By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, University of California, San Francisco; Chief of Epidemiology, San Ramon (CA) Regional Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

Immediate Improvement in Childhood Vaccination

The largest epidemic of whooping cough in seven decades occurred in California from 2010 to 2014. In 2014, the California Department of Public Health (CDPH) reported a peak number of 11,203 cases of pertussis, 456 of which required hospitalization (26% in intensive care); 278 cases were in small infants younger than 4 months of age, three of whom died. One of the worst pockets of sustained pertussis infection was in and around Palo Alto, CA home of Silicon Valley entrepreneurs and vaccine deniers.

Research has shown that higher per capita income is linked to lower childhood vaccine rates. Previously, Californians were allowed a “personal belief” exemption from childhood vaccination, which effectively created pockets of unvaccinated children throughout the state, especially in more affluent areas. Exercising that right in California was as simple as checking the box on your kid’s school paperwork with no discussion as to the implications for the child or the community. By 2014, fully 800 schools in California reported non-vaccination rates of 8% or greater effectively, those schools lacked herd immunity. In reviewing California school system reportable vaccine rates for 2014, some school systems reported 100% measles, mumps, rubella (MMR) vaccine coverage of their students, while one school reported that only 43.5% of their kids had received MMR. The personal belief exemption was used for 34.8% of their children. Even more startling, one school reported that only 22.7% of their kids had received MMR, and 68.2% of children were exempt for personal belief.

These pockets of unvaccinated children can be linked directly to the observed increase in cases of pertussis and measles. In a JAMA review of 1,416 reported measles cases in the United States from 2000 to 2015, 574 cases were unvaccinated. Seventy percent had claimed non-medical exemption. The measles outbreak at Disneyland in Anaheim, CA, in 2014-2015, which resulted in 125 measles infections, garnered significant media attention and helped to sway public opinion against the anti-vaccine movement. Of the 110 Californians infected with measles at Disneyland, 45% were unvaccinated, most for non-medical exemption. On any given day, only 86% of persons at Disneyland had received MMR well below the threshold required for herd immunity against measles infection. Imagine this figure when considering that about 44,000 people visit Disneyland every day.

Because of these outbreaks, public health officials lobbied the California State Legislature to remove the personal belief clause for vaccination of school-age children. The result of these efforts was Senate Bill 277, passed in June 2015, and which took effect in July 2016 just before the school year began. California SB 277 requires school-age children to receive 10 specific vaccinations before they can attend school or day care in California, and only medical exemption certified by a physician is permissible.

The result has been a welcome success. Already, improvement in vaccine rates in school-age children has been observed. In April 2017, CDPH reported that overall vaccine rates for kindergartners hit an all-time high this year, up from 92.8% in 2015-2016 to 95.6% for 2016-2017.2 That amount of 2.8% can make all the difference in terms of herd immunity, especially for an agent as contagious as measles. Despite these efforts, nine counties, all in northern California, still reported 2016-2017 kindergarten vaccine rates below 90% although this was an improvement from 2015-2016 when 20 counties reported sub-standard vaccine rates. A small number of children (0.6%) still are not vaccinated on entry to kindergarten based on a belief exemption provided by their parents before the legislation went into effect, although these children will be required to show proof of vaccination when they enter seventh grade.

The effect of these improved vaccine rates has been immediate and substantial: Pertussis rates in California have dropped from 29.3 cases per 100,000 population in 2014 to 1.6 cases per 100,000 population in 2016.

All 50 states allow for medical exemption to vaccination. Forty-eight states allow for some kind of religious exemption (not Mississippi nor West Virginia). As of August 2016, 18 states still allow for personal belief/philosophical exemption, although legislation is being introduced in many states to reduce or eliminate personal belief as an exemption to childhood vaccination.

Steven Novella, from the Science-Based Medicine website, reminds us that the U.S. Supreme Court ruled in 1944 in Prince v. Massachusetts that “the right to practice religion freely does not include liberty to expose the community or the child to communicable disease or the latter to ill health or death.” Politically, it has been difficult to eradicate religious exemption from vaccination, although there is no right of citizens to refuse vaccination. But the anti-vaccination effort continues a veto referendum to allow personal belief as an allowable exemption did not qualify for the California Nov. 8, 2016, ballot, but hundreds of parents have continued to lobby the state capital to repeal California SB 277. Parents also can circumvent the law by choosing to home school their children.

The outbreaks of pertussis in our community putting kids at risk or keeping some out of school for 25 days has gone a long way to changing many parents’ minds in our area. Suddenly, pertussis was a real disease, not just something you read about. But it’s important to remind parents that while vaccination may protect their child, it’s ultimately for the good of the community it protects all of us, especially the weak, the very young, and the elderly.

REFERENCES

  1. Phadke VK, Bednarczyk RA, Salmon DA, Omer SB. Association between vaccine refusal and vaccine-preventable diseases in the United States: A review of measles and pertussis. JAMA 2016;315:1149-1158.
  2. Adams JM. EdSource. California Kindergarten vaccination rates reach all time high in aftermath of new law. April 12, 2017. Available at: http://bit.ly/2hZrNTu. Accessed Aug. 14, 2017.

A Better Mosquito Trap

I have always wanted to be one of our county’s sentinel chicken mommies, but San Mateo County has too many takers, and I was told my neighborhood had too many of the “wrong” mosquitoes. For years, scientists have had to resort to the insensitive and labor-intensive process of bleeding sentinel chickens for arboviral infections, such as West Nile virus or, more recently, Eastern equine encephalitis virus in Alabama. Either that, or they hang old-fashioned bug traps in trees, and then an expert has to pick through all the trapped debris, moths, and bugs to find their quarry of interest for testing. But that may change soon.

Young scientists at Microsoft, working on Project Premonition, have designed a prototype “smart” bug catcher that may revolutionize our ability to monitor mosquito populations and mosquito-borne infections. The device is designed to identify and trap only a particular species of mosquito of interest, and ignore everything else. The prototype is constructed of sturdy plastic that can withstand wind and rain, and has 64 compartments, each with a tiny plastic door, stacked like a small high-rise apartment building. When an insect flies through, an infrared beam records the size and pattern of the shadows of the beating wings. The data are uploaded to the cloud, and the machine can literally teach itself which mosquito is desirable and the door snaps shut and which gnat is not. Whenever a mosquito is captured, the time of day, wind speed, temperature, and humidity are recorded.

Ten prototypes are being trialed in Houston this summer, and thus far the machines can capture the right mosquito with 90% accuracy. Insects can be readily collected and tested with the latest molecular techniques for the presence of Zika or any other virus of interest.


Can FMT Restore Gut Flora and Eliminate Resistant Pathogens?

SOURCE: Bilinski J, Grzesiowski P, Sorensen N, et al. Fecal microbiota transplantation in patients with blood disorders inhibits gut colonization with antibiotic-resistant bacteria: Results of a prospective, single-center study. Clin Infect Dis 2017;65:364-370.

Ever since the first case landed on our doorstep 24 months ago, our hospital has been vigorously screening at-risk admissions for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE). Thus far, we’ve identified nine people, including four travelers hospitalized in India within the previous six months (three with NDM+ Escherichia coli and one with NDM+ Klebsiella pneumoniae). Four people formed a cluster of suspected transmission of NDM-KP. One elderly Indian woman, returning from a wedding in India, was found to have been positive for NDM-resistant organisms in 2013 at an outside facility and, although her current tests were negative for carbapenemase-producers, she had four CRE organisms cultured from stool. Several patients required care at a local skilled nursing facility, where they were maintained in strict contact isolation, unable to join in group activities or go to the dining room. It is not known whether such individuals, once colonized, can ever “clear” the resistant organisms from the gut flora, nor whether there is a sufficiently sensitive method for guaranteeing clearance from the gut flora. But there may be hope for these individuals.

Researchers at the University of Warsaw have demonstrated successful clearance of multidrug-resistant organisms (MDRO) from fecal samples in 15 of 20 patients (75%) with hematologic malignancy or stem cell transplants using fecal transplant material. Many of the patients were neutropenic or severely immunosuppressed. Gut colonization included NDM-K. pneumoniae (n = 14), ESBL-E. coli (n = 11), and two patients each with carbapenem-resistant K. pneumoniae, ESBL-K. pneumoniae, Metallo beta-lactamase-Pseudomonas aeruginosa, carbapenem-resistant P. aeruginosa, as well as various other MDRO. Thirteen participants (65%) were colonized with two or more MDRO.

A total of 25 fecal microbiota transplantations (FMTs) were performed in 20 patients; one patient underwent three separate transplants. Fecal transplant material was obtained from screened donors and administered intra-duodenally via nasogastric tube. Patients fasted for 12 hours before the process, were administered polyethylene glycol, and given a proton pump inhibitor to diminish gastric acid. The first three patients received their FMT just once on one day, and subsequent FMT were performed over two consecutive days. Fecal samples were obtained at one week, one month, and six months and tested by both culture and quantitative PCR for polymerase resistance genes. These results were available for 24 transplants at one month, and 14 at six months.

Complete decolonization was achieved in 15 of the 20 participants (75%), including the individual with multiple attempts. However, none of the three individuals who received a single-day FMT treatment were cleared. In those patients with available fecal data, successful clearance was demonstrated with 15 of 24 transplants at one month (62%) and 13 of 14 transplants (93%) at six months. Most importantly, six of 10 patients with NDM-KP were decolonized, and 11 of 11 patients (100%) with ESBL-E. coli were cleared. Partial eradication of one of two or more organisms was demonstrated in several additional patients.

There was diminished success at clearance of MDRO in patients receiving antibacterials within seven days of their FMT (44%) compared with those not receiving antibacterials (79%). Two patients demonstrated recolonization with the same strain of MDRO after having tested negative at least once, and one patient died of septic shock from OXA-48-E. coli, which had been “cleared” from the gut on earlier testing.

It would be beneficial to see these study results repeated, possibly in a less immunosuppressed population. If this approach works, I will be thrilled, but suspect it may not be that easy either to decolonize an individual or demonstrate successful clearance. Since the sensitivity of culture and quantitative PCR is not yet known for this situation, repeated testing over time may reveal occult residual organism in some patients. But a better “test” would be to challenge such patients with broad-spectrum therapy and see what emerges under selective pressure. One limitation to this approach is that some of these patients may have chronic colonization at other sites, such as wounds, trachs, and urinary catheters, not amenable to decolonization.