Pneumocystosis

　　1. Etiology

　　1. Pneumocystis carinii is a eukaryotic microorganism, mainly existing in two forms, i.e., cysts and trophozoites. The precystic form is an intermediate stage between the two, with unclear morphological characteristics. Cysts are round or oval, with a diameter of 4-6 nm, a cyst wall thickness of 100-160 nm, and appear brown-black under silver staining and purple-blue under toluidine blue staining. After maturation, the intracellular cytoplasm inside the cyst is absorbed, containing 8 intracystic bodies with a diameter of 1-1.5 nm, showing polymorphism, thin membranes, and a single nucleus. After the cyst ruptures, the intracystic bodies are released, develop into trophozoites, which do not stain, and reproduce by binary fission. In severely infected individuals, there are often a large number of trophozoites in the lungs, while cysts are relatively rare. Cysts are an important basis for diagnosis.

　　2. Since its trophozoites have pseudopod structures similar to protozoa, they cannot grow in fungal culture media and are sensitive to antiprotozoal drugs, so it is generally considered to belong to the phylum Protozoa and subclass Sporozoa. However, its ultrastructure is similar to that of fungi, and its 16S ribosomal RNA and mitochondrial DNA molecular analysis shows that it is closely related to yeast ascomycetes in phylogenetic terms. The nucleotide sequence of the mitochondrial DNA is more homologous to fungi (60%) than to protozoa (only 20%), so it is currently considered to belong to fungi. Although traditional antifungal drugs such as amphotericin and azoles are ineffective against it, new antifungal drugs have been proven abroad to be able to inhibit the synthesis of the cyst wall β-glucan in vitro infection models, and also have activity against the trophozoites. Therefore, there is still controversy about the taxonomic status of Pneumocystis carinii in biological classification, but most authoritative literature and textbooks have already classified it as fungi.

　　Second, pathogenesis

　　1. After infection, healthy people often present with asymptomatic infection, which can cause overt infection under the following conditions. ①Premature infants or infants with malnutrition, often develop within 10 to 24 weeks after birth; ②Congenital immunodeficiency, including humoral immunity, cellular immunity, or both; ③Acquired immunodeficiency, commonly seen in AIDS, leukemia, lymphoma, and other malignant tumors, connective tissue diseases, or organ transplantation, with the long-term and large-scale use of adrenal cortical hormones, cytotoxic drugs, or radiotherapy, all of which can cause immunosuppression of the body's immune function, an important cause of PCP.

　　2. Pneumocystis is a low-pathogenic, slow-growing and reproducing parasite. It adheres and parasitizes on the surface of type I alveolar epithelial cells in the human body, taking alveolar exudate as nutrition, presenting a potential infection. When the host's immune function is reduced, the protozoa in a latent state begin to multiply in large numbers, causing direct damage to the epithelial cells and obstructing gas exchange. The lung volume increases and becomes liver-like. The typical histological lesions are alveolar space cell infiltration, with predominantly plasma cell infiltration in infants and children, and predominantly lymphocyte infiltration in adults. Macrophages and eosinophils can also be seen. If there is no secondary bacterial infection, neutrophil infiltration is rare. The alveolar space epithelial cells proliferate, thicken, and partially shed, and may form hyaline membranes, interstitial fibrosis, and edema. The alveolar spaces expand, filled with foamy honeycomb-like eosinophilic substances, containing the bodies and debris of the parasites and shed epithelial cells.

　　The pathological and physiological changes include hypoxemia, increased alveolar-arterial pressure difference (PaO2), respiratory alkalosis; diffusion capacity impairment, indicating alveolar-capillary block; changes in lung compliance, and decreased lung volume. These changes may be related to abnormalities in the lung surfactant system. Analysis of bronchoalveolar lavage fluid (BALF) shows a decrease in surfactant phospholipid components and an increase in proteins. In vitro experiments show that the protozoa inhibit the secretion of surfactant phospholipid components.

　　Complications include cytomegalovirus infection, tuberculosis, fungal infection, or toxoplasmosis, etc.

　　1. Giant cell inclusion disease, also known as giant cell virus infection, is a congenital or acquired systemic infectious disease caused by human cytomegalovirus infection. It is named giant cell inclusion disease because human cytomegalovirus inclusions can be found in the nuclei and cytoplasm of many infected organs and tissues. In recent years, with the development of molecular biology technology, the diagnosis of active cytomegalovirus infection no longer depends on the detection of viral inclusions in the pathological tissue cells, so giant cell inclusion disease is often referred to as giant cell virus infection.

　　2. Toxoplasmosis (toxoplasmosis), also known as toxoplasmosis, is a parasitic protozoan disease caused by Toxoplasma gondii. The disease is widely distributed worldwide and has a wide range of natural foci. Many mammals and birds, including various domestic animals and poultry, are infected. The infection in humans is also very common. Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. It can be infected through both congenital and acquired routes. After infection, humans often present with asymptomatic infection, with no or few clinical manifestations, and it is not easy to detect the pathogen by routine methods. When the immune function is impaired, it can cause central nervous system damage and systemic disseminated infection. Congenital infection often leads to fetal malformation and has a high mortality rate, which is a serious concern in eugenics.

　　1. Epidemic type

　　Also known as infantile type, it is more common in low birth weight infants, malnourished or congenital immune deficiency infants, with a hidden onset, increased respiratory rate as the earliest respiratory symptom, followed by dry cough, dyspnea, flaring of the nostrils, cyanosis, and other signs. The mortality rate of those who do not receive timely treatment can reach 50%.

　　2. Sporadic type

　　Also known as pediatric-adult type, it is more common in individuals with impaired or defective immune function, with an acute onset, rapid onset of fever, cough, dyspnea, cyanosis, and other symptoms, but few rales. Short-term courses can die within 4 to 8 days, chest X-ray changes are often delayed compared to clinical manifestations. Without effective treatment, the mortality rate of both adults and children can reach 90% to 100%. Both types of lung X-ray manifestations are diffuse, with bilateral streaky or spotted shadows. Pneumonia and lung base are less involved, which can rapidly develop into lung consolidation. There are often widespread or localized atelectasis in the consolidation lesions, and some cases may show pneumothorax, pleural effusion, pulmonary nodular shadows, etc. The arterial oxygen partial pressure is often below 10.7kPa (80mmHg), the CO2 partial pressure is normal or low, and the arterial blood pH is often increased.

　　Patients should be isolated to prevent respiratory transmission. Improve the nutritional status of patients, reduce unnecessary immunosuppressive chemotherapy and radiotherapy. For susceptible populations and high-risk populations, drug prophylaxis can be adopted. For example, sulfamethoxazole-trimethoprim, TMP at 5mg/kg per day, SMZ at 25mg/kg per day, taken twice a day, three times a week, for a course of 5 to 18 months. Pentamidine aerosol and dapsone can also be used for prophylaxis. At present, there is no vaccine available.

　　1. Blood count

　　White blood cell count is normal or elevated, mostly (15-20)×10^9/L, classification is normal or left shift, eosinophils can be slightly increased.

　　2. Pathogen examination

　　Sputum examination is the most convenient, safe, and can be confirmed by centrifugal sedimentation, staining, and microscopic examination after smearing, bronchoalveolar lavage fluid, or lung biopsy specimens. The detection of Pneumocystis carinii trophozoites and cysts can confirm the diagnosis. The application of various staining methods (such as methylene blue staining method) and PCR technology in recent years has greatly improved the detection rate.

　　In addition to conventional treatment, the following aspects should be paid attention to in diet for patients with Pneumocystis carinii pneumonia: The patient's diet should be light and balanced, and the diet should be reasonable. Eat less spicy and irritating foods.

　　I. Treatment

　　1. General treatment: Oxygen therapy and auxiliary ventilation therapy are important measures for those with hypoxemia and respiratory insufficiency. Continuous low-flow oxygen inhalation is preferable. Within 72 hours after the start of pathogen treatment, the use of adrenal cortical hormones can improve lung function and reduce the mortality rate.

　　2. Pathogen treatment: If antiparasitic treatment is performed before respiratory failure, it can greatly reduce the mortality rate.

　　(2) Sulfamethoxazole/Trimethoprim (Co-trimoxazole): It is the first-line anti-pneumocystis drug. Methotrexate (TMP) is taken at 20mg/kg per day, and sulfamethoxazole (SMZ) at 100mg/kg per day, divided into 2 to 4 doses. The first dose is doubled. The general course is 2 weeks, and the course for concurrent AIDS is 3 weeks. If the treatment is ineffective after 1 week, consider changing to pentamidine.

　　(2) Pentamidine: Mainly used for those who are ineffective with sulfamethoxazole/trimethoprim (SMZ/TMP) treatment or allergic to sulfonamides. 4mg/kg per day, intramuscular injection, 2 weeks as one course. Possible adverse reactions include heart, kidney, and liver damage, bone marrow suppression, hypoglycemia, etc.

　　(3) Others: Atovaquone, dapsone (DDS), α-difluoromethyl ornithine (DFMO), dapsone plus sulfadoxine-pyrimethamine, primaquine plus clindamycin, and other drugs can be used.

　　II. Prognosis

　　The mortality rate of those who do not receive timely treatment reaches 50%, and if there is no effective treatment, the mortality rate of both adults and children can reach 90% to 100%.