Integrating viral hepatitis into yellow fever surveillance—reflections on Modiyinji et al.

Highlights

• •Modiyinji et al. report viral hepatitis in Yellow fever suspected cases in Cameroon, underscoring the diagnostic complexity of febrile jaundice.
• •Molecular assays add critical specificity and genotype-level insights to outbreak surveillance.
• •Integration of hepatitis testing into Yellow fever surveillance would improve accuracy and align with World Health Organization’s hepatitis elimination targets.
• •Table 1 illustrates the broader differential diagnosis of febrile jaundice, supporting the case for integrated algorithms.

Dear Editor,

We commend Modiyinji et al. [1] for their timely study examining viral hepatitis as a differential diagnosis among Yellow fever (YF) suspected cases in Cameroon. Their molecular analyses confirm the co-circulation of hepatitis B virus (HBV) and hepatitis E virus (HEV) among patients presenting with jaundice, underscoring the diagnostic challenges clinicians face at the frontline.

Their use of molecular assays to characterize circulating genotypes provides actionable insights, as genotype distribution can influence disease severity, vaccination strategies, and outbreak response [2]. However, the study highlights systemic limitations: hepatitis testing was restricted to a subset of suspected YF cases, and malaria—the most frequent cause of febrile jaundice in the region—was not consistently screened. Such gaps can compromise the accuracy of national surveillance and affect timely outbreak control.

To address these issues, we suggest three approaches. First, integrating viral hepatitis, particularly HEV, into YF surveillance protocols would enhance differential diagnosis and outbreak verification [3].Second, adopting multiplex diagnostics and next-generation sequencing as routine public health tools, rather than isolated research methods, can improve detection of co-infections and track transmission patterns [4]. Third, synchronizing YF vaccination campaigns with HBV immunization scale-up may generate synergistic health benefits, especially in resource-constrained settings [5].

Febrile jaundice in Sub-Saharan Africa often stems from multiple etiologies beyond hepatitis and YF. Malaria, leptospirosis, rickettsial infections, and drug-induced hepatotoxicity collectively contribute to the clinical spectrum [[6], [7], [8]]. Table 1 summarizes these common causes, highlighting geographic distribution, diagnostic challenges, and public health relevance. By linking this information to a practical diagnostic algorithm—incorporating syndromic triage, rapid tests, and molecular assays—clinicians can reduce misclassification and optimize patient management.

Table 1.

Common differential diagnoses of febrile jaundice in sub-Saharan Africa (adapted from Modiyinji et al. 2025 and supporting studies [[1], [2], [3], [4], [5], [6], [7], [8]]).

Condition/Pathogen	Geographic evidence	Key diagnostic challenges	Public health relevance
YF virus	Central & West Africa	Clinically overlaps with hepatitis and malaria	Vaccine-preventable; outbreak-prone
Hepatitis B virus	Cameroon, Nigeria, Ghana	Acute hepatitis mimics YF symptoms	Chronic infection drives liver cancer burden
Hepatitis E virus	Chad, Sudan, Central Africa	Epidemics in displaced populations; high maternal risk	Leading cause of acute viral hepatitis outbreaks
Malaria (Plasmodium falciparum)	All endemic regions	Severe malaria frequently presents with jaundice	Major contributor to febrile jaundice and mortality
Leptospira spp.	West & East Africa	Mimics viral hepatitis; frequently underdiagnosed	Zoonotic; associated with flood outbreaks
Rickettsial infections	East and Central Africa	Nonspecific febrile jaundice presentation	Often overlooked contributor to acute febrile illness
Drug-induced hepatotoxicity	Urban referral centers	Difficult to distinguish from viral hepatitis without laboratory tests	Linked to tuberculosis and antimalarial therapy

YF, Yellow fever.

Table 1 contextualizes the primary differential diagnoses for febrile jaundice, providing a practical framework for integrated surveillance and diagnostic prioritization.

The findings of Modiyinji et al. [1] bring to light not only a national challenge in Cameroon but also a regional need for harmonized multi-pathogen surveillance frameworks. Without integrated diagnostics, misclassification will persist, compromising YF elimination and obscuring hepatitis epidemiology. By embedding molecular tools, updating algorithms, and linking vaccination strategies, public health systems can strengthen both outbreak control and long-term disease prevention.

Declaration of competing interest

The authors have no competing interests to declare.