Saturday, February 21, 2015

Measles outbreak: Sue the Anti Vax group.


Infectious disease represents a much lesser threat than what it used to be just a few decades ago. About half a century ago, cases such as Polio or Small pox was just so common. The technique of vaccination has brought in so much relief to the world population, that some of the nightmare infections, is now a matter of history. One of the classical example is small pox. Polio is the next obvious contender of the list and a polio free world would have been a reality already, if it is not for a bunch of idiots calling themselves "Anti-vaccine group". There is a bigger worry that has now hit the public, a proof of concept that the public health has been endangered by this group by acting intentionally on anti-scientific grounds. Yes you are right- I'm talking about "Measles outbreak". US which was declared as "Measles free" in 2000 is now seeing an upsurge of infections which is correlated with lack of vaccination coverage. The official evidence of what I just talked about.

Fig 1: Measles Virus. Source

Measles virus (MV) is an enveloped single-stranded, negative-sense, RNA virus of the genus Morbillivirus within the family Paramyxoviridae. Humans are the natural hosts of the virus with no known animal reservoirs thus making them an ideal case for eradication. The structure of MV is shown in Fig 1. The most important part of the structure is its glycoproteins- (i)F (fusion) protein, which helps in fusion of virus and host cell membranes, viral penetration, and haemolysis (ii) H (haemagglutinin) protein, which is responsible for binding of virus to the cells. As of now there are 8 clades of measles (designated A–H) and subtypes are designed with numerals. The strains are designated as A2, B1 etc. There are a total of 23 subtypes known.

The receptor in human cell for the binding of H protein are CD46 and CD150 (SLAM; signalling lymphocyte activation molecule) CD46 is a complement regulatory molecule expressed on all nucleated cells in humans. SLAM is expressed on activated T and B lymphocytes and antigen-presenting cells. Antibodies against the H protein are neutralizing antibodies.

In brief, this is what happens in the measles infection. The virus is inhaled and infects the epithelial cells in nasal tract. The virus replication continues and reaches the lymph nodes. From there there is a primary viremia. Subsequently, it spreads into multiple tissues and secondary viremia ensues, with infection established in skin and reticulo-endothelial tissues. The rashes developed at this time is referred to as the Koplik's spots. The infection subsides with the appearance of antibodies and immunity is protective for lifetime. There is some clue that this traditional thought is not right and new challenging works have been published. As per the model published by Leonard etal the virus is carried primarily by lymphatic immune cells and are directly carried to the reticuloendothelial system where it further replicates. It doesn't replicate in nasal epithelial cells. Despite being an infection passed through the airway, the infection is largely considered as an infection of immune system. This is consistent with the fact that the receptors for virus are predominantly seen in immune cells.

Subacute sclerosing panencephalitis (SSPE) is a progressive, brain disorder which occurs post measles infection and seen only in people who have not been vaccinated. The average number of cases reported is less than 15 cases per million. The neurotropism of the virus is not well understood, though studies have been performed in hamster models. 

Fig 2: R0 values.
One of the most important factors that determine the mathematical predictions and ability of outbreak, is based on a measure called as R0. R0, is an epidemiological parameter in infectious disease, which basically means basic reproduction number/ rate. It is the number of people who transmit the infection from one sick person, on average, in an outbreak, in other word "contagiousness". It should be noted that R0 represents the potential for transmission in a totally susceptible population and hence does not depend on the level of susceptibility. That means R0 will not change for a given infectious disease despite vaccination. But by vaccinating the "Susceptible population" number can be reduced which leads to decline in number of infected. In other words "Herd immunity". The R0 for MV is one of the highest in infectious diseases. For comparison I have shown the R0 for some common viral infections. The R0 for MV is 12- 18. That means Every individual case can infect upto a maximum of 18 fresh new susceptible cases. That means, you need to vaccinate at least 80% of the population to achieve a good cover. The best performing vaccine is a triple vaccine called as MMR. It contains measles, mumps, and rubella (German measles). 

Fig 3: Increase in number of measles cases
The measles vaccination program has been a highly successful camp at least in the US. The country was declared as Measles free and cases would pop up as imported cases. However, the vaccine coverage has decreased slowly. It has been estimated that from a loss of coverage of less than 2% in 2000 the current coverage has dropped to more than 80%. As given in nature news "And by 2013, the proportion of eligible children who had been vaccinated had dropped by 2% since 2004, to 91%". A rough idea of the trend can be inferred from the Fig 3, cases per year in US based on CDC data. 

What leads the parents to take a decision of not vaccinating the child? The discredited study of Wakefield published in lancet, 1998 had made a statement that vaccination causes autism!! Of course the study was biased and probably intentionally fabricated to produce a result making headlines. An excellent post on the whole story is posted in the Huffington post (Link). Ever since this has been studied in great deal and shown not to be the case. However, it has been hard to convince people. There is a great post explaining why it is difficult to debunk certain facts (Link).

The whole scenario has reached a tipping point. The current upsurge of cases has been attributed to parents who have decided not to vaccinate. Interestingly famous peoples involved in anti vaccine campaign have suddenly backed off. In a news feed by BMJ reads so "The instructor of a first year health course at Queen’s University in Kingston, Ontario, has taken a leave of absence after local media reported that she was teaching antivaccine material .." I wonder how could the person have become a professor in first place. Moreover, parents of infected child have now come up strongly against the people who don't consider vaccination.

The Disneyland outbreak has finally provided a strong case to the public they are being led on the wrong pathway. People have questioned that why has this come so late. Let me quickly consider an example. The following quote of incompetence by an anti-vaccine person, “I’m a big fan of what’s called paleo-nutrition, so our children eat foods that our ancestors have been eating for millions of years, that’s the best way to protect.” (Source). What the person forgot is our ancestors had suffered enough of measles and vaccination protected us. The fact that we have been vaccinated for so many infections and protected from it has led us to forget the times when this luxury was not available.

I think it is time public rise from the mistakes and correct themselves, and not punish the children for whom health is a basic human right.
Gay NJ (2004). The theory of measles elimination: implications for the design of elimination strategies. The Journal of infectious diseases, 189 Suppl 1 PMID: 15106086

Moss WJ, & Griffin DE (2006). Global measles elimination. Nature reviews. Microbiology, 4 (12), 900-8 PMID: 17088933

Leonard VH, Sinn PL, Hodge G, Miest T, Devaux P, Oezguen N, Braun W, McCray PB Jr, McChesney MB, & Cattaneo R (2008). Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. The Journal of clinical investigation, 118 (7), 2448-58 PMID: 18568079

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