Influenza in Refugees on the Thailand–Myanmar Border, May–October 2009

TOC Summary: Influenza viruses can be identified in up to 22% of patients who have acute respiratory infections.

We describe the epidemiology of infl uenza virus infections in refugees in a camp in rural Southeast Asia during May-October 2009, the fi rst 6 months after identifi cation of pandemic (H1N1) 2009 in Thailand. Infl uenza A viruses were detected in 20% of patients who had infl uenza-like illness and in 23% of those who had clinical pneumonia. Seasonal infl uenza A (H1N1) was the predominant virus circulating during weeks 26-33 (June 25-August 29) and was subsequently replaced by the pandemic strain. A review of passive surveillance for acute respiratory infection did not show an increase in acute respiratory tract infection incidence associated with the arrival of pandemic (H1N1) 2009 in the camp. P andemic (H1N1) 2009 emerged in April 2009 and subsequently spread around the globe. The World Health Organization issued a pandemic declaration on June 11, 2009 (1,2). By October 25, 2009, >440,000 laboratory-confi rmed cases, including >5,700 deaths, had been reported to WHO (3). The fi rst case of pandemic (H1N1) 2009 infection was diagnosed in Thailand on April 28, 2009, and subsequently the virus was detected in all provinces. The Thailand Ministry of Public Health reported 27,639 confi rmed cases and 170 deaths as of October 10, 2009 (4). Myanmar (Burma) reported its fi rst confi rmed case of pandemic (H1N1) 2009 infection during the week beginning July 5, 2009, and by the end of October 2009 had reported <100 confi rmed cases with no deaths (5). Although most infections caused by this new virus have been mild, severe disease has been reported, particularly in young adults (6).
Data regarding the effect of infl uenza in rural areas of the developing world are scarce, as are etiologic data from refugee populations (7)(8)(9). A recent review of published reports from Southeast Asia concluded that infl uenza infection may be identifi ed in up to 26% of outpatients with febrile illness and in 14% of hospitalized patients with pneumonia (10). In Thailand, seasonal infl uenza virus activity peaks during the rainy season (June-September), with smaller peaks occurring during the cold months (January and February) (11). Incidence of infl uenza infections in Thailand was 64-91 cases/100,000 persons per year during 1999-2002; the infl uenza-related hospitalization rate was 21/100,000 persons during 1999 (11). Infl uenza infections in Myanmar are also seasonal; cases are documented predominantly in the rainy season (May-October) (12)(13)(14). Incidence data for infl uenza virus infections in Myanmar are not readily available.
Of 15.2 million refugees worldwide, approximately one third live in camps (15). These refugees often live in crowded conditions and have contact with populations from the host country and the country of origin, where public health infrastructure and surveillance may be poor (16,17).
Approximately 150,000 refugees from Myanmar are housed in several camps on the Thailand-Myanmar border. Maela Temporary Shelter (Maela, Thailand) is the largest of these camps, with a population of >40,000, predominantly of the Karen ethnic group, housed in a 4-km 2 area (18). This camp is located in the hills adjoining the Myanmar border, ≈500 km northwest of Bangkok, and has been in operation since 1984. Primary health and sanitation services are provided by nongovernmental or-

Methods
From May 1 through October 31, 2009, trained local fi eld workers visited the hospital in Maela daily (Monday-Saturday). Patients whose illnesses met clinical case defi nitions for infl uenza-like illness (ILI) or pneumonia (Table  1) were identifi ed by clinic staff at the time of examination, and these patients were asked to complete an additional clinical interview. Inpatient and outpatient department cases were included in the surveillance. From July 27 through October 31, 2009, original clinical case defi nitions were modifi ed to capture each patient who had a history of fever during the current illness but who was not febrile at the clinic visit (either because of the intermittent nature of fever or self-administration of antipyretics).
A nasopharyngeal aspirate (NPA) was collected from each patient; a sterile 8-French infant feeding tube was inserted into the nasopharynx and then withdrawn while suction was applied with a 20-mL syringe attached to the feeding tube. The nasopharyngeal secretions and the tip of the feeding tube were transferred to a 1-mL tube of viral transport medium and stored in a cool box until transfer, within 24 h, to a -80°C freezer before analysis.
All NPA specimens were subjected to a panel of realtime reverse transcription-PCR (rRT-PCR) assays for the following viruses: infl uenza A (separate primer/probe sets for infl uenza A [universal], pandemic [H1N1] 2009, seasonal subtype H1N1, and seasonal subtype H3N1 detection) (20); infl uenza B (CDC in-house assay [details available on request]); respiratory syncytial virus (RSV; CDC in-house assay [details available on request]); and human metapneumovirus (HMPV) (21). An internal control PCR specifi c for the human RNAseP gene was used to monitor sample adequacy and to detect the presence of PCR inhibitors (22). Positive and negative controls were included in each PCR run. A Rotorgene 6000 real-time PCR thermocycler (Corbett Life Science, Mortlake, New South Wales, Australia) and SuperScript III One-Step RT-PCR Kits (Invitrogen, Carlsbad, CA, USA) were used throughout. All laboratory work was conducted at the Shoklo Malaria Research Unit microbiology laboratory in Mae Sot, Tak Province, Thailand.
To compare virologic results from 2009 with our surveillance data from 2008, we subsequently restricted the 2009 dataset to match data collected in 2008 (i.e., we included only patients whose illnesses met the strict case defi nitions and who were sampled on either Monday or Tuesday in the outpatient department). Clinical and laboratory data collected in 2008 were identical to data collected in 2009.
To estimate the incidence of infl uenza-associated illness, we reviewed passive disease surveillance data collected by the hospital in Maela and collated by the Com- mittee for Coordination of Services for Displaced Persons in Thailand. This surveillance system captured data only on patients visiting the hospital for treatment. The number and incidence rate (calculated by using monthly camp population census data) of clinically diagnosed upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) were reported by month. No information was available to determine the number of ILI cases; therefore, we could not estimate the proportion of URTIs caused by infl uenza viruses in Maela. However, because most LRTIs reported are likely to be clinical pneumonia, we estimated the incidence of infl uenza-associated pneumonia as the incidence of LRTI multiplied by the percentage of pneumonia patients with specimens positive for infl uenza A. To determine the effect of pandemic (H1N1) 2009 on overall case numbers, we compared 2008 data with 2009 data.

Ethics
The Human Studies Oversight and Review Team of CDC reviewed the surveillance project and declared it to be a nonresearch activity, as defi ned by US 45 CFR 46.102(d). Therefore our study was exempt from the need for full review by an institutional review board.

Statistical Analysis
All statistical analyses were performed by using STATA version 10.1 software (StataCorp, College Station, TX, USA). Categorical variables were analyzed by using the Fisher exact test; continuous variables were analyzed by using the Wilcoxon rank-sum test (because none were normally distributed). Two-tailed p values <0.05 were considered signifi cant. Epidemiologic week numbers were calculated by using standard criteria (23).

Results
During May 1-October 31, 2009, a total of 324 patients were included in the surveillance. Of these, 19 were excluded from further analysis; 18 patients did not meet the clinical case defi nitions, and no NPA specimen was received for 1 patient (Figure 1).
Pneumonia was diagnosed for 234 (77%) of the 305 eligible patients, and ILI was diagnosed for 71 (24%). For patients with pneumonia, median age was 2.0 years (range 0.1-68 years) and 55% were male; for those with ILI, median age was 1.4 years (range 0.2-10 years) and 54% were male.
Fifty seasonal infl uenza A infections and 17 pandemic (H1N1) 2009 infections were detected by rRT-PCR. Fortynine of the 50 seasonal infl uenza A infections were subtyped as H1N1; one was subtype H3N1 (Figure 2;  with dual virus infection were not signifi cantly more ill than those with infl uenza A infection alone (3/7 vs. 26/60; p = 1.0). Illnesses for 205 (67%) patients met the strict case definition for ILI or pneumonia; 100 (33%) met only the expanded case defi nitions. Age distribution and proportion of infl uenza A viruses did not differ signifi cantly between the strict and expanded case defi nition groups. However, a signifi cantly higher proportion of patients with ILI (18/25 vs. 6/46; p<0.001) or pneumonia (99/180 vs. 5/54; p<0.001) whose illnesses met the strict case defi nition were hospitalized, which suggests that the expanded case defi nitions captured patients with milder illnesses.

Discussion
Our study demonstrates that infl uenza virus infections are common etiologic agents of respiratory infection in a Southeast Asian refugee population living in crowded conditions. During the 6 months of surveillance in 2009, infl uenza A viruses were detected by rRT-PCR in 23% of clinical pneumonia and 20% of ILI cases sampled, representing a considerable impact that this vaccine-preventable disease has among patients with ARI.
Maela is an overcrowded and relatively closed refugee camp and therefore might be considered an ideal location for a novel infl uenza virus to cause an explosive outbreak. However, the number of confi rmed cases indicated that no major outbreak occurred in 2009. After the fi rst case of pandemic (H1N1) 2009 was identifi ed in August, these cases increased modestly in September, then substantially declined during October. Overall, only 25% of all infl uenza A viruses were determined to be the pandemic strain. However, supportive data show a change of the predominant infl uenza virus. In late August 2009, seasonal infl uenza A (H1N1) was the predominant circulating virus; during the subsequent 2 months, only cases of pandemic (H1N1) Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16   2009 were detected. During May-August, the incidence of LRTI and URTI in cases captured by the passive surveillance system was higher each month in 2009 than in 2008. The rates of URTI were similar in September and October of both years, whereas the LRTI rate was higher in October 2008 than in October 2009. Pandemic (H1N1) 2009 did not clearly increase in case-patients with ARI after its fi rst detection in the camp in August 2009. However, surveillance did not capture mild infections that did not result in visits to the outpatient department. The occurrence of most infl uenza A infections in patients who had pneumonia most likely refl ects a sampling bias, although infl uenza is a generally underrecognized cause of pneumonia in the tropics (24). ILI is not a routinely used diagnosis for the clinic staff at Maela, so most of the ILI case-patients likely were not interviewed and sampled. However, when infl uenza A was identifi ed, pandemic (H1N1) 2009 case-patients were less likely than seasonal infl uenza case-patients to have been hospitalized. This information suggests that, in this population, illness caused by pandemic (H1N1) 2009 was no more severe than illness associated with seasonal infl uenza A. Several confounding factors, unrelated to the innate pathogenicity of the viruses, may account for this fi nding: 1) the timing of the modifi cation of case defi nitions in relation to the appearance of pandemic (H1N1) 2009; 2) differences in age distribution; and 3) presence of underlying illnesses in the patient groups. Data regarding underlying medical conditions were not collected as part of this surveillance so the effect of other conditions cannot be assessed. To prevent spread of infection, public health systems may request persons with ILI to self-quarantine, which might result in underestimation of the number of cases identifi ed in clinic-or hospital-based surveillance systems. During the 2009 infl uenza season, announcements regarding infl uenza and the need for good hygiene were made on the Maela public address system; healthcare workers reinforced these messages by home visits. Whether this intervention had any effect on healthseeking behavior remains unclear. An infl uenza triage system was in operation at the hospital, but our surveillance staff had access to patients seen and treated in this area.
Our study has several limitations. Most importantly, not every patient eligible for sampling was included, frequently because the patient refused or clinic staff failed to identify patients with illnesses that met the case criteria. These data were not recorded, so the effect of this bias cannot be estimated. As previously discussed, ILI is not a frequently used diagnosis outside this surveillance program, and most cases with this clinical syndrome were diagnosed as common cold. Many of the ILI cases documented were miscategorized in the clinic as pneumonia but were subsequently found not to meet the case defi nition, explaining the presence of persons hospitalized with ILI. Overall, these factors may bias toward sampling of case-patients who had more severe symptoms. Also, screening took place in only 1 of the 2 hospital outpatient clinics. However, because both are general clinics, the impact of this screening is likely to be refl ected in the absolute number of cases detected rather than in the proportion of ILI and pneumonia cases caused by infl uenza viruses. Regarding laboratory data, the likelihood of confi rmation of infl uenza infection is associated with the clinical case defi nitions in use: the strict ILI case defi nition used in our surveillance has a sensitivity of 98.4%-100% but a specifi city of only 7.1%-12.9% (25). In another study, the probability of having a positive infl uenza virus PCR was directly related to magnitude of fever (26). Therefore, given the bias toward severe cases, we may have considerably underestimated the impact of infl uenza in Maela.
As a result of the limitations noted above, we could  (27). Given the likely health inequalities between our refugee population and rural provinces in Thailand, direct comparison of these datasets is diffi cult. However, the incidence of infl uenza-associated pneumonia in Maela was ≈5× higher than in the Thai provinces (27).
Population structure, such as the number of young children and elderly persons, may account for some of this difference, because the incidence of infl uenza infection is highest in these age groups. As with ILI, the case defi nitions used may have affected the data or the use of different laboratory confi rmation tests for infl uenza infection may have resulted in considerable variation in disease rates between studies; the study in Thailand used RT-PCR for laboratory confi rmation. Although the rates of infl uenzaassociated pneumonia were different in the refugee camp, the proportions of pneumonia cases associated with infl uenza were similar (23% vs. 18%).
Methods of preventing or mitigating infl uenza outbreaks in a community include vaccination; use of antiviral drugs; and basic infection control measures, particularly good respiratory etiquette, hand washing, and social distancing (28). The World Health Organization has devised a specifi c infl uenza pandemic preparedness and mitigation plan for refugee and displaced populations, but implementation requires the coordinated efforts of healthcare providers (frequently nongovernmental organizations) and governments to ensure that control measures are available and used effectively (29). Because resources are likely to be strained during an infl uenza pandemic, refugee and displaced populations might not be adequately represented in a country's pandemic preparedness plan. Availability of items required to control infl uenza transmission (personal protective equipment, vaccines, and antiviral medication) may be limited for this population without robust planning at the local and national levels. In addition to pandemic preparedness, camp administrators and donor agencies should consider routine vaccination for seasonal infl uenza in these populations.
Continuation and refi nement of this surveillance as the pandemic continues may provide further insight into the epidemiology of infl uenza in resource-poor rural Asian populations. Work such as this solidifi es the need of inclusion of refugee populations in infl uenza vaccine strategies and pandemic planning.