Investigation of the antimycobacterial activity of African medicinal plants combined with chemometric analysis to identify potential leads.

The emergence of drug-resistant Mycobacterium tuberculosis strains is a threat to global health necessitating the discovery of novel chemotherapeutic agents. Natural products drug discovery, which previously led to the discovery of rifamycins, is a valuable approach in this endeavor. Against this backdrop, we set out to investigate the in vitro antimycobacterial properties of medicinal plants from Ghana and South Africa, evaluating 36 extracts and their 252 corresponding solid phase extraction (SPE) generated fractions primarily against the non-pathogenic Mycobacterium smegmatis and Mycobacterium aurum species. The most potent fraction was further evaluated in vitro against infectious M. tuberculosis strain. Crinum asiaticum (bulb) (Amaryllidaceae) emerged as the most potent plant species with specific fractions showing exceptional, near equipotent activity against the non-pathogenic Mycobacterium species (0.39 µg/ml ≤ MIC ≤ 25 µg/ml) with one fraction being moderately active (MIC = 32.6 µg/ml) against M. tuberculosis. Metabolomic analysis led to the identification of eight compounds predicted to be active against M. smegmatis and M. aurum. In conclusion, from our comprehensive study, we generated data which provided an insight into the antimycobacterial properties of Ghanaian and South African plants. Future work will be focused on the isolation and evaluation of the compounds predicted to be active.

Antibody response to malaria vaccine candidates in pregnant women with Plasmodium falciparum and Schistosoma haematobium infections.

Malaria in pregnancy has severe consequences for the mother and foetus. Antibody response to specific malaria vaccine candidates (MVC) has been associated with a decreased risk of clinical malaria and its outcomes. We studied Plasmodium falciparum (Pf) and Schistosoma haematobium (Sh) infections and factors that could influence antibody responses to MVC in pregnant women. A total of 337 pregnant women receiving antenatal care (ANC) and 139 for delivery participated in this study. Pf infection was detected by qPCR and Sh infection using urine filtration method. Antibody levels against CSP, AMA-1, GLURP-R0, VAR2CSA and Pfs48/45 MVC were quantified by ELISA. Multivariable linear regression models identified factors associated with the modulation of antibody responses. The prevalence of Pf and Sh infections was 27% and 4% at ANC and 7% and 4% at delivery. Pf infection, residing in Adidome and multigravidae were positively associated with specific IgG response to CSP, AMA-1, GLURP-R0 and VAR2CSA. ITN use and IPTp were negatively associated with specific IgG response to GLURP-R0 and Pfs48/45. There was no association between Sh infection and antibody response to MVC at ANC or delivery. Pf infections in pregnant women were positively associated with antibody response to CSP, GLURP-R0 and AMA-1. Antibody response to GLURP-R0 and Pfs48/45 was low for IPTp and ITN users. This could indicate a lower exposure to Pf infection and low malaria prevalence observed at delivery.

Atypical memory B cell frequency correlates with antibody breadth and function in malaria immune adults.

Clinical immunity to malaria develops slowly after repeated episodes of infection and antibodies are essential in naturally acquired immunity against malaria. However, chronic exposure to malaria has been linked to perturbation in B-cell homeostasis with the accumulation of atypical memory B cells. It is unclear how perturbations in B cell subsets influence antibody breadth, avidity, and function in individuals naturally exposed to malaria. We show that individuals living in high malaria transmission regions in Ghana have higher Plasmodium falciparum merozoite antigen-specific antibodies and an increased antibody breadth score but lower antibody avidities relative to low transmission regions. The frequency of circulating atypical memory B cells is positively associated with an individual's antibody breadth. In vitro growth inhibition is independent of the ability to bind to free merozoites but associated with the breadth of antibody reactivity in an individual. Taken together, our data shows that repeated malaria episodes hamper the development of high avid antibodies which is compensated for by an increase in antibody breadth. Our results provide evidence to reinforce the idea that in regions with high malaria prevalence, repeated malaria infections lead to the broadening of antibody diversity and the continued presence of atypical memory B cell populations.