Measles epidemiology and outbreak response immunization in a rural community in Peru.

Only limited data are available on the impact of measles outbreak response immunization (ORI) in developing countries. We conducted a community survey in Espindola, a rural border community in northern Peru, following a measles outbreak and subsequent ORI to study the epidemiology and impact of the outbreak and to evaluate the costs and benefits of measles ORI. During the outbreak, 150 of the 553 Espindola residents developed clinical cases of measles. Adults accounted for 44.0% of cases, and were frequently identified as primary cases. The attack rate among all susceptible people was 45.5% and was highest (61.2%) for the 16-20 year age group. Among adults, significant risk factors for developing measles included being aged 16-20 years (relative risk [RR] = 3.06, 95% CI = 2.08, 4.49) and being male (RR = 1.73, 95% CI = 1.11, 2.71). Among serologically confirmed cases, 60.7% developed diarrhoea and 32.1% pneumonia. The overall case-fatality rate was 3.3%, but reached 19.1% in the 0-23-month age group. Failure to reach children through either routine immunization or national campaigns made this community vulnerable to the severe and extensive impact of measles virus importation. The ORI campaign targeted non-measles case children aged 6 months to 15 years, regardless of their previous immunization status, and was effective in terminating this measles outbreak and in preventing morbidity, loss of livelihood and death despite the involvement of large numbers of adults in measles transmission. The last measles case occurred within 3 weeks of completing ORI. The ORI campaign, which would have cost approximately US$ 3000 in 1998, saved as many as 1155 person-days of work among 77 adults, prevented an estimated 87 cases of diarrhoea and 46 cases of pneumonia, and averted 5 deaths.

PIP: A community survey of the epidemiology and impact of measles outbreak response immunization (ORI) in Espindola, Peru. Blood specimens from 29 clinical cases having the onset of symptoms within 5 weeks to collection were tested for the anti-measles virus nucleoprotein antibody. Questionnaires were given to the head of the household and the 29 clinical cases to identify clinical symptoms an disease outcomes and to determine vaccination coverage. Attack rates, vaccine effectiveness, and predictive value positive was also calculated. Findings showed that primary cases were frequent among adults, who accounted for 44% of cases. The attack rate among all susceptible people was 45.5% and was highest among adults aged 16-20 (61.2%). For the serologically confirmed cases, 60.7% developed diarrhea and 32.1% pneumonia. Case fatality rate was 19.1% for children aged 0-23 months and 1.5% for adults aged 16-40 years. The lack of national campaigns or access to routine immunization caused the severe impact of measles virus outbreak. The ORI campaign targeted nonmeasles case children aged 6 months to 15 years regardless of immunization status, which was effective in terminating measles outbreak, morbidity, and mortality. This campaign cost approximately US$3000 and in 1998 saved 1155 person-days of work among 77 adults. It also prevented 87 diarrhea and 46 pneumonia cases and averted 5 deaths.

Impact of Uruguay's introduction of the Haemophilus influenzae type b (Hib) vaccine.

PIP: In August 1994, the National Advisory Commission for Vaccination of Uruguay recommended that the vaccine against Haemophilus influenzae type b (Hib) should be incorporated into the Expanded Program of Immunization vaccination schedule, as follows: 1) newborns should receive the first dose at 2 months, a second and a third dose (to be administered simultaneously with the DPT and the OPV vaccines) at 4 and 6 months, respectively, and a booster between 12 and 15 months; 2) children between the ages of 7 and 11 months should receive 2 doses at intervals of at least 2 months, and a booster between 12 and 15 months (not within 2 months of the date of the last dose); and 3) children 12 months and older should receive 1 dose only. 90,000 doses of vaccine were administered to children less than 1 year old; the cohort numbers approximately 50,000. 130,000 doses were administered to children 1-4 years old. This resulted in a 100% reduction in the number of meningitis cases due to Hib in 1996; 1 reported case was in a non-immunized child. In 1995, 5 cases were reported; only 1 of these was adequately vaccinated with 3 doses of Hib vaccine. During a 1996 epidemiological surveillance study of respiratory infections in children under 5 years old at 2 reference hospitals in Montevideo, no Hib was isolated from 520 reported cases. A histogram plots the number of cases of meningitis due to Hib per month for 1993, 1994, and 1995; the point where vaccination began, August 29, 1994, is marked. Prior to vaccination the number of cases per month cycled, with the highest number occurring during August (7 in 1993, 10 in 1994); after October 1994, the number remained at zero or 1 throughout the year.^ieng

Safety and immunogenicity of oral killed whole cell recombinant B subunit cholera vaccine in Barranquilla, Colombia.

In January and February 1992, an assessment was conducted of the safety and immunogenicity of two doses of a new oral cholera vaccine prepared from the recombinant B subunit of the toxin and from killed whole cells (rBS/WC) in 1,165 individuals between the ages of 12 months and 64 years in Barranquilla, Colombia. This was a randomized, double-blind placebo-controlled study. Participants received two doses of either the vaccine or a placebo (killed Escherichia coli K12) over a two-week interval. Few symptoms were detected during the three days following administration of the initial dose and even fewer following the second. Sera obtained upon administration of the first dose and two weeks after administration of the second were tested for Vibrio cholerae 01 Inaba vibriocidal antibodies and antitoxins. Geometric mean titers (GMT) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine. In the paired samples taken from vaccinated subjects, two-fold or greater increases were observed in 44% and four-fold or greater increases were observed in 34%, as compared to similar increases in 9.2% and 2.2% of the sera taken from those receiving the placebo (P < 0.05). The GMTs of IgG and IgA antitoxins, as determined by ELISA, increased by factors of 4 and 3.2, respectively, in those receiving the vaccine, as compared to factors of 1.1 and 1.1 in those given the placebo (P < 0.001 for IgG, P < 0.01 for IgA). Approximately 80% of the paired samples from the vaccinated group showed an increase of both IgG and IgA antitoxins > or = 1.5, as compared to only about 20% of those in the placebo group (P < 0.000001). Belonging to the O blood group did not significantly affect the immune response. Children under age four tended to show a weaker vibriocidal antibody response and a stronger antitoxin response than older subjects. The two doses of oral vaccine were found to be safe and without attributable side-effects. The vibriocidal antibody and antitoxin responses were similar to those obtained previously with the conventional oral killed whole cell B subunit cholera vaccine.

PIP: In a randomized, double-blind, placebo-controlled study in January and February 1992, the safety and immunogenicity of two doses of a new oral cholera vaccine was assessed. The vaccine was prepared from the recombinant B subunit of the toxin and from killed whole cells (rBS/WC) in 1165 individuals between the ages of 12 months and 64 years in Barranquilla, Colombia. Participants received two doses of either the vaccine or a placebo (killed Escherichia coli K12) over a 2-week interval. Few symptoms were detected during the 3 days following administration of the initial dose and even fewer following the second one. Sera obtained upon administration of the first dose and 2 weeks after administration of the second dose were tested for Vibrio cholera 01 Inaba vibriocidal antibodies and antitoxins. Geometric mean titers (GMTs) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine. In the paired samples taken from vaccinated subjects, two-fold or greater increases were observed in 44% and four-fold or greater increases were observed in 34%. In comparison, similar increases were found only in 9.2% and 2.2% of the sera taken from those receiving placebo (p .05). The GMTs of IgG and IgA antitoxins, as determined by ELISA, increased by factors of 4 and 3.2, respectively, in those receiving the vaccine as compared with factors of 1.1 and 1.1, respectively, in those given the placebo (p .001 for IgG and p .01 for IgA). Approximately 80% of the paired samples from the vaccinated group showed an increase of both IgG and IgA antitoxins or= 1.5 as compared with only about 20% of those in the placebo group (p .000001). Belonging to the O blood group did not significantly affect the immune response. Children under the age of 4 years tended to show a weaker vibriocidal antibody response and stronger antitoxin response than did older subjects. The two doses of oral vaccine were found to be safe and without attributable side effects.

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.