The team, led by Olena Zubach of Danylo Halytsky Lviv National Medical University together with colleagues at the Lviv Oblast Clinical Hospital of Infectious Diseases and the Lviv Oblast Center for Diseases Control and Prevention, performed a lumbar puncture and recovered cerebrospinal fluid for analysis. The fluid showed moderate lymphocytic pleocytosis, an elevated count of lymphocytes that serves as a cellular fingerprint of viral central nervous system infection. Serological testing then delivered the first answer. The patient’s serum contained diagnostic levels of both IgM and IgG antibodies against tick-borne encephalitis virus, the flavivirus transmitted by Ixodes ticks across much of Europe and Asia, while her cerebrospinal fluid carried IgG antibodies against the same virus. Combined with her epidemiological history, which included travel to an endemic region and a documented tick bite, the diagnosis of tick-borne encephalitis was firmly established.

But the cerebrospinal fluid held a second surprise. Polymerase chain reaction testing detected DNA from human herpesvirus 7, a betaherpesvirus better known as a ubiquitous, usually silent passenger in the human population. The detection of HHV-7 DNA in the central nervous system of an immunocompetent patient already fighting tick-borne encephalitis raised an immediate and difficult question: was the herpesvirus an innocent bystander, a latent virus passively present in the sample, or was it actively replicating and contributing to the neurological damage? The authors of the report, published in Virology Journal, framed their case precisely around this interpretive dilemma, and their literature review situates it within a growing but still incomplete body of evidence on viral co-infections of the brain.

Human herpesvirus 7 was first isolated in 1990 and is closely related to human herpesvirus 6, the other member of the Roseolovirus genus. Like its relative, HHV-7 infects the vast majority of people early in life, typically causing a mild febrile illness or the childhood rash known as roseola, after which it establishes lifelong latency in T lymphocytes and other tissues. In healthy carriers, the virus usually remains dormant, controlled by cellular immunity. Reactivation is a well-recognized complication in transplant recipients and other immunosuppressed patients, in whom HHV-7 has been implicated in febrile syndromes, encephalitis, and graft complications. Detection of the virus in the cerebrospinal fluid of an immunocompetent adult, however, is genuinely uncommon, and determining whether such detection reflects true productive infection rather than latent viral DNA is a persistent technical challenge in clinical virology.

This challenge stems from the biology of herpesviruses themselves. Latent HHV-7 genomes can persist in cells that traffic through the central nervous system, and PCR amplification alone cannot always distinguish between low-level latent DNA and the replicating viral genomes that would indicate an active infection. Quantitative viral load measurements, detection of viral mRNA transcripts, and demonstration of intrathecal antibody synthesis are among the tools virologists use to strengthen the case for active replication, but each has limitations. In the Ukrainian case, the detection of HHV-7 DNA in the cerebrospinal fluid was unexpected precisely because the patient’s immune status gave no obvious reason for herpesvirus reactivation, and the clinical picture was already well explained by tick-borne encephalitis. The co-occurrence forced the clinicians to consider whether the two viruses might be interacting in ways that shaped the severity or course of the disease.

Viral co-infections of the central nervous system are an area of intensifying research interest, and the mechanisms by which one virus can modify the pathogenesis of another are varied and, in many cases, still hypothetical. Direct interference is one possibility: one virus may upregulate or suppress cellular pathways that the second virus depends on. Immune-mediated effects are another. A primary viral infection can transiently perturb the antiviral response, altering interferon signaling, T cell function, or cytokine profiles in ways that permit a second, normally controlled agent to reactivate from latency. Tick-borne encephalitis virus itself is known to affect immune cells, and herpesviruses such as HHV-7 reside within CD4-positive T lymphocytes, creating a plausible cellular environment in which acute flaviviral infection and herpesvirus reactivation could intersect. The authors emphasize that the infectious process resulting from the combined influence of neurotropic viruses may differ in important ways from infection with either agent alone, complicating both diagnosis and the interpretation of disease severity.

The literature review accompanying the case report surveys what is known about HHV-7 as a cause of meningoencephalitis. Reports of HHV-7-associated encephalitis cluster heavily among immunocompromised populations, particularly hematopoietic stem cell transplant recipients, in whom the virus has been detected in cerebrospinal fluid during episodes of neurological deterioration. In immunocompetent patients, documented cases are rare and often rest on single-center detections without definitive proof of causality. This evidentiary gap mirrors a broader problem in clinical virology: the widespread use of sensitive multiplex PCR panels on cerebrospinal fluid increasingly uncovers viral sequences whose clinical significance is uncertain. A positive PCR result for a latent herpesvirus in a patient with another clear diagnosis, such as tick-borne encephalitis, exemplifies the interpretive tightrope that clinicians must walk between over-attributing disease to an incidental finding and missing a genuine co-pathogen.

In the present case, the practical outcome was favorable. The patient received prescribed therapy, her condition improved steadily, and she was discharged on the twenty-third day of her hospital stay. The report does not claim that anti-herpesvirus treatment was decisive, nor does it attribute any specific portion of her neurological illness to HHV-7; instead, it uses the case to illustrate how diagnostic reasoning must accommodate the possibility of coexisting viral processes. For clinicians working in tick-borne encephalitis endemic zones, the case is a reminder that a confirmed flaviviral diagnosis does not automatically explain every feature of a patient’s course, and that molecular testing of cerebrospinal fluid can reveal additional agents whose contribution requires careful weighing.

Beyond its immediate clinical message, the case carries implications for surveillance and research. Tick-borne encephalitis is expanding its geographic footprint in Europe, with rising case numbers and newly affected regions reported in recent years, and Ukraine sits within the endemic belt where awareness of the disease is critical for early diagnosis and supportive care. As molecular diagnostics become more widely deployed, detecting additional viruses in the cerebrospinal fluid of TBE patients will likely become more common, and the field will need systematic studies, with quantitative viral loads, longitudinal sampling, and matched controls, to determine when such findings represent reactivation, co-infection, or noise. The Lviv team’s report, grounded in a single well-documented patient and an honest acknowledgment of interpretive complexity, contributes to exactly that foundation. It also underscores a broader truth of modern virology: the human body is a layered ecosystem of persistent viruses, and acute infections can disturb that equilibrium in ways medicine is only beginning to map.

For now, the case stands as both a clinical observation and a caution. A febrile immunocompetent woman with meningoencephalitis, a tick bite, and serology pointing squarely at tick-borne encephalitis virus turned out to carry the DNA of a second neurotropic virus in her spinal fluid. Her recovery suggests that the combined infection was survivable with appropriate care, but the virological questions her case raises, about viral interference, latency, and the true pathogenic potential of HHV-7 in the healthy brain, remain open. The authors’ literature review makes clear that answering them will require more than isolated case reports; it will require the kind of structured, comparative research that turns surprising laboratory findings into actionable clinical knowledge.

Subject of Research: Co-infection of tick-borne encephalitis virus and human herpesvirus 7 in a patient with meningoencephalitis

Article Title: Tick-borne encephalitis co-occurring with human herpesvirus 7 replication: a case report and literature review

Article References: Zubach, O., Prykuda, N., Zadorozhnyi, A., Fedorenko, S., Zbarashchuk, L., Romaniuk, U., & Zinchuk, A. (2026). Tick-borne encephalitis co-occurring with human herpesvirus 7 replication: a case report and literature review. Virology Journal. https://doi.org/10.1186/s12985-026-03313-z

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03313-z

Keywords: tick-borne encephalitis, human herpesvirus 7, meningoencephalitis, viral co-infection, cerebrospinal fluid, PCR diagnostics, flavivirus, herpesvirus latency, immunocompetent patient, case report, neurotropic viruses, Ukraine

The research team, led by Helen Fifer and Helen Peters with colleagues from sexual health, paediatric infectious diseases and pathology services across the United Kingdom, reviewed 79 reported cases through a multidisciplinary Clinical Expert Review Panel. Using strict clinical-pathological criteria, the panel classified 67 infants as confirmed or probable cases of congenital syphilis. These infants were born to 65 women, including two sets of twins. The outcomes were stark: 54 were liveborn, of whom five died within the first month of life, and 13 were stillborn. Over half of the liveborn infants — 37 of 67 — arrived preterm, and half weighed less than 2.5 kilograms at birth. Against a background of roughly 4.96 million live births in England during the study period, the absolute numbers are small, with an incidence of 0.023 per 1,000 live births still below the World Health Organization elimination threshold of 0.5 per 1,000. But each case represents a failure of a system designed to prevent exactly this outcome.

The epidemiological backdrop explains much of the rise. England recorded 9,535 cases of early infectious syphilis in 2024, the highest annual figure since the 1940s. Although most infections occur among gay and bisexual men, diagnoses in women tripled between 2015 and 2024, climbing from 273 to 830. This resurgence in adults of reproductive age inevitably feeds into pregnancy. Yet in 1999, researchers had proposed removing syphilis from the antenatal screening panel altogether because congenital cases had all but disappeared. The new data show how quickly that calculus changed: since 2019, an average of ten congenital cases per year have been reported, compared with just one or two per year in the early 2010s.

Perhaps the most striking finding is that nearly half of the affected infants — 30 of 65 pregnancies ending in congenital syphilis — were born to mothers who screened negative for syphilis at their first antenatal appointment and then acquired the infection later in pregnancy. Because England offers only a single universal screen at booking, supplemented by risk-based repeat testing, these women were never re-tested. The risk-based strategy depends on women disclosing new sexual partners, partner sexually transmitted infection diagnoses, drug injection, or sex work, and on clinicians recognising and acting on those disclosures. Many of the mothers in this study had no identifiable risk factors at all and would only have been caught by a universal repeat screen later in gestation, as is practised in higher-prevalence regions of the United States and Europe.

Diagnostic delays compounded the harm. Clinicians repeatedly reported being falsely reassured by a negative antenatal screening result. Infants born to these mothers often arrived at or shortly after birth with non-specific, multisystem illness — irritability, respiratory compromise, thrombocytopaenia, jaundice — that was frequently mistaken for presumed neonatal sepsis. Yet almost all affected infants showed additional features uncommon in sepsis: hepatosplenomegaly, rash or skin and mucosal lesions, desquamation, and abnormalities of the long bones. In one neonatal death, an infant with respiratory symptoms, thrombocytopaenia and anaemia was never tested for syphilis during life; the diagnosis emerged only at postmortem. Several children with persistent symptoms were not tested for months or years, with some cases identified only between 12 and 24 months of age, sometimes incidentally when the mother was screened during a subsequent pregnancy.

Even among infants whose mothers were diagnosed antenatally or in labour, clinical recognition proved challenging. Of 28 such livebirths, eight infants had no symptoms at birth, and the most common signs among symptomatic babies were hepatosplenomegaly in 11, rash or mucocutaneous lesions in seven, and bone abnormalities in five, typically accompanied by thrombocytopaenia, anaemia or jaundice. More unusual complications included hydrops in four infants, hydrocephalus and nephrotic syndrome in two each, and meningitis in one. The authors note that syphilis has long been called ‘the great imitator’, and the study confirms that congenital disease lives up to the name. They endorse proposals to broaden the traditional ‘TORCH’ screen for suspected congenital infection — toxoplasmosis, rubella, cytomegalovirus and herpes simplex — to a ‘SCORTCH’ panel that explicitly includes syphilis, alongside chickenpox and blood-borne viruses.

The study also exposes weaknesses in laboratory diagnosis. Serology in newborns is inherently difficult because maternal IgG antibodies cross the placenta, and a non-treponemal titre four times higher than the mother’s is considered diagnostic — yet only 24 per cent of the 41 mother–infant pairs with comparable results met that threshold, rising to 50 per cent among infants whose mothers acquired syphilis after a negative booking screen, presumably because those mothers went untreated. By contrast, treponemal IgM, which does not cross the placenta, was positive in 86 per cent of the 35 infants tested. Polymerase chain reaction (PCR) testing for Treponema pallidum DNA proved a highly useful adjunct, with positive results from nasal and throat swabs, skin lesions, blood, cerebrospinal fluid, placenta and even bone biopsy, and all four stillbirths with PCR results testing positive. Yet fewer than a quarter of liveborn infants had any specimen sent for PCR, a gap the UK Health Security Agency is now addressing by providing free PCR testing to all UK laboratories.

Behind the clinical statistics lies a darker pattern of social vulnerability. Just over half of the women — 34 of 65 — had at least one complex social factor documented during pregnancy, and most of those experienced multiple overlapping disadvantages. These included involvement with social services in 25 cases, insecure housing in 19, mental health problems in 14, difficulties engaging with healthcare in 14, drug or alcohol misuse in 12, intimate partner violence in nine, and sex work in six. Many women booked late for antenatal care, after 12 weeks, or not at all, and treatment completed too close to delivery to cure the fetus. For cure to succeed, penicillin therapy must finish at least four weeks before birth, so late booking combined with preterm delivery leaves an impossibly narrow window. Several mothers were also treated with macrolide antibiotics, a regimen now known to fail frequently because of widespread macrolide resistance in syphilis strains; UK guidelines were amended in 2019 to remove this option and now explicitly advise against it.

The authors are careful to acknowledge the limitations of their work. Prospective surveillance only began in 2020, with data for 2015 to 2020 collected retrospectively, so early cases were probably undercounted. Reporting was voluntary until April 2025, when congenital syphilis became a notifiable disease in England. The cases captured are also likely skewed towards the severe end of the spectrum, and an unknown number of asymptomatic infants may remain undiagnosed, carrying a risk of late congenital syphilis with its devastating effects on bones, teeth, eyes and the nervous system. International comparisons suggest the problem is not unique to England: series from the United States, Argentina and Western Australia describe similar patterns of asymptomatic birth followed by early symptom onset, and diagnostic difficulty.

The message for policymakers is clear. The UK National Screening Committee, which concluded in 2019 that universal repeat screening at 28 weeks would not be cost-effective, is reviewing that position, and the new data suggest many cases would have been caught by such a policy. Alongside repeat screening, the authors call for greater awareness among clinicians that a negative early screen offers no protection for the rest of pregnancy, improved recognition of maternal symptoms such as vulval lesions and rashes, wider use of PCR and IgM testing, and closer collaboration with inclusion health services — housing, drug treatment and outreach teams — to reach socially excluded women. With the World Health Organization targeting triple elimination of syphilis, HIV and hepatitis B transmission by 2030, England’s decade of surveillance data serves as a reminder that elimination is not achieved by screening programmes alone, but by the clinical vigilance, timely treatment and social support that make those programmes work.

Subject of Research: Congenital syphilis transmission, clinical presentation and diagnostic challenges in England, 2015–2024

Article Title: Clinical characteristics and factors contributing to transmission of congenital syphilis in England, 2015–24: a national surveillance study

Article References: Fifer, H., Peters, H., Kingston, M., Francis, K., Till, R., Thorne, C., Lyall, H., Dermont, S., Cohen, M. C., Sultan, B., Oomeer, S., Bamford, A., Hoodbhoy, S., Permalloo, N., Dickins, D., Emonts, M., Jones, C. E., Andrews, S., & Elbech, A. (2026). Clinical characteristics and factors contributing to transmission of congenital syphilis in England, 2015–24: a national surveillance study. The Lancet Regional Health – Europe, 70, Article 101864. https://doi.org/10.1016/j.lanepe.2026.101864

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101864

Keywords: congenital syphilis, antenatal screening, Treponema pallidum, stillbirth, neonatal death, vertical transmission, PCR diagnostics, pregnancy, public health surveillance, England, social vulnerability, Lancet Regional Health Europe