The 2024 Oropouche epidemic attracted worldwide attention for several reasons. The virus expanded geographically into regions where it had never before been detected, the number of reported cases rose substantially, and the first globally documented Oropouche-associated fatalities occurred. In parallel, several studies provided evidence of vertical transmission and raised concerns about the potential impact of maternal infection on fetal development and survival. Notably, pregnancy losses among Oropouche-infected women were reported in Brazil as far back as the 1980s, predating the current wave of warnings by decades. What has been missing, the authors argue, is a systematic strategy to move from suggestive case reports to robust causal inference.

The evidence that currently fuels concern comes largely from individual case reports. Researchers have described Oropouche virus RNA or antigens in placental and fetal tissues, and anti-Oropouche IgM antibodies have been detected in microcephalic newborns. These findings support the plausibility of vertical transmission, but they fall short of demonstrating that the virus actively replicates in fetal tissue, which would substantially strengthen the biological case for fetal injury. The authors emphasize that viral infections can damage tissue indirectly, for example through immune imbalance, yet direct evidence of replication remains the gold standard for establishing pathogenicity.

To close that gap, the framework proposes molecular techniques capable of detecting positive-sense viral RNA, the form of viral genetic material produced during active replication. Strand-specific reverse transcription PCR assays, designed to target complementary RNA and viral messenger RNA rather than the negative-sense genomic RNA packaged in virions, could provide evidence consistent with active Oropouche replication in placental or fetal samples. Complementing this, signal-amplified in situ hybridization methods such as RNAscope coupled with confocal microscopy, or PrimeFlow RNA assays combined with flow cytometry, could localize viral replication within tissues and identify which specific cell populations harbor replicating virus. Histopathological and immunohistochemical analyses using antibodies against non-structural viral proteins expressed only during replication could further link viral activity to tissue damage.

Animal models form the second pillar of the proposed framework. Previous studies have demonstrated vertical transmission of Oropouche virus and fetal impairment in mice, including infection with an ancestral viral strain. However, these results were consistently observed only in animals with impaired type I interferon signaling, suggesting that vertical transmission in this setting is context-dependent and limiting extrapolation to natural human infection. The authors point instead to golden hamsters, which have been proposed as a model for Oropouche pathogenesis and may represent a promising in vivo system for investigating fetal effects without genetic or immunological manipulation. They also suggest examining SJL mice, a strain likely more susceptible to viral infection, which gained attention during the Zika epidemic for their permissiveness to viral teratogenicity studies.

Non-human primates offer a third experimental avenue. These animals have been used successfully to investigate virus-associated fetal outcomes for other pathogens, including Zika virus and congenital cytomegalovirus, and could prove suitable for Oropouche studies. Intrauterine infection of immunocompetent animals would provide a proof-of-concept approach to evaluate the direct fetal consequences of Oropouche infection, a strategy previously applied to teratogenic viruses including Zika and Cache Valley virus, an orthobunyavirus in the same genus as Oropouche. Intracranial inoculation in neonatal animal models and embryonated chicken eggs could also be employed, as these approaches were previously used to characterize the teratogenic potential of other orthobunyaviruses such as Aino, Akabane and Cache Valley viruses.

The authors stress that any such experiments should use both historical and recently circulating Oropouche strains to detect possible differences in fetal effects between lineages, and should employ minimally passaged viruses to avoid adaptive mutations that would distort the wild-type phenotype. Testing at different stages of gestation would further clarify whether particular windows of pregnancy carry heightened risk, a question of direct clinical relevance for counseling pregnant women in endemic areas.

Viral reverse genetics represents a particularly promising tool within the framework, especially for probing the role of the type I interferon response. Because in vivo studies have shown possible vertical transmission only in animals lacking an adequate interferon response, and because interferon antagonism is an established pathogenicity mechanism of orthobunyaviruses, including the teratogenic Schmallenberg virus, the Oropouche NSs gene, which encodes a known type I interferon antagonist, becomes a prime suspect. Reverse genetics could be used to manipulate this gene, identify the residues and domains involved in interferon antagonism, and test whether these functions contribute to adverse fetal outcomes. Such findings could also inform genomic surveillance by identifying molecular signatures in circulating strains that are potentially associated with fetal injury.

On the epidemiological side, the framework calls for well-designed case-control studies, modeled on those conducted during the Zika epidemic, to estimate the likelihood of miscarriage or developmental abnormalities among Oropouche-infected pregnant women and to identify other risk factors, such as the most vulnerable gestational period. Prospective postnatal follow-up of exposed newborns would be timely for investigating potential later neurodevelopmental effects, including those occurring in the absence of microcephaly, a pattern documented in congenital Zika infection. Close immunological monitoring of infected pregnant women, focusing on type I and type III interferons and interferon-stimulated genes such as IFIT1, could reveal host factors that modulate vertical transmission. The authors acknowledge real obstacles: infections outside outbreak periods are rarely reported, outbreaks have historically been concentrated in remote areas, and the recent decline in transmission across several affected regions may limit participant recruitment. Multicenter studies and prospective surveillance strategies, they argue, are the practical answer.

The overarching message is one of scientific caution paired with methodological ambition. Despite recent advances in understanding Oropouche virus, its potential for vertical transmission and adverse fetal outcomes remains unproven, and establishing causality will require the deliberate integration of molecular virology, animal modeling, reverse genetics and epidemiology. The authors contend that such efforts are essential not only for resolving a pressing scientific uncertainty but also for improving surveillance strategies, guiding clinical management of pregnancies in endemic regions, and mitigating whatever impact Oropouche infection may ultimately prove to have on fetal health. As the virus continues to expand its footprint in the Americas, the framework offers a roadmap for converting alarming anecdotes into actionable evidence.

Subject of Research: Assessment of potential Oropouche virus-associated adverse fetal outcomes through experimental and epidemiological approaches

Article Title: A framework for assessing potential Oropouche virus-associated adverse fetal outcomes

Article References: Tanaka, L. F., Dutra, N. B. D. M., Lopes, T. R. R., Carmo, R. F., Oliveira-Filho, E. F. D., Gil, L. H. V. G., & Silva Júnior, J. V. J. (2026). A framework for assessing potential Oropouche virus-associated adverse fetal outcomes. BMC Infectious Diseases, 26(1), Article 1739. https://doi.org/10.1186/s12879-026-14420-1

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14420-1

Keywords: Oropouche virus, vertical transmission, adverse fetal outcomes, microcephaly, pregnancy, orthobunyavirus, type I interferon, reverse genetics, animal models, case-control studies, placental infection, neurodevelopment

The research was led by Geoffrey E. Lynn of Texas A&M AgriLife Research and Tammi L. Johnson, together with colleagues at Texas A&M University, the Centers for Disease Control and Prevention, and the University of Minnesota. Over a 14-month longitudinal field study in a Madrean riparian–grassland system, the team combined serology, molecular screening of thousands of ticks and rodent samples, and laboratory feeding experiments with field-collected adult female ticks. The work was funded by the United States Department of Defense Tick and Tick-borne Disease Research Program and by National Institute of Food and Agriculture Hatch projects.

Rickettsia parkeri is a tick-borne bacterium associated with Amblyomma ticks throughout the Western Hemisphere and is a recognized cause of spotted fever rickettsiosis in people. In southern Arizona it co-occurs with “Candidatus Rickettsia andeanae,” a closely related species whose pathogenic significance remains uncertain. The co-occurrence offered the researchers a rare opportunity to evaluate transmission pathways and possible interactions between two sympatric rickettsiae sharing the same tick vector in the same landscape.

The vertebrate side of the story turned out to be less dramatic than expected. The team screened 320 rodent serum samples collected across the study period for antibodies reactive to R. parkeri using the indirect immunofluorescence assay, the standard serological tool for rickettsial exposure. A striking 63 percent of the rodents showed reactive antibodies, indicating that exposure to the bacterium is frequent in the rodent community. Yet when the researchers looked for direct evidence of infection, the picture changed sharply. Molecular screening detected R. parkeri DNA in only 3.1 percent of 1378 rodent ear biopsies, the tissue sampled at the skin sites where immature ticks attach and feed, and the bacterium was entirely absent from 211 rodent whole blood specimens.

That combination of high seroprevalence and near-absence of detectable bacterial DNA carries a specific technical meaning. It suggests that rodents are bitten often enough to mount antibody responses, but that the bacterium rarely establishes itself in rodent tissues at feeding sites and does not produce detectable rickettsemia, the presence of bacteria in circulating blood. Without rickettsemia, feeding ticks are unlikely to acquire infection from their hosts in quantities sufficient to sustain horizontal transmission. In other words, the mammalian hosts experience frequent exposure but appear to contribute little to maintaining or amplifying the bacteria in the environment.

The tick side of the story was far more consequential. To test whether the bacteria pass from one tick generation to the next, the researchers allowed field-collected adult female A. maculatum s.l. ticks to feed on heifers and then examined the post-oviposition carcasses of the mothers and the resulting first-generation larvae. The results were unambiguous: filial infection rates reached 100 percent in clutches produced by females positive for either R. parkeri or “Ca. R. andeanae” that carried high maternal rickettsial loads. Every larva in those clutches inherited the infection. Such highly efficient transovarial transmission means that an infected female effectively reproduces the entire bacterial population in her offspring, generation after generation, without any need for a vertebrate host to become infected.

Vertical transmission of this kind has important epidemiological implications. When a pathogen is maintained transovarially within a tick lineage, the tick population functions as both vector and reservoir, and the pathogen can persist even if susceptible vertebrate hosts are absent or fail to develop systemic infections. For R. parkeri, which causes disease in humans bitten by infected adult ticks, this means that the risk of human exposure is tied directly to the prevalence of infected ticks in the environment rather than to the dynamics of infection in rodents or other small mammals. Surveillance and risk assessment, the study suggests, should therefore focus on the tick population itself.

The study also uncovered evidence of competition between the two rickettsial species inside their shared tick host. Among the 1941 immature-stage A. maculatum s.l. ticks screened for Rickettsia DNA, co-infections with both R. parkeri and “Ca. R. andeanae” occurred significantly less often than would be expected by chance. This pattern is consistent with competitive exclusion, a well-known ecological principle in which two species competing for the same niche cannot stably coexist, with one excluding the other. Within an individual tick, the two bacteria apparently compete for intracellular resources or space, so that infection with one species reduces the likelihood of a successful co-infection with the other.

Prevalence ratios calculated by the team also addressed a second possible horizontal route: co-feeding transmission, in which uninfected ticks acquire bacteria while feeding adjacent to infected ticks on the same host, without any systemic infection in the vertebrate itself. The data indicated that co-feeding may play some role, but the authors concluded that vertebrate-mediated horizontal amplification is limited and likely inefficient in this system. For “Ca. R. andeanae,” the conclusion was even stronger: the bacterium appears to be maintained almost exclusively through vertical transmission, making it even more dependent on the tick lineage than R. parkeri.

Taken together, the results portray a maintenance strategy in which the tick population is the primary biological reservoir for both rickettsiae, with competitive interactions between the bacteria acting as a brake on how common each species can become where they co-occur. The findings carry practical weight for public health in the region, since R. parkeri rickettsiosis is a recognized human illness and understanding where the bacterium persists helps target surveillance. They also contribute to a broader shift in tick-borne disease ecology, away from models centered exclusively on vertebrate reservoir hosts and toward models that recognize the tick itself, with its remarkable capacity to carry bacteria across generations, as the engine of pathogen persistence in semi-arid landscapes like the Madrean riparian–grassland system of southern Arizona.

Subject of Research: Vertical transmission and competitive exclusion of Rickettsia parkeri and "Candidatus Rickettsia andeanae" in Amblyomma maculatum tick populations

Article Title: Vertical transmission drives the persistence of Rickettsia parkeri and “Candidatus Rickettsia andeanae” in Amblyomma maculatum sensu lato populations in a semi-arid Madrean riparian–grassland system

Article References: Lynn, G. E., Ludwig, T. J., Paddock, C. D., Allerdice, M. E. J., Cull, B., Hays, S. R., Chapman, T. J., Donaldson, T. G., Teel, P. D., & Johnson, T. L. (2026). Vertical transmission drives the persistence of Rickettsia parkeri and “Candidatus Rickettsia andeanae” in Amblyomma maculatum sensu lato populations in a semi-arid Madrean riparian–grassland system. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07687-5

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07687-5

Keywords: Rickettsia parkeri, Candidatus Rickettsia andeanae, Amblyomma maculatum, vertical transmission, transovarial transmission, spotted fever group rickettsiae, tick-borne disease, competitive exclusion, rodent serology, co-feeding transmission, southern Arizona, Parasites & Vectors

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