What is atypical pneumonia?

Pneumonia is one of the leading causes of hospital admission and death worldwide.¹ While there is some debate regarding the terminology, cases can generally be classified into two groups: typical and atypical. What separates the two is the pathogen responsible for pneumonia. The vast majority of pneumonia cases are typically caused by three main pathogens: S. pneumoniae, H. influenzae, and S. aureus-hence the name  “typical pneumonia.”² If a case is caused by any pathogen outside of these three, it is usually classified as atypical. Here are some examples of pathogens associated with atypical pneumonia: M. pneumoniae, C. pneumoniae, and L. pneumophila, to name a few. Atypical pneumonia makes up approximately 15% of all pneumonia cases.³ Atypical pneumonia has also been called “walking pneumonia” due to the mildness of the symptoms,  where infected individuals may not even realise they are sick.⁴ However, this may only be the case for people with no underlying medical conditions. Symptoms can be severe or potentially life-threatening in individuals with weakened immune systems, such as those living with HIV. 

Symptoms of atypical pneumonia in HIV/AIDS

People living with HIV are more likely to develop severe infections. This is because HIV weakens the immune system by destroying cells responsible for detecting and eliminating disease-causing pathogens.⁵ As a result, infections that would be a mere inconvenience for most people, such as oral thrush, can develop into life-threatening conditions if left untreated. These types of infections are called opportunistic infections, as they only have the opportunity to become severe when the immune system is weakened. 

In most cases, atypical pneumonia symptoms include:

• Fever
• Headaches
• Muscle aches⁶

However, in people living with HIV, more severe symptoms can develop, such as:

• Coughing 
• Body chills
• Shortness of breath
• Diarrhoea 
• Joint pain
• Anaemia
• Delirium^{7, 8}

In some cases, chronic conditions such as arteriosclerosis, cardiovascular disease or bronchitis can also occur. Lung lesions and respiratory failure have been reported in immunosuppressed patients.⁸

Diagnostic challenges

For typical pneumonia, chest X-rays are commonly used. Diagnosing atypical pneumonia can be difficult for several reasons. Atypical pneumonia can be caused by various pathogens, including viruses and bacteria, each with different structures (e.g. distinct proteins, genetic makeup, etc.). As such, there is no one-size-fits-all diagnostic method for atypical pneumonia,  making diagnosis a process of elimination in most cases. Similar respiratory diseases, such as tuberculosis, which can present with overlapping symptoms, further complicate the diagnosis. Identifying the pathogen responsible determines the course of treatment. We will explore some of these pathogens in more detail:

L. pneumophila

This pathogen is responsible for approximately 20% of pneumonia cases in adult HIV-associated cases. However, diagnosing these cases can be difficult, especially in immunosuppressed patients. Urine antigen tests can be used to identify L. pneumophila-related cases, but in immunosuppressed patients, there is a risk of false-negative results. For this reason, polymerase chain reaction (PCR) tests are used instead. Additionally, tests for L. pneumophila are not routinely conducted in most clinical lab settings and are only performed if specifically requested, leading to potentially missed cases. It is also not uncommon for HIV-positive patients to be fighting multiple infections. One of the co-pathogens could mask the pneumonia-causing pathogen, further complicating diagnosis.⁸

M. pneumoniae

M. pneumoniae is responsible for 11–21% of pneumonia cases in HIV-infected individuals, with even higher infection rates in immunosuppressed patients. Due to the similarity in symptoms between HIV-positive patients and the general population, diagnosing cases based on clinical presentation alone is nearly impossible. Blood serum tests were once the test of choice, but they are not viable for immunosuppressed patients. This is because immunosuppressed patients may not produce enough antibodies for the pathogens to be detected, leading to a false-negative result.³   

C. pneumoniae 

C. pneumoniae is responsible for the majority of pneumonia cases in HIV-positive children. Similar to M. pneumoniae, using blood serum tests in immunosuppressed patients, such as HIV-positive individuals, could result in a false-negative outcome. A Nucleic Acid Amplification Test (NAAT) is more suitable. These types of tests are similar to the nasal and mouth swabs used for COVID-19 testing.⁸ 

Treatment options

A range of different antibiotics can be used to treat pneumonia, such as:

• Macrolides: kill bacteria by preventing them from producing the parts needed to survive and have anti-inflammatory properties^{9, 10}
• Fluoroquinolones: stop bacterial growth by preventing replication¹¹
• Tetracyclines: kill bacteria by preventing them from producing the parts needed to survive¹²

Antibiotics stop the growth of pneumonia-causing pathogens, thus reducing the infection. However, there are a few considerations to take into account for HIV-positive patients. Antimicrobial resistance is a major challenge in antibiotic treatments. This occurs when a virus, bacterium, or fungus changes in a way that renders the treatment ineffective. This is why clinicians emphasise the importance of completing any prescribed course of antibiotics, rather than stopping when symptoms disappear. Finishing the prescribed antibiotic course increases the likelihood of completely eradicating the infection and prevents the development of resistance. Antimicrobial resistance is particularly dangerous for individuals with weakened immune systems, such as people living with HIV, as their bodies may be less equipped to fight infections on their own. For this reason, macrolides alone are not recommended for treating HIV-positive patients due to the significant risk of antimicrobial resistance. Instead, macrolides are typically paired with another group of antibiotics called beta-lactams to reduce this risk. However, some studies suggest that beta-lactams and sulfa drugs may be less effective against atypical pneumonia infections. Doxycycline has been shown to be an effective alternative.⁸ If you are allergic to penicillin, macrolides can be paired with fluoroquinolones instead, as beta-lactams work similarly to penicillin.¹³   

Drug burden, drug interactions, and timing of treatment must be considered for HIV-positive patients on antiretroviral therapy (ART). Starting ART too soon after the onset of infection can increase the risk of Immune Reconstitution Inflammatory Syndrome (IRIS). Recent studies suggest that an appropriate time to start ART is 14 days after beginning pneumonia treatment.¹⁴

Prevention and risk reduction

To reduce the risk of pneumonia infection, U.S. guidelines recommend that HIV-positive individuals with a CD4 cell count greater than 200 cells per cubic millilitre, should receive the 23-valent polysaccharide pneumococcal vaccine (PPSV23) every 5 years. Whereas in the UK, most adults only need the Pneumovax 23 vaccine once for long-term protection. The vaccine can also provide limited protection for immunosuppressed patients or those with a CD4 cell count of less than 200 cells per cubic millilitre. Additionally, oral prophylaxis can reduce the risk of bacterial pneumonia and other opportunistic infections, such as:

• Trimethoprim-sulfamethoxazole
• Azithromycin
• Clarithromycin¹³  

The old adage goes, “Prevention is better than the cure”. In the case of pneumonia, this advice is even more important. Various risk factors can affect a patient’s likelihood of contracting pneumonia, including:

• Older age
• Detectable HIV load
• CD4 cell count
• The previous occurrence of pneumonia¹⁴

Studies have suggested that low CD4 cell counts and high HIV load are associated with a higher risk of being admitted to the Intensive Care Unit (ICU) or dying from pneumonia. Many studies have shown that cigarette smoking significantly increases the risk of pneumonia, along with recreational injection drug use, such as meth, heroin, cocaine, and opioids. Therefore, if you are currently dealing with any of these addictions, it is highly recommended that you seek assistance in reducing your use to lower your risk of pneumonia infection.¹³  

Early and accurate detection of pneumonia cases is vital to improving the likelihood of recovery and reducing the risk of relapse. If you experience any of the symptoms listed, it is vital that you seek urgent medical attention from your local GP.

Summary 

Atypical pneumonia is caused by any pathogen outside of the three most common pathogens: S. pneumoniae, H. influenzae, and S. aureus. The infection can be bacterial, viral, or fungal. It may present with mild symptoms such as fever, headache, and muscle aches in the general population but can be severe or even life-threatening in people living with HIV. Therefore, it is important to see your GP if symptoms develop. Smoking and past or current use of injecting drugs can increase the risk of infection. 

There are various diagnostic tests and treatment options that can be used depending on the pathogen causing the infection. Treatment typically includes a range of antibiotics to fight the infection, but it is important to complete the entire course of antibiotics to prevent antimicrobial resistance. If antimicrobial assistance occurs, the treatment will no longer be effective against the infection. Vaccines such as PPSV23 (U.S.) and Pneumovax 23 (UK), along with oral prophylactic tablets, can be used to reduce the risk of pneumonia infection.