February 7th 2015
Measles is a serious viral respiratory infection which remains a major cause of morbidity and mortality in developing countries. It’s most serious complications include measles encephalitis and a rare condition called subacute sclerosing panencephalitis (SSPE). In 2012, there were an estimated 122,000 deaths from measles globally. There is a safe and effective live, attenuated vaccine, most often given in a combination with mumps and rubella vaccines as MMR. The WHO has a goal of eradication of measles, but it continues to cause epidemics worldwide, not just in developing countries.
Epidemics have been in the news in recent years in developed countries with good immunization programs. The latest outbreak affecting a country with high vaccination rates is the Disneyland outbreak, which has resulted in more than 100 cases of measles in more than 14 states of the US.(1,2) It is thought the outbreak originated from an overseas visitor, and most cases were unvaccinated.
In Australia the largest measles outbreak since 1997 occurred in 2012, with 168 cases in Western and South Western Sydney.(3) Some have argued that low vaccination rates are to blame,(4) but this misses the complexity of measles transmission, and that fact that measles epidemics can occur despite high rates of vaccination and despite the vaccine itself having high efficacy (>90%). Much fuss is being made about poor vaccination rates in children in the US - however, overall vaccination rates are 92% in the US and similarly high in Australia. In the affected areas in Sydney, measles vaccination rates according to the Australian Childhood Vaccination Register were over 95%, but the register only captures children under the age of 7 registered in Australia. Furthermore, measles is declared eliminated in both the US and Australia.(1,5)
Elimination vs eradication
Elimination refers to the end of transmission within the resident population of a particular country, whereas eradication is a global phenomenon. The eradicability of an infection depends on several factors, including the reproductive number (the number of secondary cases arising from an index case), and whether the infection has an animal host. Infections such as influenza and Ebola, for example, affect various animals as well as humans, which makes eradication difficult, if not impossible. The reproductive number, R, determines the required herd immunity (the required proportion of the population with immunity to prevent transmission in the population). Measles is technically eradicable, as it’s only host is humans. However, it has a very high reproductive number, estimated to be around 15, making it one of the most infectious viruses known. The graph below shows the relationship of the reproductive number, R (on the x axis) to the required herd immunity, h, on the Y axis, and illustrates the case of smallpox compared to measles. Smallpox, which had a much lower R than measles, could be eliminated (and eradicated) by achieving immunity (by vaccination) of about 60% of the population, whereas measles, having a much higher R, requires in excess of 93% of the population to be immune to prevent transmission. Whilst measles elimination in countries has been achieved, eradicating measles globally, therefore (a goal of the WHO) will be a much harder task than eradicating smallpox.
Why does measles occur when vaccination rates are high?
Why then, do epidemics occur in countries which have eliminated indigenous transmission of measles, in the presence of high measles vaccination rates?
Whilst outbreaks of measles do occur in communities of vaccine refusers, such the Ohio outbreak of 383 cases in 2014,(1) mostly measles is an imported infection in countries such as the US and Australia. That is, it does not arise in the country, but is introduced into the country from someone coming from outside. This is confirmed by genotyping studies, which show that such outbreaks are caused by imported strains of measles. Most commonly it is imported through travellers. In the 2012 Sydney epidemic, pockets of under-vaccinated Pacific Islander communities were disproportionately represented among cases. (3) However, once introduced into the community, non-immigrant people were also affected.(3) Surveillance of the child hood vaccination register would not have flagged this part of Sydney as being at risk for a measles epidemic, because of high vaccination rates among registered children under 7. Many cases of measles are imported through adolescents or young adults, who would not be captured on the immunization register.
In Australia, measles vaccination is given as a 2 dose schedule at 12 months and 4 years; in the US, from 12-15 months and then 4-6 years. The Australian measles cotrol campaign in 1997-1998 included moving the 2nd dose of vaccine to 4 years of age and simultaneously rolling out a catch-up vaccination program for adolescents. This resulted in a large decline in measles in Australia in the ensuing decade, as shown below
However, we have showed that overall vaccination coverage rates are only part of the picture, and that large variations can exist in vaccine uptake between small geographic areas.(6,7) Small geographic areas which are vulnerable to outbreaks can be predicted using mathematical modeling. (8) This is useful for identifying areas where additional interventions may be needed. We have shown that there is an increasing risk future of measles outbreaks in Australia, particularly in NSW and Queensland, and the modeling predictions correspond with regions where outbreaks have actually been observed.(8) The presence of under-vaccinated pockets of the population gives rise to ideal conditions for an epidemic, should measles be imported into the country, and this is exactly what we have seen.
However, doing such modelling depends on having good vaccine coverage estimates. Most measles epidemics in countries such as Australia and the US are imported, and as such, risk will not necessarily be detected by vaccine coverage surveillance of the local population. In the 2012 Sydney outbreaks, for example, vaccination rates were higher than the national average in the affected areas.(3) Instead, highly mobile groups of Pacific Islander people moving between New Zealand and Australia, and under the radar for routine vaccination coverage measurements, were thought to have introduced the epidemic.(3) Some were children, but some were young adults. In response, a high school vaccination campaign and other targeted efforts were conducted in the affected area. However, this is a reactive, stop-gap measure, and does not address the root cause of ongoing epidemics, which is under-vaccinated groups of migrants – people who have missed out on routine vaccines and who may be either children or adults.
The need for systematic catch up vaccination and a whole-of life vaccination register
In Australia, there is no universal mechanism for identifying such people at risk (such as a whole of life register with country of birth recorded). Certain refugee health services provide vaccination, but these are ad hoc and vary by jurisdiction. In 2013 we brought together for the first time, all stakeholders in traveller, migrant and refugee immunization through the NHMRC Centre of Research ExcellenceImmunisation in Under Studied and Special Risk Populations.(10) The report arising (attached to the blog if you wish to download it - see below) from this identified that people of migrant or refugee backgrounds are at greater risk of being under-immunised, and that this is a gap in disease control.(11) The key recommendations of that report were:
· Articulation of specific gaps in immunisation policy for refugee and migrants, the most important being funding of universal catch-up immunisation.
· Explicitly addressing the immunisation needs of migrants and refugees in the implementation of the National Immunisation Strategy for Australia 2013-2018;
· Funding of vaccines for catch-up immunisation for recently arrived migrants and refugees;
· Renewed advocacy for a whole-of-life immunisation register in Australia, to enable primary care providers to identify people of any age of refugee or migrant background and evaluate their immunisation needs;
· Improvements in the identification of refugee and migrants in hospital, primary health and population health databases to identify risk groups for under-immunisation or infectious diseases and to enable targeted health education and health care delivery;
· Improvements to refugee service coordination and support for immunisation delivery in the primary care sector; and
· Community engagement and education to improve immunisation coverage.
Waning vaccine immunity?
There is also the issue of waning of vaccine immunity, which has not been recognized until recently. In the past, when large proportions of the population had immunity to measles conferred from natural infection, it was assumed that immunity conferred by measles vaccine was lifelong. Today in countries like Australia, the proportion of people with naturally induced immunity (mainly older people) is much lower than 20 years ago. There is now evidence that, despite good efficacy, waning of vaccine immunity can occur, even after 2 doses. (12) This is an unfolding story, and more evidence is needed, but waning may actually threaten elimination status in countries like Australia, if a sufficiently large proportion of the vaccinated population become susceptible to measles over time. Different dosing schedules with varying spacing between doses, and consideration of an additional dose (3 vs 2 doses) will be questions that will need to be asked in the future.
While cases of measles can and will continue to be imported through travellers into countries which have achieved elimination status, the under-vaccination of pockets of migrant groups can be readily addressed by following the recommendations above. This would have a meaningful impact on the control of measles. In Australia, we continue to see outbreaks in 2015 in several states such as Queensland and Western Australia,(13,14) but also in Victoria and the ACT (15,16). In the meanwhile, measles will not be easily eradicable. For countries like Australia, the most pressing disease control priority should be finding a mechanism to provide universal catch-up vaccination for migrants.
About the author: Professor Raina MacIntyre has been studying vaccines and vaccine-preventable diseases for over 20 years, and was the first person to do small area modelling predictions of measles epidemics in Australia.
1. McCarthy, M. Measles cases exceed 100 in US outbreak. MJ 2015; 350:h622 http://www.bmj.com/content/350/bmj.h622.long
3. Najjar,Z, Hope, K, Clark, P, Nguyen, O, Rosewell, A and Conaty, S. Sustained outbreak of measles in New South Wales, 2012: risks for measles elimination in Australia. Western Pac Surveill Response J. 2015 Jan 30;5(1):14-20. doi: 10.5365/WPSAR.2013.4.4.002. eCollection 2014 Jan-Mar. http://ojs.wpro.who.int/ojs/index.php/wpsar/article/view/220/370
5. Heywood A, Gidding H, Riddell M, McIntyre PB, MacIntyre CR, Kelly H,. Elimination of endemic measles transmission in Australia. Bulletin of the World Health Organization. 2009 Jan;87(1):64-71. http://www.scielosp.org/scielo.php?pid=S0042-96862009000100015&script=sci_arttext
6. MacIntyre CR, Hull B, Burgess MA, Gay NJ. Measles control in NSW Divisions of General Practice. NSW Public Health Bulletin. 2003; 14:13-17
7. MacIntyre CR, Gay NJ, Gidding H, Hull B, Gilbert GL, McIntyre P. A mathematical model to measure the impact of the Measles Control Campaign on the potential for measles transmission in Australia. Int J Infect Dis. 2002 Dec;6(4):277-81. http://www.ncbi.nlm.nih.gov/pubmed/12718821
8. Wood JG, Heywood AE, Menzies RI, McIntyre PB, MacIntyre CR. Predicting localised measles outbreak potential in Australia. Vaccine. 2015 Jan 22. pii: S0264-410X(14)01726-5. doi: 10.1016/j.vaccine.2014.12.071. [Epub ahead of print] http://www.sciencedirect.com/science/article/pii/S0264410X14017265
11. Protecting Australia – closing the gap in immunisation for migrants and refugees. Proceedings from a stakeholder work. August 2013. http://creimmunisation.com.au/sites/default/files/newsevents/events/Proceedings_CREMigrantRefugeeWorkshop.pdf