A global perspective on the influence of environmental exposures on the nervous system.

Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, ultrafine particulate matters. Individual susceptibilities to exposure-related diseases are modified by genetic, epigenetic and metagenomic factors. The existence of several uniquely exposed populations, including those in the areas surrounding the Niger Delta or north western Amazon oil operations; those working in poorly regulated environments, such as artisanal mining industries; or those, mostly in sub-Saharan Africa, relying on cassava as a staple food, offers invaluable opportunities to advance the current understanding of brain responses to environmental challenges. Increased awareness of the brain disorders that are prevalent in low- and middle-income countries and investments in capacity for further environmental health-related research are positive steps towards improving human health.

Heart Failure Etiologies and Challenges to Care in the Developing World: An Observational Study in the Democratic Republic of Congo.

BACKGROUND: Limited data are available regarding causes and outcomes of heart failure as well as organization of care in the developing world. METHODS AND RESULTS: We included consecutive patients diagnosed with heart failure from November 2014 to September 2016 in a university and private hospital of Lubumbashi, Democratic Republic Congo. Baseline data, including echocardiography, were analyzed to determine factors associated with mortality. Cost of hospitalization as well as challenges for care regarding follow-up were determined. A total of 231 patients (56 ± 17 years, 47% men, left ventricular ejection fraction 29 ± 15%, 20% atrial fibrillation) were diagnosed, more during heart failure hospitalizations (69%) than as outpatients (31%). Main risk factors for heart failure included hypertension (59%), chronic kidney disease (51%), alcohol abuse (38%), and obesity (32%). Dilated cardiomyopathy was the most prevalent etiology (48%), with ischemic cardiomyopathy being present in only 4%. In-hospital mortality rate was 19% and associated with an estimated glomerular filtration rate of <60 mL·min-1·1.73 m-2 (P < .01) and atrial fibrillation (P = .02). One hundred six patients (46%) were lost to follow-up, which was mainly related to lack of organization of care, poverty, and poor health literacy. Of the remaining 95 subjects, another 33 (35%) died within 1 year after presentation. The average cost of care for a 10-day hospitalization was higher in a private than in a university hospital (885 vs 409 USD). CONCLUSIONS: Patients admitted for heart failure in DRC have a high incidence of nonischemic cardiomyopathy and present late during their disease, with limited resources being available accounting for a high mortality rate and very high loss to follow-up.

Lead exposure and early child neurodevelopment among children 12-24 months in Kinshasa, the Democratic Republic of Congo.

Childhood lead exposure remains a problem in developing countries, and little is known about its effects on early child neurodevelopment and temperament in the Democratic Republic of Congo (DRC). We, therefore, conducted this study to determine the association between lead exposure and the neurodevelopment and behaviour of children aged 12-24 months in Kinshasa, DRC. A cross-sectional study was conducted between February and June 2012, and parents of 104 children were invited to participate. Blood lead levels (BLLs) of each child were tested using the flame atomic spectrophotometry method. All children were subject to a clinical examination and assessed with two selected early child neurodevelopmental tools, the Gensini-Gavito and the baby characteristics questionnaire, to measure their neurodevelopment and temperament. Detectable BLLs ranged from 1 to 30 µg/dl with a geometric mean of 6.9 (SD 4.8) µg/dl. BLLs at 5-9 and ≥10 µg/dl were significantly associated with the child temperament (p <0.05). Perinatal and maternal factors did not seem to affect early child neurodevelopment and temperament. Children exposed to lead were reported with more temperament difficulties at even blood lead levels <10 µg/dl, suggesting the need for preventive and intervention measures to reduce lead exposure among children in Kinshasa, DRC.

Glutathione peroxidase 3 is a potential biomarker for konzo.

Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the world's poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.

Cost-effectiveness of incorporating Ebola prediction score tools and rapid diagnostic tests into a screening algorithm: A decision analytic model.

BACKGROUND: No distinctive clinical signs of Ebola virus disease (EVD) have prompted the development of rapid screening tools or called for a new approach to screening suspected Ebola cases. New screening approaches require evidence of clinical benefit and economic efficiency. As of now, no evidence or defined algorithm exists. OBJECTIVE: To evaluate, from a healthcare perspective, the efficiency of incorporating Ebola prediction scores and rapid diagnostic tests into the EVD screening algorithm during an outbreak. METHODS: We collected data on rapid diagnostic tests (RDTs) and prediction scores' accuracy measurements, e.g., sensitivity and specificity, and the cost of case management and RDT screening in EVD suspect cases. The overall cost of healthcare services (PPE, procedure time, and standard-of-care (SOC) costs) per suspected patient and diagnostic confirmation of EVD were calculated. We also collected the EVD prevalence among suspects from the literature. We created an analytical decision model to assess the efficiency of eight screening strategies: 1) Screening suspect cases with the WHO case definition for Ebola suspects, 2) Screening suspect cases with the ECPS at -3 points of cut-off, 3) Screening suspect cases with the ECPS as a joint test, 4) Screening suspect cases with the ECPS as a conditional test, 5) Screening suspect cases with the WHO case definition, then QuickNavi™-Ebola RDT, 6) Screening suspect cases with the ECPS at -3 points of cut-off and QuickNavi™-Ebola RDT, 7) Screening suspect cases with the ECPS as a conditional test and QuickNavi™-Ebola RDT, and 8) Screening suspect cases with the ECPS as a joint test and QuickNavi™-Ebola RDT. We performed a cost-effectiveness analysis to identify an algorithm that minimizes the cost per patient correctly classified. We performed a one-way and probabilistic sensitivity analysis to test the robustness of our findings. RESULTS: Our analysis found dual ECPS as a conditional test with the QuickNavi™-Ebola RDT algorithm to be the most cost-effective screening algorithm for EVD, with an effectiveness of 0.86. The cost-effectiveness ratio was 106.7 USD per patient correctly classified. The following algorithms, the ECPS as a conditional test with an effectiveness of 0.80 and an efficiency of 111.5 USD per patient correctly classified and the ECPS as a joint test with the QuickNavi™-Ebola RDT algorithm with an effectiveness of 0.81 and a cost-effectiveness ratio of 131.5 USD per patient correctly classified. These findings were sensitive to variations in the prevalence of EVD in suspected population and the sensitivity of the QuickNavi™-Ebola RDT. CONCLUSIONS: Findings from this study showed that prediction scores and RDT could improve Ebola screening. The use of the ECPS as a conditional test algorithm and the dual ECPS as a conditional test and then the QuickNavi™-Ebola RDT algorithm are the best screening choices because they are more efficient and lower the number of confirmation tests and overall care costs during an EBOV epidemic.

Predictive Factors of HIV-1 Drug Resistance and Its Distribution among Female Sex Workers in the Democratic Republic of the Congo (DRC).

The predictive factors of HIV-1 drug resistance and its distribution are poorly documented in female sex workers (FSWs) in the Democratic Republic of the Congo (DRC). However, the identification of predictive factors can lead to the development of improved and effective antiretroviral therapy (ART). The objective of the current study was to determine the predictive factors of HIV-1 drug resistance and its distribution based on FSWs in the studied regions in the Democratic Republic of the Congo (DRC). HIV-positive FSWs who were diagnosed as part of the DRC Integrated Biological and Behavioral Surveillance Survey (IBBS) were included in this study. A total of 325 FSWs participated. The HIV-1 viral load (VL) was measured according to the Abbott m2000sp and m2000rt protocols. The homogeneity chi-square test was conducted to determine the homogeneity of HIV-1 drug resistance distribution. Using a significance level of 0.05, multivariate analyses were performed to identify factors associated with HIV-1 drug resistance to ART. HIV drug resistance mutation (HIVDRM) distribution was homogeneous in the three study regions (p = 0.554) but differed based on the HIV-1 VLs of the FSWs. FSWs with high HIV-1 VLs harbored more HIVDRMs (p = 0.028) of predominantly pure HIV-1 strains compared with those that had low HIV-1 VLs. Sexually transmitted infection (STI) history (aOR [95%CI] = 8.51 [1.62, 44.74]), high HIV-1 VLs (aOR [95%CI] = 5.39 [1.09, 26.74]), and HIV-1-syphilis coinfection (aOR [95%CI] = 9.71 [1.84, 51.27]) were associated with HIV drug resistance among FSWs in the DRC. A history of STIs (e.g., abnormal fluid) in the 12 months prior to the survey, a high HIV-1 VL, and HIV-1-syphilis coinfection were associated with HIV-1 drug resistance among FSWs in the DRC. Efforts should be made to systematically test for other infections which increase the HIV-1 VL, in the case of HIV-1 coinfection, in order to maintain ART effectiveness across the DRC.

DNA methylation patterns associated with konzo in Sub-Saharan Africa.

Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks, is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic-sensitive regions of the genome, providing the first study of epigenomic alterations associated with a clinical phenotype of konzo.

Development of Ebola virus disease prediction scores: Screening tools for Ebola suspects at the triage-point during an outbreak.

BACKGROUND: The control of Ebola virus disease (EVD) outbreaks relies on rapid diagnosis and prompt action, a daunting task in limited-resource contexts. This study develops prediction scores that can help healthcare workers improve their decision-making at the triage-point of EVD suspect-cases during EVD outbreaks. METHODS: We computed accuracy measurements of EVD predictors to assess their diagnosing ability compared with the reference standard GeneXpert® results, during the eastern DRC EVD outbreak. We developed predictive scores using the Spiegelhalter-Knill-Jones approach and constructed a clinical prediction score (CPS) and an extended clinical prediction score (ECPS). We plotted the receiver operating characteristic curves (ROCs), estimated the area under the ROC (AUROC) to assess the performance of scores, and computed net benefits (NB) to assess the clinical utility (decision-making ability) of the scores at a given cut-off. We performed decision curve analysis (DCA) to compare, at a range of threshold probabilities, prediction scores' decision-making ability and to quantify the number of unnecessary isolation. RESULTS: The analysis was done on data from 10432 subjects, including 651 EVD cases. The EVD prevalence was 6.2% in the whole dataset, 14.8% in the subgroup of suspects who fitted the WHO Ebola case definition, and 3.2% for the set of suspects who did not fit this case definition. The WHO clinical definition yielded 61.6% sensitivity and 76.4% specificity. Fatigue, difficulty in swallowing, red eyes, gingival bleeding, hematemesis, confusion, hemoptysis, and a history of contact with an EVD case were predictors of EVD. The AUROC for ECPS was 0.88 (95%CI: 0.86-0.89), significantly greater than this for CPS, 0.71 (95%CI: 0.69-0.73) (p < 0.0001). At -1 point of score, the CPS yielded a sensitivity of 85.4% and specificity of 42.3%, and the ECPS yielded sensitivity of 78.8% and specificity of 81.4%. The diagnostic performance of the scores varied in the three disease contexts (the whole, fitting or not fitting the WHO case definition data sets). At 10% of threshold probability, e.g. in disease-adverse context, ECPS gave an NB of 0.033 and a net reduction of unnecessary isolation of 67.1%. Using ECPS as a joint approach to isolate EVD suspects reduces the number of unnecessary isolations by 65.7%. CONCLUSION: The scores developed in our study showed a good performance as EVD case predictors since their use improved the net benefit, i.e., their clinical utility. These rapid and low-cost tools can help in decision-making to isolate EVD-suspicious cases at the triage point during an outbreak. However, these tools still require external validation and cost-effectiveness evaluation before being used on a large scale.

Cost-effectiveness of a wetting method intervention to reduce cassava cyanide-related cognitive impairment in children.

Cassava cyanide-related neurocognitive impairment may persist for years in Central African children who rely on cassava as a dietary staple. In the Democratic Republic of the Congo, a cassava processing method, the 'wetting method', reduced cyanide in cassava, prevented konzo, and proved a cost-effective intervention to improve children's cognitive development. Scaling up use of the wetting method may help prevent neurocognitive impairment in millions of at-risk children in sub-Saharan Africa.

Concurrent Heavy Metal Exposures and Idiopathic Dilated Cardiomyopathy: A Case-Control Study from the Katanga Mining Area of the Democratic Republic of Congo.

Blood and/or urine levels of 27 heavy metals were determined by ICPMS in 41 patients with dilated cardiomyopathy (DCM) and 29 presumably healthy subjects from the Katanga Copperbelt (KC), in the Democratic Republic of Congo (DRC). After adjusting for age, gender, education level, and renal function, DCM probability was almost maximal for blood concentrations above 0.75 and 150 µg/dL for arsenic and copper, respectively. Urinary concentrations above 1 for chromium, 20 for copper, 600 for zinc, 30 for selenium, 2 for cadmium, 0.2 for antimony, 0.5 for thallium, and 0.05 for uranium, all in µg/g of creatinine, were also associated with increased DCM probability. Concurrent and multiple exposures to heavy metals, well beyond permissible levels, are associated with increased probability for DCM. Study findings warrant screening for metal toxicity in case of DCM and prompt public health measures to reduce exposures in the KC, DRC.

The gut microbiome in konzo.

Konzo, a distinct upper motor neuron disease associated with a cyanogenic diet and chronic malnutrition, predominately affects children and women of childbearing age in sub-Saharan Africa. While the exact biological mechanisms that cause this disease have largely remained elusive, host-genetics and environmental components such as the gut microbiome have been implicated. Using a large study population of 180 individuals from the Democratic Republic of the Congo, where konzo is most frequent, we investigate how the structure of the gut microbiome varied across geographical contexts, as well as provide the first insight into the gut flora of children affected with this debilitating disease using shotgun metagenomic sequencing. Our findings indicate that the gut microbiome structure is highly variable depending on region of sampling, but most interestingly, we identify unique enrichments of bacterial species and functional pathways that potentially modulate the susceptibility of konzo in prone regions of the Congo.

HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo.

BACKGROUND: Complex mosaic structures of HIV-1 were found in the Democratic Republic of Congo (DRC). Currently, there is limited information on the circulating HIV-1 strains, the distribution of these strains and antiretroviral (ART) resistant viruses in different regions of the country, and the HIV-1 strains harbored by the high-risk groups like female sex workers (FSW) reported to be the source of recombinant and ART resistant viruses. METHODS: Dried Blood Spots (DBS), collected from 325 infected FSWs in ten cities from 2012 DRC HIV/STI Integrated Biological and Behavioral Surveillance Survey, were tested for HIV-1 genotypes and antiretroviral resistance mutations. Regional segregation of HIV-1 clades was detected using phylogenetics. The significance for differences in HIV-1 subtype and drug resistance mutations were evaluated using Chi-square tests. RESULTS: There were 145 (env) and 93 (pol) sequences analyzed. Based on env sequences, the predominant subtype was A1 (44%), and recombinants as defined pol sequences comprised 35% of the total sample. Paired sequences of pol and env from DRC FSW revealed mosaic recombinant in 54% of the sequences. Distinct geographic distributions of different HIV-1 subtypes and recombinants were observed. Subtype A1 was prevalent (40%) in Goma located in the East and significantly higher than in Mbuji-Mayi (p<0.05) in the South-central region, or in Lubumbashi in the South. Antiretroviral resistance was detected in 21.5% of 93 pol sequences analyzed, with the M184I/V and K103N mutations that confer high-level resistance to NRTI and NNRTI, respectively, being the most frequent mutations. However, the K103N mutant viruses were found only in the East. CONCLUSION: HIV-1 variants found in DRC FSW reflect those reported to circulate in the general population from the corresponding geographical locations. HIV-1 mosaic genetics were readily detected in FSW. Importantly, ART resistance mutations to NNRTI and NRTI were common in the DRC sex workers.

New insights into mechanisms of gamma-diketone-induced axonopathy.

We analyzed the impact of axonopathy-inducing agents 1,2-diacetylbenzene (1,2-DAB) and 2,5-hexanedione (2,5-HD) on membrane-bound protein disulfide isomerase (mPDI) versus soluble PDI (sPDI), or PDI-family member thioredoxin (THX), and asked whether changes in PDI/THX were associated with production of oxidative/nitrosative species in the Sprague-Dawley rat. We show that 1,2-DAB and 2,5-HD lower the abundance of sPDI and THX. However, the protein expression of mPDI is increased in 1,2-DAB axonopathy and neuroproteins became more S-nitrosylated. The abundance of heme oxygenase-1 (HO-1) and isoforms of nitric oxide synthase (neuronal, endothelial, and inducible NOS) remained unchanged suggesting that S-nitrosylation occured via increased mPDI-transnitrosylation and/or diminished THX-denitrosylation. The transcription of PDI and glucose regulated protein-78 (GRP-78) remained unchanged indicating that post-translational modifications, e.g. S-nitrosylation, mediate the pathogenesis of gamma-diketone axonopathy. These findings open opportunities for new therapeutic testing (e.g., supplementation with denitrosylating THX) in gamma-diketone-induced axonal disease.

Viral infections of the central nervous system in Africa.

Viral infections are a major cause of human central nervous system infection, and may be associated with significant mortality, and long-term sequelae. In Africa, the lack of effective therapies, limited diagnostic and human resource facilities are especially in dire need. Most viruses that affect the central nervous system are opportunistic or accidental pathogens. Some of these viruses were initially considered harmless, however they have now evolved to penetrate the nervous system efficiently and exploit neuronal cell biology thus resulting in severe illness. A number of potentially lethal neurotropic viruses have been discovered in Africa and over the course of time shown their ability to spread wider afield involving other continents leaving a devastating impact in their trail. In this review we discuss key viruses involved in central nervous system disease and of major public health concern with respect to Africa. These arise from the families of Flaviviridae, Filoviridae, Retroviridae, Bunyaviridae, Rhabdoviridae and Herpesviridae. In terms of the number of cases affected by these viruses, HIV (Retroviridae) tops the list for morbidity, mortality and long term disability, while the Rift Valley Fever virus (Bunyaviridae) is at the bottom of the list. The most deadly are the Ebola and Marburg viruses (Filoviridae). This review describes their epidemiology and key neurological manifestations as regards the central nervous system such as meningoencephalitis and Guillain-Barré syndrome. The potential pathogenic mechanisms adopted by these viruses are debated and research perspectives suggested.

Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning.

Epidemics of neurodegenerative diseases putatively caused by food toxins have been reported in the tropics with no clear understanding of their pathogenetic mechanisms. These diseases include the disease named Konzo that has been well documented in sub-Sahara Africa, mostly among children and women of childbearing age. Outbreaks of Konzo have occurred in the Democratic Republic of Congo, Mozambique, Tanzania, Central African Republic, Angola, Cameroun, and most recently in Zambia. The main clinical picture consists of a symmetrical, permanent and irreversible spastic paraparesis (motor neuron disease) with no signs of sensory or genitourinary impairments. Recently, cognitive impairments and neurodevelopmental delays have been reported among school-aged and very young children. The exact pathogenetic mechanisms of the disease remain unknown. Epidemiological studies consistently show an association between outbreaks of the disease and chronic dietary reliance on insufficiently processed cyanogenic cassava (manioc or tapioca). Biochemical and toxicological studies suggest that the metabolites of linamarin (α-Hydroxyisobutyronitrile ß-D-glucopyranoside, the main cassava cyanogen), notably cyanide (mitochondrial toxin), thiocyanate (AMPA chaotropic agent), and cyanate (protein carbamoylating agent) may play an important role in the pathogenesis of Konzo. Experimental data suggest that thiol-redox and protein- folding mechanisms may also be perturbed. Factors of susceptibility including genetics, poor nutrition, poverty and dietary cyanogen exposure, or their interactions have been suggested. Serological studies have ruled out the role of retroviruses such as the human lymphotropic viruses HIV-I/II or HTLV-I/II. Because there is no cure for Konzo, prevention of the disease remains of paramount importance. Prospects for cognitive rehabilitation still need to be explored and tested.

Concurrent exposure to heavy metals and cognition in school-age children in Congo-Kinshasa: A complex overdue research agenda.

The impact of concurrent exposure to neurotoxic metals is a significant threat to brain function, mostly in contexts of multiple exposures as seen in the developing world. Ninety-five children (46 boys and 49 girls, 6 to 11-year old) from Congo-Kinshasa were assessed for cognition using the Kaufman Assessment Battery for Children (2nd edition) and exposure to Cr, Cu, Zn, Co, Mn, As, Cd, Se, Hg, Fe, and Pb by inductively coupled plasma mass spectrometry (ICPMS) in serum and urine collections. Concentrations of elements were all above normal ranges except for Cd, Se and Hg. General linear mixed effects models were used to predict neurocognitive outcomes with variable selection methods including backward elimination, elastic net, or subsets identified based on subject matter expertise. After adjusting for sex, age, and SES, urinary Co > 5 µg/l was associated with poor simultaneous processing (memory) (p = 0.0237). Higher excretion but normal concentration of Cd in serum was associated with better memory (p = 0.03), planning (p = 0.05), and overall performance scores (p < 0.01); thus appeared to be neuroprotective. However, higher excretion of Zn had negative influence on the overall performance scores (p = 0.02). Predictive neurotoxicology is a challenging task in contexts of multiple and concurrent exposures. Urinary Co > 5 µg/l is a risk factor for poor neurodevelopmental outcomes in such contexts. The impact of heavy metals on cognition is dependent on concentrations of and interactions between toxic and essential elements.

Integrating environmental health and genomics research in Africa: challenges and opportunities identified during a Human Heredity and Health in Africa (H3Africa) Consortium workshop.

Individuals with African ancestry have extensive genomic diversity but have been underrepresented in genomic research. There is also extensive global diversity in the exposome (the totality of human environmental exposures from conception onwards) which should be considered for integrative genomic and environmental health research in Africa. To address current research gaps, we organized a workshop on environmental health research in Africa in conjunction with the H3Africa Consortium and the African Society of Human Genetics meetings in Kigali, Rwanda. The workshop was open to all researchers with an interest in environmental health in Africa and involved presentations from experts within and outside of the Consortium. This workshop highlighted innovative research occurring on the African continent related to environmental health and the interplay between the environment and the human genome. Stories of success, challenges, and collaborative opportunities were discussed through presentations, breakout sessions, poster presentations, and a panel discussion. The workshop informed participants about environmental risk factors that can be incorporated into current or future epidemiology studies and addressed research design considerations, biospecimen collection and storage, biomarkers for measuring chemical exposures, laboratory strategies, and statistical methodologies. Inclusion of environmental exposure measurements with genomic data, including but not limited to H3Africa projects, can offer a strong platform for building gene-environment (G x E) research in Africa. Opportunities to leverage existing resources and add environmental exposure data for ongoing and planned studies were discussed. Future directions include expanding the measurement of both genomic and exposomic risk factors and incorporating sophisticated statistical approaches for analyzing high dimensional G x E data. A better understanding of how environmental and genomic factors interact with nutrition and infection is also needed. Considering that the environment represents many modifiable risk factors, these research findings can inform intervention and prevention efforts towards improving global health.

Baseline characterization of epilepsy in an onchocerciasis endemic area of the Democratic Republic of Congo.

Increased epilepsy prevalence is reported in onchocerciasis (OC) endemic areas and is associated with the occurrence of distinct syndromes such as nodding disease and Nakalanga syndrome. To date, a causal relationship between OC and epilepsy is still a matter of controversy. We conducted a case-control study of participants with epilepsy and age- and gender-matched presumably healthy controls to elucidate the relationships between OC and epilepsy and explore the role of inflammation and growth factors in an OC endemic area in the Democratic Republic of Congo (DRC). Eighty-two participants with epilepsy (mean age ± SD: 23.2 ± 8.7 years) and 27 controls (mean age ± SD: 22.3 ± 12.0 years) underwent snip skin biopsies to determine Onchocerca volvulus infection status. Serum concentrations of cytokines, chemokines, and growth factors were measured using a Luminex Multiplex Assay kit. Children <19 years of age underwent neurocognitive assessments using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II). Overall, epilepsy was associated with OC (OR = 4.51, z = 3.11, p = 0.0019), and children with OC were more likely to be severely stunted (OR = 11.67, z = 2.62, p = 0.0087). The relationship between epilepsy and OC was no longer significant (z = 1.27, p = 0.20) when stunting was included as a correcting covariate. Epilepsy was associated with poor KABC-II test scores, high serum levels of IL-17, and low levels of IL-1RA, IL-8, and EGF. KABC-II testing scores correlated with serum levels of IL-10, MCP-1 and HGF. Familial history of epilepsy occurred frequently. Future studies should consider cytokines and/or growth factors when assessing susceptibility to epilepsy in OC endemic areas. Additional investigations, preferentially in low-prevalence OC areas, may provide further insights into the concept, risk, and burden of river epilepsy.

Mortality trends and risk factors in advanced stage-2 Human African Trypanosomiasis: A critical appraisal of 23 years of experience in the Democratic Republic of Congo.

We conducted a retrospective study on mortality trends and risk factors in 781 naïve cases of advanced stage-2 sleeping sickness admitted between 1989 and 2012 at the National Reference Center for Human African Trypanosomiasis (HAT), Department of Neurology, Kinshasa University, Democratic Republic of Congo (DRC). Death was the outcome variable whereas age, gender, duration of disease, location of trypanosomes in body fluids, cytorachy, protidorachy, clinical status (assessed on a syndromic and functional basis) on admission, and treatment regimen were predictors in logistic regression models run at the 0.05 significance level. Death proportions were 17.2% in the standard melarsoprol schedule (3-series of intravenous melarsoprol on 3 successive days at 3.6 mg/kg/d, with a one-week interval between the series, ARS 9); 12.1% in the short schedule melarsoprol (10 consecutive days of intravenous melarsoprol at 2.2 mg/kg/d, ARS 10), 5.4% in the first-line eflornithine (14 days of eflornithine at 400 mg/kg/d in 4 infusions a day DFMO B), 9.1% in the NECT treatment regimen (eflornithine for 7 days at 400, mg/kg/d in 2 infusions a day combined with oral nifurtimox for 10 days at 15 mg/kg/d in 3 doses a day); and high (36%) in the group with select severely affected patients given eflornithine because of their clinical status on admission, at the time when this expensive drug was kept for treatment of relapses (14 days at 400 mg/kg/d in 4 infusions a day, DFMO A). After adjusting for treatment, death odds ratios were as follows: 10.40 [(95% CI: 6.55-16.51); p = .000] for clinical dysfunction (severely impaired clinical status) on admission, 2.14 [(95% CI: 1.35-3.39); p = .001] for high protidorachy, 1.99 [(95% CI: 1.18-3.37); p = .010] for the presence of parasites in the CSF and 1.70 [(95% CI: 1.03-2.81); p = .038] for high cytorachy. A multivariable analysis within treatment groups retained clinical status on admission (in ARS 9, ARS 10 and DFMO B groups) and high protidorachy (in ARS 10 and DFMO B groups) as significant predictors of death. The algorithm for initial clinical status assessment used in the present study may serve as the basis for further development of standardized assessment tools relevant to the clinical management of HAT and information exchange in epidemiological reports.

[Socioemotional disorders in children living in Konzo-affected areas, an epidemic paralytic disease associated with cyanide poisoning from food in sub-Saharan Africa]. / Troubles socio-émotionnels de l'enfant en milieu Konzo, un syndrome paralytique de nature épidémique associé à une intoxication cyanhydrique d'origine alimentaire en Afrique sub-saharienne.

INTRODUCTION: the aim of this study was to describe the socioemotional profile of children living in Konzo-affected areas, an epidemic toxico-nutritional palsy in sub-Saharan Africa. METHODS: we evaluated the socioemotional profile of 210 children, 123 with Konzo and 87 presumed to be healthy (4-17 years) based on a structured interview conducted with their parents during an epidemioclinic survey of Konzo in Congo-Kinshasa in 2011. Neurocognitive profile was identified by the KABC-II, the BOT-2 and the global neurological symptom index of Konzo. Associative tests were carried out by using chi-square test, logistic regression and, where applicable, generalized linear model, at the significance threshold of 0.05. RESULTS: in general, irritability, physical violence or inhibition with or without sadness were found in 46.0%, 30.2%, 18.7% of children respectively, with an increased risk of Konzo (OR = 2.6; CI95%: 1.4-4.8; p = 0.001). Socioemotional disorder was associated with underweight (OR: 0.49; CI95%: 0.31-0.78; p = 0.002) and with an elevated global neurological symptom index of Konzo (OR: 1.33; CI 95%: 1.1-1.63; p = 0.019); furthermore it exacerbated cognitive impairment in children with Konzo (interaction neurological status-socioemotional disorders D = 6.297; p = 0.013). High cognitive performances were observed in children without Konzo but with socioemotional disorders. The average concentration (standard deviation ± SD) of urinary thiocyanate was higher (554.8 ± 371.6 µmol/l) among children with Konzo associated with socioemotional disorders. CONCLUSION: children living in Konzo-affected areas have socioemotional disorders. Their psychopathological status and the effect of Konzo on cognition require in-depth studies.