Suboptimal antimicrobial stewardship in the COVID-19 era: is humanity staring at a postantibiotic future?

In the absence of potent antimicrobial agents, it is estimated that bacterial infections could cause millions of deaths. The emergence of COVID-19, its complex pathophysiology and the high propensity of patients to coinfections has resulted in therapeutic regimes that use a cocktail of antibiotics for disease management. Suboptimal antimicrobial stewardship in this era and the slow pace of drug discovery could result in large-scale drug resistance, narrowing future antimicrobial therapeutics. Thus, judicious use of current antimicrobials is imperative to keep up with existing and emerging infectious pathogens. Here, we provide insights into the potential implications of suboptimal antimicrobial stewardship, resulting from the emergence of COVID-19, on the spread of antimicrobial resistance.

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.

Mansonella perstans 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.

The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-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 M. perstans-driven immune responses. A hindrance in obtaining data on M. perstans-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 Mansonella perstans worm antigen extract as stimulant to obtain filarial-specific recall and immunoglobulin responses from M. perstans 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-1ß as well as increased M. perstans-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, M. perstans-specific immune responses using worm antigen extract and shows that patent M. perstans infections have distinct Th2, Breg and Treg subsets accompanied with reduced systemic innate and adaptive immune responses and dominant filarial-specific IgG4 levels.