Measles virus transmission patterns and public health responses during Operation Allies Welcome: a descriptive epidemiological study

Abstract

Background: On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures.

Methods: We conducted a measles outbreak investigation among Afghan evacuees who were resettled in the USA as part of OAW. Patients with measles were defined as individuals with an acute febrile rash illness between Aug 29, 2021, and Nov 26, 2021, and either laboratory confirmation of infection or epidemiological link to a patient with measles with laboratory confirmation. We analysed the demographics and clinical characteristics of patients with measles and used epidemiological information and whole-genome sequencing to track transmission pathways. A transmission model was used to evaluate the effects of vaccination and other interventions.

Findings: 47 people with measles (attack rate: 0·65 per 1000 evacuees) were reported in six US locations housing evacuees in four states. The median age of patients was 1 year (range 0-26); 33 (70%) were younger than 5 years. The age distribution shifted during the outbreak towards infants younger than 12 months. 20 (43%) patients with wild-type measles virus had rash onset after vaccination. No fatalities or community spread were identified, nor further importations after flight resumption. In a non-intervention scenario, transmission models estimated that a median of 5506 cases (IQR 10-5626) could have occurred. Infection clusters based on epidemiological criteria could be delineated into smaller clusters using phylogenetic analyses; however, sequences with few substitution count differences did not always indicate single lines of transmission.

Interpretation: Implementation of control measures limited measles transmission during OAW. Our findings highlight the importance of integration between epidemiological and genetic information in discerning between individual lines of transmission in an elimination setting.

Funding: US Centers for Disease Control and Prevention.

Figure 1:. Epidemiological curve of measles cases during Operation Allies Welcome, August–October, 2021

Cases are shown according to location and date of rash onset. For two cases, the date of onset of rash could not be determined; therefore, the date that the case was identified is shown. Cases were reported in six locations: Hotel A (12 cases), Joint Base McGuire-Dix-Lakehurst (one case), Holloman Air Force Base (two cases), Fort McCoy (22 cases), Fort Pickett (one case), and Marine Corps Base Quantico (nine cases). The first flight with Afghan evacuees arrived on Aug 17, 2021. Flights from international locations were temporarily paused on Sept 10, 2021, and resumed on Oct 5, 2021 (indicated by vertical red dashed lines). The cumulative proportion of MMR vaccine doses administered to eligible Afghan evacuees in domestic sites is shown in grey; routine immunisation of arriving Afghan evacuees started on Aug 24, but vaccine efforts started to increase once cases were identified at domestic sites, and accelerated with the issuance of a directive for mass MMR vaccination across domestic and international sites on Sept 14. CDC=US Centers for Disease Control and Prevention. MMR=measles, mumps, and rubella.

Figure 2:. Length of time between MMR vaccine and onset of rash and timeline of probable exposure period for 20 patients who developed wild-type measles after receiving MMR vaccine during Operation Allies Welcome, August–October, 2021

Genotype B3 was identified in all specimens. (A) Histogram and kernel density plot of the time in days between MMR vaccination and onset of rash. The kernel density has a probability of 0 after 17 days (bandwidth=0·8488, selected using unbiased cross validation). (B) Timeline for each of the patients, including date of arrival from overseas location, inferred exposure period, and the time between MMR vaccination and rash onset, colour-coded by domestic location. MCB=Marine Corps Base. MMR=measles, mumps, and rubella. pct=percentile.

Figure 3:. Model simulations of the probability distribution of measles attack rates among susceptible evacuees in five military bases with measles cases, under various scenarios

(A) Mass vaccination not conducted, shown in orange (median attack rate 87·33%, IQR 0·15–89·23). (B) Age of measles, mumps, and rubella vaccine administration not lowered to 6 months (ie, those aged 6–11 months were not vaccinated, shown in red; median attack rate 0·44%, 0·10–1·53). (C) Vaccination delayed by 7 days (ie, vaccination uptake as it occurred but shifted by 7 days, shown in green; median attack rate 0·68%, 0·15–2·66). (D) Vaccination delayed by 14 days (ie, vaccination uptake as it occurred but shifted by 14 days, shown in green; median attack rate 1·14%, 0·15–4·67). (E–G) Two additional importations, one at Fort McCoy and one at MCB Quantico, on Sept 24 (median attack rate 0·58%, 0·12–1·61), Sept 17 (median attack rate 0·67%, 0·13–1·75), or Sept 10 (median attack rate 0·76%, 0·18–2·00); intervention scenarios are shown in purple. Each panel compares the base-case scenario (model results using vaccination uptake as it occurred), shown in blue (median attack rate 0·44%, IQR 0·12–1·46; in reality, 35 cases were observed in this outbreak across these five bases), with the modelled scenario. Vertical dashed lines represent median modelled cases. Five military bases with reported cases are included in these results (Fort McCoy, WI; MCB Quantico, VA; Holloman Air Force Base, NM; Joint Base McGuire-Dix-Lakehurst, NJ; and Fort Pickett, VA); total population, n=35 951, total estimated susceptible population, n=6305. Hotel A was modelled separately (appendix pp 19, 21). Medians and IQRs for the attack rates among susceptible evacuees and the total number of cases were generated from 1000 simulations per military base, which were pooled to create these combined estimates. MCB=Marine Corps Base.

Figure 4:. Trajectories and infectious and exposure periods of patients with measles during Operation Allies Welcome, August–October, 2021.

For each patient, we reviewed the overseas location before travel to the USA, flight information, US arrival date, receiving US airport, domestic location, barrack or bay housing, and information on relatives who were also patients. Each patient was assigned a number based on the order in which they were identified and plotted by their domestic and overseas location and date of onset of rash. For two patients, the date of onset of rash could not be determined, so the date that the patient was identified is shown. Exposure and infectious periods are shown for each patient to allow for a visual comparison of potential sources of infection among patients at various locations. Two patients arrived to the USA through PHL, the rest arrived through IAD (four times the number of evacuees arrived through IAD compared with PHL). Highly probable transmission pairs are noted by black lines, with arrows indicating the direction of transmission (1→4, 3→8, and 30→28). AFB=Air Force Base. IAD=Dulles International Airport. JB=Joint Base. MCB=Marine Corps Base. PHL=Philadelphia International Airport.

Figure 5:. Phylogenetic data for viral whole genomes obtained from patients with measles during OAW, August–October, 2021.

(A) Complete topology of the phylogenetic tree obtained from all measles virus B3 sequences (n=114), of which the exploded lineage containing only OAW specimens is highlighted in pink. (B) Maximum clade credibility tree of measles virus sequences from OAW specimens for which WGS was successful, summarised using mean node heights in years pre-dating the most recent case. Very highly supported internal nodes (posterior probability >0·90) are shown as black dots. Inferred time in decimal calendar years of internal node (common ancestor) origins is shown as blue bars comprising the 95% HPD. 95% HPD for the common ancestor date of OAW specimens is denoted by vertical dashed lines. Cases are annotated with WHO measles sequence nomenclature; patient identifier. High-confidence transmission events informed by epidemiological information are depicted as red arrows. Transmission events of nil confidence are depicted as grey arrows. Base substitution counts for relevant exposure groupings, relative to the earliest ordinal case in that group, are shown in the appendix (pp 29–30). (C) Number of accumulated base substitutions from both the N450 region alone and the whole-genome sequence of proposed transmission pairs (1→4, 3→8, and 30→28) and unrelated control pairs. *Only N450 regions are shown because WGS for case 30 was not successful (appendix p 24). HPD=highest posterior density interval. NA=not available. OAW=Operation Allies Welcome. WGS=whole-genome sequencing.