Guilherme Gonçalves

Pertussis: increasing disease as a consequence of reducing transmission

Since the 1980s, the occurrence of pertussis cases in developed countries has increased and shifted towards older age groups. This resurgence follows 30 years of intense mass vaccination, and has been attributed primarily to three factors: (1) more effective diagnosis of the disease, (2) waning of vaccine-induced immunity, and (3) loss of vaccine efficacy due to the emergence of new Bordetella pertussis strains. Here we develop and analyse a mathematical model to assess the plausibility of these hypotheses. We consider that exposure to B pertussis through natural infection or vaccination induces an immune response that prevents severe disease but does not fully prevent mild infections. We also assume that these protective effects are temporary due to waning of immunity. These assumptions, describing the mode of action of adaptive immunity, are combined with a standard transmission model. Two distinct epidemiological scenarios are detected: under low transmission, most infections lead to severe disease; under high transmission, mild infections are frequent, boosting clinical immunity and maintaining low levels of severe disease. The two behaviours are separated by a reinfection threshold in transmission. As a result, the highest incidence of severe disease is expected to occur at intermediate transmission intensities--near the reinfection threshold--suggesting that pertussis resurgence may be induced by a reduction in transmission, independently of vaccination. The model is extended to interpret the outcomes of current control measures and explore scenarios for future interventions.

Relationships Between Rhinitis Symptoms, Respiratory Viral Infections and Nasopharyngeal Colonization With Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Children Attending Daycare

Background: Nasal bacterial colonization is often dubbed “asymptomatic.” We hypothesized that rhinitis, common in preschool children, is associated with bacterial colonization and that respiratory viruses, which cause rhinitis, interact with bacteria in ways which promote transmission. Methods: Five hundred eighty-five children (4.2–73.6 months) attending daycare had clinical information, a rhinitis score and nasal swabs collected in February 2009. Swabs in soya tryptone glucose glycerine broth were cultured for Streptococcus pneumoniae (Sp), Haemophilus influenzae (Hi) and Staphylococcus aureus and analyzed by real-time polymerase chain reaction for respiratory viruses, both semiquantitatively. Results: Rhinitis symptoms, carriage of Sp and Hi and viral infection fell, whereas S. aureus carriage rates rose with age. Significant, age-independent associations between rhinitis symptoms and detection of Hi (P < 0.033) and Hi colonization density (P < 0.027) were observed. Of the 42% with detected viruses, most (78%) had picornavirus infection. There was a significant age-independent association between viral infection (and viral load, picornavirus infection and picornaviral load) and detection of Sp (P = 0.020, 0.035, 0.005, 0.014) and between viral infection and viral load and Sp colonization density (P = 0.024, 0.028). Conclusions: Hi may promote its own transmission by inducing or amplifying rhinitis in children. There is a close quantitative relationship between respiratory viral infection, including picornavirus infection and Sp colonization. These findings have implications for understanding disease pathogenesis and formulating prevention strategies using vaccines.

Transplacental transfer of measles and total IgG

This study was conducted to evaluate factors affecting the levels of total IgG (tIgG) and measles specific IgG (mIgG) in mother and cord sera, and the efficiency of transplacental transport of tIgG and mIgG. The study was conducted in four hospitals in Oporto, Portugal, where 1539 women and their newborns were enrolled. Measles IgG levels were lower among vaccinated mothers and respective cord sera than among vaccinated counterparts. Cord mIgG was strongly correlated with maternal levels in both vaccinated and unvaccinated groups. Transplacental transport efficiency (TTE) of mIgG decreased with increasing maternal levels, although almost one third of the observed effect was due to measurement error. The TTE was not affected by vaccination status. Monitoring maternal measles antibody levels and maternal vaccination status could be useful to determine when the age for measles vaccination can be reduced.

Streptococcus pneumoniae nasopharyngeal carriage in children attending day-care centers in the central region of Portugal, in the era of 7-valent pneumococcal conjugate vaccine.

The 7-valent pneumococcal conjugate vaccine became available in Portugal in 2001. Although not included in the national immunization program, vaccination coverage is high (over 60%). We studied for the first time the rates of nasopharyngeal (NP) carriage of pneumococci, antibiotic resistance patterns and serotypes among children attending day-care centers (DCCs) in Coimbra, a city in the Central Region of Portugal. Between January and February 2007, a cross-sectional study was conducted among children aged 6 months to 6 years attending eight DCCs. NP swabs were obtained from 507 children: 76.7% had received at least one dose of 7-valent pneumococcal conjugate vaccine and 64.3% were age-appropriately vaccinated. The global pneumococcal carriage rate was 61.3%. Colonization proportions varied with age and number of children attending each DCC. Serotyping revealed that 20.7% of the pneumococci were vaccine types (VTs), 70.8% were non-VTs, and 8.5% were nontypeable. Serotype 19F was the second most frequent serotype being detected in 10.5% of the samples. While global NP carriage was not associated with vaccination status, non-VTs were predominant among vaccinated children, who had significantly lower prevalence of VT. Of all isolates, 15.7% had penicillin minimum inhibitory concentrations that ranged between 0.12 and 2 microg/ml. The proportion of resistant strains was significantly higher among VT and unvaccinated children. In conclusion, the rates of vaccination and prevalence of pneumococcal NP were high. Rates of antimicrobial resistance were similar to those found in studies conducted in Oeiras and Lisbon. This study is a platform for future surveillance activities.

Progressive changes in pneumococcal carriage in children attending daycare in Portugal after 6 years of gradual conjugate vaccine introduction show falls in most residual vaccine serotypes but no net replacement or trends in diversity

OBJECTIVESnTo track ongoing trends in pneumococcal (Sp) serotype carriage under the selection pressure of moderate pneumococcal conjugate vaccine (PCV) use, children in a community in Portugal were studied in the same months in 3 consecutive years.nnnMETHODSnNasopharyngeal specimens were collected (children aged 3 months to <7 years) in 8 urban daycare centers in February 2008 (n=561) and 2009 (n=585). Sp isolates were serotyped.nnnRESULTSnWhile demographics were similar in 2008-2009 and a previously reported sample in 2007, PCV coverage (at least one dose) in the children studied rose from 76.5% to 84% although national coverage was lower than this. Sp carriage fell from 61% to 51% with a concomitant fall in PCV7 serotype carriage from 12.1% to 4.3%. Remaining PCV7 serotypes declined to near (23F) or totally (6B, 14) undetectable levels except 19F which persisted unchanged in around 4% of children. Although carriage of 3 and 6C rose, there was no net increase in non-PCV7 serotypes and no progressive trend in serotype diversity.nnnCONCLUSIONSnEcological changes induced by PCVs where uptake is moderate appear to be different from high usage settings. We report falling Sp carriage due to PCV7 serotype disappearance with persistence of 19F and no ongoing net replacement after several years of PCV7 use and slowly rising uptake.

Outbreak of mumps associated with poor vaccine efficacy - Oporto Portugal 1996

Vaccination against mumps in Portugal began in 1987, with the introduction of the combined measles, mumps, and rubella vaccine (MMR) in the national vaccination programme (Programa Nacional de Vacinacao: PNV) for both sexes at 15 months. In November 1990,

Herd immunity: recent uses in vaccine assessment

Human communities defend themselves against specific infectious agents in a way that extends beyond the simple sum of the immune status of its individuals. By analogy with individual immunity to specific agents, the community level of immunity may vary from complete susceptibility to full protection. Herd immunity has been used to name this community property, which is the result of evolution through natural selection, leading to relationships between two species, typical of prey–predator systems. Varying uses of the term herd immunity led to the use of other expressions, such as herd protection, herd effect and community immunity. Knowledge derived from observational studies and models on herd immunity has supported decisions on the choice of vaccines and vaccination strategies for the benefit of populations. This knowledge is most likely to be extended in the future, with far-reaching effects.

Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination

BackgroundThe need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td). This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster.MethodsFollowing the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG) and antidiphtheria toxin IgG (ADT IgG) levels were measured (mIU/ml) in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants.ResultsTwenty-two women (Group A) began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022) and decreased with time since last vaccination (p = 0.016). Among the 66 women who began vaccination in adolescence and adulthood (Group B), with monovalent TT, ATT IgG levels decreased with age at first dose (p < 0.001) and with time since last vaccination (p = 0.041). In Group A, antidiphtheria toxin IgG kinetics was very similar to that observed for ATT IgG. Among women not vaccinated with diphtheria toxoid, ADT IgG levels decreased with age. Serological response to both components of Td was good but more pronounced for ATT IgG.ConclusionOur study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid). The adult booster intervals could be wider, probably of 20 years. This also seems to apply to protection against diphtheria, but issues on the herd immunity and on the circulation of toxigenic strains need to be better understood.

Antibodies to hepatitis E in Portuguese mothers and their newborns

The high mortality of pregnant women is one of the main features of hepatitis E virus (HEV) infection in endemic countries. With the emergence of genotype 3 HEV in industrialized countries, attention should be given to pregnant women from these regions since the effect of genotype 3 HEV in pregnancy is not yet known. In this study, archived sera dating from 1993 from mothers with no history of traveling to HEV endemic countries and their newborns were tested for anti‐HEV IgG antibodies. Four of the 12 maternal sera were positive for IgG anti‐HEV, indicating exposure to this virus. Their newborns were also positive, showing higher anti‐HEV IgG levels. Overall, these findings demonstrate not only an efficient transplacental transport of anti‐HEV IgG, but also circulation of autochthonous HEV in Portugal in the early 1990s. J. Med. Virol. 85:1377–1378, 2013.

Prevalence of hepatitis E virus antibodies in workers occupationally exposed to swine in Portugal

The concept of zoonotic hepatitis E in industrialized countries has emerged with the discovery of swine strains of hepatitis E virus (HEV) genotype 3, closely related to human HEV. Different routes of zoonotic HEV transmission have been recognized, including contact with infected pigs. Workers occupationally exposed to swine (WOES) have been considered a risk group for HEV infection, but contradictory results have been reported. In the present study, we searched for anti-HEV IgG in WOES (butchers, slaughterhouse workers, veterinarians and pig farmers; nxa0=xa0114) and in the general population (nxa0=xa0804) in order to investigate the potential occupational risk of zoonotic HEV infection in this work group. A significantly higher (pxa0=xa00.008) anti-HEV IgG seroprevalence was found in WOES (30.7xa0%) when compared with the general population (19.9xa0%). Multivariate analysis showed that having professions with exposure to pigs for more than 16.5xa0years was a risk factor for being positive for anti-HEV IgG (aOR of 5.4, 95xa0% CI 1.9–15.6, pxa0=xa00.002). To our knowledge, this is the first study on the prevalence of anti-HEV IgG in WOES in Portugal, also showing increased probability for infection in this group.