Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 2: Vaccination against rubella.

In 1995-96 we conducted a review of rubella immunization strategies. Worldwide, 78 countries (more than one-third) reported a national policy of using rubella vaccine. This was closely related to country economic status. Based on the United Nations country classification, rubella vaccine is used in 92% of industrialized countries, 36% of those with economies-in-transition, and 28% of developing countries. Cases of congenital rubella syndrome (CRS) may be prevented as follows: by providing direct protection to women and/or schoolgirls (a selective vaccination strategy); by vaccinating boys and girls to provide indirect protection by reducing the transmission of rubella virus (a childhood vaccination strategy); or by a combination of these approaches (a combined strategy). A combined strategy was most commonly reported (60% of countries); seven countries (9%) reported a selective strategy; and 24 countries (31%) reported only childhood immunization. Experience has shown that it is essential to include vaccination of women of childbearing age in any rubella control strategy. Childhood vaccination alone may pose a risk of an increase in CRS cases. Although many countries have introduced rubella vaccine, few report any data on the impact of vaccination. Countries using rubella vaccine need to establish surveillance for rubella and CRS and monitor coverage in each of the target groups.

Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 1: Burden of disease from CRS.

Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and cataracts, and a variety of other permanent manifestations. In developing countries, the burden of CRS has been assessed as follows: by surveillance of CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by serosurveys documenting the rubella susceptibility of women of childbearing age. During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported from industrialized countries during the pre-vaccine era. Special studies of CRS have been reported from all WHO regions. Rubella surveillance data show that epidemics occur every 4-7 years, similar to the situation in Europe during the pre-vaccination era. In developing countries, the estimated average age at infection varies from 2-3 years to 8 years. For 45 developing countries we identified serosurveys of women of childbearing age that had enrolled > or = 100 individuals. The proportion of women who remained susceptible to rubella (e.g. seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25% in 12 countries. Discussed are methods to improve the surveillance of rubella and CRS in developing countries.

The relationship between dose and response of standard measles vaccines.

A considerable number of field trials have been published over the last 30 years, showing measles vaccines to be highly effective. Due to inconsistencies in methodology, comparisons between these studies have often been difficult with regard to the potencies used and the sero-response of vaccinated children. This article reviews key studies which have measured the response of children to different potencies of vaccine. The review concludes that increasing the titre of vaccine above log10 3.0 does not appear to improve vaccine efficacy. It is recommended that standard titre measles vaccine should be administered with a minimum potency of log10 3.0 TCID50 or PFU per dose at 9 months of age or later. This recommendation is endorsed by the Global Advisory Group and the Research and Development Group of the Expanded Programme on Immunization.

[Door-to-door vaccination as a strategy for eradication of poliomyelitis]. / La vacunación casa a casa como estrategia de erradicación de la poliomielitis.

Due to persistence of poliomyelitis cases in the Pacific Coast of Mexico and particularly in the state of Sinaloa, a house to house vaccination strategy named "Sinaloa Operation" was carried out in 100% of the territory of this state. Sinaloa was divided in small geographical and statistical unit area (AGEB). Simultaneously, teams of nurse carried out a population census of children under five years old and pregnant women. Nurses vaccinated the children with Sabin trivalent vaccine in undiscriminating form. These activities were made in three phases. In the last phase (February 1991) 301, 441 Sabin vaccine doses were administered. This figure represents an extension of the vaccination coverage to the children of the seasonal migrant workers from other parts of the country. As a result of this programme. Sinaloa has not had any other polio case since two years ago.

[Immune response to poliovirus]. / Respuesta inmune a poliovirus.

General aspects on the immune response to poliovirus are described, considering it's molecular structure. Since the poliovirus is a cytocide agent, antibody immune response is the most important among those related to protection; however probably a minimum of helper T cells are required (more than 200 T lymphocytes with phenotype CD4) in order to get a best response. Phagocyte, NK cells and T lymphocytes probably take part in the viral clearance from the central nervous system, also in the host injure mechanisms. Some molecular aspects of the neutralizing antibodies combining site are described too. Activation particularities, of the common mucosal immune system confirm the importance of the secretory immune response in the control of the poliomyelitis.

[Immuno-epidemiologic considerations on the prevention of measles in Mexico]. / Consideraciones inmuno-epidemiológicas en la prevención del sarampión en México.

Study results of passive natural immunity anti-measles, and immune response to measles vaccine from different strains in Mexican children under one year old, are described in this paper. Mexican infants in these studies ended their maternal immunity at 8-10 months of age. Edmonston-Zagreb (EZ) vaccine strain had higher seroconversion rates comparing to Schwarz strain. Dose response effect was more closely related to Schwarz strain than EZ, since difference in seroconversion rates with standard, medium and high doses were statistically significant. However geometric mean post-vaccination titers were higher in children vaccinated with Schwarz strain, than EZ receptors.

[Evaluation of the cold chain and follow-up of the potency of the antimeasles vaccine in the field]. / Evaluación de la cadena de frío y seguimiento de la potencia de la vacuna antisarampión en campo.

In order to evaluate the quality of the measles vaccine, it was carried out a study in three states of Mexico (Durango, San Luis Potosi and Yucatan) during the intensive vaccination campaign in 1986. Edmonston-Zagreb measles vaccine vials were obtained from the different administrative-sanitary levels of the Ministry of Health in Mexico. Interviews were performed to the vaccine responsibles. Questionnaires had the following aspects of the cold chain: storage, preservation, control and transport of measles vaccine. Answers were evaluated through a system, where 100% indicated the necessary and sufficient level to get a good operating of the cold chain. The vaccine potency did not have variations under the minimum titre recommended for the World Health Organization (W.H.O.). The three states had the following compliment of the cold chain norms: 1) Central state level: 83% in storage, 80% in preservation, 100% in control and 100% in transport norms; 2) Regional level (jurisdiction): 87% in storage, 51% in preservation, 93% in control and 100% in transport norms; 3) Local level: 83% in storage, 64% in preservation, 83% in control and 33% in transport norms.

Immunization of six-month-old infants with different doses of Edmonston-Zagreb and Schwarz measles vaccines.

Because measles causes an estimated 2 million deaths per year among children in developing countries, including a substantial proportion of infants less than nine months old--the age at which vaccination is recommended--there has been interest in using different strains of vaccine and higher doses to achieve immunization of younger infants. We conducted a randomized trial of three different doses of Edmonston-Zagreb and of Schwarz measles vaccines in infants to evaluate the effect of the strain and dose of vaccine on the serologic response and acute adverse reactions to vaccination. Six-month-old infants received a standard, medium, or high dose of one of the vaccines, and nine-month-old infants received a standard dose. Antibody levels were measured before and after vaccination, by means of a plaque-reduction neutralization assay, in 1061 six-month-olds and 299 nine-month-olds. Edmonston-Zagreb vaccine produced higher rates of seroconversion and seropositivity than comparable doses of Schwarz vaccine. Among the six-month-old infants, the seroconversion rate 18 weeks after vaccination with the standard dose of Edmonston-Zagreb vaccine was 92 percent, that with the medium dose was 96 to 97 percent, and that with the high dose was 98 percent; the rates for the corresponding doses of Schwarz vaccine were 66 percent, 76 percent, and 91 percent, respectively. Higher seroconversion rates were observed with an increase in the dose of either Edmonston-Zagreb (P less than 0.01) or Schwarz (P less than 0.001) vaccine. The seroconversion rates produced by high and medium doses of Edmonston-Zagreb vaccine in six-month-olds were equal to or significantly higher than the rate produced by a standard dose of Schwarz vaccine in nine-month-olds (87 percent). Clinical adverse reactions were not associated with the strain or dose of a vaccine. We conclude that Edmonston-Zagreb vaccine is more immunogenic than Schwarz vaccine in infants and can induce effective immunization against measles at six months of age.

[Evaluation of the cold chain during the national antipoliomyelitis vaccination days. Mexico, 1987-1988]. / Evaluación de la cadena de frío en los días nacionales de vacunación antipoliomielítica México, 1987-1988.

An evaluation of the cold chain used during the "National Vaccination Days Against Poliomyelitis" in January and March of 1987 and 1988 was performed in 32 states of Mexico, both the potency of the trivalent Sabin vaccine and completion of requirements for the maintenance of the cold chain were evaluated at each level in the Ministry of Health's structure. Only 56 percent of the refrigeration units exclusively stored vaccines, more than 10 percent of refrigerators were broken, and 44 percent of the persons responsible for the cold chain system considered the storage capacity inadequate. A correlation was found between non-fulfillment of maintenance requirements for cold chain and a decreased in vaccine potency.

[Estimate of the cost/benefit ratio of measles vaccination]. / Estimación de la razón beneficio/costo de la vacunación contra el sarampión.

Among primary health care programs, one of those that has the highest benefit/cost ratio is measles immunization. An estimate of cases, complicated cases and deaths that could have occurred if such immunization program would not have been run, and costs of medical care (hospitalization, physician's visits, medical treatment and rehabilitation), were calculated. Since population at risk has a steady-state given by those who enter -births- and releave it -when they are 15 years old-, if the program did not exist more than 2 million cases and at least 60,000 deaths from measles would have occurred annually. This hypothetical situation is compared with the actual situation of measles in Mexico during the 80's; 1) no more than 100,000 cases could have been estimated to occur in the very extreme case of notifying only one out of 10 cases. 2) The proportions of vaccinated and immune children under five reach 70 percent; this situation has produced 3) a fade out of epidemicity and has increased the critical size of community population for epidemics and doubled the interepidemic interval with the corollary of 4) increasing the average age of infection. The average cost of vaccinating a child was estimated near 1.25 dollars (US). Estimated costs of disease are related to individual losses. Taking into account these factors, benefit/cost ratio of measles immunization in Mexico is, at least, 100:1. Measles transmission patterns in Mexico are discussed since they lead to increase the benefit/cost ratio as compared to countries where the age of infection was put up before the immunization era. To expand investments on measles immunization is recommended.

[Seroconversion with trivalent Sabin vaccine in children less than four years of age]. / Seroconversión a la vacuna Sabin trivalente en niños menores de cuatro años de edad.

A group of 58 children under 4 years old, were vaccinated with trivalent oral poliovirus vaccine Sabin (OPV), in two sanitary areas of Chiapas, Mexico. The complement of procedures for the maintenance of the cold chain, and the changes in the potency of the vaccine prior and after the vaccination were evaluated. Nurses got a blood sample of 3cc and other one, four weeks after vaccination in order to evaluate the seroconversion rate attributable to Sabin vaccine, which was analyzed through neutralization serologic test. Moreover the investigation team got a sample of feces one day prior to vaccination and other one every week in the following three weeks to vaccination date in order to isolate the poliovirus in the feces of the children. The high pre-vaccination seropositivity suggests that in these areas exist a wide circulation of poliovirus, which probably were vaccine viruses and in less proportion wild viruses. The seroconversion rates were low for the three types of poliovirus, nevertheless 83% of the children had at least one of the three possibilities of seroconversion: unique, double or triple. Children with pre-vaccine seropositive probably had a secondary immune response.