Human Parvovirus B19 (B19V) in Israel: Clinical Manifestations, Complications and Recent Incidence Trends

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Human parvovirus B19 (B19V) has been recognized as a pathogenic virus in humans for over three decades. Belonging to the Parvoviridae family, this single-stranded DNA virus exhibits a wide clinical spectrum, ranging from asymptomatic infection to severe and life-threatening conditions.

The severity of B19V-related illnesses is influenced by factors such as age, immune status, and pregnancy.

In children, the virus commonly causes erythema infectiosum, while in adults, it can lead to various cutaneous manifestations and joint involvement. Additionally, B19V has been associated with serious complications such as transient aplastic crisis, neurologic manifestations, and perilous outcomes during pregnancy.

Clinical Manifestations in Children:

In children, particularly those of school age, B19V classically induces erythema infectiosum, also known as fifth disease. This condition is characterized by a biphasic fever and rash illness. The initial phase includes flu-like symptoms such as headache, sore throat, vomiting, diarrhea, fever, and coryza, attributed to B19V viremia.

The distinctive “slapped cheek” rash, an erythematous malar-like exanthem with circumferential pallor, typically appears two to five days later, corresponding to immune activation. The rash may later spread to the trunk and limbs, often presenting as an erythematous reticular-type rash.

Clinical Manifestations in Adults:

In adults, B19V can manifest in various cutaneous forms, with polymorphous rashes being common. Gloves-and-socks involvement has been noted, and joint involvement, particularly polyarthralgia or polyarthritis, is prevalent in individuals over 18 years. Up to 60% of adult patients may experience arthropathy-related symptoms, which are usually symmetric and involve smaller extremity joints like those of the hands, wrists, knees, and feet. Although these symptoms typically resolve within a few weeks, chronic manifestations have been reported, and there is a link between B19V and other rheumatological diseases.

Serious Complications:

Transient aplastic crisis (TAC) represents a potentially more severe manifestation of B19V, characterized by a temporary suspension of red blood cell production. Severe anemia associated with TAC can lead to complications such as exacerbation of congestive heart failure, cerebrovascular events, and acute splenic sequestration. While anemia is not generally present in B19V infections, hematological abnormalities can predispose individuals, such as those with sickle cell disease, to severe cases of TAC. Other perilous complications include neurologic manifestations like encephalitis and peripheral issues such as Guillain–Barré syndrome.

Pregnancy-Related Complications:

During pregnancy, B19V infection poses risks such as fetal loss, anemia, and non-immune hydrops fetalis. The risk of fetal loss varies throughout pregnancy, with higher rates if infection occurs in the first trimester. Fetal hydrops, characterized by excessive fluid accumulation in fetal compartments, poses a significant risk during the first and second trimesters, contributing to fetal loss. Transplacental transmission of B19V leads to fetal liver infection, causing severe anemia and, at times, thrombocytopenia. Low hemoglobin levels can contribute to high-output heart failure, with direct damage to the myocardium also reported.

Epidemiology:

The lifetime prevalence of B19V is relatively high globally, with different genotypes prevalent in various regions. Genotype 1 is widespread, genotype 2 is rare and considered ancestral to genotype 1, while genotype 3 is primarily found in Africa and South America. The intergenotype genetic divergence is up to 13%. Prevalence increases with age, with school-age seroprevalence ranging from 20% to 60%, and up to 80% in adults in Western countries.

Approximately 50–75% of women of reproductive age have been infected with B19V, while half of pregnant women are susceptible. In temperate climates, a seasonal pattern is observed, with higher prevalence during late winter and early spring. Although incidence can be sporadic, large local outbreaks have been documented every few years.

Recent Incidence Trends:

Despite a relatively high prevalence of B19V, there has been a perceived rise in recent years. A retrospective study was conducted to explore the incidence rates of B19V among different population segments. The study aimed to provide updated insights into the current prevalence and patterns of B19V infections, especially considering the absence of routine monitoring programs. The collective clinical experience of the research team prompted the investigation into whether there has been a significant increase in B19V cases, shedding light on the evolving epidemiology of this pathogenic virus.


Discussion

This study represents a comprehensive analysis of Human Parvovirus B19 (B19V) in Israel, spanning nine years and including data from over 2.7 million individuals. The retrospective design allowed for the calculation of monthly rates of B19V infection, enabling a nuanced comparison of the current year to all preceding ones. The findings highlight a notable surge in B19V cases in 2023, surpassing all previous years in both incidence rates and absolute numbers.

The rate ratio for B19V infection in 2023 compared to 2015–2022 was strikingly high, reaching 6.6 (95% CI, 6.33–6.89) after adjusting for various factors, including sex, age, socioeconomic status, district of residence, social sector, and calendar month. This surge in 2023 stands out as the highest ever reported incidence rate of B19V in Israel, surpassing previous surges documented in 2008 and 2011–2012. Notably, the surge in 2023 is even more pronounced when compared to the peak years of the COVID-19 pandemic, demonstrating a nine-fold increase in incidence rates. This suggests a potential interaction between B19V and the patterns of other viral illnesses, possibly influenced by changes in social and healthcare-related behaviors during the pandemic.

An intriguing aspect of the current outbreak is its impact on the seasonality patterns of B19V. Unlike previous surges, which followed the typical pattern of temperate climates, the incidence rates in 2023 persisted into the autumn months. While September marked a slowdown, incidence rates remained higher than those observed in previous fall seasons. This alteration in seasonality warrants further investigation through continuous follow-up and additional studies.

Children continue to be the most affected age group, constituting over 80% of all documented infections during the nine years studied. The surge in 2023 maintains this trend, with school-aged children (ages 6–12) being the most affected subgroup. The elevated incidence in this age group aligns with the classic symptomatology of erythema infectiosum, leading to increased awareness, testing, and diagnosis.

In pregnant women, the relative increase in infection rates in 2023, particularly in the first trimester, suggests heightened awareness due to potential fetal complications. The surge in B19V cases in pregnant women, with an Incidence Rate Ratio (IRR) of 11.47 (95% CI, 9.44–13.97) compared to previous years, emphasizes the need for continued vigilance and targeted interventions in this vulnerable population. Secondary attack rates, particularly in occupations with substantial exposure opportunities, such as daycare center workers or schoolteachers, underscore the importance of tailored preventive strategies during outbreaks.

Despite the comprehensive nature of this study, several limitations should be acknowledged. The absence of mandatory or routine screening policies for B19V in Israel may underestimate the true incidence, particularly considering potential asymptomatic cases. Furthermore, disparities in testing practices based on demographics, including socio-economic status and ethnicity, introduce complexities in assessing relative incidence between groups. The rise in B19V incidence observed in 2023, without a corresponding increase in testing rates and the specificity of erythema infectiosum presentation, supports the validity of the surge observed.

Conclusion:

Human parvovirus B19 continues to be a significant pathogen with a diverse range of clinical manifestations and potential complications. From the classic fifth disease in children to joint involvement, transient aplastic crisis, and severe outcomes during pregnancy, B19V poses challenges across various age groups and populations. The ongoing research into recent incidence trends aims to provide valuable information for clinicians and public health professionals, informing strategies for monitoring, prevention, and management of B19V infections. As our understanding of this virus evolves, continued surveillance and research efforts will be essential to address emerging challenges and optimize patient outcomes.


reference link:https://www.mdpi.com/1999-4915/15/11/2261

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