1 Background

Adenoviruses (AdV) are members of the genus Mastadenovirus, which is part of the family Adenoviridae. The term “adenovirus” originates from its discovery in human adenoids in 1953. The genomic size of an adenovirus is between 34 and 36 K base pair, making it a non-enveloped, medium-sized (70–100 nm), double-stranded, linear DNA virus. There are seven recognized species (A through G). Adv can be found in the bodies of fish, amphibians, reptiles, birds, mammals (including humans), and even in the eggs of amphibians [1]. While there are over 100 serotypes identified, more than 60 serotypes are associated with HAdv (Human adenovirus) [2]. HAdV can infect various anatomical sites, including the gastrointestinal tract (species A, F, and G), respiratory tract (particularly species A to C, and E), conjunctivae (species B, D, and E), and urinary tract (species A, B, and C). HAdV infections predominantly manifest as keratoconjunctivitis or as infections of the upper or lower respiratory tract. Among the emergent strains, HAdV types 7, 3, 4, and 14 are frequently implicated in outbreaks. The continued circulation of these strains, especially HAdV-7 and HAdV-14, raises concerns regarding genetic drift, which may lead to enhanced population transmission rates and increased severity of disease [3]. The aim of this paper is to explore the health risks associated with adenovirus infections, highlight recent advanced cases, assess current disease management strategies, and propose effective prevention measures to reduce the future burden of these infections.

2 AdV: General Information

AdV are capable of infecting individuals of all ages; however, they are more prevalent in infants, and young children [1]. HAdV is widespread globally, although detection rates differ among years, regions, and countries. According to a recent global study, HAdV infection constituted 5%–10% of respiratory tract infections in children and could result in pneumonia in up to 20% of infants and newborns. The incidence of different complications associated with adenovirus pneumonia decreases with age, potentially due to the progressive development of the immune system [4]. The incubation time spans from 2 to 14 days, depending on the viral serotype and mode of transmission [5]. AdV can cause a wide range of symptoms similar to those of the common cold, including fever, cough, and sore throat. Severe diseases of the lower respiratory tract, such as bronchitis, bronchiolitis, and pneumonia can occur. Additionally, adenoviruses are linked to conditions such as conjunctivitis, gastroenteritis, cystitis, myocarditis, cardiomyopathy, hepatitis, nephritis, and encephalitis. An infection might persist without symptoms for weeks or even months [1].

The virus can be transmitted from one individual to another through the exchange of bodily fluids such as urine, saliva, and blood. Additionally, personal contact, such as shaking hands or touching, as well as sharing utensils with an infected person, can facilitate transmission [6, 7]. The virus may also spread through respiratory droplets released into the air during sneezing or coughing, or by contacting surfaces that have been contaminated by an infected individual. Attack rates are greater in younger children (particularly under the age of 5) [8, 9], and in persons who have environmental risk factors such as attending a daycare, living in crowded settings, or having a poor socioeconomic position [8]. The severity of the viral illness is determined by host characteristics such as malnutrition, anatomical defects, metabolic or genetic disease, chronic heart or lung disease, and immunological inadequacies [8, 10].

There is currently no recognized antiviral medication that is particularly effective for adenovirus infections. Cidofovir is frequently regarded as a treatment for AdV infections [11]; however, ribavirin and ganciclovir have also demonstrated efficacy against the virus in vitro [10]. New therapies that are emerging, like the transfusion of adenovirus-specific T-lymphocytes and brincidofovir could expand the treatment options for AdV. Most treatment is symptomatic; depending on the clinical symptoms, certain children may require hospitalization, while others may require aid breathing with oxygen. Upholding one's standards of personal cleanliness is critical [11].

Vaccines that protect against the illnesses caused by HAdV4 and HadV7 are now under production. They were first developed to protect military recruits against infection, but they have not yet gained widespread acceptance among the general population [11]. Diagnosis of AdV infections can be done through various laboratory tests, including viral culture, PCR testing, serological tests, immunoassays, immunofluorescence tests, and rapid antigen testing [12].

3 Recent Cases and Prevalence of AdV/HAdV

Pakistan experienced an upward trend of AdV outbreaks, attributed to climate variations and environmental contamination. Other contributing factors include fecal contamination, inadequate hygiene practices, limited availability of clean water and sanitation facilities, and transmission through airborne droplets. Based on recent data from February 2024, there were 782 and 1275 cases of AdV-related severe respiratory tract infection documented in just 2 days. This rise in cases aligns with the pattern observed in February 2023, when government-run hospitals experienced a daily influx of over 1000 individuals with symptoms such as fever, headaches, chills, and runny noses. Additionally, a notable surge in cases of adenoviral conjunctivitis in September 2023 was documented, primarily in Punjab. The outbreak resulted in an alarming total of 86,133 cases, with an average of 13,000 new cases documented daily. Furthermore, approximately 100 instances of the infection were recorded within a 24-h timeframe during that same period [13].

Between January and March 2023, over 12,000 confirmed cases of Adenoviruses were recorded in West Bengal, India. Tragically, 150 children lost their lives due to acute respiratory infections and related complications resulting from a lack of immunity to common infections [14].

In China, studies have shown that the positive detection rates of HAdV in acute respiratory tract infections range from 5.8% to 13%, primarily affecting children [4, 15]. In the southern region of China, children admitted to hospitals with adenovirus associated pneumonia encountered two periods of heightened activity: the primary peak from December to January during winter and a secondary peak from May to August during summer. From January 2016 to December 2021, 1854 children were hospitalized with AdV, accounting for 0.13% of pneumonia-related hospitalizations [4]. As of April 21, 2022, there have been documented cases of acute hepatitis of unknown origin in at least 169 individuals across 11 countries. AdV has been identified in at least 74 of these cases. However, due to limited diagnostic resources, there have been no verified instances [16]. In West Bengal, India, there has been a significant rise in the incidence of childhood pneumonia since December 2022 [9].

The rates of antibodies against various types of HAdVs differed widely across different countries and regions. Southeast Asia exhibited the highest median prevalence at 54.57%, while the Eastern Mediterranean followed with 43.31%. The Western Pacific had a median of 42.40%, Africa recorded 35.48%, and the Americas had a prevalence of 24.02%. In comparison, Europe showed the lowest median prevalence at 18.17% [2]. Immunocompromised individuals who had previous COVID-19 infections are more susceptible to adenovirus. This risk group includes around 750 million people. The virus can easily spread within the densely populated areas of South Asia, where overcrowded slums and refugee camps serve as significant sources for its transmission. In underdeveloped nations with poor diets and low immunity, the possibility of HAdV transmission increases significantly [16].

4 Current Scenario of Disease Management

HAdV infections and sporadic outbreaks are commonly seen throughout the year in both developed and developing countries. Infection can occur through the reactivation of a dormant virus or contact with an infected individual. This potentially fatal virus produces extended influenza-like symptoms that can last for weeks. Symptoms similar to those caused by COVID-19 are caused by all prevalent viruses. However, many people are not very informed about the viral infection. Instead, they believe that the flu-like symptoms are caused by a common cold or by the polluted air that is prevalent in urban areas, although some people are also considering the possibility that COVID-19 is to blame. The severity of COVID-19 in children and teenagers was not discovered to be that much severe; hence, the majority of individuals are treating the infection situations with a great deal of flippancy. Given that the prevalence of antibodies against this virus is highest in South Asian countries, Bangladesh is notably at risk from this adenovirus epidemic, primarily due to trade and travel between Pakistan and Bangladesh, as well as India and Bangladesh. Genomic analyses have disclosed the emergence of new genetic mutations in isolated viruses, indicating that, despite their relatively stable genome, human adenoviruses are continually evolving. The extent of their spread within the general population remains uncertain, primarily due to the lack of clinical diagnostic testing outside of critically ill patient groups. Additionally, it is still unclear how both viral and host factors may influence the heightened pathogenesis of emerging strains of HAdV. Unfortunately, there is currently minimal organized surveillance of HAdV infections in clinical and public health contexts, which typically only occurs when a larger outbreak is detected. The recent introduction of rapid molecular diagnostic tests has significantly enhanced the detection of adenovirus infections. However, the cost of these assays and the limited frequency of their use restrict the rate of specific viral identification in clinical specimens. Consequently, the actual number of adenovirus infections, hospitalizations, and fatalities is likely much higher than what is reflected in current outbreak reports. This discrepancy arises because many patients presenting to emergency departments are often treated symptomatically and are not specifically screened for adenovirus infection [3].

5 Proposed Strategy for Disease Prevention

Due to past encounters with COVID-19, the general public has gained familiarity with hygiene protocols. It is essential for individuals to follow hygiene practices and avoid touching the face, nose and eyes with filthy hands. Sanitizers should also be used. In crowded areas, it is important to take precautions against the spread of disease by routinely washing hands with soap and water and wearing protective gear like a face mask [14]. Infected individuals should remain at home, while hospitalized patients with HAdV infection should be isolated from immunocompromised patients.

Timely responses are vital in addressing adenovirus infections, encompassing the swift mobilization of medical resources, healthcare personnel, and the establishment of treatment facilities. Providing clinical, nutritional, and psychosocial support to patients with adenovirus is essential. Healthcare providers must implement strategies to prevent the spread of the disease to noninfected individuals when treating these patients. Improving immunity through various programs can reduce mortality in immunocompromised individuals affected by this self-limiting viral infection. Immunity-boosting programs, including regular exercise and a nutritious diet, can help reduce mortality. Furthermore, the implementation of infection prevention and control protocols in healthcare, communal, and residential settings is crucial for effectively managing the transmission of adenovirus.

Establishing a secure and efficacious treatment strategy is crucial. Medium- and long-term scientific initiatives should prioritize the development of vaccines, antiviral medications, and the improvement of diagnostic facilities. Diagnostic system should be backed by skilled staff and suitable equipment. It is crucial to engage in collaborative research, conduct clinical trials, and invest in healthcare infrastructure to ensure continued advancements in the fight against adenovirus. The government should enhance healthcare infrastructure and technical resources. Researchers should focus on understanding the virus's characteristics, symptoms, and mutation trends for future treatment directions. It is imperative for international organizations, NGOs, and government institutions to promptly revive campaigns to raise awareness. Community engagement in decision-making, the provision of accessible healthcare services, and the cultivation of trust between healthcare providers and communities are critical for encouraging preventive measures among vulnerable populations.

6 Conclusion

Despite an increase in research on monitoring HAdV infection, there is a scarcity of nationwide research on the prevalence of adenovirus pneumonia, particularly multi-center investigations into the clinical epidemiology and burden of the disease in hospitalized children. The heightened transmissibility and severity of adenovirus infection is indeed alarming for the global population. To minimize the transmission of adenoviruses and to mitigate additional outbreaks, it is imperative to implement stronger hygiene practices, raise public awareness, and provide appropriate medical interventions. Individually, people should practice hand hygiene, maintain distance, dispose of waste properly, and isolate infected individuals. These measures can significantly contribute to reducing the spread of the virus and effectively alleviating the burden of outbreaks. By strengthening healthcare systems, enacting extensive public health measures, and allocating resources to research and innovation, we can mitigate the consequences of adenovirus outbreaks and safeguard the well-being of our communities. Collaboration between governmental organizations, healthcare professionals, and the general populace is crucial in tackling this urgent public health concern and ensuring a more robust and well-being-oriented future for everyone.

Author Contributions

Taslima Jamal Urmi: conceptualization, writing – original draft. Jannatul Mabia Rahman: resources. Syed Masudur Rahman Dewan: conceptualization, writing – review and editing, supervision.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Transparency Statement

The lead author Syed Masudur Rahman Dewan affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Guarantor

All authors have read and approved the final version of the manuscript. SMRD, the corresponding author, had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.