ÐÇ¿ÕÓéÀÖ¹ÙÍø

Mumps

Q: What tests are most important to perform to diagnose when a mumps case is suspected?
A: PCR is the preferred test type to confirm mumps infection, and a buccal swab is the preferred specimen. Specimens should ideally be collected within 3 days of parotitis onset but can be tested up to 10 days after parotitis onset. If it has been more than 3 days since parotitis onset, a serum specimen for IgM testing is also recommended.

Q: Why do so many mumps outbreaks occur in fully vaccinated adults?
A: The mumps component of the MMR vaccine has lower vaccine effectiveness than the measles and rubella components, about 72% for 1 dose and 86% for 2 doses, with some documented waning of immunity. Additionally, the circulating strain of mumps in the US is typically genotype G, while the mumps vaccine strain used in the MMR/MMRV vaccines is genotype A. Thus, it is thought that both waning of immunity and antigenic mismatch contribute to cases of mumps occurring in fully vaccinated individuals.

Q: Why was the mumps case definition changed in 2023?
A: The case definition was updated to increase the specificity for mumps surveillance, address false positive IgM results due to the high volume of positive IgMs performed on low-suspect cases, and to improve capture of the true burden of mumps (including characterization of the full spectrum of illness/atypical presentations). In particular, individuals who are PCR+ now are classified as confirmed cases regardless of presentation, while individuals who are IgM+ now need clinical documentation of mumps to be classified as suspect cases.

Measles

Q: Why is measles incidence higher in 2024 compared to recent years?
A: Overall, measles risk in the United States is determined primarily by 2 factors; measles immunity in the U.S. population, and the global measles situation. As with most years, the majority of cases in 2024 occurred in people who were unvaccinated or had unknown vaccination history; we did not see a rise in cases among people with documentation of vaccination that would make us concerned about changes in our vaccine efficacy.

Q: If a jurisdiction is trying to determine the immune status of a contact, is there a timeframe after exposure when an IgG test needs to be performed to be reliable?
A: ÐÇ¿ÕÓéÀÖ¹ÙÍø recently added information about this to our update for the measles surveillance chapter in the VPD surveillance manual. Overall, for people who do not have pre-existing immunity to measles, IgG is not expected to be present in people who go on to develop measles until after rash onset; therefore, presence of IgG at any point up to rash onset is evidence of pre-existing immunity. If we draw this back to measles contacts who are being evaluated after exposure but who do not have any symptoms suggestive of measles, this means that any detection of IgG after exposure is evidence of pre-existing immunity, either due to prior measles infection or measles vaccination. This means that any asymptomatic contact who has detectable IgG in a serum sample, regardless of how long it is after their contact with a measles case, has evidence of pre-existing immunity.

Rubella

Q: Should IgM testing be used for assessing rubella immunity?
A: No, IgM should not be used for assessing rubella immunity. Rubella immunity should only be assessed based on IgG testing. In the U.S., rubella immunity is routinely assessed in pregnant women and for certain individuals with occupational requirements. Although rubella immunity should be assessed based on IgG testing alone, some commercial labs provide both IgG and IgM results when immunity testing is requested. Consequently, false-positive IgM results are sometimes reported, causing burdensome public health investigations and inaccurate classification of rubella in situations where no clinical or epidemiologic suspicion exists.

Q: When should rubella case investigations begin and what contacts should be prioritized?
A: In the rubella post-elimination era, a single reported case is considered a public health priority that requires rapid and appropriate public health response. All reports of suspected rubella cases should be investigated immediately.

Any person with direct contact with a patient with rubella during the infectious period, 7 days before to 7 days after rash onset, is defined as a contact. High priority groups for follow up include 1) household contacts, 2) close contacts other than household (such as persons who shared the same room or airspace in various settings), and 3) schools/childcare centers, college, or other close settings where a defined number of persons have congregated. All contacts should be evaluated for evidence of immunity and pregnancy status.

Q: Should reflex laboratory testing for rubella be conducted after a negative measles result?
A: Yes, it is important to consider rubella in the differential diagnoses of patients under evaluation for other febrile rash illnesses, including measles, parvovirus, dengue, Kawasaki disease, and scarlet fever. Anytime rubella is suspected, specimens should be collected for both molecular and serologic testing at the time of the initial investigation.

Rotavirus

Q: Is rotavirus a nationally notifiable vaccine preventable disease?
A: No, rotavirus gastroenteritis is not a nationally notifiable disease in the U.S. Instead, estimates of disease burden are made through various surveillance mechanisms, including laboratory-based sentinel surveillance, healthcare utilization datasets such as hospital discharge data, and more intensive active, population-based surveillance at some sentinel sites.

Varicella

Q: Why was the varicella outbreak definition changed from 5 to 3 cases?
A: There were several reasons for this change:

When we analyzed the surveillance data for the recent years, we saw that when varicella zoster virus transmission occurred, it commonly resulted in clusters of 3-4 cases rather than outbreaks with 5+ cases.

With a significant drop in varicella incidence, we thought it was an appropriate time to update the varicella outbreak definition; many jurisdictions were already using 3 cases to define an outbreak.

This change also harmonized with the outbreak definition used for other pathogens, such as measles and mumps.

Q: Can providers use serology testing to confirm varicella?
A: No, serology has limited use for confirmation of varicella. First, IgM testing is not recommended for diagnostic confirmation, because available assays lack sensitivity and specificity. IgM cannot distinguish between primary infection (varicella) and reinfection or reactivation from latency (herpes zoster) since IgM antibodies are produced with each exposure to varicella zoster virus. Additionally, IgM can yield false positive results through cross-reactivity with other herpesvirus antigens.

Second, for IgG one needs to detect a significant rise in serum IgG antibodies between the acute and convalescent phase. Paired IgG acute- and convalescent-phase antibody tests are not practical for immediate clinical management of varicella.

As mentioned, PCR testing of skin lesion specimens is the preferred test for laboratory confirmation of varicella.

Acute flaccid myelitis/polio

Q: What are the criteria for reporting a possible case of Acute Flaccid Myelitis (or AFM)?
A: The reporting criteria for AFM includes: 1) a patient with acute onset of flaccid limb weakness, AND 2) at least some gray matter involvement in the spine MRI.

Q: What specimens should be collected from a patient that is suspected of having AFM?
A: Specimens should be collected as early as possible to increase the chance of finding a cause for AFM. The specimens to collect are: cerebrospinal fluid; respiratory, either nasopharyngeal or oropharyngeal swab; serum; and 2 stools collected at least 24 hours apart. Stool specimens are especially important to help rule out polio.

Q: Hasn't polio been eradicated, why is ÐÇ¿ÕÓéÀÖ¹ÙÍø still talking about polio? And how do you tell the difference between AFM and polio?
A: Even though polio has been eradicated in the United States, we are still at risk of importations from other countries. We saw this in 2022 when a case of polio was identified in New York. The patient came to the health department's attention through AFM surveillance and because they collected stool specimens, they were able to detect poliovirus and send to ÐÇ¿ÕÓéÀÖ¹ÙÍø for confirmation. AFM and polio appear similar clinically and radiographically (on MRI) so the only way to distinguish between the two is through testing of stool to detect the presence of poliovirus.

Meningococcal disease

Q: Is decreased vaccination coverage during the pandemic causing the increase in meningococcal disease cases?
A: No, the increase in meningococcal disease cases is being driven primarily by serogroup Y sequence type 1466, and the majority of those cases are 30 to 60 years of age. This age group is not routinely recommended to receive meningococcal vaccine.

Q: What influences the likelihood of developing meningococcal disease?
A: The risk factors that influence the development of meningococcal disease fall into three broad categories. The first is pathogen virulence factors - including the polysaccharide capsule mentioned earlier in this session.

There are also host factors that affect whether someone develops invasive disease.

People with complement deficiencies, people who are asplenic, and people with HIV are at higher risk for meningococcal disease.

And finally, there are population and environmental factors that influence risk, including factors that increase exposure and factors that influence the health of the nasopharynx and the body's ability to prevent invasion, like active or passive smoking and having an upper respiratory tract infection.

Q: Based on preliminary data so far, did the number of meningococcal disease cases increase during 2024?
A: Yes, we did see increases in meningococcal disease in 2024, due to both serogroup Y ST-1466 cases and ciprofloxacin resistant cases. We are asking that health departments continue to timely submit isolates to ÐÇ¿ÕÓéÀÖ¹ÙÍø as part of enhanced surveillance, to monitor for ciprofloxacin resistance and to inform potential changes to prophylaxis.

Q: What risk factor data is collected through meningococcal disease surveillance?
A: As part of enhanced meningococcal disease surveillance, we ask that health departments collect information on whether the case was part of a meningococcal disease outbreak. In addition, the investigation should collect epidemiologically important information to inform public health.

Invasive pneumococcal disease

Q: How many cases of invasive pneumococcal disease are there in the United States each year?
A: In the United States, there are an estimated 30,000 cases of IPD and 3,000 IPD deaths each year. There are over 100 distinct serotypes of Streptococcus pneumoniae however, serotypes vary in their ability to cause disease.

Q: What are the two surveillance systems for IPD in the U.S.?
A: One platform is ÐÇ¿ÕÓéÀÖ¹ÙÍø's Active Bacterial Core Surveillance system, or ABCs. The other is the Nationally Notifiable Diseases Surveillance System or (NNDSS). The rapid changes in IPD rates during the COVID-19 pandemic and the recent introduction of new, higher-valency vaccines highlight the importance of continued IPD surveillance to monitor trends.

Although ABCs provides detailed information on IPD cases from 10 areas of the U.S, it cannot provide information on the impact of each state's pneumococcal conjugate vaccine program. Nationally notifiable diseases surveillance data is important for that purpose. IPD cases in people of all ages are nationally notifiable.

Q: What lab tests are most important and available for IPD surveillance?
A: It is important to serotype isolates from IPD cases. Without serotype information, it is much more difficult to determine the impact of serotype-specific pneumococcal vaccines and to identify potential serotypes for use in future vaccines. It is also valuable to obtain antimicrobial susceptibility testing, or AST, for IPD isolates to monitor antibiotic resistance. There are several options available for jurisdictions to perform serotyping and AST. State public health labs, clinical, and commercial labs can use Polymerase Chain Reaction, or PCR, for serotyping.

ÐÇ¿ÕÓéÀÖ¹ÙÍø has developed a protocol to identify pneumococcal serotypes using PCR. A link to that protocol was presented earlier in this session.

Phenotypic serotyping can be performed by Quellung. And whole genome sequencing can be used to predict serotype and antimicrobial resistance patterns.

If states are unable to perform serotyping or AST, two reference laboratories which are part of the ÐÇ¿ÕÓéÀÖ¹ÙÍø-funded Antimicrobial Resistance Laboratory Network (or ARLN) can assist states with CLIA-approved serotyping and AST for IPD isolates that meet certain criteria. Links with information on testing through ARLN were also provided earlier in this session.

Additionally, ÐÇ¿ÕÓéÀÖ¹ÙÍø's Streptococcus laboratory can assist with non-CLIA serotyping of potential outbreak isolates. And AST can be performed for isolates with unusual resistance features.

Haemophilus influenzae

Q: Should everyone with Haemophilus influenzae be serotyped? What kind of specimen does that require? Where do I send the specimen?
A: Every case of H. influenzae invasive disease should be serotyped, and in particular those occurring in persons younger than 15 years of age. Clinical specimens from normally sterile sites should be used. Contact your state health department to determine availability of serotyping at the state public health laboratory.

Q: Does the ÐÇ¿ÕÓéÀÖ¹ÙÍø know what is driving the increase in nontypeable Haemophilus influenzae cases since 2021?
A: We are not sure. Notably, given that 2023 data are preliminary, we are not yet sure whether this is a meaningful increase versus general noise in the data. If it is a true increase, a few possibilities exist. Cases could be rebounding because young children did not have as much exposure to nontypeable Haemophilus influenzae during the COVID-19 pandemic. Additionally, we are aware of strains of nontypeable H. influenzae that seem to be unusually virulent. For example, sequence type1714 caused an outbreak in an elementary school in Detroit and has also caused a cluster of cases in the Atlanta area.

Q: Do Haemophilus influenzae type b (or Hib) vaccines provide any cross-protection against other serotypes of non-typeable Haemophilus influenzae?
A: No, Hib vaccines only provide protection against type b.

Q: Considering data collection related to surveillance for Haemophilus influenzae: How important is it to collect Hib vaccine manufacturer and type?
A: For cases caused by Hib or an unknown serotype of Haemophilus influenzae, it is very important to collect thorough Hib vaccine information, including Hib vaccine manufacturer and vaccine type. Vaccine information is important for identifying possible vaccine breakthrough cases (that is, cases occurring in children who have been vaccinated against Hib.) Vaccine type is particularly important following a recent Hib vaccine policy change in 2024: the combination vaccine Vaxelis was included with PedvaxHIB in the preferential recommendation for American Indian and Alaska Native infants based on the Hib component. Although Vaxelis is anticipated to be as effective as PedvaxHIB at preventing invasive Hib disease in American Indian and Alaska Native infants, collecting Hib vaccine type is important to monitor for possible breakthrough cases.

Tetanus

Q: What age group has the highest risk of death due to tetanus?
A: The answer is people older than 60 years. Since 2013, all tetanus-related deaths have occurred among this older age group.

Q: If there is a suspected case of Tetanus, what laboratory test can be used to diagnose tetanus?
A: There is no laboratory test that diagnoses or rules out a tetanus diagnosis; the diagnosis must be made entirely using clinical judgment. Tetanus diagnosis is based solely on clinical presentation consistent with tetanus in the absence of an alternative or more likely cause. ÐÇ¿ÕÓéÀÖ¹ÙÍø does not conduct or offer tetanus laboratory testing. Prompt clinical recognition of tetanus is important because hospitalization and treatment are required.

Q: About how many tetanus cases have been reported in the U.S. each year in the last decade?
A: An average of 27 cases of tetanus per year have been reported in the U.S. since 2013.

Pertussis

Q: Based on preliminary data so far, did the number of pertussis cases increase during 2024?
A: Yes, we saw reported pertussis cases increase across the US in 2024, indicating a return to more typical trends following the COVID-19 pandemic. The number of reported cases in 2024 was higher than what was seen at the same time of the year in 2019, prior to the pandemic. However, this was not unexpected. Pertussis is cyclical and we typically see peaks in disease every 3-5 years. We understand that the COVID-19 pandemic interrupted typical whooping cough patterns.

Q: Please summarize the current ÐÇ¿ÕÓéÀÖ¹ÙÍø guidance for pertussis surveillance. When should pertussis be suspected and how is it laboratory confirmed?
A: Pertussis should be suspected in persons with cough illness lasting more than 7 days with coughing fits, inspiratory whoop, or a cough that induces vomiting. Cough is typically the hallmark of pertussis, but very young infants with pertussis may present with apnea or long pauses in breathing, with little to no cough present.

Q: When pertussis is clinically suspected, what appropriate specimens should be obtained for laboratory testing?
A: For national case notification, there are two different methods by which cases can be laboratory confirmed. These methods are isolation of Bordetella pertussis from a clinical specimen or a positive PCR test. Commercial serologic tests for pertussis infection are not standardized; therefore, results of serologic testing are NOT used for case confirmation for national reporting.

Q: In conducting surveillance, what demographic and clinical information should be collected for pertussis cases?
A: Demographic information like age is important to collect as well as clinical data, such as the duration of cough, and the presence of paroxysms, whoop, and post-tussive vomiting. This information is important because laboratory testing cannot always be obtained or may not be conclusive. The clinical data can be used to determine if the person has met the clinical case definition for pertussis reporting.

In addition, it is important to know the severity of the illness, including complications such as pneumonia, and whether or not the patient survived. And of course, knowing the vaccination history is critical.

Q: Looking at data for the past few years, did decreased vaccination coverage during the pandemic cause the increase in pertussis cases?
A: No, pertussis vaccination coverage has remained stable in recent years. As we return to our typical infection patterns, we expect pertussis cases to increase both in unvaccinated and vaccinated populations. As was the case before the pandemic, we do expect to see cases in fully vaccinated individuals due to waning immunity from acellular vaccines, but vaccinated individuals will typically have milder disease.

Diphtheria

Q: Considering surveillance guidance, when should a case and contact investigation be initiated for suspect diphtheria cases?
A: If a suspect case has clinical symptoms consistent with toxin mediated disease (such as pseudomembrane, bull neck, cardiomyopathy, or neuritis) a case and contact investigation should be started immediately.

Q: Is testing for the presence of diphtheria toxin via Elek testing the only way to confirm diphtheria?
A: Yes, testing for the presence of diphtheria toxin via Elek testing is the only way to confirm diphtheria. However, MALDI-TOF can be used as a preliminary test to identify C. diphtheriae in many labs.

Q: Looking at the historical trends, have both C. diphtheriae infections and diphtheria increased in the U.S?
A: Although C. diphtheriae infections have recently increased in the U.S., diphtheria has not. Remember that prior to 2019, only respiratory diphtheria was reportable in the U.S. However, given that cutaneous and other forms of non-respiratory diphtheria can be transmitted and cause respiratory diphtheria, the U.S. case definition was revised in 2019 to include disease caused by toxin-producing C. diphtheriae from any site, including cutaneous sites.

Q: Can you clarify the recent trend in the increase in the number of C. diphtheriae infections in the U.S. resulting in a 5-fold increase in C. diphtheriae isolates submitted to ÐÇ¿ÕÓéÀÖ¹ÙÍø between 2019 and 2023?
A: Answering this question requires a bit of background on C. diphtheriae and diphtheria toxin. Unlike some toxin-producing bacteria, not all strains of C. diphtheriae produce diphtheria toxin. C. diphtheriae doesn't naturally possess the gene, called tox, that encodes diphtheria toxin. Instead, tox is encoded by a virus, called a phage, that's capable of infecting some corynebacteria. Only C. diphtheriae that have been infected with the phage, or are descended from a bacteria that was previously infected, are potentially capable of producing diphtheria toxin and being toxigenic. Uninfected strains are non-toxigenic.

Importantly, it's this diphtheria toxin that diphtheria vaccines provide antibodies against, not C. diphtheriae bacteria. This means fully vaccinated people can have C. diphtheriae infection, including with a toxigenic strain, without developing diphtheria because the vaccine protects them against diphtheria toxin.

Simply put, diphtheria is a vaccine preventable disease, C. diphtheriae infection is not.