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Article ; Online: Acute rotavirus infection is associated with the induction of circulating memory CD4+ T cell subsets

Chikondi Malamba-Banda / Chimwemwe Mhango / Prisca Benedicto-Matambo / Jonathan J. Mandolo / End Chinyama / Orpha Kumwenda / Kayla G. Barnes / Nigel A. Cunliffe / Miren Iturriza-Gomara / Kondwani C. Jambo / Khuzwayo C. Jere

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 12

Abstract: Abstract Strong CD4+ T cell-mediated immune protection following rotavirus infection has been observed in animal models, but its relevance in humans remains unclear. Here, we characterized acute and convalescent CD4+ T cell responses in children who were ...

Abstract	Abstract Strong CD4+ T cell-mediated immune protection following rotavirus infection has been observed in animal models, but its relevance in humans remains unclear. Here, we characterized acute and convalescent CD4+ T cell responses in children who were hospitalized with rotavirus-positive and rotavirus-negative diarrhoea in Blantyre, Malawi. Children presenting with laboratory-confirmed rotavirus infection had higher proportions of effector and central memory T helper 2 cells during acute infection i.e., at disease presentation compared to convalescence, 28 days post-infection defined by a follow-up 28 days after acute infection. However, circulating cytokine-producing (IFN-γ and/or TNF-α) rotavirus-specific VP6-specific CD4+ T cells were rarely detectable in children with rotavirus infection at both acute and convalescent stages. Moreover, following whole blood mitogenic stimulation, the responding CD4+ T cells were predominantly non-cytokine producers of IFN-γ and/or TNF-α. Our findings demonstrate limited induction of anti-viral IFN-γ and/or TNF-α-producing CD4+ T cells in rotavirus-vaccinated Malawian children following the development of laboratory-confirmed rotavirus infection.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Differential localization and limited cytotoxic potential of duodenal CD8+ T cells

Leonard Mvaya / Trevor Khaba / Agness E. Lakudzala / Thandeka Nkosi / Ndaru Jambo / Innocent Kadwala / Anstead Kankwatira / Priyanka D. Patel / Melita A. Gordon / Tonney S. Nyirenda / Kondwani C. Jambo / Zaza M. Ndhlovu

JCI Insight, Vol 7, Iss

2022 Volume 3

Abstract: The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8+ T cells. The role of duodenal Trm CD8+ T cells in viral control is still not well defined. We examined ... ...

Abstract	The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8+ T cells. The role of duodenal Trm CD8+ T cells in viral control is still not well defined. We examined the spatial localization, phenotype, and function of CD8+ T cells in the human duodenal tissue from people living with HIV (PLHIV) and healthy controls. We found that Trm (CD69+CD103hi) cells were the predominant CD8+ T cell population in the duodenum. Immunofluorescence imaging of the duodenal tissue revealed that CD103+CD8+ T cells were localized in the intraepithelial region, while CD103–CD8+ T cells and CD4+ T cells were mostly localized in the lamina propria (LP). Furthermore, HIV-specific CD8+ T cells were enriched in the CD69+CD103–/lo population. However, the duodenal HIV-specific CD8+ Trm cells rarely expressed canonical molecules for potent cytolytic function (perforin and granzyme B) but were more polyfunctional than those from peripheral blood. Taken together, our results show that duodenal CD8+ Trm cells possess limited perforin-mediated cytolytic potential and are spatially separated from HIV-susceptible LP CD4+ T cells. This could contribute to HIV persistence in the duodenum and provides critical information for the design of cure therapies.
Keywords	AIDS/HIV ; Immunology ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The COVID-19 pandemic in the African continent

Godfrey Bwire / Alex Riolexus Ario / Patricia Eyu / Felix Ocom / Joseph F. Wamala / Kwadwo A. Kusi / Latif Ndeketa / Kondwani C. Jambo / Rhoda K. Wanyenze / Ambrose O. Talisuna

BMC Medicine, Vol 20, Iss 1, Pp 1-

2022 Volume 23

Abstract: Abstract In December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus spread quickly and in March, 2020, it was declared ...

Abstract	Abstract In December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus spread quickly and in March, 2020, it was declared a pandemic. Scientists predicted the worst scenario to occur in Africa since it was the least developed of the continents in terms of human development index, lagged behind others in achievement of the United Nations sustainable development goals (SDGs), has inadequate resources for provision of social services, and has many fragile states. In addition, there were relatively few research reporting findings on COVID-19 in Africa. On the contrary, the more developed countries reported higher disease incidences and mortality rates. However, for Africa, the earlier predictions and modelling into COVID-19 incidence and mortality did not fit into the reality. Therefore, the main objective of this forum is to bring together infectious diseases and public health experts to give an overview of COVID-19 in Africa and share their thoughts and opinions on why Africa behaved the way it did. Furthermore, the experts highlight what needs to be done to support Africa to consolidate the status quo and overcome the negative effects of COVID-19 so as to accelerate attainment of the SDGs.
Keywords	COVID ; Africa ; Pandemic ; Infectious disease ; Health ; Epidemiology ; Medicine ; R
Subject code	390
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines

Prisca Benedicto-Matambo / Julie E. Bines / Chikondi Malamba-Banda / Isaac T. Shawa / Kayla Barnes / Arox W. Kamng’ona / Daniel Hungerford / Kondwani C. Jambo / Miren Iturriza-Gomara / Nigel A. Cunliffe / Katie L. Flanagan / Khuzwayo C. Jere

Vaccines, Vol 10, Iss 418, p

2022 Volume 418

Abstract: Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live- ...

Abstract	Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.
Keywords	rotavirus ; off-target effects ; neonatal ; live attenuated ; RV3-BB ; epigenetic modulation ; Medicine ; R
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Implementation of Antibody Rapid Diagnostic Testing versus Real-Time Reverse Transcription-PCR Sample Pooling in the Screening of COVID-19

Tinashe K. Nyazika / Rabelani Kaela / Mathias Mugoni / Kudakwashe Musomekwa / Eric Kyei-Baafour / Simbarashe Chiwanda / Prichard T. Mapondera / Tatenda S. Makawa / Elliot M. Sithole / George Mavunganidze / Justen Manasa / Kondwani C. Jambo / Cuthbert Musarurwa

mSphere, Vol 5, Iss 4, p e00524-

a Case of Different Testing Strategies in Africa

2020 Volume 20

Abstract: Coronavirus disease 2019 (COVID-19) has wreaked havoc across the globe; although the number of cases in Africa remains lower than in other regions, it is on a gradual upward trajectory. To date, COVID-19 cases have been reported in 54 out of 55 African ... ...

Abstract	Coronavirus disease 2019 (COVID-19) has wreaked havoc across the globe; although the number of cases in Africa remains lower than in other regions, it is on a gradual upward trajectory. To date, COVID-19 cases have been reported in 54 out of 55 African countries. However, due to limited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription-PCR (rRT-PCR) testing capacity and scarcity of testing reagents, it is probable that the total number of cases could far exceed published statistics.Coronavirus disease 2019 (COVID-19) has wreaked havoc across the globe; although the number of cases in Africa remains lower than in other regions, it is on a gradual upward trajectory. To date, COVID-19 cases have been reported in 54 out of 55 African countries. However, due to limited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription-PCR (rRT-PCR) testing capacity and scarcity of testing reagents, it is probable that the total number of cases could far exceed published statistics. In this viewpoint, using Ghana, Malawi, South Africa, and Zimbabwe as examples of countries that have implemented different testing strategies, we argue that the implementation of sample pooling for rRT-PCR over antibody rapid diagnostic testing could have a greater impact in assessing disease burden. Sample pooling offers huge advantages compared to single test rRT-PCR, as it reduces diagnostic costs, personnel time, burnout, and analytical run times. Africa is already strained in terms of testing resources for COVID-19; hence, cheaper alternative ways need to be implemented to conserve resources, maximize mass testing, and reduce transmission in the wider population.
Keywords	antibody rapid diagnostic test ; sample pooling ; rrt-pcr ; covid-19 ; africa ; Microbiology ; QR1-502 ; covid19
Subject code	306
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	American Society for Microbiology
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2

BMC Medicine, Vol 20, Iss 1, Pp 1-

2022 Volume 10

Abstract: Abstract Background Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the ... ...

Abstract	Abstract Background Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination. Methods Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Šídák's or Holm-Šídák's test. Results We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30–60 days vs. 210–270 days; Log ID50 6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants. Conclusions These findings show that the AstraZeneca COVID-19 ...
Keywords	SARS-CoV-2 ; Spike ; RBD ; AstraZeneca COVID-19 vaccine ; Antibodies ; VOC ; Medicine ; R
Subject code	570
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Different clinical features in Malawian outpatients presenting with COVID-19 prior to and during Omicron variant dominance

Marah G Chibwana / Herbert W Thole / Cat Anscombe / Philip M Ashton / Edward Green / Kayla G Barnes / Jen Cornick / Ann Turner / Desiree Witte / Sharon Nthala / Chikondi Thom / Felistas Kanyandula / Anna Ainani / Natasha Mtike / Hope Tambala / Veronica N'goma / Dorah Mwafulirwa / Erick Asima / Ben Morton /

Markus Gmeiner / Zaziwe Gundah / Gift Kawalazira / Neil French / Nicholas Feasey / Robert S Heyderman / Todd D Swarthout / Kondwani C Jambo

PLOS Global Public Health, Vol 3, Iss 3, p e

A prospective observational study.

2023 Volume 0001575

Abstract: The SARS-CoV-2 Omicron variant has resulted in a high number of cases, but a relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants. Therefore, we assessed the differences in symptom prevalence between Omicron and pre- ...

Abstract	The SARS-CoV-2 Omicron variant has resulted in a high number of cases, but a relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants. Therefore, we assessed the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population. We collected data from outpatients presenting at two primary healthcare facilities in Blantyre, Malawi, from November 2020 to March 2022. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19, from whom we collected nasopharyngeal swabs for SARS-CoV-2 PCR testing, and sequenced positive samples to identify infecting-variants. In addition, we calculated the risk of presenting with a given symptom in individuals testing SARS-CoV-2 PCR positive before and during the Omicron variant-dominated period. Among 5176 participants, 6.4% were under 5, and 77% were aged 18 to 50 years. SARS-CoV-2 infection prevalence peaked in January 2021 (Beta), July 2021 (Delta), and December 2021 (Omicron). We found that cough (risk ratio (RR), 1.50; 95% confidence interval (CI), 1.00 to 2.30), fatigue (RR 2.27; 95% CI, 1.29 to 3.86) and headache (RR 1.64; 95% CI, 1.15 to 2.34) were associated with a high risk of SARS-CoV-2 infection during the pre-Omicron period. In comparison, only headache (RR 1.41; 95% CI, 1.07 to 1.86) did associate with a high risk of SARS-CoV-2 infection during the Omicron-dominated period. In conclusion, clinical symptoms associated with Omicron infection differed from prior variants and were harder to identify clinically with current symptom guidelines. Our findings encourage regular review of case definitions and testing policies to ensure case ascertainment.
Keywords	Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 exposure in Malawian blood donors

BMC Medicine, Vol 19, Iss 1, Pp 1-

an analysis of seroprevalence and variant dynamics between January 2020 and July 2021

2021 Volume 10

Abstract: Abstract Background By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi. ...

Abstract	Abstract Background By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi. Methods We measured the seroprevalence of anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera in Malawi from January 2020 to July 2021 using a cross-sectional study design. In a subset, we also assessed in vitro neutralisation against the original variant (D614G WT) and the Beta variant. Results A total of 5085 samples were selected from the blood donor database, of which 4075 (80.1%) were aged 20–49 years. Of the total, 1401 were seropositive. After adjustment for assay characteristics and applying population weights, seropositivity reached peaks in October 2020 (18.5%) and May 2021 (64.9%) reflecting the first two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity in the second wave, Balaka (rural, 66.2%, April 2021), Blantyre (urban, 75.6%, May 2021), Lilongwe (urban, 78.0%, May 2021), and Mzuzu (urban, 74.6%, April 2021). Blantyre and Mzuzu also show indications of the start of a third pandemic wave with seroprevalence picking up again in July 2021 (Blantyre, 81.7%; Mzuzu, 71.0%). More first wave sera showed in vitro neutralisation activity against the original variant (78% [7/9]) than the beta variant (22% [2/9]), while more second wave sera showed neutralisation activity against the beta variant (75% [12/16]) than the original variant (63% [10/16]). Conclusion The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. The dynamics of SARS-CoV-2 exposure will therefore need to be taken into account in the formulation of the COVID-19 vaccination policy in Malawi and across the region. Future studies should use an adequate sample size for the assessment of neutralisation activity ...
Keywords	SARS-CoV-2 ; Seroprevalence ; Malawi ; Blood donors ; Medicine ; R
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: B cell, CD8+ T cell and gamma delta T cell infiltration alters alveolar immune cell homeostasis in HIV-infected Malawian adults [version 3; referees

Andrew Mwale / Annemarie Hummel / Leonard Mvaya / Raphael Kamng'ona / Elizabeth Chimbayo / Joseph Phiri / Rose Malamba / Anstead Kankwatira / Henry C Mwandumba / Kondwani C Jambo

Wellcome Open Research, Vol

2 approved, 1 approved with reservations]

2018 Volume 2

Abstract: Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI). However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the ... ...

Abstract	Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI). However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. Results: We found that the numbers of CD8 + T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p<0.05). In contrast, there was no difference in the numbers of alveolar CD4 + T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065). Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%), while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (1 × 10 5 vs. 2.8 × 10 5 cells/100ml of BAL fluid, p=0.0001). The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p<0.05). Conclusions: Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4 + T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults.
Keywords	Airway/Respiratory Physiology ; HIV Infection & AIDS: Basic Science ; Immune Response ; Immunological Biomarkers ; Respiratory Infections ; Virology ; Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distinct clinical and immunological profiles of patients with evidence of SARS-CoV-2 infection in sub-Saharan Africa

Ben Morton / Kayla G. Barnes / Catherine Anscombe / Khuzwayo Jere / Prisca Matambo / Jonathan Mandolo / Raphael Kamng’ona / Comfort Brown / James Nyirenda / Tamara Phiri / Ndaziona P. Banda / Charlotte Van Der Veer / Kwazizira S. Mndolo / Kelvin Mponda / Jamie Rylance / Chimota Phiri / Jane Mallewa / Mulinda Nyirenda / Grace Katha /

Paul Kambiya / James Jafali / Henry C. Mwandumba / Stephen B. Gordon / Blantyre COVID-19 Consortium / Jennifer Cornick / Kondwani C. Jambo

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 12

Abstract: Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and ... ...

Abstract	Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.
Keywords	Science ; Q
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
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Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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