Infecția cu virusul West Nile la copil: particularități clinice, diagnostice și prognostice în practica pediatrică

1. Introduction

West Nile virus (WNV) is an enveloped single-stranded RNA virus of the Flaviviridae family, genus Flavivirus. The natural cycle of the virus occurs predominantly between mosquitoes and birds, with humans and horses as incidental hosts. Human transmission is mainly through the bite of infected mosquitoes, especially of the genus Culex. Rare routes of transmission by transfusion, organ transplantation and, in some cases, vertical transmission or breastfeeding have also been described^(4,5).

WNV infection has a wide clinical spectrum. Most infected individuals are asymptomatic, and of those who are symptomatic, most develop a nonspecific febrile illness. A small proportion develop neuroinvasive disease, characterized by meningitis, encephalitis, meningoencephalitis or acute flaccid paralysis^(2-4).

The importance of infection in children is related to the difficulty of clinical recognition and the possibility of severe neurological forms. Pediatric data are, however, considerably less available than in adults. A review of pediatric neuroinvasive disease identified over 700 pediatric cases of neuroinvasive disease reported in the United States of America between 2003 and 2016, highlighting the lack of child-specific prognostic factors⁽⁶⁾.

In the context of epidemiological changes and continued transmission in Europe, WNV represents a relevant public health problem. In 2025, by 3 December, 14 European countries had reported 1112 indigenous human cases, of which 49 were in Romania⁽⁷⁾. These data support the need for increased clinical vigilance, including in pediatrics.

2. Epidemiology of WNV infection in children

Children can be infected at any age, but the incidence of neuroinvasive disease is much lower than in older adults. A large epidemiological study conducted in the United States analyzed all pediatric cases reported during the period 1999-2007. Of 1478 cases in children, 1009 (68%) were classified as West Nile fever and 443 (30%) as neuroinvasive disease. Three neuroinvasive cases were fatal. Most pediatric cases began between July and September, and the median annual incidence of neuroinvasive disease was 0.07/100,000 children⁽¹⁾.

An important aspect of this study was the difference in neurological phenotype according to age. In children and young adults, meningitis was the predominant neuroinvasive manifestation, while encephalitis was more common in older adults⁽¹⁾. This observation is relevant for the differential diagnosis of pediatric aseptic meningitis in the summer and early autumn months.

European data demonstrate the persistence and geographical extension of WNV circulation. In 2024, 1436 indigenous human cases were reported in 19 European countries, including 99 in Romania, with 125 deaths reported at the European level⁽⁷⁾. In 2025, Romania reported 49 indigenous cases by early December⁽⁷⁾. Although these data are not specific to the pediatric population, they are relevant for assessing the pretest probability in a child with a suggestive clinical picture.

The statistics of the “Sf. Parascheva” Clinical Hospital for Infectious Diseases, Iași, Romania, regarding West Nile virus infections in the last 10 years (2016-2026) total 94 patients, mostly male (57 patients), most of them in the age range of 65-74 years old (Figures 1 and 2).

3. Clinical spectrum

3.1. Asymptomatic infection and West Nile fever

Most WNV infections are asymptomatic. When clinical disease occurs, the manifestations are nonspecific and may include fever, headache, fatigue, myalgias, arthralgias, nausea, vomiting and rash^(4,5). In children, the picture can be confused with other seasonal viral infections. For this reason, the epidemiological history – exposure to mosquitoes, residence or travel to an affected area and time of year – is of particular importance.

A meta-analysis published in 2026 included 4062 patients from 39 studies and demonstrated significant heterogeneity in clinical manifestations. Central nervous system manifestations were the predominant category, being reported in 39.39% of clinically recognized cases. The cumulative mortality was 6.23%, but this estimate cannot be directly extrapolated to children, since the mean age of the population analyzed was 52 years old⁽³⁾.

3.2. Neuroinvasive disease

Neuroinvasive disease represents the most severe clinical form and includes the following manifestations:

• West Nile meningitis;
• West Nile encephalitis;
• meningoencephalitis;
• acute flaccid paralysis/West Nile poliomyelitis;
• mixed forms with bulbar involvement and respiratory failure.

In the pediatric population, meningitis appears to be relatively more common than encephalitis. In the American epidemiological study, meningitis was the predominant form of neuroinvasive disease in children⁽¹⁾. The review dedicated to the pediatric population confirms that the disease can also evolve with severe encephalitis, acute flaccid paralysis, seizures, impaired consciousness and respiratory failure⁽⁶⁾.

A meta-analysis by Roberts et al., published in 2025, included 47 studies of neuroinvasive WNV disease. The most common manifestations were fever (88%), nausea/vomiting (58%), fatigue (50%), headache (50%), altered mental status (39%) and focal weakness (32%). The cumulative mortality was 9.2%, and 42.1% of patients required intensive care unit admission⁽²⁾.

Although these values are predominantly from adult populations, they demonstrate the severe potential of the disease and justify close monitoring of children with neurological involvement.

The proportion of pediatric patients in the 10-year cohort studied was 24 cases. Of these, only three patients showed different stages of neurological impairment (Figure 3), as well as complications of the disease, most of them having a self-limited evolution of symptoms, with an average duration of hospitalization of 16 days.

4. Pathogenesis and severity factors

After inoculation by mosquito bite, the virus initially multiplies locally and can disseminate systemically. In a subset of patients, the virus enters the central nervous system and causes damage to neurons and glial cells.

The pathogenesis of neuroinvasive disease is the result of the interaction between viral replication and the host immune response. Inflammation can contribute to the elimination of the virus, but an excessive inflammatory response can lead to disruption of the blood-brain barrier and neurological damage.

A systematic review published in 2024 analyzed 136 articles on the inflammatory response associated with WNV neuroinvasive disease. The most frequently elevated cytokines were IL-6 and TNF-, but the authors highlighted the significant heterogeneity of the available data and the need for further studies to identify prognostic biomarkers⁽⁸⁾.

In adults, older age, diabetes mellitus, hypertension and chronic kidney disease were associated with increased risk of mortality. In the meta-analysis by Roberts et al., chronic kidney disease was associated with an OR of 5.99, diabetes with an OR of 2.43, and hypertension with an OR of 4.01 for mortality⁽²⁾.

These factors cannot be automatically transferred to the pediatric population. In children, immunosuppression, organ transplantation and other conditions that alter the immune response are relevant clinical contexts⁽⁶⁾.

Historically, children included in the cohort studied between 2016 and 2026 “imported” West Nile virus infection during travel to endemic areas (mostly for recreational purposes), and the symptoms developed later, upon returning to the country.

5. Diagnosis

The diagnosis of WNV infection is based on the integration of clinical, epidemiological and laboratory data. In a child with suspected neuroinvasive disease, the evaluation should include a complete blood count, inflammatory markers, biochemistry, blood cultures as appropriate and, if there are no contraindications, a lumbar puncture. The cerebrospinal fluid usually shows pleocytosis, predominantly lymphocytic, and a moderate increase in protein. The etiological diagnosis is mainly supported by the identification of WNV-specific IgM antibodies in serum and/or CSF⁽⁹⁾.

According to current CDC recommendations, WNV IgM may become detectable approximately 3-8 days after the onset of illness. A very early negative result does not exclude infection and may require repeat testing⁽⁹⁾. A positive IgM result should be interpreted in the clinical and epidemiological context because cross-reactions between flaviviruses may occur. In selected situations, confirmation by neutralization tests, such as plaque reduction neutralization test (PRNT), is recommended, especially when there is a possibility of exposure to other flaviviruses, atypical or severe presentations, or transmission through transplantation or transfusion⁽⁹⁾. Detection of viral RNA by RT-PCR can confirm the infection, but the sensitivity is limited in immunocompetent patients, because viremia is usually transient. Molecular testing may have greater utility in immunocompromised patients⁽⁹⁾.

All patients included in the cohort of 94 cases – adults and pediatric population – benefited from biological diagnosis by positivity of Ig M anti-WNV serology.

The differential diagnosis in children should include:

• bacterial meningitis;
• enteroviral meningitis and encephalitis;
• herpes simplex virus infection;
• varicella-zoster virus infection;
• other arboviruses;
• autoimmune encephalitis;
• Guillain-Barré syndrome;
• poliomyelitis and other causes of acute flaccid paralysis.

6. Treatment

Currently, the treatment of WNV infection is predominantly supportive. There is no specific antiviral demonstrated by clinical trials of sufficient quality and there is no licensed human vaccine for the prevention of the disease^(5,6).

Hydration, fever control and clinical surveillance are recommended in mild cases. In neuroinvasive disease, the treatment should be individualized according to severity, and it may require:

• monitoring of neurological status;
• control of seizures;
• correction of fluid and electrolyte disturbances;
• monitoring of respiratory function;
• mechanical ventilation in cases of respiratory failure;
• treatment of intensive care complications;
• nutrition and prevention of aspiration;
• early neurological recovery.

Various therapies have been evaluated, including intravenous immunoglobulins, interferon, ribavirin and other antiviral or immunomodulatory treatments. However, the evidence is insufficient to routinely recommend any one of these therapies^(5,6). The lack of specific antiviral treatment represents one of the main therapeutic gaps of WNV infection and underlines the need to develop multicenter clinical trials.

In the study conducted, all patients (24 cases) benefited from symptomatic treatment (antipyretics, hydration, correction of hydroelectrolyte and acid-base imbalances, nutrition appropriate to the clinical condition). In addition, the three children diagnosed with neurological impairment received intravenous immunoglobulin and corticosteroid therapy, considering their age and the clinical evolution (Figure 4).

It is noteworthy that no patient required anticonvulsant therapy, a routine treatment stated in the specialized literature.

7. Prognosis and sequelae

The prognosis depends largely on the type of neurological involvement. Patients with isolated meningitis generally have a better prognosis than those with severe encephalitis, acute flaccid paralysis, or bulbar involvement.

A 2025 meta-analysis of neuroinvasive disease demonstrated a cumulative mortality of 9.2% and a rate of intensive care admission of 42.1%⁽²⁾. A 2026 meta-analysis confirmed the significant impact of the disease on mortality, with a cumulative mortality of 6.23% and with much higher rates in patients requiring intensive care⁽³⁾.

Survival does not always equate to complete recovery. Persistent fatigue, memory impairment, concentration deficits and depressive symptoms were reported in the studies included in the meta-analysis by Roberts et al.⁽²⁾

A systematic review of recovery from WNV neuroinvasive disease highlighted the potential benefits of a multidisciplinary approach, including physiotherapy, occupational therapy, neurocognitive interventions and speech therapy, depending on the patient’s deficit⁽¹⁰⁾.

In children, the problem extends beyond immediate neurological recovery. Severe encephalitis can have consequences for cognitive development, school performance, behavior and social adaptation. For this reason, the child who presented WNV neuroinvasive disease should be followed longitudinally, with neurological and, when necessary, neuropsychological assessments.

8. Prevention

In the absence of a human vaccine, prevention is based on reducing exposure to mosquitoes and controlling vectors. Individual measures include the use of authorized repellents, wearing clothing that covers as much of the body surface as possible, using mosquito nets and reducing exposure during periods of intense vector activity. At the community level, epidemiological surveillance, monitoring of mosquito populations and control of breeding sites are important.

A systematic review of the population’s knowledge and behaviors regarding WNV showed that the level of information and adoption of preventive measures varies considerably between populations, which supports the need for health education⁽¹¹⁾.

In Romania, the maintenance of WNV circulation and the periodic reporting of autochthonous cases justify the inclusion of the infection in vector-borne disease surveillance strategies⁽⁷⁾.

9. Limitations of the available evidence

A major limitation of scientific literature is the small number of exclusively pediatric studies. Most recent meta-analyses include predominantly adults, and therefore estimates of mortality, risk factors and sequelae cannot be extrapolated without reservation to children^(2,3). In addition, studies are heterogeneous in terms of the definition of neuroinvasive disease, methods of microbiological confirmation, severity of cases and duration of follow-up. A 2026 meta-analysis found that only 53% of cases analyzed were confirmed by PRNT, which may contribute to the heterogeneity of estimates⁽³⁾.

Another problem is the sporadic and seasonal nature of the disease, which makes it difficult to conduct randomized clinical trials and sufficiently large pediatric cohorts⁽⁶⁾. Therefore, multicenter pediatric registries and prospective studies that follow neurological and neurocognitive evolution over the long term are needed.

10. Conclusions

West Nile virus infection is an important cause of vector-borne disease and should be considered in the differential diagnosis of fever, meningitis and encephalitis in children, especially during seasonal transmission and in regions with documented viral circulation.

Available pediatric epidemiological data demonstrate that, although neuroinvasive disease is rare, it can have severe consequences. In children, meningitis appears to be more common than encephalitis, but forms with severe neurological involvement, acute flaccid paralysis, respiratory failure and death have also been described^(1,6).

Recent meta-analyses confirm the significant mortality and morbidity of neuroinvasive disease but should be interpreted with caution in pediatrics, because the populations studied are predominantly adults^(2,3).

Early diagnosis is based on clinical and epidemiological suspicion, followed by the determination of WNV-specific IgM in serum and/or CSF, with confirmation by neutralization tests in appropriate situations^(9,12). The treatment is currently supportive, and the prevention of mosquito exposure is the main method of risk reduction^(13,14,15).

In the context of the maintenance of West-Nile virus transmission in Europe and the constant reporting of cases in Romania, increased awareness in pediatrics is justified.

Prospective pediatric studies are particularly needed to identify risk factors for neuroinvasion, prognostic biomarkers and the disease’s impact on long-term neurocognitive development.

Conflict of interests: none declared.

Financial support: none declared.

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