The COVID-19, tuberculosis and HIV/AIDS: Ménage à Trois

In December 2019, a novel pneumonic condition, Coronavirus disease 2019 (COVID- 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in China and spread globally. The presentation of COVID-19 is more severe in persons with underlying medical conditions such as Tuberculosis (TB), Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and other pneumonic conditions. All three diseases are of global concern and can significantly affect the lungs with characteristic cytokine storm, immunosuppression, and respiratory failure. Co-infections of SARS-CoV-2 with HIV and Mycobacterium tuberculosis (Mtb) have been reported, which may influence their pathogenesis and disease progression. Pulmonary TB and HIV/AIDS patients could be more susceptible to SARS-CoV-2 infection leading to lethal synergy and disease severity. Therefore, the biological and epidemiological interactions of COVID-19, HIV/AIDS, and TB need to be understood holistically. While data is needed to predict the impact of the COVID-19 pandemic on these existing diseases, it is necessary to review the implications of the evolving COVID-19 management on HIV/AIDS and TB control, including therapy and funding. Also, the impact of long COVID on patients, who may have this co-infection. Thus, this review highlights the implications of COVID-19, HIV/AIDS, and TB co-infection compares disease mechanisms, addresses growing concerns, and suggests a direction for improved diagnosis and general management

Pausing the Fight Against Malaria to Combat the COVID-19 Pandemic in Africa: Is the Future of Malaria Bleak?

Malaria remains a major global health burden, killing hundreds of thousands annually, especially in sub-Saharan Africa. In 2019, a Phase IV Expanded Programme on Immunization (EPI)-linked malaria vaccine implementation was underway. However, in December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many clinical, epidemiological, and biological parallels to malaria, was reported in Wuhan, China. COVID-19 is spreading rapidly, and, as of the 3rd of June, 2020, more than 382,507 persons had died from COVID-19. Children under 5 years who suffer high malaria-attributable mortalities are largely asymptomatic for COVID-19. Considering that the malaria burden is highest in low-income tropical countries with little capacity to fund malaria control and eradication programs, the fight against malaria in these regions is likely to be hampered. Access to healthcare has generally been limited, while malaria interventions, such as seasonal malaria chemotherapy and distribution of insecticide-treated bed nets, have been suspended due to lockdowns. Likewise, the repurposing of antimalarials for treatment of COVID-19 shared symptoms and the shift in focus from the production of malaria rapid diagnostic tests (RDTs) to COVID-19 RDTs is a cause for concern in malaria-endemic regions. Children are less affected by the COVID-19 pandemic compared to the elderly. However, due to the fears of contracting SARS-CoV-2, the elderly who are worst affected by COVID-19 may not take children for malaria medication, resulting in high malaria-related mortalities among children. COVID-19 has disproportionately affected developed countries, threatening their donation capacity. These are likely to thwart malaria control efforts in low-income regions. Here, we present perspectives on the collateral impact of COVID-19 on malaria, especially in Africa

COVID-19 pandemic in Africa: Is it time for water, sanitation and hygiene to climb up the ladder of global priorities?

The authors would like to thank the authors of the freely-usable images from Unsplash and Pixnio included in the Graphical Abstract: photos by Janice-Haney Carr and Dr. Ray Butler (USCDCP), USCDCP and Crystal Thompsom (USAID) on Pixnio; photos by CDC, UN COVID- 19 response and Raymond Hui on Unsplash.Wewould also like to thank the reviewers for their comments and keen interest in this article.In the current pandemic context, it is necessary to remember the lessons learned from previous outbreaks in Africa, where the incidence of other diseases could rise if most resources are directed to tackle the emergency. Improving the access to water, sanitation and hygiene (WASH) could be a win-win strategy, because the lack of these services not only hampers the implementation of preventive measures against SARS-CoV-2 (e.g. proper handwashing), but it is also connected to high mortality diseases (for example, diarrhoea and lower respiratory infections (LRI)). This study aims to build on the evidence-based link between other LRI andWASH as a proxy for exploring the potential vulnerability of African countries to COVID-19, as well as the role of other socioeconomic variables such as financial sources or demographic factors. The selected methodology combines several machine learning techniques to single out the most representative variables for the analysis, classify the countries according to their capacity to tackle public health emergencies and identify behavioural patterns for each group. Besides, conditional dependences between variables are inferred through a Bayesian network. Results show a strong relationship between low access toWASH services and high LRI mortality rates, and that migrant remittances could significantly improve the access to healthcare and WASH services. However, the role of Official Development Assistance (ODA) in enhancing WASH facilities in the most vulnerable countries cannot be disregarded, but it is unevenly distributed: for each 50–100 US$of ODA per capita, the probability of directing more than 3 US$ toWASH ranges between 48% (Western Africa) and 8% (Central Africa)

Pathogen-Induced Epigenetic Modifications in Cancers: Implications for Prevention, Detection and Treatment of Cancers in Africa

Cancer is a major public health burden worldwide. Tumor formation is caused by multiple intrinsic and extrinsic factors. Many reports have demonstrated a positive correlation between the burden of infectious pathogens and the occurrence of cancers. However, the mechanistic link between pathogens and cancer development remains largely unclear and is subject to active investigations. Apart from somatic mutations that have been widely linked with various cancers, an appreciable body of knowledge points to alterations of host epigenetic patterns as key triggers for cancer development. Several studies have associated various infectious pathogens with epigenetic modifications. It is therefore plausible to assume that pathogens induce carcinogenesis via alteration of normal host epigenetic patterns. Thus, Africa with its disproportionate burden of infectious pathogens is threatened by a dramatic increase in pathogen-mediated cancers. To curb the potential upsurge of such cancers, a better understanding of the role of tropical pathogens in cancer epigenetics could substantially provide resources to improve cancer management among Africans. Therefore, this review discusses cancer epigenetic studies in Africa and the link between tropical pathogens and cancer burden. In addition, we discuss the potential mechanisms by which pathogens induce cancers and the opportunities and challenges of tropical pathogen-induced epigenetic changes for cancer prevention, detection and management

<i>Mansonella perstans</i> microfilaremic individuals are characterized by enhanced type 2 helper T and regulatory T and B cell subsets and dampened systemic innate and adaptive immune responses

<div><p>The filarial nematode <i>Mansonella perstans</i> is endemic throughout Africa, northern South America and the Caribbean. Interestingly, <i>M</i>. <i>perstans</i>-infected individuals present no distinct clinical picture associated with certain pathology. Due to its relatively silent nature, research on this tropical disease has been neglected, especially <i>M</i>. <i>perstans</i>-driven immune responses. A hindrance in obtaining data on <i>M</i>. <i>perstans</i>-specific responses has been the inability to obtain adult worms since their habitats in serous cavities are difficult to access. Thus, in this study, for the first time, we used <i>Mansonella perstans</i> worm antigen extract as stimulant to obtain filarial-specific recall and immunoglobulin responses from <i>M</i>. <i>perstans</i> microfilaremic individuals (Mp MF+) from Cameroon. Moreover, systemic immune profiles in sera and immune cell composition in peripheral blood from Mp MF+ and amicrofilaremic individuals (Mp MF-) were obtained. Our data reveal that Mp MF+ individuals showed significantly reduced cytokine (IL-4, IL-6 and IL-12p70) and chemokine levels (IL-8 and RANTES), but significantly higher MIP-1β as well as increased <i>M</i>. <i>perstans</i>-specific IgG4 levels compared to Mp MF- individuals. In contrast, upon re-stimulation with worm antigen extract, IFN-γ, IL-13, IL-10 and IL-17A secretion was enhanced in cell cultures from Mp MF+ individuals when compared to those from cultures of healthy European individuals. Moreover, analysis of immune cell composition in peripheral blood from Mp MF+ individuals revealed increased type 2 helper T (Th2), natural killer (NK), regulatory B and T cell (Breg and Treg) subsets but decreased type 1 regulatory T (Tr1) cells. In summary, this study deciphers for the first time, <i>M</i>. <i>perstans</i>-specific immune responses using worm antigen extract and shows that patent <i>M</i>. <i>perstans</i> infections have distinct Th2, Breg and Treg subsets accompanied with reduced systemic innate and adaptive immune responses and dominant filarial-specific IgG4 levels.</p></div

Reduced systemic IL-13, IL-4 and IL-17A levels in <i>M</i>. <i>perstans</i> microfilaremic individuals.

<p>Sera from <i>M</i>. <i>perstans</i>-microfilaremic (Mp MF+, n = 11) and amicrofilaremic (Mp MF-; n = 28) individuals were analyzed for the contents of (<b>A</b>) IFN-γ, (<b>B</b>) IL-5, (<b>C</b>) IL-13, (<b>D</b>) IL-4, (<b>E</b>) IL-10 and (<b>F</b>) IL-17A using luminex technology. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Mann-Whitney-U-tests.</p

Increased frequencies of regulatory T and B cells (Tregs and Bregs) but decreased type 1 regulatory T (Tr1) cell populations in <i>M</i>. <i>perstans</i> microfilaremic individuals.

<p>Using flow cytometry, peripheral whole blood cells from <i>M</i>. <i>perstans</i> microfilaremic (Mp MF+; n = 11) and amicrofilaremic (Mp MF-; n = 10) individuals were analyzed for frequencies (%) of (<b>A</b>) CD4⁺CD127⁺ expressing CD25^high Tregs, (<b>B</b>) CD4+α/βTCR⁺ expressing CD49b and LAG3 Tr1 cells and (<b>C</b>) CD19⁺CD24^highCD38^high expressing CD1d^high Bregs. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Mann-Whitney-U-test.</p

Dominant <i>M</i>. <i>perstans</i>-specific IL-10, IFN-γ, IL-13 and IL-17A production by peripheral cells from <i>M</i>. <i>perstans</i> microfilaremic individuals.

<p>Freshly isolated peripheral whole blood cells (100μl/well) from <i>M</i>. <i>perstans</i> microfilaremic individuals (Mp MF+; n = 9) and healthy European non-endemic normals (NEN; n = 4) were cultivated in 10% BCS/RPMI-1640 medium (100μl/well) and left either un-stimulated (Cntl) or cultured with <i>M</i>. <i>perstans</i>-derived worm antigen extract (Mp Ag, 50μg/ml) at 37°C for 72 hours. Thereafter, culture supernatants were analysed for levels of (<b>A</b>) IFN-γ, (<b>B</b>) IL-4, (<b>C</b>) IL-5 (<b>D</b>) IL-13, (<b>E</b>) IL-10 and (<b>F</b>) IL-17A by ELISA. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Kruskal-Wallis-test and, if significant, followed by a Dunn`s multiple comparison test for further comparison of the groups.</p

Increased CD4⁺CRTH2⁺ Th2 cell frequencies in peripheral blood of <i>M</i>. <i>perstans</i> microfilaremic individuals.

<p>Using flow cytometry, peripheral whole blood cells from <i>M</i>. <i>perstans</i> microfilaremic (Mp MF+; n = 11) and amicrofilaremic (Mp MF-; n = 10) individuals were analyzed for frequencies (%) of (<b>A</b>) CD4⁺ T cells on lymphocytes and CD4⁺ T cells expressing (<b>B</b>) CXCR3, (<b>C</b>) CD161, (<b>D</b>) CRTH2, (<b>E</b>) CTLA-4 or (<b>F</b>) PD-1. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Mann-Whitney-U-test.</p

Elevated frequencies of CD3^-CD16⁺CD56⁺ natural killer cells in peripheral blood of <i>M</i>. <i>perstans</i>-microfilaremic individuals.

<p>Using flow cytometry, peripheral whole blood cells from <i>M</i>. <i>perstans</i> microfilaremic (Mp MF+; n = 11) and amicrofilaremic (Mp MF-; n = 10) individuals were analyzed for frequencies (%) of (<b>A</b>) CD3⁺ T cells co-expressing CD16 and CD56 for NKT cells and (<b>B</b>) CD3^- cells co-expressing CD16 and CD56 to determine NK populations. Graphs show box whiskers with median, interquartile ranges and outliers. Statistical significances between the indicated groups were obtained using the Mann-Whitney-U-test.</p