This is to certify that this dissertation titled “A STUDY ON THE PATTERN OF FUNGAL INFECTIONS AND CLINICAL PROFILE IN IMMUNOCOMPROMISEDPATIENTS WITH SPECIAL REFERENCE TO CHARACTERISATION AND MOLECULAR STUDY OF CANDIDA SPECIES IN A TERTIARY CARE HOSPITAL” is a bonafide record of work done by Dr.M.AKILAMANI during the period of March 2017 to February 2018 under the guidance of Prof.Dr.C.P.RAMANI .M.D., Professor of Microbiology, Institute of Microbiology , Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai - 600003, in partial fulfillment of the requirement of M.D. MICROBIOLOGY Degree Examination of The Tamilnadu Dr.M.G.R. Medical University to be held in May 2019.
Invasive fungal sinusitis (IFS) is a rare disease largely attributable to Aspergillus and Mucor in patients with stem cell transplants and hematological disease . Though the mortality of IFS in immunocompromisedpatients ranges from 50% to 80% [7,9,10], early physical findings are non- specific and ambiguous (i.e., nasal obstruction, purulent dis- charge, and epistaxis). Water’s view plain radiographs do not distinguish invasive fungal sinusitis from chronic al- lergic sinusitis. Bony erosion and tissue destruction are often found only in the advanced stage by computed to- mography [11,12]. Recent introduction of serial Aspergil- lus galactomannan antigen test may provide early evi- dence of IFS. As data regarding this issue are scarce in our region of southern Iran, we performed this study to deter- mine the epidemiology of IFS and the drug sensitivities of the etiological factors in Shiraz, southern Iran.
In order to find out, psychotic illness in immunocompromisedpatients, a survey was conducted. The aim of this study is to determine the prevalence of psychotic illness among immunocompromisedpatients. To conduct this survey, a questionnaire was designed that consisted of several questions. The survey was not only conducted in the general public but also in the hospitals. JPMC hospital and Abbasi Shaheed is the hospitals that were visited for the survey. The total sample size was 700 [table 1]. 400 forms were distributed in patients of the hospitals and 300 forms were distributed in the general public. After completing the Survey, data was collected and was converted in to graphs for statistical analysis to evaluate the result.
Hepatitis E virus (HEV) can cause chronic infections in immunocompromisedpatients, including solid-organ transplant (SOT) recipients. Two strains that had undergone recombination with human ribosomal genes were described recently. The strains with inserted sequences replicated better in vitro. Little is known about the frequency of such recombinant events or how such an insertion enhances replication. We therefore investigated 59 SOT patients infected with HEV and found 3 strains with 4 re- combinant events in 27 of these patients whose infection became chronic. The 4 inserted sequences were of different origins (hu- man gene or HEV genome), but all were enriched in aliphatic and basic amino acids and provided potential regulation sites. Our data indicate that recombinant events occur in approximately 11% of strains isolated from chronically infected patients. The structures of the inserted sequences provide new clues as to how the inserted sequences could foster virus replication.
PIV infection in immunocompromisedpatients is relatively common and can be associated with a spectrum of diseases, ranging from mild URI symptoms to severe respiratory fail- ure and death. Risk of progression to pneumonia appears to be related to use of steroids and lymphopenia. Once pneumonia has developed, death rates are high and at the present time, effective antiviral therapy is not available. Randomized controlled trials of ribavirin to prevent progression of PIV from the upper to the lower respiratory tract are needed. New information on the structure and function of PIV proteins and the cellular processes of the PIV life cycle should provide new areas of research for antiviral agents.
The ethics committee of the French Society for Critical Care approved the study (SRLF-CE 07-188). This prospec- tive observational study was conducted in the medical ICU of the Saint Louis teaching hospital in Paris (France) over a 6-mo period (February-July 2007). We included all immunocompromisedpatients defined as patients with any of the following: HIV infection (all stages), neutrope- nia (neutrophil count < 1 × 10 9 /L), exposure to glucocorti- coids (> 0.5 mg/kg for > 30 d) and/or immunosuppressive or cytotoxic medications, solid organ transplantation, allo- geneic or autologous stem cell transplantation, hematolo- gical malignancy, or solid tumor. Each of the included patients or next of kin received written information and give oral consent. Our IRB waived the need for written consent according to French Law.
Identification of norovirus polymorphisms in the specimen population and comparison to circulating viruses. To further investigate the RNA virus population (quasispecies of each speci- men), specimens from patients A, B, and C and the IC patient were analyzed by deep sequencing using Roche 454 sequencing. The A ⫹ 5 sample was not processed further because of the presence of a mixed infection. Genetic polymorphisms from the deep-se- quencing data were summarized as bit scores as previously de- scribed. Bit scores for each gene were then overlaid on the P values obtained from the MEME analysis to identify similar sites between noroviruses from the immunocompromisedpatients and circu- lating noroviruses. In the GII.4 circulating population, a total of 113 positively selected codon sites were identified by MEME anal- ysis with a P value score of ⱕ 0.1 (Table 2). All scores from the MEME analysis that were ⱕ0.1 were selected and binned accord- FIG 2 Patristic and P-distance comparison of novel GII.4 variants. The nucleotide maximum likelihood tree (ML-NT), amino acid maximum likelihood tree (ML-AA), nucleotide P-distance (P-NT), and amino acid P-distance (P-AA) between GII.4 variants were graphed. The error bars represent ⫾ 2 SDs for each group comparison. UNK1 and UNK2 are described in this study. The other variants and their GenBank accession numbers are GII495.96 (United States, 1995-1996),AY741811; GII4Henry (Henry, 2001), EU310927; GII4FHills (Farmington Hills, 2002), AY502023; GII4Apeldoorn (Apeldoorn, 2008), HQ009513; GII4NewOrleans (New Orleans, 2009), GU445325; and GII4Sydney (Sydney, 2012), JX459908. PA, PB, and PC refer to patients A, B, and C, respectively.
Candida species were C. glabrata and C. tropicalis. Compared with other Candida species, C. krusei and C. glabrata are generally documented as the causes of inva- sive candidiasis with reduced susceptibility to FLU. The MIC 90 values for FLU in C. albicans and C. glabrata in our study were 2 μg/ml and 16 μg/ml in the two groups, respectively. The MIC90 values for FLU in Castanheira et al. in clinical C. albicans and C. glabrata isolates were reported as 0.25 μg/ml and 32 μg/ml with resistance rates of 0.3 and 7.9%, respectively . The resistance rate to FLU was reported 2.6% in infected patients in Korea . In Pfaller et al. “resistance to fluconazole was seen in 0.5% of C. albicans isolates, 11.1% of C. glabrata isolates, 2.5% of C. parapsilosis isolates, 4.5% of C. tropi- calis isolates, and 20.0% of C. guilliermondii isolates” . In the present study, the resistance rates to ITR in C. glabrata INFEC and COL isolates were 77.8% (14/18) and 15% (8/53), respectively (P < 0.05). This resistance rate in INFECT was similar to the results obtained in immunocompromisedpatients in our previous study (i.e. 85.5%) . Resistance to ITR was reported in many studies [11, 14, 17]. In Haddadi et al., this rate was 22.5% (49/217) in all COL isolates . In Cuenca- Estrella et al. resistance of all Candida species to ITR was seen, especially in C. glabrata . Strains suscep- tible dose dependent to ITR were reported in many studies [11, 14, 17]. Susceptible dose dependence in the present study for ITR was seen in many Candida species, especially COL C. glabrata isolates. Itraconazole and FLU are the most commonly prescribed azole agents in our re- gion, which may explain the increased resistance rates and susceptible dose dependence observed for these antifungal agents in our study. The presence of many susceptible dose dependent isolates may suggest the future emergence of these species with resistant isolates.
The diagnostic yield of BAL in immunocompromisedpatients presenting with lung infiltrates in an ambulatory setting was 60.8% and in the majority of cases, the posi- tive BAL findings impacted clinical management. Infec- tious etiologies accounted for 97% of the positive diagnoses which reinforces current clinical practice of early use of empiric antibiotics. In addition, our study found no impact of prior anti-microbial therapy or dur- ation of antibiotics on diagnostic yield. The mismatch between positive yield and post-BAL result treatment modification may be attributable to the fact that 40.5% (64/158) of pathogens detected were respiratory viruses for which therapeutic options were limited. In addition, in none of the 16 isolates of cytomegalovirus was there inclusion bodies detected in the corresponding cytology. This raises doubts over the pathogenic nature of the cytomegalovirus isolates. Cases where the BAL cyto- megalovirus isolate was the only finding (including no antigenemia) were not labelled as positive diagnostic yield. There were 17.1% (37/217) cases of Pneumocystis jirovecii, 6.0% (13/217) cases of tuberculosis, 4.6% (10/ 217) cases of Aspergillosis and 3.7% (8/217) cases of Pseudomonas infection. In addition, in 14.3% (31/217) BAL Galactomannan was positive.
the first case of C. membranaefaciens in Iran, which occurred in a 70-year-old woman, who had coronary artery bypass grafting(34). They isolated germ-tube negative yeast from both blood culture and central venous catheter (CVC) tip culture. They confirmed the results by sequence analysis of internal transcribed spacer region of rDNA. After the removal of the CVC and initiation of fluconazole therapy, the patient was gradually improved and discharged from the hospital. In 2009, Shahhosseiny et al.,(2010), isolated 14 Candida spp. from 2516 blood culture samples (0.5%), and reported Candidaalbicans as the most prevalent species(35).Ghahri et al.,(2012) identified 48 clinical isolates of Candida species from blood specimen cultures of immunocompromisedpatients by PCR- RFLP method (36). They reported Candidaparapsilosis as the most frequent agent of candidemia, whereas Candidaparapsilosiswas the least frequent species in the present investigation. In 2013, Kalantaret al.,(2013) isolated 5 Candida spp. from 68 blood samples (7.3%) (37). Ahmad et al.,(2002) used the species-specific primers for species- specific identification of Candida species including Candidaalbicans, Candidatropicalis, Candidaparapsilosis, and Candidaglabrata(20). Similar to this study, Horn et al.,(2009) showed that Candidaalbicans was the most common Candida strain in their investigation (45.6%) followed by Candida
The prevalence of intestinal cryptosporidiosis among immunocompromised Iraqi patients including malignancy, receiving corticosteroid drugs, sicklers or protein-malnutrition is reviewed. The prevalence is also reviewed in relation to age and sex. Cryptosporidiosis is quite common in Iraq and it is considered as a public health problem among immunocompromised individuals. The combination between formalin-ether sedimentation plus modified cold Ziehl-Neelsen stain methods has been regarded with high sensitivity and specificity. The highest isolation rate for Cryptosporidium oocysts was observed during rainy winter season. Keywords: Cryptosporidiosis, Immunocompromisedpatients, Iraq, Sickle-cell anemia, Protein malnutrition.
15 patients had underlying disease, including he- matologic neoplasm, such as Hodgkin's disease, chronic hepatitis, diabetes mellitus, acquired immunodeficiency syndrome (AIDS), tuberculosis and immunosuppression due to kidney transplantation. Herpes zoster infection was severe in all cases and the involved sites included the maxillary nerve in eleven, mandibular nerve in eighteen, ophthalmic and maxillary nerve in one, and maxillary and mandibular nerve in two patients. Maxil- lary and mandibular alveolar bone necrosis appeared 9- 150 days (with a mean of 30 days) after the onset of herpes zoster. Thirteen patients required extraction a few teeth, while the others required extensive tooth ex- traction. The teeth in the affected segment spontaneous- ly exfoliated 9-150 days after infection with HZ in some cases [1-9].
Because scientific doubts were repeatedly expressed on this topic, this study was conducted with constant attention to any source of contamination; this went as far as performing the BDV-infected C6 cell cultures in a level 3 containment labo- ratory otherwise dedicated to HIV culture diagnostic proce- dures and located in a building distant from the laboratory where patients samples were analyzed. Negative controls in- cluded “RT-minus,” RT-PCR MV and VSV because of the structural similarities among Mononegavirales, and none were positive. In addition, sequencing of our PCR products never indicated any contamination with the plasmid used as a posi- tive control. On the other hand, the RT-nested PCR technique used in this study was reasonably sensitive, since it allowed the detection of 0.075 in vitro-infected cell (such cells were shown to contain approximately 0.0008 infectious BDV each ) or 1,000 copies of the RNA-transcribed plasmid. mRNAs of the first gene to be transcribed, p40, represent most of the viral RNA species present in infected cells and were therefore cho- sen as the main RT-nested PCR target. Finally, hybridization of the amplified DNA fragments enhanced the specificity of the detection because a specific probe was used.
Nasal endoscopy was performed in all patients, and we scored as “0” when normal or “1” when any suspicious mucosal alteration (pale area, darkened tissue, crust, ulcer or hyphae) was observed. Areas systematically evaluated during the nasal endoscopy were nasal septum, middle and inferior turbinates, lateral nasal wall, and nasopharynx. If any mucosa alteration was detected, three 5-mm specimens of the suspicious area were col- lected using nasal punch forceps: one for frozen-section biopsy, one for routine FFPE analysis (HE and GMS staining) and the third specimen for fungal culture. As routine in our service, complete blood count is per- formed daily in these patients. In severe thrombocytope- nic patients (those with less than 20,000 platelets/ml), nasal endoscopy and biopsy were performed immedi- ately after platelet transfusion. In all other patients, biop- sies were obtained without major complications. Some patients received cotton embedded with vasoconstrictor to contain local bleeding.
Among the three hundred patients screened in renal transplant OP six patients had warts. Verrucae vulgaris was the most common, seen in four cases followed by plane wart, digitate warts, genital wart, one each. All of the six allograft recipients were males of age between 24 to 62 years. All had transplants from related donors. The duration of follow up was 16 to 172 months. All the patients received kidneys from living donors and were kept on immunosupression with daily doses of predisolone, azathioprine and cyclosporine respectively. All the six patients gave a history of sun exposure.
The available studies rely on a small yet very heterogenous patient collective and are predominantly characterised by the lack of control groups and a low level of specificity. No randomised controlled studies on immunosuppression and dental implant rehabilitation were available. Further limitations were seen in the dif- ferent methodological approaches of the analysed pro- spective and retrospective studies. Only few studies had a control group, usually the studies compared with healthy patients or provided no control group at all. Re- sults were often summed up and not clearly identified or patient related, i.e. implant loss per patient. Further- more, the exclusion of implant-related diseases such as peri-implantitis may be considered as a limitation. It re- mains unknown whether these factors are influenced by immunosuppression and may lead to implant failure at a time-point that exceeds the follow-up of the patient. Only studies in English or German language were con- sidered accordingly data maybe missing. Such limited quality of primary studies leads to the urgent need for randomised controlled studies with more patients on the effects of immunosuppression on dental implants.
The immune response by CD8 + is not immediate and the presence of the time delay between infection and this immune response was observed in HBV infection  and this delay was quantify with a given data  and . The problem is that quantification has a lot of uncer- tainty when consider patients with co-infection and immunocompromise, which is the case for big population of the HBV positive. Therefore our goal is to take this fact into consideration particularly when it comes to antiviral therapy management.