Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Mucuna pruriens to treat Parkinson's disease in low-income countries: Recommendations and practical guidelines from the farmer to clinical trials. Paving the way for future use in clinical practice.

Parkinson's disease (PD) is a progressive and disabling neurodegenerative disease that rapidly worsens and results in premature mortality if left untreated. Although levodopa is the gold standard treatment for PD globally, its accessibility and affordability are severely limited in low- and middle-income countries worldwide. In this scenario, Mucuna pruriens (MP), a leguminous plant growing wild in tropical regions, emerges as a potential alternative or adjunct to levodopa-based medications due to its cost-effectiveness and global natural availability. Recent studies have demonstrated that MP can significantly ameliorate motor symptoms, although tolerability may vary. The proposition that MP could play a pivotal role in providing affordable and symptomatic relief for PD in low- and middle-income countries is grounded in its promising therapeutic profile, yet caution is warranted until more comprehensive data on the long-term safety and efficacy of MP become available. This manuscript summarizes the knowledge gained about MP by the authors, focusing on how to cultivate, store, and provide it to patients in the safest and most effective way in clinical trials. We aim to increase clinical trials investigating its safety and efficacy in PD, before promoting individual use of MP on a global scale, particularly in countries where availability and affordability of levodopa-based medications is still limited.

Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

Parkinson's Disease in Sub-Saharan Africa: Pesticides as a Double-Edged Sword.

Long-term exposure to pesticides used in agriculture is increasingly being identified as a risk factor for developing Parkinson's disease. How chronic pesticide exposure might contribute to the growth of Parkinson's disease in the mainly agricultural communities of Sub-Saharan Africa has thus far received limited attention. There are specific concerns in this area of the world: aging of the population, in combination with chronic exposure to widely used pesticides, including those that have been restricted elsewhere in the world because of neurotoxicity and other health risks. Of interest, the prevalence of Parkinson's disease among specific (semi)nomadic populations in Tanzania seems very low, possibly due to their lack of exposure to agricultural chemicals. But at the same time, pesticides have also brought important benefits to this part of the world. Specifically, in Sub-Saharan Africa, pesticides have been directly helpful in preventing and controlling famine and in containing major human infectious diseases. This creates a complex risk-benefit ratio to the use of pesticides within a global perspective, and urgently calls for the development and implementation of affordable alternatives for areas such as Sub-Saharan Africa, including non-neurotoxic compounds and non-chemical alternatives for the use of pesticides.

Delivery of Allied Health Therapies to People with Parkinson's Disease in Africa.

Allied health therapies refer to a range of healthcare professionals, including physiotherapists, occupational and speech-language therapists, who aim to optimize daily function and quality of life in conjunction with medical care. In this narrative review of literature on allied health therapies in people with Parkinson's disease (PD), we focused on the diversity in healthcare access, state of the art, current challenges in the African continent, and proposed solutions and future perspectives. Despite the increasing prevalence and awareness of PD in Africa, numerous challenges persist in its management. These include resource limitations, geographical barriers, sociocultural beliefs, and economic constraints. Nevertheless, innovative solutions, including telerehabilitation and community-based rehabilitation, offer hope. Collaborative efforts within the continent and internationally have shown potential in bridging training and resource gaps. Significant strides can be made with tailored interventions, technological advancements, and multifaceted collaborations. This review offers practical insights for healthcare professionals, policymakers, and caregivers to navigate and optimize PD care in the African context.

Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease.

The biological basis of the neurodegenerative movement disorder, Parkinson's disease (PD), is still unclear despite it being 'discovered' over 200 years ago in Western Medicine. Based on current PD knowledge, there are widely varying theories as to its pathobiology. The aim of this article was to explore some of these different theories by summarizing the viewpoints of laboratory and clinician scientists in the PD field, on the biological basis of the disease. To achieve this aim, we posed this question to thirteen "PD experts" from six continents (for global representation) and collated their personal opinions into this article. The views were varied, ranging from toxin exposure as a PD trigger, to LRRK2 as a potential root cause, to toxic alpha-synuclein being the most important etiological contributor. Notably, there was also growing recognition that the definition of PD as a single disease should be reconsidered, perhaps each with its own unique pathobiology and treatment regimen.

Long COVID? Fatal case report of ischemic stroke and pulmonary embolism post COVID-19 infection.

Coronavirus disease 19 (COVID-19) may lead to post-COVID syndrome a few weeks to months after the infection with various symptoms. Post-COVID thromboembolic syndrome may be a result of coagulopathy that occurs in both the arterial and venous circulation. Apart from direct cellular infection, post-COVID syndrome may occur due to immune system dysregulation, endothelial injury, and hypercoagulability, leading to thrombosis. We present a 32-year-old man who was diagnosed with mild symptoms of COVID-19 infection 4 months before an acute ischemic stroke and an asymptomatic pulmonary embolism. A COVID-19 antigen test was negative. An analysis of prothrombotic factors was negative. He could not receive any therapeutic intervention before his demise. The extent of COVID-19 infection after the onset of symptoms is a mystery and poses a fatal concern due to the increasing number of complications. The long-term complications after COVID-19 infection are still not understood. Clinicians need to be aware of any signs and symptoms that may arise months after COVID-19 infection and its possible causal relationship.

Idiopathic Arachnoiditis of the Cauda Equina: A Case Report from Tanzania.

Arachnoiditis is a rare clinical entity that usually presents with severe debilitating radiating pain that can pose a challenge in diagnosis especially in areas without appropriate imaging modalities. We present a 26-year-old male with progressive lower back pain with radiation to the lower extremities, aggravated by movement and touch. We diagnosed idiopathic arachnoiditis based on cerebrospinal fluid analysis and magnetic resonance imaging. He was managed with a 5-day course of methylprednisolone and analgesics with a good outcome. Severe back pain without a specific cause in a young patient should be investigated with proper imaging modalities and lumbar puncture if warranted to evaluate the cause.

Fatal cerebral venous sinus thrombosis as a manifestation of uncontrolled systemic lupus erythematosus in a young African female.

In a young patient with systemic lupus erythematosus presenting with status epilepticus and neurological deficits, early brain imaging, risk factor identification and prompt treatment of underlying lupus flare-up and cerebral venous sinus thrombosis could significantly improve the management and prognosis.

Altitude-Related Disorders on Mount Kilimanjaro, Tanzania: Two-Year Survey in a Local Referral Center.

INTRODUCTION: A significant number of climbers on Mount Kilimanjaro are affected by altitude-related disorders. The aim of this study was to determine the main causes of morbidity and mortality in a representative cohort of climbers based on local hospital records. METHODS: We conducted a 2-y retrospective chart review of all patients presenting to the main referral hospital in the region after a climb on Mount Kilimanjaro, including all relevant records and referrals for postmortem studies. RESULTS: We identified 62 climbers who presented to the hospital: 47 inpatients and 15 outpatients. Fifty-six presented with high altitude illness, which included acute mountain sickness (n=8; 14%), high altitude pulmonary edema (HAPE) (n=30; 54%), high altitude cerebral edema (HACE) (n=7; 12%), and combined HAPE/HACE (n=11; 20%). The mean altitude of symptom onset ranged from 4600±750 m for HAPE to 5000±430 m for HAPE/HACE. The vast majority of inpatients (n=41; 87%) were improved on discharge. Twenty-one deceased climbers, most having died while climbing (n=17; 81%), underwent postmortem evaluation. Causes of death were HAPE (n=16; 76%), HAPE/HACE (n=3; 14%), trauma (1), and cardiopulmonary (1). CONCLUSIONS: HAPE was the main cause of death during climbing as well as for hospital admissions. The vast majority of climbers who presented to hospital made a full recovery.

Ox cart accidents as a cause of spinal cord injury in Tanzania.

STUDY DESIGN: Prospective Study. OBJECTIVES: To describe a unique site-specific injury mechanism for spinal cord injury: incidents involving ox-carts. SETTING: Main referral hospital for North-eastern Tanzania. METHODS: A prospective cohort study on Spinal Cord Injury (SCI) in a tertiary referral center in North-eastern Tanzania was examined for accidents related to the use of ox-carts, a major means of transport in a rugged rural area where the economy is largely based on agricultural practices. RESULTS: Five out of a total of 163 individuals admitted with SCI were injured in incidents directly related to the use of ox-carts. On admission each of the five individuals had different neurological level and corresponding injury severity as follows; C4 (American Spinal Injury Association Impairment Scale) AIS A), C5 (AIS D), C7 (AIS C), T1 (AIS C) and L1 (AIS D). Two out of the five patients developed secondary complications during their hospital stay. CONCLUSION: The nature of these injuries highlights the influence of one's environment and social circumstances on the risk of sustaining a SCI. Such cases also serve to illustrate the need for tailored prevention, rehabilitation, and reintegration into society.

Intermittent catheterisation for individuals with disability related to spinal cord injury in Tanzania.

STUDY DESIGN: Cross-sectional pilot study on spinal cord injury (SCI) among in- and outpatients. OBJECTIVES: To evaluate the challenges faced by individuals with SCI during Clean Intermittent Catheterisation (CIC). SETTING: Kilimanjaro Christian Medical Center (KCMC), a tertiary referral hospital in Moshi, Tanzania. METHODS: A questionnaire was sent to individuals with SCI who were either admitted to the Orthopedic Rehabilitation Unit or attended the Outpatient clinic between January and April 2018. Inpatients were less than 1 year post-injury and outpatients were one to 3 years post-injury. RESULTS: In total, 48 individuals responded: 28 outpatients and 20 inpatients. Among the inpatient group, 80% were performing CIC as compared with 25% of outpatient group. Of the entire cohort, 35.4% reported doing well without catheter-based management. Failure to perform CIC was present in 16.7% of all individuals. CIC-equipment was unavailable in local villages for 58.3% of all patients. The most frequent complications of CIC were urinary tract infections (20.8%) and mild bleeding (14.6%). The majority of individuals (79.2%) reported satisfaction with their situation, regardless of the severity. CONCLUSIONS: Some individuals performed CIC upon discharge, but the majority discontinued use, for which unavailability of CIC-equipment was a major determinant. While all individuals reported concerns prior to CIC, only a small minority actually experienced anxiety, pain or shame. Through targeted counselling and enhanced regular follow-up we will likely improve compliance to CIC. SPONSORSHIP: We are grateful to the International Network of SCI Nurses in collaboration with Wellspect Health Care for funding this study.

Parkinson's Disease Research on the African Continent: Obstacles and Opportunities.

The burden of Parkinson's disease (PD) is becoming increasingly important in the context of an aging African population. Although PD has been extensively investigated with respect to its environmental and genetic etiology in various populations across the globe, studies on the African continent remain limited. In this Perspective article, we review some of the obstacles that are limiting research and creating barriers for future studies. We summarize what research is being done in four sub-Saharan countries and what the key elements are that are needed to take research to the next level. We note that there is large variation in neurological and genetic research capacity across the continent, and many opportunities for unexplored areas in African PD research. Only a handful of countries possess appropriate infrastructure and personnel, whereas the majority have yet to develop such capacity. Resource-constrained environments strongly determines the possibilities of performing research locally, and unidirectional export of biological samples and genetic data remains a concern. Local-regional partnerships, in collaboration with global PD consortia, should form an ethically appropriate solution, which will lead to a reduction in inequality and promote capacity building on the African continent.

Ellis-van Creveld syndrome in a patient from Tanzania.

We report an African infant with Ellis-van Creveld (EVC) syndrome. EVC syndrome is a chondral and ectodermal dysplasia with autosomal recessive transmission. The baby presented with polydactyly, short limbs and atrioventricular septal defect, but was withdrawn from clinical follow up for the first year of life. Initial hematological abnormalities could not be explained and normalized later. EVC syndrome was confirmed by genetic analysis that showed two pathogenic mutations in the EVC2 gene, c.653_654del, p.Val218Glyfs*12 in exon 5, and c.2710C>T, p.Gln904* in exon 16. The variant c.653_654del; p.Val218Glyfs*12 in exon 5 has not been described before. Our review of medical literature suggested this is the first molecularly confirmed case of EVC syndrome in sub-Saharan Africa.

Inspiratory Myoclonus.

Background: Movement disorders of respiration are rare and are restricted to a phase of the respiratory cycle. Phenomenology Shown: The intermittent inspiratory myoclonus in this patient with post-anoxic encephalopathy is likely to be of brainstem origin. Educational Value: Rare movement disorders can be identified even in remote areas of the world where access to neurological care is limited.

Comprehensive management of epilepsy in onchocerciasis-endemic areas: lessons learnt from community-based surveys.

BACKGROUND: Onchocerciasis-endemic regions are known to have a high epilepsy prevalence. Limited resources in these areas and poor access to healthcare by persons with epilepsy (PWE) result in a wide anti-epileptic treatment gap, poor seizure control and a high burden of seizure-related complications. Recent community-based surveys highlight the need for epilepsy management strategies suitable for remote onchocerciasis-endemic villages to ensure better health outcomes for PWE. In this paper, we propose a feasible approach to manage PWE in such settings. MAIN TEXT: Improved management of PWE in onchocerciasis-endemic areas may be achieved by decentralizing epilepsy care. Simplified approaches for the diagnosis and treatment of epilepsy may be used by non-physicians, under the supervision of physicians or specialists. To reduce the treatment gap, a regular supply of subsidized anti-epileptic drugs (AED) appropriate for different types of onchocerciasis-associated epilepsy should be instituted. Setting up a community-based epilepsy surveillance system will enable early diagnosis and treatment of PWE thereby preventing complications. Community awareness programs on epilepsy must be implemented to reduce stigma and facilitate the social rehabilitation of PWE. Finally, strengthening onchocerciasis elimination programs by optimizing community-directed treatment with ivermectin (CDTI) and considering alternative treatment strategies might reduce the incidence of epilepsy. CONCLUSIONS: A community-based approach with task-shifting of epilepsy care from specialists to non-physician health workers will reduce epilepsy-associated morbidity. Increased advocacy and collaboration with various stakeholders is needed to establish a sustainable, cost-effective chronic care model for epilepsy that will significantly improve the quality of life of PWE in onchocerciasis-endemic regions.

Paroxysmal Kinesigenic Dyskinesia: First Molecularly Confirmed Case from Africa.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder, with an excellent response to carbamazepine treatment. It has been described in various populations, but not yet in an African population. Case report: In a patient who reported to clinic with side effects of carbamazepine, PRRT2 gene screening was performed based on a clinical history compatible with PKD. A common PRRT2 mutation was identified in this patient, hereby the first genetically confirmed PRRT2-associated PKD in Africa. Discussion: Reporting genetic confirmation of an unusual movement disorder from an equally unusual location shows the wide geographical distribution of PRRT2-associated disease. It also illustrates recognizability of this treatable disorder where the easiest accessible diagnostic tool is neurological history and examination.

Aeromonas caviae mimicking Vibrio cholerae infectious enteropathy in a cholera-endemic region with possible public health consequences: two case reports.

BACKGROUND: Aeromonas species have been documented to yield false positive results in microbiological tests for Vibrio cholerae. They share many biochemical properties with Vibrio species, with which they were jointly classified in the family Vibrionaceae until genotypic information provided new insights. Aeromonas species are increasingly associated with gastrointestinal infections, albeit with great apparent variation in pathogenicity and virulence both between and within species of the genus. We report two cases with clinically mild cholera-like symptoms, at a time when a cholera outbreak was unfolding in other regions of the country (Tanzania). These are the first cases to be reported with Aeromonas mimicking cholera in our area. CASE PRESENTATION: Two patients were admitted at the isolation unit designated by the Kilimanjaro Christian Medical Centre for emerging infectious diseases and provided informed consent about regular stool analysis and culture under the provisional diagnosis of gastroenteritis. The first patient was a 23-year-old black African woman with a 2-day history of watery diarrhea and vomiting associated with a temperature of 39.7 °C. The second patient was a 47-year-old black African woman with a 2-day history of diarrhea and vomiting with a temperature of 37.7 °C, and she was hemodynamically stable. Both patients were isolated in a specific area for infection control and treated with fluids and orally administered rehydration solution, ciprofloxacin, metronidazole, and paracetamol. Stool culture was done. The isolated colonies were reported as V. cholerae and transferred to the research laboratory of Kilimanjaro Clinical Research Institute for confirmation using whole genome sequencing. Microbiological testing determined colonies isolated from stool to be V. cholerae, and warranted the conclusion "presumptive cholera." Whole genome sequencing, however, established the presence of Aeromonas caviae rather than V. cholerae. CONCLUSIONS: The co-existence of Aeromonas species with V. cholerae in cholera-endemic regions suggests the possibility that a proportion of suspected cholera cases may be Aeromonas infections. However, with close to no epidemiological data available on Aeromonas infection in cases of diarrhea and dysentery in Sub-Saharan Africa, it is not currently possible to establish the extent of misdiagnosis to any degree of certainty. Whole genome sequencing was shown to readily exclude V. cholerae as the etiological agent and establish the presence of Aeromonas species.

Psychogenic non-epileptic seizures among patients with functional neurological disorder: A case series from a Tanzanian referral hospital and literature review.

Objective: Functional neurological disorders (FNDs) and psychogenic nonepileptic seizures (PNES) are likely as common in Sub-Saharan Africa (SSA) as in the rest of the world, but there is a dearth of literature on the epidemiology and clinical presentation of these disorders in Africa. The purpose of this paper is to describe a case series of FNDs presenting to a referral hospital in SSA. In addition, we review the existing literature on FNDs in Africa. Methods: A hospital-based retrospective cross-sectional study was conducted to determine the prevalence, epidemiology, and clinical phenotype of FNDs and PNES in a referral hospital in Northern Tanzania over a 6-year period (2007-2013). Results: Of 2,040 patients presenting with neurological complaints, 44 (2.2%) were diagnosed with FNDs. Half (n = 22) had the clinical presentation of PNES. Age of presentation for FNDs and PNES peaked in the teen years 12-19 (n = 21 48%; and n = 14, 63%, respectively), and the majority were female (n = 30, 68%; and n = 14, 63%, respectively). The majority presented acutely with short-lived and self-limiting symptoms (only 2 recurrent cases). Literature review revealed multiple reports of "mass hysteria" in SSA often meeting the clinical criteria of epidemic FNDs. Significance: FNDs and PNES occur in Africa with age and gender distribution comparable to that found elsewhere. Although the percentage of FND cases overall was relatively low (2.2%), it is likely to be an underestimate because not all cases were recorded, and cases may be appropriately managed locally before patients are referred to a hospital. PNES was the most common phenotype of FNDs reported, and the African phenotype may be short-lived and self-limiting rather than chronic and recurrent, as reported elsewhere in the world. PNES presentations may also occur in clusters, which may have cultural significance in Africa. FNDs in Africa appear to be underreported, particularly over the last 30 years.