
==== Front
Public Health Pract (Oxf)
Public Health Pract (Oxf)
Public Health in Practice
2666-5352
Elsevier

S2666-5352(24)00072-7
10.1016/j.puhip.2024.100535
100535
Short Communication
An opportunity missed: Strengthening health system data on multisystem inflammatory syndrome in children from low- and middle-income countries in Asia
Ong D.S. darren.ong@mcri.edu.au
ab⁎
Licciardi P.V. paul.licciardi@mcri.edu.au
ab
Mulholland K. kim.mulholland@lshtm.ac.uk
ac
Do L.A.H. lienanhha.do@mcri.edu.au
ab
a Infection, Immunity & Global Health, Murdoch Children's Research Institute, The Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria, 3052, Australia
b Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria, 3052, Australia
c Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom
⁎ Corresponding author. Murdoch Children's Research Institute, The Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria, 3052, Australia. darren.ong@mcri.edu.au
18 8 2024
12 2024
18 8 2024
8 10053519 3 2024
8 7 2024
12 7 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication associated with SARS-CoV-2 infection. The clinical epidemiology of MIS-C is not completely understood in low- and middle-income countries (LMICs) due to limited reporting, including in Asia where there was a substantial burden of COVID-19. We aimed to discuss the challenges of diagnosing MIS-C and factors which may cause children from Asian LMICs to have an increased risk of MIS-C.

Methods

Not applicable.

Results

The burden of MIS-C in Asian LMICs may be disproportionately high due to underlying risk factors, resource-limited health systems, and the increased infectivity and transmissibility of recent SARS-CoV-2 variants. Complex clinical features of MIS-C contributed to missed or delayed diagnosis and treatment, while underlying risk factors including ethnicity, chronic health conditions, and socioeconomic factors may have predisposed children in Asian LMICs to MIS-C.

Conclusions

There was a lack of data on the clinical epidemiology of MIS-C in Asian LMICs during the COVID-19 pandemic, despite reports of higher paediatric mortality rates compared to high-income countries. This highlights the need for LMICs to have strong surveillance systems to collect high-quality and timely data on newly emerging complications associated with a pandemic, such as MIS-C. This will lead to rapid understanding of these emerging complications, and inform clinical management, disease prevention and health system planning.

Keywords

MIS-C
COVID-19
Global health
Public health
Child health
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pmc1 What this study adds

• MIS-C may have disproportionately affected children in low- and middle-income countries in Asia.

• There was limited data on the clinical epidemiology of MIS-C from this region, which experienced a high burden of COVID-19.

• Complex clinical features and the lack of surveillance data may have contributed to missed or delayed diagnosis and treatment of MIS-C in the region.

2 Implications for policy and practice

• It is important to have active surveillance systems in low- and middle-income countries that are able to collect high-quality and real-time data on pandemic-associated complications.

• There is a need to have a multinational consortium and specific national bodies to coordinate surveillance efforts and to share timely data during health crisis events.

• Robust and active surveillance data can inform disease prevention, clinical management, and health system planning.

3 Main text

Multisystem inflammatory syndrome in children (MIS-C) causes severe morbidity and mortality in paediatric populations infected with SARS-CoV-2. During the COVID-19 pandemic, high quality data on MIS-C was reported from high-income countries (HICs), where the clinical epidemiology, laboratory findings, and outcomes of MIS-C were well described. The United States (US), which has one of the most comprehensive MIS-C surveillance programs globally, experienced a peak incidence of 6.8 (95 % confidence interval [CI]: 6.6–7.0) MIS-C cases per million person-months between October 2020 to April 2021 [1]. However, there was a lack of MIS-C data from low- and middle-income countries (LMICs), particularly in Asia, despite a significant burden of COVID-19 during the Delta and Omicron variant waves. A hospital cohort study in central Thailand estimated an incidence of 15.0 (95 % CI: 9.7–22.1) MIS-C cases per 100,000 person days between 2020 and 2021 [2]. However, this is one of the very few studies describing the burden of MIS-C in Asian LMICs, and population-wide data is not available.

A review of the epidemiological, clinical, and prognostic characteristics of global MIS-C cases noted the lack of data availability from Asia [3]. Children in the region may have an increased risk of delayed or missed MIS-C diagnosis due to several reasons, including complexities in diagnosis, an elevated risk of other clinically similar diseases, poor determinants of health, and limited health resources. We provide an overview of some studies that described the clinical epidemiology of MIS-C in Asian LMICs and discuss the need for enhanced surveillance and capacity to improve health equity of children living in the region.

3.1 Complexities in MIS-C diagnosis, management, and outcomes

MIS-C cases in LMICs were more likely to fulfil the diagnosis criteria of incomplete or complete Kawasaki Disease [4], which may have resulted in an underestimation of its true burden. Importantly, clinical features of MIS-C, such as erythema and gastrointestinal symptoms, are similar to those of dengue fever and enteric infections which are endemic to the region [5]. These overlapping clinical features may have exacerbated incorrect diagnoses, especially when countries scaled back COVID-19 public health and social measures which resulted in the recirculation of these pathogens [6,7].

Accurate and timely diagnosis of MIS-C has implications on clinical management. In Singapore, a HIC in Southeast Asia, positive clinical outcomes were attributed to multidisciplinary management, timely diagnosis, and early initiation of treatment [8]. An Indonesian study presented similar findings [9]. However, healthcare systems in the region are often resource-limited and it is difficult to implement timely diagnosis and management to improve clinical outcomes.

Long-term complications following a MIS-C diagnosis were not common. An Indian study found very few children with long-term sequelae at 1–2 years post-diagnosis, including none with remaining abnormal echocardiography, which often presents with acute MIS-C [10]. These findings are similar to studies from other HICs, which suggests significant systemic abnormalities during the acute phase while only a small subset of patients had persistent sequelae [11,12].

3.2 MIS-C and ethnicity

There are conflicting findings from the few studies of the association between MIS-C and ethnicity. An 11-fold (95 % CI: 2.2–57) increase was observed in the relative risk of developing MIS-C in Asian versus Caucasian children in HICs, although the sample size was small [13]. A study from the US found a higher incidence of MIS-C in Asian and Pacific Islander children (adjusted incidence rate ratio: 2.9, 95 % CI: 1.4–5.8), compared to Caucasian children [14]. A meta-analysis found low-certainty evidence that Asian children may be at increased risk of MIS-C compared to Caucasian children (odds ratio: 1.7, 95 % CI: 0.9–3.2) [15], while another meta-analysis found a reduced risk (risk ratio: 0.2, 95 % CI: 0.2–0.2) [4]. However, these analyses did not consider potential confounders such as demographic denominators or equitable access to health services amongst different ethnic groups, and included limited studies from Asia and LMICs. We also note that all the above studies did not explore specific ethnicities beyond the broader “Asian” ethnicity.

Findings from HICs are not directly applicable to LMICs due to inherent differences in the socioeconomic landscape, determinants of health, and overall ethnic composition. Understanding MIS-C in a regional context would have enabled identification of vulnerable groups or settings where targeted and timely interventions were needed.

3.3 Chronic health conditions and socioeconomic risk factors

Chronic conditions which are not prevalent in HICs may contribute to a higher risk of MIS-C in LMICs. An analysis of the Indonesian COVID-19 paediatric registry found a high prevalence of malnutrition (18.0 %) and malignancy (17.3 %) amongst non-survivors [16]. A Middle Eastern study also found that most hospitalised, paediatric COVID-19 patients had underlying comorbidities, including malnutrition (77.4 %), neurologic or learning disorders (21.4 %), and malignancy (10.2 %) [17]. Nutritional disorders are prevalent in the region, with 5.4 % and 23.2 % of children aged 5–18 years in the Asia-Pacific region experiencing under- and over-nutrition, respectively [18].

Differences in socioeconomic, cultural, and environmental determinants of health may also contribute to the risks of MIS-C. A US study found that 51 % of children with MIS-C were from neighbourhoods with the lowest quartile socioeconomic status and 53 % from the highest quartile of the social vulnerability index [19]. Several factors have been proposed to explain the uneven burden of COVID-19 outcomes in Black and Hispanic adults in the US. Health inequity and food insecurity may have led to a high incidence of underlying comorbidities, high-density living conditions, and systemic discrimination which resulted in a general distrust of the health system, delays in seeking care, and differences in quality of care [20]. The extent to which these factors contribute to disproportionate MIS-C outcomes is not known but health and social inequities are not isolated to HICs and are prevalent in Asian LMICs. The lack of universal health coverage and inadequate health systems lead to diminished health-seeking behaviours, which exacerbate the risk of unfavourable MIS-C outcomes.

3.4 Variants, disease burden and relative risks of MIS-C

The region has faced substantial COVID-19 burdens, mostly during the Delta and early Omicron variant waves. Before the Omicron period, South Asia had the highest cumulative number of cases, with an estimated 1.34 billion infections and reinfections combined, and some areas experiencing cumulative death rates of over 450 deaths per 100,000 population [21]. However, trends in paediatric SARS-CoV-2 cases have been poorly described for the region. Although the Omicron wave caused a substantial peak in case numbers and hospitalisations in all age groups [22,23], surveillance data from HICs did not indicate an equivalent spike in MIS-C cases and deaths, as was seen with Delta [24,25]. A review found that studies from LMICs showed less frequent MIS-C patients than HICs, but there was a higher proportion of mortality, suggesting that the true number of MIS-C cases could be largely underestimated in LMICs [26].

The paucity of local MIS-C data in Asian LMICs highlighted a major gap in paediatric COVID-19 knowledge. This was particularly true for Asia where outbreaks of endemic diseases, such as dengue fever, occurred concurrently with the Omicron wave and posed challenges to distinguish between COVID-19-related diseases versus other clinically-similar endemic diseases [27]. Further understanding of MIS-C in the local context was critical to improve disease prevention, management, and treatment.

4 Conclusion

Although SARS-CoV-2 is seemingly on the path towards endemicity, it is not known whether future variants may cause children to become more susceptible to developing MIS-C. COVID-19 vaccines are effective against MIS-C and are available for children, but there is poor uptake globally and many LMICs have limited access. Cases of MIS-C continue to be reported from the US, which has one of the strongest MIS-C surveillance networks [1]. The lack of MIS-C data from Asia in the first year of the pandemic could have been due to the low burden of disease [28], but data collection and reporting did not seem to improve despite the substantial COVID-19 burden caused by the Delta and Omicron waves. The systematic collection, analysis, and interpretation of MIS-C data from LMICs in Asia was crucial given reports of higher paediatric deaths in LMICs compared to HICs [26]. This could have improved clinical management of the acute phase of MIS-C, and informed health system planning and paediatric COVID-19 vaccination strategies.

Multiple competing priorities arise during a health crisis event, and it is often easier to reflect in hindsight. Establishing and maintaining a robust surveillance network of serious complications associated with a newly emerging disease is a top priority for LMICs, where these diseases often spread rapidly and over-burden health systems. A surveillance network would provide timely and comprehensive understanding of these complications to improve disease prevention, diagnosis and management, and facilitate effective resource allocation in an over-stretched system. Ultimately, a strong surveillance system would prevent the further stressing of local healthcare systems and limit the exacerbation of health inequities.

Authors’ contributions

DSO conceptualised, performed literature search, drafted, and finalised the manuscript. LAHD and PVL provided supervision to DSO and critically reviewed the manuscript. KM provided expert advice and reviewed and edited the manuscript.

Ethics approval

This work did not require human research ethics approval.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

KM was a member on the Data Safety Monitoring Board of a Novavax COVID-19 vaccine trial. All other authors have no conflicts of interest to declare.

Acknowledgments

This work did not receive any grants from funding agencies. The authors acknowledge support provided to the Murdoch Children's Research Institute through the Victorian Government's Operational Infrastructure Support Program.
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