IgG anti-toxoplasma antibodies among asymptomatic HIV-infected patients in Marrakesh-Morocco

Detection and monitoring of anti-Toxoplasma gondii antibodies are of a great interest among human immunodeficiency virus (HIV)-infected patients, since cerebral toxoplasmosis is a life-threatening opportunistic infection within this vulnerable population. The IgG anti-T. gondii seroprevalence was assessed in 95 asymptomatic HIV-infected adults living in Marrakesh city and its surrounding areas. Our results showed a seroprevalence of 62.1%, which is high compared to most other countries. The mean of CD(4+) T-cells count of involved patients was 381.9cells/μl. Given these results, HIV-infected patients in Marrakesh region could be at high risk to develop toxoplasmosis disease, especially when CD(4+) T-cells count falls below 100cells/μl. Accordingly, there is a serious need of widening antiretroviral therapy and chemoprophylaxis against toxoplasmosis, when indicated, to ovoid toxoplasmosis reactivation among this population.     

抗肺孢子虫药物的研究进展

肺孢子虫（Pneumocystis）是一种机会性致病真菌,能引起免疫力低下宿主严重的肺孢子虫肺炎（Pneumocystis pneumonia,PCP）。近年来,随着艾滋病、器官移植、放,化疗肿瘤患者等高危人群的增加,PCP发病呈明显上升趋势。开发新药物或老药新用以治疗、预防PCP成为研究热点。本文对近年来抗肺孢子虫药物及其筛选技术的研究进展进行综述。     

Reduced concentrations of IgG antibodies to Pneumocystis carinii in HIV-infected patients during active Pneumocystis carinii infection and the possibility of passive immunisation

The relationship between Pneumocystis carinii antibody concentrations and acute Pneumocystis infection was investigated by testing sequential samples of serum from HIV antibody-positive patients with respiratory symptoms and HIV-negative immunocompromised patients by means of an indirect immunofluorescence assay for specific IgG antibodies to P. carinii. Loss of circulating antibody at the time of active Pneumocystis infection was observed in five patients with proven infection. Three others showed recovery of antibody coinciding with treatment and clinical recovery from infection. Concentrations of specific IgG antibody against P. carinii were measured in 40 blood donors and in six different batches of an intravenous immunoglobulin (IV Ig) preparation. Titres greater than 128 were found in the IV Ig batches examined. The use of IV Ig, either alone or in conjunction with other therapeutic agents, should therefore be considered in patients suffering from acute infection with P. carinii.     

Pathogenesis of pneumocystis carinii pneumonia

Pneumocystis carinii is a ubiquitous fungus and opportunistic resident of the bronchoalveolar lumen of men and a variety of other mammalian species. This microorganism replicates under immunosuppressive conditions, ultimately resulting in lethal pneumonia (PcP) if left untreated. In the past decade, considerable progress has been made concerning the understanding of the underlying pathogenic mechanisms of this infection, mostly with the help of animal models such as SCID (severe combined immunodeficiency) or gene-knock-out mice. Partially conflicting data derived from animal studies lead to the assumption that there is no single relevant model for PcP. The T cell-mediated branch of the immune system is recognised as the major component in the host's ability to resist or overcome an infection with P. carinii. Natural, nonspecific immune mechanisms involving mononuclear phagocytes and elaborating a variety of cytokines and other immunomediators play an important role in initiating the immunoresponse as well as in its effector phase, but it is the CD4+ T lymphocytes which are essential for coordinating the complete eradication of this pathogen. The biological function and immunological effects of antigens expressed on the surface of or secreted by P. carinii organisms is not yet fully known. Hopefully, characterisation of these molecules, clarification of their immunological properties and the evaluation of the interactions between humoral and cellular as well as specific and nonspecific parts of the immune system will lead to new insights into the pathogenesis of P. carinii pneumonia.     

BAL and serum IgG levels in healthy asymptomatic HIV-infected patients

OBJECTIVES: To determine if the increased susceptibility to bacterial infection in asymptomatic HIV-infected patients is associated with decreased total IgG or IgG2 levels in lung epithelial lining fluid. BACKGROUND: A decrease in lung IgG levels or subtypes has been proposed as contributing to the increased risk of bacterial lung infections in HIV-infected patients. Previous studies measuring lung lavage IgG concentrations have been inconsistent. METHODS: Twenty-three HIV patients and 25 control subjects underwent BAL. Both patient groups were of similar age, and had similar pulmonary function studies and body mass index. Smokers were equally represented in both groups, and the majority of subjects in both groups were male. Total IgG and IgG2 levels in lavage fluid were assayed in both cohorts and compared using a two-tailed Student's t test. RESULTS: The lung lining fluid IgG level in HIV-infected patients was 0.19 +/- 0.13 microg/microg of protein (mean +/- SD) vs 0.11 +/- 0.09 microg/microg of protein in control subjects (p < 0.05). The IgG(2) level in HIV patients was 0.034 +/- 0.038 microg/microg of protein and 0.014 +/- 0.01 microg/microg of protein in control subjects (p = 0.054). Lavage IgG levels reflected serum IgG values (correlation coefficient, 0.56; p < 0.001) but did not correlate with lung immunoglobulin-producing cells. CONCLUSIONS: The increased susceptibility to bacterial pneumonia in asymptomatic HIV-infected individuals is neither explained by depressed total IgG levels nor a deficiency in IgG(2) levels in the lungs. The strong correlation between serum and lavage IgG levels suggests that lavage IgG derives from serum.     

Unusual pulmonary manifestations of pneumocystis carinii infection in immunocompromised patients

Three proven cases and one presumed case of Pneumocystis carinii pneumonia are presented in which the radiological appearance mimics tuberculosis. The classic and unusual X-ray findings of P. carinii pneumonia are discussed.     

艾滋病继发卡氏肺囊虫肺炎28例影像学表现

目的探讨艾滋病患者继发卡氏肺囊虫肺炎影像学的表现。方法回顾性分析2009-01～2011-12经临床确诊为艾滋病合并卡氏肺囊虫肺炎28例患者的影像学表现。结果典型的肺部影像学表现为双侧肺野弥漫性渗出性病变分布于肺门两侧周围肺野,病灶呈磨砂玻璃状、网格状、地图样或碎石路征。结论胸部X线片及CT扫描对艾滋病继发卡氏肺囊虫肺炎有重要诊断价值。     

艾滋病患者耶氏肺孢子菌肺炎的影像学分析

目的通过对艾滋病（AIDS）患者耶氏肺孢子菌肺炎（PCP）的影像学特点分析,提高PCP的诊断水平。方法回顾性分析45例AIDS患者PCP的胸部x线、cT表现。结果45例均表现为两肺弥漫性病变,呈两肺网状合并斑片状、小片状、大片状、结节状及两肺磨玻璃状改变。少见的合并表现有少量胸腔积液、肺气囊、肺大泡、结节灶、空洞、气胸。4例胸片两肺未见异常。结论胸部x线及CT对AIDS患者PCP具有重要的诊断价值。     

Low sensitivity of a nested polymerase chain reaction in oropharyngeal washings for the diagnosis of pneumocystis pneumonia in HIV-infected patients

STUDY OBJECTIVE: To compare the relative yield and diagnostic utility of the polymerase chain reaction (PCR) analysis for Pneumocystis jirovecii DNA in oropharyngeal washings using transbronchial biopsy (TBBx) and BAL as "gold standards." DESIGN: Prospective study. SETTING: Academic tertiary center. PATIENTS: Oropharyngeal washes were obtained in 50 consecutive patients with clinical pneumocystis pneumonia (PCP). Because of varying clinical severity, not all patients tolerated bronchoscopy. Thirty-five patients underwent TBBx, and 48 patients underwent BAL. METHODS: DNA extracted from oropharyngeal washings and BAL was subjected to a nested PCR test using primers for the large subunit mitochondrial ribosomal RNA of P jirovecii. Oropharyngeal washings were compared with BAL PCR and TBBx. RESULTS: Sixteen of the 35 TBBx procedures had positive results for PCP (46%). Oropharyngeal washings yielded positive results for pneumocystis in 7 of the 16 patients (sensitivity, 44%; specificity, 79%). Thirty-five of 48 patients (73%) had positive PCR results on BAL analysis. The relative yield of the PCR in oropharyngeal washes compared with BAL fluid was 40% (14 of 35 washes), giving a sensitivity of 40% and specificity of 77%. CONCLUSION: PCR DNA amplification of oropharyngeal washings in HIV-seropositive subjects has a low sensitivity and specificity for the diagnosis of PCP.     

Isolated antibodies against the core antigen of hepatitis B virus in HIV-infected patients

The aim of this study was to describe the frequency and significance of isolated antibodies against the hepatitis B virus (HBV) core antigen (HBc) in 2185 HIV-infected patients of the Aquitaine Cohort. Antibodies against HBc were found in 372 subjects (17%). Patients with isolated anti-HBc antibodies were more frequently coinfected with hepatitis C virus (HCV) (58.2%) than those who were anti-HB surface (HBs) antibody positive (22.9%, P<0.001) and those who were dually reactive anti-HBs/anti-HBc antibody positive (27.3%, P<0.001). These results suggest interactions between HBV and HCV. As observed in patients not infected with HIV, the "anti-HBc-alone" serological profile could reflect essentially late immunity with undetectable anti-HBs antibodies. However, an occult HBV infection cannot be ruled out.     

Low prevalence of occult HBV infection among HIV-infected patients in southern Spain

IntroductionThe aim of this study was to assess the prevalence of occult HBV infection in HIV-positive patients in a centre in Southern Spain.MethodsThe HBV serological markers were investigated in all the patients and the presence of HBV-DNA was tested by PCR in patients with isolated anti-HBc.ResultsAn isolated anti-HBc pattern was detected in 144/520 (27.7%) patients. HBV-DNA was detected in one of these patients (0.7%).ConclusionsIn Southern Spain, there is a low prevalence of occult HBV infection among HIV-infected patients, despite increasing immigration from endemic countries.     

Evaluation of vitamin D levels among HIV-infected patients in New York City

Few studies have examined the vitamin D status in HIV-infected patients. A cross-sectional retrospective chart review of 2992 HIV-infected patients was conducted from 9/2008 to 5/2009. A total of 274 adult patients had 25-hydroxyvitamin D [25(OH)D] obtained by radioimmunoassay. None was receiving vitamin D (vitD) supplements. Vitamin D status was defined as the following: vitD deficiency (vitDd) as 25(OH)D <25?nmol/liter, vitD insufficiency (vitDi) as 25(OH)D 25-74?nmol/liter, and vitD optimal (vitDo) as 25(OH)D ≥75?nmol/liter. We analyzed demographic/laboratory data. vitDd, vitDi, and vitDo were 21.2% (58 patients, 58/274), 68.6% (188 patients, 188/274), and 10.2% (28 patients, 28/274), respectively. There were significant racial differences. Blacks were 60.3% (35 patients, 35/58), 40.4% (76 patients, 76/188), and 28.6 % (8 patients, 8/28) in vitDd, vitDi, and vitDo, respectively, p=0.002. CD4 T cell count was not different in these three groups. However, HIV viral load was significantly different. Median log (10) HIV viral load was 2.31 with IQR 1.70-409, 1.70 with IQR 1.70-2.96, and 1.70 with IQR 1.70-2.78 in vitDd, vitDi, and vitDo, respectively, p=0.039. Multivariate logistic regression analysis showed that black race [odd ratio (OR) 4.108, 95% confidence interval (CI) 1.462-11.543, p=0.007] and HIV viral load>50 copies/ml (OR 2.396, 95% CI 1.120-5.127, p=0.024) were significantly associated with vitamin D deficiency. Vitamin D deficiency was highly prevalent in HIV-infected patients. Detectable HIV viremia and dark skin (black ethnicity) were significantly associated with vitamin D deficiency. Evaluation of vitamin D status in HIV-infected patients should be considered and further studies are needed to define the effects of vitamin D.     

Pneumocystis carinii pneumonia in HIV-infected patients in the HAART era

Since the advent of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections (OI) in patients with HIV has markedly decreased. Despite this, there are still large numbers of Pneumocystis carinii pneumonia (PCP) cases at Cook County Hospital (CCH). To better understand this patient group, we performed a retrospective chart review of 120 pathologically proven cases of PCP from January 1998 to June 2001. One hundred four patients were included in the study. Sixty-nine percent of our patients were active substance abusers and 50% had previous knowledge of HIV disease. Of our patients, fewer than 5% were on HAART or PCP prophylaxis on study admission. The overall mortality rate was 14%. Of discharged patients, 65% were placed on HAART therapy and 59% of these achieved a viral load of less than 1000 copies per milliliter in the year postdischarge. Patients who failed to achieve a viral load less than 1000 copies per milliliter were more likely active substance abusers or had a viral load greater than 100,000 copies per milliliter prior to study admission. Our study shows that patients are still being admitted with PCP in the HAART era. Active substance abuse and failure to recognize HIV status contributed heavily to this late presentation of HIV disease. An aggressive approach toward HIV identification and substance abuse treatment may decrease admissions to the hospital for PCP and improve response to HAART therapy.     

Surfactant analysis during Pneumocystis carinii pneumonia in HIV-infected patients.

Pulmonary surfactant is altered in experimental Pneumocystis carinii pneumonia. Although P carinii is a major causative agent of pneumonia in immunocompromised patients, the pathophysiology of lung injury caused by this organism is poorly understood. Therefore, we studied bronchoalveolar lavage specimens obtained from 19 HIV-infected subjects with PCP compared with specimens from ten healthy control subjects. As iterative BAL was performed, 37 BAL specimens were analyzed for protein and phospholipid. The BAL samples were divided into two groups as follows: 22 BAL samples with the presence of P carinii and 15 BAL samples without P carinii. Compared to control subjects, HIV+ BAL presented a significant increase of PR and a decrease of total PL in both P carinii+ and P carinii- BAL, but in P carinii+ BAL, the fall of PL/PR ratio was significantly more pronounced compared to P carinii- (0.09 +/- 0.02 vs 0.19 +/- 0.04, p less than 0.02). The BAL performed during the recovery of PCP showed an improvement of initial biochemical abnormalities. Surfactant composition was also altered, with a phosphatidylcholine and phosphatidylglycerol drop and a sphingomyelin and lysophosphatidylcholine increase. The presence, even in P carinii- BAL, of less polar compounds of undetermined nature, was revealed. We concluded that in HIV+ patients, abnormalities of pulmonary surfactant were present before PCP, and that the development of PCP enhances these abnormalities. These surfactant alterations may contribute to the saprophyte-pathogen transformation of P carinii, but this hypothesis requires further investigation that is presently in progress.     

Pneumocystis carinii pneumonia in HIV-infected patients: diagnostic yield of induced sputum and immunofluorescent stain with monoclonal antibodies.

The purpose of this study was to evaluate the diagnostic yield of induced sputum (IS), assessing the reliability of indirect immunofluorescent stain with monoclonal antibodies (IFMoAb) and methenamine silver (Met-Ag) and analysing factors likely to influence the sensitivity of these techniques. An analysis was prospectively carried out on IS specimens collected from 61 human immunodeficiency virus (HIV)-infected patients during 69 episodes of suspected Pneumocystis carinii pneumonia. Ultrasonic nebulizers with hypertonic 2% saline were used. IFMoAb to P. carinii and Met-Ag were performed after cytocentrifugation of the specimen. Results were compared with those of bronchoalveolar lavage (BAL) with/without transbronchial biopsy (TBB), performed not more than seven days after induction of sputum. P. carinii pneumonia was confirmed in 32 episodes, of which IS was diagnostic in 23. The sensitivity of the staining procedures was 69% for IFMoAb, and 28% for Met-Ag. The three episodes of P. carinii pneumonia in patients on oral chemoprophylaxis yielded negative IS results; in contrast, IS was negative in only 6 of the 29 cases not receiving chemoprophylaxis. IS is a non-aggressive procedure that diagnosed P. carinii pneumonia in 72% of our cases. The yield increased significantly when IFMoAb was used in patients not receiving oral chemoprophylaxis.     

卡氏肺囊虫肺炎临床诊治的初步体会

目的提高对卡氏肺囊虫肺炎（ＰＣＰ）的认识。方法回顾性分析６例ＰＣＰ患者资料。结果６例ＰＣＰ基础疾病为白血病、淋巴瘤、肾移植和溶血性贫血。临床表现为呼吸困难、咳嗽和发热。Ｘ线表现为双肺弥漫性肺泡性或间质性改变或无改变。治疗首选复方新诺明（ＳＭＺｃｏ）和氨苯砜。３例并发呼吸衰竭，表现与成人呼吸窘迫综合征（ＡＲＤＳ）相似的低氧血症、肺内分流和顺应性下降。持续气道正压通气／呼气末正压通气（ＣＰＡＰ／ＰＥＥＰ）为常用模式。顽固性低氧血症可试用高水平（＞１４７ｋＰａ）ＰＥＥＰ治疗。结论卡氏肺囊虫肺炎并发急性呼吸衰竭者预后差，争取早期诊断与治疗是提高生存率的关键。     

肾移植受者卡氏肺囊虫肺炎的肺泡损伤

目的　通过观察肾移植后卡氏肺囊虫肺炎 (PCP)患者的肺泡超微结构改变 ,探讨其与病原学的关系。方法　对可疑PCP的肾移植受者 ,进行支气管肺泡灌洗 (BAL)和 (或 )经支气管肺组织活检 (TBLB) ,以发现卡氏肺囊虫为确诊依据 ,通过光镜和电镜下的观察 ,结合其临床特点 ,分析病原体与宿主肺泡病理反应的关系。结果　确诊PCP 2 3例 ,发病距肾移植时间平均 5 6个月 ,发病至就诊时间平均 5 5d ;临床以发热、呼吸困难为主要症状 ,胸部CT表现为两肺弥漫性肺间质及肺泡改变。通过BAL检查发现卡氏肺囊虫者 18例 ,通过TBLB电镜检查发现卡氏肺囊虫者 14例 ,虫体以滋养体与包囊两种形式存在。肺组织光、电镜检查 :可见Ⅰ型上皮细胞变性、Ⅱ型细胞增生、Ⅰ型和Ⅱ型上皮细胞脱落、上皮细胞脱落后其下的基底膜暴露于肺泡腔等 ;肺间质及肺泡内出现少量炎症细胞 ;肺泡腔内见少量蛋白样物质渗出 ,部分可见空泡样细胞及泡沫样组织 ;肺间质中可见不同程度胶原纤维增生 ,肺泡间隔增宽。结论　肾移植后PCP患者存在明显的肺泡损伤 ,以肺泡内渗出、炎症细胞浸润、上皮细胞受损及间质纤维组织增生为特征 ,为其发病的主要病理基础     

Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV-infected patients

OBJECTIVE: To describe clinical experience with atovaquone suspension for the treatment of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: A retrospective chart review. METHODS: The medical records of 54 HIV-infected patients with PCP treated with atovaquone were examined. The outcomes of 34 patients treated with atovaquone suspension (750 mg twice a day) were compared with those of 20 patients treated with atovaquone tablets (750 mg three times a day). RESULTS: The proportion of patients successfully treated was similar with the suspension (74%) and tablet (70%) formulations of atovaquone. The proportion of patients with an inadequate response to therapy was lower for patients treated with atovaquone suspension (15%) than tablets (30%). Both formulations were well tolerated. CONCLUSION: Atovaquone suspension is effective and well tolerated for the treatment of PCP.