Polysaccharide vaccine did not affect carriage nor interrupt transmission of an epidemic strain.
During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies.
In Brazil, meningococcal disease is endemic; 1.5–2.0 cases per 100,000 inhabitants were reported during 2000–2009. Since 2002, a substantial increase has been observed in the proportion of cases attributed to meningococcus serogroup C (MenC) that is associated with the sequence type (ST) 103 complex, and MenC is currently responsible for most cases of meningococcal disease in Brazil (
Several outbreaks of MenC disease have been reported in Brazil in recent years (
Published data describing meningococci carriage in Brazil are limited. Few studies have been conducted that assess 1) the role of carriage prevalence in the dynamics of carriage and disease or 2) the potential effect of control programs, such as vaccination, on the transmission of meningococci. Thus, we conducted a cross-sectional study with the primary objective of assessing the prevalence of meningococcal carriage among workers at 2 oil refineries in São Paulo State, Brazil, where outbreaks of MenC disease occurred in 2010. We also investigated the effect of meningococcal A/C polysaccharide vaccination and risk factors on pharyngeal carriage of meningococci.
During March 29–June 30, 2010, an outbreak of MenC disease, associated with the ST103 complex, occurred in an oil refinery (Refinery A) with 17,590 workers in São Paulo State, Brazil. A total of 18 cases and 3 deaths (case-fatality rate 16.7%) were associated with the outbreak. Six of the cases and 2 deaths involved Refinery A workers, and 12 of the cases and 1 death involved contacts (family members) of the refinery workers. The case-patients were residents of Cosmópolis, a municipality with 59,000 inhabitants located near Refinery A.
On March 29, health authorities were notified of the first 3 case-patients (2 adult workers at Refinery A and an 8-month-old child whose father worked at Refinery A). An investigation was initiated, and chemoprophylaxis with rifampin was recommended for all close contacts of the 3 index case-patients. During the following 2 weeks, 5 new cases of MenC disease were identified (3 in Refinery A workers and 2 in children who were relatives of Refinery A workers). With these new cases, the incidence of meningococcal disease reached 34.1 cases/100,000 persons at Refinery A. Meningococcal A/C polysaccharide vaccination was recommended for all 17,590 workers at Refinery A. Vaccination began on April 16, and 1 week later, 91% coverage of workers at Refinery A was achieved. However, despite the vaccination program, 10 new cases of MenC disease occurred: 9 cases were in family contacts and 1 case was in a Refinery A worker who had received vaccine 1 day before symptom onset.
The incidence of MenC disease in Cosmópolis subsequently reached 20.2 cases/100,000 persons. Cases occurred in relatives (8 months to 16 years of age) of Refinery A workers, prompting a mass vaccination of 18,571 inhabitants of Cosmópolis who were 2 months to 19 years of age. Vaccination began on June 30, and 90.5% coverage was achieved 1 week later. Infants and toddlers received MCC vaccine, and persons 2–19 years of age received meningococcal A/C polysaccharide vaccine. In the months following the vaccination campaign, no more MenC cases were reported, and the outbreak was considered controlled.
The second outbreak of MenC disease occurred in a refinery with 16,000 workers (Refinery B) in São José dos Campos, a city with 610,095 inhabitants in São Paulo State. On July 10, 2010, a worker at Refinery B was reported to have MenC disease, and on July 18, a second worker was reported to be infected. An investigation identified 10 other reported cases in São José dos Campos during April–July, 2010; the 10 cases were in children <4 years of age who were household contacts of Refinery B workers. Of the 12 identified case-patients, 6 died. As in Cosmópolis, these initial cases were considered the index cases. In Refinery B, the incidence of meningococcal disease reached 12.5 cases/100,000 persons, and a decision was made to provide chemoprophylaxis, but not vaccine, to all close contacts of index case-patients. On August 8, 1 new case of meningococcal disease was reported in a family contact of a Refinery B worker; no further cases were reported in 2010.
Beginning in December 2010, we conducted a cross-sectional study of 483 workers (18–39 years of age) from Refinery A, where mass vaccination had been recommended, and Refinery B, where mass vaccination had not been advised. All study participants gave informed consent. A questionnaire was used to obtain information regarding age, sex, recent respiratory tract infections, active and passive smoking, alcohol consumption, recent antimicrobial drug use, length of employment at the refinery, number of household members living in the same room, level of education, and meningococcal A/C polysaccharide vaccination status.
During the first 2 weeks of December, 2010, we obtained oropharyngeal swab samples from 483 refinery workers (238 vaccinated workers from Refinery A and 245 nonvaccinated workers from Refinery B). The samples were immediately put into transport medium (
DNA from each sample was extracted and purified by using the QIAamp DNA MiniKit (QIAGEN, Alameda, CA, USA) or a similar testing kit according to the manufacturer’s instructions. Primers and fluorescent probes were used for the detection of
Serotyping for all
Using an estimate that the prevalence of meningococci carriage among adults would be ≈18% (±5%), we calculated that ≈225 study participants from each refinery would be needed to analyze all variables. Demographic data for all participants and typing results of
Of the 483 oropharyngeal samples tested, 104 (21.5%; 95% CI 18.0%–25.5%) were positive for meningococci. Carriage rates were similar among workers from both refineries (21.4% vs. 21.6%). Of the 104 positive samples, 95 were detected by culture and real-time PCR, 1 was detected by culture only, and 8 were detected by real-time PCR only.
The serogroup and genogoup could be determined for 56 of the 104 meningococci-positive samples: 27 (48.2%) were serogroup C, 9 (16.1%) serogroup B, 8 (14.3%) serogroup E, 7 (12.5%) serogroup Y, and 5 (8.9%) serogroup W. The serogroup could not be determined for 48 (46.1%) isolates. The difference in MenC carriage rates among workers at the 2 refineries was not significant: 6.3% at Refinery A and 4.9% at Refinery B (p = 0.48) (
| No. (%) workers | p value‡ | |||
|---|---|---|---|---|
| Refinery A* | Refinery B† | Total | ||
| All | 51 (21.4) | 53 (21.6) | 104 (21.5) | 1.00 |
| C | 15 (6.3) | 12 (4.9) | 27 (5.6) | 0.64 |
| B | 4 (1.6) | 5 (2.0) | 9 (1.9) | 1.00 |
| W | 4 (1.6) | 1 (0.4) | 5 (1.0) | 0.35 |
| Y | 5 (2.1) | 2 (0.8) | 7 (1.4) | 0.43 |
| E | 3 (1.2) | 5 (2.0) | 8 (1.7) | 0.76 |
| Nongroupable | 20 (8.4) | 28 (11.4) | 48 (9.9) | 0.34 |
| Negative | 187 (78.6) | 192 (78.4) | 379 (78.5) | |
| Total | 238 (100.0) | 245 (100.0) | 483 (100.0) | |
*Vaccinated workers.
†Unvaccinated workers.
A total of 38 different serotype–serosubtype antigen combinations were identified among the 96
| Refinery, | Serotype:serosubtype | ST | Clonal complex |
|---|---|---|---|
| A | |||
| B | |||
| 20 | 4,7:NST | 9858 | |
| 29 | 19,1:P1.14 | 6481 | ST213 complex |
| 19 | 17:P1.5 | 8035 | ST41/44 complex/Lineage 3 |
| C | |||
| 26 | 23:P1.14–6 | 3780 | ST103 complex |
| 28 | 23:P1.14–6 | 8730 | NA |
| 21 | 23:P1.14–6 | 8730 | NA |
| 22 | 23:P1.14–6 | 8730 | NA |
| 20 | 23:P1.14–6 | 8730 | NA |
| W | |||
| 21 | 2b:P1.2 | 11 | ST11 complex/ET-37 complex |
| 27 | 2b:P1.5,2 | 11 | ST11 complex/ET-37 complex |
| 24 | 2b:P1.5,2 | 11 | ST11 complex/ET-37 complex |
| Y | |||
| 23 | 2a:P1.5,2 | 11 | ST11 complex/ET-37 complex |
| 26 | 17,7:P1.5 | 6525 | NA |
| 22 | 17,7:P1.5 | 6525 | NA |
| B | |||
| B | |||
| 26 | 19,1:NST | 1869 | ST461 complex |
| 19 | 4,7:P1.19,15 | 7594 | ST32 complex/ET-5 complex |
| 28 | 4,7:P1.19,15 | 7594 | ST32 complex/ET-5 complex |
| C | |||
| 25 | 23:P1.14–6 | 3780 | ST103 complex |
| 21 | 23:P1.14–6 | 3780 | ST103 complex |
| 25 | 23:NST | 3780 | ST103 complex |
| 28 | 23:P1.5 | 3779 | ST103 complex |
| 23 | 4,7:P1.19,15 | 3773 | ST32 complex/ET-5 complex |
| 28 | 23:P1.14–6 | 3780 | ST103 complex |
| 25 | 23:P1.14–6 | 8730 | NA |
| 23 | 23:P1.14–6 | 3780 | ST103 complex |
| W | |||
| 26 | 2b:P1.2 | 11 | ST11 complex/ET-37 complex |
| Y | |||
| 19 | 19,7:P1.5 | 6525 | NA |
*NST, not serosubtypeable; ST, sequence type; NA, assigned without clonal complex.
We did not find an increased risk of meningococci carriage associated with any of the potential risk factors studied, except low level of education. A low education level (i.e., not completing secondary education) was significantly associated with a higher risk for carriage of meningococci, regardless of serogroup identification (
| Variable | All | Serogrouped | |||||
|---|---|---|---|---|---|---|---|
| % Workers exposed | % Workers not exposed | p value* | % Workers exposed | % Workers not exposed | p value* | ||
| Antimicrobial drug use† | 12.9 | 22.1 | 0.16 | 3.2 | 12.0 | 0.11 | |
| Crowded living conditions | 17.4 | 22.9 | 0.14 | 9.9 | 12.3 | 0.35 | |
| Active smoking | 23.2 | 21.2 | 0.41 | 11.6 | 11.6 | 0.58 | |
| Respiratory symptoms† | 24.2 | 20.9 | 0.26 | 10.1 | 11.9 | 0.44 | |
| Low level of education‡ | 32.9 | 19.2 | 0.01 | 17.0 | 10.6 | 0.07 | |
*By Fisher exact test. †In the 15 d before the collection of the nasopharyngeal sample. ‡Defined as not completing secondary education.
Most published studies report a consistently low rate (usually <1%) of MenC carriage during outbreaks of MenC disease (
Mass vaccination with a meningococcal A/C polysaccharide vaccine was conducted at Refinery A, and high coverage (91%) was achieved among workers. This intervention controlled the MenC outbreak in the refinery; only 1 new case occurred after the vaccination campaign, but that case cannot be considered the result of a vaccine failure because it occurred <14 days after the refinery worker was vaccinated. These findings likely indicate that the workers received direct protection against MenC from vaccine. However, after the vaccination campaign, 9 new cases of MenC infection occurred in children who were household contacts of vaccinated workers, without any known contact among them.
The prevalence of MenC carriage was high among workers at both refineries, even though 91% of Refinery A workers had received meningococcal A/C polysaccharide vaccine 6 months before our study began. More striking, carriage rates among vaccinated and nonvaccinated workers were similar. These findings suggest that meningococcal A/C polysaccharide vaccine had no effect on MenC carriage. Most of the studies conducted among nonmilitary populations demonstrated that these vaccines cannot significantly reduce meningococcal carriage (
In contrast to polysaccharide vaccines, conjugate vaccines lead to the production of very high antibody concentrations, even in infants, and induce immunologic memory with higher antibody avidity and increased serum bactericidal activity, thus providing more robust long-term protection. In addition, conjugate vaccines also prevent the acquisition of carriage among vaccinees and, by interrupting transmission, provide indirect protection to unvaccinated, susceptible persons; this herd immunity proved key to the success of MCC vaccination programs in various countries (
The characterization of the
Meningococcal carriage was not associated with any of the risk factors evaluated in our study, except the level of education, which was inversely related to the prevalence of carriage. The higher percentage of MenC carriers among study participants with a lower level of education presumably reflects associated socioeconomic conditions and social behaviors. Less-educated workers in oil refinery settings are also more likely to perform activities that require the use of ear devices as protection from the loud environment. The wearing of such devices forces workers to stay very close to each other to facilitate conversation among them, and such close working situations also facilitate transmission of meningococci.
Although the relationship between meningococci carriage prevalence and disease incidence is not fully understood, the evidence gathered during this study showed a dominance of the C:23:P1.14–6 phenotype strain among workers from both refineries, reinforcing the concept that the dominance of a particular strain is an important marker of epidemic conditions (
Suggested citation for this article: Sáfadi MAP, Carvalhanas TRMP, de Lemos AP, Gorla MC, Salgado M, Fukasaka LO. Carriage rate and effects of vaccination after outbreaks of serogroup C meningococcal disease, Brazil, 2010. Emerg Infect Dis. 2014 May [date cited].
We thank Marcelle Viçoso dos Santos, Conceição Zanelato, Maria Vaneide de Paiva, and Martha Galhardo for assistance in conducting microbiological tests.
An unrestricted education grant from Sanofi Pasteur vaccines was provided for this study.
M.A.P.S. has been a scientific consultant and a speaker for GlaxoSmithKline, Novartis, Wyeth/Pfizer, Sanofi Pasteur, and MSD (MerckSharpDohme); J.C.M. has been a scientific consultant for Novartis, Wyeth/Pfizer, and Sanofi Pasteur. M.C.C.B. has been a speaker for Sanofi-Pasteur, Pfizer, and Glaxo Smith Kline. A.P.L. has been a speaker for Novartis and Sanofi Pasteur. M.C.O.G. has been a speaker for Novartis.
Dr Sáfadi is a pediatric infectious disease specialist and an assistant professor in the Department of Pediatrics at Faculdade de Ciências Médicas da Santa Casa, São Paulo. His primary research interests include epidemiology and prevention of childhood infectious diseases.