Vaccines and measles: the debate has moved towards religion, freedom and the detection of sects. But is it fair?

http://www.derives-sectes.gouv.fr/sites/default/files/publications/francais/rapport_miviludes_2017_web_v2_0.pdf#page=118

This survey of the section of the French parliament Miviludes investigating groups and organizations to detect sects, posed more questions than it has provided answers based on evidence.
1/ is there measles epidemics in Switzerland after those cases in religious schools? Why is it only a French issue?
https://www.lematin.ch/monde/gamine-suisse-origine-rougeole-france/story/12925561

The debate is about the reliability of geographical data, their confrontation with virus typing and vaccination status

2/ The geographical data are not sufficient to identify the origin and the sequence of the outbreak.
For instance, CDC recommends:

Laboratory Testing

Collection of virologic and serologic specimens is recommended for every case.

Laboratory confirmation is essential for all outbreaks and all sporadic measles cases. Detection of measles-specific IgM antibody and measles RNA by real-time RT-PCR are the most common methods for confirmation of measles infection. Efforts should be made to obtain a serum sample and throat swab (or nasopharyngeal swab) from suspected cases at first contact. Urine samples may also contain virus and when feasible to do so, collection of both respiratory and urine samples can increase the likelihood of detecting virus. Staff at the CDC Measles Laboratory are available for consultation and can assist with confirmatory testing as needed for measles. For details on all types of specimens (serum, respiratory, urine) collection and transport, see the CDC Measles Lab website.

Because measles is a rare disease in the United States, even with the excellent laboratory tests available, false positive results for measles IgM will occur. To minimize the problem of false positive laboratory results, it is important to restrict case investigation and laboratory tests to patients most likely to have measles (i.e., those who meet the clinical case definition, especially if they have risk factors for measles, such as being unvaccinated, recent history of travel abroad, without an alternate explanation for symptoms, for example epi-linked to known parvovirus case) or those with fever and generalized maculopapular rash with strong suspicion of measles.

During a measles investigation when community awareness is increased, many cases of febrile rash illness may be reported as suspected measles, and the magnitude of the situation may be exaggerated if these cases are included in the absence of laboratory confirmation. This is particularly important as the investigation is ending; at that point, laboratory confirmation should be sought for all suspected cases. Occasionally, suspected cases may include vaccinated individuals. For these cases, laboratory confirmation may be challenging. An overview of diagnostic tools is described below.

Virus isolation in cell culture and measles RNA detection (RT-PCR)

Clinical specimens for real-time polymerase chain reaction (RT-PCR) and virus isolation should be collected at the same time as samples taken for serologic testing. The preferred specimens for virus isolation or RT-PCR are throat or nasopharyngeal swabs, but urine may also contain virus. Virus isolation and RNA detection are more likely to be successful when the specimens are collected early (ideally within three days of rash onset, but up to ten days post rash may be successful). Isolation of measles virus in cell culture or detection of measles RNA by RT-PCR in clinical specimens confirms the diagnosis of measles.

However, a negative virus isolation or negative RT-PCR results do not rule out measles because both methods are affected by the timing of specimen collection and the quality and handling of the clinical specimens.

Successful isolation of measles virus in culture or direct detection of measles RNA by RT-PCR in the clinical sample is particularly helpful for case confirmation when serology results are inconclusive. The Vero/hSLAM cell line, a recombinant cell line with a receptor for measles virus, has greatly improved the ability to isolate measles virus in cell culture.

Molecular analysis to determine genotype of measles

Determination of the measles genotype provides the only means to distinguish between wild-type virus infection and a rash caused from a recent measles vaccination. In addition, the collection of appropriate specimens from which virus or viral RNA can be obtained or amplified is extremely important for molecular epidemiologic surveillance to identify the genotypes associated with imported cases of measles. This information is used to track transmission pathways, link cases to countries overseas, and to document the absence of endemic circulation of measles in the United States. [30] Sequence analysis and genotyping for measles virus is conducted at the CDC Measles Laboratory. Refer to the CDC Measles Laboratory website for additional information on sample collection, processing and the genetic analysis of measles.

Serologic testing

The state health department can provide guidance regarding available laboratory services. At the direction of the state health department, health care providers and state and local health departments may send serum specimens from suspected measles cases to the CDC Measles Laboratory. For detailed information on blood collection and shipping, refer to the CDC Measles Laboratory website.

There is no single serologic laboratory test capable of confirming with 100% confidence every true case of measles. Public health laboratories that use commercial measles assay kits are encouraged to fully characterize and validate the kits in their laboratories using known test panels of positive and negative specimens. Information regarding the performance characteristics of many of the commercially available enzyme immunoassays (EIA) kits is available by contacting the CDC Measles Laboratory. The reference laboratory at CDC uses an IgM assay developed at CDC for measles serologic testing of IgM. The assay is a capture IgM format EIA that utilizes a recombinant measles nucleoprotein (NP) antigen and tends to have high sensitivity and specificity compared to some commercial EIAs.

Use of IgM for confirmation of measles

Unvaccinated persons. Following measles virus infection in an unvaccinated individual, measles IgM antibodies appear within the first few days (1–4 days) of rash onset, peak within the first week post rash onset and are rarely detected after 6–8 weeks. Measles IgG antibodies are generally produced and detectable a few days after the IgM response. The timing of the IgM and the IgG response varies among individuals but IgG should be detectable by 7–10 days post rash onset. IgG levels peak approximately two weeks post rash onset and persist for life.

Upon exposure to wild type measles virus, an unvaccinated person may have detectable IgM as soon as the first day of rash onset. However, depending on the sensitivity of the assay used, a proportion of serum samples (23% in a study using CDC capture IgM assay [31]) collected within 72 hours after rash onset may give false negative results. If a negative result is obtained from serum collected within 72 hours after rash onset, a second serum should be collected ≥72 hours after rash onset. Measles IgM is detectable for at least 30 days after rash onset and frequently longer.

Following vaccination, measles IgM may not be detectable until 8–14 days after vaccination and measles IgG may not be detectable for up to three weeks post vaccination. [32]

Note: When a patient with suspected measles has been recently vaccinated (6–45 days prior to blood collection) neither IgM nor IgG antibody responses can distinguish measles disease from the response to vaccination. Determination of the measles genotype is necessary when measles symptoms occur following an exposure to wild type virus and MMR vaccine had been provided as postexposure prophylaxis.

Vaccinated persons. Individuals who have been previously exposed to measles antigen may have a modified disease presentation. These cases are usually detected during an outbreak or after a known exposure to a confirmed measles case. In rare instances, such cases can occur without a known exposure or other risk factor.

Vaccinated persons may not have an IgM response or it may be transient and not detected depending on timing of specimen collection, therefore a negative IgM test in vaccinated persons suspected of having measles should not be used to rule out the case; RT-PCR testing may be the best method to confirm such cases. If viral testing results are noncontributory, additional serological testing can be performed for highly suspicious cases. See the sections below.

Additional tests for measles infection

Testing for measles-specific IgM from persons with rash and fever can produce false positive IgM results. As discussed above, false negative results can also occur in a previously vaccinated person.

Ruling out a false positive IgM by testing a second serum

• If the acute sample was IgG negative, a second serum can be collected at ≥10 days after the acute sample. If this serum is IgG negative, measles can be ruled out.
• If the acute serum was IgG positive, a second serum, collected ≥2 weeks after the acute specimen, can be tested for a significant rise in IgG between paired serum samples.

Tests for IgG rise or seroconversion such as plaque reduction neutralization (PRN) and avidity testing may be helpful in certain situations. A brief description for the utility of these assays is given below. More information is available on the CDC Measles webpage. Requests for testing should be directed to the Measles Laboratory at CDC. (See Chapter 22, Laboratory Support for the Surveillance of Vaccine-Preventable Diseases)

IgG antibody seroconversion or demonstration of a rise in titer using IgG EIA

Unvaccinated persons. If classification of a case cannot be made after testing a serum sample collected ≥72 hours after rash or detection of measles virus from a viral specimen was not successful, a convalescent serum sample can be collected. A convalescent serum sample should be collected 10–30 days after the acute serum. In immunologically naïve persons, the measles IgG response starts slowly and, depending on the assay, can be detected by day 3–7 after rash onset (range: 1–10 days), but typically persists for a lifetime.

Note:  IgG testing of paired serum samples requires the demonstration of a significant (usually four-fold) rise in the titer of antibody against measles using an assay that has been validated for this use. The test for IgG antibody should be conducted with acute and convalescent serum samples at the same time using the same test. IgG avidity assessments would also be informative on such specimens, since low avidity results would rule in a case of measles in this instance (See Avidity of IgG below). 

Note:  A recent systematic review of published literature found no reported confirmed instances of human-to-human transmission of the measles vaccine virus. [33]

Vaccinated persons. When measles is suspected in previously vaccinated persons, the acute serum may be IgM negative and IgG positive. Measles infection in such cases is characterized by a rapid and robust IgG response. [34,35] If a second serum sample collected 5–10 days later remains IgM negative, then the paired serum samples can be tested in a PRN assay or a quantitative or semi-quantitative IgG EIA validated for such use. Refer to the CDC Measles Laboratory website for more information.

The occurrence of measles-like illness in recently vaccinated persons can pose particular difficulties. Fever and rash are known to occur 6–12 days post-vaccination in a small percent of vaccinated persons.[1] A positive measles IgM test cannot be used to confirm the diagnosis of measles in persons with measles-like illness who received measles vaccine 6–45 days before onset of rash due to the measles IgM antibody response to the vaccine. Specimens for viral isolation should be obtained in addition to serologic testing (see “Laboratory Testing” section above); isolation of wild type measles virus would allow confirmation of the case. In the absence of strain typing to confirm wild type infection, cases in persons with measles-like illness who received measles vaccine 6–45 days before onset of rash should be classified as confirmed cases only if a) they meet the clinical case definition and b) they are epidemiologically linked to a laboratory-confirmed case.

Plaque reduction neutralization assay (PRN)

The gold standard test for serologic evidence of recent measles infection is a four-fold rise in titer as measured in a measles virus plaque reduction neutralization test (PRN or PRNT) between acute and convalescent serum samples. Unlike the IgG EIA, this test measures measles functional (neutralizing) antibodies, requires specialized reagents, and is labor and time intensive. Only in rare situations would such testing be deemed necessary. Prior approval should be obtained from the CDC Measles Laboratory.

Avidity of IgG

A single acute-phase serum sample can be tested for IgG avidity; however samples must have detectable IgG. Low avidity IgG confirms a recent measles infection (or recent vaccination). Avidity testing can distinguish between primary and secondary vaccine failures. Avidity testing requires specialized reagents and their use is limited to unusual cases (prior approval required) usually in an outbreak setting when cases with modified or nonclassic presentation of measles are detected.

Specimen collection

Specimen collection and shipping are important steps in obtaining laboratory diagnosis or disease confirmation. Guidelines have been published for specimen collection and handling for viral and microbiologic agents. Information is also available on using CDC laboratories as support for reference and disease surveillance; this includes:

• a central website for requesting lab testing;
• the form required for submitting specimens to CDC (See Appendix 23, Form # CDC 0.5034);
• information on general requirements for shipment of etiologic agents (see Appendix 24[1.3 MB, 7 pages])—although written to guide specimen submission to CDC, this information may be applicable to submission of specimens to other laboratories; and
• the CDC Infectious Diseases Laboratories Test Directory, which not only contains a list of orderable tests for that institution, but also detailed information such as appropriate specimen types, collection methods, specimen volume, and points of contact.

The APHL/CDC Vaccine Preventable Disease Reference Centers[2 pages] can perform RT-PCR to detect measles RNA and measles genotyping.

Specific instructions for specimen collection and shipping may be obtained from the CDC measles website or by contacting the CDC Viral Vaccine Preventable Diseases Branch at 404-639-4181. Specimens for virus isolation and genotyping should be sent to CDC as directed by the State Health Department.

For additional information on use of laboratory testing for surveillance of vaccine-preventable diseases, see Chapter 22, “Laboratory Support for the Surveillance of Vaccine-Preventable Diseases.”

3/ Are those tests available about this outbreak?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1318492/ 

4/ Due to the very sensitive nature of the geographical data and the risk of false accusation those pieces of information are crucial.


Un point très important que ne résout pas du tout la tradi obligation vaccinale la plus élevée du monde "à la française" que certains mettront toute leur intelligence à contourner (différence entre contrainte et confiance) il semble bien que même à deux injections il y ait un % non négligeable de non immunisés et que cette immunité vaccino induite par un épitope dure moins longtemps....