Reasons for the Increasing Frequency of Viral Diseases Emergence

Several global trends have significantly increased the risks associated with the emergence and spread of infectious diseases. Urbanization and population growth have transformed our cities into densely populated hubs where diseases can easily spread. Moreover, advancements in transportation have made global travel faster and more accessible than ever before, reducing the time it takes to circumnavigate the globe from months to just hours. This rapid movement of people means that viruses can potentially travel across continents within the incubation period of an infection before symptoms even manifest.

The SARS pandemic of 2002–2003 serves as a stark example of how quickly a new virus can spread globally. Originating in China, SARS-CoV spread to more than two dozen countries within a matter of months, highlighting the interconnectedness of our modern world and the challenges it poses for disease control and prevention.

In addition to human activities, environmental changes driven by agriculture and urban development play a crucial role in disease emergence. The conversion of natural habitats for agriculture or infrastructure projects creates new ecological niches that can harbour disease vectors and reservoirs. For instance, urban yellow fever likely originated when humans entered jungle areas where the virus was maintained in a cycle between monkeys and mosquitoes. The introduction of infected individuals back into urban centres facilitated the virus's adaptation to a new cycle involving mosquitoes like Aedes aegypti, which thrive in urban environments and preferentially feed on humans.

Furthermore, the intensification of agribusiness has led to the concentration of large numbers of livestock or crops in confined spaces. This practice increases the risk of rapid disease transmission among closely packed animals or plants, creating conditions ripe for the emergence of new pathogens or the spread of existing ones.

International trade in plants and animals has also contributed to the spread of diseases across borders. The 2003 outbreak of monkeypox in the United States, for example, was traced back to the importation of Gambian giant rats from Africa as exotic pets. The virus spread from these animals to domestic pets and then to humans, causing public health concerns due to its similarity to smallpox.

These interconnected factors underscore the urgent need for global cooperation and proactive measures to monitor, prevent, and respond to emerging infectious diseases. As our world becomes increasingly interconnected and urbanized, understanding and mitigating the risks posed by infectious diseases have become critical global health priorities.

In the mid-1800s, rabbits brought from Europe to Australia for sport quickly multiplied without natural predators, threatening grasslands and crops in southern Australia. To control their numbers, the myxomatosis virus was introduced in 1950, causing a devastating outbreak among the rabbit population due to its high lethality. Over time, the virus evolved, with less deadly strains becoming more common as rabbits developed genetic resistance. This natural selection favoured moderately harmful strains because milder ones struggled to spread, while highly lethal ones killed rabbits too quickly to transmit effectively.

This situation demonstrates the complexities of using viruses for population control and raises concerns about unintended consequences. Introducing viruses, even for beneficial purposes like managing wildlife, can disrupt ecosystems and pose biosecurity risks. Such considerations are crucial in both wildlife management and assessing the potential risks associated with intentional virus introductions, which could also serve as models for bioterrorism.

Significant progress has been made in the field of xenotransplantation, particularly in using genetically modified pigs as organ donors to address the shortage of human organs for transplantation. Research has focused on various areas such as pancreatic islets, neuronal cells, corneas, and vascularized organs like kidneys and hearts. However, a critical concern arises regarding the potential transmission of known or unknown latent or persistent viruses from donor organs to transplant recipients. This is especially pertinent because transplant recipients undergo immunosuppression to prevent rejection of the transplanted organ, which could make them more vulnerable to infections from viruses originating from the donor species.

In the worst-case scenario, this situation could facilitate the transmission of a foreign virus across the species barrier, allowing it to establish itself as a new human virus. Such a virus could potentially spread from the graft recipient to others, posing significant public health risks. Therefore, while xenotransplantation offers promising solutions to organ shortages, careful consideration and ongoing research are essential to mitigate the risks associated with viral transmission and ensure the safety of transplant recipients and the broader community.

Is it typical for Influenza Virus A to infect cattle?

The influenza virus, a single-stranded negative-sense RNA virus of the Orthomyxoviridae family, causes acute respiratory illness in animals, birds, and humans. It is classified into types based on genetic traits and their impact. The virus possesses surface glycoproteins hemagglutinin and neuraminidase, with 18 hemagglutinin (H1-H18) and 11 neuraminidase (N1-N11) subtypes. These glycoproteins facilitate attachment to host cell receptors.

Influenza A is the most prevalent type, causing seasonal flu outbreaks in humans and animals. Subtypes like H1N1 and H3N2 are defined by their surface proteins. Influenza B virus also infects humans, causing seasonal flu but with less variation than influenza A. Influenza C virus can infect humans but typically causes milder illness than A and B types. Influenza D virus primarily affects cattle and rarely infects humans. Understanding these distinctions aids researchers and healthcare providers in effectively monitoring and responding to influenza outbreaks.

Viruses employ host adaptation strategies to enter and cause diseases in various hosts, including birds, animals, and humans. Influenza virus can successfully cross species barriers by adapting through several key factors. These include receptor affinity, which determines its ability to bind to host cells (tropism); stability in various environments, allowing it to survive and spread effectively (environmental stability); and its capacity to evade the host immune system's defences (immune evasion). These adaptations enable the virus to infect and potentially establish new reservoirs in different species.
Domestic cattle are crucial in food and agriculture, maintaining significant importance in the modern world. However, pigs have served as mixing vessels for avian and human influenza A viruses. Human interaction with swine has facilitated the bidirectional influenza transmission at the pig-human interface. Cattle were domesticated by humans long before pigs were.
Cattle were largely unaffected by influenza A and were not considered susceptible hosts for the virus. Certain bovine host factors, including specific serum components and secretory proteins, possess anti-influenza properties. These factors may contribute to the resilience of bovines to influenza A virus (IAV). 

Swine (pigs) are the primary hosts where different subtypes of influenza viruses mix. When these subtypes replicate within the same host, antigenic shift and drift occur. Antigenic drift results from mutations in the hemagglutinin (HA) and neuraminidase (NA) genes, gradually altering the virus's surface proteins. This diminishes the effectiveness of previous immunity, requiring regular updates to influenza vaccines. Antigenic shift, meanwhile, happens when different influenza viruses exchange genetic material, creating new strains that can lead to global pandemics due to limited existing immunity in humans.

The Spanish flu in 1918 was very deadly, causing about 50 million deaths. The Asian flu in 1957-1958 started in Asia and killed 1-2 million people globally. Then, the Hong Kong flu in 1968 started in Hong Kong and caused 1-4 million deaths worldwide. In 2009, the swine flu spread from pigs to people and caused millions of illnesses worldwide, though fewer deaths compared to earlier outbreaks. These outbreaks show how flu viruses can spread worldwide and influence how we get ready for future outbreaks.

Bovine milk can interfere with the hemagglutinating property of the influenza virus. Bovine IgG present in the milk binds with viruses, aiding in phagocytosis. In milk, oligosaccharides can block the influenza virus from binding to cells' sialylated glycans by acting as dummy receptors. 

Bovine lactoferrin (bLf) is a crucial 76 kDa glycoprotein composed of a single polypeptide chain containing 689 amino acid residues. It is found in biological fluids and specific granules of polymorphonuclear leukocytes. This protein plays key roles in immunomodulation, iron absorption, and inhibiting pathogens, including enveloped viruses like influenza.

In bovine serum, there are inhibitors similar to conglutinin. These inhibitors can help by acting as opsonins, which means they assist in phagocytosis (the engulfing and digestion) of influenza A viruses. 

Aprotinin, a natural protease inhibitor derived from bovine lung, is currently used in humans for treating pancreatitis and haemorrhage. It also shows promise in suppressing the cleavage of the pandemic H1N1 influenza virus.

The global agriculture and food systems are facing a serious challenge due to an outbreak of H5N1 avian influenza, or bird flu, centred in the United States. Although it rarely spreads to mammals, authorities are working hard to control it. 

So far, there hasn't been much impact on our food and nutrition, but experts warn that this situation shows potential problems for farming and serious health risks for animals and possibly humans. It's important to closely watch and take action to protect public health and ensure our food supply stays safe and reliable despite these challenges.

Immune Amnesia Associated with Measles

 The immune responses triggered by measles virus (MV) infection can unexpectedly suppress the body's ability to respond to other unrelated antigens, a condition that may persist for weeks to years after the acute illness subsides. This immune suppression significantly increases vulnerability to secondary bacterial and viral infections such as pneumonia and diarrhea, which are major causes of illness and death following measles.

Measles infection disrupts delayed-type hypersensitivity (DTH) responses to known antigens like tuberculin, and impairs both cellular and humoral responses to new antigens. This immune dysregulation also contributes to the reactivation of tuberculosis and the worsening of autoimmune diseases post-measles.

In essence, measles-induced immune suppression not only weakens immediate defenses against pathogens but also compromises the immune system's ability to mount effective responses to a range of antigens over an extended period.

Measles-induced immune suppression can occur due to changes in antigen-presenting cells or effector lymphocytes, or through the depletion of CD150+ memory lymphocytes. Measles virus (MV) infects CD150+ immune cells, including memory T- and B-lymphocytes. Studies comparing blood samples collected from unvaccinated children before and after measles reveal incomplete reformation of B-lymphocyte pools post-infection. Additionally, measles leads to a significant reduction in circulating antibodies against various viruses and bacteria, impairing immunological memory and causing what is termed 'immune amnesia'.

This mechanism contributes to increased childhood morbidity and mortality for more than two years after measles infection. Abnormalities in both innate and adaptive immune responses are evident following MV infection. Children commonly experience transient lymphopenia, characterized by decreased T and B lymphocytes in the blood. Furthermore, immune cells such as dendritic cells, crucial for presenting antigens to lymphocytes, show impaired maturation and reduced ability to stimulate lymphocyte proliferation.

In summary, measles disrupts immune function by compromising both cellular and antibody-mediated immunity, leading to prolonged susceptibility to infections and contributing to the severity of measles-related complications in children.

Antiviral Drug Resistance: A Global Problem

 RNA viruses, renowned for their high mutation rates, undergo rapid evolution. Consequently, genotypes harbouring mutations conferring drug resistance can emerge swiftly. A virus strain is deemed 'resistant' to a drug if it can replicate in the body despite the presence of the drug at concentrations that inhibit replication of 'sensitive' strains. Drug-resistant virus isolates typically exhibit gene mutations encoding the proteins the drug targets. Most mutations leading to drug resistance in HIV-1 involve changes in amino acids. However, some mutations can also involve deletions or insertions of genetic material. In the HIV-1 virus, mutations in the reverse transcriptase gene that make it resistant to nucleoside analogues (such as AZT) occur in different specific codons compared to mutations that confer resistance to non-nucleoside inhibitors (like nevirapine). This difference is because these two classes of drugs target distinct regions within the reverse transcriptase enzyme. This specificity in mutation locations highlights how different drugs can influence HIV-1's genetic makeup differently, affecting its ability to resist treatment.

Clinical challenges arise when drug-resistant virus strains develop in patients undergoing treatment and when these resistant strains are transmitted to others. When drug-resistant HIV strains emerge during treatment, patients may switch to alternative medications. Initially, AZT was widely used for HIV treatment but resistance quickly developed. Similar challenges arose with other single-drug therapies. The current standard for treating HIV infection involves highly active antiretroviral therapy (HAART), which combines different classes of drugs like reverse transcriptase inhibitors and protease inhibitors.

Monitoring the effectiveness of HIV treatment involves measuring HIV RNA levels in the blood. HAART typically leads to a rapid reduction in HIV RNA within the first 10 days, followed by a slower decline over weeks. In some patients, HIV RNA stabilizes at low levels (5-50 copies/ml), while in others, it drops to less than 5 copies/ml over time.

HAART also reduces HIV levels in the seminal fluid of men and the genital secretions of women. While it doesn't eradicate HIV from the body, the virus persists in latent forms in macrophages, memory CD4 T cells, and possibly in immune-privileged sites like the brain and testes. Despite this persistence, HAART has significantly lowered AIDS-related mortality in developed countries. Additionally, treating HIV-positive women has substantially decreased mother-to-child transmission risks.

Overall, HAART represents a pivotal advancement in managing HIV infection, offering optimism through effective suppression of the virus and improved quality of life for patients.

Can all types of vaccines be given on the same date?

Administration of different vaccines at the same visit both live and inactivated vaccines does not result in decreased antibody responses or increased rates of adverse reaction. Simultaneous administration of all vaccines for which a child is eligible is very important in childhood vaccination programs because it increases the probability that a child will be fully immunized at the appropriate age.

For some vaccines, administration should not be done at different time intervals. The live parenteral (injected) vaccines (MMR, MMRV, varicella, zoster, and yellow fever) and live intranasal influenza vaccine (LAIV should be separated by at least 4 weeks. This interval is intended to reduce or eliminate interference from the vaccine. The yellow fever vaccine Should be administered less than 4 weeks after the single-antigen measles vaccine. A 1999 study demonstrated that the yellow fever vaccine is not affected by the measles vaccine given 1–27 days earlier. Live vaccines administered by the oral route (oral polio vaccine [OPV] oral typhoid, and rotavirus) are not believed to interfere with each other if not given simultaneously. These vaccines may be given at any time before or after each other. The Rotavirus vaccine is not approved for children older than 32 weeks, and oral typhoid is not approved for children younger than 6 years of age.

Parenteral live vaccines (MMR, MMRV, varicella, zoster, and yellow fever) and LAIV are not believed to have an effect on live vaccines given by the oral route (OPV, oral typhoid, and rotavirus). Live oral vaccines may be given at any time before or after live parenteral vaccines or LAIV. All other combinations of two inactivated vaccines, or live and inactivated vaccines, may be given at any time before or after each other.

 

HIV as the emerging infectious Viral disease

 “Infections that have newly appeared in a population or have existed previously but are rapidly increasing in incidence or geographic range” is termed as Emerging infections (EIs). In 1981, a new disease — acquired immune deficiency syndrome (AIDS)was first recognized. The emergence of HIV raised few questions, firstly the zoonotic source of HIV and its inter and intra species transmission.
Simian immunodeficiency virus (SIV)may have transmitted to humans in at least four separate occasions, identified by individual HIV-1 lineages called groups (M, N, O, P). The most important was the M group of HIV-1, main cause of human infections. HIV-1 is most closely related to SIVcpz, the SIV strain infecting two subpopulations of chimpanzees. Different segments of the SIVcpz genome, are closely related to genome segments of two SIVs of African monkeys, red-capped monkeys and Cercopithecus monkeys.

It is assumed that chimpanzees, regularly kills monkeys, were infected during consumption of their prey; and this infection may have led to a recombination event producing SIVcpz, which was derived from parts of the genomes of the two acquired monkey viruses. Further transmission from Chimpanzee to humans may have occurred during butchering of non-human primates mainly in rural Africa.

During the period from 1930 to 1980 the virus remained as a rare and unrecognized infection in residents of jungle villages in West Africa during this time, reuse of unsterilized needles occurred, a frequent practice during the period of colonial rule, could have helped to spread the virus. 

 

In 1980, the virus began to spread more rapidly. Accelerated spread began in the region centered on Kinshasa (previously Leopoldville) in the Democratic Republic of the Congo (previously the Belgian Congo, then Zaire) and Brazzaville, just across the Congo River in Congo. Transmission was enhanced by the chaos in postcolonial Zaire.
During the period 1985–2004, HIV infection spread widely in Africa. And the prevalence of infection among adults aged 15–49years reached levels higher than 30%. 

The rapid spread was driven by many factors ,such as a high frequency of concurrent sexual contacts in some segments of the population and the hidden nature of sexual networks., the long asymptomatic incubation period during which infected individuals able to transmit the virus were sexually active, the spread along commercial routes of travel within Africa; the failure of health systems to publicize the risks and the under utilization of condoms and other measures to reduce transmission the slow introduction of antiviral treatment after it became available in the northern countries about 1996.

With the spread of HIV in Africa, the M group of HIV-1 evolved into nine different subtypes (A–D, F–H, J, K), based on sequence diversity. Subtype C is most frequent in southern Africa, and subtypes A and D are most frequent in eastern Africa. During the 1980s, HIV spreaded globally, although prevalence rates lower than in some African countries. Subtype B is dominant in the western hemisphere and Europe, while subtype C is most frequent in India and some other Asian countries. Although the global incidence of HIV has fallen slightly since 2010, there are still more than two million new infections each year.

Subacute sclerosing pan encephalitis (SSPE): Persistent measles Virus infection

Subacute sclerosing pan encephalitis (SSPE), also called Dawson’s encephalitis, is a persistent measles infection of the central nervous system. SSPE is a progressive, fatal, encephalopathy characterized by personality changes, mental deterioration, involuntary movements, muscular rigidity, and death. SSPE usually begins 4–10 years after the patient has recovered from naturally acquired measles.
Successful isolation of measles virus from brain and lymphoid tissues of SSPE patients clearly established measles virus as the etiologic agent of the disease. Molecular characterization of measles virus nucleic acid sequences derived from brain biopsy or autopsy has identified wild-type measles sequences with few exceptions, and not those of the vaccine strains.
Measles virus genotypes found in association with SSPE clinical specimens are generally the circulating sequences, in the geographic region where the patients acquired natural infection. No vaccine sequences were identified from tissues of SSPE patients.
SSPE is a very rare but lethal disease, persisting in the human central nervous system (CNS). It is characterized by the absence of viral budding, reduced expression of the viral envelope proteins and spread through the CNS despite massive immune responses. The persistence of measles virus in the brain cells may be due to mutations in the MV genes that were introduced not only due to errors of the MV polymerase, but also in clusters due to hypermutations. The other reasons may be the MV matrix (M) gene, which is most heavily mutated, mutation in the transmembrane glycoproteins, which may be the cause of genetic defects in the persisting measles virus.
The diagnosis is clinical and immunological evidence of measles infection. Management of the disease includes seizure control and avoidance of secondary complications associated with the progressive disability.
Treatment with interferon, ribavirin, and Isoprinosine have reported to give beneficial results. However, the disease shows continuous progression; only 5% of individuals with SSPE undergo spontaneous progress, with the remaining 95% dying within 5 years of diagnosis.