AIDS (Acquired Immune Deficiency Syndrome) is the most severe immunosuppressive clinical syndrome caused by human immunodeficiency virus infection, and patients with advanced disease often develop various opportunistic infections due to immune deficiency.
Cytomegalovirusemia can be contracted mainly through close contact, blood transfusion, sexual intercourse, and mother-to-child transmission. Epidemiological data show that about half of AIDS patients develop cytomegalovirus infections in different organs before the advent of HAART treatment, and that reactivation of latent viruses or infection with new CMV strains during AIDS-induced immune deficiency can cause viral multiplication, leading to injury and disease. The advent of HAART treatment has reduced the incidence of cytomegalovirusemia in AIDS patients to about 10%. Due to immune deficiency, patients with HIV/AIDS are often negative for CMV-IgM, and currently the main test is CMV-DNA to determine cytomegalovirus infection. Therefore, there are many misdiagnoses and omissions.
The Infection Center of Beijing Ditan Hospital is a center for the diagnosis and treatment of AIDS and its opportunistic infections, and we treat nearly 300 cases of AIDS patients each year. In order to improve clinicians’ diagnosis of combined cytomegalovirusemia in HIV/AIDS patients, this paper initially discusses the clinical features of combined cytomegalovirusemia in AIDS patients.
Subjects and methods.
I. Diagnostic basis.
The diagnostic criteria of AIDS were referred to the “Guidelines for the diagnosis and treatment of AIDS” developed by the AIDS Group of the Infectious Diseases Branch of the Chinese Medical Association in 2006. The clinical data of 249 AIDS patients hospitalized in Beijing Ditan Hospital from October 2008 to November 2009 were retrospectively studied. 43 of them were diagnosed with cytomegalovirusemia after CMV pp65 antigen and CMV-DNA testing and were treated systemically with ganciclovir or sodium phosphonate.
II. Clinical data.
Among the 43 patients, we focused on whether they had homosexuality, respiratory symptoms such as fever and cough, gastrointestinal symptoms such as abdominal pain, diarrhea, dysphagia and retrosternal pain, ocular symptoms such as floating objects in front of the eyes, vision loss and blindness, and neurological lesions such as lower limb paralysis. In addition, we also focused on other opportunistic pathogenic infections of the respiratory system, digestive system, nervous system, and eyes in 43 patients with AIDS combined with cytomegalovirusemia. The above information was used to create a database through Excel software.
III. Laboratory and physical examinations.
Blood was drawn for T-cell subsets on admission in 43 patients. This laboratory test mainly reflects the level of cellular immunity of the body, with particular attention to the CD4+ T-cell count; CMV pp65 antigen and CMV-DNA quantitative tests were detected. For patients with cough, chest tightness, breath-holding and other respiratory tract patients, fiberoptic bronchoscopy was improved, and alveolar lavage fluid was sent for cytological examination; for patients with diarrhea, colonoscopy was improved; for those with upper gastrointestinal symptoms such as retrosternal pain and swallowing difficulties, gastroscopy was improved; for patients who underwent gastroscopy and colonoscopy, biopsies were taken to improve pathological examination. Fundoscopy was performed for those with visual lesions.
IV. Statistical analysis.
The statistical analysis software SPSS12.0 was used to correlate the above CD4+ T cells and CMV-DNA levels.
Results.
I. Clinical presentation.
Among 249 AIDS patients hospitalized in our hospital from October 2008 to November 2009, 43 cases (17.3%) were diagnosed with cytomegalovirusemia after CMV pp65 antigen and CMV-DNA testing. Among the 43 CMV-infected patients, 9 were homosexuals; all 43 patients had various clinical symptoms, including fever, cough, abdominal pain, diarrhea, retrosternal pain, vision loss and even blindness. Among the 43 infected patients, 29 patients had fever; 22 had cough; 17 had abdominal pain and diarrhea; 12 had retrosternal pain; 14 had decreased vision and 4 had blindness.
Second, the results of physical examination of CMV infection.
Fundoscopic examination was performed in 43 patients, respectively, and it was found that fundoscopic examination in 14 patients suggested yellowish-white retinal exudate or retinal hemorrhage distributed along the perivascular area; 4 cases showed fundus retinal exudate or hemorrhage followed by mechanization, which was consistent with the number of cases of vision loss and blindness observed clinically.
Among the 43 patients with fever, cough and other respiratory symptoms, chest X-ray, chest-enhanced CT and fiberoptic bronchoscopy were perfected, and alveolar lavage fluid was sent for pathological examination. The alveolar lavage fluid revealed alveolar exfoliated cell nuclei and cytoplasmic inclusions, i.e. “owl’s eye” structures.
Among the 43 patients with abdominal pain, diarrhea, and retrosternal pain, fiberoptic colonoscopy and gastroscopy were completed, and pathological tissue biopsies were obtained.
Among the 43 patients with neurological localization signs, cranial CT, lumbar puncture and cerebrospinal fluid examination were completed, and cerebrospinal fluid CMV-IgM and pp65 antigen examination was completed. CMV-IgM(+).
III. CMV-infected patients with other opportunistic pathogenic infections or complications.
As seen in Table 1, there may be a variety of other multiple sources of opportunistic pathogenic infections or other complications mixed in the lungs, colon, esophagus, brain and eye, where CMV is commonly infected.
IV. Correlation analysis of immune status and CMV-DNA levels in HIV CMV-infected patients.
All 43 patients had less than 100 CD4+ T cells/ul, CMV-DNA level fluctuated in (2.1×104–2.96 x106) copies/ml, SPSS1.5 software analysis of low level CD4+ T cells and CMV-DNA positivity had correlation (P<0.05), that is, the lower the level of CD4+ T cells, the CMV-DNA levels were higher.
Discussion.
Cytomegalovirusemia is a common source of opportunistic pathogenic infection among AIDS patients, and the rate of cytomegalovirusemia among AIDS patients was reported to be 7.3% in foreign countries and 11.4% in Peking Union Medical College Hospital by Li Taisheng et al. The present study collected 249 AIDS patients hospitalized in our hospital from October 2008 to November 2009 and found that 17.3% of them were infected with CMV This is higher than previous national and international reports, and is considered to be related to the high sensitivity of the current assay using pp65 antigen and CMV-DNA and the increased awareness of CMV infection among our physicians. In the late stage of AIDS, CMV-IgM is often negative due to immune deficiency, and the correct diagnosis of CMV infection cannot be made. The application of fluorescent quantitative PCR for CMV DNA and pp65 antigen is considered to be a sensitive method, which not only has a high positive rate, but also can be used as an indicator to observe the efficacy of treatment.
The gold standard for the diagnosis of CMV retinitis is the presence of typical retinal lesions on fundoscopic examination, such as retinal vasculitis, hemorrhage, massive exudate, and irregular yellow-white granules, which may involve the macula but no clouding of the crystal. In this study, there were 14 cases of visual loss and 4 cases of blindness in 43 patients, and the incidence of cytomegalovirus retinitis was 41.9%. In patients with initial visual changes such as decreased vision and floating objects in front of the eyes, fundoscopy suggested yellowish-white retinal exudates or retinal hemorrhages distributed along the perivascular area, which were better treated with sodium phosphonate or ganciclovir. related to CMV retinitis, therefore, early detection and early treatment with sodium phosphonate or ganciclovir are more effective.
The respiratory system is the most common site of opportunistic pathogenic infections in patients with AIDS, and in clinical practice the most common are bacterial infections of the lungs, tuberculosis, pneumocystis pneumonia, and pulmonary aspergillosis, often overlooking cytomegalovirus pneumonia. Cytomegalovirus pneumonia often coexists with Pneumocystis carinii pneumonia and can result in fever, cough, dyspnea, and interstitial infiltration of the lung. Among 43 AIDS patients with cytomegalovirusemia, chest radiographs, chest-enhanced CT, and fiberoptic bronchoscopic alveolar lavage and cytology were completed in those with fever, cough, and dyspnea. Bronchoscopic alveolar lavage and cytology combined with chest CT are good methods to diagnose cytomegalovirus pneumonia; however, compared with other opportunistic pathogenic infections of the lung, the diagnostic rate of cytomegalovirus pneumonia is significantly low, and it is questionable whether pp65 antigen or CMV-DNA testing of alveolar lavage fluid exfoliated cells can be performed in addition to exfoliative cytopathology.
Cytomegalovirusemia can lead to gastrointestinal symptoms such as abdominal pain, diarrhea, and retrosternal pain. In this study, fiberoptic colonoscopy was perfected in 17 patients with abdominal pain and diarrhea and gastroscopy was performed in 12 patients with retrosternal pain among those with cytomegalovirusemia, and histopathological biopsies were also taken. Although these patients tested positive for CMV-DNA, no specific CMV-positive pathological findings were found, suggesting that although patients with CMV viremia, it did not indicate the presence of CMV end-organ disease.
In this study, all 43 CMV-infected patients had less than 100 CD4+ T cells/ul, CMV-DNA levels fluctuated from 2.1x10E4–2.96 x10E6copies/ml, and low levels of CD4+ T cells and CMV-DNA positivity were correlated, suggesting that in AIDS patients when CD4+ T cells are less than 100 cells/ul, to If the results are positive, anti-CMV treatment with phosphonate or ganciclovir should be used to prevent CMV damage to multiple organs of the body.
In AIDS patients, cytomegalovirusemia can lead to different tissue and organ damage, such as retinitis or even blindness, esophagitis, colitis, encephalitis and other end-organ lesions, and the current anti-CMV treatment with sodium phosphonate or ganciclovir is more effective. Therefore, in AIDS patients, especially when CD4+ T cells are less than 100 cells/ul, cytomegalovirusemia should be detected promptly and anti CMV therapy to prevent end-organ damage.
In this study, 43 patients had other opportunistic pathogenic infections in addition to cytomegalovirus infection, such as PCP, fungal infection, tuberculosis, Cryptococcus, Toxoplasma, syphilis, etc. Therefore, opportunistic pathogenic infections in AIDS patients are often diverse and should be taken into account in the treatment process.