Mictobiology . - virology GRP 16 micro b 3-1 (2)final.pptx

Introduction to virology

1. MICROBIOLOGY . 3 COURSE WORK GROUP 16 MEMBERS HAMALA INNOCENT LUCKY- VU-BPC-2307-0058-DAY GWEBAYANGA COLLINE- VU-BPC-2209-0819-DAY EMULU ENOS CHARLES- VU-BPC-2209-0148-DAY IGOLE PAUL JONATHAN- VU-BPC-2301-1232-DAY IGA IVAN- VU-BPC-2209-0376-DAY

2. QUESTIONS 1 . What are the key structural characteristics and replication mechanisms of Rubella virus and group A arboviruses, and how do these properties affect their role in human infections? 2. Analyze the transmission dynamics and epidemiological patterns of Rubella virus and group A arboviruses. How do their modes of transmission impact public health strategies? 3. What are the typical clinical manifestations of Rubella virus and group A arbovirus infections? Discuss the risks of congenital rubella syndrome and its implications for disease control. 4. Evaluate the role of vaccines in preventing Rubella and group A arbovirus infections. How effective are current vaccination programs in controlling outbreaks?

3. continued; Mononegavirales : Paramyxoviridae (Measles, Mumps, Human Respiratory Syncytial Virus, Parainfluenzae , Metapneumovirus ): How do the structural and genomic features of Paramyxoviridae viruses contribute to their infectivity and pathogenesis in humans? Focus on measles, mumps, and respiratory viruses . Discuss the clinical manifestations and complications of infections caused by Measles virus, Mumps virus, and Human Respiratory Syncytial Virus. What are the age-related differences in disease severity ? What are the current global challenges in controlling measles, mumps, and respiratory viral outbreaks despite the availability of vaccines?

4. RUBELLA VIRUS . Rubella virus ( Rubivirus genus, family Matonaviridae ) An enveloped, single-stranded, positive-sense RNA virus. It primarily causes rubella (German measles), a mild viral illness. But can result in congenital rubella syndrome (CRS) if contracted during pregnancy.

5. Continued ; Structural Characteristics 1. Genome : Rubella virus has a linear, single-stranded, positive-sense RNA genome. It contains two open reading frames (ORFs) that encode nonstructural and structural proteins. Nonstructural proteins : Involved in viral replication. Structural proteins : Include the E1 and E2 glycoproteins , which are important for host cell entry and immune evasion.

6. Continued; 2. Envelope . The virus is enveloped. H as a lipid bilayer derived from the host cell membrane. The surface glycoproteins E1 and E2 facilitate attachment and fusion with host cells. 3. Capsid . Inside the envelope, the viral RNA is encapsulated in a protein shell (capsid), which protects the RNA genome. Replication Mechanism 1. Attachment and Entry . Rubella virus attaches to host cell receptors via its E1 glycoprotein. it enters the host cell through receptor-mediated endocytosis .

7. continued; 2 ) Uncoating : Upon entry, the viral envelope fuses with the endosomal membrane, releasing the viral RNA into the cytoplasm. 3 ) Translation and Replication . The positive-sense RNA acts as mRNA and is directly translated into nonstructural proteins by host ribosomes. These proteins form a replication complex that synthesizes a negative-sense RNA intermediate, which is used to produce more positive-sense RNA genomes. 4) Assembly and Release . Structural proteins are synthesized . New viral particles are assembled in the cytoplasm. Virions are then enveloped as they bud off from the host cell membrane.

8. Continued; Role in Human infections 1. Congenital Rubella Syndrome (CRS) . If a pregnant woman contracts rubella, the virus can cross the placenta , causing developmental defects in the fetus, including heart, brain, and eye abnormalities. 2. Vaccine : The rubella vaccine (MMR) has reduced incidence of occurrences, as immunity prevents the virus from infecting susceptible populations, especially pregnant women.

9. CRS

10. GROUP A ARBOVIRUSES Are primarily represented by the Togaviridae family, particularly the Alphavirus genus . Are also enveloped, single-stranded, positive-sense RNA viruses . Examples include, Eastern equine encephalitis virus (EEEV) and Chikungunya virus (CHIKV) . These viruses are typically transmitted by mosquitoes. Structural Characteristics 1. Genome : Similar to Rubella, the Alphaviruses have a linear, single-stranded, positive-sense RNA genome encoding both nonstructural and structural proteins.

11. Continued; 2. Envelope . The virus is enveloped, with E1 and E2 glycoproteins embedded in the lipid bilayer. 3. Capsid . The RNA genome is encased in a nucleocapsid composed of capsid proteins . Replication Mechanism. 1. Attachment and Entry . The virus attaches to host cell receptors via E2 glycoprotein, followed by receptor-mediated endocytosis. 2. Uncoating : Acidification within the endosome triggers conformational changes in E1, facilitating fusion of the viral envelope with the endosomal membrane and releasing RNA into the cytoplasm.

12. Continued; 3. Translation and Replication . The viral RNA serves as mRNA, and nonstructural proteins are translated first. A replication complex forms, synthesizing a negative-sense RNA intermediate to produce more positive-sense genomes. 4. Subgenomic RNA . Structural proteins are translated from a subgenomic RNA, produced after genome replication. 5. Assembly and Release . New virions are assembled at the plasma membrane and bud from the cell, acquiring their envelope from the host membrane.

13. Continued; Role in Human Infections Vector Transmission . These viruses are transmitted through mosquito bites, leading to diseases like encephalitis or arthralgia . Immune Evasion : Structural features like the E2 glycoprotein allow the virus to evade the host immune response temporarily, leading to a quick systemic spread. Public Health Impact : Alphaviruses cause significant morbidity and occasional mortality in humans. They are challenging to control due to their vector-borne nature, which depends on environmental factors influencing mosquito populations.

14. Continued; Comparison and Impact on Human Infection. Mode of Transmission : Rubella is transmitted person-to-person via respiratory droplets, while Group A arboviruses rely on arthropod vectors (e.g., mosquitoes), giving arboviruses a unique ecological niche. Disease Mechanisms : Rubella generally causes mild disease in children and adults but severe congenital defects in fetuses, whereas Group A arboviruses can cause severe neuroinvasive diseases or febrile illnesses depending on the virus strain. Immunity : Vaccines like the MMR have effectively controlled rubella. In contrast, vector control and vaccine development for arboviruses are more challenging due to the complexity of zoonotic transmission.

15. Transmission Dynamics and Epidemiology of Rubella Virus Transmission Dynamics Person-to-Person Transmission : Rubella virus is transmitted directly through respiratory droplets when infected individuals cough or sneeze. The virus enters the body via the nasopharyngeal route and multiplies in the respiratory tract before spreading to lymphoid tissues. Incubation Period . is typically 12–23 days , during which the infected person is asymptomatic but contagious. The virus can be shed from 7 days before to 7 days after the rash appears, making it difficult to control transmission based solely on visible symptoms.

16. Continued; Congenital Transmission : If a pregnant woman contracts rubella, the virus can cross the placenta and infect the developing fetus, leading to Congenital Rubella Syndrome (CRS) , which includes a range of developmental defects (e.g., cardiac, ocular, and neurological).

17. Continued; Epidemiology Geographic Distribution : Prior to the introduction of the rubella vaccine, the virus was endemic worldwide, causing seasonal outbreak. However , due to vaccination campaigns, many countries have now eliminated endemic rubella transmission . Age Group : Before widespread vaccination, rubella was primarily a childhood disease . However, in populations with low vaccination coverage, it can also affect adolescents and adults. Outbreaks : Outbreaks occur primarily in populations where vaccine coverage is low . Due to its high reproductive number , rubella spreads rapidly in non-immune populations, particularly in community settings like schools and daycares.

18. Continued; Impact on Public Health. Congenital Rubella Syndrome : The major public health concern is the risk of CRS, which can lead to severe lifelong disabilities. Preventing rubella transmission among pregnant women is a high priority. Vaccination Strategy : The rubella vaccine, typically combined with measles and mumps (MMR vaccine), is the most effective public health strategy. Vaccination programs aim for herd immunity , requiring at least 85-90% coverage to prevent outbreaks.

19. Continued; Surveillance : Monitoring rubella and CRS cases is essential, especially in countries with low vaccination rates. Vaccine hesitancy and access to healthcare can undermine immunization programs, leading to outbreaks. Elimination Efforts : Many countries have successfully eliminated rubella through widespread vaccination. The WHO has set goals for rubella elimination, but progress is uneven across regions due to vaccine access problems

20. Transmission Dynamics and Epidemiology of Group A Arboviruses Transmission Dynamics 1. Vector-Borne Transmission : Group A arboviruses, such as Chikungunya virus (CHIKV) and Eastern equine encephalitis virus (EEEV) , are transmitted primarily by mosquito vectors , including species like Aedes and Culex . These viruses have complex life cycles that involve an animal reservoir (typically birds or small mammals) and an arthropod vector, with humans often being incidental hosts .

21. Continued; Mosquito Life Cycle : The virus is acquired by the mosquito during blood meals from infected animals and replicates in the mosquito's tissues. After an incubation period within the mosquito, it can be transmitted to new hosts during subsequent blood meals. Human Infections : Transmission to humans occurs when a mosquito carrying the virus bites a person. Unlike Rubella, there is no direct person-to-person transmission , except in rare cases like transfusions or vertical transmission. 2. Incubation and Transmission Period : The incubation period in humans ranges from 2 to 12 days , depending on the virus. Transmission is heavily influenced by environmental factors (e.g., temperature, rainfall), which affect mosquito populations and their biting rates.

22. Continued; Epidemiology. Geographic Distribution : Arboviruses are common in tropical and subtropical regions where mosquito populations thrive . However, due to climate change, urbanization, and increased human mobility, arboviruses like Chikungunya have expanded their geographic range, including parts of Europe and North America. Seasonality : Transmission of arboviruses typically follows a seasonal pattern , with peaks occurring during warmer months when mosquito activity is highest.

23. Continued; Outbreaks : Arbovirus outbreaks tend to be localized and often occur in response to environmental changes or disruptions (e.g., deforestation, urbanization) that affect mosquito breeding habitats. For instance, Chikungunya outbreaks have occurred in both rural and urban areas. Epidemiologic Patterns EEEV : Outbreaks are rare but have high case fatality rates, primarily affecting children and elderly individuals in regions where mosquito vectors overlap with human populations. CHIKV : Causes large outbreaks, with symptoms like fever, rash, and joint pain, affecting all age groups. Human-mosquito-human transmission chains can sustain epidemics, especially in urban settings.

24. Continued; Impact on Public Health. Surveillance and Vector Control : Controlling arboviruses is complex due to their vector-borne nature . Public health strategies focus on vector control (e.g., eliminating mosquito breeding sites, insecticide use), surveillance of mosquito populations , and monitoring human cases . Epidemic Preparedness : Arboviruses can spread rapidly due to environmental factors, so early detection of outbreaks through effective surveillance is crucial for limiting transmission. Public health agencies also promote personal protective measures (e.g., using insect repellent, bed nets).

25. Continued; Vaccine Development : Unlike rubella, there are no widely available vaccines for most arboviruses, though vaccines for some, like EEEV, are in development. This makes vector control and public health messaging essential to reducing infection risk. Climate Change Impact : The geographic spread of arboviruses is expanding due to global warming and increased mosquito habitat range. Public health systems must adapt to these emerging challenges by improving cross-border coordination and response strategies .

26. Public Health Strategies Impacted by Transmission Modes 1 . Rubella . Vaccination is the primary strategy. Achieving herd immunity protects vulnerable groups like pregnant women from infection and prevents CRS. Countries need robust immunization programs and catch-up campaigns to maintain high coverage. Surveillance : Systems to detect rubella cases and monitor vaccine coverage are essential for preventing outbreaks. Targeted Interventions : Special attention to women of childbearing age ensures they are immune before pregnancy, reducing the risk of congenital transmission.

27. Continued; 2. Group A Arboviruses . Vector Control : Unlike rubella, control efforts must focus on reducing mosquito populations through environmental management (e.g., eliminating stagnant water ) and insecticide use . Personal Protection : Public health campaigns emphasize the use of mosquito repellents, bed nets , and protective clothing , particularly in endemic areas. Surveillance and Emergency Response : Public health systems need strong surveillance networks for early detection of arbovirus outbreaks. Vector-borne diseases can spread quickly, so prompt public health responses are essential.

28. What are the typical clinical manifestations of rubella virus and group A arbovirus infections

29. Rubella Virus (German Measles) Rubella is a togavirus and primarily affects unvaccinated children and young adults. It can also cause serious complications in pregnant women, leading to congenital rubella syndrome (CRS). Clinical Manifestations: Prodromal Symptoms (1-5 days before rash): Mild fever (usually less than 39°C) Malaise Lymphadenopathy (especially postauricular, cervical, and occipital nodes)

30. Con’t Rash : A maculopapular rash that begins on the face and spreads to the rest of the body. The rash typically lasts 3 days. Unlike measles, the rash is not as confluent and may resolve without desquamation (peeling). Other Symptoms : Mild conjunctivitis Arthralgia or arthritis (more common in adults, particularly females) Forchheimer spots (small red spots on the soft palate) may appear, but are not always present.

31. Complications : Congenital Rubella Syndrome (CRS) : If infection occurs in early pregnancy, it can cause severe fetal malformations, including cataracts, deafness, heart defects, and developmental delays.

32. Group A Arboviruses (Eastern Equine Encephalitis, Western Equine Encephalitis, etc.) These arboviruses are transmitted through mosquito bites and are primarily associated with encephalitis (brain inflammation). Group A arboviruses are from the Togavirus family (like rubella) but have much more severe neurological effects. Clinical Manifestations: Initial Symptoms (after an incubation period of 4-10 days): Sudden onset of fever , chills, and malaise Myalgias (muscle aches) and arthralgias (joint pains) Headache (often severe)

33. Neurological Symptoms : As the infection progresses, encephalitis (inflammation of the brain) can develop, particularly with Eastern Equine Encephalitis Virus (EEEV) , which is one of the most severe forms. Symptoms include: Severe headache Altered mental status , ranging from confusion to coma Seizures Stiff neck (sign of meningeal areas of the body) irritation) Photophobia (sensitivity to light) Focal neurological deficits (e.g., weakness or paralysis in certain

34. Con’t Severe Complications : Coma Neurological sequelae (long-term effects) such as cognitive impairment, seizures, or motor dysfunction, especially with EEEV. Mortality rates can be high in cases of severe encephalitis, particularly for EEEV (up to 30%). Milder Arboviral Infections : Infections with some other Group A arboviruses, like Western Equine Encephalitis Virus (WEEV) , may have a more benign course, often involving flu-like symptoms without severe neurological complications.

35. Congenital Rubella Syndrome (CRS) is a major public health concern due to the severe and permanent disabilities it causes in affected infants. Effective disease control measures, including vaccination, are crucial to prevent outbreaks and reduce the incidence of CRS. Let's break down the risks of CRS and its implications for disease control : Risks of Congenital Rubella Syndrome (CRS) Risk of Severe Fetal Malformations : The risk of CRS is highest when maternal rubella infection occurs during the first trimester of pregnancy, especially in the first 12 weeks . At this stage, the virus can severely disrupt organ development. CRS can cause a range of congenital anomalies, including:

36. Cardiac defects : Patent ductus arteriosus (PDA), pulmonary artery stenosis Eye defects : Cataracts, congenital glaucoma, microphthalmia (small eyes) Hearing loss : Sensorineural deafness is one of the most common manifestations. Neurological impairments : Intellectual disability, microcephaly, motor disabilities Other issues : Low birth weight, hepatosplenomegaly, and thrombocytopenic purpura (blueberry muffin rash).

37. Long-Term Morbidity : Children with CRS often suffer from lifelong disabilities , including developmental delays, learning difficulties, and significant sensory impairments like deafness and blindness. These disabilities place a considerable burden on families and healthcare systems due to the need for ongoing medical care, special education, and rehabilitation services . Stillbirths and Miscarriages : Rubella infection during pregnancy can result in fetal death, stillbirths, or miscarriages, adding further emotional and psychological trauma for the parents.

38. Maternal Infection Timing : Infection in the first trimester poses the highest risk (~90%) of CRS. The risk decreases after the first trimester but remains a concern throughout the pregnancy. Implications for Disease Control Given the devastating consequences of CRS, disease control efforts focus on prevention , primarily through vaccination and surveillance . Here are the key implications for public health and disease control strategies:

39. Rubella Vaccination Programs Widespread Vaccination : The rubella vaccine, often administered as part of the MMR vaccine (Measles, Mumps, Rubella) , is the cornerstone of CRS prevention. Vaccination programs aim to immunize children, adolescents, and women of childbearing age to create herd immunity and prevent the circulation of the rubella virus. Herd immunity helps protect those who cannot be vaccinated, such as pregnant women who are unvaccinated and vulnerable.

40. Con’t Two-Dose Strategy: A two-dose MMR vaccination schedule is recommended in most countries to ensure immunity. Elimination of Rubella and CRS: Some regions, such as the Americas and parts of Europe, have eliminated rubella and CRS through robust vaccination programs, greatly reducing the incidence of both the disease and CRS.

41. Preconception and Prenatal Screening Preconception Screening : Women planning a pregnancy are often screened for rubella immunity. If they are found to be non-immune, vaccination is recommended before conception. Prenatal Screening : Pregnant women are screened for rubella immunity early in pregnancy to identify those at risk. However, rubella vaccination is contraindicated during pregnancy , so unvaccinated pregnant women must rely on avoiding exposure to the virus.

42. Public Health Surveillance Monitoring Rubella and CRS Cases : Effective surveillance systems are crucial for detecting rubella outbreaks and tracking cases of CRS. This allows for timely public health interventions. Reporting and Case Investigations : Health authorities must investigate rubella cases, especially in pregnant women, to prevent further transmission and ensure that at-risk populations (e.g., pregnant women) are protected.

43. Health Education and Awareness Public Awareness Campaigns : Educating the public, particularly women of reproductive age, about the risks of rubella during pregnancy and the importance of vaccination is vital. Addressing Vaccine Hesitancy : In regions where vaccine hesitancy exists, targeted efforts are needed to counteract misinformation and promote the benefits of vaccination.

44. Con’t Challenges in Low-Income Countries Limited Access to Vaccination : In some low- and middle-income countries, rubella vaccination coverage remains low, leaving women of childbearing age and their infants at risk of CRS. Burden of CRS : Countries with lower vaccination rates see a higher incidence of CRS, with significant public health, economic, and social consequences. These countries must prioritize rubella vaccination within their immunization programs to reduce the burden of CRS.

45. Con’t Global Health Goal: Elimination of Rubella and CRS The World Health Organization (WHO) and many national health organizations have set goals for the elimination of rubella and CRS through comprehensive vaccination programs. By eliminating rubella, the aim is to reduce, and ultimately eradicate, CRS. Many countries have made significant progress, but achieving global elimination requires sustained efforts to improve vaccine coverage , particularly in regions with gaps in immunization.

46. Evaluate the role of vaccines in preventing Rubella virus and group A arbovirus infections. how effective are current vaccination programs in controlling outbreaks?

47. Role of Vaccines in Preventing Rubella Virus and Group A Arbovirus Infections Vaccines play a critical role in preventing both Rubella virus and Group A arbovirus infections, though their availability and efficacy differ significantly between these two groups. Here's an evaluation of how vaccines work for each and their effectiveness in controlling outbreaks:

48. Rubella Virus Role of the Rubella Vaccine The rubella vaccine is a live-attenuated vaccine, typically administered as part of the MMR vaccine (Measles, Mumps, Rubella) . It induces long-term immunity against rubella infection, preventing both the acute illness and the devastating consequences of Congenital Rubella Syndrome (CRS) .

49. Effectiveness of Rubella Vaccination Programs High Efficacy : The rubella vaccine is highly effective. A single dose provides 95-97% protection , and a second dose ensures nearly complete immunity. Vaccination during childhood, typically at 12-15 months and a second dose at 4-6 years, results in lifelong immunity for most individuals.

50. Reduction of Rubella and CRS : Countries with high MMR vaccination coverage have seen a drastic reduction or even elimination of rubella and CRS. The Americas and parts of Europe have eliminated endemic rubella and CRS through robust vaccination programs, with continuous efforts to maintain high coverage rates to prevent reintroduction.

51. Herd Immunity : Vaccination not only protects individuals but also contributes to herd immunity , which is crucial for protecting unvaccinated individuals, such as pregnant women who cannot receive the live-attenuated vaccine. Herd immunity requires at least 85-90% coverage to prevent transmission in a population.

52. Challenges and Global Coverage Gaps in Vaccination Coverage : In some low- and middle-income countries, rubella vaccination coverage remains low, particularly in regions without a comprehensive immunization program. This can lead to rubella outbreaks and subsequent cases of CRS. Vaccine hesitancy is another challenge in some high-income countries, where misinformation has led to lower vaccination rates, causing isolated outbreaks.

53. Global Elimination Goals : The World Health Organization (WHO) aims to eliminate rubella and CRS globally, but this goal is still unmet in many regions. Efforts focus on expanding vaccination programs, improving access to vaccines, and addressing gaps in immunity, especially in women of reproductive age.

54. Group A Arbovirus Infections Group A arboviruses (such as Eastern Equine Encephalitis Virus (EEEV) , Western Equine Encephalitis Virus (WEEV) , and others) are transmitted by mosquitoes and primarily cause encephalitis in humans and animals. Currently, there are no human vaccines for most arboviruses in this group, unlike rubella. Instead, control efforts focus on vector control and animal vaccination .

55. Current Status of Vaccines for Group A Arboviruses Human Vaccines : There is no widely available human vaccine for most Group A arboviruses, including EEEV and WEEV. In some cases, experimental vaccines are available for high-risk populations , such as laboratory workers or military personnel, but these are not used in the general population.

56. Animal Vaccines : Equine vaccines (for horses) are available for EEEV and WEEV and are used to protect livestock, as these viruses primarily infect horses and can cause high mortality. Vaccinating horses helps reduce the reservoir of the virus in animals, indirectly lowering the risk of transmission to humans.

57. Effectiveness of Current Control Measures for Arboviruses Lack of Human Vaccines : In the absence of a human vaccine, vector control (targeting mosquitoes) is the primary strategy to reduce the risk of infection. Measures include: Mosquito population control : Using insecticides, eliminating standing water (breeding sites), and introducing biological controls (e.g., larvicide, mosquito predators).

58. Personal protection: Encouraging the use of mosquito repellents, bed nets, and protective clothing, especially in high-risk areas. Challenges in Outbreak Control: Vector control is often difficult to sustain, especially in regions with large mosquito populations or limited public health infrastructure. Outbreaks of arboviral diseases, like Eastern Equine Encephalitis, occur sporadically and can be severe, with high mortality rates in humans and horses. Climate change and changing ecosystems have also expanded the range of mosquito populations, making arboviral outbreaks more difficult to predict and control.

59. Overall Effectiveness of Vaccination Programs in Controlling Outbreaks Rubella : Vaccination programs have been highly successful in controlling and even eliminating rubella in many parts of the world. Where vaccination coverage is high, rubella outbreaks are rare, and the incidence of CRS is greatly reduced. Global elimination of rubella and CRS is an achievable goal with continued efforts to expand vaccine access and maintain high coverage. Group A Arboviruses : Without human vaccines, controlling these infections relies on mosquito control and personal protective measures . While these efforts can reduce the risk, they are less effective than vaccination programs and are challenging to maintain. Development of vaccines for high-risk populations would significantly enhance control efforts.

60. Clinical Manifestations, Complications, and Age-Related Differences in Measles, Mumps, and RSV Infections Measles (Rubeola): Clinical Manifestations: Measles typically begins with fever, cough, coryza (runny nose), and conjunctivitis (red eyes). The characteristic Koplik's spots (small, white spots inside the mouth) appear 1-2 days before the rash. A maculopapular rash then erupts, starting on the face and spreading downwards. Complications : Pneumonia is a common and potentially serious complication, especially in young children and immunocompromised individuals. Encephalitis (brain inflammation) is a rare but severe complication that can lead to permanent neurological damage. Other complications include otitis media (middle ear infection), diarrhea, and dehydration. Age-Related Differences: Measles is generally more severe in infants under 6 months of age and immunocompromised individuals due to their underdeveloped or compromised immune systems. Older children and adults usually experience milder symptoms, but complications are still possible.

61. QUESTION How do the structural and genomic features of Paramyxoviridae viruses contribute to their infectivity and pathogenesis in humans? Focus on measles, mumps, and respiratory viruses.

62. MEASLES is a highly contagious viral infection caused by the measles virus, a member of the Paramyxoviridae family. primarily affects children but can occur in any age group. Measles spreads through respiratory droplets from coughing and sneezing . Has a high transmission rate. Symptoms Fever (often very high, up to 40°C or 104°F ) Cough Runny nose Red, watery eyes (conjunctivitis) Koplik’s spots (tiny white spots inside the mouth) A rash starts on the face and spreads downward to the rest of the body

63. Continued; Complications: Measles can lead to severe health presentations, particularly in malnourished and immunocompromised individuals. Pneumonia, Encephalitis (inflammation of the brain), Ear infections, Diarrhea Prevention: The measles vaccine, commonly given as part of the MMR (measles, mumps, rubella) vaccine, is highly effective. Two doses are recommended, with the first dose typically given to children around 12-15 months and a second dose at 4-6 years.

64. Structural and genomic features of the M V These play important roles in its high infectivity and pathogenesis in humans . As an enveloped, single-stranded, negative-sense RNA virus of the Paramyxoviridae family, the structure of MV allows it to efficiently invade host cells, replicate, and cause widespread disease. Structural Features of the Measles Virus. Envelope and Glycoproteins .The MV is enveloped , has a lipid bilayer derived from the host cell membrane.Embedded in this envelope are two essential glycoproteins. Hemagglutinin (H) protein : Responsible for binding to host cell receptors. It facilitates attachment to cellular receptors, which include CD150 (SLAM, found on immune cells) and Nectin-4 (found on epithelial cells). This binding is important for the initial step of infection.

65. Continued; b) Fusion (F) protein : Facilitates the fusion of the viral envelope with the host cell membrane, allowing the viral RNA to enter the host cell cytoplasm. It also mediates cell-to-cell fusion, leading to the formation of syncytia (giant multinucleated cells), which allows the virus to spread between cells without needing to be released into the extracellular space. These glycoproteins play a critical role in the virus’s ability to attach, enter, and spread between human cells, contributing to its infectivity.

66. Continued, 2. Matrix (M) Protein : is located underneath the viral envelope . maintains the structural integrity of the virus. It also plays a key role in viral assembly and budding from the host cell . Efficient virus assembly and release are essential for spreading infection.

67. Continued, Genomic Features and Their Role in Infectivity The measles virus has a single-stranded, negative-sense RNA genome of approximately 15,894 nucleotides. Its genome codes for 6 main proteins, which are involved in different aspects of viral replication, immune evasion, and pathogenesis: Nucleoprotein ( N) . Encloses the viral RNA, forming a ribonucleoprotein complex. This protects the viral RNA from degradation and allows it to be transcribed and replicated within host cells.

68. Continued; 2. Phosphoprotein (P) and Large (L) Protein : These 2 proteins form part of the viral RNA polymerase complex. The P protein is an essential cofactor that helps the L protein (the RNA-dependent RNA polymerase) to transcribe the viral RNA genome into mRNA, which is then used to produce viral proteins. Efficient replication and transcription are crucial for rapid virus multiplication. 3. V and C Proteins (Encoded by the P gene): These are involved in antagonizing the host immune response, particularly by interfering with interferon signaling. By inhibiting the host's innate immune defenses, the virus can replicate more efficiently without being cleared early by the immune system.

69. Pathogenesis in Humans Immune System Evasion and Spread The use of the CD150 receptor (SLAM) allows the virus to target immune cells such as macrophages and dendritic cells leading to immune suppression. This is a key feature of measles pathogenesis, as it can result in a transient but profound weakening of the immune system, making the host susceptible to secondary infections. The ability of the virus to target Nectin-4 on epithelial cells, especially in the respiratory tract, facilitates its spread to the respiratory mucosa, leading to respiratory symptoms and making it highly contagious through aerosolized droplets.

70. Continued; Cell-to-Cell Spread . The fusion protein (F) allows for the formation of syncytia, where infected cells fuse with neighboring uninfected cells, enabling the virus to spread without exposure to extracellular immune factors. This enhances viral spread and contributes to the development of large areas of infected tissue, particularly in the respiratory tract and skin (leading to the characteristic rash). Systemic Spread . After initial infection in the respiratory epithelium, the virus spreads systemically through the bloodstream (viremia) to other organs, including the skin, where it produces the characteristic measles rash.

71. Continued; 3. I mmune Suppression : Measles virus can cause a long-lasting suppression of the immune system, This weakens the body’s ability to fight off other infections, which can lead to complications such as pneumonia or diarrhea , which are both major causes of measles-related mortality.

72. MUMPS A contagious viral disease caused by the mumps virus, a member of the Paramyxoviridae family. primarily affects the salivary glands, particularly the parotid glands . causes swelling in these glands, located near the jaw, resulting in the characteristic puffy cheeks and swollen jaw appearance .

73. Continued; Symptoms . Swollen parotid glands (leading to puffy cheeks and a swollen jaw) Fever, Headache, Muscle aches, Tiredness and fatigue, Loss of appetite. Some individuals may be asymptomatic but can still spread the virus.

74. Transmission . S preads through respiratory droplets (coughing, sneezing) and direct contact with saliva or contaminated objects. It is highly contagious, especially in close-contact settings like schools or colleges. Incubation Period . The time between exposure and symptoms onset is typically 12 to 25 days, with symptoms usually appearing around 16-18 days after exposure.

75. Mumps virus is an enveloped, single-stranded, negative-sense RNA virus belonging to the Paramyxoviridae family, similar to measles, but with different structural proteins and mechanisms of infection. These features enable the mumps virus to infect cells, replicate, and cause the characteristic symptoms of mumps, including parotitis (inflammation of the parotid glands) and, in some cases, complications such as meningitis and orchitis .

76. Structural Features of the Mumps Virus: Envelope and Glycoproteins . Just like other paramyxoviruses , the mumps virus is enveloped with a lipid bilayer derived from the host cell membrane. Embedded in the envelope are two important glycoproteins: a) Hemagglutinin-neuraminidase (HN) protein . This protein serves two roles. Hemagglutination . It binds to sialic acid-containing receptors on the surface of host cells, facilitating viral attachment. Neuraminidase activity : It cleaves sialic acid residues, allowing the release of newly formed viral particles from infected cells, preventing reattachment to the same cell.

77. b) Fusion (F) protein . Mediates the fusion of the viral envelope with the host cell membrane, allowing entry of the viral RNA into the host cell cytoplasm. The F protein also enables cell-to-cell fusion, leading to the formation of syncytia, which enhances the spread of the virus within tissues without needing to exit cells. These glycoproteins are important for the virus’s ability to attach to, enter, and spread between host cells.

78. Continued; 2. Matrix (M) Protein . The matrix protein plays a key role in the structure of the virus, linking the viral envelope with the nucleocapsid . It also mediates the assembly and budding of new viral particles from the host cell. Efficient viral budding ensures rapid spread of infection.

79. Genomic Features and Their Role in Infectivity: The mumps virus genome is about 15,384 nucleotides in length and encodes 7 proteins, each with specific roles in the replication and pathogenesis of the virus. The genome is divided into 6 transcription units that produce these proteins: Nucleoprotein ( N) . Encloses the viral RNA, forming a stable ribonucleoprotein complex. This protects the RNA from degradation by host nucleases and allows for efficient transcription and replication by the viral polymerase complex. Phosphoprotein (P) and Large (L) Protein . The P protein is an essential cofactor for the L protein, which serves as the RNA-dependent RNA polymerase. Together, they carry out transcription of the viral RNA genome into mRNA for the synthesis of viral proteins and replication of the viral genome.

80. Continued; 3. Small Hydrophobic (SH) Protein : The SH protein is unique to mumps virus and is believed to play a role in modulating the host immune response, potentially by inhibiting tumor necrosis factor-alpha (TNF-α), an important cytokine involved in the host’s inflammatory response. 4. V and I Proteins (Encoded by the P gene): These interfere with the host immune response, particularly by inhibiting interferon signaling pathways. By preventing the host's innate immune response, the virus can evade early detection and clearance, allowing it to replicate more efficiently and cause infection.

81. Pathogenesis in Humans Initial Infection and Spread . The virus primarily enters the human body via the respiratory tract through inhalation of airborne droplets. Once it binds to sialic acid receptors on epithelial cells using the HN protein, the F protein mediates viral entry. After replication in the epithelial cells of the upper respiratory tract, the virus spreads to local lymph nodes and then disseminates systemically through the bloodstream (viremia), reaching various organs . Target Organs and Tissue Damage . The mumps virus has a particular tropism for glandular and nervous tissues, leading to the characteristic symptoms of the disease: Parotitis , meningitis and Orchitis .

82. Continued; 3. Cell-to-Cell Spread and Syncytia Formation . The fusion (F) protein enables the virus to spread directly between neighboring cells by creating multinucleated giant cells This d allows the virus to bypass extracellular immune defenses and infect large areas of tissue. 4. Immune Response and Complications . The immune response to the mumps virus, particularly the production of antibodies against the HN and F proteins, is crucial in clearing the infection. However, the immune response also contributes to the symptoms, such as the swelling and inflammation in the parotid glands. 5. Viral Evasion of Immune Response . The SH, V, and I proteins help the virus evade the host immune system by inhibiting interferon production and other antiviral responses.

83. Diagnosis . Diagnosis is based on clinical symptoms (especially parotid gland swelling) and can be confirmed through; laboratory tests such as RT-PCR (to detect viral RNA) and Serological testing for antibodies (IgM ) and IgG serological testing. RT-PCR is preferred method because its more sensitive and specific than serological assays to detect IgM. Treatment . There is no specific antiviral treatment for mumps. Management focuses on relieving symptoms. Rest, Pain relievers like acetaminophen or ibuprofen, Cold or warm compresses on swollen glands.

84. Prevention . The MMR vaccine (measles, mumps, and rubella) is the most effective way to prevent mumps. The vaccine is typically given in two doses during childhood: The first dose is administered at 12-15 months of age. The second dose is given at 4-6 years old. Two doses of the vaccine provide about 88% protection against mumps.

85. RESPIRATORY VIRUSES Respiratory viruses encompass a wide range of viral families, such as Paramyxoviridae (e.g., respiratory syncytial virus [RSV], parainfluenza virus, Human metapneumovirus ). Despite their diversity, the structural and genomic features of respiratory viruses play similar roles in driving their infectivity and pathogenesis in humans by facilitating efficient entry into host cells, evasion of immune responses, and rapid viral replication

86. Respiratory Syncytial Virus (RSV) and Parainfluenza Virus ( Paramyxoviridae ) Structural and Genomic Features. Negative-Sense RNA Genome . These viruses have a single-stranded, negative-sense RNA genome, similar to influenza and other paramyxoviruses. Fusion (F) Protein : RSV and parainfluenza viruses use their F protein to mediate fusion with host cell membranes, allowing viral entry. This protein is also responsible for causing infected cells to fuse, forming multinucleated, which helps the virus spread from cell to cell without being exposed to immune defenses.

87. Continued; Hemagglutinin-Neuraminidase (HN) Protein (in parainfluenza viruses): This glycoprotein has dual functions: Hemagglutinin binds to host cell receptors, aiding in viral attachment. Neuraminidase helps release viral particles from infected cells. Nucleocapsid (N) Protein : Like other paramyxoviruses, the N protein binds to viral RNA, forming a nucleocapsid that protects the genome and facilitates replication.

88. Infectivity and Pathogenesis . Tropism for Lower Respiratory Tract : RSV and parainfluenza viruses primarily infect the lower respiratory tract, especially in infants and young children, leading to bronchiolitis and pneumonia. RSV, in particular, is a leading cause of severe respiratory illness in young children. Syncytia Formation : The F protein’s ability to induce syncytia formation allows RSV to evade immune defenses and spread efficiently through respiratory epithelial tissue. Immune Evasion : These viruses can suppress the host immune response, particularly by interfering with the production of type I interferons, which are crucial for antiviral defense. This allows them to replicate extensively before the host immune system responds.

89. Human metapneumovirus ( HMPV) is a significant cause of respiratory tract infections, particularly in children, the elderly, and immunocompromised individuals. HMPV belongs to the family Paramyxoviridae and has a single-stranded, negative-sense RNA genome. The genome codes for eight proteins, many of which contribute directly to its infectivity . Its structural and genomic features play a key role in its infectivity and pathogenesis.

90. Genomic features Nucleoprotein (N) : Encloses the viral RNA, forming the ribonucleoprotein (RNP) complex. This shields the viral RNA from host immune responses and is essential for viral replication. Phosphoprotein (P) : Acts as a cofactor for the RNA-dependent RNA polymerase (L protein). It stabilizes the RNP complex, ensuring efficient transcription and replication. L Protein (RNA-dependent RNA polymerase) : Catalyzes the synthesis of viral mRNA and genomic RNA, making it central to the virus's ability to replicate.

91. Matrix (M) Protein : Plays a role in viral assembly and budding. It interacts with other viral proteins to drive the formation of new virions and their release from infected cells. F (Fusion) Protein : This glycoprotein mediates the fusion of the viral envelope with the host cell membrane, facilitating viral entry into host cells. It also triggers cell-to-cell fusion, creating syncytia (multinucleated giant cells), a hallmark of HMPV infection that enhances viral spread. G (Attachment) Protein : This glycoprotein assists in virus attachment to the host cell receptors, although its role in HMPV is less pronounced compared to other paramyxoviruses like respiratory syncytial virus (RSV). It still plays a role in pathogenesis by evading host immune responses.

92. Structural Features Enveloped Virus : HMPV is enveloped, meaning its virions are surrounded by a lipid bilayer derived from the host cell membrane. This envelope incorporates the F and G proteins, which are critical for virus entry and immune evasion. Fusion (F) Protein : The F protein is a key determinant of infectivity. It is synthesized as an inactive precursor (F0) and must be cleaved into two subunits (F1 and F2) for activation. This cleavage, typically performed by host proteases, exposes a fusion peptide that facilitates merging of the viral and cellular Genetic Variability : HMPV is divided into two major genotypes (A and B), each with sublineages . These genotypes show some degree of antigenic variation, which may contribute to immune evasion and affect the severity of infection.

93. Infectivity and Pathogenesis Cellular Entry : The attachment and fusion proteins (G and F) are central to viral entry into host cells. After attachment to a receptor (likely a glycosaminoglycan or integrin), the F protein facilitates membrane fusion, allowing the viral RNA to enter the host cell. Replication Strategy : As a negative-sense RNA virus, HMPV relies on its RNA-dependent RNA polymerase (L protein) to transcribe and replicate its genome inside the host cell. The viral genome is replicated in the cytoplasm of the infected cell, with the resulting mRNA being translated into viral proteins that form new virions .

94. Immune Evasion : HMPV evades the host immune response through several mechanisms: The G protein may interfere with the recognition of the virus by the host immune system. The virus can suppress interferon (IFN) production and signaling, which are crucial components of the host's antiviral response. Syncytia formation, driven by the F protein, allows the virus to spread directly between cells without exposure to the extracellular environment, helping it avoid neutralizing antibodies.

95. General Mechanisms of Infectivity and Pathogenesis in Respiratory Viruses: Entry and Replication . Most respiratory viruses bind to receptors on epithelial cells of the respiratory tract After entry, viral RNA genomes are replicated, and new virions are assembled and released, often damaging the respiratory epithelium and causing inflammation. Immune Evasion . Many respiratory viruses produce proteins that interfere with host immune responses, particularly by inhibiting interferon signaling, which delays the antiviral immune response and allows the virus to replicate extensively before being cleared. Direct and Indirect Tissue Damage . Direct cytopathic effects from viral replication lead to cell death, loss of epithelial integrity, and exposure of underlying tissues. Indirect damage occurs through the host's immune response, including inflammation, mucus overproduction, and recruitment of immune cells to the site of infection, which can cause airway obstruction and exacerbate respiratory symptoms.

96. Mumps: Clinical Manifestations : Mumps is characterized by painful swelling of the salivary glands (parotid glands), usually bilateral. Fever, headache, muscle aches, and fatigue are common.   Complications : The most serious complication is meningitis (inflammation of the brain and spinal cord), which can lead to permanent neurological damage. Orchitis (inflammation of the testicles) in males and oophoritis (inflammation of the ovaries) in females can occur during puberty and can cause sterility in rare cases. Pancreatitis (inflammation of the pancreas) and deafness are other less common complications.   Age-Related Differences: Mumps is generally more severe in adults than in children. Complications are more frequent in adults, particularly orchitis. Infants under 1 year old are less likely to develop clinical mumps due to passive immunity from maternal antibodies.  

97. Respiratory Syncytial Virus (RSV): Clinical Manifestations : In most infants and young children, RSV causes mild upper respiratory tract infections (URTIs) with symptoms like runny nose, cough, and mild fever. However, in some cases, it can lead to bronchiolitis (inflammation of the small airways in the lungs) and pneumonia. Complications : Bronchiolitis can cause severe respiratory distress, requiring hospitalization, especially in infants under 6 months of age, premature infants, and children with underlying heart or lung conditions. Pneumonia can also be severe, leading to respiratory failure. In rare cases, RSV can cause apnea (cessation of breathing).   Age-Related Differences: RSV is most severe in infants under 6 months of age, particularly premature infants and those with underlying health conditions. Older children and adults usually experience milder symptoms, often resembling a common cold. However, RSV can still cause severe illness in older adults, especially those with chronic lung or heart disease.

98. Global Challenges in Controlling Measles, Mumps, and RSV Outbreaks Despite the availability of effective vaccines for measles and mumps, and various treatment options for RSV, several global challenges hinder their control:   Vaccine hesitancy and misinformation: Anti-vaccine sentiments and misinformation campaigns significantly reduce vaccination coverage, leaving populations vulnerable to outbreaks.   Inequity in vaccine access: Many low- and middle-income countries lack adequate resources for vaccine procurement, storage, and delivery, resulting in low vaccination rates.   Complexities of RSV: Unlike measles and mumps, there is no widely available RSV vaccine, although several are under development. Treatment focuses on supportive care, which can be challenging in resource-limited settings.  

99. Population density and mobility: High population density and increased global travel facilitate the rapid spread of these viruses.   Weak surveillance systems: Inadequate surveillance systems in many parts of the world make it difficult to monitor outbreaks effectively and implement timely interventions.   Climate change: Changes in climate patterns may influence the transmission dynamics of these respiratory viruses.   Emerging variants: The emergence of new viral variants can affect vaccine efficacy and complicate control efforts