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Why has resurgence of pertussis occurred in recent years

The resurgence of pertussis in the recent past has been a cause for concern. The disease remained under control for several decades in countries with good vaccine coverage and the recent outbreaks have occurred in populations that have been covered under the vaccine program, particularly, in the USA, UK and Australia as reported by Sheridan et al. (1). New South Wales in Australia has also registered an increase in cases and outbreaks have occurred in the recent years. Infants too young to have received vaccination for pertussis have been affected as reported by Donnan et al. (2). The occurrence of pertussis among the adolescent and pre-adolescent population has the health establishment searching for possible reasons for the recent outbreaks. Principle among the causes could be the need to reassess the efficacy of vaccines that were used to immunise the affected population. The propensity of bacteria to mutate and evolve may also have played a role as determined by Carbonetti (3). Public health approaches to prevent the mortality and morbidity caused due to Bordetella pertussis, which is a preventable infectious disease include an assessment and deployment of the possible approaches in increasing awareness among the healthcare staff and the public (2). Changes in the vaccine regimen may have to be made through regular booster vaccines to control the incidence of pertussis and reduce disease burden.

Since the resurgence of pertussis began in the early part of this decade, the highest number of notifications, about 1800 cases in New South Wales were received in November, 2015 among patients older than 5 years. Among children below 5 years of age, the highest numbers of notifications were received between November, 2015 and January, 2016. The number of notifications dipped in June, 2016 and again rose in the quarter that began in September 2016 and lasted until January, 2017. It is evident that most cases are notified during the spring season.

In the period between August 2014 to July 2017,  pertussis notifications among the residents of NSW among children aged between the ages of 5 to 9 years were the highest at about 7000. Disease notifications for children between the ages of 10 -14 years of age were about 5500 and those for children below 4 years of age were 4500. About 1500 notifications were registered for the age group between 15 and 19 years. In all these age groups the incidence was almost equal for both genders. Notifications close to a thousand were received for age groups up to the age of 54. Syed (4) reported that the acellular vaccines were given from the year 1999 as a solution to the reactogenic whole cell vaccines. But these have now been found to give inadequate protection, due to waning immunity with time and that could be the reason for the higher rates of pertussis among the adolescents.

Bordetella pertussis: Causes and incidence of pertussis

Bordetella pertussis is the causative organism that causes pertussis which is known in common parlance as whooping cough though B. parapertussis has also been reported to be the causative organism in some cases as mentioned on the Immunise Australia website (5) The disease was widely under control due to vaccination programs in all regions of the world. But the World Health Organisation has reported the recurrence of the disease in large numbers in developing and developed countries inspite of wide vaccination coverage of populations. According to Gabutti and Rota, 16 million cases worldwide resulted in about 195,000 fatalities. As per the NSW health department (6) it is a bacterial infection that affects the respiratory system and can be even fatal in case of small infants if they have not received the vaccination. The major disease burden of the disease is in children but the incidence of pertussis among adults has also been reported. Studies by Karki et al. (7) concluded that hospitalization due to pertussis among elderly patients was high in cases where the patients were smokers. Among infants less than six weeks of age, the high incidence of pertussis could be due to the fact that they have not received the vaccination and are unprotected. The incidence of pertussis is more common among infants who are too young to be immunised, children who are yet to be completely immunised and completely immunised adults with waning immunity.

Why has resurgence of pertussis occurred in recent years

Reasons for the resurgence of pertussis outbreaks in New South Wales in recent years have been studied. In the year 2012, Roswell et al. reported the occurrence of 5838 cases of pertussis  which was much lesser than the 13183 cases in 2011 (8). These included infants who were too young to be immunised, and were yet to receive the three doses of vaccination. As per studies by Gaillard et al. (9) about 7.6% children below the age of four years had not been immunised and 2.6% of the children had not received all the three doses. The waning of the effectiveness of the pertussis vaccine over time has been another cause that may have led to the pertussis outbreaks in recent years. Clark et al. reported that the effectiveness of the acellular vaccine and for how long these remain protective have been under scrutiny (10). Whole cell vaccines have been known to offer greater protection than the acellular pertussis vaccines. Disease notifications in New South Wales increased due to changed diagnostic parameters after 2008. Quinn et al. (11) reported that vaccine schedules changed with time and the anti pertussis toxin IgG titres dropped among all age groups. The incidence of pertussis was reported by Liko et al. (12) to be higher among children who had received a first vaccination dose of DTaP (Diptheria, Tetanus with acellular pertussis) than those who had received a DPwP (Diptheria, Tetanus with whole cell pertussis). A similar observation was made in another study conducted in Australia by Sheridan et al. (1) and the whole cell pertussis vaccine was fond to confer better immunity than the acellular pertussis vaccine. Another observation that was made with regard to the recent pertussis epidemics was that adolescents and pre-adolescents formed a large part of the patient population in the US and Australia. Sheridan (13) has reported that these children were a cohort that received the acellular pertussis vaccine for the first time in the latter half of the 1990s and their immunity against pertussis waned rather rapidly as compared with that of children who had received the cellular pertussis vaccine. Sheridan (13) also reports that longer lasting and stronger immunity against pertussis has been recorded in cases where the first dose of vaccination has been whole cell pertussis vaccine rather than the acellular vaccine. The discontinuace of the vaccine given at 18 months of age may have reduced immunity and caused higher incidence in children aged 9 -14 years of age. So, every time an alteration is made to the vaccine schedule, it may be a while before repercussions are felt in the public domain.

The need to reassess the efficacy of vaccines

Virulence of strains of circulating Bordetella pertussis has occurred due to genetic changes that have been caused in the post-vaccination period, that is an emergence of mutant strains that can escape and survive vaccines. According to Carbonetti (3) new vaccines have been designed by incorporation of antigens such as, pertussis toxin (ptx), Fha (fha), pertactin (prn), and Fim (fim) and it is genes encoding these antigens are undergoing evolution while antigens that are not part of the vaccine arsenal have remained unchanged.

With a high number notifications of pertussis through 2016 and 2017, the Health department has to work with the health professionals and increase public awareness about the disease, the age-groups at risk, the need for vaccination and importance of antenatal vaccination in protection of the neonates. The Immunise Australia website recommends vaccination of health workers and adults caring for infants and children below the age of five is an important step in reducing the number of cases of whooping cough (5). Educating public about how to watch out for symptoms specific to whooping cough and the need to isolate children from people who are suffering from cough are important steps in controlling the spread of infection. Educating the maternity health care staff about the importance of vaccination, distribution of stickers that remind the staff and parents about the vaccination schedule can help reduce infections. Stickers that warn parents and remind parents about the importance of vaccination against pertussis can be placed on the immunisation record book of each newborn in the state of New South Wales. According to the health department at New South Wales, emphasis on receiving the booster vaccines for pertussis at age 4, 12 and 50 years of age should be given more publicity to reduce incidence (14).

Studies have found that almost all precautionary measures directed at reducing the incidence of pertussis among populations revolve around the vaccination program. It is possible to reduce the risk of pertussis among neonates through vaccination of expectant mothers during the third trimester. According to the New South Wales Health Department (14) the antenatal pertussis vaccination program is one of the new measures that have been adopted to reduce the incidence of pertussis among new borns. This mode offers passive protection to the neonates through transfer of high titres of pertussis antibodies via the maternal placental route. It is recommended that family members or carers who come in close contact with infants take a booster vaccine for pertussis, under the cocooning strategy. Donnan et al. (2) found that upon an assessment of the community, there was high awareness about the cocooning strategy but uptake of the vaccine among adults remains low. There is another problem with current vaccines, as time passes after a vaccine dose, the immunity wanes with time and increase in age, making the children increasingly susceptible to infection. The Department of Health reports that although vaccinated children suffer from milder forms of the disease, the infection poses a risk to the infants who are in their vicinity and have still not been vaccinated (14).

Strategies to control pertussis outbreaks

Prevention through vaccines remains the main strategy for controlling the incidence of pertussis. Several doubts were cast on the whole cell vaccine in the 1970s. According to Skerry et al. (15) more basic research has helped to understand the pathogenesis and novel therapeutic targets are being studied in animal models.

Introduction of a third generation vaccine that could be an attenuated vaccine, a safe whole cell vaccine with fewer side effects than before or an acellular vaccine that has a newer set of adjuvants and above all, a vaccine that provides long lasting immunity is the need of current times. However, vaccine development and release for public use is a time consuming process and hence is a few years away, as stated by the Australian department of health. According to Mills et al. (16) a switch from alum to other potent adjuvants may increase the cell-mediated immunity of vaccines.

According to the Australian Department of Health (17) serological testing among adult patients and the use of PCR based diagnosis for pertussis has increased notifications and a clear picture of the extent of the epidemic among different age-groups has emerged.

Conclusion

In conclusion, the statistics for New South Wales make it amply clear that the region is affected by the resurgence of whooping cough and that there is a considerable disease burden among the different age-groups of the population. The occurrence of the disease among adolescents is an indication that the acellular pertussis vaccine used from the year 1999 does not protect the immunised individuals for long and the immunity begins to wane after a while. The acellular vaccine had replaced the whole cell pertussis vaccine that caused side effects but provided better immunity for a long time. As part of the public health strategy to tackle the problem of resurgence involves the introduction of a pertussis vaccine to pregnant mothers during  the third trimester. Booster doses by adults who take care of infants, including family members and healthcare workers in maternity wards can protect infants who are yet to receive vaccination. Awareness among maternity hospital staff about the vaccine regimen and reminders to parents about immunisation programs for infants can control the incidence of pertussis among the new-borns. A new vaccine that is more long lasting and contains new antigens that the pathogen has evolved to circumvent immunization needs to be developed. Together, these strategies can reduce incidents of pertussis cases and prevent outbreaks in future. 

Vaccination schedules and the importance of booster vaccines

References

Sheridan S, Frith K, Snelling T, Grimwood K, McIntyre P, Lambert S. Waning vaccine immunity in teenagers primed with whole cell and acellular pertussis vaccine: recent epidemiology. Expert review of vaccines. 2014;13(9):1081-106.

2. Donnan E, Fielding J, Rowe S, Franklin L, Vally L. A cross sectional survey of attitudes, awareness and uptake of the parental pertussis booster vaccine as part of a cocooning strategy, Victoria, Australia. BMC Public Health. 2013;13(676):doi: 10.1186/1471-2458-13-676.

Carbonetti N. Bordetella pertussis: new concepts in pathogenesis and treatment. Current Opinion in Infectious Diseases. 2016;29(3):287-294. 11. Department of Health | Pertussis control in Australia – the current state of play [Internet]. Health.gov.au. 2017 [cited 2 October 2017]. Available from: https://www.health.gov.au/internet/main/publishing.nsf/content/cda-cdi3803a.htm

Syed M. Choosing from Whole Cell and Acellular Pertussis Vaccines-Dilemma for the Developing Countries. Iranian Journal of Public Health. 2017;46(2):272-273.

Immunise.health.gov.au. | The Australian Immunisation Handbook Immunise.health.gov.au 2017 [ cited 2 October 2017]. Available from https://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-12.

Gabutti, G, & Rota, MC. Pertussis: review of disease epidemiology worldwide and in Italy. International Journal of Environmental Research and Public Health,. 2012;9(12):4626-4638.

Karki S, McIntyre P, Newall A, MacIntyre, C, Banks E, Liu B. Risk factors for pertussis hospitalizations in Australians aged 45 years and over: A population based nested case-control study. Vaccine. 2015;33(42):5647-53.

Roswell, A, Spokes, P, Gilmour, R. New South Wales annual vaccine-preventable disease report, 2012. Western Pacific Surveillnce and Response Journal,. 2014; WPSAR, 5(2):15-22.

Gaillard M, Bottero D, Moreno G, Rumbo M, Hozbor D. Strategies and new developments to control pertussis, an actual health problem. Pathogens and Disease. 2015;73(8):ftv059.

Clark C. Changing pertussis epidemiology: everything old is new again. The journal of infectious diseases. 2014;209(7):978-981.

Quinn H, Mahajan D, Heusten L, Campbell P, Menzies R, Gilbert G et al. The seroepidemiology of pertussis in NSW: fluctuating immunity profiles related to changes in vaccination schedules. NSW Public Health Bulletin. 2011;22:224-229.

Liko J, Robison S, Cieslak P. Priming with whole-cell versus acellular pertussis vaccine. New England Journal of Medicine,. 2013;368:581-582.

Sheridan S, Ware R, Grimwood K, Lambert S. Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients is not confounded by age or receipt of booster-doses. Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients is not confounded by age or receipt of booster-doses vaccine. 2015;33(39):5027-30.

Pertussis-Vaccination-2015.pdf [Internet]. https://www.health.nsw.gov.au:. 2015 [cited 2 October 2017]. Available from: https://www.health.nsw.gov.au/Infectious/whoopingcough/Documents/Pertussis-Vaccination-2015.pdf

Skerry C, Scanlon K, Ardanuy J, Roberts D, Zhang L, Rosen H et al. Reduction of Pertussis Inflammatory Pathology by Therapeutic Treatment With Sphingosine-1-Phosphate Receptor Ligands by a Pertussis Toxin-Insensitive Mechanism. The Journal of Infectious Diseases,. 2017;215(2):278-286.

Mills K, Ross P, Allen A, Wilk M. Do we need a new vaccine to control the re-emergence of pertussis?. Trends in Microbiology,. 2014;22(2):49-52.

Department of Health | Pertussis control in Australia – the current state of play [Internet]. Health.gov.au. 2017 [cited 2 October 2017]. Available from: https://www.health.gov.au/internet/main/publishing.nsf/content/cda-cdi3803a.htm

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