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Despite substantial progress in the long-term follow-up strategies for lung transplant recipients, morbidity and mortality remain high mostly due to the elevated infectious risk and to the development of chronic lung allograft dysfunction. The high immunosuppressive levels necessary to prevent acute rejection and the graft's constant exposure to the environment come at the high price of frequent infectious complications. Moreover, some infectious agents have been shown to trigger acute rejection or chronic allograft dysfunction. A rapid diagnostic approach followed by an early treatment and follow-up strategy are of paramount importance. They are, however, challenging endeavors due to the vast spectrum of possible pathogens and to the discrete clinical features as a consequence of transplant recipients' impaired immune response. This review proposes a stratified diagnostic strategy, discusses the most relevant pathogens and the corresponding therapeutic approaches while also offering an insight in the infection prevention strategies: vaccination, prophylaxis, preemptive therapy, antibiotic stewardship.

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Method This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL (hazard ratio [HR] 5.50, p=0.003), other DMARDs (HR 5.98, p=0.002), and serum albumin

Accurate diagnosis and treatment of patients with febrile respiratory symptoms is critical. Clinicians should not only focus on the most common conditions but also remain vigilant for other conditions that may exacerbate or result in similar presenting complaints. A detailed history is key to a successful diagnosis.

An elderly patient with multiple myeloma (MM) was being treated with several regimens and developed a severe drug eruption, necessitating the use of atovaquone instead of trimethoprim-sulfamethoxazole for pneumocystis pneumonia (PCP) prophylaxis. For progressive MM, treatment with isatuximab, an anti-CD38 monoclonal antibody, was started. During the treatment, he developed Listeria monocytogenes bacteremia and recovered quickly with ampicillin administration. CD38 is closely related to the innate immune response against L. monocytogenes, and isatuximab may increase the risk of infection. Therefore, trimethoprim-sulfamethoxazole may be useful in the prevention of not only PCP but also L. monocytogenes infection.

A 94-year-old woman with rheumatoid arthritis who had been treated with low-dose methotrexate was referred to our hospital because of a 3-day history of a fever and pancytopenia. With a diagnosis of febrile neutropenia of unknown origin, empirical antibiotic treatment and folinic acid therapy were initiated. Despite a recovery from pancytopenia, the high fever remained, and dyspnea developed. She was clinically diagnosed with Pneumocystis jirovecii pneumonia (PCP) and successfully treated with trimethoprim/sulfamethoxazole and adjunctive corticosteroid therapy. Folinic acid treatment effectively brought about rapid immune recovery but might have led to a clinical manifestation of PCP resembling immune reconstruction inflammatory syndrome.

The early initiation of antiretroviral therapy (ART) in HIV-infected patients shortly after the initiation of treatment for Pneumocystis pneumonia (PCP) has not been fully validated in a clinical s...

Objectives. The aim of the study was to investigate the cause of death of tuberculosis patients infected with the human immunodeficiency virus (HIV). Many researchers and experts note the urgency of the problem of tuberculosis combined with HIV infection in the world and in Russia. One of the main criteria for assessing the effectiveness of medical care for tuberculosis patients infected with the human immunodeficiency virus is the mortality rate.Materials and methods. For a detailed study of the causes of death of patients with tuberculosis in combination with HIV infection, we analyzed the causes of death of this contingent of patients in 5 regions of the Russian Federation.Results. The social characteristics of patients, the forms and course of the disease, the main and immediate causes of death of 223 patients with co-infection with HIV and tuberculosis were studied.Conclusion. Half of the deaths of tuberculosis patients infected with human im­munodeficiency virus were not associated with tuberculosis. Among these cases, there was either the presence of several infections at the same time, equally leading to death, or separate opportunistic infections (candidiasis, Pneumocystis pneumonia, toxoplasmosis), or cancer. In addition, the lifestyle of patients often became the cause of deaths, namely: drug poisoning and accidents, or cirrhosis of the liver, which develops as a result of alcoholism or hepatitis C infection which occurred during intravenous administration of drugs.

BACKGROUND The main aim of this study was to determine some simple but meaningful parameters that indicate immunochemotherapy-related interstitial lung disease (ILD) early in B-cell lymphoma and provide direction to hematologists. METHODS The clinical and laboratory characteristics, the treatments and outcomes of 21 B-cell lymphoma patients with ILD who underwent rituximab (RTX) -based immunochemotherapy were collected and retrospectively analyzed. RESULTS More cycles of immunochemotherapy and higher cumulative doses of RTX and doxorubicin hydrochloride liposome conferred a high risk of ILD. Compared to the baseline, patients had a significantly lower white blood cell count (WBC), absolute lymphocyte count (ALC), and albumin level (4.95×109 vs. 6.32×109, 0.71×109 vs. 1.61×109, 34.1 vs. 40.4 g/L; P

Summary Background HIV-infected patients with Pneumocystis-pneumonia (PCP) may develop paradoxical immune reconstitution inflammatory syndrome (IRIS), when combination antiretroviral therapy (cART) is started early during the course of PCP-treatment (PCPT). The aim of this study was to identify risk factors and predictors for PCP-IRIS and to improve individualized patient care. Methods An ICD-10 code hospital database query identified all Frankfurt HIV Cohort patients being diagnosed with PCP from January 2010 – June 2016. Patient charts were evaluated retrospectively for demographic, clinical and therapeutic (cART/PCPT) characteristics and incidence of paradoxical IRIS according to French's case definitions. Results IRIS occurred in 12/97 patients that started cART while on PCPT (12.4%). They had a higher rate of re-hospitalization (41.7vs. 4.7%; odds ratio (OR) 14.46; p = 0.009), intensive care treatment (66.7vs. 30.6%; OR = 4.54; p = 0.018), and longer median hospitalization (48 days vs. 23; p 6Log10/ml) before cART initiation was associated with IRIS development (41.6vs. 15.0%; OR 4.05; p = 0.042). Serum immunoglobulin G-levels (IgG) [mg/dl] were lower (894.0 vs. 1446.5; p = 0.023). Conclusion Higher hospitalization rate and morbidity parameters underscore the clinical importance of PCP-related paradoxical IRIS. A baseline viral load of > 6Log10/ml and serum IgG may help to assess individual risks for PCP-IRIS.

Background Pneumonia due to Pneumocystis jirovecii (PCP) is a frequent infection in HIV-positive and also in immunocompromised HIV-negative patients. PCR analysis of pulmonary samples has become an essential element in PCP laboratory diagnosis. Currently, many commercially PCR-based tests are available for P jirovecii detection and need to be evaluated. Objectives We evaluated the performance of the RealStar® P jirovecii PCR kit for PCP diagnosis. Methods We performed the RealStar® P jirovecii PCR and an in-house PCR in 219 pulmonary samples. We then assessed the performance of the RealStar® P jirovecii PCR kit by classifying patients in proven, probable, possible PCP or no final diagnosis, on the basis of the clinical and radiological signs and direct examination of bronchoalveolar lavage samples. Results The results showed excellent concordance (96.8%) with another in-house PCR, previously used in the laboratory. The available clinical data allowed classifying 219 patients as having proven PCP (n = 6), probable PCP (n = 27), possible PCP (n = 29) and no final diagnosis of PCP (n = 157). The RealStar® P jirovecii PCR kit performed well with samples from patients with proven and probable PCP, as indicated by the detection of P jirovecii DNA in all these samples. The percentage of positive samples in the possible PCP category was 75.9%. In patients with no final diagnosis of PCP, P jirovecii DNA was detected in 13.4% of samples, indicating colonisation by this pathogen. Conclusions The RealStar® P jirovecii PCR kit shows excellent performance for PCP diagnosis.

s Background Pneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality. Methods This is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis. Results A total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03-19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27-10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72-22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44-19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure. Conclusion Early identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.

Background Pneumocystis pneumonia (PCP) severely menaces modern chemotherapy and immunosuppression. Detailed description of the epidemiology of Pneumocystis jirovecii today is needed to identify candidates for PCP-prophylaxis. Methods We performed a 12-year retrospective study of patients with P. jirovecii detected by polymerase chain reaction in Central Norway. In total, 297 patients were included. Comprehensive biological, clinical and epidemiological data were abstracted from patients’ medical records. Regional incidence rates and testing trends were also assessed. Results From 2007 to 2017 we found a 3.3-fold increase in testing for P. jirovecii accompanied by a 1.8-fold increase in positive results. Simultaneously, regional incidence rates doubled from 5.0 cases per 100,000 person years to 10.8. A majority of the study population had predisposing conditions other than human immunodeficiency virus (HIV). Hematological (36.0%) and solid cancers (25.3%) dominated. Preceding corticosteroids were a common denominator for 72.1%. Most patients (74.4%) presented with at least two cardinal symptoms; cough, dyspnea or fever. Main clinical findings were hypoxia, cytopenias and radiological features consistent with PCP. A total of 88 (29.6%) patients required intensive care and 121 (40.7%) suffered at least one complication. In-hospital mortality was 21.5%. Three patients (1.0%) had received prophylaxis. Conclusions P. jirovecii is re-emerging; likely due to increasing immunosuppressants use. This opportunistic pathogen threatens the life of heterogenous non-HIV immunosuppressed populations currently at growth. Corticosteroids seem to be a major risk factor. A strategy to increase prophylaxis is called for.

Background Indonesia is a tropical country, warm and humid, with numerous environmental fungi. Data on fungal disease burden helps policy makers and clinicians. Objectives We have estimated the incidence and prevalence of serious fungal diseases. Methods We found all published and unpublished data and estimated the incidence and prevalence of fungal diseases based on populations at risk. HIV data were derived from UNAIDS (2017), pulmonary tuberculosis (PTB) data from 2013-2019, data on chronic pulmonary aspergillosis (CPA) was used to estimate CPA prevalence and likely deaths, COPD data from Hammond (2020), lung cancer incidence was from Globocan 2018, and fungal rhinosinusitis was estimated using community data from India. Results Overall ~7.7 million Indonesians (2.89%) have a serious fungal infection each year. The annual incidence of cryptococcosis in AIDS was 7,540. Pneumocystis pneumonia incidence was estimated at 15,400 in HIV and an equal number in non-HIV patients. An estimated 1% and 0.2% of new AIDS patients have disseminated histoplasmosis or Talaromyces marneffei infection. The incidence of candidemia is 26,710. The annual incidence of invasive aspergillosis was estimated at 49,500 and the prevalence of CPA is at 378,700 cases. Allergic bronchopulmonary aspergillosis prevalence in adults is estimated at 336,200, severe asthma with fungal sensitization at 443,800, and fungal rhino sinusitis at 294,000. Recurrent vulvovaginal candidiasis is estimated at 5 million/ year (15 - 50 years old). The incidence of fungal keratitis around 40,050. Tinea capitis prevalence in schoolchildren about 729,000. Conclusions Indonesia has a high burden of fungal infections.

One of the phenomena during the current Covid-19 pandemic is Early Detection of In-Patient Deterioration by public health services, especially general hospitals for early detection patients who admit with respiratory tract infections (RTIs) symptoms. However, there is a risk of misdiagnosis in differential diagnoses. Pneumocytis Carinii Pneumonia (PCP) is an opportunistic infection that can occur in immunocompromised patients. Symptoms that often appear are similar to Covid-19, such as fever, cough, runny nose, dyspnoea, diarrhea or others. It makes some difficulties for early diagnosing PCP infection during Covid-19 pandemic, whereas if it is not early treated it is could be a fatal case. Thus, during Covid-19 pandemic, it is necessary to consider other differential diagnoses in patients with RTIs symptoms or respiratory distress. It can be supported if other characteristic signs are found during clinical examination, especially if the nasopharyngeal and oropharyngeal swab results are negative.

Objectives: An elevated serum (1-3)-β-D-glucan (BDG) concentration has high sensitivity for a diagnosis of Pneumocystis pneumonia (PCP) in people with HIV (PWH). At the current manufacturer-recommended positive threshold of 80 pg/mL (Fungitell), specificity for PCP is variable and other diagnostic tests are required. We evaluated the utility of serum BDG for diagnosis of suspected PCP in PWH at three inner-London hospitals to determine BDG concentrations for diagnosis and exclusion of PCP. Methods: From clinical case records, we abstracted demographic and clinical information and categorised patients as having confirmed or probable PCP, or an alternative diagnosis. We calculated sensitivity, specificity and positive predictive value (PPV) of serum BDG concentrations >400 pg/mL and negative predictive value (NPV) of BDG 400 pg/mL had a sensitivity of 83%, specificity of 97% and PPV 97% for diagnosis of PCP; BDG 400 pg/mL effectively confirm the diagnosis. Values 80–400 pg/mL should prompt additional diagnostic tests.

Background Pneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance. Methods We retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis. Results Among 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients’ mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts. Conclusion Renal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome.

Background Pneumocystis pneumonia (PcP), which is caused by Pneumocystis carinii, is a life-threatening infection that affects immunocompromised individuals. Unfortunately, chemoprophylaxis and dapsone are only effective for half of the patients with PcP, indicating that additional preventive methods are needed. We predicated the pneumocystis surface protein A12 sequence 1–85 by DNAStar software and BepiPred, and identified it as a potential vaccine candidate by bioresearch. Methods We used recombinant A121–85 as antigen to immunized mice and detected serum titer of IgG, expression of inflammatory factors by EILSA, qRT-PCR and flow cytometry. Results Our results showed that immunization with recombinant A121–85 increased the serum titer of IgG, promoted the secretion of T lymphocytes, increased the expression of inflammatory factors, and elevated lung inflammatory injury in mice. Conclusions Our findings suggest that A121–85 is a potential vaccine target for preventing Pneumocystis carinii. The evaluation of A121–85-elicited antibodies in the prevention of PcP in humans deserves further investigation.

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.

HIV-infection is a long-term infectious disease, characterized by deterioration of the immune system and it is often complicated by the development of opportunistic diseases, mainly of infectious origin. HIV-associated infections become generalized in the late stages of the disease and often may combine, that makes challenges in the diagnosis of these diseases. Differential morphological diagnosis of HIV-associated lung infections is quite complex. Most frequently, there is the need to differentiate between tuberculosis, bacterial or septic pneumonia, cytomegalovirus lung lesions, and deep mycoses. The aim. To demonstrate the expediency and necessity to apply special complex morphological methods in HIV-infected patients with secondary lung lesions using the series of clinical cases as an example. Materials and methods. The case series consisted of 7 cases with discordance between the clinical-radiologic, laboratory data and histological conclusions. Of these, there were 5 cases of life-time and 2 autopsy diagnoses. All the clinical and laboratory data of these cases were retrospectively analyzed, and a number of additional special histological examinations were performed. The Ziehl–Neelsen and fluorescent methods, Gomori–Grocot and alcian blue-PAS staining as well as immunohistochemical examinations were used for the detection of mycobacterial antigens with different antibodies to M. tuberculosis. Results. The case series of initial morphological misdiagnosis or indeterminate histological diagnosis was revealed among hospitalized HIV-infected patients. Clinical data did not provide an accurate diagnosis of pulmonary pathology. According to the traditional histological examination, a tuberculous process was diagnosed in 3 cases, a chronic granulomatous process – in 2 cases, but without specifying the etiology. In two cases of autopsy, pneumocystis pneumonia was suspected in combination with other infections. Additional morphological examination with using 2–6 special methods made it possible to determine the correct diagnosis. In 2 cases of provisional diagnosis of tuberculosis, invasive cryptococcosis and “pneumonia in a drug user” were revealed. Cryptococcosis and pneumocystis pneumonia were detected in 2 cases with an unspecified process. In the autopsy cases, the diagnosis of pneumocystis pneumonia was ruled out, while viral-bacterial pneumonia and tuberculosis associated with cytomegalovirus infection were detected. Conclusions. The presented factual material demonstrates the principal importance of using a comprehensive morphological examination in cases of lung inflammatory processes in HIV-infected patients. Clinical patient data, namely HIV-status at the time of diagnostic procedures as well as radiological and microbiological findings serve as a substantial aid in the diagnosis.

Objective – to establish the spectrum of secondary pathology of the thoracic organs in HIV-infected patients of phthisiopulmonary profile with inpatient treatment in the last 5 years, taking into account the appointment of antiretroviral therapy (ART) and the level of CD4+ T-lymphocytes in peripheral blood. Materials and methods. A cohort retrospective study was carried out. The group included 434 indivi-duals who were hospitalized in the clinic of the SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMN of Ukraine» in the period 2015—2019, with a confirmed diagnosis of HIV infection. Anamnestic, and clinical and laboratory data of patients were obtained from paper out patient and inpatient case histories, the electronic database of the Institute EMCIMED.Results and discussion. The data on the number of cases and the time of ART administration, the established CD4+ cell level, and final diagnoses of secondary diseases of various thoracic organs in hospitalized patients with HIV were analyzed and compared. On the whole, an unsatisfactory situation with the appointment of ART was established in accordance with the latest WHO and Ukrainian protocols on the medical management of people living with HIV. Surgical mini-invasive therapeutic and diagnostic manipulations and surgical interventions were performed in 183 (42.2 %) patients. Low levels of CD4 cells were determined in all patients, regardless of the type of established secondary disease. In 53.2 % of cases with various types of tuberculous lesions (lungs, pleura, peripheral lymph nodes) and when TB is combined with other secondary diseases, the level of CD4 T-lymphocytes was less than 200 cells/µL. In the spectrum of secondary diseases, TB of one or more organs of the thorax predominated, 75.8 % of cases. Among other secondary diseases, Pneumocystis pneumonia and lymphadenitis took the second and third places in the frequency of detection. Conclusions. In the structure of secondary diseases of thoracic organs among hospitalized patients with HIV infection in the last five years, as before, tuberculosis is in the lead. Among all patients with HIV and secondary diseases of the thorax organs, regardless of the type of diseases, cases with an average CD4-lymphocyte level less than 400 cells/µL prevailed.Only 53.0 % of patients received ART, and more than a third of them were prescribed ART during hospitalization at the Institute’s clinic. In another third of cases, specific therapy was not prescribed at all.

Pneumocystis jirovecii, the fungal agent of human Pneumocystis pneumonia, is closely related to macaque Pneumocystis. Little is known about other Pneumocystis species in distantly related mammals, none of which are capable of establishing infection in humans. The molecular basis of host specificity in Pneumocystis remains unknown as experiments are limited due to an inability to culture any species in vitro. To explore Pneumocystis evolutionary adaptations, we have sequenced the genomes of species infecting macaques, rabbits, dogs and rats and compared them to available genomes of species infecting humans, mice and rats. Complete whole genome sequence data enables analysis and robust phylogeny, identification of important genetic features of the host adaptation, and estimation of speciation timing relative to the rise of their mammalian hosts. Our data reveals insights into the evolution of P. jirovecii, the sole member of the genus able to infect humans., Cissé, Ma et al. utilize genomic data from Pneumocystis species infecting macaques, rabbit, dogs and rats to investigate the molecular basis of host specificity in Pneumocystis. Their analyses provide insight to the specific adaptations enabling the infection of humans by P. jirovecii.

People with HIV can present to acute medicine services with problems related to their HIV or the consequences of a weakened immune system. A basic understanding of how to evaluate the risk of opportunistic infections and how to recognize the syndromes caused by them is essential. Expert help is often needed, but prompt recognition and good early management of the acutely unwell patient with HIV can prevent further deterioration.

Genetic diagnostic tools including whole-exome sequencing (WES) have advanced our understanding in human diseases and become common practice in diagnosing patients with suspected primary immune deficiencies. Establishing a genetic diagnosis is of paramount importance for tailoring adequate therapeutic regimens, including identifying the need for hematopoietic stem cell transplantation (HSCT) and genetic-based therapies. Here, we genetically studied two adult patients who were clinically diagnosed during infancy with severe combined immune deficiency (SCID). Two unrelated patients, both of consanguineous kindred, underwent WES in adulthood, 2 decades after their initial clinical manifestations. Upon clinical presentation, immunological workup was performed, which led to a diagnosis of SCID. The patients presented during infancy with failure to thrive, generalized erythematous rash, and recurrent gastrointestinal and respiratory tract infections, including episodes of Pneumocystis pneumonia infection and Candida albicans fungemia. Hypogammaglobulinemia and T-cell lymphopenia were detected. Both patients were treated with a 10/10 HLA matched sibling donor unconditioned HSCT. Retrospective genetic workup revealed homozygous bi-allelic mutations in IL7RA in one patient and in RAG2 in the other. Our study exemplifies the impact of retrospectively establishing a genetic diagnosis. Pinpointing the genetic cause raises several issues including optimized surveillance and treatment, understanding disease mechanisms and outcomes, future family planning, and social and psychological considerations.

The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18 years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according to the administration of AP: (1) treated with AP (N= 34; 51%) and (2) not treated with AP (N=33, 49%). AP consisted of combined trimethoprim/sulfamethoxazole (TMP/SMX) and acyclovir (AC) in half of patients. TPM/SMX as a single agent was adopted in 32% patients and one patient received only AC. Overall, infections were experienced in 15% of patients during follow-up with a similar proportion in the 2 groups (treated and not treated) of patients (14.7% vs 15%). Clinical course of infections was however, less severe in patients treated with AP, where all infections were grade 2 and did not require hospitalization. In neither group of patients was reported Pneumocystis pneumonia. In conclusion, despite the absence of clear evidence, our analysis shows that AP in patients with ITP receiving RTX is frequently adopted, even if in the absence of well-defined criteria. Prophylaxis administration is quite consistent within the same haematological Center; thus, it seems related to clinicians' experience.

Background. Pneumocystis jirovecii pneumonia (PCP) is an opportunistic and prevalent fungal infection in immunocompromised hosts, including patients after kidney transplantation (KTx). It is a life threatening infection. While with effective prophylaxis it became less common, it still remains an issue among solid organ transplant (SOT) recipients during the first year. There are no specific clinical signs for PCP. Computed tomography (CT) is a better method for detecting PCP, but definite diagnosis can only be made by identification of the microorganism either by a microscopy or by a polymerase chain reaction (PCR).Clinical case. We present a case of a 17 year old with severe PCP 13 months after KTx followed by reduction in kidney function and respiratory compromise. The pathogen was detected by PCR from bronchoalveolar lavage fluid (BALF) and patient was treated successfully with trimethoprim-sulfamethoxazole (TMP-SMX). Patient’s condition, respiratory status and kidney function gradually improved. Our presented case is unusual because patient had no known risk factors for PCP and he was more than one year after KTx, what is considered rare. In addition patient and his parents delayed in notifying the treating physician about ongoing symptoms because did not deem them important enough.Conclusions. Clinicians treating patients in risk groups for PCP must always remain vigilant even in era of effective prophylaxis. The vigilance should also extend to the patient and patient’s family.

To differentiate between infectious and non-infectious diseases occurring in immunocompromised patients without acquired immunodeficiency syndrome (AIDS) using high-resolution computed tomography (HRCT).HRCT images of 555 patients with chest complications were reviewed retrospectively. Infectious diseases (n=341) included bacterial pneumonia (n=123), fungal infection (n=80), septic emboli (n=11), tuberculosis (n=15), pneumocystis pneumonia (n=101), and cytomegalovirus pneumonia (n=11), while non-infectious diseases (n=214) included drug toxicity (n=84), infiltration of underlying diseases (n=83), idiopathic pneumonia syndrome (n=34), diffuse alveolar haemorrhage (n=8), and pulmonary oedema (n=5). Lung parenchymal abnormalities were compared between the two groups using the χThe χ2 test results showed significant differences in many HRCT findings between the two groups. Multiple logistic regression analysis results indicated the presence of nodules with a halo and the absence of interlobular septal (ILS) thickening were the significant indicators that could differentiate infectious from non-infectious diseases. ILS thickening was generally less frequent among most infectious diseases and more frequent among most non-infectious diseases, with a good odds ratio (7.887, p0.001). The sensitivity and accuracy for infectious diseases in the absence of ILS thickening were better (70% and 73%, respectively) than those of nodules with a halo (19% and 48%, respectively), while the specificity in the nodules with a halo was better (93%) than that of ILS thickening (78%).The presence of nodules with a halo or the absence of ILS thickening tends to suggest infectious disease. Specifically, ILS thickening seems to be a more reliable indicator.

Introduction: In recent years, there has been an increase in the number of systemic fungal infections among HIV-infected individuals. The article aimed to examine the frequency of invasive mycoses among the HIV-infected patients at the time of their urgent and/or planned admission to a specialized hospital. Methods: The diagnostic methods used in this study involved physical examination, laboratory testing, bacteriological examination, immunological examination, molecular genetic testing, and radiological imaging. The study was conducted under the ethical guidelines for retrospective studies and does not disclose data on individual patients. Results: Between 2016 and 2018, 85 HIV patients who died with HIV history underwent a series of clinical and pathomorphological examinations at the Novgorod Regional Infectious Diseases Hospital. Systemic mycoses frequently occur in the respiratory system and less often in the brain. Their incidence is severe and the mortality rates associated with it are high. In this study, PCP was the most common cause of death provoked by mycoses. Discussion/Conclusion: Systemic fungal disease can be diagnosed through a combination of diagnostic methods. A crucial factor in the reduction of mortality rates for systemic mycosis is the early diagnosis and intensive antimicrobial therapy.

Background Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection. Methods This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR. Results Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (pp=0.002), dyspnea (p=0.003), crept (p=0.01), and chest X-ray findings (p Conclusion Confirmed cases of P. jirovecii showed higher IL-2, IL-4, IL-10, and IL-13 mRNA expression comparatively to negative cases. Increased expression of cytokines may be indicative of infection severity and could help in patients’ management.

A 67-year-old woman with rheumatoid arthritis (RA) presented with fever and dyspnea. Chest radiography and computed tomography (CT) revealed pulmonary infiltrates with ground-glass opacities. We considered bacterial or pneumocystis pneumonia because she was immunocompromised due to RA treatment. However, she had tachycardia and elevated D-dimer levels. We performed contrast-enhanced CT and subsequently diagnosed her with pulmonary embolism (PE). Though PE is not usually accompanied by parenchymal pulmonary shadows, pulmonary infarction may cause pulmonary infiltrates that can be mistaken for pneumonia. As RA is a thrombophilic disease, clinicians should be aware of PE and pneumonia as differential diagnoses in such patients.

Pneumocystis pneumonia (PCP) and pulmonary tuberculosis infection (PTB) are important opportunistic infections in HIV-infected patients. The diagnosis remains challenging since Pneumocystis jirovecii cannot be cultured, and expectorated-sputum is frequently difficult to obtain. The monoclonal-antibody detection for P. jirovecii from induced sputum is promising in diagnosing PCP. This study determined the percentage of PCP in HIV-infected patients with pulmonary infiltrates at three government hospitals in Jakarta. The concurrent infection of PTB was carefully documented as well. This cross-sectional study was carried out by documenting the clinical symptoms, laboratory findings, chest X-ray, while clinical outcomes were evaluated during hospitalization. The sputum induction was conducted for P. jirovecii with monoclonal antibody detection at the laboratory of Parasitology Department, Faculty of Medicine Universitas Indonesia, as well as Ziehl-Nielsen staining for PTB. The results indicated that of 55 HIV-infected patients with pulmonary infiltrates, the positive monoclonal antibody for P. jirovecii was detected in eight patients (14.6%). Weight loss, fever, shortness of breath, and crackles were found in all PCP patients; while dry cough in five patients. Moreover, PTB cases with positive acid-fast bacilli (AFB) was detected in five patients (9.1%), the PTB cases with negative AFB was 43.6% (24 out of 55 patients), and the rest 26 patients (47.3%) were not proven to have PTB. The concurrent infections of PCP and PTB were documented in three out of five positive AFB patients. The clinical outcome of eight PCP patients showed improvement in five patients, but the other three patients died. Laboratory findings play an important role in the diagnosis of PCP and PTB, along with clinical characteristics and radiological features. Low CD4+ cell count was considered a possible risk factor for PCP and poor clinical outcomes.

Pulmonary specimen pairs from five patients who presented with pulmonary colonization and later developed Pneumocystis Pneumonia (PcP) were retrospectively examined for P. jirovecii genotyping. A match of genotypes in pulmonary specimen pairs of three patients was observed, whereas a partial match and a mismatch were observed in the fourth and fifth patients, respectively. The genotyping results suggest that the colonization state can differ from PcP but can also represent the incubation period of PcP. Clinicians should not systematically rule out the treatment of putative colonized patients and should at least discuss the initiation of prophylaxis on a case-by-case basis.The results suggest that clinicians should not systematically rule out the treatment of putative patients colonized by Pneumocystis jirovecii and should at least discuss prophylaxis initiation on a case-by-case basis.

Introduction: Nigeria has a large estimated burden of AIDS-related mycoses. We aimed to determine the proportion of pa- tients with AIDS-related opportunistic fungal infections (OFIs) at an urban antiretroviral treatment (ART) centre in Nigeria. Methods: A retrospective analysis of a cohort of ART-naïve, HIV-infected patients, assessed for ART eligibility and ART- experience at the PEPFAR outpatient clinic at Lagos University Teaching Hospital over a 12-year period (April 2004-Feb- ruary 2016) was conducted. Results: During this period, 7,034 patients visited the clinic: 4,797 (68.2%) were female; 6161 patients had a recorded base- line CD4 count, and the median CD4 count was 184 cells/µl (IQR, 84-328). A baseline HIV-1 viral load (VL) was recorded for 5,908 patients; the median VL was 51,194 RNA copies/ml (IQR, 2,316-283,508) and 6,179/7046(88%) had initiated ART. Some 2,456 (34.9%) had a documented opportunistic infections, of whom 1,306 (18.6%) had an opportunistic fungal infection. The total number of OFI episodes was 1,632: oral candidiasis (n=1,473, 90.3%), oesophageal candidiasis (n=118; 8%), superficial mycoses (n=23; 1.6%), Pneumocystis pneumonia (PJP) (n=13; 0.8%), and cryptococcal meningitis(CM) (n=5; 0.4%). 113 (1.6%) were known to have died in the cohort. Conclusion: Approximately 1 in 5 HIV-infected patients in this retrospective cohort, most of whom had initiated ART, were clinically diagnosed with an OFI. Improved access to simple accurate diagnostic tests for CM and PJP should be pri- oritised for this setting. Keywords: Opportunistic fungal infections; ART Adherence; Advanced HIV disease.