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Pneumocystis jirovecii pneumonia (PJP) is one of the leading opportunistic infections seen in people living with HIV. Bilateral infiltrations characterize PJP and miliary involvement is very rare. In this article, we report a 32-year-old person living with HIV who was followed up with a diagnosis of miliary PJP. Our patient was admitted to the hospital with complaints of cough, sputum, and weight loss. Initially, miliary tuberculosis was considered due to the presence of miliary involvement on chest radiography, but the diagnosis was made with P. jirovecii PCR positivity. This article aims to report a case of miliary PJP, a rare clinical form of PJP., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Seronegative human immunodeficiency virus (HIV) infection, where an HIV-specific antibody response is lacking even in chronic or late-stage HIV infections, is extremely rare. Here, we report the case of a 50-year-old Japanese man presenting with Pneumocystis pneumonia who did not produce antibodies against HIV-1 until the initiation of antiretroviral therapy (ART). Fourth-generation antigen-antibody testing temporarily reverted from weakly positive to negative soon after initiating ART, likely due to a reduction in viral load (assessed by p24 antigen levels). His HIV-1 antibody titers remained low or indeterminate even after four years of ART. A literature review suggested that the absence of HIV-1-specific antibody production may be associated with unimpeded HIV replication and rapid CD4 + T cell decline. Seronegative HIV infection can lead to deferred diagnosis and treatment, thereby increasing the risk of transmitting the virus to others or developing opportunistic illnesses. It is important to combine multiple tests for diagnosis, depending on the medical condition. Further studies are required to investigate the host factors involved in the production of HIV-1-specific antibodies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

We assessed predictive models (PMs) for diagnosing Pneumocystis jirovecii pneumonia (PCP) in AIDS patients seen in the emergency room (ER), aiming to guide empirical treatment decisions. Data from suspected PCP cases among AIDS patients were gathered prospectively at a reference hospital's ER, with diagnoses later confirmed through sputum PCR analysis. We compared clinical, laboratory, and radiological data between PCP and non-PCP groups, using the Boruta algorithm to confirm significant differences. We evaluated ten PMs tailored for various ERs resource levels to diagnose PCP. Four scenarios were created, two based on X-ray findings (diffuse interstitial infiltrate) and two on CT scans ("ground-glass"), incorporating mandatory variables: lactate dehydrogenase, O2 sat , C-reactive protein, respiratory rate (> 24 bpm), and dry cough. We also assessed HIV viral load and CD4 cell count. Among the 86 patients in the study, each model considered either 6 or 8 parameters, depending on the scenario. Many models performed well, with accuracy, precision, recall, and AUC scores > 0.8. Notably, nearest neighbor and naïve Bayes excelled (scores > 0.9) in specific scenarios. Surprisingly, HIV viral load and CD4 cell count did not improve model performance. In conclusion, ER-based PMs using readily available data can significantly aid PCP treatment decisions in AIDS patients., (© 2024. The Author(s).)

Pneumocystis jirovecii is an opportunistic fungus that can cause severe and potentially fatal Pneumocystis pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic polymorphisms of P. jirovecii at eight different loci, including six nuclear genes (ITS, 26S rRNA, sod , dhps , dhfr and β-Tub) and two mitochondrial genes (mtLSU-rRNA and cyb ) in three PCP cases, including two patients with HIV infection and one without HIV infection in Shanxi Province, P.R. China. The gene targets were amplified by PCR followed by sequencing of plasmid clones. The HIV-negative patient showed a coinfection with two genotypes of P. jirovecii at six of the eight loci sequenced. Of the two HIV-positive patients, one showed a coinfection with two genotypes of P. jirovecii at the same two of the six loci as in the HIV-negative patient, while the other showed a single infection at all eight loci sequenced. None of the three drug target genes ( dhfr, dhps and cyb ) showed mutations known to be potentially associated with drug resistance. This is the first report of genetic polymorphisms of P. jirovecii in PCP patients in Shanxi Province, China. Our findings expand our understanding of the genetic diversity of P. jirovecii in China., (© 2022 Ting Xue et al., published by Sciendo.)

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: Mannose-binding lectin (MBL) plays a pivotal role in innate immunity; however, its impact on susceptibility to opportunistic infections (OIs) has not yet been examined in a natural history cohort of people living with HIV/AIDS., Methods: We used archived samples to analyze the association between MBL expression types and risk of major OIs including Pneumocystis jirovecii pneumonia (PCP), cryptococcosis, talaromycosis, toxoplasmosis, and tuberculosis in a prospective cohort in Northern Thailand conducted from 1 July 2000 to 15 October 2002 before the national antiretroviral treatment programme was launched., Results: Of 632 patients, PCP was diagnosed in 96 (15.2%) patients, including 45 patients with new episodes during the follow-up period (1006.5 person-years). The total history of PCP was significantly associated with low MBL expression type: high/intermediate (81/587, 13.8%), low (10/33, 30.3%) and deficient (5/12, 41.7%) (p = 0.001), whereas the history of other OIs showed no relation with any MBL expression type. Kaplan-Meier analysis (n = 569; log-rank p = 0.011) and Cox's proportional hazards model revealed that deficient genotype dramatically increased the risk of PCP, which is independent upon sex, age, CD4 count, HIV-1 viral load and hepatitis B and C status (adjusted hazard ratio 7.93, 95% confidence interval 2.19-28.67, p = 0.002)., Conclusions: Deficiency of MBL expression is a strong risk factor determining the incidence of PCP but not other major OIs., Competing Interests: The authors have declared that no competing interests exist.

Pneumocystis carinii pneumonia (PCP) is an opportunistic infection of the lung occurring primarily in patients with HIV infection with a CD4 cell count <200 mm 3 , solid organ transplant recipients and those taking immunosuppressive therapy. The 1980s heralded the HIV pandemic, turning PCP into a major medical and public health problem worldwide. Manifestations of unusual infections such as pneumocystis and Kaposi's sarcoma, were, after all, the first signs of the emerging pandemic to be recognised and may indeed, be the presenting feature of a previously undiagnosed HIV infection. With the advent of pneumocystis chemoprophylaxis and the initiation of highly active antiretroviral therapy, there has been a decreased incidence in developed countries, but it remains high in developing countries. Unfortunately, late presentation of HIV remains a problem resulting in significant morbidity and mortality. The authors report the case of a new diagnosis of HIV infection in a 45-year-old woman, presenting with a dry cough, dyspnoea, unintentional weight loss and PCP. Two weeks after commencing highly active antiretroviral therapy, she was diagnosed with immune reconstitution inflammatory syndrome. Research shows that stigma and discrimination in the healthcare setting contributes to keeping individuals from accessing HIV prevention, care and treatment services and adopting key preventive behaviours. The barriers to HIV testing and stigma eradication in primary care will be explored as well as missed opportunities to diagnosis HIV in primary care in individuals presenting with signs and symptoms of immunosuppression, in this case shingles., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND Patients with HIV infection tend to have poor intensive care unit (ICU) outcomes; however, survival in the modern combination antiretroviral therapy (cART) era has markedly improved, but Pneumocystis jirovecii pneumonia (PJP) still remains a preeminent cause of respiratory failure in AIDS patients. Extracorporeal membrane oxygenation (ECMO) is an adapted cardiopulmonary bypass circuit for temporary life support for patients not responding to conventional treatment. CASE REPORT A 43-year-old male HIV "late presenter" was admitted to our hospital for fever and dyspnea. A chest CT scan revealed bilateral ground-glass opacities. Empiric antibiotic treatment and cART were started. The emergence of ARDS due to PJP dictated urgent veno-venous (VV) ECMO placement. One week later, radiologic findings and respiratory function had improved and the patient was started on a weaning trial from ECMO and removed 12 days after placement. CONCLUSIONS Acute respiratory distress syndrome (ARDS) is a potentially reversible clinical syndrome with a high mortality rate. ECMO is a rescue therapy allowing lung recovery during acute processes and should be considered an adequate treatment option in HIV+ patients with respiratory failure. ECMO should be considered a useful and adequate treatment option in AIDS patients who have a high risk of dying from respiratory failure.

Subsequent to the increasing use of immunosuppressant therapy, Pneumocystis jirovecii pneumonia (PcP) has emerged as a life-threatening condition in human immunodeficiency virus (HIV)-negative patients. We investigated changes in epidemiological and clinical characteristics among PcP cases with and without HIV infections. Data of 424 patients diagnosed with PcP in a 2,700-bed Korean tertiary care hospital between February 2003 and April 2017 were retrospectively analyzed. The study included patients with compatible clinical findings in whom PcP was confirmed via direct immunofluorescence assay. The annual average number of cases increased from 12.2 (initial 5-year period) to 42.2 (recent 5-year period). In HIV-negative patients, hematologic malignancy (34.8%) and solid organ transplantation (32.9%) were the most frequent major underlying conditions, and immunosuppressive therapies including corticosteroids (342/362, 94.5%) and chemotherapy (122/362, 33.7%) were significantly associated with PcP infection (p ＜ 0.001 for both). The incidence of PcP has continued to increase among non-HIV-infected immunocompromised patients in recent years.

Background: Pneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-β-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients., Methods: This was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5 days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4 + cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria., Results: All patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200 pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum., Conclusion: In this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13 years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.

Background: Fibrosing interstitial lung disease is the poor prognostic non-infectious lung disease by unknown etiology. Here, we present one case developing interstitial pneumonia with fibrosis after treatment of pneumocystis pneumonia (PCP) in newly diagnosed HIV-1 infected case., Case Presentation: A previously healthy 63-year old male was referred to our institute because of protracted dyspnea on effort in 2 weeks after pneumocystis pneumonia treatment. At referral, arterial blood oxygen pressure was within normal range (93.5 mmHg) at rest, but decreased rapidly 30 s after a slow walk (44.5 mmHg). Respiratory function tests showed severe restrictive ventilator impairment (vital capacity = 36.5%; forced expiratory volume in 1 s = 107.4%). Chest computed tomography showed severe fibrotic changes at bilateral basal parts and diffuse fibrotic changes in which PCP lesions were seen initially in previous images although β-D glucan was not elevated and P. jirovecii was not detected in saliva at referral. Other etiologies of fibrotic IP including infectious and/or autoimmune diseases were excluded by serology. Fibrotic lesion did not expand thereafter although it had not responded to the high-dose corticosteroid therapy., Conclusion: We report the first case of fibrosing interstitial lung disease triggered by HIV-related PCP.

Concurrent Pneumocystis jirovecii (PJ) and pulmonary histoplasmosis (PHP) are rare in a single HIV individual. We present a challenging case of concomitant PJ and PHP in a young HIV individual. A 44-year-old man presented to the emergency department with progressive pulmonary symptoms. He was hypoxic with bilateral pulmonary opacities on chest radiograph. CT of the chest showed a geographical pattern of ground-glass attenuation. He started receiving intravenous antibiotics in addition to oral Bactrim for suspected PJ. He also began receiving itraconazole, given suspected PHP with recent bat-droppings exposure. HIV test was positive, though history was negative; the CD4 count was 5 cells/mm 3 Later, he developed respiratory failure without clinical improvement. First bronchoalveolar lavage (BAL) failed to confirm opportunistic pathogens. Repeat BAL revealed PJ but no Histoplasma. Histoplasma antigens were positive, confirming histoplasmosis. The patient died despite aggressive treatment with intravenous Bactrim and amphotericin B., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: A clinical study was conduct in HIV-infected children to evaluate the prophylactic doses of cotrimoxazole [sulfamethoxazole (SMX) and trimethoprim (TMP)] advised by the WHO., Methods: Children received lopinavir-based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/40 mg of TMP once daily). A nonlinear mixed effects modelling approach was used to analyse plasma concentrations. Factors that could impact the pharmacokinetic profile were investigated. The model was subsequently used to simulate individual exposure and evaluate different administration schemes., Results: The cohort comprised 136 children [average age: 1.9 years (range: [0.7-4]), average weight: 9.5 kg (range: [6-16.3])]. A dose per kg was justified by the significant influence of implementing an allometrically scaled body size covariate on SMX and TMP pharmacokinetics. SMX and TPM clearance were estimated at 0.49 l h -1 /9.5 kg and 3.06 l h -1 /9.5 kg, respectively. The simulated exposures obtained after administration of oral dosing recommended by the WHO for children from 10 to 15 kg were significantly lower than in adults for SMX and TMP. This could induce a reduction of effectiveness of cotrimoxazole. Simulations show that regimens of 30 mg kg -1 of SMX and 6 mg kg -1 of TMP in the 5-10 kg group and 25 mg kg -1 of SMX and 5 mg kg -1 of TMP in the 10-15 kg group are more suitable doses., Conclusions: In this context of high prevalence of opportunistic infections, a lower exposure to cotrimoxazole in children than adults was noted. To achieve comparable exposure to adults, a dosing scheme per kg was proposed., (© 2017 The British Pharmacological Society.)

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life-threatening opportunistic infection in HIV-infected patients. However, non-HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co-infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non-HIV patients. Two cases of pulmonary co-infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non-HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non-Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co-infection by P. jirovecii and other fungi in non-HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion., (© 2017 Blackwell Verlag GmbH.)

Pneumocystosis (PCP) mortality in the U.S. has received less attention in recent years. This study describes recent trends in mortality and the estimated burden of PCP in the U.S., using the national multiple cause of death data during 1999-2014. PCP mortality rates were calculated for age, sex, race and year. Demographic differences were presented for decedents with and without a human immunodeficiency virus (HIV) co-diagnosis. Matched odds ratios (MOR) were generated to describe associations between non-HIV conditions and PCP mortality. In total, 11 512 PCP deaths occurred during 1999-2014. Annual age-adjusted PCP mortality decreased over this time period, from 0.479 to 0.154 per 100 000 population (1999 vs 2014 respectively). Over two-thirds of decedents were male and Blacks had the highest mortality as compared to Whites. HIV co-diagnosis accounted for 48% of all PCP deaths in 2014 vs 71% in 1999. Comorbid conditions such as connective tissue disorders (MOR=12.29; 95% confidence interval=[10.26, 14.71]) were associated with a PCP diagnosis. Productivity losses amounted to >$12 billion during the study period. Although widespread use of antiretroviral therapy and PCP prophylaxis for HIV infection likely contributed to the overall decline in PCP deaths during 1999-2014, a continual need exists to prevent and treat this fungal disease in immune-compromised populations that are not infected with HIV., (© 2017 Blackwell Verlag GmbH.)

Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP., (Copyright © 2017 American Society for Microbiology.)

Pneumocystosis is an opportunistic disease caused by invasion of unicellular fungus Pneumocystic jirovecii which is responsible for febrile pneumonia among patients with cellular immunodeficiency especially those HIV infected. Despite the decreasing of its incidence due to the introduction of antiretroviral therapy, as well as anti-Pneumocystis prophylaxis among these patients, Pneumocystis pneumonia remains the first AIDS-defining event and a leading cause of mortality among HIV-infected patients. The usual radiological presentation is that of diffuse interstitial pneumonia. The diagnosis is confirmed by the detection of trophozoides and/or cysts P. jirovecii in bronchoalveolar lavage (BAL) samples using several staining techniques. The use of polymerase chain reaction in the BAL samples in conjunction with standard immunofluorescent or colorimetric tests have allowed for more has allowed for more rapid and accurate diagnosis. The standard regimen of treatment is the association of trimethoprim-sulfamethoxazole which has been utilized as an effective treatment with a favourable recovery. Early HIV diagnosis and antiretroviral therapy should reduce the incidence of this dreaded disease., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Before antiretroviral therapy (ART) became widely available in sub-Saharan Africa, several studies demonstrated that daily trimethoprim-sulfamethoxazole (TS) prophylaxis reduced morbidity and mortality among HIV-infected adults. As a result, the World Health Organization (WHO) recommended administering TS prophylaxis to this group. However, the applicability of the results to individuals taking ART and living in sub-Saharan Africa has not been definitively evaluated. This study aims to determine if TS prophylaxis benefits HIV-infected Malawian adults after a good response to ART. If TS prophylaxis does indeed show benefit, it is important to determine if this is due to its antibacterial and/or antimalarial properties., Methods/design: A randomized, controlled, open-label, phase III trial of continued standard of care prophylaxis with daily trimethoprim-sulfamethoxazole (TS) compared to discontinuation of standard of care TS prophylaxis and starting weekly chloroquine (CQ) prophylaxis or discontinuation of standard of care TS prophylaxis. The study will randomize 1400-1500 HIV-infected adults (equally divided over the three study arms) with a nondetectable viral load and a CD4 count of 250/mm(3) or more from antiretroviral therapy clinics in Blantyre and Zomba. The expected rate of primary endpoint events of death and WHO stage 3 and 4 events is 6.8 per 100 person-years of follow-up in all participants. Assuming the number of events follows a Poisson distribution and average participant follow-up after 10 % loss to follow-up is 41.6 months, the study will have approximately 85 % power to rule out a reduction of 35 % or more in primary endpoint events in the TS or CQ arms compared to discontinuation of TS prophylaxis-i.e., to show that discontinuation of TS prophylaxis is noninferior to either TS or CQ, with a noninferiority margin of 35 %. Ethical and regulatory approvals were obtained from the University of Malawi College of Medicine Research Ethics Committee; the Malawi Pharmacy, Medicines and Poisons Board; and the University of Maryland Baltimore Institutional Review Board., Discussion: The study began recruitment activities at the Ndirande site in November 2012. The sponsor agreed to extend and expand the study in early 2015, and a second site, Zomba, was added for recruitment and follow-up in mid-2015., Trial Registration: ClinicalTrials.gov Identifier: NCT01650558 (registered on 6 July 2012)., Protocol Version: Letter of amendment #1 to the DAIDS-ES 10822 TSCQ Malawi Protocol, Version 4.0, 16 December 2014.

Background: Fungal infections have been commonly diagnosed in individuals with advanced HIV disease. Cryptococcosis, pneumocystosis, and histoplasmosis are the most frequent systemic mycoses in people suffering from HIV/AIDS., Case Report: We report a case of multiple fungal infections in an advanced AIDS-patient. A 33-year-old HIV-positive man from Brazil was hospitalized due to diarrhea, dyspnea, emaciation, hypoxemia, extensive oral thrush, and a CD4+ T lymphocyte count of 20cells/mm(3). Honeycombed-structures consistent with Pneumocystis jirovecii were observed by direct immunofluorescence in induced sputum. Cryptococcus neoformans was recovered from respiratory secretion and cerebrospinal fluid cultures. Histopathology of the bone marrow also revealed the presence of Histoplasma capsulatum. Molecular assays were performed in a sputum sample. Nested-PCR confirmed the presence of P. jirovecii and H. capsulatum; qPCR multiplex was positive for C. neoformans and H. capsulatum. With the treatment of antifungal drugs the patient progressed satisfactorily., Conclusions: The diagnosis of several systemic mycoses demonstrates the vulnerability of advanced AIDS-patients. Thus, the detection of AIDS cases in the early stages of infection is necessary for a prompt and adequate introduction of HAART therapy, and the use of prophylaxis to control opportunistic infections., (Copyright © 2015 Asociación Española de Micología. Published by Elsevier Espana. All rights reserved.)

Objective: To review the evidence for discontinuing primary and secondary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in HIV-infected patients with a CD4 count <200 cells/mm(3)., Data Sources: We conducted a literature search in MEDLINE, EMBASE, Cochrane Library, Google Scholar, and the International Aids Society Library (up to August 2015) using the following key search terms: Pneumocystis jirovecii, pneumonia, human immunodeficiency virus, primary prophylaxis, secondary prophylaxis, and discontinuation., Study Selection and Data Extraction: All English-language studies that evaluated discontinuation of primary and/or secondary PJP prophylaxis in HIV-infected patients with CD4 count <200 cells/mm(3) were included., Data Synthesis: Five studies were identified, which varied in design, sample size, outcomes, and duration of follow-up. Three studies examined discontinuation of primary and secondary PJP prophylaxis; 1 study evaluated discontinuing primary PJP prophylaxis; and 1 study evaluated stopping secondary PJP prophylaxis. Two out of the 5 studies pooled data for all opportunistic infections. Overall, there was a low incidence of PJP among HIV-infected patients who discontinued primary PJP prophylaxis and were well controlled on antiretroviral therapy (ART)., Conclusions: Discontinuation of primary PJP prophylaxis appears to be safe in patients on combination ART with a suppressed HIV viral load and a CD4 count >100 cells/mm(3). Additional data are needed to support the safety of discontinuing secondary PJP prophylaxis. Decisions to discontinue PJP prophylaxis in patients with a CD4 count <200 cells/mm(3) should be done on an individual patient basis, taking into consideration clinical factors, including ongoing adherence to ART., (© The Author(s) 2015.)

Pneumocystis pneumonia is an opportunistic disease caused by invasion of unicellular fungus Pneumocystis jirovecii. Initially, it was responsible for majority of morbidity and mortality cases among HIV-infected patients, which later have been reduced due to the introduction of anti-retroviral therapy, as well as anti-Pneumocystis prophylaxis among these patients. Pneumocystis pneumonia, however, is still a significant cause of mortality among HIV-negative patients being under immunosuppression caused by different factors, such as transplant recipients as well as oncologically treated ones. The issue of pneumocystosis among these people is particularly emphasized in the article, since rapid onset and fast progression of severe symptoms result in high mortality rate among these patients, who thereby represent the group of highest risk of developing Pneumocystis pneumonia. In contrast, fungal invasion in immunocompetent people usually leads to asymptomatic colonization, which frequent incidence among healthy infants has even suggested the possibility of its association with sudden unexpected infant death syndrome. In the face of emerging strains with different epidemiological profiles resulting from genetic diversity, including drug-resistant genotypes, the colonization phenomenon desires particular attention, discussed in this article. We also summarize specific and sensitive methods, required for detection of Pneumocystis invasion and for distinguish colonization from the disease.

In order to achieve the programmatic goals established in the National HIV/AIDS Strategy, virologic suppression remains the most important outcome within the HIV care continuum for individuals receiving antiretroviral therapy (ART). Therefore, clinicians have dedicated substantial resources to improve adherence and clinic retention for individuals on ART; however, these efforts should be focused first on those most at risk of morbidity and mortality related to AIDS. Our study aimed to characterize the factors that are associated with AIDS-defining illnesses (ADIs) amongst people living with HIV (PLHIV) who are poorly adherent or retained in care in order to identify those at highest risk of poor clinical outcomes. We recruited 99 adult PLHIV with a history of poor adherence to ART, poor clinic attendance, or unsuppressed viral load (VL) from the Infectious Disease Program (IDP) of the Grady Health System in Atlanta, Georgia between January and May 2011 to participate in a survey investigating the acceptability of a financial incentive for improving adherence. Clinical outcomes including the number of ADI episodes in the last five years, VLs, and CD4 counts were abstracted from medical records. Associations between survey items and number of ADIs were performed using chi-square analysis. In our study, 36.4% of participants had ≥1 ADI in the last five years. The most common ADIs were Pneumocystis jirovecii pneumonia, recurrent bacterial pneumonia, and esophageal candidiasis. Age <42.5 years (OR 2.52, 95% CI = 1.08-5.86), male gender (OR 3.51, 95% CI = 1.08-11.34), CD4 nadir <200 cells/µL (OR 11.92, 95% CI = 1.51-94.15), unemployment (OR 3.54, 95% CI = 1.20-10.40), and travel time to clinic <30 minutes (OR 2.80, 95% CI = 1.20-6.52) were all significantly associated with a history of ≥1 ADI in the last five years. Awareness of factors associated with ADIs may help clinicians identify which poorly adherent PLHIV are at highest risk of HIV-related morbidity.

A high prevalence of Pneumocystis jirovecii colonization was observed in patients positive for the human immunodeficiency virus (HIV) admitted to a tertiary hospital in southern Brazil between August 2012 and December 2012. Amplification of the mitochondrial large subunit ribosomal RNA gene in oropharyngeal samples through nested polymerase chain reaction identified P. jirovecii colonization in 26 of 58 (44.8%) HIV-positive patients admitted for causes other than Pneumocystis pneumonia. Colonization was more frequent among patients with an absolute CD4 count ≤200 cells/μl. These findings suggest that the HIV-infected population is a major reservoir and source of P. jirovecii infection and that identification of such individuals may contribute to future strategies for improving management of HIV-infected patients., (© The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pneumocystis pneumonia (PcP) is a significant cause of morbidity and mortality in immunocompromised patients. In humans, PcP is caused by the opportunistic fungal species Pneumocystis jirovecii. Progress in Pneumocystis research has been hampered by a lack of viable in vitro culture methods, which limits laboratory access to human-derived organisms for drug testing. Consequently, most basic drug discovery research for P. jirovecii is performed using related surrogate organisms such as Pneumocystis carinii, which is derived from immunosuppressed rodents. While these studies provide useful insights, important questions arise about interspecies variations and the relative utility of identified anti-Pneumocystis agents against human P. jirovecii. Our recent work has identified the histone acetyltransferase (HAT) Rtt109 in P. carinii (i.e., PcRtt109) as a potential therapeutic target for PcP, since Rtt109 HATs are widely conserved in fungi but are absent in humans. To further address the potential utility of this target in human disease, we now demonstrate the presence of a functional Rtt109 orthologue in the clinically relevant fungal pathogen P. jirovecii (i.e., PjRtt109). In a fashion similar to that of Pcrtt109, Pjrtt109 restores H3K56 acetylation and genotoxic resistance in rtt109-null yeast. Recombinant PjRtt109 is an active HAT in vitro, with activity comparable to that of PcRtt109 and yeast Rtt109. PjRtt109 HAT activity is also enhanced by the histone chaperone Asf1 in vitro. PjRtt109 and PcRtt109 showed similar low micromolar sensitivities to two reported small-molecule HAT inhibitors in vitro. Together, these results demonstrate that PjRtt109 is a functional Rtt109 HAT, and they support the development of anti-Pneumocystis agents directed at Rtt109-catalyzed histone acetylation as a novel therapeutic target for human PcP., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Immune reconstitution syndrome is a set of acute inflammatory phenomena that occur as a result of restored immunity generating a paradoxical worsening of a prior infection or an inflammatory process. This syndrome occurs in human immunodeficiency virus infected patients after starting antiretroviral treatment. The most frequent associated infections are those produced by mycobacteria, herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We present the case of a patient with human immunodeficiency virus who developed the immune reconstitution syndrome secondary to Pneumocystis jirovecii.

Background: Reports from Africa have suggested that pneumocystis pneumonia (PCP) is a less important cause of morbidity than in the developed world. However, more recent studies have shown high seroprevalence rates of P. jirovecii in healthy individuals with HIV as well as high rates of clinical disease in African children. This suggests that PCP may be more common in Africa than was previously recognised. Understanding the contribution of PCP to disease in HIV-infected individuals in sub-Saharan Africa (SSA) has important implications for diagnosis, management and resource allocation. We therefore propose to conduct a systematic review and meta-analysis in order to investigate the burden of PCP in this population., Methods and Design: We plan to search electronic databases and reference lists of relevant articles published from 1995 to May 2013 using broad terms for pneumocystis, HIV/AIDS and sub-Saharan Africa. Studies will be included if they provide clear diagnostic criteria for PCP and well-defined study populations or mortality data (denominator). A novel quality score assessment tool has been developed to ensure fidelity to inclusion criteria, minimise risk of selection bias between reviewers and to assess quality of outcome ascertainment. This will be applied to eligible full-text articles. We will extract data using a standardised form and perform descriptive and quantitative analysis to assess PCP prevalence, mortality and case fatality, as well as the quality of included studies. This review protocol has been published in the PROSPERO International Prospective Register of systematic reviews, registration number CRD42013005530., Discussion: Our planned review will contribute to the diagnosis and management of community-acquired pneumonia in HIV-infected individuals in SSA by systematically assessing the burden of PCP in this population. We also describe a novel quality assessment tool that may be applied to other prevalence reviews.

More than 90% of cases of pneumocystis pneumonia (PCP) in adults occur in patients with chronic HIV infection with CD4 counts lower than 200 cells/ml. Even though primary HIV infection can cause transient profound CD4 lymphocytopenia, PCP is rarely reported during primary HIV infection. We report a case of a 26-year-old man who was diagnosed with PCP in the setting of primary HIV infection. He was successfully treated with a 21-day course of oral co-trimoxazole.

Pneumocystis jirovecii pneumonia (PcP) is a well-recognized major opportunistic infection in HIV-infected patients. During the 1980s, the HIV pandemic turned PcP into a major worldwide medical and public health problem. With the introduction of Pneumocystis chemoprophylaxis and the development of highly active antiretroviral therapy (ART) for the treatment of HIV infection, there has been a decrease in PcP incidence in developed countries. However, the prevalence of AIDS-related PcP in developing countries remains high because a lot of people do not have access to ART or ignore their HIV infection status. This article discusses the information available about PcP among Latin American countries where there is a great regional heterogeneity in the prevalence of HIV infection and in ART coverage, as well as in the observed frequencies of PcP that range from 5.9 to 55% in this area.

Genetic diversity of Pneumocystis jirovecii isolates based on internal transcribed spacer (ITS) of the nuclear rRNA locus has previously been reported. The information about ITS genotype and epidemiology of this organism in Chinese human immunodeficiency virus-infected patients has not been available. In this study, 12 bronchoalveolar lavage fluid specimens obtained from HIV-infected patients were analyzed by PCR followed by cloning, sequencing and typing. Three ITS1 genotypes (E, B and 'H') and four ITS2 genotypes (b, g, i and r) as previously reported were identified, the most common of which were E, b and i. Five ITS haplotypes (Eg, Eb, Bi, Er and 'H'r) and 19 new combination types were also identified with the most common types being Eg (four of 12 patients, 10 of 60 clones), Eb (three of 12 patients, 11 of 60 clones) and Bi (three of 12 patients, 10 of 60 clones). Nine patients were found to be co-infected with more than one ITS genotype of P. jirovecii. The prevalence of ITS genotypes in HIV patients from one Chinese hospital did not seem to be significantly different when compared to reports from other countries.

Introduction: Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in HIV-infected adults. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, recent advances in the diagnostic tools have been changing the situation., Areas Covered: Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Nested or conventional polymerase chain reaction (PCR) has a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash, but often produces false positives. Although quantitative real-time PCR is promising for discriminating colonization from PCP, the targeted DNA sequences and the cut-off values remain to be standardized. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for evaluation of immunocompromised patients with suspected PCP and normal chest radiography., Expert Opinion: Although these new tools have been making the diagnosis of PCP less invasive and more accurate, any one of them can not make a definitive diagnosis by itself. The diagnostic criteria based on the combination of the testing ought to be established.

Background: Pneumocystis pneumonia (PcP) is the second leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients in the United States. Although the host risk factors for the development of PcP are well established, the environmental (climatological, air pollution) risk factors are poorly understood. The major goal of this study was to determine the environmental risk factors for admissions of HIV-positive patients with PcP to a single medical center., Methods: Between 1997 and 2008, 457 HIV-positive patients with microscopically confirmed PcP were admitted to the San Francisco General Hospital. A case-crossover design was applied to identify environmental risk factors for PcP hospitalizations. Climatological and air pollution data were collected from the Environmental Protection Agency and Weather Warehouse databases. Conditional logistic regression was used to evaluate the association of each environmental factor and PcP hospital admission., Results: Hospital admissions were significantly more common in the summer than in the other seasons. Increases in temperature and sulfur dioxide levels were independently associated with hospital admissions for PcP, but the effects of sulfur dioxide were modified by increasing carbon monoxide levels., Conclusions: This study identifies both climatological and air pollution constituents as independent risk factors for hospitalization of HIV-positive patients with PcP in San Francisco. Thus, the environmental effects on PcP are more likely complex than previously thought. Further studies are needed to understand how these factors exert their effects and to determine if these factors are associated with PcP in other geographic locations.

Background: Acquired immunodeficiency syndrome (AIDS) is a pandemic disease commonly associated with respiratory infections, hypoxemia, and death. Noninvasive PEEP has been shown to improve hypoxemia. In this study, we evaluated the physiologic effects of different levels of noninvasive PEEP in hypoxemic AIDS patients., Methods: Thirty AIDS patients with acute hypoxemic respiratory failure received a randomized sequence of noninvasive PEEP (5, 10, or 15 cm H(2)O) for 20 min. PEEP was provided through a facial mask with pressure-support ventilation (PSV) of 5 cm H(2)O and an F(IO(2)) of 1. Patients were allowed to breathe spontaneously for a 20-min washout period in between each PEEP trial. Arterial blood gases and clinical variables were recorded after each PEEP treatment., Results: The results indicate that oxygenation improves linearly with increasing levels of PEEP. However, oxygenation levels were similar regardless of the first PEEP level administered (5, 10, or 15 cm H(2)O), and only the subgroup that received an initial treatment of the lowest level of PEEP (ie, 5 cm H(2)O) showed further improvements in oxygenation when higher PEEP levels were subsequently applied. The P(aCO(2)) also increased in response to PEEP elevation, especially with the highest level of PEEP (ie, 15 cm H(2)O). PSV of 5 cm H(2)O use was associated with significant and consistent improvements in the subjective sensations of dyspnea and respiratory rate reported by patients treated with any level of PEEP (from 0 to 15 cm H(2)O)., Conclusions: AIDS patients with hypoxemic respiratory failure improve oxygenation in response to a progressive sequential elevation of PEEP (up to 15 cm H(2)O). However, corresponding elevations in P(aCO(2)) limit the recommended level of PEEP to 10 cm H(2)O. At a level of 5 cm H(2)O, PSV promotes an improvement in the subjective sensation of dyspnea regardless of the PEEP level employed.

The antiretroviral agent atazanavir is associated with mild asymptomatic hyperbilirubinemia. We report two cases of symptomatic hyperbilirubinemia attributed to atazanavir in conjunction with the Pneumocystis jirovecii pneumonia prophylaxis agent dapsone. Symptoms and laboratory evidence of hemolysis resolved upon discontinuation of dapsone, enabling successful antiretroviral therapy. Symptomatic hyperbilirubinemia due to hemolytic anemia is a potential adverse event when using the combination of atazanavir and dapsone in the treatment of patients with the human immunodeficiency virus.

Background: Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality., Methods: TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models., Results: There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p<0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years., Conclusions: Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.

Background: Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms., Methods: We conducted a prospective study of 550 patients, both HIV-positive (n = 467) and HIV-negative (n = 83), hospitalized with cough ≥2 weeks in Kampala, Uganda, to evaluate the association between HIV status, CD4 cell count, and other clinical predictors and antibody responses to P. jirovecii. We utilized ELISA to measure the IgM and IgG serologic responses to three overlapping recombinant fragments that span the P. jirovecii major surface glycoprotein: MsgA (amino terminus), MsgB (middle portion) and MsgC1 (carboxyl terminus), and to three variations of MsgC1 (MsgC3, MsgC8 and MsgC9)., Results: HIV-positive patients demonstrated significantly lower IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 compared to HIV-negative patients. We found the same pattern of low IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 among HIV-positive patients with a CD4 cell count <200 cells/µl compared to those with a CD4 cell count ≥200 cells/µl. HIV-positive patients on PCP prophylaxis had significantly lower IgM responses to MsgC3 and MsgC9, and lower IgG responses to MsgA, MsgC1, MsgC3, and MsgC8. In contrast, cigarette smoking was associated with increased IgM antibody responses to MsgC1 and MsgC3 but was not associated with IgG responses. We evaluated IgM and IgG as predictors of mortality. Lower IgM responses to MsgC3 and MsgC8 were both associated with increased in-hospital mortality., Conclusions: HIV infection and degree of immunosuppression are associated with reduced IgM responses to Msg. In addition, low IgM responses to MsgC3 and MsgC8 are associated with increased mortality.

A 47-year-old man with optimally controlled type-2 diabetes mellitus and chronic hepatitis B was admitted to a local hospital because of a 1-week history of cough and high-grade fever. He was diagnosed with Pneumocystis pneumonia (PCP) and Klebsiella pneumonia from a chest radiograph and sputum. Simultaneously, he was found to have HIV infection with a CD4 count of 76/μl. Despite alteration of treatment secondary to the development of allergic reaction to trimethoprim-sulfamethoxazole (TMP-SMX), the patient was able to complete a 3-week therapy for PCP after being switched to pentamidine isetionate. After the treatment of PCP, he was referred to our hospital for the initiation of anti-HIV therapy. He presented with recurrent high-grade fever of a few days' duration prior to his initial visit, which subsequently led to his admission. Chest computed tomography (CT) showed the enlargement of a previously identified infiltrate in the left upper lung field, and the sputum culture upon admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia exalbida. Due to his allergy to sulfonamide, the patient was treated with imipenem (IMP) and amikacin (AMK) given intravenously for 17 days, followed by garenoxacin (GRNX) taken orally for 6 months, without any adverse effects. The chest infiltrate resolved completely, and he remains stable without relapse 8 months after the completion of the therapy. Pulmonary nocardiosis should be considered as a differential diagnosis of recurring pneumonia in immunocompromised patients, especially in HIV-infected individuals. Oral administration of GRNX following IMP and AMK can be used as an alternative to TMP-SMX therapy in cases of pulmonary nocardiosis caused by N. exalbida.

Background: Pneumocystis jirovecii pneumonia (PJP) remains the leading cause of opportunistic infections and deaths among human immunodeficiency virus (HIV)-infected patients. We would like to identify the predictors of mortality of these patients at initial presentation, and assist clinicians to aware the patients in risk of mortality earlier., Methods: From 1997 to 2009, adults with HIV infection and a discharge diagnosis of PJP at Mackay Memorial Hospital were included in this retrospective study. Patients' demographic data and laboratory data were analyzed by reviewing the medical records., Results: Eighty-five patients were included in this study. The overall mortality rate was 37.7%. Univariate analysis revealed several host factors significantly related to mortality, including age, systolic blood pressure, diastolic blood pressure, partial pressure of oxygen in arterial blood (PaO(2)), percentage of lymphocyte, percentage of CD4 lymphocyte, CD4 counts, serum total protein, serum albumin, and blood urea nitrogen. Multivariate analysis identified three independent predictors associated with mortality, i.e. systolic blood pressure ≤110 mmHg [adjusted odds ratio (AOR) 3.88; 95% confidence interval (CI) 1.17-12.83; p = 0.03], PaO(2) at room air ≤60 mmHg (AOR 4.97; 95% CI 1.34-18.23; p = 0.01), and lymphocytes ≤10% (AOR 8.19; 95% CI 1.48-45.36; p = 0.02). With these predictors, we can stratify patients into three groups with increasing risks for mortality, ≤one predictor (mortality rate 14%), any two predictors (47%), and three predictors (75%)., Conclusions: HIV-infected patients with PJP can be clinically stratified by three prognostic variables identified by multivariate analysis. Early recognition of patients in higher risk can assist clinicians to prevent rapid deterioration and seek for better outcomes., (Copyright © 2011. Published by Elsevier B.V.)

World Health Organization-classified very severe pneumonia due to Pneumocystis jirovecii infection is recognized as a life-threatening condition in human immunodeficiency virus (HIV) infected infants. We recount the use of nasal bubble continuous positive airway pressure (BCPAP) in an HIV-infected African infant with very severe pneumonia and treatment failure due to suspected infection with P. jirovecii. We also examine the potential implications of BCPAP use in resource-poor settings with a high case index of acute respiratory failure due to HIV-related pneumonia, but limited access to mechanical ventilation.

Pneumocystis pneumonia (PcP) remains a significant cause of morbidity and mortality in immunocompromised persons, especially those with human immunodeficiency virus (HIV) infection. Pneumocystis colonization is described increasingly in a wide range of immunocompromised and immunocompetent populations and associations between Pneumocystis colonization and significant pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have emerged. This mini-review summarizes recent advances in our clinical understanding of Pneumocystis and PcP, describes ongoing areas of clinical and translational research, and offers recommendations for future clinical research from researchers participating in the "First centenary of the Pneumocystis discovery".

Background: Pulmonary tuberculosis (TB), bacterial pneumonia (BP) and Pneumocystis pneumonia (PCP), account for the major causes of pneumonia-like syndromes seen in HIV-AIDS patients and have overlapping clinical and chest x-ray findings pausing challenge to early diagnosis and treatment in Africa. The accuracy of chest x-ray (CXR) interpretations, inter-observer agreement, degree of chest x-ray overlapping, and distinguishing features among these common lung infections was assessed at Tĩkur Anbessa hospital, a tertiary care referral hospital in Addis Ababa, Ethiopia., Patients and Methods: chest x-rays were independently assessed by two radiologists blinded to the clinical between March 2004 and July 2005, the radiographic presentation of 131 smear-negative, HIV-positive patients with atypical laboratory data., Results: One hundred and twenty-four definite diagnoses were made in 107 (82%) of the 131 patients and PCP, BP and pulmonary TB combined accounted for 92% of the diagnoses. The chest x-ray interpretation had high sensitivity (88%), negative predictive value (NPV) (90%), and inter-observer agreement (84%) for PCP Thirty-six percent of the infections mimicked one another, of which BP accounted for the major share. BP mimicked PCP and pulmonary TB in 39% and 20% respectively. Diffuse and bilateral alveolar infiltrates (DBAI) and acinar CXR features discriminated between PCP, pulmonary TB and BP (P < 0.05) while Diffuse bilateral fine interstitial infiltrates (DBFI) did not (p > 0.05). The level of agreement between the radiologists was 79%. There was no exclusively distinguishing radiographic feature amongst the three diseases., Conclusions: Overlapping clinical and radiographic features often occurs as is co-existing infections in HIV-AIDS patients with respiratory symptoms. Therefore, definitive microbiological method should be the main tool to expedite early diagnosis and treatment in HIV-infected patients with respiratory symptoms.

Introduction: Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations' (55th and 57th codon) association with prior sulfa prophylaxis failure has been reported from both developed and developing countries. We conducted a prospective study to determine the prevalence of P. jirovecii DHPS mutations from 2006 to 2009 on P. jirovecii isolates obtained from HIV-infected patients with a clinical diagnosis of Pneumocystis carinii pneumonia (PCP) admitted to our tertiary care reference health center in New Delhi, India., Methodology: Detection of P. jirovecii cysts was performed by direct fluorescent antibody (DFA) staining and by Grocott's-Gomori methenamine silver staining (GMS). DNA detection was performed by polymerase chain reaction (PCR) using primers for the major surface glycoprotein (MSG) gene. P. jirovecii DHPS gene was amplified by nested PCR protocol and sequenced for detecting mutations at the 55th and 57th codons., Results: Out of 147 HIV-positive patients with suspected Pneumocystis pneumonia (PCP), 16 (10.8%) PCP positive cases were detected. Of 16 cases, nine (56.2%) were positive by DFA staining, four (25%) were positive by Grocott's-Gomori methenamine silver staining, and all 16 were positive by MSG PCR. DHPS mutations at the 55th and 57th codons were observed in 6.2% of HIV patients studied, which was relatively low compared to reports from developed nations., Conclusions:   Prevalence of Pneumocystis jirovecii DHPS mutations associated with cotrimoxazole treatment failure may be low in the Indian subpopulation of HIV-positive patients and warrants larger studies to elucidate the true picture of Pneumocystis jirovecii sulfa drug resistance in India.

Lung cancer risk is significantly increased among persons with AIDS (PWA), and increased smoking may not explain all of the elevated risk, suggesting a role for additional cofactors. We investigated whether AIDS-defining pulmonary infections (recurrent pneumonia, Pneumocystis jirovecii pneumonia, and pulmonary tuberculosis) affected the risk of subsequent lung cancer over 10 years after AIDS onset among 322,675 PWA, whose records were linked with cancer registries in 11 US regions. We assessed lung cancer hazard ratios (HRs) using Cox regression and indirectly adjusted HRs for confounding by smoking. Individuals with recurrent pneumonia (n = 5317) were at significantly higher lung cancer risk than those without [HR = 1.63, 95% confidence interval (CI) = 1.08 to 2.46, adjusted for age, race, sex, HIV acquisition mode, CD4 count, and AIDS diagnosis year]. This association was especially strong among young PWA (<50 years HR = 1.99 vs. ≥50 years HR = 1.10) and was significantly elevated during 5-10 years after recurrent pneumonia diagnosis (HR = 2.41; 95% CI = 1.07 to 5.47). Although attenuated, HRs for recurrent pneumonia remained nonsignificantly elevated after indirect adjustment for smoking. Lung cancer risk was unrelated to tuberculosis [(n = 13,878) HR = 1.12, 95% CI = 0.82 to 1.53] or Pneumocystis jirovecii pneumonia [(n = 69,771) HR = 0.97, 95% CI = 0.80 to 1.18]. The increased lung cancer risk associated with recurrent pneumonia supports the hypothesis that chronic pulmonary inflammation arising from infections contributes to lung carcinogenesis.