Pneumocystis Pneumonia - Transmission and Treatment.

Introduction:

The infection was first identified in Europe after World War II in malnourished infants living in orphanages. Initially, the causative organism was not recognized. The research gained importance in the 1980s after the HIV (human immunodeficiency virus) epidemic. Pneumocystis jirovecii pneumonia was earlier referred to as pneumocystis carinii pneumonia. It is a fungal infection that usually occurs in immunocompromised patients and is life-threatening in severe cases. Generally, individuals at risk are those with diseases that alter the immunity of the host, like cancer, human immunodeficiency virus (HIV), and organ transplant patients.

What Is the Cause of Pneumocystis Pneumonia?

Pneumocystis was thought initially to be a member of the protozoan family, and its life cycle showed similarities to both the protozoan and fungus, which led to further studies to identify its correct classification. However, in 1988 it was classified as an ascomycetous fungus. The careful phylogenetic analysis of small subunit ribosomal RNAs concluded that pneumocystis is a member of the fungi family based upon:

• Cell wall composition.

• Structure of key enzymes.

• Gene sequencing.

How Is Pneumocystis Pneumonia Transmitted?

Pneumocystis pneumonia is transmitted from person to person through the air. Sometimes healthy individuals are carriers of the pneumocystis fungus without symptoms, which can spread to other individuals, especially with weakened immune systems.

Pneumocystis may infect children, but it does not cause any illness because of their high immunity. In the past, studies have revealed that individuals exposed to pneumocystis as children later develop pneumocystis pneumonia as their immune system gets weakened when they grow up.

What Are the Signs and Symptoms of Pneumocystis Pneumonia?

The symptoms of pneumocystis pneumonia usually present include:

• Fever.

• Cough.

• Difficulty in breathing.

• Pain in the chest.

• Chills.

• Fatigue or tiredness.

Immunocompromised patients, such as patients with Human immunodeficiency virus (HIV) infection, show the subtle onset of symptoms that include:

• A non-productive and dry cough.

• Low-grade fever.

• Progressive dyspnea (shortness of breath).

On the contrary, individuals not infected with the Human immunodeficiency virus (HIV) show an abrupt onset of symptoms accompanied by respiratory distress or failure. However, in both cases, some degree of hypoxia (low oxygen level in the body tissues) is always present.

Other common physical examination findings include:

• Tachypnea (abnormally rapid breathing).

• Tachycardia (heart rate over 100 beats per minute).

Asymptomatic cases can also develop in people with normal immune systems, and the fungus may colonize the lungs and become carriers for spreading pneumocystis to immunocompromised individuals.

Pneumocystis pneumonia is one of the most common opportunistic respiratory infections affecting individuals with autoimmune immunodeficiency syndrome (AIDS). However, the incidence of the infection has declined considerably with the use of antiretroviral therapy.

How Is Pneumocystis Pneumonia Diagnosed?

The diagnosis of Pneumocystis pneumonia is multifactorial and includes the following:

• Laboratory Evaluations: These findings can be nonspecific for pneumocystis pneumonia, and an elevated serum lactate dehydrogenase (LDH) in HIV-infected patients is detected. However, for various reasons, immunocompromised patients without HIV may have elevated serum lactate dehydrogenase (LDH). Therefore, lactate dehydrogenase (LDH) level is not a valued diagnostic tool in patients.

• Chest Radiograph: A chest radiograph is used to detect diffuse bilateral perihilar interstitial infiltrates, and these changes become more homogenous as the disease progresses. Other radiographic findings may include single or multiple nodules that may develop into cavitary lesions, lobar infiltrates in patients undergoing antimicrobial therapy, and pneumothorax in some cases.

• Computed Tomographic Scan of the Chest: If the chest radiograph does not present the above features, a computed tomographic scan of the chest can be performed that might show a ground-glass appearance or cystic lesions.

• Sputum Studies and Evaluation of Bronchoalveolar Lavage Fluid: Pneumocystis cannot be cultured. Therefore, proper diagnosis requires the identification of the organism by polymerase chain reaction. This testing involves a microscopic examination of a patient's sputum or bronchoalveolar lavage fluid; these samples should be taken when the patient is stable.

• Lung Biopsies: These can be performed in severe cases when the infection is associated with malignancies.

How Is Pneumocystis Pneumonia Treated?

Treatment of pneumocystis pneumonia should be started immediately in patients when clinical suspicion of infections exists. For mild cases, treatment can be initiated with oral medications on an outpatient basis.

• The first-line treatment for both HIV-infected and uninfected patients involves the administration of Trimethoprim-Sulfamethoxazole for 21 days.

• In mild to moderate cases, 15 to 20 mg/kg of Trimethoprim and 75 to 100 mg/kg of Sulfamethoxazole are administered orally in three doses per day. In addition, two tablets of Trimethoprim-Sulfamethoxazole thrice daily can also be administered.

• In moderate to severe cases, 15 to 20 mg/kg of Trimethoprim and 75 to 100 mg/kg of Sulfamethoxazole are given intravenously (IV) every six to eight hours, converted to an oral dose when the patient shows improvement.

• Desensitization can be performed in patients with a mild allergy to Trimethoprim-Sulfamethoxazole as this is the most effective drug of choice. However, desensitization in patients with severe allergies is no longer recommended, and it is better to choose a different drug.

Alternative drug therapy is used for treating patients with sulfa allergies.

For Mild to Moderate Cases:

• Atovaquone 750 mg orally twice per day.

• Trimethoprim 15 mg/kg/day orally twice per day plus Dapsone 100 mg by mouth daily.

• Primaquine 30 mg orally every day plus Clindamycin orally 450 mg every six hours or 600 mg every eight hours.

For Moderate to Severe Cases:

• Pentamidine 4 mg/kg intravenously once daily for over 60 minutes.

• Primaquine 30 mg orally daily plus Clindamycin intravenously 600 mg every six hours or 900 mg every eight hours.

Primaquine can only be administered orally. However, patients who cannot tolerate oral medications should be given intravenous Pentamidine with caution due to its increased toxicity and side effects compared to Primaquine. Patients must be monitored for any adverse side effects, and signs of treatment failure should be recognized when antimicrobial therapies are initiated.

Conclusion:

Previously, pneumocystis pneumonia had a high mortality rate. However, the mortality rates have decreased over the past two decades due to diagnosis and treatment advancements. Pneumocystis pneumonia shows a poor prognosis even in patients without HIV infection, with mortality rates around 50 %. Generally, the mortality rates are much higher when there is an underlying lung disorder. Pneumocystis pneumonia infection should be managed by a team of professionals, including a pulmonologist, an infectious disease expert, a pharmacist, a nurse, a respiratory therapist, and a dietitian.

Once the infection has been diagnosed, the patient should be encouraged to quit smoking, as nicotine worsens symptoms. Since most patients with pneumocystis pneumonia are very weak, a dietitian should be consulted to increase calorie intake. Finally, a lifelong follow-up of these patients is required.