Detection of modified measles and super-spreader using a real-time reverse transcription PCR in the largest measles outbreak, Yamagata, Japan, 2017 in its elimination era

Abstract

We aimed to verify the effectiveness of real-time reverse transcription (rRT) polymerase chain reaction (PCR) for detecting cases of modified measles (M-Me) and for predicting super-spreader candidates through the experience of a measles outbreak dominated by M-Me in Yamagata, Japan, during March-April 2017. We applied rRT-PCR to specimens from 35 cases of M-Me, nine cases of typical measles (T-Me) and nine cases of prodromal stage of T-Me (P-Me). From rRT-PCR among the M-Me cases, peripheral blood mononuclear cells (PBMC) showed the highest positive rate (80.0%), followed by throat swab (48.6%), urine (33.3%) and serum (3.1%). The negative result of PBMC in M-Me cases was recovered by the result of a throat swab. In specimens of PBMC, throat swab and urine, M-Me group showed the significantly higher cycle of threshold (i.e., lower viral load) in the rRT-PCR than T-Me and P-Me groups, respectively. Furthermore, three super-spreaders in T-Me or P-Me showed an extremely low cycle of threshold in their throat swab specimens. rRT-PCR using PBMC and throat swab might be helpful for clinical management and measles control by certain detection of M-Me cases and by predicting super-spreading events resulting from measles cases with the high viral load.

Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections

“…It is noteworthy that two patients in our study transmitted the infection to the majority of the other cases in the outbreak. Both had very high measles RNA levels in nasopharyngeal samples taken at onset of rash, which is in line with another recent report [18].…”

“…Our data indicate that patients with breakthrough infections seem to present with lower levels of measles RNA at rash onset, most probably because partial immunity reduces viral replication. By contrast, those with naïve infections seem to have a high viral load [18] and are more likely to transmit the infection. Even though the measurement of measles RNA load is semiquantitative, a Ct value of 18 in a nasopharyngeal sample, as in the index case in the outbreak described here, translates to a viral load that is ca 10,000 times greater than that of Ct 32, as in the cases with breakthrough infections.…”

“…primary) infections based on clinical presentation alone [13]. Measles-specific IgG antibody titres are usually high in acute-phase serum but IgM may be undetectable, making analysis of measles virus RNA by real-time PCR the preferred diagnostic method for breakthrough infections [17,18]. Analysis of measles IgG antibody avidity or measles neutralising antibodies by plaque reduction neutralisation assays (PRN) in acute serum samples are used to confirm breakthrough infections [10,15,19,20].…”

Longitudinal Epidemiology of Viral Infectious Diseases Combining Virus Isolation, Antigenic Analysis, and Phylogenetic Analysis as Well as Seroepidemiology in Yamagata, Japan, between 1999 and 2018

“…These findings suggested that, in general, those aged 20-39 years with insufficient immunity against measles virus should be provided with additional doses of vaccine to prevent measles importation and endemicity (71). We also verified the effectiveness of real-time RT-PCR in that outbreak and found that throat swabs and peripheral blood mononuclear cell specimens were useful for the detection of the measles virus genome among modified measles cases and that the high viral loads suggested by real-time RT-PCR for pharyngeal specimens are important for predicting super-spreading events primary cases as typical measles (72).…”

Precision public health to inhibit the contagion of disease and move toward a future in which microbes spread health

“…Super-spreaders or super-shedders are individuals who disproportionately infect others and may dominate the epidemiology of infectious disease [43][44][45][46]. In some contexts super-spreaders of infectious agents might be identified prospectively by molecular criteria rather than by post facto epidemiology [47,48].…”