Geographic Variations in the Clinical and Hematological Manifestations of Pediatric Visceral Leishmaniasis: A Systematic Review

Background: Visceral leishmaniasis (VL), or kala-azar, is one of the most devastating neglected tropical diseases, disproportionately affecting children in resource-limited endemic regions across four major geographic zones. Despite decades of research, no comprehensive systematic review has rigorously compared clinical and hematological manifestations of pediatric VL across these regions, leaving clinicians without evidence-based, region-specific guidelines. Objectives: To analyze and compare the clinical, hematological, and epidemiological patterns of pediatric VL across four major endemic regions: Mediterranean/Europe, Latin America, East/Central Africa, and Asia (West, Central, and East). Secondary objectives included comparing parasite species distributions, diagnostic approaches, treatment regimens, complication profiles, and case-fatality rates. Methods: A systematic literature search following PRISMA 2020 guidelines and PRISMA-S reporting standards was conducted across PubMed/MEDLINE, Scopus, ISI Web of Science, EMBASE, and CINAHL. The review protocol was retrospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; Registration No.: CRD420261446750). Retrospective PROSPERO registration is acknowledged as a limitation of this review. Duplicate records were removed using Rayyan software. From 1480 identified records, after removing 117 duplicates and applying pre-specified inclusion/exclusion criteria, 38 studies met all eligibility criteria: Mediterranean/Europe (n = 11), Latin America (n = 6), East/Central Africa (n = 6), and Asia (n = 15). Study quality was evaluated using the Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Checklist. Exploratory inter-group comparisons of study-level aggregate data were performed using chi-square, Fisher’s exact, and Kruskal–Wallis tests; results are presented as narrative synthesis. Results: Apparent geographic variations were observed. Fever was near-universal (91–100%) across all regions. Splenomegaly ranged from 85% to 98%, and hepatomegaly from 65% to 89%. Anemia prevalence ranged from 78% to 96%, pancytopenia from 45% to 72%, and thrombocytopenia from 62% to 92% (based on exploratory cross-tabulations). Leishmania infantum predominated in Mediterranean/European, Latin American, and most West/Central/East Asian studies; Leishmania donovani was reported in all East/Central African and South Asian (India, Nepal, Pakistan) studies. Treatment regimens, diagnostic methods, and complication profiles showed substantial regional differences. Conclusions: Apparent geographic variations exist in pediatric VL manifestations, which may be associated with differences in parasite species, host genetics, nutritional status, healthcare infrastructure, and co-infection patterns. These findings suggest that region-specific approaches to pediatric VL diagnosis and management may be warranted; however, the development of formal region-specific guidelines requires prospective comparative studies with standardized outcome definitions. Enhanced surveillance and collaborative international research remain priorities.