What are the clinical presentation, diagnostic methods, and recommended treatment for human metapneumovirus infection?

Human Metapneumovirus (hMPV) Infection

Clinical Presentation

Human metapneumovirus causes respiratory tract infections with symptoms indistinguishable from other common respiratory viruses, ranging from mild upper respiratory symptoms to severe pneumonia, particularly in young children, elderly patients, and immunocompromised individuals. 1, 2

Typical Symptoms in Children

• Rhinorrhea, nasal congestion, cough, and fever are the hallmark upper respiratory symptoms 2
• Fatigue, expectoration, diarrhea, and headache may accompany respiratory symptoms 2
• Progression signs include dyspnea, cyanosis, malaise, restlessness, poor feeding, and reduced activity 2
• Severe cases can evolve to respiratory failure unresponsive to conventional oxygen, septic shock, metabolic acidosis, and coagulation dysfunction 2
• hMPV is responsible for 5-10% of pediatric hospitalizations for acute respiratory infections 1, 3, 4

Adult Presentation

• Symptoms often mimic influenza and can exacerbate chronic conditions like COPD or asthma 4
• Patients with chronic cardiac or pulmonary diseases face substantially elevated risk of severe disease and mortality 2

High-Risk Immunocompromised Populations

• Symptomatic hMPV occurs in 2.5-9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients within the first two years post-transplant 5
• Mortality among HSCT patients with lower respiratory tract disease ranges from 10-30% 5, 2
• Higher corticosteroid exposure, neutropenia, and lymphopenia increase severe disease risk 6
• Asymptomatic and prolonged viral shedding are common in HSCT patients, complicating infection control 5, 6, 2

Key Clinical Challenge

• No clinical or radiographic criteria reliably distinguish hMPV from bacterial infection, necessitating a low threshold for empirical antibiotics in severe cases 2
• Coinfection with other respiratory viruses (especially RSV) is common and obscures attributable morbidity 2

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Diagnostic Methods

Nucleic acid amplification tests (NAATs) are the preferred diagnostic modality for hMPV due to the virus's fastidious growth in cell culture. 1, 3, 7, 8

Specimen Collection

• Respiratory secretions or nasopharyngeal swabs placed in appropriate viral transport medium (VTM) are the specimens of choice 1
• Specimens should be transported at room temperature within 2 hours 1

Recommended Testing Approach

• Rapid PCR respiratory panels should be considered for detection of hMPV along with RSV, influenza, parainfluenza, adenovirus, and rhinovirus in patients with cough and/or shortness of breath 1
• NAATs (particularly reverse transcriptase PCR) are now common in commercial respiratory panels and are superior to culture 1
• Immunofluorescent assays are available but less sensitive than molecular methods 1

Testing Considerations

• Molecular methods are preferred over culture due to slow viral growth (4-7 days for detection) 3, 7, 8
• The combination of PCR-based methods with conventional techniques improves diagnostic yield significantly 1
• Asymptomatic shedding rates may be substantial in immunocompromised populations, potentially leading to overestimation of clinically significant disease when using sensitive detection methods 5

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Treatment Recommendations

For immunocompetent adults and children, supportive care is the only recommended treatment, as no antiviral agent has established efficacy for hMPV. 6, 2

Supportive Care (All Patients)

• Rest, hydration, and symptomatic management are the mainstays of therapy 6
• Oxygen therapy titrated to maintain adequate saturation 6
• Monitoring of vital signs, oxygen saturation, and respiratory status 6
• Fluid and electrolyte management 6
• High-protein, high-vitamin, carbohydrate-containing diets for nutritional support 6
• Treatment of bacterial superinfection if suspected or documented 6

Respiratory Support Escalation

• High-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) as initial escalation for moderate to severe ARDS 6
• Invasive mechanical ventilation with prone positioning for severe ARDS 6

Immunocompromised Patients with Severe Disease

The CDC and American Society of Hematology recommend considering ribavirin and/or intravenous immunoglobulin (IVIG) for hMPV lower respiratory tract disease in immunocompromised patients, despite lack of randomized controlled trial data. 6

• This consideration applies specifically to HSCT recipients and leukemia patients with pneumonia or lower respiratory tract involvement 6
• Upper respiratory tract infection alone does not typically warrant antiviral therapy 6
• Ribavirin has shown activity in vitro and in animal models but remains a category 3 recommendation due to limited data and strong panel disagreement 1, 8
• No general recommendation for antiviral treatment can currently be made based on available evidence 6

Critical Pitfall

• Single cases of severe disease and fatal outcomes have been reported even with treatment attempts, underscoring the limitations of current therapeutic options 6

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Infection Control

Standard and droplet precautions are essential to prevent nosocomial transmission, given the 3-5 day incubation period and high rates of asymptomatic shedding. 5, 6

• Prolonged viral shedding has been documented in HSCT patients, emphasizing the importance of sustained infection control measures 6
• Nosocomial outbreaks can occur given the estimated incubation period of 2.6 days and asymptomatic shedding 6
• Transmission occurs through droplets, direct contact, and surface contamination, with crowded spaces and healthcare facilities serving as key amplifiers 9