Early Detection of Pandemic (H1N1) 2009, Bangladesh

To explore Bangladesh’s ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June–July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population.

To explore Bangladesh's ability to detect novel infl uenza, we examined a series of laboratory-confi rmed pandemic (H1N1) 2009 cases. During June-July 2009, event-based surveillance identifi ed 30 case-patients (57% travelers); starting July 29, sentinel sites identifi ed 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population.
A fter 2 children in North America were confi rmed to have pandemic (H1N1) 2009 infections on April 17, 2009 (1), the virus rapidly spread throughout the world. By July 2, 2009, Southeast Asia had reported 1,866 cases (2). Offi cials worried about the effects of pandemic (H1N1) 2009 on the 147,030,000 million population (1,021 persons/km 2 ) of Bangladesh (3), where 41% of children <5 years of age are underweight (4). These concerns prompted Bangladesh to leverage 3 existing surveillance systems (5), preparedness plans, and personal protective equipment and oseltamivir stockpiles to guide the response to the pandemic.
During April 2009, Bangladesh enhanced surveillance by implementing border screenings. Upon identifi cation of pandemic (H1N1) 2009 in the general population, Bangladesh encouraged physicians to empirically treat patients who had acute respiratory infection with free oseltamivir if they had risk factors for complications from infl uenza (i.e., age <5 years or >65 years; diabetes; chronic heart, lung, or liver disease; asthma; neurologic, neuromuscular, hematologic, or metabolic disorders; immune suppression; cancer; obesity; pregnancy; danger signs [rapid, labored or noisy breathing, lethargy, cyanosis, inability to drink, or convulsion], or hospitalization) (6). We report the effects of this strategy on a case-series of laboratory-confi rmed pandemic (H1N1) 2009 infection identifi ed through enhanced surveillance.

The Study
During 2007, Bangladesh started event-based surveillance for the early detection of public health events of international concern. At 6 government and 6 private hospitals ( Figure 1), physicians identifi ed >2 epidemiologically linked severe acute respiratory infections, defi ned as subjective fever within the past 21 days and cough or sore throat (5), or severe pneumonia, defi ned as cough or diffi culty breathing, chest in-drawing, stridor while calm, convulsions, inability to drink, lethargy, unconsciousness, or intractable vomiting. During April through November 2009, staff also administered ≈455,000 questionnaires to incoming land and air passengers, contacts, and referrals and collected throat and nasal swab specimens from those who reported cough, sore throat, or shortness of breath and had fever >38°C when assessed with thermal scanners.
During 2007, Bangladesh started sentinel-site surveillance for the early detection of novel infl uenza. During 2 days per month, physicians collected swab specimens from ambulatory case-patients at hospital clinics with infl uenza-like illnesses defi ned as sudden onset fever and cough or sore throat. Physicians also collected swab specimens from children <5 years of age hospitalized with severe pneumonia and person >5 years of age with severe acute respiratory infections ( Figure 1).
To explore the epidemiology of seasonal infl uenza, community-based surveillance began in Bangladesh during 2004. Teams visited an estimated 6,600 preselected households 2×/week to identify acute respiratory infections, defi ned as the manifestation of 1 major sign (i.e., reported fever; rapid, labored or noisy breathing; lethargy; cyanosis; inability to drink; or convulsion) or 2 minor signs (i.e., cough, rhinorrhea, sore throat, muscle/joint pain, chills, headache, irritability, decreased activity, or vomiting). During 2008, Bangladesh also established a birth cohort of 334 children to explore the potential effects of infl uenza on DISPATCHES their development. Teams visited preselected households 2×/week to identify acute respiratory infections among children <2 years of age. At both sites, teams referred casepatients to physicians who collected nasal wash specimens and provided free care.
Laboratorians tested samples from the 3 surveillance systems for pandemic (H1N1) 2009 virus by using realtime reverse transcription PCR (7). Investigators shipped a convenience subset of 28 virus samples to the Centers for Disease Control and Prevention, Atlanta, for antiviral testing and strain characterization.
Investigators described the epidemiology, healthseeking, treatment, and outcome of case-patients who had laboratory-confi rmed subtype H1N1 infection by using Pearson χ 2 , Fisher exact, and Wilcoxon rank-sum tests when appropriate. To estimate case-fatality proportion, teams telephoned case-patients or their families >1 month after illness onset.
The Government of Bangladesh conducted enhanced event-based surveillance in the context of emergency response. Ethics committees approved sentinel and community-based surveillance protocols.
During Isolates from case-patients were antigenically related to A/California/07/2009 (H1N1) and sensitive to oseltamivir. Of the 1,271 case-patients at high risk for complications, 535 (42%) sought treatment within 72 hours of symptom onset, and 7 (3%) of 207 case-patients at sentinel hospitals received oseltamivir ( Table 2). The proportion of treatmenteligible case-patients who received oseltamivir decreased from 100% to 0% from June 2009 to October 2010.
We identifi ed 3 (2%) of 182 event-based and 25 (5%) of 527 sentinel-site decedents (p<0.001) (Tabl e 2). Casepatients who subsequently died, sought treatment a median  Despite government efforts, case-patients sought treatment late, and oseltamivir was underutilized. Less than half (42%) of high-risk patients sought care within 48 hours of disease onset, when oseltamivir is most effi cacious. As in other studies (9), even severely ill persons who subsequently died were late in seeking treatment. Ill persons frequently were unfamiliar with risk communication messages and may have avoided the expense of seeking treatment. During 2009, only 34% of surveyed households recalled risk communication messages, none could identify oseltamivir (10), and those with a history of infl uenza-like illness paid an average of US $3 when seeking care (i.e., 9% of monthly household expenditure) (11).
While the government of Bangladesh provided initial case-patients with oseltamivir, community clinicians provided oseltamivir once pandemic (H1N1) 2009 had spread to the general population. Only a fraction of eligible case-patients then received oseltamivir. Possible explanations for the underutilization of oseltamivir include clinicians' lack of suspicion of infl uenza, awareness of treatment guidelines, familiarity with antiviral agents, access to oseltamivir stockpiles, or knowledge of the potential severity of pandemic virus.
Our fi ndings are based on a small case series. Although we identifi ed only 28 decedents, an ongoing study suggests that ≈6,000 persons died as a result of the pandemic (12). Nevertheless, we believe that our fi ndings are generalizable to Bangladesh because hospitals were selected as sentinel sites to provide geographically representative data.

Conclusions
Bangladesh has an effective surveillance system in place for detection of emerging infectious diseases. In spite of timely surveillance, prompt risk communications and free oseltamivir, response may have been hampered by persons' delays in seeking treatment and by the underutilization of oseltamivir. Our investigation suggests the utility of diverse surveillance systems, the limitations of antiviral drug campaigns, and the importance of infl uenza prevention through vaccines (e.g., 15 million pandemic [H1N1] 2009 vaccine doses donated to Bangladesh during 2010) and nonpharmaceutical interventions. Such campaigns remain insuffi ciently used in low-income countries where vaccines are expensive, access to clean water is inadequate, and covering a cough is not customary (13,14).