.
Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Anticorpos Antibacterianos/sangue , Ascaríase/tratamento farmacológico , Ascaríase/imunologia , Ascaris lumbricoides , Vacinas Bacterianas/imunologia , Vacinas contra Cólera/imunologia , Vacinas Atenuadas/imunologia , Adolescente , Animais , Formação de Anticorpos , Ascaris lumbricoides/efeitos dos fármacos , Antígenos de Grupos Sanguíneos/imunologia , Criança , Interações Medicamentosas , Equador , Feminino , Humanos , Masculino , Trichuris/efeitos dos fármacosRESUMO
Several live oral vaccines (polio, bovine rotavirus, CVD 103-HgR cholera) are less immunogenic in developing than in industrialized countries. It was hypothesized that proximal small bowel bacterial overgrowth (common in children in less developed countries but rare in industrialized settings) diminishes the vibriocidal antibody response to CVD 103-HgR. In total, 202 fasting Santiago schoolchildren aged 5-9 years had lactulose breath H2 tests to detect proximal small bowel bacteria 1 day before ingesting CVD 103-HgR. Florid small bowel overgrowth was observed in 10 (5.6%) of 178 analyzable children. In children with florid overgrowth, vibriocidal seroconversion differed little from other children (60% vs. 67%), but the geometric mean titer was lower (160 vs. 368; P=.25). By logistic regression, increased peak breath H2 at small bowel time points was associated with diminished seroconversion (P=.04), as was the interaction of H2 value and weight (children >25 kg had lower seroconversion rates among subjects with heaviest overgrowth).
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/imunologia , Intestino Delgado/microbiologia , Vibrio cholerae/imunologia , Administração Oral , Testes Respiratórios , Criança , Pré-Escolar , Feminino , Humanos , Hidrogênio/análise , Lactulose/metabolismo , MasculinoRESUMO
BACKGROUND: Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age. METHODS: The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingested > or =70 ml were considered fully vaccinated. FINDINGS: Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested > or =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose. INTERPRETATION: Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Vibrio cholerae/imunologia , Administração Oral , Chile , Vacinas contra Cólera/efeitos adversos , Método Duplo-Cego , Fezes/microbiologia , Humanos , Lactente , Paladar , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Vibrio cholerae/isolamento & purificaçãoRESUMO
To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. A total of 170 partially-immune American soldiers stationed in Panama received one of the following five formulations: (a) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(7) CFU, (b) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(6) CFU, (c) CVD 103-HgR alone at 10(8) CFU, (d) CVD 111 alone at 10(7) CFU, or (e) inactivated Escherichia coli placebo. Among those who received CVD 111 at the high or low dose either alone or in combination with CVD 103-HgR, 8 of 103 had diarrhea, defined as three or more liquid stools. None of the 32 volunteers who received CVD 103-HgR alone or the 35 placebo recipients had diarrhea. CVD 111 was detected in the stools of 46% of the 103 volunteers who received it. About 65% of all persons who received CVD 103-HgR either alone or in combination had a fourfold rise in Inaba vibriocidal titers. The postvaccination geometric mean titers were comparable among groups, ranging from 450 to 550. Ogawa vibriocidal titers were about twice as high in persons who received CVD 111 as in those who received CVD 103-HgR alone (600 versus 300). The addition of CVD 111 improved the overall seroconversion rate and doubled the serum Ogawa vibriocidal titers, suggesting that the combination of an El Tor and a classical cholera strain is desirable. While CVD 111 was previously found to be well tolerated in semiimmune Peruvians, the adverse effects observed in this study indicate that this strain requires further attenuation before it can be safely used in nonimmune populations.
Assuntos
Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Militares , Qualidade de Produtos para o Consumidor , Humanos , Panamá , Estados Unidos , Vacinas Atenuadas/imunologiaRESUMO
BACKGROUND: The cost of Haemophilus influenzae type b (Hib) conjugate vaccines has limited their use in non-industrialised countries. To identify more economical vaccination schedules, we carried out a randomised trial of the immunogenicity of alternative regimens to the standard three-dose series. METHODS: 627 Chilean infants were randomly allocated to one of four regimens with either Hib polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) or Hib oligosaccharide-diphtheria mutant toxoid conjugate vaccine (PRP-CRM197), for a total of eight groups. All infants receive diphtheria-tetanus-pertussis (DTP) vaccine at ages 2, 4, and 6 months. The regimens included three full doses, three fractional doses consisting of one half or one third of the full dose, and a regimen of two full doses (at age 4 and 6 months). The primary outcome was the proportion of infants with serum anti-polyribosylribitol phosphate (PRP, the type b capsular polysaccharide) concentrations of 0.15 microg/mL or more at age 8 months. FINDINGS: 93% (95% CI 85-98) of infants vaccinated with three full doses of PRP-T or PRP-CRM197 (95% CI 84-98) achieved anti-PRP concentrations of 0.15 microg/mL or more at age 8 months, compared with 91% (83-96) to 100% (95-100) of infants immunised with any fractional-dose regimen. Of the infants vaccinated with two doses of PRP-T or PRP-CRM197, 99% (93-100) and 87% (77-93) developed anti-PRP concentrations of 0.15 microg/mL or more, respectively. INTERPRETATION: 91% (83-96) to 100% (95-100) of infants immunised with one-half or one-third of a full dose of Hib conjugate developed protective antibody concentrations. Carrier priming with DTP may make two-dose schedules an option in some places. These alternative regimens could bring the cost of Hib vaccines within reach of countries that currently cannot afford them.
Assuntos
Proteínas de Bactérias/administração & dosagem , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b , Toxoide Tetânico/administração & dosagem , Vacinação/economia , Proteínas de Bactérias/economia , Chile/epidemiologia , Custos e Análise de Custo , Países em Desenvolvimento , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Relação Dose-Resposta Imunológica , Infecções por Haemophilus/epidemiologia , Vacinas Anti-Haemophilus/economia , Humanos , Esquemas de Imunização , Lactente , Toxoide Tetânico/economia , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/economiaRESUMO
To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. In the first study, 23 U.S. adult volunteers received CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(8), 10(7), or 10(6) CFU, CVD 111 alone at 10(7) CFU, or placebo. In the second study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 10(9) CFU plus CVD 111 at 10(9) or 10(8) CFU, CVD 111 alone at 10(9) CFU, CVD 103-HgR alone at 10(9) CFU, or placebo. Three of 15 U.S. volunteers who received CVD 111 at 10(7) or 10(8) CFU developed mild diarrhea, compared to none of 4 who received CVD 111 at 10(6) CFU and 1 of 4 who received placebo. Twelve (63%) of 19 vaccine recipients shed the El Tor vaccine strain. All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers. Volunteers who received CVD 111 at 10(7) CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose. In the second study, all dosage regimens were well tolerated in Peruvians. About 20% of volunteers who received CVD 111 at the high dose excreted the El Tor organism, compared to 7% in the low-dose group. CVD 111 was detected in the stools of two placebo recipients, neither of whom had symptoms or seroconverted. In all vaccine groups, 69 to 76% developed fourfold rises in Inaba vibriocidal antibodies. Among those who received the bivalent vaccine, 53 to 75% also developed significant rises in Ogawa vibriocidal antibodies. We conclude that it is feasible to produce a single-dose, oral bivalent vaccine that is safe and immunogenic against both biotypes (El Tor and classical) and both serotypes (Inaba and Ogawa) of cholera for populations in both developed and developing parts of the world.
Assuntos
Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Vibrio cholerae/imunologia , Administração Oral , Adulto , Anticorpos Antibacterianos/imunologia , Cólera/imunologia , Vacinas contra Cólera/normas , Relação Dose-Resposta Imunológica , Fezes/microbiologia , Humanos , Imunoglobulina G/imunologia , Peru , Estados UnidosRESUMO
To assess whether combining a Haemophilus influenzae type b conjugate vaccine (PRP-T) and diphtheria-tetanus toxoid-pertussis (DTP) vaccine in a single syringe would impact adversely the antibody response and clinical protection conferred by pertussis vaccine, surveillance and a nested serosurvey were conducted among infants in a large-scale evaluation of PRP-T in Santiago. Infants received either combined PRP-T/DTP or DTP only at 2, 4, and 6 months of age. At 8 months, pertussis agglutinin, anti-pertussis toxin, and anti-filamentous hemagglutinin antibody levels in the PRP-T/DTP (137.7, 23.1, and 12.2, respectively) and DTP (142.9, 20.6, and 13.0, respectively) groups were comparable. The incidence of pertussis was similar among infants assigned to health centers administering combined PRP-T/DTP and those administering DTP alone (13.1 vs. 12.2 cases/10(5) child-years). Combined PRP-T/DTP vaccine did not diminish protection against pertussis.
Assuntos
Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/efeitos adversos , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/efeitos adversos , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Coqueluche/imunologia , Coqueluche/prevenção & controle , Testes de Aglutinação , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/análise , Bordetella pertussis/imunologia , Chile/epidemiologia , Humanos , Imunoglobulina G/análise , Lactente , Estudos Soroepidemiológicos , Vacinação/efeitos adversos , Coqueluche/epidemiologiaRESUMO
Persons of blood group O are at increased risk of developing cholera gravis. In a randomized, placebo-controlled, double-blind safety-immunogenicity trial of live oral cholera vaccine CVD 103-HgR in 5- to 9-year-old Chilean children, vibriocidal antibody seroconversion (74% overall) did not differ by blood group. However, the reciprocal geometric mean titer (GMT) in blood group O vaccines (GMT = 486) was higher than that in non-O vaccines (GMT = 179) (P < 0.02).
Assuntos
Sistema ABO de Grupos Sanguíneos , Anticorpos Antibacterianos/imunologia , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Vibrio cholerae/imunologia , Atividade Bactericida do Sangue , Criança , Chile , Cólera/imunologia , Citotoxicidade Imunológica , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Humanos , Vacinas Atenuadas/imunologiaRESUMO
Groups of 122 Peruvian adults of low socioeconomic level (SEL) and 125 of high SEL received a randomly allocated 5 x 10(9)- or 5 x 10(8)-CFU dose of CVD 103-HgR live oral cholera vaccine or a placebo. The vaccine was well tolerated. Vibriocidal seroconversions occurred in 78% of high-SEL and 72% of low-SEL subjects who ingested the high dose and in 78 and 49%, respectively, of those who received the low dose.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/imunologia , Vibrio cholerae/imunologia , Administração Oral , Adulto , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/efeitos adversos , Método Duplo-Cego , Humanos , Peru , Fatores Socioeconômicos , VacinaçãoRESUMO
CVD 103-HgR is an attenuated, AB+, live, recombinant vaccine strain, developed by deletion of the toxA gen in a virulent Vibrio cholerae 01, Inada classical strain (569B). In phase II studies conducted to date, CVD 103-HgR has been well tolerated and immunogenic in volunteers from both industrialized countries and cholera-endemic areas. In this study of safety, immunogenicity and excretion, 81 Chilean adults were randomly allocated to receive, in a double blind fashion, a single oral dose of 5 x 10(9) FU of CVD 103-HgR or placebo, (5 x 10(9) heat-killed E. Coli K12 organisms), in 100 ml of buffered water. Side effects were assessed by daily visits to the participants. Immunogenicity, (vibriocidal seroconversion), was investigated in blood drawn before and on days 8 and 28 after immunization, while stool cultures to assess excretion of the vaccine strain were performed on specimens obtained on days 1 and 7. None of the participants, (40 vaccinees and 41 placebo recipients), experienced untoward effects during 30 minutes of close surveillance after ingestion of the preparation; upon follow up, neither adverse events were more frequently reported by the vaccinees. 34/40 vaccinees, and 2/41 participants receiving placebo had a significant raise, (> = fourfold), in their vibriocidal titers; (85 vs 2%, p < 0.001). The peak postimmunization geometric mean titer, (222), was ten fold higher than the baseline vibriocidal titer. The vaccine strain was recovered in stool cultures from 8 participants, one of them excreted the strain in both specimens. We conclude that CVD-103-HgR is safe and immunogenic in Chilean adults.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/imunologia , Vibrio cholerae/imunologia , Administração Oral , Adolescente , Adulto , Anticorpos Antibacterianos/imunologia , Antitoxinas/sangue , Antitoxinas/imunologia , Chile , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/efeitos adversos , Método Duplo-Cego , Humanos , Imunização , Imunoglobulina G/imunologia , Masculino , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologiaRESUMO
Milk was collected from 56 New York and 70 Venezuelan mothers participating in Rhesus rotavirus (RRV) pediatric vaccine trials. Plaque reduction neutralization antibody (PRNA) to RRV (VP7:3, VP4:RRV) and human P rotavirus (VP7:3, VP4:P) and epitope-blocking antibody to one RRV VP4 and VP7 epitope were determined. Controlling for postpartum age, more Venezuelan milk samples had detectable RRV and P PRNA, RRV VP4 epitope-blocking antibody (P less than or equal to .001), and higher RRV and P PRNA geometric mean titers (P = .01) than New York samples. Using a logistic regression model, both milk and infants' serum preimmunization RRV PRNA titers had a negative effect on seroconversion (P = .008 and .02, respectively). Only 25% (2/8) infants fed milk containing greater than or equal to 1:160 RRV PRNA seroconverted compared with 83% (5/6) fed milk containing less than 1:160 RRV PRNA (P = .1). Of milk samples containing greater than or equal to 1:160 RRV PRNA, seven (88%) of eight had greater than fourfold neutralizing activity against RRV versus P (P = .035), suggesting that VP4-specific milk antibodies may interfere with RRV seroconversion.
Assuntos
Anticorpos Antivirais/análise , Leite Humano/imunologia , Rotavirus/imunologia , Vacinas Virais/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Ligação Competitiva , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Feminino , Humanos , Lactente , Recém-Nascido , Testes de Neutralização , New York/epidemiologia , Gravidez , Prevalência , Infecções por Rotavirus/epidemiologia , Vacinação , Venezuela/epidemiologiaRESUMO
PIP: Since rotavirus infection is common in Caracas, Venezuela and seasonal in Rochester, New York USA, researchers analyzed at least 65 and 58 breast milk samples form women in Caracas and Rochester respectively to identify rotavirus specific antibodies. The mothers had earlier participated in Rhesus rotavirus serotype 3 (RRV) vaccine trials. The Plaque reduction neutralization assay revealed that 84.6% of breast milk samples from Venezuela had detectable antibody to RRV compared to only 50% in the US samples (p=.00009). Yet when the researchers compared US winter breast samples with the Venezuelan samples the difference was no longer significant (p=0.2). Further 50% of US nonwinter samples had rotavirus specific antibody which indicated either low level rotavirus infectious activity continuing during the nonwinter months, antigenic stimulation with cross reacting antigens, or active memory. The leading antibody responses to RRV and human P rotavirus in all breast milk samples were against VP7 antigens (62% Venezuela, 42% USA; p=.04). Only 9% of positive US samples had VP4 antigens whereas 36% of the positive Venezuelan samples had them (p=.003). 60% of the 15 4-10 month old infants in Caracas who had received RRv 10 thousand vaccine responded to the vaccine. Moreover 55% of infants who consumed breast milk with epitope blocking VP7 antibody also responded. Yet 75% of RRV vaccinated infants who took in breast milk with epitope blocking VP4 activity did not experience a seroresponse. Further 71% of those fed with breast milk negative for VP4 antibody and positive for VP7 antibody did experience a seroresponse. Thus VP4 activity in breast milk appeared to interfere with vaccine take in breast fed RRV immunized infants.^ieng
Assuntos
Anticorpos Antivirais/análise , Proteínas do Capsídeo , Leite Humano/imunologia , Rotavirus/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Aleitamento Materno , Capsídeo/imunologia , Feminino , Humanos , Lactente , Recém-Nascido , Minnesota , Rotavirus/classificação , Infecções por Rotavirus/prevenção & controle , Estações do Ano , Venezuela , Vacinas Virais/imunologiaRESUMO
To examine whether prior immunity against a carrier protein modulates the serological response to injected peptide haptens attached to the same carrier in man, baseline tetanus antitoxin levels in volunteers who received a malaria sporozoite peptide-tetanus toxoid conjugate vaccine were compared with post-vaccination IgM and IgG antibody titres against the sporozoite antigen. In tetanus-vaccinated North American recipients of low doses of conjugate vaccine there were significant dose-dependent negative correlations between these variables, which suggests that epitopic suppression may occur in man. In contrast, Venezuelans living in non-malarious areas and mostly naive to tetanus toxoid showed a notable IgM response to the sporozoite antigen. The findings indicate that epitopic suppression and immune enhancement occur in man, and that the specific immunological responses to conjugate peptide vaccines may be difficult to predict.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Proteínas de Transporte/imunologia , Malária/imunologia , Oligopeptídeos/imunologia , Toxoide Tetânico/imunologia , Tétano/imunologia , Vacinas Sintéticas/imunologia , Vacinas/imunologia , Adolescente , Adulto , Idoso , Animais , Anticorpos Antiprotozoários/análise , Epitopos/análise , Feminino , Haptenos/imunologia , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Malária/sangue , Malária/prevenção & controle , Masculino , Maryland , Pessoa de Meia-Idade , Plasmodium/imunologia , Tétano/sangue , Tétano/prevenção & controle , Antitoxina Tetânica/análise , Fatores de Tempo , VenezuelaRESUMO
An enzyme-linked immunosorbent assay (ELISA) measuring, in serum, immunoglobulin G (IgG), IgM, and IgA to Vi capsular polysaccharide antigen that was tyraminated (Vi-Tyr) to increase its binding efficiency to microtiter plates was compared with the standard passive hemagglutination assay (PHA) as a screening test for chronic Salmonella typhi carriers. Initially, three populations were evaluated: 22 healthy U.S. adults, 17 young Chilean adults with acute typhoid fever, and 51 Chileans who had bacteriologically confirmed S. typhi chronic carriage. IgG-specific Vi-Tyr antibodies were preferentially present in the S. typhi chronic carrier state. A total of 44 of 51 (81%) chronic carriers, 0 of 22 (0%) healthy U.S. adults, and 2 of 17 (12%) Chileans with acute typhoid fever had reciprocal IgG Vi-Tyr ELISA antibody titers in serum of greater than or equal to 200. The IgG Vi-Tyr ELISA was then compared with the PHA as a screening test for chronic carriers in 141 Chilean female food handlers. One woman was serologically incriminated as a carrier by both the IgG ELISA and PHA; her coprocultures were positive for S. typhi. One other woman, identified as a carrier by PHA, was negative by culture and IgG ELISA. The IgG Vi-Tyr ELISA is as sensitive as the PHA (86 versus 76%) and as specific (95 versus 95%) in screening for chronic carriers.