The significance of polymicrobial infections is increasingly being recognized especially in a biofilm context wherein multiple bacterial species – including both potential pathogens and members of the commensal flora – communicate, cooperate and compete with each other. Two important bacterial pathogens that have developed a complex network of evasion, counter-inhibition and subjugation in their battle for space and nutrients are Pseudomonas aeruginosa and Staphylococcus aureus. Their strain- and environment-specific interactions, for instance in the cystic fibrosis lung or in wound infections, show severe competition that is generally linked to worse patient outcomes. For instance, the extracellular factors secreted by P. aeruginosa have been shown to subjugate S. aureus to persist as small colony variants. On the other hand, data also exist where S. aureus inhibits biofilm formation by P. aeruginosa but also protects the pathogen by inhibiting its phagocytosis. Interestingly, such interspecies interactions differ between the planktonic and biofilm phenotype, with the extracellular matrix components of the latter likely being a key, and largely underexplored, influence.This review attempts to understand the complex relationship between P. aeruginosa and Staphylococcus spp., focusing on S. aureus, that not only is interesting from the bacterial evolution point of view, but also has important consequences for our understanding of the disease pathogenesis for better patient management.

Background: The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship betweenOnchocerca volvulusand epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.Methods: PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection withO.volvulusand epilepsy, including the nodding syndrome.Results: Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes.Conclusion: Applying the Bradford Hill criteria suggests consistent epidemiological evidence thatO.volvulusinfection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.

Background: Around 2007, a nodding syndrome (NS) epidemic appeared in onchocerciasis-endemic districts of northern Uganda, where ivermectin mass distribution had never been implemented. This study evaluated the effect of community-directed treatment with ivermectin (CDTI) and ground larviciding of rivers initiated after 2009 and 2012 respectively, on the epidemiology of NS and other forms of epilepsy (OFE) in some districts of northern Uganda. Methods: In 2012, a population-based community survey of NS/epilepsy was carried out by the Ugandan Ministry of Health in Kitgum and Pader districts. In August 2017, we conducted a new survey in selected villages of these districts and compared our findings with the 2012 data. In addition, two villages in Moyo district (where CDTI was ongoing since 1993) served as comparative onchocerciasis-endemic sites in which larviciding had never been implemented. The comparison between 2012 and 2017 prevalence and cumulative incidence were done using the Fisher’s and Pearson’s Chi-square tests at 95% level of significance. Results: A total of 2138 individuals in 390 households were interviewed. In the selected villages of Kitgum and Pader, there was no significant decrease in prevalence of NS and OFE between 2012 and 2017. However, the cumulative incidence of all forms of epilepsy decreased from 1165 to 130 per 100 000 persons per year (P = 0.002); that of NS decreased from 490 to 43 per 100 000 persons per year (P = 0.037); and for OFE from 675 to 87 per 100 000 persons per year (P = 0.024). The median age of affected persons (NS and OFE) shifted from 13.5 (IQR: 11.0–15.0) years in 2012 to 18.0 (IQR: 15.0–20.3) years in 2017; P < 0.001. The age-standardized prevalence of OFE in Moyo in 2017 was 4.6%, similar to 4.5% in Kitgum and Pader. Conclusions: Our findings support the growing evidence of a relationship between infection by Onchocerca volvulus and some types of childhood epilepsy, and suggest that a combination of bi-annual mass distribution of ivermectin and ground larviciding of rivers is an effective strategy to prevent NS and OFE in onchocerciasis-hyperendemic areas.

High epilepsy prevalence and incidence were observed in onchocerciasis-endemic villages in the Democratic Republic of Congo (DRC). We investigated the clinical characteristics of onchocerciasis-associated epilepsy (OAE), and the relationship between seizure severity and microfilarial density. In October 2017, ivermectin-naive persons with epilepsy (PWE) were recruited from onchocerciasis-endemic areas in the Logo health zone in the DRC. Additional PWE were enrolled in the Aketi health zone, where ivermectin had been distributed annually for 14 years. Past medical history, clinical characteristics and skin snips for Onchocerca volvulus detection were obtained from participants. Bivariate and multivariable analyses were used to investigate associations with microfilarial density. Of the 420 PWE in the Logo health zone, 392 were skin snipped (36.5% positive). Generalized motor seizures were most frequent (392 PWE, 93.3%), and nodding seizures were reported in 32 (7.6%) participants. Twelve PWE (3.1%) presented Nakalanga features. Sixty-three (44.1%) skin snip-positive PWE had a family history of epilepsy, compared to only 82 (32.9%) skin snip-negative PWE (p = 0.027). Eighty-one onchocerciasis-infected PWE were recruited in the Aketi health zone. Positive correlations between seizure frequency and microfilarial density were observed in Logo (Spearman-rho = 0.175; p<0.001) and Aketi (Spearman-rho = 0.249; p = 0.029). In the multivariable model adjusted for age, gender, and previous treatment, high seizure frequency was associated with increasing microfilarial density in Aketi (p = 0.025) but not in Logo (p = 0.148). In onchocerciasis-endemic regions in the DRC, a wide spectrum of seizures was observed. The occurrence of Nodding seizures and Nakalanga features, as well as an association between seizure severity and O. volvulus microfilarial density suggest a high OAE prevalence in the study villages. ClinicalTrials.gov NCT03052998. Several epidemiological surveys suggest that onchocerciasis (a disease resulting from an infection with the parasite Onchocerca volvulus) is a cause of epilepsy. We conducted a study to describe the clinical characteristics of persons with epilepsy (PWE) living in onchocerciasis-endemic villages in the Democratic Republic of Congo. In some study sites, the frequency of seizures increased with increasing number of O. volvulus microfilariae detected in the skin snips of participants. A wide spectrum of seizures was observed, including generalized tonic-clonic seizures, absence seizures, and focal seizures. Growth retardation and household clustering of PWE were common. Specific clinical presentations such as nodding seizures and Nakalanga features were encountered. These results suggest a high prevalence of onchocerciasis-associated epilepsy (OAE) in the study villages.

A high prevalence of epilepsy has been observed in many onchocerciasis endemic regions. This study is to estimate the prevalence of active epilepsy and exposure to Onchocerca volvulus infection in a rural population in Ituri province, Democratic Republic of Congo. In August 2016, a community-based cross-sectional study was conducted in an onchocerciasis endemic area in the rural health zone of Logo, Ituri Province. Households within two neighbouring health areas were randomly sampled. To identify persons with epilepsy, a three-stage approach was used. In the first stage, all individuals of the selected households were screened for epilepsy by non-medical field workers using a validated 5-item questionnaire. In the second and third stage, suspected cases of epilepsy were examined by non-specialist medical doctors, and by a neurologist, respectively. A case of epilepsy was defined according to the 2014 International League Against Epilepsy (ILAE) guidelines. Exposure to O. volvulus was assessed by testing for IgG4 antibodies to an O. volvulus antigen (OV16 Rapid Test,) in individuals aged 3 years and older. Out of 1389 participants included in the survey, 64 were considered to have active epilepsy (prevalence 4.6%) (95% confidence interval [CI]: 3.6–5.8). The highest age-specific epilepsy prevalence estimate was observed in those aged 20 to 29 years (8.2%). Median age of epilepsy onset was 10 years, with a peak incidence of epilepsy in the 10 to 15 year-old age group. OV16 test results were available for 912 participants, of whom 30.5% (95% CI, 27.6–33.6) tested positive. The prevalence of OV16 positivity in a village ranged from 8.6 to 68.0%. After adjusting for age, gender and ivermectin use, a significant association between exposure to onchocerciasis and epilepsy was observed (adjusted odds ratio = 3.19, 95% CI: 1.63–5.64) (P < 0.001). A high prevalence of epilepsy and a significant association between epilepsy and exposure to O. volvulus were observed in the population in Ituri province, Democratic Republic of Congo. There is an urgent need to implement a CDTI programme and to scale up an epilepsy treatment and care programme.