There have been, in the last 20 years, natural, or perhaps unnatural,  experiments that have helped shed light on the efficacy of vaccines.  Many societies, for reason of political unrest, religion, or a lack of understanding of science and medicine have seen the rates of vaccination decline and with that decline, an increase in the cases of vaccine preventable diseases

Infectious disease spread in populations is not simple.  Hygiene, nutrition, access to health care, and education all play a role in the spread of communicable diseases.  Vaccines have been critical in driving the rates of vaccine preventable illnesses to almost zero, but they are not the only intervention in our armamentarium.

The Soviet Experience.

When the Soviet Union fell apart in the 1980’s, its medical system followed.  Some totalitarian states have been especially good at getting their populations vaccinated.  However, after the fall of Communism, the vaccination rates declined and the diseases they prevented surged.

“...Diphtheria morbidity in Moscow in 1958-1999 are presented. The last epidemic which started at the end of the 1980s and reached its peak in 1994, giving a 59-fold rise in morbidity in comparison with the pre-epidemic period, is characterized in detail. During the epidemic 12,267 persons fell ill, 454 of them died (mortality rate was 4%). Having started in Moscow, the epidemic gradually spread not only over the territory of Russia, but also over some other republics of the former Soviet Union (Ukraine, Belarus, etc.). Possible causes of this epidemic emergency are considered. The ever increasing share of adult population among persons affected by the epidemic (75%) is noted. The infection adults is characterized by severity of clinical manifestations and increased morbidity among adults, is shown. Under complicated social and economic conditions (crisis situation) the increase of groups of high risk which included unemployed adults of working age, retirees as well as socially non-adapted persons, was registered.”

“The massive diphtheria epidemic in the former Soviet Union provides important lessons for all diphtheria immunization programs: It is important to achieve a high level of childhood immunization, maintain immunity against diphtheria in older age groups, and use anti-epidemic measures, including immunization, to control epidemics in the early phase. The immunization coverage among children should be at least 90%.”

“Failure to achieve high levels of immunity among children contributed to the epidemic of diphtheria that occurred in the Russian Federation during the 1990s. A major factor in this failure was the extensive list of contraindications to vaccination that was in use throughout the countries of the former Soviet Union. In 1980, the Ministry of Health (MOH) of the Soviet Union adopted an extensive list of contraindications for use of the diphtheria-tetanus toxoids-pertussis (DTP) vaccine. In 1994, the MOH of the Russian Federation revised the list of contraindications to vaccination to be largely in accord with World Health Organization recommendations. Since then, age-appropriate vaccination coverage has increased markedly: In 1996, DTP3 coverage among children 12 months of age had increased to 87% from 60% in 1990. ”

In the end the only way diphtheria came under control was by increasing vaccination rates.

Similar problems were seen with pertussis.

“The aim of the current study was to assess the epidemiological situation concerning the emergence of a pertussis outbreak, as well as potential contributing factors and vaccine effectiveness. A retrospective epidemiological description and an analysis of the outbreak among students were performed. The basic school in Adavere had a total of 150 students in 2003. Of these, 54 cases of pertussis, with median age 12 y, all corresponding to clinical case definition, were identified with an attack rate of 36%. Regarding confirmation of the diagnosis, out of all clinical cases, 18 were confirmed by laboratory testing (2 by isolation of B. pertussis and 16 serologically based on single sera) and 36 with epidemiological linkage only. Of all the students with pertussis, 35 (65%) had received 4 doses and 6 (11%) 3 doses of DTwP vaccine; 13 (24%) students had received fewer than 3 doses or were unvaccinated. The contributing factors in generating this outbreak were close epidemiological contacts, late identification of pertussis diagnosis in the primary, secondary and later cases, as well as a too late initiated active surveillance. In this outbreak, low vaccine effectiveness and low vaccination coverage also played an important role. ”

As well as rubella and measles outbreaks.

“The data suggest that rubella is endemic in Kyrgyzstan with periodic epidemics every 3-5 years. From January to August 2001, 1936 rubella case-patients were reported from Bishkek City and Chui Oblast; 242 were tested and 176 (73%) were laboratory confirmed. Most case-patients were 3-14 years old. However, the incidence rate per 100,000 among persons aged 15-35 years increased >/=40-fold from 1 in 2000 to 41 in 2001. These findings highlight the importance of introducing rubella-containing vaccine in conjunction with measles elimination activities. ”

While the cause of the outbreaks was multi-factorial, it is interesting how rapidly these infections returned with only a small decline in herd immunity. The control of these diseases was expensive and resource intensive in countries with little economic reserve. These outbreaks represent a subset of the countries that were plagued by vaccine preventable infections after the disintegration of the USSR.  Pubmed (to my mind a verb like google) almost any of the states of the former USSR and you will find other examples of the outbreaks from the decline in the use of vaccines.

Polio

Polio was almost eradicated in Africa.  So close you almost wanted to close down the crutch factories.  Then, in the 2003, religious leaders in Northern Nigeria banned the polio vaccine under the belief that the vaccine was being used as a vector by the West to spread both HIV and sterility, specifically targeting Muslims.  And you thought formaldehyde in the vaccine was bad.

“In northern Nigeria in 2003, the political and religious leaders of Kano, Zamfara, and Kaduna states brought the immunization campaign to a halt by calling on parents not to allow their children to be immunized. These leaders argued that the vaccine could be contaminated with anti-fertility agents (estradiol hormone), HIV, and cancerous agents.”

Even though the ban lasted a mere 11 months, Nigeria saw a resurgence in polio.  Again, we remain at the edge of the infectious precipice and it takes only a tiny push to send people over the edge.    Nigeria also served as a reservoir for polio that subsequently spread to 15 other African countries and beyond.

“After the 1988 World Health Assembly resolution to eradicate poliomyelitis globally,  the number of polio-endemic countries decreased from 125 in 1988 to six (Afghanistan, Egypt, India, Niger, Nigeria, and Pakistan) in 2003 . However, during 2002–2005, a total of 21 previously polio-free countries were affected by importations of wild poliovirus (WPV) type 1 from the six remaining countries (primarily Nigeria) where WPV was endemic.”

Polio is coming under control in Nigeria with increased vaccination, with case falling from 1,129 in 2006 to 285 in 2007. Remember that most children who get ill with the polio virus do not develop clinical polio,  a complication of about 1% of the infections.  So 258 cases represent the tip of the polio iceberg (will this metaphor die in the next 100 years? And if so, what will be the replacement be in a world without icebergs?).

The damage, however, has been done and even though education programs have increased the utilization of the polio vaccine, there are still those who will not let their child receive the vaccine due to fears of contamination with birth control. And this in a society without internet connections.  Fear is much more contagious than infection and harder to prevent or treat. As a result of ongoing fear of vaccines, cases of wild type polio continue in Northern Nigeria with 258 cases in 2009, primarily in the Muslim community.

Most of the world uses the live-attenuated oral polio vaccine as it results in a better response.  The problem with live-attenuated viruses, like any virus, is it likes to mutate when it multiplies.  If the immunity to the virus is high in a population and the hosts are immunologically sound, a live vaccine has no place to go even if it mutates.  It requires non-immune hosts to perpetuate.  Herd immunity keeps any mutated strain at bay.  However, if there are populations whose immune function is compromised by poor nutrition or HIV and there are large numbers of unvaccinated people in the community, then odd things may happen. Vaccine strains can spread.  Because of the perfect storm in Nigeria, the vaccine strain was able to perpetuate in a vulnerable community and now there is a mutated strain of polio vaccine that is causing disease in Nigeria.  The vaccine strain escaped and, thanks to a little evolution, changed to have increased virulence.  This would have been much less likely to occur if the population had maintained their herd immunity.

“The number of polio cases caused by the vaccine has doubled: 124 children have so far been paralyzed, compared to 62 in 2008, out of about 42 million children vaccinated.  There have been at least 7 outbreaks in Nigeria from the vaccine strain.”

The point, and I cannot wait for some of the comments this little factoid will engender (not), is that vaccines work best when everyone participates, and as soon as compliance slips even a little, the replicative and mutational capacity of germs guarantees that they may evolve and escape into the wild.

And even stranger things have happened.

“The biological properties of poxvirus isolates from skin lesions on dairy cows and milkers during recent exanthem episodes in Cantagalo County, Rio de Janeiro State, Brazil, were more like vaccinia virus (VV) than cowpox virus. PCR amplification of the hemagglutinin (HA) gene substantiated the isolate classification as an Old World orthopoxvirus, and alignment of the HA sequences with those of other orthopoxviruses indicated that all the isolates represented a single strain of VV, which we have designated Cantagalo virus (CTGV). HA sequences of the Brazilian smallpox vaccine strain (VV-IOC), used over 20 years ago, and CTGV showed 98.2% identity; phylogeny inference of CTGV, VV-IOC, and 12 VV strains placed VV-IOC and CTGV together in a distinct clade. Viral DNA restriction patterns and protein profiles showed a few differences between VV-IOC and CTGV. Together, the data suggested that CTGV may have derived from VV-IOC by persisting in an indigenous animal(s), accumulating polymorphisms, and now emerging in cattle and milkers as CTGV. CTGV may represent the first case of long-term persistence of vaccinia in the New World”

Of course, the West does not, yet, have a meltdown of the medical-industrial complex nor do we have religious leaders saying vaccines are designed to spread disease and sterility.  Our vaccines cause autism. Hah. Take that Nigeria. Still, we have our own problems with declining vaccination rates.

US  and Great Britain

H. influenzae is killing again.  There have been two mini-outbreaks in the US, one in Minnesota, with five cases and one death and another in Philadelphia, with 6 cases and 2 deaths.  In both outbreaks, the deaths were in unvaccinated children.

Measles has been on the upswing in Great Britain, in large part to a decrease in vaccination.

“The national average (of MMR) in Great Britain is 84 percent, but in some areas of London the vaccination rate hovers at a dangerously low 65 percent. Areas with vaccination rates that are consistently below 80 percent run a high risk of an outbreak.”

There have been over measles 1200 cases in Britain with one death.  At work one of the social workers has been collecting a three word sentence from everyone  that would be your legacy, three words you would want to be remembered by.  I chose “Left them laughing.”  Dr Wakefields may be “Let measles return.”

Measles is back in the US as well.

“During 2008, more measles cases were reported than in any other year since 1997. More than 90% of those infected had not been vaccinated, or their vaccination status was unknown. “

“The number of measles cases reported during January 1–July 31, 2008, is the highest year-to-date since 1996. This increase was not the result of a greater number of imported cases, but was the result of greater viral transmission after importation into the United States, leading to a greater number of importation-associated cases. These importation-associated cases have occurred largely among school-aged children who were eligible for vaccination but whose parents chose not to have them vaccinated.”

Mumps is also making a comeback in the US.  The index case acquired his disease in Great Britain (over 7900 cases) and brought it to the NE, another failure of homeland security.  Since

“January 29, 2010, a total of 1,521 cases had been reported, with onset dates from June 28, 2009, through January 29, 2010, a substantial increase from the 179 cases reported as of October 30, 2009 (1). The outbreak has remained confined primarily to the tradition-observant Jewish community, with <3% of cases occurring among persons outside the community. The largest percentage of cases (61%) has occurred among persons aged 7–18 years, and 76% of the patients are male. Among the patients for whom vaccination status was reported, 88% had received at least 1 dose of mumps-containing vaccine, and 75% had received 2 doses. This is the largest mumps outbreak that has occurred in the United States since 2006.”

Letting vaccination rates decine is associated with increasing disease from vaccine preventable illnesses in part due to a decline in herd immunity.  A recent study in Jama demonstrated the converse: increasing vaccination rates leads to decreased disease in unvaccinated populations.

They vaccinated the children of 25 Hutterite colonies with the influenza vaccine and the children of  another 24 colonies with the hepatitis A vaccine and then looked at the rates of PCR proven influenza in those that did not get the vaccine.  In the influenza group, 39 (3.1%) of those who did not get the vaccine developed influenza while 80 (7.6%) of the unvaccinated in the hepatitis A vaccine groups developed influenza.  This  suggested the overall effectiveness of the influenza vaccine in protecting those who did not get the vaccine, herd immunity, at 60%.  Herd immunity, it seems works. And do let Dr. Jefferson know that the rates of influenza in the influenza colonies was  about half that of the hepatitis A vaccinated colonies.

“Immunizing children and adolescents with inactivated influenza vaccine significantly protected unimmunized residents of rural communities against influenza.”

So vaccines work.  They prevent disease in those who get the vaccine and they can prevent disease those that do not or can not get vaccinated.

Unfortunately, fear of vaccines is increasing in the US .

“Our study indicates that a disturbingly high proportion of parents, > 1 in 5, continue to believe that some vaccines cause autism in otherwise healthy children”

Despite at least 15 studies that show no link between autism and vaccines (except the recent study from Poland that suggested the MMR may protect against autism), the unwarranted fear persists. Irrational fear, as Nigeria has demonstrated, is hard to remove.

If I were convinced that vaccines, despite all the evidence to the contrary,  were the cause of autism or other disease s, and I were to read the that fear of vaccines was up and vaccine use was down, I hope  I would not gloat.  In medicine I am used to bad outcomes occurring as a consequence of what I know to be the correct course of action.  No good deed ever goes unpunished in health care.  I would not be proud that my actions have lead to an increase in morbidity and mortality in children.  I would hope it would be a bittersweet, sad victory, since my success at burning down the vaccine house will take many children with it.  If vaccine rates fall further, some may have the legacy of “Helped plagues return.”