Measles outbreak in a migrant laborer population in the wake of COVID-19 pandemic: Kathmandu, Nepal, 2020

We describe a measles outbreak in migrant laborers working in a carpet factory in Kathmandu, the capital of Nepal. The outbreak occurred during the nationwide lockdown enforced to contain the COVID-19 pandemic and 2 weeks after the Supplmentary Immunization Activities done for measles elimination. We included all the patients from the factory presenting to Mulpani Primary Health Centre, Kathmandu, Nepal with acute febrile rash illness. Recovered patients with history of fever and rash within the dened outbreak period with a clear epidemiological linkage were also included. Laboratory conrmation was done by detection of immunoglobulin M (IgM) in serum samples against the measles virus via enzyme-linked immunosorbent assay (ELISA). We compared attack rates (ARs) between those less than 5 years and 5 years or older. We identied 11 case patients ranging from 7 months to 27 years of age (3 below 5years of age); rash onsets were from 28 March-20 April 2020. All case-patients were laborers who had immigrated to Kathmandu from rural parts of the country. We sent serum samples of 7 patients for laboratory conrmation; 5 patients tested positive. The remaining four patients had a clear epidemiological linkage. The average attack rate was 30.5% with no signicant difference between attack rates among the <5 years and the ≥ 5 years reported as 37.5 and 28.5 respectively. Migrant population from rural regions with poor outreach of essential health services like vaccination can act as pockets of measles susceptible individuals if not measles reservoirs. The squalid conditions in which the migrant laborers live-in can also compound the risk of outbreak in such populations. It is prudent to address the vaccination status of such population and timely correct their vaccine status if unvaccinated in order to meet the goal of measles elimination by 2023. lling the epidemiological case sheets for patients with their due consent. We report results for categorical values as proportions or frequencies and results for continuous values as medians or range. We calculated attack rates (AR) and compared them among those below 5 years of age and those who were 5 years or older. Distinction at 5 years was used because SIAs vaccinate children below this age. ARs were calculated as the number of conrmed measles case-patients divided by corresponding populations. We compared ARs across the two groups using Fisher exact tests. Analyses were performed using IBM SPSS version 20. Statistical signicance was dened as a 2-sided P value < 0.05. children also mostly immigrant children. This vaccination coverage at an early also helps to explain the workings of herd immunity to contain the disease as no cases were native to the community(22). Results from this report show very high attack rates in the people living inside the factory. A study of unvaccinated children in Bajura district of Nepal too showed a high attack rate among unvaccinated children(23). All of our case-patients, immigrants without the certainty of full immunization, showed high susceptibility to the disease. The districts of origins of our case-patients have low coverage of the MR2 vaccine(9). Since no cases were from the local population, a population with high vaccination coverage, our report highlights the pertinence of the MR vaccination. This outbreak report is unique in the sense that the measles outbreak occurred in an urban area and the case-patients encompassed both adults and children. Most outbreak reports from Nepal have been from rural areas of the country involving children(23, 24). Eight (72%) of our case-patients were above the age of 5-years. Children below this age threshold are targeted by RIs and SIAs for MR vaccination. Our report highlights a changing epidemiological trend where more adults, deprived of the MR vaccine during childhood, are beginning to make up for the burden of measles-cases. An outbreak study that was done in Dhankutta, a district in the eastern region of Nepal also found more than 50% of the case patients to be above 10 years of age; all patients were fully immunized(25). Studies across Southeast Asia have similar ndings where, as more children get immunized, adults represent the larger proportion of the outbreaks(26)(27). Outbreaks involving adults have been reported from factories, hostels, oce complexes, detention centers, and airports(28)(12, 27, 29–31). vaccine ecacy(23, 25). These studies have recommended improved cold chain maintenance to increase vaccine ecacy. Studies in Africa showed vaccines administered in rural regions had diminished seroconversion rates (far below 95% required for measles elimination) and low virus titers(32, 33). These ndings were attributed to poor cold chain management and sub potent vaccines. Proper logistics and highly trained manpower are necessary to improve vaccine ecacy and achieve higher seroconversion rates and thus measles elimination.


Background
Measles is a highly contagious vaccine-preventable febrile rash illness caused by the measles virus of the Paramyxoviridae family (1). A highly contagious, yet a vaccine-preventable disease, measles has been a leading infectious cause of morbidity and mortality across the world; close to 110,000 deaths were reported in 2017. New cases continue to be reported even from developed countries with high vaccination rates(2).
A total of 170 countries reported 112,163 measles cases to the World Health Organization (WHO) in 2019, a 300% increase compared to 2018(2). The data shows a soaring number of cases for 2 consecutive years. The South-East Asian and Western Paci c Region saw an increase in the number of measles cases by 40%(2). In Nepal, a low income country in Southeast Asia, there were 430 con rmed cases in 2019. And as of April 2020, 320 con rmed cases have been reported (3).
Floating populations like migrant laborers and refugees have poor access to health facilities including vaccination and live in poor, squalid conditions (4). They are highly susceptible to infectious diseases and are frequent harbingers of outbreaks. These mobile populations whose vaccination status is di cult to ascertain can also introduce disease into their destination communities.
Measles elimination has been di cult to achieve partly due to such populations who travel in search of jobs or safety. Mostly a disease of children, a measles outbreak in such population is represented by a more homogenous distribution across the age groups (5).
Measles elimination, de ned as the absence of endemic measles transmission in a country for ≥ 12 months, has been a di cult task for countries with weak health systems like Nepal (6). Following the introduction of the Measles-Rubella (MR) vaccine, Nepal along with other member states of the WHO Southeast Asian Region (SEAR) had aspirations of eliminating measles by 2020, but with more cases being reported, the plan has been postponed to 2023 (7). As of today, 5 out of 11 countries in SEAR have achieved measles elimination (8).
Despite a reduction in the number of con rmed measles cases by 98% as compared to the year 2000, 5 con rmed measles outbreaks were reported in 2018 in Nepal (9). We describe a measles outbreak in a carpet factory among the families of domestic migrant laborers in Kathmandu, the capital of Nepal, 2 weeks after the completion of Supplementary Immunization Activities at the local administrative level during the nation-wide lockdown enforced to contain the COVID-19 pandemic.

Case De nitions
We de ned a clinical case of measles as per the WHO de nition as any person with fever, and generalized maculopapular (i.e. nonvesicular) rash, and either cough, coryza, or conjunctivitis(10). Laboratory con rmation was done by detection of measles-speci c immunoglobulin M (IgM) with enzyme-linked immunosorbent assay (ELISA). Any case which ful lled the clinical case de nition of measles but was not completely investigated was classi ed as a clinically-con rmed case. Any case that lacked serological evidence of measles despite complete investigation was discarded. A case that met the clinical case de nition of measles and was linked epidemiologically to a laboratory-con rmed or another epidemiologically-con rmed case of measles was classi ed as an epidemiologically con rmed case (11).
As per the guidelines for Nepal, we de ned a con rmed measles outbreak as the occurrence of 3 or more con rmed measles cases in a health facility in a month (11). The outbreak period was de ned as starting from 2 maximum incubation periods (42 days) before the rash onset of the rst-identi ed case-patient through 2 maximum incubation periods after the rash onset of the last casepatient (11 February 2020-8 June 2020) (12).

Statistical Analysis
We performed descriptive analyses of categorical and continuous values that were obtained after lling the epidemiological case sheets for patients with their due consent. We report results for categorical values as proportions or frequencies and results for continuous values as medians or range. We calculated attack rates (AR) and compared them among those below 5 years of age and those who were 5 years or older. Distinction at 5 years was used because SIAs vaccinate children below this age. ARs were calculated as the number of con rmed measles case-patients divided by corresponding populations. We compared ARs across the two groups using Fisher exact tests. Analyses were performed using IBM SPSS version 20. Statistical signi cance was de ned as a 2-sided P value < 0.05.

Outbreak Setting
Kageshwori-Manohara municipality is one of the 11 municipalities in Kathmandu district. Located north-east of Kathmandu metropolitan city, this municipality is divided into 9 wards. Ward no. 6, where the carpet factory is located, has 2467 households with a total population of 11742(14).
The carpet factory had a total of 36 people including 8 children below 5 years of age living and working within its premises at the start of the outbreak. All the workers were migrants from various rural districts of Nepal. The factory had a steady turnover of workers. During the day, the workers came together in a hall where the weaving machines were kept. They slept in small huts made as satellite units to the big hall. A total of three huts with 9 rooms, each room of around 36 square feet, housed the workers and their families. Beds, utensils, and lavatories were shared. While the main working hall was spacious, the living quarters were overcrowded (15). Each person occupied an average of 10.125 square feet of the oor space of living area.

Detection
On the 6th of April, 2020, 3 patients, aged 11, 18, and 20 years were brought to the emergency department of Mulpani Primary Health Centre, Kathmandu with complaints of fever with rashes across the body and cough. All the patients were currently working at the carpet factory and had immigrated to Kathmandu from Rautahat, a district in the southern plains of Nepal. The patients had a history of contact with a person, their sibling, who had a similar illness and had now recovered. They had all arrived at the factory 3 months before the onset of the rash. After a detailed history and physical examination, we sent serum samples of all three patients to the National Public Health Laboratory for measles con rmation. Two out of the three patients tested positive for measles-speci c IgM by ELISA.
The index case had been working and living in the factory for 3 months before developing the acute febrile rash illness. The index was symptomatic for 6 days. Since the maximum incubation period for measles is 21 days, we inferred the index case had contracted the disease from within the community.

Response
We managed all the patients supportively until all their symptoms subsided. All patients received 2 age-appropriate doses of Vitamin-A. We obtained information regarding demographic characteristics, vaccination status, clinical complaints and signs, and outcomes of case-patients through face-to-face or telephone interviews.
Immediately after the presentation of the rst three cases, we visited the carpet factory to search for more cases. We were able to identify the index case on the rst visit. However, no new cases were found during the visit. We noti ed the various responsible authorities including the District Health O ce of Kathmandu, the WHO-IPD o ce, the health section of Kageshwori-Manohara municipality, and local administrative and security authorities. The inhabitants of the factory were asked to remain indoors. All the residents of the carpet factory were vaccinated with a single subcutaneous dose of the MR vaccine.
Active surveillance was done through phone calls to the factory each day. We mobilized the Female Community Health Volunteers (FCHV) of Ward no. 6 to go door to door searching for people with an acute febrile rash illness. FCHVs are the indispensable bridges between health personnel and the community. They are aware of any health issues in the community at household and individual levels. FCHVs were pivotal in our active surveillance and ensuring its validity (16).
The municipality put out notices regarding the outbreak of measles and its signs and symptoms; radio programs were broadcasted asking people to seek immediate medical attention upon having suspicious symptoms. We called other facilities within the vicinity of the municipality to ask if they had received similar patients. We went through patient registers of other government health facilities inside the municipality searching for cases that may have been overlooked.
We convened a meeting of the rapid response team once the outbreak was con rmed. A prompt outbreak response immunization was carried out in the ward where the outbreak was recorded. A total of 2658 children from 6 months to 15 years of age were vaccinated in a bid to contain the outbreak on the 4th of May, 2020. FCHVs were again called upon to inform the community regarding the single-day outbreak immunization program. They were able to disseminate the information in a single day and worked tirelessly along with our vaccinators to provide the MR vaccine to a huge turnout.
Despite an extensive search for the course of the outbreak duration, the source of the infection could not be found.

Patient Characteristics
We identi ed a total of 11 cases with acute febrile rash illness. The rash onset duration was from the 28th of March to the 20th of April, 2020 [ Figure 1].
We sent a total of 7 serum samples to the NPHL for serologic testing. Five out of the 7 serum samples tested positive for Measlesspeci c IgM. Thus, 5 cases were classi ed as laboratory-con rmed cases and 2 cases were discarded. Since a clear epidemiological linkage could be identi ed in the other 4 patients whose serum sample collection was not possible, we classi ed them as epidemiologically-con rmed cases of measles as per the WHO guidelines (11).
Amongst the cases, 2(18%) patients required hospital admissions due to severity of the symptoms. Complications were not observed in any of the cases. [ Table 1].
Only 1 case-patient who was 15-months of age was vaccinated with a single dose of MR vaccine. This case-patient was unable to receive a timely dose of MR2 following the disruption of RIs due to the lockdown enforced to contain the COVID-19 pandemic. A 6month-old case-patient who was not eligible for vaccination was classi ed as 'not applicable'. In the rest of the case-patients, a clear history of immunization could not be ascertained and thus, were labeled to have an 'unknown' vaccination status [ Table 1]. The attack rate for children below 5 years of age was 37.5%, and that for those ≥ 5 years was 28.5. The total attack rate was 30.5.
No statistical signi cance was observed between attack rates between the age groups of < 5 years and ≥ 5 years [ Table 2].  (17). In its quest to eliminate measles, Nepal has been conducting supplementary immunization activities (SIA) where children between 9 months to 59 months are vaccinated with a single dose of MR every 2 years (18). The immunity conferred by vaccination against measles is considered to last for at least 20 years (19).
Since their introduction in 2013 and 2015 respectively, the coverage of MR1 and MR2 vaccine was 81% and 66% in 2018 (9). A coverage of over 95% is required for measles elimination (9). The Nepal Demographic Health Survey (NDHS) of 2016 showed that 22% of children from 12-23 months were not fully immunized and 1% received no vaccination at all (20). Only 43% of the children received age-appropriate vaccination (20). The percentage of children of the same age group exempt from complete immunization was 13% according to NDHS of 2011; 3% of the children had not received any vaccination (21). Given the increasing number of cases and poor coverage of the measles-containing vaccine, more exercise is required to eliminate measles by 2023.
Kageshwori-Manohara municipality had MR1 vaccine coverage of 106% in 2019, the highest coverage among the municipalities in Kathmandu District. This percentage purports that apart from achieving the complete vaccination of the target population, additional children were also immunized, mostly immigrant children. This high vaccination coverage at an early age also helps to explain the workings of herd immunity to contain the disease as no cases were native to the community (22).

Results from this report show very high attack rates in the people living inside the factory. A study of unvaccinated children in
Bajura district of Nepal too showed a high attack rate among unvaccinated children (23). All of our case-patients, immigrants without the certainty of full immunization, showed high susceptibility to the disease. The districts of origins of our case-patients have low coverage of the MR2 vaccine (9). Since no cases were from the local population, a population with high vaccination coverage, our report highlights the pertinence of the MR vaccination.
This outbreak report is unique in the sense that the measles outbreak occurred in an urban area and the case-patients encompassed both adults and children. Most outbreak reports from Nepal have been from rural areas of the country involving children (23,24). Eight (72%) of our case-patients were above the age of 5-years. Children below this age threshold are targeted by RIs and SIAs for MR vaccination. Our report highlights a changing epidemiological trend where more adults, deprived of the MR vaccine during childhood, are beginning to make up for the burden of measles-cases. An outbreak study that was done in Dhankutta, a district in the eastern region of Nepal also found more than 50% of the case patients to be above 10 years of age; all patients were fully immunized (25). Studies across Southeast Asia have similar ndings where, as more children get immunized, adults represent the larger proportion of the outbreaks(26) (27). Outbreaks involving adults have been reported from factories, hostels, o ce complexes, detention centers, and airports(28) (12,27,(29)(30)(31).
Previous studies of outbreaks in Nepal, mostly describing children, have pointed towards poor vaccine e cacy (23,25). These studies have recommended improved cold chain maintenance to increase vaccine e cacy. Studies in Africa showed vaccines administered in rural regions had diminished seroconversion rates (far below 95% required for measles elimination) and low virus titers (32,33). These ndings were attributed to poor cold chain management and sub potent vaccines. Proper logistics and highly trained manpower are necessary to improve vaccine e cacy and achieve higher seroconversion rates and thus measles elimination.
Floating populations like the domestic migrant workers in our report have been attributed to disease outbreaks across the globe.
They come from areas with poor access to health care and are thus likely to have not been vaccinated in their places of origin.
Since vaccinations require multiple doses to ensure protection against diseases, these populations, as they move about are exempt from completing the course of their vaccination. An increase in oating populations across the world following wars and civil unrest has led to the increase in outbreaks of many communicable diseases including measles (4,34,35). In our report, the migrant workers came from within Nepal, from rural parts of the country where MR vaccine coverage has been poor through the years. We recommend an active search for unvaccinated individuals in the districts of origin of our case-patient and mass vaccination of such communities indiscriminate of age to prevent further outbreaks.
Our index case, who had been living in the factory for 3 months before the start of the outbreak, was likely to have acquired the virus from the community and went on to introduce the disease to a highly susceptible population. In our investigation, we could not ascertain the source of the outbreak. Every effort was made in determining the source of outbreaks since the lack of sustained transmission in an endemic region is the major criterion for establishing elimination (12).
During the outbreak duration, the Government of Nepal had enforced a country-wide lockdown to contain the COVID-19 pandemic. While the lockdown was likely to have helped contain the spread of measles in the community, it could also have prevented more patients from reaching health facilities and thus a smaller number of case-patients in our outbreak. Since measles and COVID-19 share some similar symptoms like fever and cough, some patients were unlikely to have visited health facilities due to the social stigma associated with COVID-19 in the community. Conversely, local health facilities too were less likely to have seen patients with such symptoms owing to the unavailability of personal protective equipment (36), leading to more cases being missed. During the lockdown, routine immunization services were halted, which could lead to the resurgence of cases of vaccine-preventable diseases.
The population under investigation in this report, lived in overcrowded spaces (15), which is already a risk factor for infectious disease transmission including measles. This was added upon by lockdown where the close contact between the people was increased to 24 hours a day in the migrant labor population. The authorities need to consider such living conditions of such populations and strengthen surveillance of immunization preventable disease in such population pockets.
Several limitations should be considered, including underreporting of the symptoms. Many of the adult-case patients may have endured the disease without seeking medical care to avoid the epidemiological investigation. The enforced nation-wide lockdown may have deterred case-patients with milder symptoms from seeking medical care. The social ostracism brought on by the COVID-19 pandemic also may have led to underreporting. Interviewing of all the residents present at the beginning of the outbreak was not possible as some had returned to their villages just a few days before the lockdown began.

Conclusion
Urban areas are likely to have measles outbreak due to the high in ux of populations migrating from areas with poor vaccination coverage. As measles vaccination coverage increases, adults who missed immunization would be the population at risk and are likely to represent a higher proportion of case-patients. Age-indiscriminate vaccination campaigns in areas with poor vaccine coverage are necessary to achieve measles-elimination status faster. Surveillance activities should focus on nding at-risk migrant labor populations who are likely to act as reservoirs or susceptible individuals for communicable diseases and immunization activities should be focused towards fully immunizing such cohorts to prevent future outbreaks. Surveillance and reporting of measles and non-measles non-rubella illnesses are cornerstones for fact-checking the status of the country in terms of proximity towards measles elimination and the work required towards that end. This outbreak investigation was conducted as per the standard Outbreak Investigation protocol of the Ministry of Health & Population, Nepal. Ethical principles of research was followed when writing this paper and written informed consent was taken from the participants.

Consent for publication
Not applicable Availability of data and materials All data generated or analysed during this study are included in this published article.

Competing interests
The authors declare that they have no competing interests.

Funding
None declared. Figure 1 Epidemic curve for the measles outbreak Age and sex distribution of measles case-patients (n=11) Figure 3