What are the clinical manifestations and laboratory diagnostic approaches for Measles, Mumps, Poliomyelitis, Hepatitis viruses, Influenza, Parvovirus, Viral Haemorrhagic Fever, Zika virus infections, Dengue, Novel Coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) or COVID-19 (Coronavirus Disease 2019), Monkeypox, Herpes Simplex Virus (HSV) infections, Varicella-zoster virus (VZV) infections, Cytomegalovirus (CMV) infections, and Epstein-Barr Virus (EBV) infections?

From the Guidelines

Viral infections require a comprehensive approach to diagnosis, incorporating clinical presentation, laboratory testing, and epidemiological context to ensure accurate identification and effective management, prioritizing morbidity, mortality, and quality of life as the primary outcomes. The clinical manifestations of viral infections are diverse, ranging from mild symptoms to severe and life-threatening conditions. For instance, measles typically presents with fever, cough, coryza, conjunctivitis, and a characteristic maculopapular rash, with diagnosis confirmed through serology for IgM antibodies or RT-PCR from respiratory specimens 1. Mumps causes parotid gland swelling, fever, and headache, diagnosed via RT-PCR of saliva or serology.

Key Considerations for Diagnosis

• Measles, Mumps, and Rubella (MMR): Diagnosed through serology or RT-PCR from respiratory specimens.
• Poliomyelitis: Diagnosis relies on virus isolation from stool or CSF and serology.
• Hepatitis Viruses: Diagnosed through serological markers and nucleic acid testing.
• Influenza: Confirmed by rapid antigen tests or RT-PCR from nasopharyngeal swabs.
• Parvovirus B19: Diagnosed through serology or PCR.
• Viral Hemorrhagic Fevers: Require specialized PCR testing in high-containment laboratories.
• Zika Virus: Diagnosed via RT-PCR or serology.
• Dengue: Diagnosed through NS1 antigen detection or serology.
• COVID-19: Diagnosed primarily through RT-PCR of respiratory specimens.
• Monkeypox: Confirmed by PCR of lesion material.
• Herpes Simplex: Diagnosed via PCR or viral culture.
• Varicella-Zoster: Diagnosed through clinical presentation and PCR.
• Cytomegalovirus (CMV): Often remains asymptomatic but can cause mononucleosis-like syndrome or severe disease in immunocompromised patients, diagnosed via PCR or antigen detection, as outlined in guidelines for the utilization of the microbiology laboratory for diagnosis of infectious diseases 1.
• Epstein-Barr Virus (EBV): Causes infectious mononucleosis with fever, sore throat, and lymphadenopathy, diagnosed through heterophile antibody tests and specific serology.

Laboratory Diagnosis

The choice of laboratory test depends on the clinical presentation, the stage of the illness, and the availability of testing facilities. For example, CMV infection in immunocompetent individuals is typically diagnosed through testing for CMV-specific antibodies, with the presence of IgM class antibodies indicating recent infection 1. In contrast, the diagnosis of COVID-19 associated bacterial and fungal infections requires a comprehensive approach, considering the epidemiology, diagnostic methods, and treatment recommendations, as outlined in recent guidelines 1.

Approach to Diagnosis

A stepwise approach to diagnosis is recommended, starting with clinical evaluation and epidemiological assessment, followed by the selection of appropriate laboratory tests based on the suspected viral infection. This approach ensures that the diagnosis is accurate and timely, allowing for the initiation of appropriate treatment and management strategies to improve patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

The efficacy of oseltamivir phosphate in preventing naturally occurring influenza illness has been demonstrated in three seasonal prophylaxis (community outbreak) clinical trials and one post-exposure prophylaxis trial in household contacts The efficacy endpoint for all of these trials was the incidence of laboratory-confirmed clinical influenza defined as meeting all the following criteria (all signs and symptoms must have been recorded within 24 hours): oral temperature greater than or equal to 99.0ºF (37. 2ºC), at least one respiratory symptom (cough, sore throat, nasal congestion), at least one constitutional symptom (aches and pain, fatigue, headache, chills/sweats), and either a positive virus isolation or a four-fold increase in virus antibody titers from baseline In a pooled analysis of two seasonal prophylaxis trials in healthy unvaccinated adults (aged 18 to 65 years), oseltamivir phosphate 75 mg once daily taken for 42 days during a community outbreak reduced the incidence of laboratory-confirmed clinical influenza from 5% (25/519) for the placebo group to 1% (6/520) for the oseltamivir phosphate group

The clinical manifestations of Influenza include:

• Oral temperature greater than or equal to 99.0ºF (37.2ºC)
• At least one respiratory symptom (cough, sore throat, nasal congestion)
• At least one constitutional symptom (aches and pain, fatigue, headache, chills/sweats) The approach to laboratory diagnosis of Influenza includes:
• Positive virus isolation
• Four-fold increase in virus antibody titers from baseline The FDA drug label does not provide information on the clinical manifestations and laboratory diagnosis of the other listed viral infections, including Measles, Mumps, Poliomyelitis, Hepatitis viruses, Parvovirus, Viral haemorrhagic fever, Zika virus infections, Dengue, Novel Coronavirus SARS-CoV-2 (COVID-19), Monkey pox, Herpes simplex virus (HSV) infections, Varicella-zoster virus (VZV) infections, Cytomegalovirus (CMV) infections, and Epstein-Barr Virus (EBV) infections 2

From the Research

Clinical Manifestations of Viral Infections

• Measles: characterized by fever, cough, runny nose, and a rash that spreads from the head to the rest of the body 3
• Mumps: typically causes swelling in the parotid glands, fever, headache, muscle aches, tiredness, and loss of appetite 3
• Poliomyelitis: can cause mild symptoms such as fever, headache, and vomiting, or more severe symptoms like paralysis and respiratory failure
• Hepatitis viruses: can cause liver inflammation, leading to symptoms like jaundice, fatigue, and abdominal pain
• Influenza: characterized by fever, cough, sore throat, runny or stuffy nose, muscle or body aches, headaches, fatigue, and some people may experience vomiting and diarrhea 4
• Parvovirus: can cause fifth disease, which is characterized by a rash on the face, arms, and legs, as well as fever and cold-like symptoms 3
• Viral haemorrhagic fever: can cause severe bleeding, fever, and organ failure
• Zika virus infections: can cause fever, rash, joint pain, and conjunctivitis, as well as birth defects like microcephaly 5
• Dengue: characterized by fever, severe headache, pain behind the eyes, joint and muscle pain, rash, and mild bleeding 5
• Novel Coronavirus SARS-CoV-2 (COVID-19): can cause fever, cough, shortness of breath, and pneumonia, as well as more severe symptoms like respiratory failure and death 4
• Monkey pox: can cause fever, headache, muscle aches, and a rash that progresses to blisters
• Herpes simplex virus (HSV) infections: can cause oral or genital herpes, characterized by blisters and sores 6
• Varicella-zoster virus (VZV) infections: can cause chickenpox and shingles, characterized by a rash and blisters 6
• Cytomegalovirus (CMV) infections: can cause fever, fatigue, and swollen glands, as well as more severe symptoms like pneumonia and organ failure 5
• Epstein-Barr Virus (EBV) infections: can cause infectious mononucleosis, characterized by fever, sore throat, and swollen lymph nodes

Approach to Laboratory Diagnosis

• Measles: diagnosis can be made through clinical presentation, laboratory tests like PCR and serology 3
• Mumps: diagnosis can be made through clinical presentation, laboratory tests like PCR and serology 3
• Poliomyelitis: diagnosis can be made through laboratory tests like PCR and serology
• Hepatitis viruses: diagnosis can be made through laboratory tests like PCR, serology, and liver function tests
• Influenza: diagnosis can be made through laboratory tests like PCR and rapid antigen tests 4
• Parvovirus: diagnosis can be made through laboratory tests like PCR and serology 3
• Viral haemorrhagic fever: diagnosis can be made through laboratory tests like PCR and serology
• Zika virus infections: diagnosis can be made through laboratory tests like PCR and serology 5
• Dengue: diagnosis can be made through laboratory tests like PCR and serology
• Novel Coronavirus SARS-CoV-2 (COVID-19): diagnosis can be made through laboratory tests like PCR and rapid antigen tests 4
• Monkey pox: diagnosis can be made through laboratory tests like PCR and serology
• Herpes simplex virus (HSV) infections: diagnosis can be made through laboratory tests like PCR and serology 6
• Varicella-zoster virus (VZV) infections: diagnosis can be made through laboratory tests like PCR and serology 6
• Cytomegalovirus (CMV) infections: diagnosis can be made through laboratory tests like PCR and serology 5
• Epstein-Barr Virus (EBV) infections: diagnosis can be made through laboratory tests like PCR and serology

Laboratory Tests

• PCR (polymerase chain reaction): a molecular test used to detect the genetic material of a virus
• Serology: a test used to detect antibodies against a virus in the blood
• Rapid antigen tests: a test used to detect the presence of a virus in a sample
• Liver function tests: a test used to assess the health of the liver
• Antibody indices (AIs): a test used to detect the presence of antibodies against a virus in the cerebrospinal fluid and serum 7