The role of epidemiology in the introduction of vi polysaccharide typhoid fever vaccines in Asia.

Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the programme, (b) generation of policy-relevant data, (c) providing the 'backbone' for the implementation of other multidisciplinary projects, and (d) generation of unexpected but useful information relevant for the introduction of vaccines. Epidemiological studies contribute to all stages of development of vaccine evaluation and introduction.

Acceptability of oral typhoid vaccine in Thai children.

To determine the acceptability of oral typhoid vaccine to Thai children, 434 volunteers, aged 4-15 years (average age = 8.2 years), were assigned to take three capsules of oral typhoid vaccine (one capsule every other day). Success was defined as the subjects' being able to swallow all three capsules. Information concerning the subjects' level of education, eating habits, and ability to take medicines in a variety of preparations (syrups, tablets and capsules) was obtained. The overall success rate was 94.2%; the rates were 84.4%, 94.9%, and 100% in the age groups 4-6 years, 7-9 years, and 10-12 years respectively. The rates were 82%, 85.7%, 93.3%, 96.4%, 98.8%, 100% and 100% in the students of kindergarten 1, kindergarten 2, elementary grade 1, grade 2, grade 3, grade 4, and grade 5 respectively. There was a correlation between a child's prior ability to take tablets/capsules and his success in swallowing the oral typhoid vaccine.

Efficacy of Purified Vi Polysaccharide Typhoid Vaccine

This experiment was conducted to assess the efficacy of typhoid vaccine newly produced by purifying Vi antigen of Salmonella typhi. With Karber method, LD50 of challenging organism (S. typhi ty2) was determined as 6.31 CFU/mouse, and then the organism was used for the study. With Probits method, ED50 of the vaccine was determined as 0.016 microgram / 0.5 ml / mouse. The ELISA titer (0.5097+/-0.0606) was 4 times in the group treated with high dose (0.25 microgram/0.5ml) as in control (0.1113+/-0.0110). Six major protein bands of 66, 55, 35, 33, 18, and 9 kd were detected in Western blot analysis with serum of a vaccine treated mouse, whereas only one weak band of about 35 kd was detected with serum of a control mouse. We concluded that typhoid vaccine produced by purifying Vi antigen of S. typhi very effectively prevent S. typhi infection in mice.

Typhoid vaccines.

Typhoid fever continues to be a major public health problem in developing countries with about 33 million cases per year. Protective efficacy of traditional acetone/phenol killed vaccines is similar to newer typhoid vaccines (Ty21A and Vi antigen vaccine) but side effects of these newer vaccines are considerably less. Though the mortality is low, typhoid fever causes considerable morbidity and loss of working days. Problems during treatment are increasing due to emergence and spread of multidrug resistant S. typhi. Hence to decrease the incidence of typhoid fever in addition to ensuring safe water supply and excreta disposal a typhoid vaccine needs to be introduced in the National Immunization Schedule.

Reassessment of frequency of occurrence of typhoid fever and cost efficacy analysis of antibiotic therapy.

Typhoid fever has assumed importance due to the increased incidence of drug resistance in India. The exact magnitude of the problem is not accurately known. The objective of this study was to collect retrospectively the data on the incidence and frequency of typhoid fever among hospital admissions at St. Johns Medical College Hospital (SJMCH), Bangalore during the year 1987 to 1992 and also to study the sensitivity pattern and the use of antibiotics. The study was also aimed at comparison of immunogenicity and tolerance of conventional vaccine to the newer polysaccharide vaccine. It was found that the incidence of typhoid fever showed change from epidemic to endemic situation with outbreaks of epidemics. Sensitivity pattern also showed change during the same period and antibiotic resistance was increasingly demonstrated from 1989. Cost per patient and total cost to the hospital due to increased admissions also showed progressive increase. The polysaccharide vaccine (recently made available in India) had very low adverse reaction profile with higher immunogenicity as compared to conventional vaccine. Its single dose effect with long lasting immunity indicates it probable usefulness in the eradication of disease.

Fiebre tifoidea: brote epidémico en el reten de Catia: diciembre 1991-Septiembre 1992: Hospital General del Oeste / Thiphoid fever: epidemie outbreaks in the reten of Catia: december 1991-September 1992: General Hospital of the west

Evaluamos 23 historias médicas con diagnóstico de fiebre tifoidea, de pacientes provenientes del Reten de Catia durante el período Diciembre 1991 -Septiembre 1992. Conseguimos edad, sexo, ocurrencia estacional, motivo de consulta, sintomas, signos complicaciones, paraclínicos y mortalidad. Todos los pacientes fueron varones con edad promedio de 25-78 años. El mayor número de casos ocurrió en Mayo 1992, el tiempo de convalescencia fue de 41-57 días. Los hallazgos más frecuenttes fueron: como motivos de consulta y datos de la enfermedad actual, fiebre, disminución de peso, diarrea, dolor abdominal, taquicardia, hipotensión taquipnea al examen físico y perforación intestinal y sepsis como complicaciones Serología y cultivos fuerron positivos en un 69.57 por ciento y 43.48 por ciento respectivamente. Encontramos elevado porcentaje de complicaciones y alta mortalidad debido al traslado tardio de los pacientes al hospital (entre la tercera y cuarta semana). Sugerimos medidas preventivas

Vacunación contra la fiebre tifoidea / Vaccination against typhoid fever

La fiebre tifoidea es una enfermedad infecciosa aguda y febril causada por Salmonella typhi. La infección se adquiere por medio de la ingestión de alimentos o agua masivamente contaminados con la bacteria. Debido a que este microorganismo afecta sólo al ser humano y no hay reservorios animales, el elemento más importante en la cadena de transmisión son los individuos que no presentan sintomatología clínica pero son portadores y excretores activos del agente (portadores asintomáticos). En México, la enfermedad tiene características endémico-epidémicas relacionadas con deficiencias en el saneamiento ambiental y el aprovisionamiento de agua potable. La tasa de letalidad es de alrededor del 1 por ciento, sin embargo en los casos complicados puede ascender hasta el 30 por ciento. La vacuna que se utiliza más ampliamente en la actualidad es la inactivada por calor y fenol, la cual tiene efectos colaterales debido al LPS que siempre lo contamina. Además, confiere protección parcial y de corta duración, por lo tanto su empleo se ha limitado a grupos considerados como de alto riesgo y no está indicada en niños. La vacuna de Germanier -mutante avirulenta de Salmonella que se administra por vía oral- proteje hasta un 95 por ciento, siempre y cuando antes de administrarse se neutralice el jugo gástrico, aunque su utilización general en Salud Pública es impráctica. Ya que las porinas son buenos inmunógenos en modelos animales, la obtención de un conjugado antígenico Vi-porinas puede ser una excelente opción como vacuna contra la fiebre tifoidea

Clinical experience with typhoid vaccine in Thailand.

A brief report of the typhoid vaccine trials in Thailand is reviewed, and discussed in relation to other clinical and field studies.

Systemic and intestinal immunities after different typhoid vaccinations.

The comparative studies of systemic and intestinal immunities to S. typhi were performed in 29 healthy volunteers during 2 years after receiving oral vaccination with attenuated S. typhi Ty21a in gelatin capsule, parenteral vaccination with acetone inactivated or heat inactivated-phenol preserved S. typhi Ty2. The methods used were immunobead ELISA for total secretory IgA and indirect ELISA for specific secretory IgA in the intestinal lavage fluid. The specific systemic IgG, IgM and anti-O, anti-H agglutinins were measured by indirect ELISA and Widal test respectively. The leukocyte migration inhibition test was used for the measurement of systemic cell mediated immunity. The results indicate that the oral S. typhi Ty21a stimulated intestinal immunity better than both parenteral vaccines but evoked less systemic antibody response. The stimulation of systemic cell-mediated immunity by the live attenuated and acetone inactivated vaccine was comparable while stimulation by heat inactivated-phenol preserved vaccine was less pronounced. The same studies were performed in 26 healthy volunteers during 6 months following different doses of oral vaccination with S. typhi Ty21a in enteric-coated capsule. The results suggest that the stimulation of intestinal and systemic immunities by this vaccine is dosage dependent. Three doses of vaccine provide better stimulation than two doses and one dose, respectively.