Brendan Flannery

Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study

BACKGROUNDnIn March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children.nnnMETHODSnInvasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype).nnnFINDINGSnIn 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules.nnnINTERPRETATIONnIn the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes.nnnFUNDINGnBrazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.

Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis

A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age.

Leptospiral Proteins Recognized during the Humoral Immune Response to Leptospirosis in Humans

ABSTRACT Leptospirosis is an emerging zoonosis caused by pathogenic spirochetes belonging to the genus Leptospira. An understanding of leptospiral protein expression regulation is needed to develop new immunoprotective and serodiagnostic strategies. We used the humoral immune response during human leptospirosis as a reporter of protein antigens expressed during infection. Qualitative and quantitative immunoblot analysis was performed using sera from 105 patients from Brazil and Barbados. Sera from patients with other diseases and healthy individuals were evaluated as controls. Seven proteins, p76, p62, p48, p45, p41, p37, and p32, were identified as targets of the humoral response during natural infection. In both acute and convalescent phases of illness, antibodies to lipopolysaccharide were predominantly immunoglobulin M (IgM) while antibodies to proteins were exclusively IgG. Anti-p32 reactivity had the greatest sensitivity and specificity: positive reactions were observed in 37 and 84% of acute- and convalescent-phase sera, respectively, while only 5% of community control individuals demonstrated positive reactions. Six immunodominant antigens were expressed by all pathogenic leptospiral strains tested; only p37 was inconsistently expressed. Two-dimensional immunoblots identified four of the seven infection-associated antigens as being previously characterized proteins: LipL32 (the major outer membrane lipoprotein), LipL41 (a surface-exposed outer membrane lipoprotein), and heat shock proteins GroEL and DnaK. Fractionation studies demonstrated LipL32 and LipL41 reactivity in the outer membrane fraction and GroEL and DnaK in the cytoplasmic fraction, while p37 appeared to be a soluble periplasmic protein. Most of the other immunodominant proteins, including p48 and p45, were localized to the inner membrane. These findings indicate that leptospiral proteins recognized during natural infection are potentially useful for serodiagnosis and may serve as targets for vaccine design.

Socioeconomic inequalities and vaccination coverage: results of an immunisation coverage survey in 27 Brazilian capitals, 2007–2008

Background Since 1988, Brazils Unified Health System has sought to provide universal and equal access to immunisations. Inequalities in immunisation may be examined by contrasting vaccination coverage among children in the highest versus the lowest socioeconomic strata. The authors examined coverage with routine infant immunisations from a survey of Brazilian children according to socioeconomic stratum of residence census tract. Methods The authors conducted a household cluster survey in census tracts systematically selected from five socioeconomic strata, according to average household income and head of household education, in 26 Brazilian capitals and the federal district. The authors calculated coverage with recommended vaccinations among children until 18u2005months of age, according to socioeconomic quintile of residence census tract, and examined factors associated with incomplete vaccination. Results Among 17u2008295 children with immunisation cards, 14u2008538 (82.6%) had received all recommended vaccinations by 18u2005months of age. Among children residing in census tracts in the highest socioeconomic stratum, 77.2% were completely immunised by 18u2005months of age versus 81.2%–86.2% of children residing in the four census tract quintiles with lower socioeconomic indicators (p<0.01). Census tracts in the highest socioeconomic quintile had significantly lower coverage for bacille Calmette-Guérin, oral polio and hepatitis B vaccines than those with lower socioeconomic indicators. In multivariable analysis, higher birth order and residing in the highest socioeconomic quintile were associated with incomplete vaccination. After adjusting for interaction between socioeconomic strata of residence census tract and household wealth index, only birth order remained significant. Conclusions Evidence from Brazilian capitals shows success in achieving high immunisation coverage among poorer children. Strategies are needed to reach children in wealthier areas.

Elimination of Rubella and Congenital Rubella Syndrome in the Americas

In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling for rubella and congenital rubella syndrome (CRS) elimination in the Americas by the year 2010. To accomplish this goal, PAHO advanced a rubella and CRS elimination strategy including introduction of rubella-containing vaccines into routine vaccination programs accompanied by high immunization coverage, interruption of rubella transmission through mass vaccination of adolescents and adults, and strengthened surveillance for rubella and CRS. The rubella elimination strategies were aligned with the successful measles elimination strategies. By the end of 2009, all countries routinely vaccinated children against rubella, an estimated 450 million people had been vaccinated against measles and rubella in supplementary immunization activities, and rubella transmission had been interrupted. This article describes how the region eliminated rubella and CRS.

Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H. influenzae type b in Brazil.

Following routine childhood vaccination against Haemophilus influenzae type b (Hib) disease in Brazil in 1999, passive laboratory surveillance reported increasing numbers of non-b serotypes and nontypeable H. influenzae (NTHi) from meningitis cases. To characterize this increase, we analyzed data on 3910 H. influenzae isolated from cerebrospinal fluid or blood from meningitis cases that were sent to the national reference laboratory for serotyping from 1990 to 2008. Hib accounted for 98% of H. influenzae meningitis isolates received during 1990-1999 versus 59% during 2000-2008, while non-b serotypes increased from 1% to 19% and NTHi increased from 2% to 22% of H. influenzae isolates received during the two periods. Higher proportions of non-b serotypes and NTHi than Hib were isolated from blood rather than cerebrospinal fluid. Estimated incidence rates for H. influenzae meningitis for Sao Paulo state remained below 1 case per million population during 2000-2008, although annual incidence of NTHi meningitis (mean, 0.03 cases per 100,000 population) increased in several age groups. Changes in surveillance for H. influenzae following introduction of Hib conjugate vaccine likely contributed to increased numbers of non-b and nontypeable H. influenzae meningitis isolates received at the national reference laboratory.

Household survey of hepatitis B vaccine coverage among Brazilian children.

We conducted a multi-stage household cluster survey to calculate hepatitis B vaccine coverage among children 18-30 months of age in 27 Brazilian cities. Hepatitis B vaccine is administered at birth, 1 month and 6 months of age by Brazils national immunization program. Among 17,749 children surveyed, 40.2% received a birth dose within one day of birth, 94.8% received at least one dose of hepatitis B vaccine, and 86.7% completed the three-dose series by 12 months of age. Increased coverage with the birth dose and administration of hepatitis B in combination with diphtheria-tetanus-pertussis-Haemophilus influenzae type b antigens could improve protection against hepatitis B.

Follow-up Study of Unknowingly Pregnant Women Vaccinated Against Rubella in Brazil, 2001–2002

BACKGROUNDnBrazil conducted mass immunization of women of childbearing age in 2001 and 2002. Surveillance was initiated for vaccination of women during pregnancy to monitor the effects of rubella vaccination on fetal outcomes.nnnMETHODSnWomen vaccinated while pregnant or prior to conception were reported to the surveillance system. Susceptibility to rubella infection was determined by anti-rubella immunoglobulin (Ig) M and IgG immunoassays. Susceptible women were observed through delivery. Live-born infants were tested for anti-rubella IgM antibody; IgM-seropositive newborns were tested for viral shedding and observed for 12 months for signs of congenital rubella syndrome. Incidence of congenital rubella infection was calculated using data from 7 states.nnnRESULTSnA total of 22 708 cases of rubella vaccination during pregnancy or prior to conception were reported nationwide, 20,536 (90%) of which were from 7 of 27 states in Brazil. Of these, 2332 women were susceptible to rubella infection at vaccination. Sixty-seven (4.1%) of 1647 newborns had rubella IgM antibody (incidence rate, 4.1 congenital infections per 100 susceptible women vaccinated during pregnancy [95% confidence interval, 3.2-5.1]). None of the infants infected with rubella vaccine virus was born with congenital rubella syndrome.nnnCONCLUSIONSnAs rubella elimination goals are adopted worldwide, evidence of rubella vaccine safety aids in planning and implementation of mass adult immunization.

Carriage of Haemophilus influenzae among Brazilian children attending day care centers in the era of widespread Hib vaccination

Haemophilus influenzae type b vaccine was introduced into the Immunization Program of Brazil in 1999 and no study has evaluated the impact of Hib vaccination in H. influenzae carriage so far. In June 2010, Brazil introduced the 10-valent pneumococcal nontypeable H. influenzae (NTHi) conjugate vaccine (PHiD-CV). We investigated the prevalence of encapsulated H. influenzae and NTHi isolates in nasopharyngeal samples of 1192 children attending day-care centers in Goiânia, central Brazil. H. influenzae carriage rate was 32.1% and 38.4% of them carried β-lactamase TEM-1 gene. Serotype f (4.6%) was the most frequent encapsulated isolate, type b was recovered in only 0.7% and carriage rate of NTHi was 23.3%. Recurrent acute otitis media and NTHi were independently associated with colonization by β-lactamase producing H. influenzae. Changes in frequency of H. influenzae carriage isolates should be carefully monitored to assess the impact of the PHiD-CV on NTHi carriage in young children.

Clinical outcome of pneumococcal meningitis during the emergence of pencillin-resistant Streptococcus pneumoniae: an observational study

BackgroundPrior to the availability of generic third-generation cephalosporins, penicillins were widely used for treatment of pneumococcal meningitis in developing countries despite concerns about rising levels of penicillin resistance among pneumococcal isolates. We examined the impact of penicillin resistance on outcomes of pneumococcal meningitis over a ten year period in an infectious diseases hospital in Brazil.MethodsClinical presentation, antimicrobial therapy and outcomes were reviewed for 548 patients with culture-confirmed pneumococcal meningitis from December, 1995, to November, 2005. Pneumococcal isolates from meningitis patients were defined as penicillin-resistant if Minimum Inhibitory Concentrations for penicillin were greater than 0.06 μg/ml. Proportional hazards regression was used to identify risk factors for fatal outcomes.ResultsDuring the ten-year period, ceftriaxone replaced ampicillin as first-line therapy for suspected bacterial meningitis. In hospital case-fatality for pneumococcal meningitis was 37%. Of 548 pneumococcal isolates from meningitis cases, 92 (17%) were resistant to penicillin. After controlling for age and severity of disease at admission, penicillin resistance was associated with higher case-fatality (Hazard Ratio [HR], 1.62; 95% Confidence Interval [CI], 1.08-2.43). Penicillin-resistance remained associated with higher case-fatality when initial therapy included ceftriaxone (HR, 1.68; 95% CI 1.02-2.76).ConclusionsFindings support the use of third generation cephalosporin antibiotics for treatment of suspected pneumococcal meningitis even at low prevalence of pneumococcal resistance to penicillins.