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Emergence of Aureobasidium pullulans as human fungal pathogen and molecular assay for future medical diagnosis

Chan GF, Puad MS, Chin CF, Rashid NA

Folia Microbiol (Praha), 2011 Sep;56(5):459-67.
PMID: 21909832 DOI: 10.1007/s12223-011-0070-9

Despite the great importance of Aureobasidium pullulans in biotechnology, the fungus had emerged as an opportunistic human pathogen, especially among immunocompromised patients. Clinical detection of this rare human fungal pathogen presently relies on morphology diagnosis which may be misleading. Thus, a sensitive and accurate quantitative molecular assay for A. pullulans remains lacking. In this study, we presented the microscopy observations of A. pullulans that reveals the phenotypic plasticity of the fungus. A. pullulans-specific primers and molecular beacon probes were designed based on the fungal 18S ribosomal RNA (rRNA) gene. Comparison of two probes with varied quencher chemistry, namely BHQ-1 and Tamra, revealed high amplification efficiency of 104% and 108%, respectively. The optimized quantitative real-time PCR (qPCR) assays could detect and quantify up to 1 pg concentration of A. pullulans DNA. Both assays displayed satisfactory performance parameters at fast thermal cycling mode. The molecular assay has great potential as a molecular diagnosis tool for early detection of fungal infection caused by A. pullulans, which merits future study in clinical diagnosis.

Matched MeSH terms: Immunocompromised Host
Fulltext Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry

Al-Herz W, Essa S

Front Immunol, 2019;10:1231.
PMID: 31191561 DOI: 10.3389/fimmu.2019.01231

Objective: To present the frequency and spectrum of viral infections in primary immunodeficient children. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders (PIDs) Registry during the period of 2004-2018. Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Overall infectious complications affected 82.4% of the patients, and viral infections affected 31.7% of the registered patients. Forty-five patients (16.4%) developed viral infections caused by at least 2 organisms, among those 20 patients were affected by three or more viral infections. There was a statistically significant association between viral infections and PID category. However, there was no statistically significant association between viral infections and gender or the patients' onset age. There was a total of 170 viral infections during the study period and the causes of these infections were predominated by CMV (22.2%), adenovirus (11.7%), EBV (11.1%), and enteroviruses (7.4%). CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The most common presentation was viremia (28.8%) followed by pneumonia (28.2%) and skin infections (17.6%). The most common causes of viremia were CMV followed by adenovirus and EBV, while the most common organisms causing pneumonia were CMV followed by rhinovirus and parainfluenza. There were 80 deaths among the registered patients, 10% were caused by viral infections. Conclusions: Viral infections are common in PIDs and result into a wide-range of clinical manifestations causing significant morbidity and mortality.

Matched MeSH terms: Immunocompromised Host
Fulltext Evaluation of Immunoprotection Conferred by the Subunit Vaccines of GRA2 and GRA5 against Acute Toxoplasmosis in BALB/c Mice

Ching XT, Fong MY, Lau YL

Front Microbiol, 2016;7:609.
PMID: 27199938 DOI: 10.3389/fmicb.2016.00609

Toxoplasmosis is a foodborne disease caused by Toxoplasma gondii, an obligate intracellular parasite. Severe symptoms occur in the immunocompromised patients and pregnant women leading to fatality and abortions respectively. Vaccination development is essential to control the disease. The T. gondii dense granule antigen 2 and 5 (GRA2 and GRA5) have been targeted in this study because these proteins are essential to the development of parasitophorous vacuole (PV), a specialized compartment formed within the infected host cell. PV is resistance to host cell endosomes and lysosomes thereby protecting the invaded parasite. Recombinant dense granular proteins, GRA2 (rGRA2) and GRA5 (rGRA5) were cloned, expressed, and purified in Escherichia coli, BL21 (DE3) pLysS. The potential of these purified antigens as subunit vaccine candidates against toxoplasmosis were evaluated through subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Results obtained demonstrated that rGRA2 and rGRA5 elicited humoral and cellular-mediated immunity in the mice. High level of IgG antibody was produced with the isotype IgG2a/IgG1 ratio of ≈0.87 (p < 0.001). Significant increase (p < 0.05) in the level of four cytokines (IFN-γ, IL-2, IL-4, and IL-10) was obtained. The antibody and cytokine results suggest that a mix mode of Th1/Th2-immunity was elicited with predominant Th1-immune response inducing partial protection against T. gondii acute infection in BALB/c mice. Our findings indicated that both GRA2 and GRA5 are potential candidates for vaccine development against T. gondii acute infection.

Matched MeSH terms: Immunocompromised Host
Salmonella thyroid abscess-two case reports

Khoo KS, Koh PS, Ng KL

Gland Surg, 2020 Dec;9(6):2198-2203.
PMID: 33447571 DOI: 10.21037/gs-20-474

Acute suppurative thyroiditis account for <1% of thyroid diseases and is uncommon because of the gland's encapsulation, iodine-rich environment, good vascular supply and extensive lymphatic drainage. It has been reported in patients with underlying goiters, thyroid cancers and in immuno-compromised patients. The usual causative organisms are Staphylococci spp. and Streptococci spp. Rarer organisms include Klebsiella spp. and Salmonella spp. Due to its rarity (as there have been only 28 cases of Salmonella thyroid abscess being reported in the literature till 2020), only case reports are available to guide management. We report two cases of thyroid abscess due to Salmonella enteritidis in our institution that may herald the re-emergence of this uncommon infection of the thyroid gland and to raise awareness for all clinicians. Both patients presented with neck swelling, dysphagia and sepsis. Surgical intervention was warranted in both patients due to the severity of the disease and failed medical therapy. Recovery was uneventful following adequate surgical intervention and antibiotic therapy according to the culture and sensitivity report of the pathogen. This case report highlights that both patients were immunocompromised, and they contracted Salmonella thyroid abscess without any gastrointestinal involvement. Thus, a high index of suspicion for Salmonella thyroid abscess in immunocompromised patients can expedite the diagnosis and appropriate management can be commenced such as antibiotic therapy, percutaneous aspiration and surgical drainage in the event of failed medical therapy.

Matched MeSH terms: Immunocompromised Host
A repeated point prevalence survey of antimicrobial use in specialized cancer care hospital of Pakistan: findings and implications

Saleem Z, Hassali MA, Hashmi FK, Godman B, Bhutta OA

Hosp Pract (1995), 2019 Aug;47(3):149-154.
PMID: 31180791 DOI: 10.1080/21548331.2019.1628614

Background: The extensive use of broad-spectrum antimicrobials in immunocompromised patients is inevitable in situations where culture and sensitivity testing is challenging. However, their overuse leads to an increase in antimicrobial resistance (AMR), which is a growing concern. Method: A repeated point prevalence survey (PPS) was conducted to assess the pattern of antimicrobial prescribing in a specialized cancer care hospital in Pakistan using the methodology employed by the European Centre of Disease Prevention and Control. Results: Out of 313 hospitalized patients, 156 (49.8%) were prescribed one or more antimicrobials, 82 (50.9) in 2017 and 74 (48.7) in 2018. The average bed occupancy in the hospital was 80.3%. Fever in neutropenic patients (20.2%), lower respiratory tract infections (17.8%), and sepsis (14.9%) were the three most common clinical indications. The total number of prescribed antimicrobials was 242, of whom, 41 (16.9%) were given orally and 201 (83.1%) were given parenterally. The most commonly used antimicrobials were piperacillin plus enzyme inhibitor (31.8%), meropenem (7.9%), ceftriaxone (6.2%) and vancomycin (6.2%). Of the total prescribed antimicrobials, 42 (17.3%) antimicrobials were used in surgical departments, 89 (36.8) in adult medical departments, 73 (30.1%) in pediatric medical departments and 38 (15.7) in the intensive care unit (ICU). In addition to these antibacterials, there was relatively high use of antivirals (acyclovir; 4.1%) and antifungals (fluconazole; 3.7%, amphotericin B; 2.9%). Conclusion: The study concluded that broad-spectrum antimicrobial usage in cancer hospitals in Pakistan is high, which can be a risk factor for the emergence of AMR. Repeated PPS is a fruitful way to maintain a focus on inappropriate antimicrobial use and develop pertinent intervention programs targeteing specific issues to improve future use.

Matched MeSH terms: Immunocompromised Host
Antifungal prophylaxis in lung transplantation

Neoh CF, Snell G, Levvey B, Morrissey CO, Stewart K, Kong DC

Int J Antimicrob Agents, 2014 Sep;44(3):194-202.
PMID: 25123811 DOI: 10.1016/j.ijantimicag.2014.05.013

Lung transplant (LTx) patients have an increased risk of developing invasive fungal infections (IFIs), particularly invasive aspergillosis. Rapid identification of the causative fungal pathogen, to allow for early administration of appropriate initial antifungal therapy, in LTx patients has been challenging due to the limited sensitivity and specificity of the diagnostic tools. Hence, there is increasing emphasis on antifungal prophylaxis in the LTx setting, given the high mortality rates and substantial cost of treating IFIs. Evidence for the optimal antifungal prophylactic approach in this setting, however, remains scant and inconsistent. This review will briefly discuss the epidemiology, risk factors, timing and clinical manifestations of fungal infections in LTx patients and will focus primarily on the available evidence related to the efficacy, safety and practicality of current prophylactic strategies in LTx recipients as well as challenges and gaps for future research.

Matched MeSH terms: Immunocompromised Host
Lupus vulgaris in an immunocompromised patient

Jalalonmuhali M, Lee YY, Lee CK, Ismail R, Chandran PA

Int J Dermatol, 2014 Feb;53(2):234-7.
PMID: 22913324 DOI: 10.1111/j.1365-4632.2012.05463.x
Matched MeSH terms: Immunocompromised Host*
Fulltext First isolation of Burkholderia tropica from a neonatal patient successfully treated with imipenem

Deris ZZ, Van Rostenberghe H, Habsah H, Noraida R, Tan GC, Chan YY, et al.

Int J Infect Dis, 2010 Jan;14(1):e73-4.
PMID: 19482535 DOI: 10.1016/j.ijid.2009.03.005

We report the first case of a human Burkholderia tropica infection. The patient was a premature neonate who had necrotizing enterocolitis with bowel perforation requiring surgical intervention. The stoma care and difficulties in feeding were a chronic problem. At the age of almost 4 months he developed septicemia due to B. tropica. Three consecutive blood cultures grew this organism. The organism was cleared from the blood after a course of imipenem and resolution of post-operative ileus. Our case suggests that environmental and plant pathogens can cause human infection especially in those in an immunocompromised condition.

Matched MeSH terms: Immunocompromised Host
Fulltext COVID-19 infection in patients with systemic lupus erythematosus: Data from the Asia Pacific Lupus Collaboration

Cho J, Kandane-Rathnayake R, Louthrenoo W, Hoi A, Golder V, Chen YH, et al.

Int J Rheum Dis, 2020 Aug;23(9):1255-1257.
PMID: 32841510 DOI: 10.1111/1756-185X.13937
Matched MeSH terms: Immunocompromised Host
Primary Adenotonsillar Tuberculosis in an Immunocompetent Child -A Case Report

Lim CC, Misron K, Loong SP, Liew YT, Sawali H

Iran J Otorhinolaryngol, 2019 Sep;31(106):319-322.
PMID: 31598501

Introduction: Primary tuberculosis (TB) of the oropharynx and nasopharynx is an extremely rare form of extra-pulmonary TB in children. Primary tuberculosis occurs more likely secondary to pulmonary TB and is more common in immunocompromised patients.
Case Report: We reported the case of a young male presented with the symptoms of non-specific chronic adenotonsillitis, mild obstructive sleep apnoea, and cervical lymphadenopathy. Subsequently, he underwent adenotonsillectomy and excision of the cervical lymph node with the tissue specimens came back strongly positive for TB. Then, he started using antituberculous medication and recovered well.
Conclusion: The authors would like to highlight this rare clinical entity in which accurate diagnosis is essential for complete treatment.

Matched MeSH terms: Immunocompromised Host
Fulltext Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial

Bastidas A, de la Serna J, El Idrissi M, Oostvogels L, Quittet P, López-Jiménez J, et al.

JAMA, 2019 07 09;322(2):123-133.
PMID: 31287523 DOI: 10.1001/jama.2019.9053

Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster.
Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients.
Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT.
Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter.
Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases.
Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P

Matched MeSH terms: Immunocompromised Host*
Fulltext Cell surface proteins of cryptococcus neoformans mediate adherence and internalisation into mammalian cells

Choo, K.K., Chin, V.K., Chong, P.P., Ho, S.H., Yong, V.C.

JUMMEC, 2019;22(2):24-30.
MyJurnal

Cryptococcus neoformans is an encapsulated fungal pathogen that causes severe disease primarily in
immunocompromised patients. Adherence and internalisation of microbial pathogens into host cells often
begin with engagement of microbes to the surface receptors of host. However, the mechanisms involved
remain poorly understood. In this study, we investigated the association of cell surface determinants of C.
neoformans with mammalian cells. Our results showed that treatment with trypsin, but not paraformaldehyde
or heat killing, could reduce host-cryptococci interaction, suggesting the involvement of cell surface proteins
(CSPs) of C. neoformans in the interaction. We extended our investigations to determine the roles of CSPs
during cryptococci-host cells interaction by extracting and conjugating CSPs of C. neoformans to latex beads.
Conjugation of CSPs with both encapsulated and acapsular C. neoformans increased the association of latex
beads with mammalian alveolar epithelial cells, alveolar macrophages and monocyte-derived macrophages.
Further examination on the actin organisation of the host cells implied the involvement of actin-dependent
phagocytosis in the internalisation of C. neoformans in CSP-conjugated latex beads. We hypothesised that
CSPs present on the cell wall of C. neoformans mediate the adherence and actin-dependent phagocytosis
of cryptococci by mammalian cells. Our results warrant further studies on the exact role of CSPs in the
pathogenesis of cryptococcosis.

Matched MeSH terms: Immunocompromised Host
Tongue necrosis secondary to mucormycosis in a diabetic patient: A first case report in Malaysia

Fattah SY, Hariri F, Ngui R, Husman SI

J Mycol Med, 2018 Sep;28(3):519-522.
PMID: 30205883 DOI: 10.1016/j.mycmed.2018.06.004

Mucormycosis is a rare fungal infection and high mortality that commonly affects patients with the weakened immune system. We present an unusual case of tongue necrosis probably due to the healthcare-associated mucormycosis (HCM) in a diabetic patient. Although cannot be proved with certainty, we surmise that intubation as a risk factor in our case. The diagnosis was confirmed by histopathological examination (HPE) of the necrotic tissue specimen. The patient was responded well to lipid complex amphotericin B (250mg) regime after surgery. Subsequent follow up revealed that no signs of recurrence. Early, recognition, diagnosis, prompt treatment and awareness among clinician are representing the most effective way of managing the disease.

Matched MeSH terms: Immunocompromised Host
Fulltext A rare case of Tuberculous Prostatitis

Nurul Yaqeen Esa, Mohammad Hanafiah, Marymol Koshy, Hilmi Abdullah, Ahmad Izuanuddin Ismail, Mohamed Fauzi Abdul Rani

Journal of Clinical and Health Sciences, 2016;1:33-36.

Tuberculous prostatitis is an uncommon form of tuberculosis infection. It is commonly seen in immunocompromised patients and in those of middle or advanced age. The diagnosis is often not straight forward due to the nature of its presentation. We report a case of tuberculous prostatitis in a young, healthy and immunocompetent patient, who initially presented with respiratory features, followed by episodes of seizures and testicular swelling. He was finally diagnosed with tuberculous prostatitis after prostatic biopsy. This case illustrates that in a high TB prevalence environment, when symptoms warrant, there should be a high clinical suspicion coupled with a thorough approach in order to arrive at a correct diagnosis of TB prostatitis.

Matched MeSH terms: Immunocompromised Host
Fulltext A case report of Intramuscular Abscess Secondary to Epicoccum Nigrum infection

Azira NMS, Zeehaida M, Nazli Z, Suraiya S

Journal of Clinical and Health Sciences, 2016;1:48-51.

A 36-year-old man with underlying chronic lymphocytic leukemia had left arm swelling for a duration of 3 months. Clinically, the affected arm was swollen, erythematous and tender. Epicoccum nigrum was isolated from the culture of the tissue that was obtained intraoperatively. He was treated and responded to voriconazole therapy. To the best of our knowledge, this is the first case of intramuscular abscess as a result of E. nigrum infection in an immunocompromised patient.

Matched MeSH terms: Immunocompromised Host
Fulltext A rare and challenging case of pulmonary mycobacterium genavense in an immunocompetent adult

Nur ‘Aini Eddy Warman, Nurul Yaqeen Mohd Esa

Journal of Clinical and Health Sciences, 2018;3(1):47-50.
MyJurnal

Mycobacterium genavense, a non-tuberculous mycobacterium (NTM), usually affects patients severely immunodeficient from human immunodeficiency virus (HIV) infection or any other immunocompromised states. We reported a case in a 70-year-old female with well-controlled diabetes and history of proximal cystic bronchiectasis. She presented with 2 months history of cough, haemoptysis, and night sweats of which serial sputa were positive for acid-fast bacilli and the culture repeatedly grew M. genavense. Treatment with rifampicin, ofloxacin, and clarithromycin was complicated with drug-induced liver injury and intractable gastrointestinal side effects. We also presented a brief review of relevant literature.

Matched MeSH terms: Immunocompromised Host
Fulltext A rare case of Tuberculous Prostatitis

Nurul Yaqeen Esa, Mohammad Hanafiah, Marymol Koshy, Hilmi Abdullah, Ahmad Izuanuddin Ismail, Mohamed Fauzi Abdul Rani

Journal of Clinical and Health Sciences, 2016;1(2):33-36.
MyJurnal

Tuberculous prostatitis is an uncommon form of tuberculosis infection. It is commonly seen in immunocompromised patients and in those of middle or advanced age. The diagnosis is often not straight forward due to the nature of its presentation. We report a case of tuberculous prostatitis in a young, healthy and immunocompetent patient, who initially presented with respiratory features, followed by episodes of seizures and testicular swelling. He was finally diagnosed with tuberculous prostatitis after prostatic biopsy. This case illustrates that in a high TB prevalence environment, when symptoms warrant, there should be a high clinical suspicion coupled with a thorough approach in order to arrive at a correct diagnosis of TB prostatitis.

Matched MeSH terms: Immunocompromised Host
Fulltext A case report of Intramuscular Abscess Secondary to Epicoccum Nigrum infection

Azira NMS, Zeehaida M, Nazli Z, Suraiya S

Journal of Clinical and Health Sciences, 2016;1(2):48-51.
MyJurnal

A 36-year-old man with underlying chronic lymphocytic leukemia had left arm swelling for a duration of 3 months. Clinically, the affected arm was swollen, erythematous and tender. Epicoccum nigrum was isolated from the culture of the tissue that was obtained intraoperatively. He was treated and responded to voriconazole therapy. To the best of our knowledge, this is the first case of intramuscular abscess as a result of E. nigrum infection in an immunocompromised patient.

Matched MeSH terms: Immunocompromised Host
Chronic mucocutaneous candidiasis with deficient CD2 (E receptor) but normal CD3 mononuclear cells

Noh LM, Hussein SH, Sukumaran KD, Rose I, Abdullah N

J Clin Lab Immunol, 1991 Jun;35(2):89-93.
PMID: 1688166

A case of chronic mucocutaneous candidiasis in a Malaysian child who subsequently developed disseminated tuberculosis and toxoplasmosis is described. The phenotype of her peripheral blood mononuclear cells showed discordance for her T cell markers. The presence of a subpopulation of CD2-/CD3+ mononuclear cells leading to an immunodeficiency state is consistent with failure of activation of CD2-mediated alternative pathway resulting in immunodeficiency. Such abnormal CD2-/CD3+ subpopulations have been described in lepromatous leprosy and foetal abortuses.

Matched MeSH terms: Immunocompromised Host
Fulltext Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment

Looi CK, Chung FF, Leong CO, Wong SF, Rosli R, Mai CW

J Exp Clin Cancer Res, 2019 Apr 15;38(1):162.
PMID: 30987642 DOI: 10.1186/s13046-019-1153-8

BACKGROUND: Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME).
MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.
CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.

Matched MeSH terms: Immunocompromised Host*

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