Cases Of Pneumocystis Carinii Pneumonia Research Articles

Comparative effectiveness of trimethoprim-sulfamethoxazole versus atovaquone for the prophylaxis of pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids

We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18years who were treated with a prolonged course (≥ 4weeks) of glucocorticoids (≥ 20mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19-5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.

HIV: the next decade

40 years since the first published descriptions of disease caused by HIV, Talha Burki talks to some of the leading figures in the fight against HIV/AIDS about what must be achieved in the next decade. Marking 40 years of the HIV/AIDS responseIn June, 1981, a Morbidity and Mortality Weekly Report (MMWR) article briefly described five cases of Pneumocystis pneumonia among homosexual men in Los Angeles (CA, USA). This case series, which provides the first description of what came to be known as AIDS, takes just a minute or so to read but was the first tremor of a seismic upheaval in global health that continues to reverberate four decades on. Full-Text PDF

A pandemic anniversary: 40 years of HIV/AIDS

A pandemic anniversary: 40 years of HIV/AIDS

Recurrent Pneumocystis jirovecii pneumonia in an HIV-infected patient: A case report

We present a case of Pneumocystis pneumonia (diagnosis was based on imaging X-ray and CAT examinations, and real-time PCR) in an HIV-infected patient with relapse four months later and long lasting colonization as detected by the positive real-time PCR results and lack of clinical symptoms during the follow up of the patient after second course of treatment with trimethoprim/sulfamethoxazole. The wild-type P. jirovecii DHPS genotype was identified in all patient samples tested.

Genetic and Epidemiologic Analyses of an Outbreak of Pneumocystis jirovecii Pneumonia Among Kidney Transplant Recipients in the United States

Abstract Background Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. Methods Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. Results Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. Conclusions Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.

Genetic and Epidemiologic Analyses of an Outbreak of  <i>Pneumocystis jirovecii</i> Pneumonia Among Kidney Transplant Recipients in the United States

Background: Pneumocystis jiroveciii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. Methods: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. Findings: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7·5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. Interpretation: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions. Funding Information: This study was support in part by intramural research funds from the NIH Clinical Center. Declaration of Interests: No conflicts of interest to declare. Ethics Approval Statement: The Yale Institutional Review board approved this study (IRB# 2000023859).

Pneumocystis Pneumonia: Immunity, Vaccines, and Treatments.

For individuals who are immunocompromised, the opportunistic fungal pathogen Pneumocystis jirovecii is capable of causing life-threatening pneumonia as the causative agent of Pneumocystis pneumonia (PCP). PCP remains an acquired immunodeficiency disease (AIDS)-defining illness in the era of antiretroviral therapy. In addition, a rise in non-human immunodeficiency virus (HIV)-associated PCP has been observed due to increased usage of immunosuppressive and immunomodulating therapies. With the persistence of HIV-related PCP cases and associated morbidity and mortality, as well as difficult to diagnose non-HIV-related PCP cases, an improvement over current treatment and prevention standards is warranted. Current therapeutic strategies have primarily focused on the administration of trimethoprim-sulfamethoxazole, which is effective at disease prevention. However, current treatments are inadequate for treatment of PCP and prevention of PCP-related death, as evidenced by consistently high mortality rates for those hospitalized with PCP. There are no vaccines in clinical trials for the prevention of PCP, and significant obstacles exist that have slowed development, including host range specificity, and the inability to culture Pneumocystis spp. in vitro. In this review, we overview the immune response to Pneumocystis spp., and discuss current progress on novel vaccines and therapies currently in the preclinical and clinical pipeline.

A Case of Pneumocystis Pneumonia during Bioradiotherapy with Cetuximab

A Case of Pneumocystis Pneumonia during Bioradiotherapy with Cetuximab

Mortality rate and prognostic factors for poor outcome in HIV-infected Bulgarian patients with Pneumocystis pneumonia over a 3-year period

Background: In spite of the use of combination antiretroviral therapy and specific prophylaxis, Pneumocystis pneumonia remains one of the most common AIDS-defining disease with high mortality rate. The aim of this study is to analyze the cases of pneumocystis pneumonia over a three-year period by means of assessing the mortality rate and the prognostic factors for the outcome of the disease. Material and methods: Epidemiological, clinical, laboratory and demographic data were analyzed for 13 HIV-infected patients with proved pneumocystis pneumonia, hospitalized at the AIDS Department over the period January 2017–December 2019. For data processing we used different methods of descriptive statistics. Results: All presented patients have extremely severe immune deficiency and other opportunistic infections or AIDS-related diseases. The diagnosis of pneumocystis pneumonia was confirmed with PCR in 76.9% of the patients and with Giemsa staining for cysts and trophozoites in 23,1% of the patients. Most of our patients are male (84,6%) and the leading mechanism of HIV infection is unprotected homosexual contact. The mean age of the patients presented is 37.4 ± 10.27. Our results showed high PJP mortality (46.3 %), despite the applied etiological therapy. Conclusions: Pneumocystis jirovecii pneumonia (PJP) continues to be a life-threatening infection in HIV-infected patients with severe immune suppression. PJP mortality continues to be high, and there is a statistically significant dependence on age, male sex, low CD 4 T+ cell count, high viral load of HIV, low blood albumin, and the number and severity of comorbidities.

Impact of Increased Duration of Trimethoprim-Sulfamethoxazole Prophylaxis for Pneumocystis Pneumonia After Renal Transplant.

BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) is recommended as prophylaxis against Pneumocystis pneumonia (PCP) in renal transplant recipients. The optimal duration of prophylaxis is unknown. Longer duration of prophylaxis may increase the risk of adverse effects. The aim of this retrospective observational cohort study was to assess the impact of increasing duration of TMP-SMX prophylaxis from 3 to 6 months after transplant on drug-resistant urinary tract infection (UTI), hyperkalemia, peripheral blood cytopenias, and incidence of PCP.Material/MethodsPatients transplanted over a 4.5-year period before and after a change in protocol from 3- to 6-months TMP-SMX prophylaxis in our unit were grouped according to planned duration of prophylaxis, and results were analyzed on an intention-to-treat basis. Baseline characteristics, laboratory values, and all urine microbiology results in the 6 months after transplant were analyzed.ResultsThe overall UTI incidence rate was higher in the 3-month (3-m) treatment group than the 6-month (6-m) treatment group (0.52 vs. 0.33 UTI per 100 patient days; rate ratio 1.56 [95% CI 1.27–1.95]). However, this was not attributable to TMP-SMX: the incidences were significantly different in months 0–3 but not months 4–6. Twenty-eight multi-resistant UTIs occurred in the 3-m group, but there were none in the 6-m group (p=0.004). There were no significant differences in renal function, serum potassium, or cytopenias during the first 6 months. There were 15 cases of PCP in the 3-m group, 3 cases in the 6-m group, and no cases during prophylaxis.ConclusionsExtending the duration of TMP-SMX prophylaxis was not associated with change in frequency of UTIs or multi-drug-resistant UTIs, nor was it associated with increased adverse events. TMP-SMX is an effective PCP prophylaxis, and these data support recommendations to extend the duration of prophylaxis after transplant.

Disseminated lung disease in elderly patient with multimorbidity and HIV infection (clinical case)

Disseminated lung diseases have similar non-specific manifestations in various etiologies, pathogenesis, and morphology. Pulmonary dissemination is the concept of X-ray, there are no pathognomonic symptoms on a radiograph that are inherent in a particular disease with pulmonary dissemination, therefore, in real clinical practice, differential diagnosis in pulmonary dissemination is the prerogative of the physician. Diseases that are manifested by pulmonary dissemination can be classified by dissemination of infectious causes (tuberculosis, HIV-associated dissemination, fungal lesions), malignant pulmonary lesions (carcinomatosis, cancer lymphangitis), cardiogenic dissemination and interstitial lung diseases. In recent years, the incidence of allergic interstitial lung diseases has increased. Infectious lesions of the lungs in patients with HIV infection and reduced immune status in many cases also have a disseminated form and cause difficulties in the differential diagnosis of tuberculosis. The article presents a clinical case of pneumocystis pneumonia in an HIV-infected patient with pulmonary dissemination syndrome on X-ray. The difficulties of the diagnostic search with low compliance of the patient and the physician are shown (a patient registered with HIV for 10 years hid this fact of his history from the attending physician and gave a written refusal to get tested for HIV fibrobronchoscopy). The possibility of introducing compulsory HIV screening for all patients admitted to the hospital with disseminated processes in the lungs has been considered.

Changing Trends in the Epidemiology and Risk Factors of Pneumocystis Pneumonia in Spain.

Objective: The information about the epidemiology of Pneumocystis pneumonia (PcP) in Europe is scarce, and in Spain there are only data nationwide on patients with HIV infection. This study has been carried out with the aim of knowing in our country the current epidemiological spectrum and the risk factors of PcP.Methods: Observational, descriptive transversal study that included all patients admitted in Spain with diagnosis upon discharge of PcP registered in the National Health System's Hospital Discharge Records Database of Spain, between 2008 and 2012.Results: Four thousand five hundred and fifty four cases of PcP were reported, 1,204 (26.4%) in HIV-negative patients. During the study period, mean annual incidence (cases per million) was 19.4, remaining globally stable, increasing from 4.4 to 6.3 in HIV-negative patients and decreasing from 15.5 to 13.4 among HIV-infected patients. Risk factors were identified in 85.5% of HIV-negative cases, the most frequent being hematological neoplams (29%), chronic lung diseases (15.9%), and non-hematological cancers (14.9%). Mean mortality and hospitalization cost were high (25.5% and 12,000 euros, respectively).Conclusions: The results of this first nationwide study in Spain allow a change in the misconception that, after the AIDS epidemic, PcP is an infrequent disease, showing that today it is an emerging problem in patients without HIV infection. These findings underlines the need for increased efforts toward a better characterization of risk groups to improve prophylactic strategies and reduce the burden of disease.

BACTRIM-RESPONSIVE HIGHLY SUSPECTED PNEUMOCYSTIS PNEUMONIA IN ETANERCEPT-TREATED RHEUMATOID ARTHRITIS PATIENT WITH CHRONIC ADRENAL INSUFFICIENCY: CASE REPORT

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pneumocystis pneumonia (PCP) is a life-threatening infection that mainly occurs in immunocompromised patients. Etanercept inhibits tumor necrosis factor-alpha (TNFα) and has FDA approval to treat inflammatory arthritis including rheumatoid arthritis (RA). There are only a few cases of PCP have been reported in association to etanercept-treated RA. We report a patient with etanercept-treated RA who likley developed PCP that responded to Bactrim. CASE PRESENTATION: A 50 year old Caucasian woman with polysubstance abuse history, chronic adrenal insufficiency on hydrocortisone, and rheumatoid arthritis (RA) treated with etanercept presented from a rehabilitation facility with lethargy and sepsis. HIV was negative. Urinalysis showed 15 WBC, 4+ bacteria and + nitrite and chest X-ray (CXR) showed right lower lobe (RLL) opacities compatible with aspiration pneumonia. She was treated with IV fluids, stress dose hydrocortisone, metronidazole, and ceftriaxone and etanercept was put on hold. Blood cultures showed no bacterial growth and the urine culture grew pan-sensitive E.coli. Her lethargy improved, and sepsis resolved by day-4 of admission. On day-5, she started to have episodes of shortness of breath and became hypoxic. Arterial blood gas (ABG) on room air showed PaO2 of 46 mmHg. CXR showed worsening infiltrates. Chest computed tomography angiography showed three small peripheral pulmonary emboli, extensive bilateral interstitial infiltrates and RLL airspace disease. She was started on IV heparin. 2D echocardiogram was unremarkable. Azithromycin was added without improvement. On day-8, LDH was 277 U/L; Bactrim and prednisone were initiated and the other antibiotics were discontinued. On day-11, CXR revealed partial resolution of the bilateral infiltrates and the patient underwent bronchoscopy with bronchial washings, which were inconclusive. The patient refused a repeat diagnostic bronchoscopy. She continued to clinically improve and was discharged on day-20 on Bactrim. DISCUSSION: Patients with RA receiving biological antirheumatic drugs are at risk for developing life-threatening pulmonary fungal infections. In our case, the clinical and radiographic findings were highly suggestive of PCP despite having an inconclusive BAL, which could be explained by a low burden of organisms, inadequate specimen, and/or prior treatment. Although the patient had multiple small peripheral pulmonary embolisms, it did not explain the degree of her hypoxia and the fact that she improved with Bactrim making the diagnosis of PCP more likely. CONCLUSIONS: PCP should be suspected in hypoxic patients on etanercept therapy. In such cases coverage with Bactrim (sulfamethoxazole/trimethoprim) should be initiated on suspicion and etanercept should be discontinued. Reference #1: Tanaka M, Sakai R, Koike R, et al. Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors. Mod Rheumatol. 2012;22(6):849-858. Reference #2: Galli M, Antinori S, Atzeni F, et al. Recommendations for the management of pulmonary fungal infections in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2017;35(6):1018-1028. DISCLOSURES: No relevant relationships by Muhammad Hammami, source=Web Response No relevant relationships by ahmad irshad, source=Web Response No relevant relationships by Navneet Kaur, source=Web Response No relevant relationships by Levonti Ohanisian, source=Web Response

Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids\u2014clinical implication of primary prophylaxis using trimethoprim\u2013sulfamethoxazole

ObjectivesTo investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis.MethodsThis study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim–sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis.ResultsOne-year PCP IR in the low-dose group was 0.01 (95% CI 0.001–0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2–1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1–8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001–2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3–71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17–226)) was lower than the number needed to harm by serious ADR (45 (15–∞)).ConclusionIncidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.

Estimated Burden of Fungal Infections in Namibia.

Namibia is a sub-Saharan country with one of the highest HIV infection rates in the world. Although care and support services are available that cater for opportunistic infections related to HIV, the main focus is narrow and predominantly aimed at tuberculosis. We aimed to estimate the burden of serious fungal infections in Namibia, currently unknown, based on the size of the population at risk and available epidemiological data. Data were obtained from the World Health Organization (WHO), Joint United Nations Programme on HIV/AIDS (UNAIDS), and published reports. When no data existed, risk populations were used to estimate the frequencies of fungal infections, using the previously described methodology. The population of Namibia in 2011 was estimated at 2,459,000 and 37% were children. Among approximately 516,390 adult women, recurrent vulvovaginal candidiasis (≥4 episodes /year) is estimated to occur in 37,390 (3003/100,000 females). Using a low international average rate of 5/100,000, we estimated 125 cases of candidemia, and 19 patients with intra-abdominal candidiasis. Among survivors of pulmonary tuberculosis (TB) in Namibia 2017, 112 new cases of chronic pulmonary aspergillosis (CPA) are likely, a prevalence of 354 post-TB and a total prevalence estimate of 453 CPA patients in all. Asthma affects 11.2% of adults, 178,483 people, and so allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) were estimated in approximately 179/100,000 and 237/100,000 people, respectively. Invasive aspergillosis (IA) is estimated to affect 15 patients following leukaemia therapy, and an estimated 0.13% patients admitted to hospital with chronic obstructive pulmonary disease (COPD) (259) and 4% of HIV-related deaths (108) — a total of 383 people. The total HIV-infected population is estimated at 200,000, with 32,371 not on antiretroviral therapy (ART). Among HIV-infected patients, 543 cases of cryptococcal meningitis and 836 cases of Pneumocystis pneumonia are estimated each year. Tinea capitis infections were estimated at 53,784 cases, and mucormycosis at five cases. Data were missing for fungal keratitis and skin neglected fungal tropical diseases such as mycetoma. The present study indicates that approximately 5% of the Namibian population is affected by fungal infections. This study is not an epidemiological study—it illustrates estimates based on assumptions derived from similar studies. The estimates are incomplete and need further epidemiological and diagnostic studies to corroborate, amend them, and improve the diagnosis and management of these diseases.

The Burden of Serious Fungal Infections in Tajikistan.

Tajikistan is a low-income country in Middle Asia with a population of 8.9 million people. Five percent of the population lives on less than 1.9 USD a day and 54% live on less than 5.5 USD a day. We have estimated the burden of serious fungal infections in Tajikistan. It was estimated that 168,834 Tajik women develop recurrent vulvovaginal candidiasis. Among HIV-positive patients, we estimate 490 patients with oesophageal candidiasis and 1260 patients with oral candidiasis, 41 cases of cryptococcal meningitis and 210 cases of Pneumocystis pneumonia annually. According to our estimations there are 774 cases of chronic pulmonary aspergillosis (CPA) as a sequel of tuberculosis; CPA may occur as a consequence of multiple pulmonary conditions and the total prevalence of 4161 cases was estimated. We have estimated 6008 cased of allergic bronchopulmonary aspergillosis (ABPA) and 7930 cases of severe asthma with fungal sensitisation (SAFS), and 137 fungal asthma deaths annually. We have estimated 445 cases of candidemia a year applying a low European rate. There are approximately 283 cases of invasive aspergillosis annually. There are 189,662 (2.1% of the population) people suffering from serious fungal infections in Tajikistan. Hence, improving diagnostics is the first step of understanding a scale of the fungal burden.

The Burden of Serious Fungal Infections in Kyrgyzstan.

Kyrgyzstan in Central Asia has a population of 6 million people who have high mortality rates for chronic lung diseases. The mountainous geography, widespread use of biomass fuels for cooking and indoor heating, and high rates of smoking are the major contributing factors. We have estimated the number of serious fungal infections in order to define the burden of these diseases in Kyrgyzstan. We estimated 774 cases of chronic pulmonary aspergillosis (CPA) as a sequel of tuberculosis (TB); CPA occurs as a sequel of multiple conditions, so a total prevalence of 3097 cases was estimated, which is among the highest rates in the world. An estimated 2205 patients have allergic bronchopulmonary aspergillosis (ABPA) and 2911 have severe asthma with fungal sensitization (SAFS), which may be an underestimate. There are approximately 292 cases of invasive aspergillosis annually. The number of adult women who get recurrent vulvovaginal candidiasis is 175,949. We approximated 787 cases of oral and 294 cases of esophageal candidiasis, 25 cases of cryptococcal meningitis, and 101 cases of Pneumocystis pneumonia annually in HIV-positive patients. The incidence of candidemia was estimated at 300. We have estimated that a total of 185,961 people (3% of the population) have serious fungal infection in Kyrgyzstan. Given this burden, diagnostic improvements are necessary.

Echinocandins as alternative treatment for HIV-infected patients with Pneumocystis pneumonia.

Treatment with trimethoprim-sulfamethoxazole for Pneumocystis pneumonia (PCP) is often associated with adverse effects. Echinocandins, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, clinical experience with echinocandins in the treatment of PCP remains limited among HIV-infected patients. From August 2013 to April 2018, data of HIV-infected patients with confirmed PCP who received echinocandins as alternative treatment because of intolerance or unresponsiveness to trimethoprim-sulfamethoxazole were retrospectively reviewed to assess the effectiveness and safety of echinocandins alone or in combination with other agents. In total, 34 patients were included, with a median CD4 count of 27 cells/μl [interquartile range (IQR), 20-93). Twenty-four patients (70.6%) presented with moderate-to-severe PCP. The most common adverse effects leading to withdrawal of trimethoprim-sulfamethoxazole were hepatotoxicity (29.4%), gastrointestinal upset (23.5%), and rash (17.6%). Nine patients (26.5%) were switched to echinocandins after failure of trimethoprim-sulfamethoxazole. The median interval before switch from trimethoprim-sulfamethoxazole to echinocandins was 9.0 days (IQR 5.0-14.0). The all-cause and PCP-related in-hospital mortality rate of patients receiving echinocandins as alternative therapy was 20.6% (7/34) and 14.7% (5/34), respectively. The all-cause in-hospital mortality was 0% in mild PCP cases and 29% (7/24) in moderate-to-severe PCP cases. Patients who had failed to respond to first-line trimethoprim-sulfamethoxazole treatment tended to have a higher in-hospital mortality rate than those without first-line trimethoprim-sulfamethoxazole failure (44.4% versus 12.0%, P = 0.06). Echinocandin therapy might serve as an alternative option for HIV-infected patients with PCP who are intolerable to trimethoprim-sulfamethoxazole.

Beta-d-Glucan for Diagnosing Pneumocystis Pneumonia: a Direct Comparison between the Wako β-Glucan Assay and the Fungitell Assay.

Measuring serum beta-d-glucan (BDG) is a useful tool for supporting a quantitative PCR (qPCR)-based diagnosis of suspected Pneumocystis pneumonia (PCP) with bronchoalveolar lavage (BAL) fluid. Since the 2000s, the Fungitell assay was the only BDG assay which was FDA cleared and Conformité Européenne (CE) marked. However, the Wako β-glucan test was also recently CE marked and commercialized. We analyzed archived sera from 116 PCP cases (who were considered to have PCP based on compatible clinical and radiological findings plus a BAL fluid qPCR threshold cycle value of ≤28) and 114 controls (those with a BAL fluid qPCR threshold cycle value of >45 and no invasive fungal infection) using the Fungitell and Wako assays in parallel and assessed their diagnostic performance using the manufacturer's proposed cutoffs of 80 pg/ml and 11 pg/ml, respectively. We found the Wako assay to be more specific (0.98 versus 0.87, P < 0.001) and the Fungitell assay to be more sensitive (0.78 versus 0.85, P = 0.039) at the proposed cutoffs. Overall performance, as determined by the area under the receiver operating characteristic curve, was similar for both assays. We determined a new Wako assay cutoff (3.616 pg/ml) to match the sensitivity of the Fungitell assay (0.88 at a cutoff of ≥60 pg/ml). Using this newly proposed cutoff, the specificity of the Wako assay was significantly better than that of the Fungitell assay (0.89 versus 0.82, P = 0.011). In conclusion, the Wako assay performed excellently compared to the Fungitell assay for the diagnosis of presumed PCP based on qPCR. In addition, contrary to the Fungitell assay, the Wako assay allows for single-sample testing with lower inter- and intrarun variability. Finally, we propose an optimized cutoff for the Wako assay to reliably exclude PCP.

Clinical characteristics and T-lymphocyte subsets in 48 acquired immune deficiency syndrome patients with cytomegalovirus infections

Objective: To investigate the clinical features and T lymphocytes subsets in patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) infection. Methods: A total of 48 hospitalized patients with human immunodeficiency virus (HIV)-1/AIDS and CMV infections were recruited at Peking Union Medical College Hospital from Jan 2010 to Aug 2017. Their clinical features and immune function were retrospectively analyzed. Patients with only HIV/AIDS in previous study were recruited as controls. Results: All 48 patients were at C3 stage, including 36 men and 12 women. Five of them were younger than 30 years old, 33 cases within 31-50 years old, and 10 cases older than 50 years old. Thirty-five patients had CD(4)(+)T lymphocytes ≤ 50 cells/μl, 7 cases with CD(4)(+)T cells 51-100/μl, 3 cases with 101-200 cells/μl, and 3 cases over 200 cells/μl. As to CMV infections, there were 31 cases of CMV viremia, 1 case of CMV encephalitis, 1 case of CMV enteritis, 5 cases of CMV pneumonia, and 9 cases of CMV retinitis. Other opportunistic infections were also common including 16 cases of pneumocystis pneumonia, 9 cases of tuberculosis, 5 cases of syphilis, 18 cases of digestive tract fungal infections, 8 cases of pulmonary fungal infections, 2 cases of EB virus infections, 2 cases of HIV encephalopathy/progressive multifocal leukoencephalopathy (PML), 3 cases of cryptococcal meningitis, 1 case of toxoplasma infection. In group of both CMV and HIV/AIDS infections, 100% patients had inverted CD(4)(+)/CD(8)(+) ratio. The immune activation marker CD(8)(+)CD(38)(+)/CD(8)(+) was higher (61.6%-98.8%) with a median value of 91.2% in 40 patients. HLA-DR(+)CD(8)(+)/CD(8)(+), another marker for T cell activation, was 25.5%-98.0% in 44 patients with a median value of 60.3%. Thirty-six patients had both immune activation markers positive. There was no significant difference in counts of B cells, natural killer cells, CD(4)(+) T cells, CD(8)(+) T cells and immune activation subsets stratified by gender and age (P>0.05). Meanwhile, neither serum HIV viral load nor serum CMV viral load was correlated with HLA-DR(+)CD(8)(+)/CD(8)(+), CD(8)(+)CD(38)(+)/CD(8)(+), CD(4)(+)T cell counts, and CD(4)(+)/CD(8)(+) ratio in the CMV and HIV/AIDS co-infection group (all P>0.05), while HIV viral load in HIV/AIDS only group was significantly correlated with HLA-DR(+)CD(8)(+)T/CD(8)(+), CD(38)(+)CD(8)(+)/CD(8)(+), CD(4)(+) T cell counts, CD(4)(+)/CD(8)(+) ratio (r=0.473, 0.575, -0.767 and -0.678, respectively, all P<0.05). Conclusions: CMV infections develop in HIV patients with advanced stage. CMV infection can cause life-threatening multiple organ lesions, especially in those with CD(4)(+) T cells less than 100 cells/μl. It is of great importance to screen CMV-IgM, pp65 antigen, CMV DNA to make early diagnosis and treatment.