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Article ; Online: Editorial: Immunological Memory to Fungal Infections and Vaccine Development.

Nicola, André Moraes / Desai, Jigar V / Swidergall, Marc / Shey, Muki / Dambuza, Ivy M

2022 Volume 13, Page(s) 880037

MeSH term(s)	Humans ; Immunologic Memory ; Lung Diseases, Fungal ; Mycoses/prevention & control ; Vaccine Development
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.880037
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Article ; Online: Mucosal-associated invariant T cells in natural immunity and vaccination against infectious diseases in humans.

Masina, Nomawethu / Bekiswa, Abulele / Shey, Muki

Current opinion in immunology

2021 Volume 71, Page(s) 1–5

Abstract: Mucosal-associated invariant T (MAIT) cells are subsets of T cells abundant in human mucosal tissues and in blood. These cells are activated directly by cytokines or by vitamin B metabolites antigen presentation. MAIT cells possess antimicrobial ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are subsets of T cells abundant in human mucosal tissues and in blood. These cells are activated directly by cytokines or by vitamin B metabolites antigen presentation. MAIT cells possess antimicrobial potential against viruses and bacteria through production of cytokines and cytotoxic molecules. MAIT cells generally reduce in numbers and function during viral and bacterial infections/diseases. Mice and humans lacking MAIT cells cannot effectively control bacterial infections. MAIT cells respond rapidly to infections and are rapidly recruited to the site of vaccination or infection including the lungs where they can be involved in controlling local inflammation. These characteristics of MAIT cells offer them a unique potential to be explored as potential targets for vaccines.
MeSH term(s)	Animals ; Bacterial Infections/immunology ; Humans ; Inflammation/immunology ; Mucosal-Associated Invariant T Cells/immunology ; Vaccination ; Vaccines/immunology
Chemical Substances	Vaccines
Language	English
Publishing date	2021-03-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2021.03.007
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Zs.A 2773: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 13: Show issues

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Article: Relationship Between

Stek, Cari / Shey, Muki / Mnika, Khuthala / Schutz, Charlotte / Thienemann, Friedrich / Wilkinson, Robert J / Lynen, Lutgarde / Meintjes, Graeme

Open forum infectious diseases

2023 Volume 10, Issue 7, Page(s) ofad379

Abstract: The development of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) and its prevention using prednisone may potentially be mediated by ... ...

Abstract	The development of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) and its prevention using prednisone may potentially be mediated by the
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad379
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Article ; Online: Antibody tests for diagnosing COVID-19: how relevant are they?

Shey, Muki Shehu / Schmidt, Bey-Marrié / Wiysonge, Charles Shey

The Pan African medical journal

2020 Volume 37, Issue Suppl 1, Page(s) 4

Abstract: The current standards for detecting active coronavirus disease (COVID-19) infection are molecular tests by reverse transcription polymerase chain reaction, using swabs from the lower or upper respiratory tract. Because of the expertise required and the ... ...

Abstract	The current standards for detecting active coronavirus disease (COVID-19) infection are molecular tests by reverse transcription polymerase chain reaction, using swabs from the lower or upper respiratory tract. Because of the expertise required and the long turnaround time for the availability of test results, faster and easier point-of-care methods are necessary. The latter may include the detection of antibodies specific to COVID-19. We highlight a recent Cochrane review that assessed the accuracy of antibody tests for diagnosing COVID-19. The review shows that, at present, antibodies have little use in the diagnosis of COVID-19 within the first seven days from onset of symptoms. However, as time progresses, the sensitivity of the antibody tests increases. Antibody tests are more useful in detecting previous COVID-19 infection if used 15 days or more from onset of symptoms. Data presented in the review should be interpreted with caution as most studies (85%) recruited in-hospital patients and 11% recruited suspected COVID-19 patients, while only 4% recruited convalescent patients. This limits generalisability of the results to most settings.
MeSH term(s)	COVID-19/diagnosis ; COVID-19 Serological Testing ; Humans ; Sensitivity and Specificity
Language	English
Publishing date	2020-09-08
Publishing country	Uganda
Document type	Journal Article
ZDB-ID	2514347-5
ISSN	1937-8688 ; 1937-8688
ISSN (online)	1937-8688
ISSN	1937-8688
DOI	10.11604/pamj.supp.2020.37.4.25822
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Article ; Online: How Does Large-Scale Genomic Analysis Shape Our Understanding of COVID Variants in Real Time?

van Dorp, Lucy / Shey, Muki S / Ghedin, Elodie / Michor, Franziska / Koonin, Eugene V / Hampson, Katie

Cell systems

2021 Volume 12, Issue 2, Page(s) 109–111

MeSH term(s)	COVID-19/genetics ; Genomics/methods ; Humans ; SARS-CoV-2/genetics
Language	English
Publishing date	2021-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2854138-8
ISSN	2405-4720 ; 2405-4712
ISSN (online)	2405-4720
ISSN	2405-4712
DOI	10.1016/j.cels.2021.01.004
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Article: Pharmacokinetics of antitubercular drugs in patients hospitalized with HIV-associated tuberculosis: a population modeling analysis.

Abdelgawad, Noha / Chirehwa, Maxwell / Schutz, Charlotte / Barr, David / Ward, Amy / Janssen, Saskia / Burton, Rosie / Wilkinson, Robert J / Shey, Muki / Wiesner, Lubbe / McIlleron, Helen / Maartens, Gary / Meintjes, Graeme / Denti, Paolo

Wellcome open research

2024 Volume 7, Page(s) 72

Abstract: Background: Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of ... ...

Abstract	Background: Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups. Methods: Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM Results: Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin's absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid's clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide's clearance was more variable among hospitalized patients. The variability in clearance among patients was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients. Conclusions: We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts, as well as hospitalized patients who survived vs who died within 12 weeks of hospitalization.
Language	English
Publishing date	2024-03-01
Publishing country	England
Document type	Journal Article
ISSN	2398-502X
ISSN	2398-502X
DOI	10.12688/wellcomeopenres.17660.3
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Article ; Online: Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy.

Madlala, Hlengiwe P / Myer, Landon / Geffen, Hayli / Rusch, Jody / Shey, Muki S / Meyer, Demi / Goedecke, Julia H / Malaba, Thokozile R / Gray, Clive M / Newell, Marie-Louise / Jao, Jennifer

Journal of acquired immune deficiency syndromes (1999)

2024

Abstract: Background: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH.: Setting: A total of 57 ... ...

Abstract	Background: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH. Setting: A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included. Methods: Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks. Results: Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain. Conclusion: These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000003406
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Zs.A 2442: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Global inequity of COVID-19 diagnostics: challenges and opportunities.

Narayanasamy, Shanti / Okware, Brenda / Muttamba, Winters / Patel, Kirtika / Duedu, Kwabena Obeng / Ravi, Nirmal / Ellermeier, Nathan / Shey, Muki / Woods, Christopher W / Sabiiti, Wilber

Journal of epidemiology and community health

2022

Language	English
Publishing date	2022-10-06
Publishing country	England
Document type	Journal Article
ZDB-ID	391868-3
ISSN	1470-2738 ; 0142-467X ; 0141-7681 ; 0143-005X
ISSN (online)	1470-2738
ISSN	0142-467X ; 0141-7681 ; 0143-005X
DOI	10.1136/jech-2022-219333
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Zs.A 186: Show issues

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Article ; Online: Fractional dose compared with standard dose inactivated poliovirus vaccine in children: a systematic review and meta-analysis.

Mashunye, Thandiwe R / Ndwandwe, Duduzile E / Dube, Kopano R / Shey, Muki / Shelton, Mary / Wiysonge, Charles S

The Lancet. Infectious diseases

2021 Volume 21, Issue 8, Page(s) 1161–1174

Abstract: Background: Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies ... ...

Abstract	Background: Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-dose IPV vaccination to determine when seroconversion proportions with each strategy become similar in children aged 5 years and younger. Method: In this systematic review and meta-analysis, we searched 16 databases in July, 2019, for trials and observational studies, including ongoing studies that compare immunogenicity and adverse events of fractional-dose (0·1 mL) to full-dose (0·5 mL) IPV in healthy children aged 5 years or younger regardless of study design, number of doses, and route of administration. Screening, selection of articles, data extraction, and risk of bias assessment were done in duplicate, and conflicts were resolved by discussion or arbitration by a third author. We assessed immunogenicity, the main outcome, as proportion of seroconverted participants and changes in geometric mean titres of anti-poliovirus antibodies. Timepoints were eligible for analysis if measurements were done at least 4 weeks after vaccination. Summary estimates were pooled by use of random-effects meta-analysis. Analysis was stratified by study design, type of outcome measure, type of poliovirus, and number of doses given. We assessed heterogeneity using the χ Findings: 860 records were screened for eligibility, of which 36 potentially eligible full-text articles were assessed and 14 articles were included in the final analysis: two ongoing trials and 12 articles reporting on ten completed studies. For poliovirus type 2, there were no significant differences in the proportions of seroconversions between fractional and full doses of IPV for two or three doses: the risk ratio for serconversion at one dose was 0·61 (95% CI 0·51-0·72), at two doses was 0·90 (0·82-1·00), and at three doses was 0·95 (0·91-1·00). Geometric mean titres (GMTs) for poliovirus type 2 were lower for fIPV than for full-dose IPV: -0·51 (95% CI -0·87 to -0·14) at one dose, -0·49 (-0·70 to -0·28) at two doses, and -0·98 (-1·46 to -0·51) at three doses. The seroconversion meta-analysis for the three-dose comparison was homogeneous (p=0·45; I Interpretation: There is no substantial difference in seroconversion between three doses of fIPV and three doses of full-dose IPV, although the full dose gives higher titres of antibodies for poliovirus type 1, 2, and 3. Use of fractional IPV instead of the full dose can stretch supplies and possibly lower the cost of vaccination. Funding: South African Medical Research Council and the National Research Foundation of South Africa.
MeSH term(s)	Administration, Oral ; Antibodies, Viral/blood ; Child, Preschool ; Dose-Response Relationship, Immunologic ; Humans ; Immunization Schedule ; Immunogenicity, Vaccine ; Injections, Intradermal ; Poliomyelitis/prevention & control ; Poliovirus ; Poliovirus Vaccine, Inactivated/administration & dosage ; Poliovirus Vaccine, Inactivated/immunology ; Randomized Controlled Trials as Topic ; Seroconversion
Chemical Substances	Antibodies, Viral ; Poliovirus Vaccine, Inactivated
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(20)30693-9
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Zs.A 5743: Show issues

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Article ; Online: Mycobacterial-specific secretion of cytokines and chemokines in healthcare workers with apparent resistance to infection with

Shey, Muki Shehu / Balfour, Avuyonke / Masina, Nomawethu / Bekiswa, Abulele / Schutz, Charlotte / Goliath, Rene / Dielle, Rachel / Katoto, Patrick Dmc / Wilkinson, Katalin Andrea / Lewinsohn, David / Lewinsohn, Deborah Anne / Meintjes, Graeme

Frontiers in immunology

2023 Volume 14, Page(s) 1176615

Abstract: Background: Currently, diagnosis of latent TB infection (LTBI) is based on the secretion of IFN-γ in response to : Methods: We enrolled HIV-uninfected healthcare workers who had worked in high TB-exposure environments for 5 years or longer. We ... ...

Abstract	Background: Currently, diagnosis of latent TB infection (LTBI) is based on the secretion of IFN-γ in response to Methods: We enrolled HIV-uninfected healthcare workers who had worked in high TB-exposure environments for 5 years or longer. We screened them for LTBI using the tuberculin skin test and the QuantiFERON-TB Gold Plus assay. We performed multiplex Luminex to measure concentrations of T cell-associated cytokines and chemokines as well as total antibodies in plasma collected from unstimulated fresh whole blood and supernatants from QuantiFERON-TB Gold Plus tubes following incubation of whole blood for 16-24 hours with ESAT6/CFP10 peptides. Results: Samples from 78 individuals were analyzed: 33 resisters (TST<10mm; IGRA<0.35 IU/mL), 33 with LTBI (TST≥10mm and IGRA≥0.35 IU/mL) and 12 discordant (TST=0mm; IGRA≥1.0 IU/mL). There were no differences in concentrations of cytokines and chemokines in plasma between the different groups. Resisters had significantly lower concentrations of IFN-γ, IL-2, TNF-α, MIP-1α, MIP-1β, ITAC, IL-13 and GM-CSF in supernatants compared with LTBI group. There were no significant differences in the concentrations in supernatants of IL-10, IL-1β, IL-17A, IL-21, IL-23, MIP-3α, IL-4, IL-5, IL-6, IL-7, IL-8, Fractalkine and IL-12p70 between the groups. We observed that resisters had similar concentrations of total antibodies (IgG1, IgG2, IgG3, IgG4, IgA, and IgM) in plasma and supernatants compared to the LTBI and discordant groups. Conclusion: Resistance to Mtb infection despite sustained exposure is associated with lower Mtb-specific secretion of Th1-associated cytokines and chemokines. However, resisters showed secreted concentrations after Mtb stimulation of total antibodies and cytokines/chemokines associated with innate and Th17 immune responses similar to those with Mtb infection. This suggests an ability to mount non-IFN-γ immune responses to Mtb in apparent resisters.
MeSH term(s)	Humans ; Mycobacterium tuberculosis ; Cytokines ; Tuberculosis ; Latent Tuberculosis ; Tuberculin Test ; Latent Infection
Chemical Substances	Cytokines
Language	English
Publishing date	2023-05-18
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.2023.1176615
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