Abstract

Background Invasive Candida infection remains a significant threat to neonates worldwide. Most evidence on neonatal invasive candidiasis (NIC) comes from high-income countries (HICs), leaving the burden and characteristics of NIC in low-and middle-income countries (LMICs) poorly described. This study aimed to investigate the incidence, case-fatality rates (CFR), epidemiology and aetiology of NIC in LMICs. Methods We conducted a systematic literature review and meta-analyses of all eligible studies in 17 databases published from inception until April 2022 focussing on microbiologically-confirmed NIC in LMICs. Findings A total of 257 articles were included, with 10,994 NIC cases from 27 LMICs. The overall incidence rate was 2.6% (95% CI: 2.2%-3.0%). Regional disparities were evident, with South-East Asia reporting the highest incidence rate (6.3%; 95% CI: 3.2%-10.3%). The mean gestational age and birth weight were 31.4 weeks (standard deviation [SD] 3.3) and 1,530 g (SD 644.6) respectively. Among 10,087 included isolates, the predominant species was C. albicans (39.0%), followed by C. parapsilosis (24.8%) with marked differences in species distribution across World Health Organization regions. Fluconazole was the most commonly-used agent for NIC treatment (55.4%; 1,567/2,826). Overall, 24.8% (1,128/6,613) of isolates with available data were resistant to fluconazole. The pooled estimated CFR was 18.7% (95% CI: 15.5%-22.1%). Conclusions A higher NIC incidence rate and CFR in LMICs is noted compared to HICs, although infected babies were less premature with a higher birth weight. The proportion of fluconazole-resistant isolates was high. Prevention and treatment strategies for NIC need to be targeted to LMIC settings.