Epidemiology of Pneumocystis jirovecii Pneumonia in Venezuela

Current Fungal Infection Reports - The aim of this work is to contribute to the knowledge of the epidemiology of pneumocystosis or Pneumocystis jirovecii pneumonia (PCP) in Venezuela, by an updated...     

Diagnosis,Burden and Mortality of Pneumocystis jirovecii Pneumonia in Venezuela

Current Fungal Infection Reports - The aim of this work is to contribute to the knowledge of diagnosis, burden, and mortality of pneumocystosis or Pneumocystis jirovecii pneumonia (PCP) in...     

非HIV相关卡氏肺孢子菌肺炎(NH-PCP)患者的临床特点分析

目的:采用病例对照研究的方法,总结非-HIV相关卡氏肺孢子菌肺炎(NH-PCP)的临床特点,为此类患者的临床诊治提供经验.方法:回顾性分析了302医院住院的NH-PCP患者,及在Pubmed、CHKD和万方数据库中检索到的NH-PCP患者共202例,选择65例HIV相关卡氏肺孢子菌肺炎(HIV-PCP)患者作为对照研究,比较分析前者在临床表现、病程、预防、治疗及预后等方面的特征,为今后此类疾病的临床诊治提供经验.结果:与HIV-PCP组对比,NH-PCP组采用预防性治疗的比例低(5.24％ vs.29.2％,P＜0.001);确诊后开始抗感染治疗的时间晚(5.19±0.95天VS.1.1±0.27天,P＜0.005);两组患者应用激素治疗的比例无统计学差异(69.3％ vs.76.9％,P=0.238),病死率无统计学差异(36.6％ vs.27.7％,P=0.487).结论:NH-PCP组患者采取预防治疗的比例低,开始抗感染治疗的时间也较HIV-PVP延迟.这提示我们,重视NH-PCP的风险预测,给予积极的预防治疗及PCP经验性早期治疗至关重要.     

Ambient Air Pollution Associated with Suppressed Serologic Responses to Pneumocystis jirovecii in a Prospective Cohort of HIV-Infected Patients with Pneumocystis Pneumonia

Background

Ambient air pollution (AAP) may be associated with increased risk for Pneumocystis pneumonia (PCP). The mechanisms underlying this association remain uncertain.

Objectives

To determine if real-life exposures to AAP are associated with suppressed IgM antibody responses to P. jirovecii in HIV-infected (HIV+) patients with active PCP, and to determine if AAP, mediated by suppressed serologic responses to Pneumocystis, is associated with adverse clinical outcomes.

Methods

We conducted a prospective cohort study in HIV+ patients residing in San Francisco and admitted to San Francisco General Hospital with microscopically confirmed PCP. Our AAP predictors were ambient air concentrations of particulate matter of < 10 µm in diameter (PM₁₀) and < 2.5 µm in diameter (PM_2.5), nitrogen dioxide (NO₂), ozone (O₃), and sulfur dioxide (SO₂) measured immediately prior to hospital admission and 2 weeks prior to admission. Our primary outcomes were the IgM serologic responses to four recombinant P. jirovecii major surface glycoprotein (Msg) constructs: MsgC1, MsgC3, MsgC8, and MsgC9.

Results

Elevated PM₁₀ and NO₂ exposures immediately prior to and two weeks prior to hospital admission were associated with decreased IgM antibody responses to P. jirovecii Msg. For exposures immediately prior to admission, every 10 µg/m³ increase in PM₁₀ was associated with a 25 to 35% decrease in IgM responses to Msg (statistically significant for all the Msg constructs), and every 10 ppb increase in NO₂ was associated with a 19-45% decrease in IgM responses to Msg (statistically significant for MsgC8 and MsgC9). Similar findings were seen with exposures two weeks prior to admission, but for fewer of the Msg constructs.

Conclusions

Real life exposures to PM₁₀ and NO₂ were associated with suppressed IgM responses to P. jirovecii Msg in HIV+ patients admitted with PCP, suggesting a mechanism of immunotoxicity by which AAP increases host susceptibility to pulmonary infection.     

Humoral Immune Responses to Pneumocystis jirovecii Antigens in HIV-Infected and Uninfected Young Children with Pneumocystis Pneumonia

Background

Humoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood.

Methods

Consecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC) were analyzed.

Results

149 children were enrolled of whom 96 (64%) were HIV-infected. PcP occurred in 69 (72%) of HIV-infected and 14 (26%) of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP.

Conclusions

Young HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP.     

Multicenter Study of Trimethoprim/Sulfamethoxazole-Related Hepatotoxicity: Incidence and Associated Factors among HIV-Infected Patients Treated for Pneumocystis jirovecii Pneumonia

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145–0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.     

Hypertension in Renal Transplant Recipients: Role of Bilateral Nephrectomy

Of 81 transplanted kidneys which functioned for six months or more 59 were transplanted to bilaterally nephrectomized recipients and 22 to recipients who retained their own kidneys. There was an excess of hypertension in the non-nephrectomized group (17/22) as compared to 24/59 in the nephrectomized patients, though renal function was better in the non-nephrectomized group. Hypertension became much easier to control in two of the four non-nephrectomized recipients in whom bilateral nephrectomy was performed after transplantation when renal function was good.     

耶氏肺孢子菌肺炎临床特点及KL-6诊断价值

目的分析本地区耶氏孢子菌肺炎(Pneumocystis jirovecii pneumonia,PJP)患者的流行趋势、临床特征、血清学标志物,为PJP患者的早预防、早诊断提供理论依据。方法回顾性分析江西省3所综合性医院2016年1月至2019年12月诊断为PJP的49例住院患者,收集患者临床资料,包括基本信息、危险因素、临床表现、实验室结果、影像学报告、预后等。结果49例PJP患者绝大多数HIV阴性(89.8%),且以中年男性为主。AIDS、肾脏疾病(47.7%)和结缔组织疾病(29.6%)为PJP患者主要危险因素,临床表现以干咳(83.7%)、白色黏痰,发热(79.6%)为主,其次为呼吸困难。PJP患者以低剂量/短时间(<3个月)使用糖皮质激素或免疫抑制剂为特征。85%以上PJP患者实验室指标超过参考范围的有中性粒细胞百分比、C反应蛋白、氧分压、乳酸脱氢酶和涎液化糖链抗原-6(KL-6)。结论HIV阴性患者感染PJ逐渐增多,肾脏疾病和结缔组织疾病是其主要危险因素,LDH、BG和KL-6可作为PJP患者的重要辅助检查。     

Effectiveness and Long-Term Safety of Thiazolidinediones and Metformin in Renal Transplant Recipients

ObjectiveTo investigate the long-term safety and effectiveness of thiazolidinediones and metformin in renal transplant recipients with posttransplant diabetes mellitus (PTDM) or preexisting diabetes mellitus (DM).MethodsRetrospective chart review was performed for renal transplant recipients with PTDM or preexisting DM followed up during the years 2000-2006. Data collected included baseline characteristics; glomerular filtration rate (GFR); creatinine; hemoglobin A_1c; and development of congestive heart failure, edema, and liver function abnormalities. GFR was calculated using the Modification of Diet in Renal Disease study equation calculator.ResultsThirty-two patients comprised the metformin group (PTDM = 21, preexisting DM = 11), and 46 patients were included in the TZD group (PTDM = 33, preexisting DM = 13). Only 24 patients taking metformin and 31 patients taking TZDs were included for effectiveness analysis since the others required additional medications to control their DM. Mean follow-up was 16.4 months (range, 1-55 months) for patients treated with metformin and 37.1 months (range, 6-72 months) for patients treated with TZDs. GFR was decreased from baseline in all patients, but the only significant change was in patients with preexisting DM. While there was a significant change in creatinine levels in the metformin group, only 5 patients had to discontinue the drug because of this elevation (3 in preexisting DM group, 2 in PTDM group). Change in hemoglobin A_1c from baseline was not significant in either study group. Development of congestive heart failure or liver function abnormalities was not observed.ConclusionsMetformin appears to be safe in the renal transplant population for a mean duration of 16 months, although caution should be exercised using close monitoring in patients with preexisting DM. TZDs appear to be safe for a mean duration of 37 months after renal transplant. (Endocr Pract. 2008;14:979-984)     

Effect of Mycophenolate Mofetil on Plasma Bioelements in Renal Transplant Recipients

The proper concentrations of plasma bioelements may favorably reduce the incidence of metabolic disorders, which often occur during immunosuppressive therapy. Mycophenolate mofetil (MMF) is currently one of the most frequently administered immunosuppressive agents; however, MMF treatment is often related to gastrointestinal side effects. The aim of this study was thus to verify whether the MMF treatment itself, or its metabolite pharmacokinetics, has an effect on the concentrations of plasma bioelements. To determine this, the effect of MMF on the levels of both major (sodium [Na], potassium [K], calcium [Ca], magnesium [Mg]), and trace (iron [Fe], zinc [Zn], copper [Cu]) plasma bioelements in 61 renal transplant recipients was assessed in comparison to a control group (n = 45). The pharmacokinetic parameters of mycophenolic acid were determined by the high-performance liquid chromatography method. All patients filled out a 24-h diet history questionnaire. The results showed high plasma concentrations of Fe and low plasma concentrations of Mg and Zn as compared with diagnostic norms. The patients treated with MMF had significantly lower plasma Na (P < 0.001) and significantly higher plasma Zn (P = 0.030) and Cu concentrations (P < 0.001). In conclusion, MMF treatment was found to affect plasma Fe, Zn, and Cu levels by increasing their concentrations while decreasing the plasma Na concentration. Mg and Zn deficiencies, as well as excessive Fe levels, are frequently observed irrespective of the immunosuppressive regimen applied, which suggests that monitoring of these bioelements may be favorable.     

Mortality Predictors in Renal Transplant Recipients with Severe Sepsis and Septic Shock

Introduction

The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock.

Methods

Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality.

Results

A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51±13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16–23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6–2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7–19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2–2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8–102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0–22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2–9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9–16.6; p = 0.002).

Conclusions

Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.     

Serum antibody levels to the Pneumocystis jirovecii major surface glycoprotein in the diagnosis of P. jirovecii pneumonia in HIV+ patients

Background

Pneumocystis jirovecii remains an important cause of fatal pneumonia (Pneumocystis pneumonia or PcP) in HIV+ patients and other immunocompromised hosts. Despite many previous attempts, a clinically useful serologic test for P. jirovecii infection has never been developed.

Methods/Principal Findings

We analyzed serum antibody responses to the P. jirovecii major surface glycoprotein recombinant fragment C1 (MsgC1) in 110 HIV+ patients with active PcP (cases) and 63 HIV+ patients with pneumonia due to other causes (controls) by an enzyme-linked immunosorbent assay (ELISA). The cases had significantly higher IgG and IgM antibody levels to MsgC1 than the controls at hospital admission (week 0) and intervals up to at least 1 month thereafter. The sensitivity, specificity and positive predictive value (PPV) of IgG antibody levels increased from 57.2%, 61.7% and 71.5% at week 0 to 63.4%, 100%, and 100%, respectively, at weeks 3–4. The sensitivity, specificity and PPV of IgM antibody levels rose from 59.7%, 61.3%, and 79.3% at week 0 to 74.6%, 73.7%, and 89.8%, respectively, at weeks 3–4. Multivariate analysis revealed that a diagnosis of PcP was the only independent predictor of high IgG and IgM antibody levels to MsgC1. A high LDH level, a nonspecific marker of lung damage, was an independent predictor of low IgG antibody levels to MsgC1.

Conclusions/Significance

The results suggest that the ELISA shows promise as an aid to the diagnosis of PCP in situations where diagnostic procedures cannot be performed. Further studies in other patient populations are needed to better define the usefulness of this serologic test.     

Distribution and Clinical Manifestations of Cryptosporidium Species and Subtypes in HIV/AIDS Patients in Ethiopia

Background

Cryptosporidiosis is an important cause for chronic diarrhea and death in HIV/AIDS patients. Among common Cryptosporidium species in humans, C. parvum is responsible for most zoonotic infections in industrialized nations. Nevertheless, the clinical significance of C. parvum and role of zoonotic transmission in cryptosporidiosis epidemiology in developing countries remain unclear.

Methodology/Principal Findings

In this cross-sectional study, 520 HIV/AIDS patients were examined for Cryptosporidium presence in stool samples using genotyping and subtyping techniques. Altogether, 140 (26.9%) patients were positive for Cryptosporidium spp. by PCR-RFLP analysis of the small subunit rRNA gene, belonging to C. parvum (92 patients), C. hominis (25 patients), C. viatorum (10 patients), C. felis (5 patients), C. meleagridis (3 patients), C. canis (2 patients), C. xiaoi (2 patients), and mixture of C. parvum and C. hominis (1 patient). Sequence analyses of the 60 kDa glycoprotein gene revealed a high genetic diversity within the 82 C. parvum and 19 C. hominis specimens subtyped, including C. parvum zoonotic subtype families IIa (71) and IId (5) and anthroponotic subtype families IIc (2), IIb (1), IIe (1) and If-like (2), and C. hominis subtype families Id (13), Ie (5), and Ib (1). Overall, Cryptosporidium infection was associated with the occurrence of diarrhea and vomiting. Diarrhea was attributable mostly to C. parvum subtype family IIa and C. hominis, whereas vomiting was largely attributable to C. hominis and rare Cryptosporidium species. Calf contact was identified as a significant risk factor for infection with Cryptosporidium spp., especially C. parvum subtype family IIa.

Conclusions/Significance

Results of the study indicate that C. parvum is a major cause of cryptosporidiosis in HIV-positive patients and zoonotic transmission is important in cryptosporidiosis epidemiology in Ethiopia. In addition, they confirm that different Cryptosporidium species and subtypes are linked to different clinical manifestations.     

Pneumocystis jirovecii Pneumonia in Tropical and Low and Middle Income Countries: A Systematic Review and Meta-Regression

Objective

Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings.

Design

Systematic review and meta-regression.

Methods

Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies).

Results

The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p<0.0001). This was not explained by study design or diagnostic quality. Geographical area, population age, study setting and year of study also contributed to risk of PCP. Co-infection was common (444 episodes/1425 PCP cases), frequently with virulent organisms. The predictive value of symptoms, signs or simple tests in LMIC settings for diagnosis of PCP was poor. Case fatality was >30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×10^3/ml.

Conclusions

There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii, ubiquitous in all settings, then becomes a greater relative threat.