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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 â¼50% 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.
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Malaria Falciparum , Telómero , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , África del Sur del Sahara/epidemiología , Población Negra/etnología , Población Negra/genética , Enfermedades Endémicas , Leucocitos/metabolismo , Malaria Falciparum/genética , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Pueblo Africano Subsahariano , Telómero/genética , Homeostasis del Telómero/genética , Botswana , Tanzanía , Camerún , Pueblo del Sur de ÁfricaRESUMEN
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.
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COVID-19 , África , Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Variación Genética , Humanos , Fenotipo , SARS-CoV-2/genética , Selección GenéticaRESUMEN
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.
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Neoplasias , Obesidad , Femenino , Humanos , Obesidad/complicaciones , Obesidad/metabolismo , Pronóstico , Neoplasias/epidemiología , Neoplasias/etiología , Carcinogénesis , Factores de RiesgoRESUMEN
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.
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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.
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Epilepsia , Oncocercosis , Femenino , Humanos , Adulto , Masculino , Oncocercosis/complicaciones , Oncocercosis/epidemiología , Oncocercosis/diagnóstico , Ivermectina/uso terapéutico , Prevalencia , Camerún/epidemiología , Epilepsia/complicaciones , Epilepsia/epidemiología , Epilepsia/tratamiento farmacológicoRESUMEN
Redondoviridae is a newly established family of circular Rep-encoding single-stranded (CRESS) DNA viruses found in the human ororespiratory tract. Redondoviruses were previously found in â¼15% of respiratory specimens from U.S. urban subjects; levels were elevated in individuals with periodontitis or critical illness. Here, we report higher redondovirus prevalence in saliva samples: four rural African populations showed 61 to 82% prevalence, and an urban U.S. population showed 32% prevalence. Longitudinal, limiting-dilution single-genome sequencing revealed diverse strains of both redondovirus species (Brisavirus and Vientovirus) in single individuals, persistence over time, and evidence of intergenomic recombination. Computational analysis of viral genomes identified a recombination hot spot associated with a conserved potential DNA stem-loop structure. To assess the possible role of this site in recombination, we carried out in vitro studies which showed that this potential stem-loop was cleaved by the virus-encoded Rep protein. In addition, in reconstructed reactions, a Rep-DNA covalent intermediate was shown to mediate DNA strand transfer at this site. Thus, redondoviruses are highly prevalent in humans, found in individuals on multiple continents, heterogeneous even within individuals and encode a Rep protein implicated in facilitating recombination. IMPORTANCERedondoviridae is a recently established family of DNA viruses predominantly found in the human respiratory tract and associated with multiple clinical conditions. In this study, we found high redondovirus prevalence in saliva from urban North American individuals and nonindustrialized African populations in Botswana, Cameroon, Ethiopia, and Tanzania. Individuals on both continents harbored both known redondovirus species. Global prevalence of both species suggests that redondoviruses have long been associated with humans but have remained undetected until recently due to their divergent genomes. By sequencing single redondovirus genomes in longitudinally sampled humans, we found that redondoviruses persisted over time within subjects and likely evolve by recombination. The Rep protein encoded by redondoviruses catalyzes multiple reactions in vitro, consistent with a role in mediating DNA replication and recombination. In summary, we identify high redondovirus prevalence in humans across multiple continents, longitudinal heterogeneity and persistence, and potential mechanisms of redondovirus evolution by recombination.
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Infecciones por Virus ADN/virología , Virus ADN/clasificación , Virus ADN/genética , Virus ADN/metabolismo , Boca/virología , Sistema Respiratorio/virología , Saliva/virología , África/epidemiología , Biodiversidad , Enfermedad Crítica , Infecciones por Virus ADN/epidemiología , Proteínas de Unión al ADN/metabolismo , Evolución Molecular , Genoma Viral , Humanos , Metagenómica , Periodontitis/virología , Filogenia , Prevalencia , Población Rural , Estados Unidos/epidemiología , Proteínas Virales/metabolismoRESUMEN
In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes. Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.
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Enfermedad de Alzheimer , Demencia Vascular , Demencia , Anciano , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Demencia/epidemiología , Demencia/genética , Demencia Vascular/complicaciones , Estudio de Asociación del Genoma Completo , Genotipo , HumanosRESUMEN
PURPOSE OF REVIEW: Malaria, Chagas Disease and Human African Trypanosomiasis are vector-borne protozoan illnesses, frequently associated with neurological manifestations. Intriguing but ignored, limited mainly to resource-limited, tropical settings, these disorders are now coming to light because of globalisation and improved diagnosis and treatment. Enhanced understanding of these illnesses has prompted this review. RECENT FINDINGS: Methods of diagnosis have currently transitioned from blood smear examinations to immunological assays and molecular methods. Tools to assess neurological involvement, such as magnetic resonance imaging, are now increasingly available in regions and countries with high infection loads. Sleep and other electrophysiological technologies (electroencephalography, actigraphy) are also promising diagnostic tools but requiring field-validation. Access to treatments was formerly limited, even as limitations of agents used in the treatment are increasingly recognised. Newer agents are now being developed and trialled, encouraged by improved understanding of the disorders' molecular underpinnings. SUMMARY: Prompt diagnosis and treatment are crucial in ensuring cure from the infections. Attention should also be due to the development of globally applicable treatment guidelines, the burden of neurological sequelae and elimination of the zoonoses from currently endemic regions.
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Enfermedad de Chagas , Malaria Cerebral , Tripanosomiasis Africana , Animales , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/terapia , Humanos , Tripanosomiasis Africana/diagnóstico , Tripanosomiasis Africana/epidemiología , Tripanosomiasis Africana/terapiaRESUMEN
INTRODUCTION: Epilepsy is a common yet misunderstood condition in Cameroon, including in the Batibo Health district. METHODS: This cross-sectional study describes epilepsy clinical characteristics, the treatment gap, and associated factors in a rural district in Cameroon. After screening for epilepsy using a door-to-door survey, physicians confirmed suspected cases of epilepsy. Detailed information on the medical, seizure, and treatment history was collected from everyone with epilepsy, followed by a general and neurological examination. RESULTS: We diagnosed 546 people with active epilepsy (at least one seizure in the previous 12â¯months). The mean age of people with active epilepsy was 25.2â¯years (SD: 11.1). The mean age at first seizure was 12.5â¯years (SD: 8.2). Convulsive seizures (uncertain whether generalized or focal) were the most common seizure types (60%), while 41% had focal-onset seizures. About 60% of people had seizures at least monthly. One-quarter of participants had had at least one episode of status epilepticus. Anti-seizure medication (ASM) was taken by 85%, but most were receiving inappropriate treatment or were non-adherent, hence the high treatment gap (80%). Almost a third had had seizure-related injuries. Epilepsy was responsible for low school attendance; 74% of school dropouts were because of epilepsy. CONCLUSION: The high proportion of focal-onset seizures suggests acquired causes (such as neurocysticercosis and onchocerciasis, both endemic in this area). The high epilepsy treatment gap and the high rates of status epilepticus and epilepsy-related injuries underscore the high burden of epilepsy in this rural Cameroonian health district.
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Epilepsia , Oncocercosis , Adulto , Camerún , Estudios Transversales , Humanos , ConvulsionesRESUMEN
This population-based cross-sectional survey with a follow-up case-control study assessed the prevalence, incidence, and risk factors for epilepsy in a rural health district in the North-West Region of Cameroon. Community-based epilepsy screening targeted all inhabitants, six years and older, in all 16 health areas in the Batibo Health District. During door-to-door visits, trained fieldworkers used a validated questionnaire to interview consenting household heads to screen for epilepsy in eligible residents. Trained physicians subsequently assessed people with suspected seizures. After clinical assessment, they confirmed or refuted the diagnosis and estimated the date of epilepsy onset. A trained nurse interviewed people with epilepsy and randomly selected healthy individuals, obtaining relevant demographic details and information on exposure to risk factors for epilepsy. Out of 36,282 residents screened, 524 had active epilepsy. The age-standardized prevalence of active epilepsy was 33.9/1,000 (95% CI: 31.0-37.1/1,000). We estimated the one-year age-standardized epilepsy incidence at 171/100,000 (95%CI: 114.0-254.6). Active epilepsy prevalence varied widely between health areas, ranging between 12 and 75 per 1,000. The peak age-specific prevalence was in the 25-34 age group. In adults, multivariate analysis showed that having a relative with epilepsy was positively associated with epilepsy. Epilepsy characteristics in this population, geographical heterogeneity, and the age-specific prevalence pattern suggest that endemic neurocysticercosis and onchocerciasis may be implicated. Further investigations are warranted to establish the full range of risk factors for epilepsy in this population.
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Epilepsia , Adulto , Camerún/epidemiología , Estudios de Casos y Controles , Estudios Transversales , Epilepsia/epidemiología , Humanos , Incidencia , Prevalencia , Población RuralRESUMEN
BACKGROUND: The COVID-19 pandemic has been associated with significant psychological and social distress worldwide. We investigated fear and depression among adults in Cameroon during different phases of the COVID-19 outbreak. METHODS: An online survey was conducted in Cameroon from June-December 2020 using a structured questionnaire. Socio-demographic data and information regarding COVID-19 history were obtained. Fear and depressive symptoms were assessed using the Fear of COVID-19 score (FCV-19S) and the Patient Health Questionnaire (PHQ-9), respectively. Responses were clustered in weeks to better appreciate their evolution over time. RESULTS: Overall, 7381 responses from all ten regions of Cameroon were analysed (median age: 30 years, 73.3% male). The prevalence of depression (PHQ-9 score ≥ 10) was 8.4%, and that of high fear of COVID-19 (FCV-19S scores ≥19) was 57.4%. These rates were similar across genders, age-groups, and region of residence. While mean weekly PHQ-9 scores remained fairly stable throughout the study period (range: 2.53-3.21; p = 0.101), mean FCV-19S scores were highest during the early weeks but decreased significantly thereafter (from 20.31 to 18.34; p < 0.001). Multivariate analyses revealed that having a postgraduate degree, a history of quarantine, flu-like symptoms during the past 14 days, and higher FCV-19S scores were associated with more severe depressive symptoms, while obtaining COVID-19 information from various sources reduced the odds for depression. CONCLUSION: Depression amidst the COVID-19 crisis is less prevalent in Cameroon than in other countries. Prompt and widespread dissemination of adequate COVID-19 information may reduce the risks for depression by dispelling fear and anxiety among Cameroonians.
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COVID-19 , Pandemias , Adulto , Camerún/epidemiología , Depresión/epidemiología , Miedo , Femenino , Humanos , Masculino , SARS-CoV-2RESUMEN
OBJECTIVE: There is lack of Cameroonian adult neuropsychological (NP) norms, limited knowledge concerning HIV-associated neurocognitive disorders in Sub-Saharan Africa, and evidence of differential inflammation and disease progression based on viral subtypes. In this study, we developed demographically corrected norms and assessed HIV and viral genotypes effects on attention/working memory (WM), learning, and memory. METHOD: We administered two tests of attention/WM [Paced Auditory Serial Addition Test (PASAT)-50, Wechsler Memory Scale (WMS)-III Spatial Span] and two tests of learning and memory [Brief Visuospatial Memory Test-Revised (BVMT-R), Hopkins Verbal Learning Test-Revised (HVLT-R)] to 347 HIV+ and 395 seronegative adult Cameroonians. We assessed the effects of viral factors on neurocognitive performance. RESULTS: Compared to controls, people living with HIV (PLWH) had significantly lower T-scores on PASAT-50 and attention/WM summary scores, on HVLT-R total learning and learning summary scores, on HVLT-R delayed recall, BVMT-R delayed recall and memory summary scores. More PLWH had impairment in attention/WM, learning, and memory. Antiretroviral therapy (ART) and current immune status had no effect on T-scores. Compared to untreated cases with detectable viremia, untreated cases with undetectable viremia had significantly lower (worse) T-scores on BVMT-R total learning, BVMT-R delayed recall, and memory composite scores. Compared to PLWH infected with other subtypes (41.83%), those infected with HIV-1 CRF02_AG (58.17%) had higher (better) attention/WM T-scores. CONCLUSIONS: PLWH in Cameroon have impaired attention/WM, learning, and memory and those infected with CRF02_AG viruses showed reduced deficits in attention/WM. The first adult normative standards for assessing attention/WM, learning, and memory described, with equations for computing demographically adjusted T-scores, will facilitate future studies of diseases affecting cognitive function in Cameroonians.
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Atención/fisiología , Infecciones por VIH/virología , Aprendizaje/fisiología , Memoria a Corto Plazo/fisiología , Adolescente , Adulto , Camerún , Estudios de Casos y Controles , Trastornos del Conocimiento , Femenino , Genotipo , Humanos , Masculino , Trastornos de la Memoria/virología , Recuerdo Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas , Aprendizaje Verbal , Adulto JovenRESUMEN
BACKGROUND: Epilepsy affects at least 50 million individuals worldwide, especially in sub-Saharan Africa (sSA). Cognitive impairment is common in people with epilepsy (PWE) yet, little is known on the burden of cognitive impairment in people with epilepsy in sSA. This study was thus designed to assess cognitive impairment in PWE or epilepsy-associated neurocognitive disorders (EAND) in a rural population in Cameroon. METHODS: This was a case-control study including PWE and age/sex-matched healthy controls from July to September 2017 in Bilomo, a village in the Mbam and Kim Division. The Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS), Dubois' Five Word testing, Frontal Assessment Battery (FAB), Isaac's Set Test and the Clock drawing test were administered to the study participants to evaluate global and specific cognitive functions. RESULTS: Eighty participants were included (40 cases and 40 controls) with a mean age of 25.78â¯years. Using the MoCA, 87.5% of cases had cognitive impairment, against 37.5% of controls (pâ¯<â¯0.001; OR 11.67; CI 3.40-45.09). Using the IHDS, the prevalence of global cognitive impairment was 84.6% among the cases against 40% for the controls (pâ¯=â¯<0.001; OR 7.07; CI 2.29-29.19). Specifically, executive function deficits (92.5% of cases vs 40.0% of controls pâ¯=â¯<0.001 ORâ¯=â¯18.50 CI; 4.48-105.08) and decreased verbal fluency (100% of cases against 45% of controls pâ¯<â¯0.001) were the most affected cognitive domains. Longer duration of epilepsy and higher seizure frequency were associated with global cognitive impairment. Low level of education was associated with both decreased verbal fluency and executive dysfunction while a longer stay in Bilomo correlated with poor results on the Isaac's Set Test. CONCLUSION: The prevalence of cognitive impairment appears to be much higher in PWE in the Mbam valley, particularly decreased executive function and verbal fluency, than in people without epilepsy. Longer disease duration, higher seizure frequency, low level of education and length of stay in Bilomo are associated with poorer cognitive performance. More studies are needed to refine evaluation tools to better characterize and manage EAND in sSA.
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Epilepsia , Oncocercosis , Adulto , África del Sur del Sahara , Camerún/epidemiología , Estudios de Casos y Controles , Epilepsia/epidemiología , Epilepsia/etiología , Humanos , Trastornos Neurocognitivos , Pruebas Neuropsicológicas , Población RuralRESUMEN
: Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3'polypurine tract (3'-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3'-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3%-23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3'-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had 1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3'-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3'-PPT sequences could reveal treatment failure etiology.
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Farmacorresistencia Viral , Infecciones por VIH/virología , Inhibidores de Integrasa VIH/uso terapéutico , Integrasa de VIH/genética , VIH-1/genética , Polimorfismo Genético , Adulto , Camerún , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/enzimología , VIH-1/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Motivos de NucleótidosRESUMEN
There is a large body of evidence suggesting that parasites could be a major preventable risk factor for epilepsy in low- and middle-income countries. We review potentially important substrates for epileptogenesis in parasitic diseases. Taenia solium is the most widely known parasite associated with epilepsy, and the risk seems determined mainly by the extent of cortical involvement and the evolution of the primary cortical lesion to gliosis or to a calcified granuloma. For most parasites, however, epileptogenesis is more complex, and other favorable host genetic factors and parasite-specific characteristics may be critical. In situations where cortical involvement by the parasite is either absent or minimal, parasite-induced epileptogenesis through an autoimmune process seems plausible. Further research to identify important markers of epileptogenesis in parasitic diseases will have huge implications for the development of trials to halt or delay onset of epilepsy.
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Epilepsia/epidemiología , Epilepsia/parasitología , Enfermedades Parasitarias/epidemiología , Animales , Epilepsia/inmunología , Gliosis/inmunología , Gliosis/parasitología , Gliosis/patología , Humanos , Parásitos/inmunología , Parásitos/aislamiento & purificación , Enfermedades Parasitarias/inmunología , Taenia solium/inmunología , Taenia solium/aislamiento & purificación , Teniasis/epidemiología , Teniasis/inmunologíaRESUMEN
BACKGROUND: A high prevalence of epilepsy has been observed in several onchocerciasis-endemic countries, including Cameroon. However, little is known on the clinical presentations of the affected persons with epilepsy (PWE). A community-based study was conducted with the aim of describing the spectrum of seizures in selected onchocerciasis-endemic villages in Cameroon and documenting relevant medical history in patients with onchocerciasis-associated epilepsy (OAE). METHODS: We carried out door-to-door surveys in 5 onchocerciasis-endemic villages in Cameroon and recruited all consenting PWE. Epilepsy was diagnosed using a 2-step approach consisting of the administration of a standardized 5-item questionnaire followed by confirmation of the suspected cases by a neurologist. Onchocerciasis-associated epilepsy was defined as ≥2 seizures without an obvious cause, starting between the ages of 3-18â¯years in previously healthy persons having resided for at least 3â¯years in an onchocerciasis-endemic area. Ivermectin use by PWE was verified. Seizure history, relevant past medical, and family history, as well as neurological findings, were noted. RESULTS: In all, 156 PWE were recruited in the 5 villages. The modal age group for epilepsy onset was 10-14â¯years. The diagnostic criteria for OAE were met by 93.2% of the PWE. Participants had one or more of the following seizure types: generalized tonic-clonic seizures (89.1%), absences (38.5%), nodding (21.8%), focal nonmotor (7.7%), and focal motor seizures (1.9%). One case (0.6%) with the "Nakalanga syndrome" was identified. More than half (56.4%) of PWE had at least one seizure per month. In one village, 56.2% of PWE had onchocercal skin lesions. CONCLUSION: People with epilepsy in onchocerciasis-endemic villages in Cameroon present with a wide clinical spectrum including nodding seizures and Nakalanga features. A great majority of participants met the diagnostic criteria for OAE, suggesting that better onchocerciasis control could prevent new cases. Epilepsy management algorithms in these areas must be adjusted to reflect the varied seizure types.
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Epilepsia/diagnóstico , Epilepsia/epidemiología , Oncocercosis/diagnóstico , Oncocercosis/epidemiología , Adolescente , Adulto , Algoritmos , Camerún/epidemiología , Niño , Preescolar , Femenino , Humanos , Masculino , Anamnesis/métodos , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Depression affects 18-30 % of HIV-infected patients in Africa and is associated with greater stigma, lower antiretroviral adherence, and faster disease progression. However, the region's health system capacity to effectively identify and treat depression is limited. Task-shifting models may help address this large mental health treatment gap. Measurement-Based Care (MBC) is a task-shifting model in which a Depression Care Manager guides a non-psychiatric (e.g., HIV) provider in prescribing and managing antidepressant treatment. We adapted MBC for depressed HIV-infected patients in Cameroon and completed a pilot study to assess feasibility, safety, acceptability, and preliminary efficacy. We enrolled 55 participants; all started amitriptyline 25-50 mg daily at baseline. By 12 weeks, most remained at 50 mg daily (range 25-125 mg). Median (interquartile range) PHQ-9 depressive severity scores declined from 13 (12-16) (baseline) to 2 (0-3) (week 12); 87 % achieved depression remission (PHQ-9 <5) by 12 weeks. Intervention fidelity was high: HIV providers followed MBC recommendations at 96 % of encounters. Most divergences reflected a failure to increase dose when indicated. No serious and few bothersome side effects were reported. Most suicidality (prevalence 62 % at baseline; 8 % at 12 weeks) was either passive or low-risk. Participant satisfaction was high (100 %), and most participants (89 %) indicated willingness to pay for medications if MBC were implemented in routine care. The adapted MBC intervention demonstrated high feasibility, safety, acceptability, and preliminary efficacy in this uncontrolled pilot study. Further research should assess whether MBC could improve adherence and HIV outcomes in this setting.
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Fármacos Anti-VIH/uso terapéutico , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Seropositividad para VIH/tratamiento farmacológico , Cumplimiento de la Medicación/psicología , Estigma Social , Adulto , Camerún/epidemiología , Depresión/diagnóstico , Depresión/epidemiología , Progresión de la Enfermedad , Estudios de Factibilidad , Femenino , Seropositividad para VIH/epidemiología , Seropositividad para VIH/psicología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Control de Insectos , Oncocercosis , Simuliidae , Camerún , Animales , Simuliidae/parasitología , Humanos , Oncocercosis/prevención & control , Control de Insectos/métodos , Femenino , Masculino , Adulto , Insectos Vectores , Persona de Mediana Edad , Grupos Focales , Conocimientos, Actitudes y Práctica en Salud , Adulto Joven , Mordeduras y Picaduras de Insectos/prevención & controlRESUMEN
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.
Asunto(s)
Albinismo Oculocutáneo , Melaninas , Pigmentación de la Piel , Humanos , Pigmentación de la Piel/genética , Melaninas/genética , Alelos , Genómica , Pigmentación/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Represoras/genéticaRESUMEN
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 ± 4.1â g) by injecting them with 10 million tachyzoites in suspension in 500â 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.