The seasonality of influenza we documented in West Java, Indonesia during 2008-2011 showed a typical pattern for a tropical region—with year-round influenza virus circulation, sharp short-spikes, and large variation of peak timing—and is consistent with previous studies by Beckett et al between 1999-20035 and Kosasih et al during 2003-2007.9 Peaks in influenza incidence coincided with higher precipitation months which generally occurred between December to March, except for July-August 2009 when A(H1N1)pdm09 virus emerged. Periods of high influenza activity ranged from 2 to 6 months, followed by low influenza activity for 2 to 4 months. Every year, we observed two or three peaks of increased influenza activity, with each peak typically predominated by a different virus and variability in the age group with the highest proportion of influenza positives from season to season. This variation could be due to differences in immune susceptibility by age, introduction of bias from differential health seeking behavior by age group or seasonal changes in health care seeking behavior, or chance variation due to smaller sample size when stratified by season and age group. However, a previous community cohort study in Vietnam also reported differences in impacted age groups by year.15
This continuous and dynamic year-round circulation of influenza viruses in West Java suggests that the best timing of influenza vaccination is not easily defined; therefore, if a national influenza vaccination program is implemented in Indonesia, one strategy is for influenza vaccination to begin as soon as influenza vaccine is available each year. One study suggested that influenza vaccination should be given before the Hajj,16 since thousands of people travel from Indonesia to the Hajj annually and influenza vaccination is required for Hajj pilgrims at entry into Saudi Arabia. However, the dates of the Hajj pilgrimage vary from year to year, adding practical challenges to this implementation. Alternatively, since increases in influenza activity coincide with high precipitation months, influenza vaccination could be implemented before the start of the rainy season, usually around October or November.
We observed that following the introduction of the 2009 H1N1 pandemic virus in Indonesia, overall influenza virus activity in the population dropped significantly and was not detectable in our study during January 2010. This was despite the relatively higher precipitation levels during that interval (Figure 2). Other studies conducted during the same period, including a study in East Java, Indonesia by Yamaoka et al4, in rural Thailand by Baggett et al17, in an urban Kenya by Katz et al18, and in Ha Nam District, Vietnam by Horby et al15, also showed a similar pattern of low seasonal influenza A and B virus activity after the first 2009 H1N1 pandemic wave. This suggests that the first wave of the pandemic might have led to a disruption of influenza virus activity afterward; not only in Indonesia, but also in other tropical climate countries. We also observed displacement of seasonal influenza A(H1N1) virus by the emergence of influenza A(H1N1)pdm09 virus in mid-2009.
To our knowledge, there are no data on the population-based incidence of uncomplicated influenza in Indonesia. The estimated annual incidence of influenza A in the community varied from 1.6 to 2.3 per 1,000 persons during the 3 years of our study. The CHCU rates we used to adjust the incidence were comparable with the estimated medically-attended rate among cases of influenza from a study in South Africa.10 The incidence of influenza in our study was low compared to the influenza incidence based among ambulatory patients in sub-tropical China (4.1 to 19.2 per 1,000 population in 2008 and 2009),19 Kenya (13.6 to 23 per 1,000 person-years in 2007 to 2010),18 and Bangladesh (130 to 170 per 1,000 person-years in 2009 and 2010).20 The lower influenza incidence in our study might reflect differences in the study populations (health seeking behavior, demographics, nutrition, and medical risk factors) and health system factors (health care accessibility),3 or study design and methodology (inclusion criteria, case definition, laboratory testing, and estimation approach).
We found children younger than 5 years old to be the most affected age group for both influenza A- and B-associated illness, with estimated incidence of 7 to 10.6 per 1,000 person-years and 0.4 to 4.3 per 1,000 person-years, respectively. The exception was during 2010, when school-age children (6-15 years old) had the highest estimated annual incidence of influenza B. Other studies in Indonesia and Kenya reported that the highest incidence of hospitalized influenza-associated severe acute respiratory infection was in children under 5 years old.7,21 Our finding based upon virologic testing that showed young children were most affected by influenza is consistent with a community cohort study that utilized serological testing for influenza virus detection.22 School-age children had the second highest influenza incidence, similar to what was reported in a community cohort study in Vietnam.15 One study indicated that children aged 5-17 years are a driver of influenza A virus epidemics and that influenza vaccination of this group may contribute to reducing the overall impact upon the community.23
This study showed a trend of decreasing annual cumulative incidence with increasing age for both influenza A and B cases (Figure 4). The age-specific influenza incidence trends did not change when we performed stratified analyses by influenza A virus subtype, influenza B, or study sites. Persons older than 65 years old had very low estimated influenza incidence compared to younger age groups (Table 2), consistent with the findings of an influenza surveillance study conducted during a similar period in East Java, Indonesia.4 The small number of older adult subjects enrolled in this study, which appeared to be proportional with the Indonesian population age structure, implied a higher uncertainty or random error margin. It is possible that the small number of infections we detected in older adults was because elderly persons may not always seek medical care or may not manifest fever with influenza when presenting for primary care and would have been missed by our ILI case definition, so we would have underestimated influenza disease burden in the elderly population. To perform sensitivity analysis, we also calculated the annual incidence among elderly by using a lower CHCU percentage among elderly (21.7%) as reported from another Indonesian study,24 but the incidence of influenza among elderly was still the lowest among all age groups (Supplementary Table 1).
There were several limitations of this study. It is known that most persons with influenza do not seek medical care10,21 and estimates of disease burden in the community, based on passive surveillance case detection, need to account for health care utilization and other factors such as subject refusal.25 We adjusted our incidence estimates to account for health care utilization of persons with ILI to account for this bias. However, the health care utilization percentage used for adjustment in this study was derived from an unpublished survey that was conducted after our study (2014) with limited sample size. In 2014, the National Health Security program (JKN) for Indonesian universal health care was launched that increased health care utilization in general, including for persons with ILI. The three clinics that participated in ILI surveillance were open 5 days per week and it is possible that some persons with ILI were missed if the clinics were open 7 days per week. Therefore, our adjusted incidence estimates likely underestimate the incidence of ILI and influenza in the community. Moreover, health care utilization is dependent on access to medical services, which may vary by location, while we assumed the same level for the whole study area. Therefore, the adjustments made in this study might not fully address health seeking behavior that differs temporally and geographically. In addition, the confidence intervals of the incidence estimates were calculated by the WHO method, which does not address uncertainty in the proportion of ILI cases that present to included clinics, and could lead to further imprecision of the incidence estimates. We also did not assess asymptomatic influenza virus infections, and since enrollment and testing for influenza required meeting the ILI case definition, symptomatic individuals with influenza virus infection without ILI and who sought medical care were not captured. Therefore, our estimates of symptomatic influenza incidence underestimate the overall burden of influenza in the community. The refusal rate was very low, but we did not record the number and the characteristics of the refusal group and were unable to adjust for the percentage of persons who decline to participate in the study; we assumed refusals occurred similarly across age groups. To estimate the population at risk, we assumed a fixed cohort population, which may have changed over the study period. Overall, the study population in these two areas was relatively small and might limit the generalizability of findings to other areas of Indonesia.