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.