Discussion
In this literature review, articles were searched and summarized to better understand the epidemiology of respiratory virus infections in Indonesia. After reviewing the final 66 articles, we found that most of the studies focused predominately on influenza A and B, RSV, avian influenza H5N1, and SARS-CoV-2. Fewer studies were conducted on enterovirus, torque teno virus, and cytomegalovirus.
The first study reporting on the epidemiology of influenza A or B in Indonesia was conducted in Papua in 1998 16. Subsequent studies that have been published have prioritized Jakarta17, 18, 19, 20, 21, 22, 23 and Bali13, 18, 24, 25 as the main study locations. Only after the 2009 influenza H1N1 pandemic did studies on seasonal influenza increase. These studies were primarily conducted via hospital-based surveillance, with children and elderly as the main study population10. Data from these studies show that peak prevalence tended to coincide with the rainy seasons 17, 22, and males were more likely to experience ILI than females26. Meanwhile, in rural areas, there was also increasing patterns of influenza infections in households with young children and poultry 27. Although, seasonal influenza has been identified as an important contributor to acute respiratory disease in Indonesia 13, 21, and 20% of total cases of respiratory disease are attributed to influenza A and B in all regions of the world 28. A 2011 study showed that influenza virus only contributed to 6% of 333 SARI cases in Indonesia20. A lack of reliable surveillance data was acknowledged as a primary reason for this discrepancy with regional and global averages 20, 28
The studies on influenza H5N1 were primarily conducted in Jakarta and Bali 21, 22, 29, 30, 31 at the time of a national outbreak that occurred in 2006. Influenza H5N1 studies published after the outbreak included some new epidemiological studies, but also retrospective studies that used primary data from the outbreak21, 22, 32, 33. Data from the outbreak reports show that sporadic family clusters had a higher proportion of case fatality29, 34 with mild-moderate variations in symptoms13, 29, 30, 35, which especially occurred in patients under 18 years of age 22, 30 and among poultry workers36 who had direct or indirect contact with infected poultry30, 37. Although, there was no strong evidence of human-to-human transmission 31, antiviral regimens were given as early as two days following the onset of non-specific symptoms 38, 39. The mortality rate of influenza H5N1 infections among humans was still very high 32, increasing from 73% in 2005 to 100% in 2012 33.
Our review found a large number of SARS-CoV-2 papers that were published in response to the global pandemic that began in January of 2020. We also found that the majority of SARS-CoV-2 studies were conducted in densely populated areas of economic and national significance such as Jakarta 40, 41, 42, 43, 44, 45 Yogyakarta46, 47, and the islands of Java (West Central and East) and Bali 48, 49, 50, 51. Our review did not include any SARS-CoV-2 studies examining lesser populated provinces like North Kalimantan, Maluku, and West Papua which could indicate a gap in funding and infrastructure required to conduct epidemiological investigations away from populous urban centers. In terms of study populations, the majority of studies were case reports of SARS-CoV-2 patients. Studies like Baskara et al. 2021 46 found that treating SARS-CoV-2 patients in low-resource settings was challenging due to a lack of ventilation support and intensive care facilities. In these settings, there are additional difficulties in distinguishing the clinical characteristics of SARS-CoV-2 from other respiratory diseases like tuberculosis. Other case reports highlight the radiological findings and benefits of using chest X-ray’s in screening for SARS-CoV-2 among patients 47 while others describe the potential for misleading diagnoses when using unconventional methods like chest CT scans to detect SARS-CoV-2 42.
Most SARS-CoV-2 studies were conducted on younger and middle-aged adults below the age of 65. These included Widysanto et al.52, Putra et al. 43 and Kadriyan et al. 53. As for older population groups (>65 years old), Tenda et al. 45 included an individual that was 71 years old, while Rozaliyani et al.44 examined individuals from all age groups and found that older age, dyspnea, pneumonia and pre-existing hypertension were associated with death from SARS-CoV-2. The study also described how the number of deaths decreased in the weeks after the implementation of large-scale social restrictions thus supporting the efficacy of such interventions. Gunadi et al. 54 found that 39 of 60 (65%) SARS-CoV-2 samples from Indonesia had the D614G mutation which was recently discovered to be more transmissible than previous variants, which is the only report included in our review that evaluated SARS-CoV-2 variants 55. Anggraini et al.48 and Somasetia et al. 50 focused specifically on high-risk population groups where they observed that a low neutrophil-to-lymphocyte ratio decreases the risk of SARS-CoV-2 in pregnant women, and reported a case of a 6-year old child being co-infected with SARS-CoV-2 and dengue. Our review did not find any studies that evaluated the transmissibility or case fatality rate of SARS-CoV-2. It may be that this type of epidemiological data is not publicly accessible.
Studies included in our review indicated there is a significant burden of a lower respiratory tract illness (LRI) caused by RSV among the children in Indonesia 56, 57, 58. Provinces with high population densities such as West Nusa Tenggara, and West Java were represented in most of the RSV studies 56, 57, 58, 59, 60. Our review indicated that the incidence of RSV related to LRI in Lombok island and Bandung city is lower in children less than 6 months of age compared to the older children 56, 57, 59. In addition, Simoes et al. 57 reported a higher RSV incidence among children in rural areas compared to urban areas. Studies from Djelantik et al. 59, Wertheim et al.61, and Widhidewi et al. 24 reported that the peak of RSV cases occurred during the rainy season (March to July). However, there were no consistent conclusions regarding the association between seasonality and the occurrence of RSV disease in Indonesia. A study from Omer et al. 58 reported an association of rain with a 64% higher incidence of RSV disease (incidence rate ratio 1.64, 95% confidence interval 1.13-2.38), whereas, Simoes et al. 57, and Djelantik et al.59 reported no association of RSV outbreaks with humidity, temperature, or rainfall. Therefore, further investigations are required to determine the seasonality of RSV in Indonesia.
Few studies included in this review evaluated the epidemiology of enterovirus 62, 63, torque teno virus64, and cytomegalovirus virus 42. Most of these studies were conducted among children less than 5 years of age who were hospitalized with ILI or SARI in Jakarta and Java42, 62, 64, but information regarding seasonality and transmission dynamics for these viral groups is not available. Enteroviruses, including EV68, EV71, coxsackieviruses, rhinoviruses, echoviruses, and polioviruses, are the important viral group that may have the potential for zoonotic transmission between animals and humans65, 66.
Indonesia, like most countries in the world, has developed ILI and SARI surveillance networks under the WHO’s Global Influenza Surveillance and Response Systems (GISRS) 13. This network was designed to improve influenza disease control by providing support on epidemiology, research, influenza vaccine recommendations, laboratory diagnostic tools, antiviral, and public health risk assessment. However, due to challenges such as cost-effectiveness, complex computer networking and technical expertise requirements, and limited diagnostic capacities of clinical laboratories, the ability of this network to provide robust data on emerging and endemic respiratory viruses in Indonesia has been limited. Furthermore, most of the surveillance activity in Indonesia is conducted using hospital based surveillance as a response to frequent outbreaks of influenza subtypes and sporadic cases of RSV from July to November 61. As a result, there is more concentrated information on influenza viruses and RSV viruses, but sporadic or missing data for other common respiratory viruses. Additionally, limited information is available regarding the environmental persistence of influenza, RSV, and other respiratory viruses outside hospital settings. As a result, there remain large gaps of information regarding the epidemiology of respiratory viruses in Indonesia.
Our review identified only two papers from the Garuda database that evaluated the epidemiology of human respiratory viruses in Indonesia. This suggests that language is not the primary reason that data on this topic is not largely available in research journals. Additionally, our review indicated a concentration of studies conducted mostly in populated and economically developed areas, such as Jakarta, Bali, Java, (West, Central, and East), Yogyakarta, and West Nusa Tenggara. Limited research has been reported on populations living in less developed areas. In evaluating the studies, a clear publication trend was observed, where there would be a surge in published papers after a viral outbreak has occurred in Indonesia. This trend can be observed with the outbreaks of SARS in 2002-2004, avian influenza in 2005-2006, influenza A H1N1 in 2009, and most recently with SARS-CoV-2. A large proportion of the studies in our review are based on outbreak based passive surveillance, retrospective studies, hospital level ILI, and SARI surveillance systems. Fewer studies use active surveillance approaches.
Overall, our review showed a surprisingly low number of published papers assessing the epidemiology of viral respiratory pathogens in Indonesia. Of the studies included, the majority were conducted in urban centers of high population density and economic significance. Our findings also indicated a clear publication trend where papers have been published only after a large viral respiratory disease outbreak has occurred. Fewer papers have been published assessing the seasonal burden of viral respiratory disease. These observations indicate a great need to further enhance surveillance capacity for viral respiratory diseases in Indonesia to better track and characterize this important disease burden.