Impact of virus and bacteria co-detection in children with severe malaria

Abstract

Abstract Background Malaria is a leading cause of death in children under five years of age worldwide. Clinically, malaria, pneumonia, and other febrile illnesses often present with similar symptoms, complicating management. The extent to which respiratory pathogens influence the clinical outcomes of children with malaria is poorly defined. This study aimed to characterize the prevalence of respiratory pathogens and assess their potential impact on clinical outcomes among pediatric malaria cases. Methods From January 2021 through June 2023, children hospitalized with malaria in Blantyre, Malawi were enrolled, nasopharyngeal (NP) swab samples obtained and stored at -80 °C for further detection of 24 respiratory viruses, 3 herpes viruses and 10 bacteria using a PCR panel (TrueMarkTM 2.0, OpenArray). Clinical information was collected and analyses were conducted to assess the role of pathogen co-detection on clinical outcomes defined as development of sequelae or death. Results Of 91 children enrolled, median age was 4.5 years, ranging from 6 months to 13.5 years; 43% (n=39) were males. Overall, 6 (7%) children experienced severe sequelae and 15 (16%) died. Children that died were significantly younger (3.1 [2.3-4.5] yrs) compared to survivors (4.7 [3.1-7.1) yrs] and those who experienced sequelae (5.2 [3.7-6.8] yrs; p<0.01). Differences in fever, oxygen requirement, level of parasitemia and the Blantyre coma score according to severity are included in Table 1. A NP bacterial pathogen was identified in 97% (n=88/91) of children and detection rates varied by severity. Specifically, S. pneumoniae was identified in 100% of children who died compared with 67% of those with sequelae and 71% of survivors (p=0.03). H. influenzae detection ranged from 67% in children with sequelae to 76% in survivors and 93% in those who died (p>0.05). Similarly, K. pneumoniae was identified in 53% to 67% of children with no differences according to severity. A respiratory virus was detected in 69% of children, with rhinoviruses (42%) and adenoviruses (26%) being the most frequently identified, and showing comparable distributions across severity groups (p>0.05). Lastly, CMV was identified in 80% of children that died vs 33% of those with sequelae and 53% of survivors (p=0.07). Conclusion Detection of bacterial and viral pathogens in the upper respiratory tract was common in children with malaria. S. pneumoniae was identified in all children who died, and CMV in 80%. Clarifying the contribution of pathogen co-detection to adverse clinical outcomes in these children requires further studies including those examining their relationship with host immune responses.