Persistence of vaccine-derived poliovirus following a mass vaccination campaign in Cuba: implications for stopping polio vaccination after global eradication.

BACKGROUND: With substantial progress made toward polio eradication, developing the appropriate strategy for discontinuing global oral poliovirus vaccine (OPV) after global eradication becomes increasingly important. At issue is the theoretical risk of independent circulation of potentially virulent OPV-derived strains. Because Cuba uses OPV only in mass campaigns, it represents an ideal site to assess vaccine-derived poliovirus persistence. METHODS: Infants born after the 1997 biannual mass campaigns were evaluated for past (neutralizing antibody) or current (virus excretion) evidence of vaccine-derived poliovirus exposure. We obtained sera and/or stool specimens from 861 infants; a second serum from 218 infants. RESULTS: All stool specimens were poliovirus negative. Of 762 infants, 113 (14.8%) had initially detectable poliovirus type 1 antibody, 193 (25.3%) type 2, and 94 (12.3%) type 3. A precipitous antibody decline occurred in initially positive sera. CONCLUSIONS: Our results suggest that in a country with high population immunity, vaccine-derived virus is unlikely to establish ongoing circulation.

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigía Group, 1993 to 1999. PAHO Sireva-Vigía Study Group. Pan American Health Organization.

BACKGROUND: Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. METHODS: The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. RESULTS: By June, 1999, 4,105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. CONCLUSION: These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

[Poliomyelitis outbreak caused by vaccine-derived virus in Haiti and the Dominican Republic]. / Brote de poliomielitis en Haití y la República Dominicana debido a un virus derivado de la vacuna antipoliomielítica oral.

In October 2000, the Ministries of Health of the Dominican Republic and Haiti notified two cases of acute flaccid paralysis (AFP) in rural areas, one of them in a 9-month-old female, and the other in a 2-year-old female, respectively. Stool samples that were obtained from these cases, which occurred in July and August 2000, after a 9-year interruption of wild poliovirus circulation in the Western Hemisphere, revealed the presence of type 1 poliovirus. Genetic sequencing, which was later performed at the Centers for Disease Control and Prevention, in Atlanta, Georgia, United States of America, revealed an atypical descendant of the virus used in the manufacture of the oral polio vaccine (OPV), but with 3% genetic divergence with respect to the parent strain. Normally, viral isolates that derive from vaccine components show 99.5% genetic agreement with the parent strain; in wild polioviruses, on the other hand, this agreement is usually less than 82.0%. Thus, the 3% genetic divergence detected in this study suggests that, in areas with low vaccine coverage, the virus used in the vaccine remained in circulation for at least two years, during which it recovered the neurovirulence and communicability of wild poliovirus type 1. This report describes the characteristics and results of the active search for cases of AFP that was sparked by the detection of the two index cases. It also looks at the public health implications of this outbreak for the entire Region of the Americas.

Strategies to eradicate rubella in the English-speaking Caribbean.

OBJECTIVE: This report presents the strategies used to eradicate rubella in the Caribbean region and the challenges faced by that effort. METHODS: Using the surveillance system for measles cases that was instituted in all countries in the Caribbean Community (CARICOM), 12 countries confirmed cases of rubella between 1992 and 1996. Rubella infections occurred in epidemic proportions in 6 countries during that period. RESULTS: On the basis of the rubella prevalence data, rubella-congenital rubella syndrome (CRS) cost-benefit analysis, and cost-effectiveness of the mass campaign, the Council for Human and Social Development of CARICOM resolved, on April 21, 1998, that every effort would be made to eradicate rubella, as well as to prevent the occurrence of new cases of CRS by the end of 2000. Using the Pan American Health Organization's template for measles eradication, CARICOM proposed and implemented the main strategies for rubella and CRS eradication, and rubella mass campaigns were conducted in 18 countries. The target population, which included males and females (aged 20-40 years), was approximately 2.2 million. CONCLUSION: The major challenges for rubella eradication are attaining high vaccine coverage in the adult population and maintaining an effective surveillance system able to detect rubella activity.

[Introduction of a conjugate vaccine against Hib in Chile and Uruguay]. / Introducción de la vacuna conjugada contra Hib en Chile y Uruguay.

In some countries, the invasive disease caused by Haemophilus influenzae type b (Hib) has been practically eliminated thanks to vaccination. However, in much of the developing world, meningitides and pneumonias caused by these bacteria continue to be a major cause of childhood morbidity and mortality, as well as high hospitalization costs. Because safe and effective conjugate vaccines are now available, the Special Program for Vaccines and Immunization of the Pan American Health Organization has recommended introducing them into the regular vaccination regimen of as many countries as possible. This has been done in Chile and Uruguay, where the Hib vaccine now forms part of the regular vaccination routine. When the vaccine was being introduced, both countries had difficulties they could have avoided if they had known of the experiences of other nations. Therefore, these two countries now offer the lessons they learned to other nations considering introducing the vaccine into their immunization programs. The most important lessons were to: strengthen the epidemiological surveillance system sufficiently in advance of introducing the vaccine; with the support of scientific societies, present the technical information that justifies introducing the vaccine; seek community backing and acceptance; precisely establish in advance the presentation and dosage of the vaccine that is most appropriate for the country; and be certain to have the political and legal decisions needed to ensure the continuity of Hib vaccination in the future.

The immunisation programme in the Caribbean.

PIP: The Directing Council of Pan American Health Organization approved a resolution concerning the formal inauguration of the Expanded Programme on Immunization (EPI) in the Americas in October 1977. Subsequently, the EPI entered full implementation in those countries that were members of the Caribbean Epidemiology Center (CAREC) during 1978-80. All 19 CAREC Member Countries (CMC) were conducting routine immunization with diphtheria, pertussis, tetanus, poliomyelitis, measles and BCG vaccines by 1980. The establishment of the program in these countries resulted in focused activities, including training and the development of operational guidelines. Health education has been primarily used to encourage mothers to have their children vaccinated at optimum age, and to advise parents and guardians about adverse reaction to vaccines. Great efforts have been made in immunization coverage in all the CMCs for the six vaccine preventable diseases. The eradication of poliomyelitis, the interruption of measles transmission (8 years measles-free), and the implementation of strategies for the elimination of rubella and CRS have presented many challenges to public health practitioners in the region. The success of all these initiatives is a reflection of the deep commitment and strong partnerships, which have been developed between the governments, health practitioners, and people of the region. Moreover, technical and financial support from both international agencies and service clubs played a major role in the success of the program.^ieng

[Eradication of measles in Cuba]. / La eliminación del sarampión en Cuba.

The vaccine against measles came into use in Cuba in 1971. During the seventies, a new early strategy for measles control was established, and it was followed by further efforts in the early eighties. Despite improvements to the control program, disease outbreaks continued to occur. In 1986, after examining the experience acquired through the control initiatives that were already in place, a new measles vaccination strategy was adopted. In time, the new vaccination strategy against measles came to have three main components: first, a single vaccination "catching-up" campaign targeting children 1 to 14 years of age. Second, efforts were made to achieve and maintain high vaccine coverage through mandatory vaccination services for 12-month-old children ("maintenance vaccination"). Finally, periodic "follow-up" campaigns were carried out for children 2 to 6 years of age. Steps were taken, for the purpose of monitoring the progress made so far toward eliminating measles, to strengthen disease surveillance systems, including the screening of suspected cases. The "catching-up" and "follow-up" campaigns both achieved greater than 98% coverage within targeted age groups. The routine vaccination program has also maintained high coverage. The high population immunity against measles that has been attained through these vaccination strategies has resulted in a rapid decrease in the incidence of the disease. From 1989 to 1992, less than 20 laboratory-confirmed cases were reported annually. In Cuba, the last case confirmed through serologic screening was reported in July 1993. Cuba's strategy for measles elimination has interrupted disease transmission and kept the causal virus from circulating on the island. Cuba's experience with measles elimination suggests that if an appropriate vaccination strategy is applied, measles can be globally eradicated.

Measles vaccination and Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) has been associated with several infectious agents, and the possibility that the disorder may be caused by vaccination has been raised. We compared the numbers of cases of GBS observed immediately after mass measles vaccination campaigns with the numbers that would be expected from baseline rates, to assess whether there is a causal relation between measles vaccination and GBS. METHODS: We analysed data on 2296 cases of GBS reported to the Poliomyelitis Eradication Surveillance System of the Pan American Health Organization as cases of suspected poliomyelitis. These cases occurred among 73 million immunised children aged 9 months to 15 years in Argentina, Brazil, Chile, and Colombia, between January, 1990, and December, 1994. These children were targeted for mass measles vaccination campaigns (each lasting 1 month) in 1992 and 1993. The frequency of GBS cases observed during the vaccination campaigns or the next 42 days (the latent period) was compared with that during the rest of the study period, with the assumption of a Poisson distribution. FINDINGS: The average annual incidence of GBS was 0.62 per 100000 children aged 1-14 years. The number of cases that would be expected within any 72-day period would therefore be 92. The average observed number of cases during latent periods after measles vaccination was 97. The probability that 97 or more cases would occur during a period with an expected number of 92 was 0.31. INTERPRETATION: The average annual rates of GBS by age-group for the 5 years analysed were consistent with previous data; thus we are confident that the surveillance system is sufficiently sensitive. There was no statistically significant association between measles vaccination and GBS. If there is any causal relation, the number of GBS cases due to measles vaccination was so small that data from the vaccination of more than 70 million children were not sufficient to detect a rise in the number of observed GBS cases beyond the expected number.

Intradermal administration of measles vaccines.

The aim of the study reported here was to determine if bifurcated needles or multiple puncture cylinders would prove suitable for administration of measles vaccines. Children 9 to 11 months old in São Paulo, Brazil, were assigned to receive either Biken-Cam 70 (5,000 TCID50/0.5 ml) or Edmonston-Zagreb (7,000 TCID50/0.5 ml) measles vaccines intradermally with a bifurcated needle or a multiple puncture cylinder. These devices are usually used to administer smallpox or BCG vaccine. The volume of vaccine inoculated was approximately 0.003 ml. Measles IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA) at the time of vaccination and 8 weeks later. The study participants were examined 14 days after inoculation for possible adverse reactions. Overall, the children's average age was 9.5 +/- 0.66 months at vaccination. None of the 45 recipients of Biken-Cam vaccine responded serologically. The 49 Edmonston-Zagreb vaccine recipients immunized with the multiple puncture cylinder had a somewhat higher serologic response rate (35%) and mean concentration of measles antibodies (323 mIU/ml) than those 51 who received the same vaccine administered with the bifurcated needle (26% and 291 mIU/ml, respectively). The rates of reported symptoms after vaccination did not differ significantly among the groups. Overall, the low serologic response rates following intradermal immunization with for devices tested in this study indicate that this route of administration is not suitable for routine administration of standard-titer vaccines.

Lessons from Cuba: mass campaign administration of trivalent oral poliovirus vaccine and seroprevalence of poliovirus neutralizing antibodies.

The immunogenicity of trivalent oral poliovirus vaccine (TOPV), which is less effective in tropical than in temperate areas, may potentially be improved in several ways, including increasing the number of doses. Little information is available on TOPV when more than 6 doses are given. The situation in Cuba provides a unique opportunity to relate the seroprevalence of neutralizing antibodies to the dose of TOPV because Cuba has not reported culture-confirmed poliomyelitis since 1973 and TOPV is only administered in twice yearly 1-week mass immunization campaigns. Sera from 2000 children nationwide were studied for neutralizing antibody among children who received 0, 2, 4, 6 and 8 doses of TOPV. These doses were administered in the period 1989-91, when TOPV (from the USSR) was being used with 500,000, 200,000, and 300,000 median tissue-culture-infecting doses (TCID50) for types 1, 2 and 3, respectively--the 5:2:3 formulation. Seroprevalence of neutralizing antibody after two TOPV doses was 91.5% for type 1, 90.8% for type 2, and 45.9% for type 3. Seroprevalence of type-3 neutralizing antibody after 6 doses remained low (73.4%), but increased to 83.5% after 8 doses (P < 0.05). Although 16.5% of the children remained unprotected for type-3 infection even after 8 doses, mass campaign immunization strategies were sufficient to eradicate the transmission of wild poliovirus in Cuba. Because the seroprevalence of type-1 neutralizing antibody was high (91.5%) after two campaign doses, additional studies using different formulations are needed to determine whether simultaneous improvement in the type-3 response to two campaign doses can be achieved.

PIP: During December 1991-January 1992 in Cuba, health workers took blood samples from a nationwide sample of 2000 children aged 0-3 who received 0, 2, 4, 6, and 8 doses of trivalent oral poliovirus vaccine (TOPV) to determine the seroprevalence of poliovirus neutralizing antibodies for types 1, 2, and 3. Specifically, researchers wanted to learn whether TOPV becomes more effective as the number of doses increases. Since 1973, Cuba has conducted two mass immunization campaigns each year in February and April. During 1970-91, Cuba used a USSR-produced poliovirus vaccine that had 500,000, 200,000, and 300,000 median tissue-culture-infecting doses for types 1, 2, and 3, respectively. Wild poliovirus has not been transmitted in Cuba since 1973 (as of August 1993), indicating that the mass immunization campaigns without routine vaccine delivery have eradicated poliomyelitis in Cuba. The seroprevalence of poliovirus neutralizing antibodies for type 1 increased significantly between 2 and 4 doses (91.5% vs. 96.5%; p = 0.05), thereafter the increases were small and insignificant. The seroprevalence of poliovirus neutralizing antibodies for type 2 increased significantly between 2 and 4 doses (90.8% vs. 97.2%), with small insignificant increases thereafter. Two doses of TOPV induced a response against poliovirus type 3 in only 45.9% of cases. At 4 doses and 8 doses, it did increase significantly from the previous dose (71.2% and 83.5%, respectively; p 0.05). Further studies using other vaccine formulations would allow persons involved in global eradication efforts to determine whether two campaign doses can improve the immunogenicity of the type 3 poliovirus while also improving that of the type 1 poliovirus.

Direct detection of wild poliovirus circulation by stool surveys of healthy children and analysis of community wastewater.

Cartagena, Colombia, was one of the last cities in the Americas known to have endemic poliomyelitis. After 3 cases were identified in 1991, two approaches for detecting continued silent transmission of wild polioviruses within a high-risk community were used: stool surveys of healthy children and virologic analysis of community sewage. Wild type 1 polioviruses were isolated from 8% of the children studied and from 21% of sewage samples. The proportions of wild polioviruses, vaccine-related polioviruses, and nonpolio enteric viruses were similar for both approaches. Wild poliovirus sequences were also amplified directly from processed sewage samples by the polymerase chain reaction using primer pairs specific for the indigenous type 1 genotype. The last reported cases associated with wild polioviruses in the Americas occurred in Colombia (8 April 1991) and Peru (23 August 1991). Direct sampling for wild polioviruses in high-risk communities can provide further evidence that eradication of the indigenous wild polioviruses has been achieved in the Americas.

Comparison of high titer Edmonston-Zagreb, Biken-CAM and Schwarz measles vaccines in Peruvian infants.

In an effort to identify the optimal dose and strain of measles vaccination for early immunization, Peruvian infants were randomly assigned to receive one of three measles vaccines in varying doses at 5 to 6 or 8 to 9 months of age. Edmonston-Zagreb vaccines were significantly (P < 0.001) more immunogenic than equivalent or higher titers of Schwarz or Biken-CAM vaccines as determined by neutralization antibody response 3 months after vaccination. Eighty-two percent of infants who received high titer Edmonston-Zagreb vaccine at 5 to 6 months of age developed protective concentrations of measles antibody, a response rate similar to that observed after standard titer Schwarz (81%) or high titer Biken-CAM vaccine (81%) at 8 to 9 months of age. No significant differences in the rates of fever, rash or other adverse events were noted by vaccine group 10 to 14 days after vaccination. Although the high titer vaccines are more immunogenic in young infants than standard vaccines, long term safety must be assured before these vaccines can be put into widespread use.

Poliomyelitis case confirmation: characteristics for use by national eradication programmes.

Highly sensitive case definitions were first introduced by national poliomyelitis eradication programmes to avoid missing true cases of the disease, though false-positive diagnostic errors could still occur owing to low specificity. Extensive data from all 1620 cases of acute, flaccid paralysis reported in Brazil during 1987-88 provided an opportunity to study the characteristics of confirmed poliomyelitis cases and epidemiologically to evaluate potential case definitions that maximized both sensitivity and specificity. Cases that had been confirmed by wild poliomyelitis virus isolation were compared with those that had been rejected (non-polio cases). To guarantee the consistency of clinical, epidemiological and laboratory investigations, only cases less than 10 years of age that had been investigated within 15 days of the onset and with complete laboratory specimens were included. No single practical case definition combining both high sensitivity and high specificity emerged from the study. However, the results showed that poliomyelitis endemic countries with limited resources should give priority to the investigation of cases in less than 5-year-olds, cases with prodromal fever, cases without involvement in all four limbs, cases without progression greater than 3 days after the onset, and cases occurring in areas where poliomyelitis had recently been confirmed. In countries without laboratory resources, cases of acute, flaccid paralysis with initial involvement in one or both lower limbs and residual neurological sequelae at 60 days should be confirmed. Countries that are close to eradication may selectively reject any cases lacking laboratory confirmation, despite adequate specimen collection, if they do not have initial involvement in one or both lower limbs and residual neurological sequelae at 60 days.

PIP: In Sao Paulo, Brazil, physicians followed 85 full term, healthy, breast fed infants born between March 1986-September 1988 monthly for 1 year to compare their immunologic response to immunization with trivalent oral poliovirus vaccine (TOPV). They either received doses 1 day after birth and at 2, 4, and 9 months (group A) or at 2, 4, and 6 months (group B). They analyzed blood samples from the mother at childbirth, from the umbilical cord, and from the infant at 2, 4, 6, 9, and 12 months to measure poliovirus neutralizing antibodies. All but 1 infant had passively transferred antibodies at birth. Group A had higher polio antibodies during the 1st few months, greater seropositivity, and a lower proportion of susceptible infants than group B. In fact, at the end of 12 months, only 3.7% of infants in group A were susceptible to all 3 poliovirus types compared to 25.9% in group B. Seroconversion rates were considerably higher in group A infants from the 3rd dose forward (96.3-100%) than for those in group B (74.1-100%). The response for polioviruses 1 and 2 were essentially the same in both groups at 12 months (96.3-100%). The immunological response to poliovirus type 3 in group A was superior to that of group B at the end of 1 year (96.3% vs. 74.1%), however. Yet group B infants received their 1st dose of the vaccine at 2 months with a higher level of poliovirus 3 type (500,000 TCID50/dose) than group A infants received at birth (300,000 TCID50/dose). Thus immunization of newborns with TOPV provided more protection against polio than a higher vaccine concentration administered to infants beginning at months. This finding is especially relevant since polio type 3 was responsible for the polio outbreak in 1986 in northern Brazil.

Eradication of poliomyelitis: progress in the Americas.

In the span of 5 years since the eradication initiative was launched and only 3 years since external funds were made available, PAHO has been able to develop and implement a comprehensive program strategy for polio eradication that includes the following components: achievement and maintenance of high immunization levels (which include the supplemental strategies of national immunization days and mop-up operations); effective surveillance to detect all new cases; and a rapid response to the occurrence of new cases. Despite yearly increases in the number of cases of acute flaccid paralysis reported to the surveillance system, a decline in reported confirmed cases of polio has occurred since 1986 to record low levels in 1989. Cases in 1989 were reported from only 0.7% of the counties in the Americas. The occurrence of 24 wild-type virus isolates in 1989 were limited to only three geographic areas: northwestern Mexico; the northern Andean Region; and northeastern Brazil. At this writing the clock is ticking with only 3 months left to achieve the goal of interrupting transmission by the end of 1990. If the current level of effort is sustained and special efforts are directed at the remaining foci of infection, the eradication of the transmission of wild-type poliovirus from the Americas can be achieved. Continued external financial support will be critical if the effort is to succeed. The prospect of poliomyelitis eradication in the Americas led the 41st World Health Assembly of WHO to adopt a resolution in May, 1988, to eradicate the indigenous transmission of wild-type poliovirus from the world by the year 2000.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal tetanus: countdown to 1995.

Progress in the campaign against neonatal tetanus in South and Central America and the Caribbean is reviewed. The main emphasis is on immunizing women of childbearing age who live in high-risk areas, although importance also attaches to routine tetanus toxoid treatment, adequate care during the prenatal period and delivery, and epidemiological surveillance.

PIP: In 1990, the Pan American Health Organization (PAHO) announced its strategy to reduce neonatal tetanus: immunize all 12-44 year old women in high risk areas with the tetanus toxoid. As of mid-1991, health workers in Bolivia, Colombia, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Peru, and Venezuela systematically reported neonatal tetanus cases. Only Guatemala had not yet began case investigations. Workers in Argentina, Brazil, Haiti, and Paraguay did not report neonatal tetanus cases. In fact, hospital searches were the only means to detect tetanus cases in Haiti. The number of reported cases/year fluctuated between 1300-1500 between 1985-90. PAHO defined a high risk area as an area that has a neonatal tetanus morbidity or mortality rate higher than the national average for the last 3-5 years. PAHO found 50% of all cases occurred in 5% of municipios. El Salvador, however, case occurrence did not differ from 1 region to another, PAHO proposed training traditional midwives how to vaccinate women with the tetanus toxoid and children with other vaccines as has been done in Bolivia's Department of Santa Cruz. They can also report tetanus cases and refer women to health facilities if they cannot vaccinate the women themselves. Before 1990, 78% of recorded neonatal tetanus cases occurred to women with at least 2 other children. This represented at least 2 missed opportunities for vaccination/woman. In 1990, only 17 of the 212 reported tetanus cases in the Americas were born in a hospital. In 1988, the incidence rate for deliveries in hygienic conditions averaged .11/1000 compared with .5 for all deliveries. 90% of mothers who had infants with tetanus in 1990 had not received any tetanus toxoid vaccinations, and only 22% of all mothers had received the 2nd dose. In addition to prenatal and delivery care, PAHO promoted effective epidemiological surveillance systems.

Field evaluation of a simplified unit-dose syringe for administration of measles vaccine.

Ezeject is a plungerless syringe prefilled with lyophilized measles vaccine. Ezeject syringes were compared with standard 3-cc syringes and 10-dose measles vaccine vials in the vaccination of 884 Guatemalan infants 8-23 months of age. Vaccination was performed by experienced vaccinators and by individuals without prior vaccination experience who received 2.5-3 hours of training. The overall seroconversion rate following administration was 96%, regardless of the type of syringe used or of the experience of the vaccinator. No significant adverse events were observed in children vaccinated with the new syringes. Although incomplete emptying was noted in 87% of the Ezeject syringes used, this had no effect on the serologic response to measles vaccine. Aspiration for detection of blood before injection of the vaccine was performed significantly (P less than .001) less frequently with Ezeject than with 3-cc syringes by both experienced and inexperienced personnel. Inexperienced vaccinators administered measles vaccine significantly faster (P less than .001) with Ezeject than with 3-cc syringes, but the times were similar for experienced vaccinators. Ezeject is an acceptable alternative to standard syringes for the administration of measles vaccine. Several design modifications that would improve the handling of the device and eliminate the possibility of its reuse have been suggested.

Epidemiology of variola minor in Brazil based on a study of 33 outbreaks.

Surveillance-containment units were established in 1969 in four States of Brazil as part of the national smallpox eradication programme. Their responsibilities included both the investigation of reported cases and the control of outbreaks, and the further extension and development of the reporting network. Altogether, 33 outbreaks of smallpox were investigated in detail, all in endemic areas not yet reached by the attack phase of the eradication programme. Official reports of 27 cases led to the discovery of an additional 1 465 cases, suggesting that reporting was not more than 2% complete in endemic areas. The total of 1 492 cases in 33 outbreaks occurred in 493 households comprising a study population of 3 088 persons: three-quarters of the cases were in children under 15 years of age. Only 5% were in individuals aged 30 years or more. The case-fatality ratio was 0.8%. The overall attack rate among unvaccinated persons (76.2%) was 23 times that among vaccinated persons (3.3%). Age-specific vaccine effectiveness ratios ranged from 94% to 100% with an overall reduction in expected cases among the vaccinated of 95%. There was no evidence to suggest waning of immunity among persons who had been successfully vaccinated. There was an inverse relationship between susceptibility and age since a greater proportion of adults had already had smallpox or a successful vaccination; 97% of pre-school-age children and 82% of school-age children had no history of smallpox and no vaccination scar. In all 33 outbreaks, more than 60% of unvaccinated persons became ill; in 5 outbreaks the attack rate for unvaccinated persons was greater than 90%.