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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.
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INTRODUCTION: Meaningful community engagement (CE) is increasingly being considered the major determinant of successful research, innovation and intervention uptake. Community leaders, policy makers and funders have expressed the need to engage communities in research. CE in research empowers the host community to participate in addressing its own health needs and health disparities while ensuring that researchers understand community priorities. Thus, appropriate CE opens a unique way to promote coproduction, coimplementation and coevaluation, which may strengthen both the sense of inclusion, ownership and the effectiveness of the research life-cycle. The aim of this review is to synthesise available evidence on how to engage communities in research in a gender-sensitive, ethical, culture-appropriate and sustainable way in sub-Saharan Africa (SSA). This protocol has been developed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and follows the guidance provided by the Cochrane Handbook for Systematic Reviews. METHODS AND ANALYSIS: A combination of key text words and medical subject headings such as 'Community Engagement' or 'Community Involvement' will be used to search 009 databases for all literature published between 1 January 2000 and 31 July 2021. Citations retrieved from database searches will be exported into EndNote X9 to remove duplicate citations and imported into Rayyan QCRI for screening. Two independent reviewers will conduct the screening and data extraction process. Disagreements between review authors will be resolved through discussions, consensus a third reviewer serving as a tiebreaker. The risk of bias will be assessed using the 10-item Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. The three-staged process described by Thomas and Harden will be used for the thematic and narrative synthesis of findings. ETHICS AND DISSEMINATION: This is a systematic review which uses already collected data thus ethical approval not required. Findings will be published in an open access peer-reviewed journal and presented in relevant conferences and workshops. PROSPERO REGISTRATION NUMBER: This protocol has been submitted for registration in PROSPERO and has been published under registration number CRD42021282503 .
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Programas de Rastreamento , Revisão por Pares , Humanos , Metanálise como Assunto , Princípios Morais , Pesquisa Qualitativa , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
Infection with Onchocerca volvulus was recently reported to increase the risk for epilepsy in Cameroonian children. We investigated whether infection with O. volvulus may alter the cognitive function of children who may or may not develop epilepsy later in their lifetime. Using rapid diagnostic tests, we determined the presence of Ov16 antibodies in 209 school-aged children without epilepsy recruited from three Cameroonian villages, as a proxy for onchocerciasis exposure. In addition, the neurocognitive performance of these children was assessed using a battery of validated tools. Participants were aged 6-16 years, and 46.4% were Ov16 seropositive. Upon standardizing age-specific neurocognitive scores and investigating predictors of neurocognitive performance using multiple linear regression models (adjusted for gender, education level, previous ivermectin use, and anthropometric parameters), we found that being Ov16-positive was significantly associated with reduced semantic verbal fluency (estimate -0.38; 95% confidence interval -0.65 to -0.11; p = 0.006) and lower scores on the International HIV Dementia Scale (estimate -0.31; confidence interval -0.56 to -0.04; p = 0.025). Furthermore, an increasing frequency of past ivermectin use was associated with increased neurocognitive scores. Our findings suggest that exposure to O. volvulus may affect neurocognitive performance of children. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40817-021-00111-z.
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INTRODUCTION: Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, remains endemic in Cameroon despite decades of community-directed treatment with ivermectin (CDTI). CDTI is often hampered by coendemicity with loiasis (another filariasis caused by Loa loa) in some areas. Strong epidemiological evidence suggests that O. volvulus infection increases the risk for onchocerciasis-associated epilepsy (OAE) among Cameroonian children. This highlights the urgent need to strengthen onchocerciasis elimination programmes in mesoendemic/hyperendemic areas. Novel alternative strategies, such as the 'slash and clear' (S&C) vector control method, may be required to complement ongoing CDTI to accelerate elimination of transmission. The short-term impact of S&C on the biting rates of the blackfly vectors has been demonstrated in other settings. However, its long-term effectiveness and impact on parasitological and serological markers of onchocerciasis transmission as well as on OAE are still unknown. METHODS AND ANALYSIS: We aim to assess the effectiveness of annual S&C interventions combined with CDTI in reducing onchocerciasis transmission and epilepsy incidence. Eight onchocerciasis-endemic villages located <5 km from the Mbam or Sanaga rivers will be randomised to two arms: four villages will receive yearly CDTI only for two consecutive years (Arm 1), while the other four villages will receive CDTI plus annual S&C for 2 years (Arm 2). Study outcomes (blackfly biting rates, infectivity rates and seroprevalence of onchocerciasis antibodies (Ov16 antibodies) in children, prevalence of microfilaridermia and epilepsy incidence) will be monitored prospectively and compared across study arms. We expect that S&C will have an added benefit over CDTI alone. ETHICS AND DISSEMINATION: The protocol has received ethical approval from the institutional review board of the Cameroon Baptist Convention Health Board (reference number: IRB2021-03) and has been registered with the Pan African Clinical Trials Registry. Findings will be disseminated at national and international levels via meetings and peer-reviewed publications. TRIAL REGISTRATION NUMBER: PACTR202101751275357.
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Epilepsia , Oncocercose , Criança , Humanos , Incidência , Ivermectina/uso terapêutico , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos SoroepidemiológicosRESUMO
We reported recently that the elevated plus maze is a good tool for evaluating cognitive and motor functional changes in gamma-irradiated rats as a model for new drug evaluation and monitoring. The capacity of Garcinia kola to mitigate radiation-induced brain injury is currently unknown. We therefore assessed the effects of the neuroprotective medicinal plant Garcinia kola, on the cognitive and motor changes in this murine model of acute radiation syndrome. Wistar rats exposed once to an ionizing dose of Tc99m-generated Gamma radiation were treated with an ethyl acetate fraction of methanolic extract of Garcinia kola seeds (content of 100 mg/kg of extract) for 9 weeks. Cognitive and motor function indicators were assessed in the elevated plus maze in these animals and compared with irradiated control groups (vitamin C- and vehicle-treated groups) and the non-irradiated control rats. The irradiated control group displayed cachexia, shaggy and dirty fur, porphyrin deposits around eyes, decreased exploratory activity, reduced social interactions and a loss of thigmotaxis revealed by a marked decrease in rearing episodes and stretch attend posture episodes close to the walls of elevated plus maze closed arm, an increased central platform time, and decreases in open arm time and entries. This group further displayed a decrease in head dips and grooming episodes. Treatment with Garcinia kola, and in a lesser extent vitamin C, significantly prevented the body weight loss (P < 0.001) and mitigated the development of elevated plus maze signs of cognitive and motor affections observed in the irradiated control group (P < 0.05). Altogether, our data suggest for the first time that Garcinia kola seeds have protective properties against the development of cognitive and motor decline in the acute radiation syndrome-like context. Future studies are warranted to characterize the molecular mechanisms and neuronal networks of this action.
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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 , Camarões/epidemiologia , Depressão/epidemiologia , Medo , Feminino , Humanos , Masculino , SARS-CoV-2RESUMO
Since March 2020, the Cameroonian government implemented nationwide measures to stall COVID-19 transmission. However, little is known about how well these unprecedented measures are being observed as the pandemic evolves. We conducted a six-month online survey to assess the preventive behaviour of Cameroonian adults during the COVID-19 outbreak. A five-point adherence score was constructed based on self-reported observance of the following preventive measures: physical distancing, face mask use, hand hygiene, not touching one's face, and covering the mouth when coughing or sneezing. Predictors of adherence were investigated using ordinal logistic regression models. Of the 7381 responses received from all ten regions, 73.3% were from male respondents and overall mean age was 32.8 ± 10.8 years. Overall mean adherence score was 3.96 ± 1.11 on a scale of 0-5. Mean weekly adherence scores were initially high, but gradually decreased over time accompanied by increasing incidence of COVID-19 during the last study weeks. Predictors for higher adherence included higher age, receiving COVID-19 information from health personnel, and agreeing with the necessity of lockdown measures. Meanwhile, experiencing flu-like symptoms was associated with poor adherence. Continuous observance of preventive measures should be encouraged among Cameroonians in the medium- to long-term to avoid a resurgence in COVID-19 infections.
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COVID-19 , Adulto , Camarões/epidemiologia , Controle de Doenças Transmissíveis , Estudos Transversais , Humanos , Masculino , SARS-CoV-2 , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: Epilepsy is highly prevalent in onchocerciasis-endemic African regions. Various types of epilepsy have been described in such regions based essentially on clinical characteristics. METHODS: We conducted a clinical, neurophysiological and neuropsychological study of epilepsy in the onchocerciasis-endemic region of Ntui, Sanaga-Mbam area, Cameroon. RESULTS: One hundred and eighty-seven persons with presumed epilepsy were recruited in an epilepsy clinic in Ntui. Epilepsy was clinically confirmed in 144 (79%) subjects, 69 (46.0%) of them met the onchocerciasis-associated epilepsy (OAE) criteria, and 51 of 106 tested (48.1%) presented Ov16 antibodies. Electroencephalograms (EEG) were recorded in 91 participants, of which 36 (33%) were considered abnormal and 27 of 36 (75%) revealed bifrontotemporal spike and slow waves. Concerning the neuropsychological evaluation, 29% showed severe global cognitive impairment, 28% severe episodic memory impairment, and 66% severe frontal cognitive impairment. Half of the persons with epilepsy (PWE) suffered from a mental disorder. SIGNIFICANCE: In PWE in the Sanaga-Mbam area in Cameroon, we observed EEG patterns similar to those described among persons with OAE, including nodding syndrome in other onchocerciasis-endemic areas. Most PWE presented with severe cognitive impairment. We hypothesize that onchocerciasis may induce neurocognitive disorders and epilepsy via a mechanism that involves mainly the frontal and temporal regions of the brain.
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Epilepsia , Síndrome do Cabeceio , Oncocercose , Camarões/epidemiologia , Eletroencefalografia , Epilepsia/epidemiologia , Humanos , Oncocercose/complicações , Oncocercose/epidemiologiaRESUMO
Human African trypanosomiasis (HAT) remains a serious public health problem with diagnostic and treatment challenges in many African countries. The absence of a gold-standard biomarker has been a major difficulty for accurate disease staging and treatment follow-up. We therefore attempted to develop a simple, affordable, and noninvasive biomarker for HAT diagnosis and staging. Simultaneous actigraphy and polysomnography as well as cerebrospinal fluid (CSF) white blood cell (WBC) count, trypanosome presence, and C-X-C motif ligand (CXCL)-10 cytokine levels were performed in 20 HAT patients and nine healthy individuals (controls) using standard procedures. The International HIV Dementia Scale (IHDS) was scored in some patients as a surrogate for clinical assessment. From actigraphic parameters, we developed a novel sleep score and used it to determine correlations with other HAT markers, and compared their performance in differentiating between patients and controls and between HAT stages. The novel actigraphy sleep score (ASS) had the following ranges: 0-25 (healthy controls), 67-103 (HAT stage I), 111-126 (HAT intermediate), and 133-250 (HAT stage II). Compared with controls, stage I patients displayed a 7-fold increase in the ASS (P < 0.01), intermediate stage patients a 10-fold increase (P < 0.001), and HAT stage II patients an almost 20-fold increase (P < 0.001). CXCL-10 showed high interindividual differences. White blood cell counts were only marked in HAT stage II patients with a high interindividual variability. The International HIV Dementia Scale score negatively correlated with the ASS. We report the development and better performance of a new biomarker, ASS, for HAT diagnosis, disease staging, and monitoring that needs to be confirmed in large cohort studies.
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Actigrafia/métodos , Biomarcadores/análise , Trypanosoma brucei gambiense/isolamento & purificação , Tripanossomíase Africana/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Sono , Tripanossomíase Africana/líquido cefalorraquidiano , Tripanossomíase Africana/parasitologia , Adulto JovemRESUMO
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 , Oncocercose , Adulto , África Subsaariana , Camarões/epidemiologia , Estudos de Casos e Controles , Epilepsia/epidemiologia , Epilepsia/etiologia , Humanos , Transtornos Neurocognitivos , Testes Neuropsicológicos , População RuralRESUMO
To confirm our earlier evidence of a temporal and dose-response relationship between onchocerciasis and epilepsy, we conducted another cohort study in a different setting in Cameroon. Individuals whose Onchocerca volvulus microfilarial density (Ov-MFD) was measured in 1992-1994 when they were children were revisited in 2019 to determine if they acquired epilepsy. With reference to individuals with no microfilariae in 1992-1994, the relative risks of acquiring epilepsy were 0.96, 2.76, 3.67, and 11.87 in subjects with initial Ov-MFD of 1-7, 8-70, 71-200, andâ >â 200 microfilariae per skin snip, respectively. This study further demonstrates reproducibility using the Bradford Hill's criteria for causality.
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BACKGROUND: Experimental models are needed to better understand the pathophysiology of neurodegenerative diseases to develop novel therapeutics. The neuropathology and clinical signs of acute radiation syndrome resemble those of neurodegenerative conditions. We characterized elevated plus maze (EPM) indicators of cognitive and motor impairment in rats exposed to brain-damaging doses of gamma radiation to develop a model for neurological component of the acute radiation syndrome. MATERIALS AND METHODS: Technetium 99 m was administered once through tail vein to male Wistar rats to reach an absorbed dose of Gamma radiation of 667 mGy (66.7Rad). Animal performance in the EPM was assessed every 14 days. Rats were observed for 9 weeks for the occurrence of systemic and neurological signs. Comparisons were done between irradiated and nonirradiated rats, and in each group with baseline performance. RESULTS: EPM indicators of cognitive and motor impairment, anxiety, and depression were observed concomitantly and increased with the severity of acute radiation syndrome-like systemic and neurological signs. Alterations in EPM indicators appeared 3 weeks postirradiation and their severity increased with time. Notably, arm transitions and the distance covered in the maze were decreased (-56.71% and -73.62%, P < 0.001), as well as open arm entries and time spent in open arms (-77.78% and -76.19%, P < 0.05) and the indicator of thigmotaxis rearing (-92.45, P < 0.001). CONCLUSIONS: Our results suggest that irradiated rat performance in the EPM paradigm reflects disease severity and could be used to perform both acute and subchronic pharmacological studies in acute radiation syndrome-like diseases in rats.
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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.