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.

[Impact of vaccination against Haemophilus influenzae type b in Cuba]. / Impacto de la vacunación contra Haemophilus influenzae tipo b en Cuba.

OBJECTIVE: To assess the effectiveness of mass vaccination in Cuba of children under 2 years of age against Haemophilus influenzae type b (Hib), the most common causative pathogen of bacterial meningitis. METHODS: The availability of effective Hib conjugate vaccines led to a nationwide vaccination program in 1999 targeting all children under 2 years of age, with a 97% coverage rate achieved. To assess the program's impact, data from 1998 and 1999 from the National Bacterial Meningitis Reporting System were used. RESULTS: Vaccination efficacy was estimated at 99%. The overall incidence of Hib meningitis declined 46.1%, from 1.3 to 0.6 cases per 100,000 population. The greatest overall reduction, of 56.1%, occurred among children under 5 years of age. Among children under 1 year of age, the reduction was 70.5%, and among the rest of the age groups of children under 5, incidence decreased between 25.9% and 49.6%. In the group targeted for vaccination, incidence decreased 61.1%. Among children in the target group who contracted Hib meningitis, only 8 cases (24.2%) had been vaccinated, most with a single dose applied 1 month before becoming ill. CONCLUSIONS: Hib vaccination of all children under 2 years of age in Cuba greatly reduced the incidence of Hib meningitis, as measured by the National Bacterial Meningitis Reporting System.

Cloning and characterization of a Campylobacter jejuni iron-uptake operon.

We report that C. jejuni modifies its outer membrane protein (OMP) repertoire when cultivated under iron-limiting conditions such as during incubation with epithelial cells. To identify genes encoding de novo expressed OMPs, a C. jejuni cosmid library was screened with antisera raised against proteins expressed in the presence of epithelial cells. A single clone was identified encoding an 80-kDa antigen. Sequence analysis of subclones identified an operon of three open reading frames (ORFs) encoding proteins that are homologous to the E. coli ferrichrome uptake system encoded by the fhu locus. Under low-iron conditions, C. jejuni expressed the 80-kDa OMP, indicating that its expression is regulated by the presence of iron. Southern blot analysis indicated that six of eleven isolates of C. jejuni harbor a fhuA homolog which, like all other DNA in this region sequenced thus far, is strikingly GC-rich (65%) compared with the C. jejuni genome (35% G+C).

[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.

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.

[Serologic marker as indicator of no circulation of poliovirus in Cuba]. / Marcador serológico como indicador de no circulación de poliovirus en Cuba.

The surveillance of the circulation of the wild poliovirus is an essential element for the eradication of poliomyelitis. The Pan-American Health Organization emphasises on the etiological study of acute flaccid paralysis in order to achieve this aim. The characteristics of our program against this entity allowed to use the presence of antibodies in a sample obtained in February from the infant population born on July during the previous year as criteria to know the circulation of wild poliovirus. In 727 infants studies in the country (5% of the total number of births during July), 99.1% showed no antibodies with a titre equal or greater than 1:10. Low titres found in 7 infants were considered as a remnant from maternal transmission. Results obtained represent a strong evidence of the fact that there is no environmental circulation of poliovirus during the period which had the greatest incidence of the disease.

Peroxidase and gamma-glutamyl transpeptidase activities during Eimeria nieschulzi (Apicomplexa) and/or Nippostrongylus brasiliensis (Nematoda) infections in the rat.

Results suggest that malabsorption of amino acids which occurs during Eimeria nieschulzi and Nippostrongylus brasiliensis infections in rats is not due to impairment by intestinal inflammation of gamma-glutamyl transpeptidase activity.