|Year : 2018 | Volume
| Issue : 3 | Page : 408-415
Comparing the profile of respiratory fungal pathogens amongst immunocompetent and immunocompromised hosts, their susceptibility pattern and correlation of various opportunistic respiratory fungal infections and their progression in relation to the CD4+T-cell counts
Asma Husein Roohani1, Nazish Fatima1, Mohammad Shameem2, Haris Manzoor Khan1, Parvez Anwar Khan1, Anees Akhtar1
1 Department of Microbiology, JNMC, AMU, Aligarh, Uttar Pradesh, India
2 Department of TB Chest and Respiratory Disease, JNMC, AMU, Aligarh, Uttar Pradesh, India
|Date of Web Publication||14-Nov-2018|
Dr. Anees Akhtar
Department of Microbiology, JNMCH, AMU, Aligarh - 202 002, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Invasive fungal infections are increasingly common in the nosocomial setting. Materials and Methods: The patients were divided into two groups immunocompetent and immunocompromised that is, patients with significant neutropenia <500 neutrophils/μl for longer than 10 days. microscopy, culture, identification of isolates were done and some specilised tests on serum and BAL for antigen detection were performed. Results: Majority of the patients were young adult males in this study. A higher prevalence of 26.7% was seen in immunocompromised patients. Amongst yeasts, Candida albicans was the predominant species followed by the National AIDS Control that is, Candida glabrata, Candida dubliniensis, Candida parapsilosis and Candida tropicalis in the same order. Amongst moulds, Aspergillus fumigatus was the most common species followed by Aspergillus flavus and Aspergillus niger. Mucor and Penicillium marneffei were seen in a lower prevalence. By Broth microdilution method, isolates of Candida spp. were most sensitive to caspofungin, amphotericin B, ketoconazole and fluconazole in the same order. Isolates of Aspergillus spp. were most sensitive to caspofungin, amphotericin B and itraconazole in the same order. By disc diffusion method, resistance to fluconazole was observed in 6.9% isolates of C. albicans. 50% of C. dubliniensis and 20% of C. glabrata showed resistance to fluconazole. A total mortality of 27.7% was observed during this study. This was distributed as 24.1%, 26.7%, 50%, 50%, 100% and 0% among by patients of candidiasis, aspergillosis, cryptococcosis, pneumocystosis, mucormycosis and penicilliosis. Fifteen per cent were lost to follow-up. Conclusion: Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.
Keywords: CD4+ cells, immunocompetent, immunocompromised
|How to cite this article:|
Roohani AH, Fatima N, Shameem M, Khan HM, Khan PA, Akhtar A. Comparing the profile of respiratory fungal pathogens amongst immunocompetent and immunocompromised hosts, their susceptibility pattern and correlation of various opportunistic respiratory fungal infections and their progression in relation to the CD4+T-cell counts. Indian J Med Microbiol 2018;36:408-15
|How to cite this URL:|
Roohani AH, Fatima N, Shameem M, Khan HM, Khan PA, Akhtar A. Comparing the profile of respiratory fungal pathogens amongst immunocompetent and immunocompromised hosts, their susceptibility pattern and correlation of various opportunistic respiratory fungal infections and their progression in relation to the CD4+T-cell counts. Indian J Med Microbiol [serial online] 2018 [cited 2019 Dec 5];36:408-15. Available from: http://www.ijmm.org/text.asp?2018/36/3/408/245386
| ~ Introduction|| |
Invasive fungal infections are increasingly common in the nosocomial setting. Respiratory and systemic mycoses are globally emerging as problems of increasing importance in infectious diseases. Fungal spores are representing more than 50,000 spores per cubic meter of air during the fungal season., Although increasing number of AIDS cases are being reported from central India, the data on spectrum of opportunistic infections of respiratory tract in HIV seropositive patients from developing countries as well as from this region are scanty. Although most antifungal resistance occurs in Candida species, resistance in other types of fungi, such as Aspergillus, is also an emerging issue. The full extent of the problem is still unknown, but the global prevalence of azole resistance in Aspergillus is estimated to be approximately 3%–6%. The CD4 count is the most important laboratory indicator of immune function in HIV-infected patients. It is also the strongest predictor of subsequent disease progression and survival according to findings from clinical trials and cohort studies., The CD4 count is used to assess a patient's immunologic response to antiretroviral treatment (ART). It is also used to determine whether prophylaxis for opportunistic infections (OIs) can be discontinued.
| ~ Materials and Methods|| |
The patients were divided into two groups immunocompetent and immunocompromised that is, patients with significant neutropenia <500 neutrophils/μl for longer than 10 days. These patients were attending the Outpatient Department or admitted to Ward of Department of Tuberculosis (TB) and Respiratory diseases, and the Antiretroviral Clinic at Jawaharlal Nehru Medical College and Hospital, AMU. The period of study was from January 2015 to July 2016. A detailed clinical history and examination were recorded for each patient.
Collection of specimens
Expectorated sputum, induced sputum, bronchoalveolar lavage (BAL) endotracheal aspirates, pleural fluid and blood were collected and transported immediately to the microbiology laboratory and processed promptly within an hour of collection, except for serum which was stored at −20°C.
- Routine laboratory investigations such as haemoglobin, total leucocyte count, differential leucocyte count, erythrocyte sedimentation rate, liver function test, renal function test, lipid profile serology and some specialised investigations chest X-ray, high-resolution computed tomography scan, etc., when required were performed
- The following microbiological investigations were carried out:
HIV testing by ELISA/Rapid/Simple tests and CD4 cell count estimation
The HIV status of all patients was confirmed at Voluntary Counselling and Testing Centre, Department of Microbiology, JNMC. The HIV antibody assay was assessed by three (ELISA, Rapid and Simple) tests as recommended by the National AIDS Control (NAC) Organization, Ministry of Health and Family Welfare, Government of India (2007). The CD4 cell counts of all the patients were estimated by flowcytometry using Partec CyFlow® Counter (Germany).
- Microscopy: Direct microscopy of the clinical materials was performed by Grams, Giemsa staining, calcofluor white stain, India ink and potassium hydroxide preparation was done
- Culture for fungus: After initial inoculation and incubation, all culture media were examined for fungal growth daily during the 1st week and on alternate days thereafter up to 3 weeks. The isolates were identified on macroscopic and microscopic morphological characteristics using standard techniques described in medical mycology
- Identification and characterisation of fungal isolates: Yeast isolates were identified on the basis of colony characteristics and further by germ tube production, morphology on corn meal agar (HiMedia), HiCrome Candida agar (HiMedia), urease test, carbohydrate fermentation tests and assimilation tests using yeast nitrogen base agar (HiMedia). Identification and speciation of the moulds was done based on the colony characteristics, morphology on lactophenol cotton blue preparation and microslide culture. The suspected moulds were further cultured on Czapek Dox agar
- Specialised tests on serum and BAL for antigen detection: Cryptococcal Antigen Latex Agglutination System® (Meridian Bioscience, Europe) was used to detect Cryptococcal Antigen in Serum and Respiratory samples and The Platelia TM Aspergillus enzyme immunoassay (BioRad, Germany) is an immunoenzymatic sandwich microplate assay for the detection of Aspergillus galactomannan antigen
- Antifungal susceptibility testing: The Clinical and Laboratory Standards Institute (CLSI) document M44-A2 for disc diffusion testing of yeasts was followed to detail. The antifungal agents tested were amphotericin B, nystatin, ketoconazole, clotrimazole, fluconazole, itraconazole and caspofungin. Moreover, Broth microdilution method for yeasts was adopted in this study as per guidelines based on document no. M27-A3. The antifungal agents used were, amphotericin B, fluconazole, ketoconazole and caspofungin from HiMedia Laboratories. M51-A for mould disc diffusion testing was followed. The CLSI document M38-A2 for microtiter mould testing was followed to detail CLSI, 2008. The antifungal agents used were amphotericin B, itraconazole and caspofungin from HiMedia Laboratories.
| ~ Results|| |
Most of the patients that is, 47 (31.3%) were between 31 and 40 years with a mean age of 32.5 years. The male-to-female ratio was 1.8:1.
Out of 150 patients, the immunocompetent patients comprised of 70 cases whilst the immunocompromised patients comprised 80 cases. Majority of immunocompetent cases were those presenting with lung mass that is, carcinoma (26.6%) and secondaries in lung (8%), whilst HIV-positive patients constituted the maximum number (40%) of immunocompromised cases. A total of 65 (54.3%) samples were positive for fungal elements on direct microscopy. Fungal culture was found positive in 35 (58.3%) induced sputum samples, 16 (32%) BAL samples, 5 (50%) sputum samples, 2 (20%) endotracheal aspirates and 1 (10%) each of pleural fluid and intercostal tube drain samples [Table 1].
|Table 1: Distribution of cases with respect to clinical diagnosis and immune status|
Click here to view
Amongst the yeast isolates, 21 (63.6%) and 12 (36.3%) were collected from immunocompromised and immunocompetent patients, respectively. A total of 14 (42.4%) isolates were of Candida albicans; 9 (64.3%) from the immunocompromised and 5 (35.7%) from the immunocompetent cases. 10 (71.4%) isolates of these were from patients of pulmonary tuberculosis. The remaining 19 (57.5%) isolates of Candida were NAC of which, Candida dubliniensis 4 (12.1%) and Candida glabrata 5 (15.1%) represented the majority of isolates. 3 (9.1%) were represented each by Candida parapsilosis and Candida tropicalis. For each of these species, the contribution was either equal or greater in the immunocompromised patients, except for C. tropicalis where 66.6% isolates were seen in immunocompetent patients as compared to 33.3% isolate from immunocompromised patients. Two (6.1%) Cryptococcus neoformans were found in HIV-positive cases. Two (6.1%) Pneumocystis jirovecii infection diagnosed based on calciflor white staining.
Amongst the 32 (49.2%) mould isolates, 30 (93.7%) were found to be Aspergillus species. Aspergillus fumigatus was the most common (53.1%) followed by Aspergillus flavus (31.2%) and Aspergillus niger (9.3%). One (3.1%) isolate of Mucor from a diabetic patient and 1 (3.1%) isolate of Penicillium marneffei from an HIV-positive patient were detected.
The two cases of pulmonary cryptococcosis (1.3%) were positive on both culture and latex agglutination test.
Galactomannan antigen was positive in 13 (28.9%) BAL samples and in 15 (33.3%) serum samples, wherein the 45 BAL samples represented immunocompetent cases and 45 serum samples represented immunocompromised cases. Sensitivity and specificity of GM assay in BAL samples were found to be 100% and 97%, respectively. On the other hand, sensitivity and specificity in serum samples were found to be 94.1% and 100%, respectively.
In patients of HIV, 10 (33.3%) were positive for Aspergillus culture and galactomannan antigen in serum. Cases of pulmonary tuberculosis showed a positivity of 1 (50%) on culture and the same for galactomannan antigen. In patients with lung carcinoma, 10 (26.3%) were positive for culture whilst 11 (29%) were positive for galactomannan antigen. Twenty-one per cent of these patients had galactomannan in BAL whilst 7.9% of them had antigen in serum. In patients with secondaries in lung, 5 (41.7.3%) were positive for culture and 4 (33.3%) for galactomannan antigen that is, 25% in BAL and 8.3% in serum. In cases of chronic obstructive pulmonary disease (COPD), 1 (20%) was culture positive and positive for galactomannan antigen in BAL as well. In cases of pneumonia, 1 (50%) was positive for culture and galactomannan antigen in serum.
All patients were categorised into four categories as proven invasive pulmonary aspergillosis (IPA), probable IPA, possible IPA and non-IPA. 22 (24.4%) patients were of proven IPA, 7 (7.8%) of probable IPA, 2 (2.2%) belonged to possible IPA whilst 59 (65.5%) were of non-IPA [Table 2].
|Table 2: Classification of patients according to aspergillosis type (Ben De Pau et al., 2008)|
Click here to view
All of the cases of proven IPA were positive on culture. 20 (91%) of them showed fungal elements for Aspergillus on direct microscopy and 16 (72.7%) showed histopathological findings of Aspergillus. Twelve of these patients were positive for GM in BAL and 10 in serum. Furthermore, 20 cases showed radiological findings positive for pulmonary aspergillosis.
The minimum inhibitory concentration (MIC) values of both Candida and Aspergillus isolates were calculated by Broth Microdilution method and resistance was also tested by the disc diffusion method. Amongst Candida isolates, resistance to fluconazole was observed in 6.9% isolates of C. albicans. 50% of C. dubliniensis and 20% of C. glabrata showed resistance to fluconazole. In addition, resistance to ketoconazole was seen in 25% isolates of C. dubliniensis. Only 1 isolate showed resistance to AMB which was of C. glabrata (20%) and no isolate was found to be resistant to caspofungin.
Resistance to amphotericin B was observed in 11.8% of A. fumigatus, 10% of A. flavus and 33.3% of A. niger. Resistance to itraconazole was seen in 11.8% of A. fumigatus, 20% of A. flavus and 33.3% of A. niger. Resistance to ketoconazole was seen in 11.1% of A. fumigatus, 14.2% of A. flavus and 100% of A. niger. No resistance was observed against caspofungin against any species of Aspergillus. Factors affecting clinical outcome of patients were analysed and the fungal infections were correlated with their mean CD4 counts. Candida spp. were seen in 17 cases with mean of CD4 as 106.5 ± 63.5 cells/μl and from 12 immunocompetent patients with a mean of CD4 as 702.8 (± 72.0).
A total of 18 cases of IPA were seen with mean of CD4 as 101 (± 19.2). Pulmonary aspergillosis was also seen in 13 immunocompetent patients (mean CD4 range 720 ± 50.3).
C. neoformans, P. jirovecii and P. marneffei were detected from patients with mean of CD4 count <200, 114 (± 19.9) and <100, respectively.
A mortality of 27.7% (18 of 65) was observed during this study and 10 (15%) were lost to follow up. Patients of candidiasis demonstrated a mortality of 24.1%, 8 (26.7%) patients of pulmonary aspergillosis died. Of these, 6 were proven IPA and 2 of probable IPA. Cases of cryptococcosis and pneumocystosis showed a mortality rate of 50%. 100% mortality rate was observed in pulmonary mucormycosis and the single case of penicillosis survived [Table 3].
On follow-up, after 12 months of treatment, majority that is, 33 (55%) of the cases had stable CD4 counts and 35% showed improved counts. Fall in counts was observed in 5 (8.3%) patients and 1 (1.6%) was lost to follow-up [Figure 1] and [Figure 2].
|Figure 1: Clinical outcomes of the patients during follow-up with relation to fungal infection|
Click here to view
|Figure 2: Clinical outcomes of the patients during follow-up with relation to CD4 counts|
Click here to view
| ~ Discussion|| |
There has been an expansion of medical facilities with ongoing building and construction work, urbanisation, climate changes and events such as the 2004 tsunami in the Indian Ocean have affected the epidemiology of invasive fungal infections. An insight into the current scenario within the Asia-Pacific region is important. Of the total 33 isolates, 14 (42.4%) isolates were of C. albicans; 64.3% from the immunocompromised and 35.7% from the immunocompetent. Ten (71.4%) isolates of these were from patients of pulmonary tuberculosis. This is because tuberculosis has always seemed to be associated with many other secondary infections, the most common amongst them being Candida spp. infection.
The remaining 19 (57.5%) isolates of Candida were NAC. Likewise, non-albicans Candida was isolated from majority (29%) of patients whilst C. albicans were isolated from just 26% of patients in a study of. The distribution of NAC in our study was 12.1% by C. dubliniensis, 15.1% by C. glabrata, 9.1% each by C. parapsilosis and C. tropicalis. For each of these species, the contribution was either equal or greater in the immunocompromised patients, except for C. tropicalis where 2 (66.6%) were seen in immunocompetent patients as compared to just 1 (33.3%) isolate from an HIV-positive patient. The higher rate of detection can be explained by the longevity of hospitalisation of the severely immunocompromised individual (HIV-positive patients) that has allowed these species to emerge and cause diseases. Furthermore, of the various NAC, C. dubliniensis is known to be associated with HIV-positive patients which supports its higher prevalence in our study.
Pulmonary cryptococcosis was seen in 2 (1.3%) patients, both of which were HIV positive, one of which was also a case of multidrug-resistant TB. Similar observations of 1.6% and 1.2% were reported by Wadhwa et al. and Khan et al., respectively.,
P. jirovecii was found positive in 2.5% (2 out of 80) of immunocompromised patients, both of which were from children. North Indian studies with similar prevalence rates of 1.8% and 1.3% have been evidenced by Vajpayee et al. and Khan et al., respectively., This low prevalence may be due to lack of diagnosis or prevalence of more virulent conditions, such as tuberculosis, leading to pulmonary disease before pneumocystis pneumonia (PCP) could manifest. However, Wadhwa et al. found pneumocystis jirovecii pneumonia (PJP) in 8.3% of patients. However, no cases were reported amongst the immunocompetent patients in our study. PCP has been rarely reported in immunocompetent patients.
Twelve (40%) of Aspergillus isolates were found in relatively immunocompetent patients of which 1 was of COPD and the rest were of initial stages of lung cancer or secondaries. Whilst not common, IA has been noted in several reports of cases within the Asia-Pacific region.,,
Of all the Aspergillus species isolated, A. fumigatus was the most common (53.1%) followed by A. flavus (31.2%) and A. niger (9.3%). This is consistent with the fact that in Asia-Pacific countries with a temperate climate, A. fumigatus is the most common species isolated.
In the present study, GM assay was conducted in both BAL and serum samples, 45 each. BAL was taken from immunocompetent patients and serum from the immunocompromised. This was because reports have shown that in BAL samples, the test showed a high sensitivity amongst patients who have non-haematologic cancer (solid-organ transplant recipients, chronic obstructive pulmonary disease, patients in the Intensive Care Unit,,,,, whereas the sensitivity of the test in serum was particularly low in this subgroup. These differences may be explained by a lower degree of angioinvasion in these patients who are still capable of having a local inflammatory reaction confining the disease to the lung.
BAL positivity for GM was seen in 13 (28.9%) samples and culture of same samples was positive in 12 (26.6%) patients. False-positive results can be caused by various factors as coded by., Therefore, galactomannan detection does not remove the need for careful microbiological and clinical evaluations. History of intake of steroids and antibiotics was present in the single case negative for culture and positive for GM.
In serum samples, GM was positive in 15 (33.3%), the cultures of which showed positive isolates in 16 (35.5%) samples. Higher positivity in serum samples as compared to BAL samples can be attributed to the pool of samples representing immunocompromised patients. 1 (3.1%) isolate of Mucor was found in a diabetic individual. In a series from India, approximately 12% of cases occurred in immunocompetent individuals.
All patients were categorised into four categories as proven IPA, probable IPA, possible IPA and non-IPA as described by De Pauw et al. Twenty-two (24.4%) patients were of proven IPA, 7 (7.8%) of probable IPA, 2 (2.2%) belonged to possible IPA whilst 59 (65.5%) were of non-IPA. In a study conducted by Ali et al., 20% patients were found to be of proven IPA, 32.5% of probable IPA and 17.5% of possible IPA and 30% of their patients did not meet any of the criteria for IPA. Therefore, GM assay in BAL showed a sensitivity of 100% and a specificity of 97%. Overall, the assay had a sensitivity of 71% and specificity of 89% for proven cases of invasive aspergillosis. Our specificity of GM assay is similar to that analysed by Pfeiffer et al. In serum samples, however, a lower sensitivity of 94.1% was observed. According to Lahmer et al., a lower sensitivity of 35% and a specificity of 70% were observed in serum samples as compared to a sensitivity of 70% and a specificity of 94% using BAL samples in the same critically ill patients, although our study showed a higher sensitivity.
Resistance was observed in 13.8% isolates to fluconazole and clotrimazole, 6.9% isolates to ketoconazole and 3.4% isolates to amphotericin B. These findings are in agreement with a study conducted.
Resistance to fluconazole was observed in 6.9% isolates of C. albicans. Similar finding also reported by Rizvi et al. As compared to C. albicans, most of the NAC usually exhibit a reduced susceptibility to the common antifungal agents, especially C. glabrata which exhibits reduced fluconazole susceptibility. Our study also demonstrated a higher rate of fluconazole resistance amongst NAC (13.8%) as shown by Deorukhar et al. Amongst NAC, 50% of C. dubliniensis and 20% of C. glabrata showed resistance to fluconazole. In addition, resistance to ketoconazole was seen in 25% isolates of C. dubliniensis. Maheshwari M et al., in a study on HIV-positive patients from Delhi, showed that C. dubliniensis was one of the most common isolates and resistance was also significant. No isolate was found resistant to caspofungin. Caspofungin was shown to be equivalent to (and less toxic than) amphotericin B in the treatment of patients with invasive candidiasis. Moreover, they exhibit potent activity against fluconazole-resistant Candida sp.
For all the 30 Aspergillus isolates, MIC ranges for amphotericin B, itraconazole and caspofungin were identified. Resistance to amphotericin B was observed in 11.8% of A. fumigatus, 10% of A. flavus and 33.3% of A. niger. Resistance to itraconazole was seen in 11.8% of A. fumigatus, 20% of A. flavus and 33.3% of A. niger. Resistance to ketoconazole was seen in 11.1% of A. fumigatus, 14.2% of A. flavus and 100% of A. niger. No resistance was observed against caspofungin against any species of Aspergillus. Resistance to caspofungin in Aspergillus has not been reported from India. This could be because caspofungin is still the least used antifungal in India.
Most of the patients included in this study were in advanced stage of disease, 60% were categorised had their counts below 500. Fourteen (23.3%) were classified in end stage with counts below 350, whilst only 16.6% had their CD4 counts above 500. This can be attributed to lack of awareness regarding the clinical spectrum amongst the general population along with the absence of diagnostic facilities at the peripheral health centres. Hence, the consequent delay in reaching tertiary health centres. Furthermore, it is well known that the normal range of CD4+ and CD8+ lymphocyte counts varies amongst different ethnic groups with the median CD4+ count amongst normal healthy Indians being significantly lower than that in African and Caucasians.,
The occurrence of oropharyngeal candidiasis (OPC) and oesophageal candidiasis (OEC) are indicators of profound immune suppression, and these syndromes are most often observed in patients with CD4+ counts <200 cells/μL with OEC being found in a more advanced stage of AIDS than OPC. This is similar to our observation of mean of 106.5 ± 63.5 cells/μl. Isolates were also found from immunocompetent patients with a mean of CD4 as 702.8 (± 72.0).
Cornillet et al. found neutropenia during the previous 15 days as a major risk factor for pulmonary aspergillosis. Majority (58%) of our cases had a mean of CD4 below 150, as supported by Meyer RD et al. Our study also showed pulmonary aspergillosis in immunocompetent patients (mean CD4 range 720 ± 50.3) which can be attributed to predisposing risk factors such as smoking, occupational exposure and underlying chronic lung diseases.
Cryptococcus was isolated from both patients with CD4 count <200. Studies from Pune and Delhi show comparable results of 114 and 135, respectively.,
PJP was seen in HIV-positive cases with a mean of CD4 as 114 (± 19.9). A study by Vajpayee et al. also reported CD4 counts of 150.
In the current prospective study, response to treatment and mortality during follow-up were assessed with relation to fungal infection and CD4 counts. Factors influencing the clinical outcome of patients were also analysed. Out of the 65 cases with diagnosed fungal infection, an overall mortality rate of 27.7% was seen. The (crude) mortality amongst people with candidemia is approximately 30%. Our study showed 24.1% which is comparable to a rate of 19%–24% observed by Morgan et al., (2005). 8 (26.7%) patients of pulmonary aspergillosis died. Of these, 6 were proven IPA and 2 of probable IPA. IPA causes a 25%–35% mortality despite the introduction of new antifungal agents such as voriconazole and echinocandins.,,
Ten patients were lost to follow-up. Some of these patients were either referred to higher centres and some did not return for further therapy.
The CD4 count is the most important laboratory indicator of immune function in HIV-infected patients. It is also the strongest predictor of subsequent disease progression and survival according to findings from clinical trials and cohort studies., The CD4 count is used to assess a patient's immunologic response to ART. It is also used to determine whether prophylaxis for OIs can be discontinued. On monitoring, the respective CD4 counts of all the HIV-positive patients, the first follow-up at 6 months revealed that 32 (53.3%) of patients continued to have stable counts, the counts improved in 19 (31.6%) and 8 (13.3%) patients demonstrated a fall in blood counts. After 12 months of treatment, 33 (55%) of the cases had stable counts and 21 (35%) showed an improvement in counts. Fall in counts was observed in 5 (8.3%) patients. 1 (1.6%) patient each was lost to follow-up at 6 months and 12 months.
For most patients on therapy, an adequate response is defined as an increase in CD4 count in the range of 50–150 cells/mm3 during the 1st year of ART, generally with an accelerated response in the first 3 months of treatment. Subsequent increases average approximately 50–100 cells/mm3/year until a steady state level is reached. This compares well with our study where majority of the patients showed stable counts after an initial rise.
| ~ Conclusions|| |
Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Baddley JW, Stroud TP, Salzman D, Pappas PG. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001;32:1319-24.
Pashley CH, Fairs A, Free RC, Wardlaw AJ. DNA analysis of outdoor air reveals a high degree of fungal diversity, temporal variability, and genera not seen by spore morphology. Fungal Biol 2012;116:214-24.
Denning DW, Pashley C, Hartl D, Wardlaw A, Godet C, Del Giacco S, et al.
Fungal allergy in asthma-state of the art and research needs. Clin Transl Allergy 2014;4:14.
Sharma SK, Kadhiravan T, Banga A, Goyal T, Bhatia I, Saha PK, et al.
Spectrum of clinical disease in a series of 135 hospitalised HIV-infected patients from North India. BMC Infect Dis 2004;4:52.
Arendrup MC. Update on antifungal resistance in Aspergillus
. Clin Microbiol Infect 2014;20 Suppl 6:42-8.
Mellors JW, Muñoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, et al.
Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997;126:946-54.
Egger M, May M, Chêne G, Phillips AN, Ledergerber B, Dabis F, et al.
Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: A collaborative analysis of prospective studies. Lancet 2002;360:119-29.
CDC, updated screening for communicable diseases of public health significance, CDC immigration requirements, 2014;4-5.
Chander J. Medical Mycology. 3rd
ed., Vol. 24. 2009. p. 556-70.
Clinical and Laboratory Standards Institute. Method for Antifungal Disc Diffusion Testing Susceptibility Testing of Yeasts; Approved Guideline. 2nd
ed. Clinical and Laboratory Standards Institute Document M44-A2. Wayne PA: Clinical and Laboratory Standards Institute; 2009.
Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard Clinical and Laboratory Standards Institute Document M38-A2. Wayne PA: Clinical and Laboratory Standards Institute; 2008.
Clinical and Laboratory Standards Institute. Method for Antifungal Disk Diffusion Susceptibility Testing of Non-Dermatophyte Filamentous Fungi; Approved Guideline, Clinical and Laboratory Standards Institute Document M51-A. Wayne PA. Clinical and Laboratory Standards Institute; 2010.
Slavin MA, Chakrabarti A. Opportunistic fungal infections in the Asia-Pacific region. Med Mycol 2012;50:18-25.
Bharathi M, Rani AU. Pathogenic fungal isolates in sputum of HIV positive patients. J AIDS HIV Res 2011;3:107-13.
Liu ZY, Sheng RY, Li XL, Li TS, Wang AX. Nosocomial fungal infections, analysis of 149 cases. Zhonghua Yi Xue Za Zhi 2003;83:399-402.
Wadhwa A, Kaur R, Agarwal SK, Jain S, Bhalla P. AIDS-related opportunistic mycoses seen in a tertiary care hospital in North India. J Med Microbiol 2007;56:1101-6.
Khan PA, Malik A, Fatima N, Shameem M. Profile of fungal lower respiratory tract infections and CD4 counts in HIV positive patients. Virol Mycol 2013;2:113.
Vajpayee M, Kanswal S, Seth P, Wig N. Spectrum of opportunistic infections and profile of CD4+ counts among AIDS patients in North India. Infection 2003;31:336-40.
Abouya YL, Beaumel A, Lucas S, Dago-Akribi A, Coulibaly G, N'Dhatz M, et al. Pneumocystis carinii
pneumonia. An uncommon cause of death in African patients with acquired immunodeficiency syndrome. Am Rev Respir Dis 1992;145:617-20.
Harris K, Maroun R, Chalhoub M, Elsayegh D. Unusual presentation of pneumocystis pneumonia in an immunocompetent patient diagnosed by open lung biopsy. Heart Lung Circ 2012;21:221-4.
Pongbhaesaj P, Dejthevaporn C, Tunlayadechanont S, Witoonpanich R, Sungkanuparph S, Vibhagool A, et al.
Aspergillosis of the central nervous system: A catastrophic opportunistic infection. Southeast Asian J Trop Med Public Health 2004;35:119-25.
Chakrabarti A, Chatterjee SS, Shivaprakash MR. Overview of opportunistic fungal infections in India. Nihon Ishinkin Gakkai Zasshi 2008;49:165-72.
Clancy CJ, Jaber RA, Leather HL, Wingard JR, Staley B, Wheat LJ, et al.
Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J Clin Microbiol 2007;45:1759-65.
Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, et al.
Galactomannan in bronchoalveolar lavage fluid: A tool for diagnosing aspergillosis in Intensive Care Unit patients. Am J Respir Crit Care Med 2008;177:27-34.
Luong ML, Clancy CJ, Vadnerkar A, Kwak EJ, Silveira FP, Wissel MC, et al.
Comparison of an Aspergillus
real-time polymerase chain reaction assay with galactomannan testing of bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in lung transplant recipients. Clin Infect Dis 2011;52:1218-26.
He H, Ding L, Sun B, Li F, Zhan Q. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: A prospective study. Crit Care 2012;16:R138.
Zhang XB, Chen GP, Lin QC, Lin X, Zhang HY, Wang JH, et al.
Bronchoalveolar lavage fluid galactomannan detection for diagnosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease. Med Mycol 2013;51:688-95.
Aubry A, Porcher R, Bottero J, Touratier S, Leblanc T, Brethon B, et al.
Occurrence and kinetics of false-positive Aspergillus
galactomannan test results following treatment with beta-lactam antibiotics in patients with hematological disorders. J Clin Microbiol 2006;44:389-94.
Martín-Rabadán P, Gijón P, Alonso Fernández R, Ballesteros M, Anguita J, Bouza E, et al.
antigenemia due to blood product conditioning fluids. Clin Infect Dis 2012;55:e22-7.
Zmeili OS, Soubani AO. Pulmonary aspergillosis: A clinical update. QJM 2007;100:317-34.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al.
Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813-21.
Ali S, Malik A, Shahid M, Bhargava R. Pulmonary aspergillosis and aflatoxins in chronic lung diseases. Mycopathologia 2013;176:287-94.
Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: A meta-analysis. Clin Infect Dis 2006;42:1417-27.
Lahmer T, Rasch S, Schnappauf C, Beitz A, Schmid RM, Huber W, et al.
Comparison of serum galactomannan and 1,3-beta-D-glucan determination for early detection of invasive pulmonary aspergillosis in critically ill patients with hematological malignancies and septic shock. Mycopathologia 2016;181:505-11.
Xess I, Jain N, Hasan F, Mandal P, Banerjee U. Epidemiology of candidemia in a tertiary care centre of North India: 5-year study. Infection 2007;35:256-9.
Rizvi MW, Malik A, Shahid M, Singhal S. Candida albicans
infections in a North Indian tertiary care hospital: Antifungal resistance pattern and role of SDS-PAGE for characterization. Biol Med 2011;3:176-81.
Eraso E, Moragues MD, Villar-Vidal M, Sahand IH, González-Gómez N, Pontón J, et al.
Evaluation of the new chromogenic medium Candida
ID 2 for isolation and identification of Candida albicans
and other medically important Candida
species. J Clin Microbiol 2006;44:3340-5.
Deorukhkar S, Saini S. Non-Candida albicans
species: Its isolation pattern, species distribution, virulence factors and antifungal susceptibility profile. Int J Med Sci Public Health 2013;2:533-8.
Maheshwari M, Kaur R, Chadha S. Candida
species prevalence profile in HIV seropositive patients from a major tertiary care hospital in New Delhi, India. J Pathog 2016;2016:6204804.
Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al.
Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002;347:2020-9.
Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ, Jones RN, et al
. In vitro
activities of voriconazole, posaconazole, and four licensed systemic antifungal agents against Candida
species infrequently isolated from blood. J Clin Microbiol 2003;41:78-83.
Shivaprakash MR, Geertsen E, Chakrabarti A, Mouton JW, Meis JF.In vitro
susceptibility of 188 clinical and environmental isolates of Aspergillus flavus
for the new triazole is avuconazole and seven other antifungal drugs. Mycoses 2011;54:e583-9.
Kam KM, Wong KH, Li PC, Lee SS, Leung WL, Kwok MY, et al.
Proposed CD4(+) T-cell criteria for staging human immunodeficiency virus-infected Chinese adults. Clin Immunol Immunopathol 1998;89:11-22.
Thakar MR, Abraham PR, Arora S, Balakrishnan P, Bandyopadhyay B, Joshi AA, et al.
Establishment of reference CD4+ T cell values for adult Indian population. AIDS Res Ther 2011;8:35.
Lortholary O, Dupont B. Fungal infections among patients with AIDS. In: Kaufman CA, Pappas PP, Sobel JD, Dismukes WE, editors. Essential of Clinical Mycology. 2nd
ed. New York: Springer; 2011. p. 525-36.
Cornillet A, Camus C, Nimubona S, Gandemer V, Tattevin P, Belleguic C, et al.
Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: A 6-year survey. Clin Infect Dis 2006;43:577-84.
Meyer RD, Gaultier CR, Yamashita JT, Babapour R, Pitchon HE, Wolfe PR, et al.
Fungal sinusitis in patients with AIDS: Report of 4 cases and review of the literature. Medicine (Baltimore) 1994;73:69-78.
Jung N, Mronga S, Schroth S, Vassiliou T, Sommer F, Walthers E, et al.
Gardening can induce pulmonary failure: Aspergillus
ARDS in an immunocompetent patient, a case report. BMC Infect Dis 2014;14:600.
Ghate M, Deshpande S, Tripathy S, Nene M, Gedam P, Godbole S, et al.
Incidence of common opportunistic infections in HIV-infected individuals in Pune, India: Analysis by stages of immunosuppression represented by CD4 counts. Int J Infect Dis 2009;13:e1-8.
Cleveland AA, Farley MM, Harrison LH, Stein B, Hollick R, Lockhart SR, et al.
Changes in incidence and antifungal drug resistance in candidemia: Results from population-based laboratory surveillance in Atlanta and Baltimore, 2008-2011. Clin Infect Dis 2012;55:1352-61.
Morgan J, Meltzer MI, Plikaytis BD, Sofair AN, Huie-White S, Wilcox S, et al.
Excess mortality, hospital stay, and cost due to candidemia: A case-control study using data from population-based candidemia surveillance. Infect Control Hosp Epidemiol 2005;26:540-7.
Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J, et al.
Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: Analysis of multicenter prospective antifungal therapy (PATH) alliance registry. Clin Infect Dis 2009;48:265-73.
Babor F, Schuster F, Mackenzie C, Meisel R, Schaper J, Sabir H, et al.
Invasive aspergillosis in pediatric oncology patients: A rare event with poor prognosis – Case analysis to plan better targeted prophylactic or therapeutic measurement. Klin Padiatr 2012;224:160-5.
Steinbach WJ, Marr KA, Anaissie EJ, Azie N, Quan SP, Meier-Kriesche HU, et al.
Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH alliance registry. J Infect 2012;65:453-64.
Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, et al.
CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: The Swiss HIV cohort study. Arch Intern Med 2003;163:2187-95.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]