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Article: Diagnostic accuracy of different cut-off values of adenosine deaminase levels in tuberculous pleural effusion.

Masood, Kiran Iqbal / Shahid, Shayan / Jabeen, Kauser / Farooqi, Joveria / Kerawala, Sabeika Raza / Irfan, Muhammad

JPMA. The Journal of the Pakistan Medical Association

2023 Volume 73, Issue 1, Page(s) 13–16

Abstract: Objectives: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion.: Methods: The prospective study was conducted from 2014 to 2016 at the Aga ... ...

Abstract	Objectives: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion. Methods: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, NY). Results: Of 155 patients, 46(29.7%) had tuberculosis; 30(65.2%) males and 16(34.8%) females. Those who did not have tuberculosis were 109(70.3%); 69(63.3%) males and 40(36.7%) females. The adenosine deaminase levels were elevated in group A compared to group B (p<0.001). The cut-off of 30U/L showed the highest sensitivity (71.7%) and negative predictive value (87.4%), and a specificity of 82.6%. The cut-off of 50U/L showed the highest specificity (89.9%) with sensitivity 52.2%, and the cut-off of 40U/L showed the highest positive predictive value of 68.9% with sensitivity 67.4% and specificity 87.2%. Conclusions: Pleural fluid adenosine deaminase testing for diagnosing tuberculosis pleuritis revealed highest sensitivity and moderate specificity for cut-off value of 30U/L.
MeSH term(s)	Male ; Adult ; Female ; Humans ; Adenosine Deaminase/analysis ; Prospective Studies ; Pleural Effusion/diagnosis ; Tuberculosis, Pleural/diagnosis ; Exudates and Transudates/chemistry ; Sensitivity and Specificity
Chemical Substances	Adenosine Deaminase (EC 3.5.4.4)
Language	English
Publishing date	2023-02-25
Publishing country	Pakistan
Document type	Journal Article
ZDB-ID	603873-6
ISSN	0030-9982
ISSN	0030-9982
DOI	10.47391/JPMA.4773
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Article ; Online: Tuberculosis and diabetes mellitus: Relating immune impact of co-morbidity with challenges in disease management in high burden countries.

Abbas, Uzair / Masood, Kiran Iqbal / Khan, Aalia / Irfan, Muhammad / Saifullah, Nausheen / Jamil, Bushra / Hasan, Zahra

Journal of clinical tuberculosis and other mycobacterial diseases

2022 Volume 29, Page(s) 100343

Abstract: Mycobacterium ... ...

Abstract	Mycobacterium tuberculosis
Language	English
Publishing date	2022-11-29
Publishing country	England
Document type	Journal Article
ISSN	2405-5794
ISSN (online)	2405-5794
DOI	10.1016/j.jctube.2022.100343
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Article ; Online: Immune mapping of human tuberculosis and sarcoidosis lung granulomas.

Carow, Berit / Muliadi, Victoria / Skålén, Kristina / Yokota, Chika / Kathamuthu, Gokul Raj / Setiabudiawan, Todia Pediatama / Lange, Christoph / Scheu, Katrin / Gaede, Karoline I / Goldmann, Torsten / Pandita, Ankur / Masood, Kiran Iqbal / Pervez, Shahid / Grunewald, Johan / Hasan, Zahra / Levin, Max / Rottenberg, Martin E

Frontiers in immunology

2024 Volume 14, Page(s) 1332733

Abstract: Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients ... ...

Abstract	Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients using
MeSH term(s)	Humans ; Granuloma ; Tuberculosis ; Sarcoidosis, Pulmonary/genetics ; Sarcoidosis, Pulmonary/pathology ; Sarcoidosis ; Mycobacterium tuberculosis ; Lung/pathology ; RNA, Messenger
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1332733
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Article: An audit of contrast extravasation in patients undergoing contrast enhanced CTs at radiology department in a tertiary care hospital in Pakistan.

Masood, Laiba / Yasir, Sanam / Rana, Atif Iqbal / Ali, Kiran Mian / Shah, Mariam / Riaz, Nimra

JPMA. The Journal of the Pakistan Medical Association

2022 Volume 72, Issue 8, Page(s) 1603–1607

Abstract: Objective: To audit the radiology department of a health facility, focusing on contrast extravasations management pre- and post-implementation of a standard protocol.: Methods: The audit was conducted at the Radiology Department of Shifa ... ...

Abstract	Objective: To audit the radiology department of a health facility, focusing on contrast extravasations management pre- and post-implementation of a standard protocol. Methods: The audit was conducted at the Radiology Department of Shifa International Hospital, Islamabad, Pakistan and comprised reported computed tomography contrast extravasation incidents from January 2017 to December 2019 in the retrospective phase before the implementation of a standard protocol. Post-implementation, re-audit was done prospectively to assess compliance from January 2020 to May 2021. Overall score of >80% was chosen arbitrarily as a qualifying standard for adequate documentation. Results: Of the 49 total cases, 26(53%) related to the first phase and 23(47%) to the second. In the first phase, 2(20%) of the 10 parameters cleared the cut-off mark; 'study performed' 25(96%) and 'limb assessment by technician' 26(100%). In the second phase, 2(20%) parameters failed to clear the cut-off mark; site of cannula/extravasation' 18(78.3%) and 'volume of contrast' 15(65%). Conclusions: Lack of early identification and appropriate management, especially in cases of large-volume extravasation, may result in significant morbidity.
MeSH term(s)	Humans ; Retrospective Studies ; Pakistan ; Tertiary Care Centers ; Extravasation of Diagnostic and Therapeutic Materials/diagnostic imaging ; Radiology
Language	English
Publishing date	2022-10-24
Publishing country	Pakistan
Document type	Journal Article
ZDB-ID	603873-6
ISSN	0030-9982
ISSN	0030-9982
DOI	10.47391/JPMA.4591
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Article ; Online: COVID-19 diagnostic testing underestimated cases amongst females in Pakistan

Ghanchi, Najia Karim / Masood, Kiran Iqbal / Nasir, Asghar / Islam, Nazneen / Ansar, Zeeshan / Hasan, Zahra

medRxiv

Abstract: Objectives Understanding the impact of COVID-19 largely depended on information from PCR based diagnostic testing of SARS-CoV-2. It was recognized early in the pandemic that testing rates varied greatly between high and low income countries. Whilst total ...

Abstract	Objectives Understanding the impact of COVID-19 largely depended on information from PCR based diagnostic testing of SARS-CoV-2. It was recognized early in the pandemic that testing rates varied greatly between high and low income countries. Whilst total numbers of tests conducted are noted, little attention has been made to differences that may be due to gender and we examined this in the context of Pakistan. Methods We conducted a retrospective cross-sectional analysis of respiratory specimens received for SARS-CoV-2 by PCR at Aga Khan University Hospital, Karachi, Pakistan between February 2020 and February 2022. Data was analysed in six monthly intervals; P-I, February to July 2020; P-II, August 2020 to January 2021; P-III, February to July 2021 and August 2021 until February 2022. Results A total of 470,047 PCR tests were conducted. The proportion of tests conducted for females was, 35% in P-I; 40% in P-II; 44% in P-III and 46% in P-III. 21% of specimens were positive for SARS-CoV-2, only 9% of these specimens were from females. The greatest numbers of tests were conducted in males aged 31 to 45 years followed by those aged 16-30 years. The fewest tests were conducted in children aged under 15 years. The highest percentage of PCR positive tests was found in those ages 60 years and above. Compared for gender SARS-CoV-2 positivity rates were comparable across the study period. Conclusions COVID-19 data from Pakistan indicates that there are larger numbers of males as compared with females who were affected by this disease. Our results show that this may be due to a gender bias in the demographics of testing. This was especially true in the early pandemic period, leading to under- surveillance and -reporting of COVID-19 cases in females especially, in those of younger and older age groups.
Keywords	covid19
Language	English
Publishing date	2023-02-01
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.01.30.23285225
Database	COVID19

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Article ; Online: Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in Pakistan.

Masood, Kiran Iqbal / Qaiser, Shama / Abidi, Syed Hani / Khan, Erum / Mahmood, Syed Faisal / Hussain, Areeba / Ghous, Zara / Imtiaz, Khekahsan / Ali, Natasha / Hasan, Muhammad / Memon, Haris Ali / Yameen, Maliha / Ali, Shiza / Baloch, Sadaf / Lakhani, Gulzar / Alves, Paula M / Iqbal, Najeeha Talat / Ahmed, Kumail / Iqbal, Junaid /

Bhutta, Zulfiqar A / Hussain, Rabia / Rottenberg, Martin / Simas, J Pedro / Veldhoen, Marc / Ghias, Kulsoom / Hasan, Zahra

BMC infectious diseases

2023 Volume 23, Issue 1, Page(s) 846

Abstract: Background: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG ... ...

Abstract	Background: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). Methods: HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell - IFN-γ activation was assessed by ELISpot. Results: Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. Conclusions: Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/epidemiology ; Pakistan/epidemiology ; Pandemics ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus ; T-Lymphocytes ; Immunoglobulin G ; Enzyme-Linked Immunospot Assay ; Antibodies, Viral ; Antibodies, Neutralizing ; Immunity, Humoral
Chemical Substances	Spike Glycoprotein, Coronavirus ; Immunoglobulin G ; Antibodies, Viral ; Antibodies, Neutralizing ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-023-08829-1
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Article ; Online: Latent M. tuberculosis infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)-3 in the diabetic host.

Masood, Kiran Iqbal / Irfan, Muhammad / Masood, Qamar / Yameen, Maliha / Jamil, Bushra / Ram, Nanik / Rao, Shoaib / Rottenberg, Martin / Hasan, Zahra

Scandinavian journal of immunology

2021 Volume 95, Issue 4, Page(s) e13134

Abstract: Tuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood. We ... ...

Abstract	Tuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood. We investigated mycobacterial antigen-stimulated responses in peripheral blood mononuclear cell (PBMC) isolated from healthy endemic controls (EC), those with LTBi, DM groups with and without LTBi, as compared with TB patients. Cytokines were measured using a Luminex-based assay. Gene expression was determined by RT-PCR. In DM-LTBi cases, PPD-stimulated proinflammatory cytokines; IFN-γ, IL-6, IL-2, TNF-α and GM-CSF and anti-inflammatory cytokines, IL-5 and IL-13 were raised as compared with EC. DM-LTBi PPD-stimulated IFN-γ, IL-6 and TNF-α mRNA titres were found raised in DM-LTBi, whilst suppressor of cytokine signalling (SOCS)-3 expression was lowered. Within DM cases, stratification based on HbA1c levels revealed raised IFN-γ but lowered IL-6 gene expression in those with controlled levels as compared with uncontrolled glycaemic levels. Further, SOCS1 expression levels were found higher in DM cases with controlled glycaemia when compared with EC. Overall, we show that diabetics with LTBi manifest raised levels of inflammatory and anti-inflammatory cytokines concomitant with reduced SOCS3 mRNA expression. Reduced glycaemic control results in further inflammatory dysregulation impacting conversing impacting IFN-γ and IL-6 activation. These results suggest that dysregulated immune activation in diabetes is exacerbated by LTBi, lack of glycaemic control may further compromise immunity against MTB infection.
MeSH term(s)	Antigens, Bacterial ; Cytokines/metabolism ; Diabetes Mellitus, Type 2 ; Humans ; Latent Tuberculosis ; Leukocytes, Mononuclear ; Mycobacterium tuberculosis ; Tuberculosis
Chemical Substances	Antigens, Bacterial ; Cytokines
Language	English
Publishing date	2021-12-30
Publishing country	England
Document type	Journal Article
ZDB-ID	120476-2
ISSN	1365-3083 ; 0300-9475
ISSN (online)	1365-3083
ISSN	0300-9475
DOI	10.1111/sji.13134
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Article ; Online: Tracking SARS-CoV-2 variants through pandemic waves using RT-PCR testing in low-resource settings.

Nasir, Asghar / Aamir, Uzma Bashir / Kanji, Akbar / Bukhari, Ali Raza / Ansar, Zeeshan / Ghanchi, Najia Karim / Masood, Kiran Iqbal / Samreen, Azra / Islam, Nazneen / Ghani, Samina / Syed, M Asif / Wassan, Mansoor / Mahmood, Syed Faisal / Hasan, Zahra

PLOS global public health

2023 Volume 3, Issue 6, Page(s) e0001896

Abstract: COVID-19 resulted in extensive morbidity and mortality worldwide. SARS-CoV-2 evolved rapidly, with increasing transmission due to Variants of Concern (VOC). Identifying VOC became important but genome submissions from low-middle income countries (LMIC) ... ...

Abstract	COVID-19 resulted in extensive morbidity and mortality worldwide. SARS-CoV-2 evolved rapidly, with increasing transmission due to Variants of Concern (VOC). Identifying VOC became important but genome submissions from low-middle income countries (LMIC) remained low leading to gaps in genomic epidemiology. We demonstrate the use of a specific mutation RT-PCR based approach to identify VOC in SARS-CoV-2 positive samples through the pandemic in Pakistan. We selected 2150 SARS-CoV-2 PCR positive respiratory specimens tested between April 2021 and February 2022, at the Aga Khan University Hospital Clinical Laboratories, Karachi, Pakistan. Commercially available RT-PCR assays were used as required for mutations in Spike protein (N501Y, A570D, E484K, K417N, L452R, P681R and deletion69_70) to identify Alpha, Beta, Gamma, Delta, and Omicron variants respectively. Three pandemic waves associated with Alpha, Delta and Omicron occurred during the study period. Of the samples screened, VOC were identified in 81.7% of cases comprising mainly; Delta (37.2%), Alpha (29.8%) and Omicron (17.1%) variants. During 2021, Alpha variants were predominant in April and May; Beta and Gamma variants emerged in May and peaked in June; the Delta variant peaked in July and remained predominant until November. Omicron (BA.1) emerged in December 2021 and remained predominant until February 2022. The CT values of Alpha, Beta, Gamma and Delta were all significantly higher than that of Omicron variants (p<0.0001). We observed VOC through the pandemic waves using spike mutation specific RT-PCR assays. We show the spike mutation specific RT-PCR assay is a rapid, low-cost and adaptable for the identification of VOC as an adjunct approach to NGS to effectively inform the public health response. Further, by associating the VOC with CT values of its diagnostic PCR we gain information regarding the viral load of samples and therefore the level of transmission and disease severity in the population.
Language	English
Publishing date	2023-06-01
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0001896
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Article: Testing for

Masood, Kiran Iqbal / Jamil, Bushra / Akber, Alnoor / Hassan, Maheen / Islam, Muniba / Hasan, Zahra

Tropical diseases, travel medicine and vaccines

2020 Volume 6, Page(s) 3

Abstract: Introduction: There were 10 million new cases of tuberculosis (TB) in 2017. To eliminate TB, it is necessary to diagnose active TB and latent tuberculosis infection (LTBI). Diagnosis of paucibacillary disease and in extrapulmonary TB (EPTB) remains ... ...

Abstract	Introduction: There were 10 million new cases of tuberculosis (TB) in 2017. To eliminate TB, it is necessary to diagnose active TB and latent tuberculosis infection (LTBI). Diagnosis of paucibacillary disease and in extrapulmonary TB (EPTB) remains challenging; low mycobacterial load can be missed by microbiological or molecular based confirmation; EPTB, can be misdiagnosed due to absence of site specific specimens for testing. Interferon gamma release assays (IGRA) use T cell-based Interferon-gamma (IFN-γ) to identify infection with Methods: We conducted a retrospective review of 149 consecutive cases received for QuantiFERON-TB Gold In-Tube Assay (QFT-GIT) testing in routine clinical service. Results: Fifty-six cases were QFT-GIT positive and 93 were QFT-GIT negative. Thirty-six per cent of QFT-GIT tested cases had active TB. Of QFT-GIT positive cases, 59% patients had active TB; 10 with pulmonary and 23 with extra-pulmonary TB. The remaining 41% QFT-positive cases were LTBI. Of the QFT-GIT negative cases, 22% had active TB. Co-morbid conditions were present in 37% of QFT-GIT positive and 60% of QFT-GIT negative cases. Conclusions: Our study shows that IGRA is being used as an adjunct test for active TB in this population. It highlights the complexity of interpreting QFT-GIT results particularly for QFT-GIT negative cases when ruling out MTB infection.
Language	English
Publishing date	2020-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2835327-4
ISSN	2055-0936
ISSN	2055-0936
DOI	10.1186/s40794-020-0102-z
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Article ; Online: Lipid A-Ara4N as an alternate pathway for (colistin) resistance in Klebsiella pneumonia isolates in Pakistan.

Masood, Kiran Iqbal / Umar, Seema / Hasan, Zahra / Farooqi, Joveria / Razzak, Safina Abdul / Jabeen, Nazish / Rao, Jason / Shakoor, Sadia / Hasan, Rumina

BMC research notes

2021 Volume 14, Issue 1, Page(s) 449

Abstract: Objectives: This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n = 34) stored at - 80 °C as part ...

Abstract	Objectives: This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n = 34) stored at - 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR. To investigate mechanisms of resistance, other than plasmid mediated mcr-1 gene, whole genome sequencing was performed on 8 clinical isolates, including 6 with colistin resistance (MIC > 4 μg/ml) and 2 with intermediate resistance to colistin (MIC > 2 μg/ml). Results: RT-PCR conducted revealed absence of mcr-1 gene in all isolates tested. Whole genome sequencing results revealed modifications in Lipid A-Ara4N pathway. Modifications in Lipid A-Ara4N pathway were detected in ArnA_ DH/FT, UgdH, ArnC and ArnT genes. Mutation in ArnA_ DH/FT gene were detected in S3, S5, S6 and S7 isolates. UgdH gene modifications were found in all isolates except S3, mutations in ArnC were present in all except S1, S2 and S8 and ArnT were detected in all except S4 and S7. In the absence of known mutations linked with colistin resistance, lipid pathway modifications may possibly explain the phenotype resistance to colistin, but this needs further exploration.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/genetics ; Colistin/pharmacology ; Drug Resistance, Bacterial/genetics ; Humans ; Klebsiella pneumoniae/genetics ; Laboratories, Clinical ; Lipid A ; Microbial Sensitivity Tests ; Pakistan ; Plasmids ; Pneumonia/drug therapy
Chemical Substances	Anti-Bacterial Agents ; Bacterial Proteins ; Lipid A ; Colistin (Z67X93HJG1)
Language	English
Publishing date	2021-12-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-021-05867-3
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