Nicholas Wood

PERTUSSIS: REVIEW OF EPIDEMIOLOGY, DIAGNOSIS, MANAGEMENT AND PREVENTION

Bordetella pertussis--the cause of pertussis or whooping cough--is an exclusively human pathogen. Disease elimination by vaccination should, therefore, be possible, but has proved elusive. Many industrialised countries with long established immunisation programs are currently seeing a resurgence of pertussis, despite universal vaccination with high uptake, with the highest burden in the least immunised age groups (infants under 6 months of age and persons over 10 years old). However, low recognition and reporting and insensitive diagnostic tests mean that the true burden of pertussis is still underestimated. Recently, efforts to improve diagnostic yield include the expanded use of polymerase chain reaction and serological tests but both have significant limitations. The range of antibiotics available for treatment and prophylaxis has expanded to include the newer macrolides, azithromycin and clarithromycin, and a range of universal and targeted vaccination strategies have been implemented or proposed. This paper reviews the current epidemiology of pertussis in developed countries, including modes of clinical presentation, diagnosis, management and potential vaccination strategies.

Acellular Pertussis Vaccine at Birth and One Month Induces Antibody Responses By Two Months of Age

Background: Infants less than 3 months of age are at highest risk of hospitalization and death from pertussis. Several studies have examined antibody responses to pertussis vaccines at birth but no previous study has evaluated 2 doses of monovalent acellular pertussis vaccine (aPV) before 2 months of age. Methods: Seventy-six newborns were randomized at birth to 3 groups–aPV at birth and 1 month, aPV at birth, and control. All infants received hepatitis B vaccine (HBV) at birth followed at 2, 4, and 6 months by a combination vaccine including aPV, diphtheria, tetanus, Haemophilus influenzae type b (Hib), hepatitis B, polio antigens and 7 valent conjugate pneumococcal vaccine. IgG antibody responses to pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were measured in maternal serum and in infants at 2, 4, 6, and 8 months of age. Antibody responses to hepatitis B, diphtheria, tetanus, and Hib were measured at 8 months only. A parental diary and active telephone follow-up occurred for 7 days after each vaccination. Results: The aPV birth dose was well tolerated. By 2 months of age, 22 of 25 (88%) of 2 dose recipients had detectable IgG antibody to PT (IgG PT) compared with 9 of 21 (43%) who received a birth dose only and 3 of 20 (15%) of controls. Infants in the 2 dose group had a geometric mean concentration (GMC) of IgG PT of 16 ELISA units per mL (EU/mL), 95% CI: 11 to 25, significantly higher than birth dose only (5 EU/mL, 95% CI: 3–8) and controls (3 EU/mL, 95% CI: 2–5). At 8 months of age, following 5, 4, and 3 doses of aP-containing vaccine, respectively, IgG PT had plateaued but IgG to FHA and PRN increased with successive doses. There was a trend to lower antibody responses for hepatitis B and Hib with higher numbers of Pa doses. Conclusion: These data suggest that aPV at birth and 1 month induces significantly higher IgG antibody against pertussis antigens by 2 months of age without reducing subsequent pertussis antibody responses. Larger and more detailed studies of aPV from birth are needed to evaluate other antibody responses and the potential of this approach to reduce death and morbidity from Bordetella pertussis infection in the first 3 months of life.

Rapid Increase in Pertactin-deficient Bordetella pertussis Isolates, Australia

Acellular vaccines against Bordetella pertussis were introduced in Australia in 1997. By 2000, these vaccines had replaced whole-cell vaccines. During 2008–2012, a large outbreak of pertussis occurred. During this period, 30% (96/320) of B. pertussis isolates did not express the vaccine antigen pertactin (prn). Multiple mechanisms of prn inactivation were documented, including IS481 and IS1002 disruptions, a variation within a homopolymeric tract, and deletion of the prn gene. The mechanism of lack of expression of prn in 16 (17%) isolates could not be determined at the sequence level. These findings suggest that B. pertussis not expressing prn arose independently multiple times since 2008, rather than by expansion of a single prn-negative clone. All but 1 isolate had ptxA1, prn2, and ptxP3, the alleles representative of currently circulating strains in Australia. This pattern is consistent with continuing evolution of B. pertussis in response to vaccine selection pressure.

Pertussis in early infancy: disease burden and preventive strategies.

Purpose of review Severe pertussis disease in early infancy remains a significant problem, both in developed countries with long-standing pertussis immunization programs and in poor countries. We review current understanding of the disease burden and potential prevention strategies. Recent findings Even with intensive care support, infants with pertussis pneumonia still die, so prevention is the key. The source of pertussis in infants under 3 months of age is often not clear, but in countries with high childhood immunization coverage, the sources are usually adults. Strategies to protect these infants may be indirect (timely primary immunization and boosters for older children and adults) and direct (mother during pregnancy or infant soon after birth). ‘Cocooning’ by immunizing all potential adult contacts is probably the most effective indirect strategy but needs funding and programmatic support for successful implementation. Maternal immunization is attractive but unproven and has significant practical hurdles. The evidence on immunization at birth is conflicting and impact, including interference with response to other infant vaccines, is unclear. Summary Adult booster immunization, either universal or targeted (mothers during pregnancy or ‘cocoon’), would probably be effective but is challenging to implement. If shown to be safe and effective, immunization at birth has significant practical advantages. Different strategies (alone or combined) may be needed in different settings.

Uptake of influenza vaccine by pregnant women: a cross-sectional survey

Objectives: To determine influenza vaccination coverage among pregnant women in New South Wales, and factors associated with vaccine uptake during pregnancy.

Streptococcus pneumoniae – a review of carriage, infection, serotype replacement and vaccination

Invasive pneumococcal infection remains a leading global cause of morbidity and mortality in young children. In developed nations, a substantial decrease in the incidence of IPD has been achieved with inclusion of the 7 valent protein conjugated pneumococcal vaccines (7vPCV) into paediatric vaccine schedules. In contrast, the incidence of IPD has changed little in developing nations. This is likely due to poor access to medical care and pneumococcal vaccination, the accompanying HIV and malnutrition burden, and the fact that 7vPCV does not contain the most common serotypes (1,5, 6A) responsible for IPD in many developing nations. The battle against IPD in developed nations is not over, with the rise of non-7vPCV serotypes since routine 7vPCV vaccination. This has necessitated the development and distribution of pneumococcal vaccines containing 3 or 6 additional serotypes. This article provides an overview on pneumococcal carriage and risk factors for IPD, the rise of non-7vCPV serotypes in the era of 7vPCV vaccination, and the current and newly available broader valent pneumococcal vaccines.

Neonatal immunization: where do we stand?

Purpose of review Recognition of the high burden of disease in early life and advances in the understanding of neonatal immunology have resulted in renewed interest in maternal and neonatal vaccination. This article reviews existing information and recent advances in neonatal human immunization. Recent findings Recent findings have demonstrated the neonatal immune system not to be immature but rather specifically adapted for early postnatal life. This includes the preferential induction of memory B cell rather than antibody-secreting plasma cells and polarization of neonatal T-cell responses away from potentially deleterious T-helper type 1 cytokines. Recent neonatal acellular pertussis and pneumococcal conjugate vaccine trials have proven that a birth dose of acellular pertussis and/or pneumococcal vaccine, in limited samples sizes, are well tolerated and immunogenic; however they have identified vaccine interference as a critical issue to address. Summary Neonatal immunization may be a well tolerated and effective preventive strategy against early life pathogens. Research to better understand how neonatal vaccine responses are elicited and to identify optimal early life adjuvants and formulations may broaden neonatally vaccine-preventable diseases to pertussis, rotavirus and possibly influenza, further reducing disease burden in this vulnerable group. Hurdles to neonatal vaccination include safety concerns, both immunological and clinical, demonstration of vaccine efficacy and public acceptance.

Pregnant women's intention to take up a post-partum pertussis vaccine, and their willingness to take up the vaccine while pregnant: A cross sectional survey

INTRODUCTION Post-partum vaccination of new mothers is currently recommended in Australia to reduce pertussis infection in infants. Internationally, vaccination recommendations now include pregnant women in some countries. Understanding the awareness of pertussis vaccination recommendations among pregnant women, and their willingness to have the vaccine while pregnant is important for informing vaccine program implementation. OBJECTIVE To determine awareness and intentions toward current recommendations for post-partum pertussis vaccination among Australian pregnant women, and their willingness to accept pertussis vaccine during pregnancy, should it be recommended in Australia in the future. DESIGN Quantitative self-administered survey, using a non-random stratified sampling plan based on representative proportions by age, parity and region of residence. PARTICIPANTS AND SETTING Pregnant women receiving antenatal care through three large, demographically diverse referral hospitals in metropolitan, urban and rural New South Wales, Australia. RESULTS The response rate was 815/939 (87%). Most women (80%) reported willingness to have the pertussis vaccine during pregnancy, should it be recommended. Thirty four per cent of women intended to receive a pertussis vaccine post-partum, 17% had received it previously, while 45% had never heard of pertussis vaccine, had not thought about it, or were undecided about having it. Compared with those who had not received a recommendation to have the vaccine post-partum, women who had received a recommendation were 7 times more likely (95% CI 4-14) to report intention to have the vaccine. CONCLUSIONS Health care provider recommendation is paramount to raising awareness of pertussis vaccination recommendations among pregnant women. Womens willingness to have the vaccine while pregnant is encouraging, and indicates the potential for high pertussis vaccine coverage among pregnant women, should it be recommended in Australia.

Th2-polarisation of cellular immune memory to neonatal pertussis vaccination.

Current infant vaccination against pertussis in North America and Australia requires three doses of vaccines including diphtheria, tetanus and acellular pertussis antigens (DTaP) at 2, 4 and 6 months of age. Interest is growing in the possibility that vaccination at birth might provide earlier protection of infants, but early vaccination also gives rise to concerns over the potential for excessive Th2-polarisation of pertussis-specific T-cell memory profiles. We evaluated this issue as part of a small pilot study comparing infants receiving a monovalent acellular pertussis vaccine (aP) at birth or birth and at 1 month, followed by DTaP at 2, 4 and 6 months with infants receiving DTaP only from 2 months. We compared in vitro Th-memory responses at 8 months and pertussis-specific IgG in serum at 2, 4, 6 and 8 months. Neonatal vaccination elicited earlier IgG responses, but accompanying Th-memory profiles displayed a strong Th2 bias with high IL-5 and IL-13 production. The correlation between T-cell memory profiles and other clinical outcomes should be evaluated in larger trials of neonatal aP vaccine.

The epidemiology of health conditions of newly arrived refugee children: A review of patients attending a specialist health clinic in Sydney

Aim:  To determine the prevalence of common diseases in newly arrived refugee children, resettled in Sydney, by region of birth. To identify health needs of refugee children in Australia.