Therapeutic potential of Garcinia kola against experimental toxoplasmosis in rats.

Cerebral toxoplasmosis, the most common opportunistic infection in immunocompromised individuals, is increasingly reported in immunocompetent individuals due to mutant strains of Toxoplasma gondii, which, furthermore, are reported to be resistant to available treatments. We assessed the therapeutic potential of Garcinia kola, a medicinal plant reported to have antiplasmodial and neuroprotective properties, against experimental toxoplasmosis in rats. Severe toxoplasmosis was induced in male Wistar rats (156.7 ± 4.1 g) by injecting them with 10 million tachyzoites in suspension in 500 µl of saline (intraperitoneal), and exclusive feeding with a low-protein diet [7% protein (weight by weight)]. Then, animals were treated with hexane, dichloromethane, and ethyl acetate fractions of Garcinia kola. Footprints were analysed and open-field and elevated plus maze ethological tests were performed when symptoms of severe disease were observed in the infected controls. After sacrifice, blood samples were processed for Giemsa staining, organs were processed for haematoxylin and eosin staining, and brains were processed for Nissl staining and cell counting. Compared with non-infected animals, the infected control animals had significantly lower body weights (30.27%↓, P = 0.001), higher body temperatures (P = 0.033) during the sacrifice, together with signs of cognitive impairment and neurologic deficits such as lower open-field arena centre entries (P < 0.001), elevated plus maze open-arm time (P = 0.029) and decreased stride lengths and step widths (P < 0.001), as well as neuronal loss in various brain areas. The ethyl acetate fraction of Garcinia kola prevented or mitigated most of these signs. Our data suggest that the ethyl acetate fraction of Garcinia kola has therapeutic potential against cerebral toxoplasmosis.

Dementia Prevalence and Onchocerca volvulus Infection among Rural Elderly Persons in the Ntui Health District, Cameroon: A Population-Based Study.

Recent research suggests that infection with Onchocerca volvulus induces neurocognitive decline. This study sought to compare the cognitive outcomes of elderly persons based on onchocerciasis infection status and report the overall prevalence of dementia in the rural Ntui Health District in Cameroon. A community-based approach was used to recruit 103 participants aged ≥60 years. Dementia screening was done using the Community Screening Interview for Dementia (CSID) tool with a cut-off value of ≤29.5. O. volvulus infection was determined via microscopic examination of skin snips and serological testing of Ov16 antibodies using rapid diagnostic tests. Overall, the prevalence of dementia was 10.7%. Among the tested individuals, 17.9% (15/84) and 62.1% (41/66) were positive for O. volvulus and Ov16 antibodies, respectively. A multivariable linear regression model of CSID scores found a significant positive association with education level (8.654; 95% CI: 2.0870 to 15.222). However, having a positive skin snip for O. volvulus (-3.399; 95% CI: -6.805 to 0.007) and inhaling tobacco (-5.441; 95% CI: -9.137 to -1.744) tended to lower the CSID scores. Ongoing onchocerciasis transmission in the Ntui Health District may constitute a risk factor for dementia. Strengthening onchocerciasis elimination and adopting healthier lifestyles would contribute to dementia prevention among the elderly residing in endemic communities.

Community Perceptions of Blackfly Nuisance and Acceptability of the "Slash and Clear" Vector Control Approach in the Ntui Health District of Cameroon: A Qualitative Study.

Besides being vectors of the onchocerciasis parasite, blackflies are a source of nuisance in onchocerciasis-endemic communities. We investigated the experience of residents in the Ntui Health District (Cameroon) regarding blackfly nuisance and assessed their perceptions of a novel "Slash and Clear" (S&C) intervention for blackfly control. Focus group discussions were conducted before and after S&C implementation (respectively, in February 2022 and December 2023). Blackflies were known to emerge from the river areas and cause disease. To prevent blackfly bites, the population often covered their body with protective clothing and applied various substances (kerosene, oil, or lemon) to their skin. Post-intervention data showed reduced blackfly nuisance, and the willingness to sustain blackfly control in the long-term was unanimous among community leaders and members, including the village volunteers who implemented the S&C intervention. In conclusion, blackfly nuisance is evident in the Ntui onchocerciasis focus of Cameroon and led to a panoply of coping practices, some of which could be detrimental to their health. Implementing S&C for blackfly control is well accepted and could sustainably alleviate the nuisance caused by blackflies while simultaneously breaking the onchocerciasis transmission cycle.

Association between telomere length and Plasmodium falciparum malaria endemicity in sub-Saharan Africans.

Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.

The Brain Economy: Advancing Brain Science to Better Understand the Modern Economy.

The coming years are likely to be turbulent due to a myriad of factors or polycrisis, including an escalation in climate extremes, emerging public health threats, weak productivity, increases in global economic instability and further weakening in the integrity of global democracy. These formidable challenges are not exogenous to the economy but are in some cases generated by the system itself. They can be overcome, but only with far-reaching changes to global economics. Our current socio-economic paradigm is insufficient for addressing these complex challenges, let alone sustaining human development, well-being and happiness. To support the flourishing of the global population in the age of polycrisis, we need a novel, person-centred and collective paradigm. The brain economy leverages insights from neuroscience to provide a novel way of centralising the human contribution to the economy, how the economy in turn shapes our lives and positive feedbacks between the two. The brain economy is primarily based on Brain Capital, an economic asset integrating brain health and brain skills, the social, emotional, and the diversity of cognitive brain resources of individuals and communities. People with healthy brains are essential to navigate increasingly complex systems. Policies and investments that improve brain health and hence citizens' cognitive functions and boost brain performance can increase productivity, stimulate greater creativity and economic dynamism, utilise often underdeveloped intellectual resources, afford social cohesion, and create a more resilient, adaptable and sustainability-engaged population.

Integrative functional genomic analyses identify genetic variants influencing skin pigmentation in Africans.

Skin color is highly variable in Africans, yet little is known about the underlying molecular mechanism. Here we applied massively parallel reporter assays to screen 1,157 candidate variants influencing skin pigmentation in Africans and identified 165 single-nucleotide polymorphisms showing differential regulatory activities between alleles. We combine Hi-C, genome editing and melanin assays to identify regulatory elements for MFSD12, HMG20B, OCA2, MITF, LEF1, TRPS1, BLOC1S6 and CYB561A3 that impact melanin levels in vitro and modulate human skin color. We found that independent mutations in an OCA2 enhancer contribute to the evolution of human skin color diversity and detect signals of local adaptation at enhancers of MITF, LEF1 and TRPS1, which may contribute to the light skin color of Khoesan-speaking populations from Southern Africa. Additionally, we identified CYB561A3 as a novel pigmentation regulator that impacts genes involved in oxidative phosphorylation and melanogenesis. These results provide insights into the mechanisms underlying human skin color diversity and adaptive evolution.

Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals.

Comparisons of Neanderthal genomes to anatomically modern human (AMH) genomes show a history of Neanderthal-to-AMH introgression stemming from interbreeding after the migration of AMHs from Africa to Eurasia. All non-sub-Saharan African AMHs have genomic regions genetically similar to Neanderthals that descend from this introgression. Regions of the genome with Neanderthal similarities have also been identified in sub-Saharan African populations, but their origins have been unclear. To better understand how these regions are distributed across sub-Saharan Africa, the source of their origin, and what their distribution within the genome tells us about early AMH and Neanderthal evolution, we analyzed a dataset of high-coverage, whole-genome sequences from 180 individuals from 12 diverse sub-Saharan African populations. In sub-Saharan African populations with non-sub-Saharan African ancestry, as much as 1% of their genomes can be attributed to Neanderthal sequence introduced by recent migration, and subsequent admixture, of AMH populations originating from the Levant and North Africa. However, most Neanderthal homologous regions in sub-Saharan African populations originate from migration of AMH populations from Africa to Eurasia ∼250 kya, and subsequent admixture with Neanderthals, resulting in ∼6% AMH ancestry in Neanderthals. These results indicate that there have been multiple migration events of AMHs out of Africa and that Neanderthal and AMH gene flow has been bi-directional. Observing that genomic regions where AMHs show a depletion of Neanderthal introgression are also regions where Neanderthal genomes show a depletion of AMH introgression points to deleterious interactions between introgressed variants and background genomes in both groups-a hallmark of incipient speciation.

Physiological and environmental factors affecting cancer risk and prognosis in obesity.

Obesity results from a chronic excessive accumulation of adipose tissue due to a long-term imbalance between energy intake and expenditure. Available epidemiological and clinical data strongly support the links between obesity and certain cancers. Emerging clinical and experimental findings have improved our understanding of the roles of key players in obesity-associated carcinogenesis such as age, sex (menopause), genetic and epigenetic factors, gut microbiota and metabolic factors, body shape trajectory over life, dietary habits, and general lifestyle. It is now widely accepted that the cancer-obesity relationship depends on the site of cancer, the systemic inflammatory status, and micro environmental parameters such as levels of inflammation and oxidative stress in transforming tissues. We hereby review recent advances in our understanding of cancer risk and prognosis in obesity with respect to these players. We highlight how the lack of their consideration contributed to the controversy over the link between obesity and cancer in early epidemiological studies. Finally, the lessons and challenges of interventions for weight loss and better cancer prognosis, and the mechanisms of weight gain in survivors are also discussed.

A rare case of drug sensitive adult-onset temporal lobe epilepsy due to a focal cortical dysplasia revealed by ictal coughing: First report in sub-Saharan Africa.

This case suggests that clinicians should consider seizures as a differential diagnosis of paroxystic cough with loss of consciousness. Focal cortical dysplasia should equally be screened for with magnetic resonance imaging (MRI) scans even in adults with epilepsy in sub-Saharan Africa.

Genomic characterization of HLA class I and class II genes in ethnically diverse sub-Saharan African populations: A report on novel HLA alleles.

HLA allelic variation has been well studied and documented in many parts of the world. However, African populations have been relatively under-represented in studies of HLA variation. We have characterized HLA variation from 489 individuals belonging to 13 ethnically diverse populations from rural communities from the African countries of Botswana, Cameroon, Ethiopia, and Tanzania, known to practice traditional subsistence lifestyles using next generation sequencing (Illumina) and long-reads from Oxford Nanopore Technologies. We identified 342 distinct alleles among the 11 HLA targeted genes: HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1, with 140 of those alleles containing novel sequences that were submitted to the IPD-IMGT/HLA database. Sixteen of the 140 alleles contained novel content within the exonic regions of the genes, while 110 alleles contained novel intronic variants. Four alleles were found to be recombinants of already described HLA alleles and 10 alleles extended the sequence content of already described alleles. All 140 alleles include complete allelic sequence from the 5' UTR to the 3' UTR that are inclusive of all exons and introns. This report characterizes the HLA allelic variation from these individuals and describes the novel allelic variation present within these specific African populations.

Epidemiology of epilepsy and relationship with onchocerciasis prevalence in villages of the Ntui Health District of Cameroon.

BACKGROUND: A strong association between epilepsy and onchocerciasis endemicity has been reported. We sought to document the epidemiology of epilepsy in onchocerciasis-endemic villages of the Ntui Health District in Cameroon and investigate how this relates to the prevalence of onchocerciasis. METHODS: In March 2022, door-to-door epilepsy surveys were conducted in four villages (Essougli, Nachtigal, Ndjame, and Ndowe). Ivermectin intake during the 2021 session of community-directed treatment with ivermectin (CDTI) was investigated in all participating village residents. Persons with epilepsy (PWE) were identified through a two-step approach: administration of a 5-item epilepsy screening questionnaire followed by clinical confirmation by a neurologist. Epilepsy findings were analyzed together with onchocerciasis epidemiological data previously obtained in the study villages. RESULTS: We surveyed 1663 persons in the four study villages. The 2021 CDTI coverage for all study sites was 50.9%. Overall, 67 PWE were identified (prevalence of 4.0% (IQR: 3.2-5.1) with one new-onset case during the past 12 months (annual incidence of 60.1 per 100,000 persons). The median age of PWE was 32 years (IQR: 25-40), with 41 (61.2%) being females. The majority (78.3%) of PWE met the previously published criteria for onchocerciasis-associated epilepsy (OAE). Persons with a history of nodding seizures were found in all villages and represented 19.4% of the 67 PWE. Epilepsy prevalence was positively correlated with onchocerciasis prevalence (Spearman Rho = 0.949, p = 0.051). Meanwhile, an inverse relationship was observed between distance from the Sanaga river (blackfly breeding site) and the prevalence of both epilepsy and onchocerciasis. CONCLUSION: The high epilepsy prevalence in Ntui appears to be driven by onchocerciasis. It is likely that decades of CDTI have likely contributed to a gradual decrease in epilepsy incidence, as only one new case occurred in the past year. Therefore, more effective elimination measures are urgently needed in such endemic areas to curb the OAE burden.

Adherence to COVID-19 preventive measures in Sub-Saharan Africa during the 1st year of the pandemic: Pooled analysis of the International Citizen Project on COVID-19 (ICPCovid) surveys.

Introduction: While most governments instituted several interventions to stall the spread of COVID-19, little is known regarding the continued observance of the non-pharmaceutical COVID-19 preventive measures particularly in Sub-Saharan Africa (SSA). We investigated adherence to these preventive measures during the initial 6 months of the COVID-19 outbreak in some SSA countries. Methods: Between March and August 2020, the International Citizen Project on COVID-19 consortium (www.icpcovid.com) conducted online surveys in six SSA countries: Benin, Cameroon, Democratic Republic of Congo, Mozambique, Somalia, and Uganda. A five-point individual adherence score was constituted by scoring respondents' observance of the following measures: mask use, physical distancing, hand hygiene, coughing hygiene, and avoiding to touch one's face. Community behaviors (going to public places, traveling during the pandemic) were also assessed. Data were analyzed in two time periods: Period 1 (March-May) and Period 2 (June-August). Results: Responses from 26,678 respondents were analyzed (mean age: 31.0 ± 11.1 years; 54.1% males). Mean individual adherence score decreased from 3.80 ± 1.37 during Period 1, to 3.57 ± 1.43 during Period 2; p < 0.001. At the community level, public events/places were significantly more attended with increased travels during Period 2 compared to Period 1 (p < 0.001). Using linear mixed models, predictors of increased individual adherence included: higher age (Coef = 0.005; 95% CI: 0.003-0.007), female gender (Coef = 0.071; 95% CI: 0.039-0.104), higher educational level (Coef = 0.999; 95% CI: 0.885-1.113), and working in the healthcare sector (Coef = 0.418; 95% CI: 0.380-0.456). Conclusion: Decreasing adherence to non-pharmaceutical measures over time constitutes a risk for the persistence of COVID-19 in SSA. Younger persons and those with lower education levels constitute target groups for improving adherence to such measures.

Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential.

The tumor microenvironment fuels tumorigenesis and induces the development of resistance to anticancer drugs. A growing number of reports support that the tumor microenvironment mediates these deleterious effects partly by overexpressing insulin-like growth factor 1 (IGF-1). IGF-1 is known for its role to support cancer progression and metastasis through the promotion of neovascularization in transforming tissues, and the promotion of the proliferation, maintenance and migration of malignant cells. Anti-IGF therapies showed potent anticancer effects and the ability to suppress cancer resistance to various chemotherapy drugs in in vivo and in vitro preclinical studies. However, high toxicity and resistance to these agents are increasingly being reported in clinical trials. We review data supporting the notion that tumor microenvironment mediates tumorigenesis partly through IGF-1 signaling pathway. We also discuss the therapeutic potential of IGF-1 receptor targeting, with special emphasis on the ability of IGF-R silencing to overcome chemotherapy drug resistance, as well as the challenges for clinical use of anti-IGF-1R therapies.

Correction: Dusabimana et al. Surveillance for Onchocerciasis-Associated Epilepsy and Ov16 IgG4 Testing of Children 6-10 Years Old Should Be Used to Identify Areas Where Onchocerciasis Elimination Programs Need Strengthening. Pathogens 2022, 11, 281.

There was an error in the original publication [...].

Non-Communicable Neurological Disorders and Neuroinflammation.

Traumatic brain injury, stroke, and neurodegenerative diseases represent a major cause of morbidity and mortality in Africa, as in the rest of the world. Traumatic brain and spinal cord injuries specifically represent a leading cause of disability in the younger population. Stroke and neurodegenerative disorders predominantly target the elderly and are a major concern in Africa, since their rate of increase among the ageing is the fastest in the world. Neuroimmunology is usually not associated with non-communicable neurological disorders, as the role of neuroinflammation is not often considered when evaluating their cause and pathogenesis. However, substantial evidence indicates that neuroinflammation is extremely relevant in determining the consequences of non-communicable neurological disorders, both for its protective abilities as well as for its destructive capacity. We review here current knowledge on the contribution of neuroinflammation and neuroimmunology to the pathogenesis of traumatic injuries, stroke and neurodegenerative diseases, with a particular focus on problems that are already a major issue in Africa, like traumatic brain injury, and on emerging disorders such as dementias.

Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection.

Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on population health. However, genetic diversity and evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood. We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (angiotensin converting enzyme 2 [ACE2], transmembrane protease serine 2 [TMPRSS2], dipeptidyl peptidase 4 [DPP4], and lymphocyte antigen 6 complex locus E [LY6E]). We analyzed data from 2,012 ethnically diverse Africans and 15,977 individuals of European and African ancestry with electronic health records and integrated with global data from the 1000 Genomes Project. At ACE2, we identified 41 nonsynonymous variants that were rare in most populations, several of which impact protein function. However, three nonsynonymous variants (rs138390800, rs147311723, and rs145437639) were common among central African hunter-gatherers from Cameroon (minor allele frequency 0.083 to 0.164) and are on haplotypes that exhibit signatures of positive selection. We identify signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage compared with the chimpanzee genome. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19. Our study provides insights into global variation at host genes related to SARS-CoV-2 infection, which have been shaped by natural selection in some populations, possibly due to prior viral infections.