Disparities in the non-laboratory INTERHEART risk score and its components in selected countries of Europe and sub-Saharan Africa: analysis from the SPICES multi-country project.

Aims: Accurate prediction of a person's risk of cardiovascular disease (CVD) is vital to initiate appropriate intervention. The non-laboratory INTERHEART risk score (NL-IHRS) is among the tools to estimate future risk of CVD. However, measurement disparities of the tool across contexts are not well documented. Thus, we investigated variation in NL-IHRS and components in selected sub-Saharan African and European countries. Methods and results: We used data from a multi-country study involving 9309 participants, i.e. 4941 in Europe, 3371 in South Africa, and 997 in Uganda. Disparities in total NL-IHRS score, specific subcomponents, subcategories, and their contribution to the total score were investigated. The variation in the adjusted total and component scores was compared across contexts using analysis of variance. The adjusted mean NL-IHRS was higher in South Africa (10.2) and Europe (10.0) compared to Uganda (8.2), and the difference was statistically significant (P < 0.001). The prevalence and per cent contribution of diabetes mellitus and high blood pressure were lowest in Uganda. Score contribution of non-modifiable factors was lower in Uganda and South Africa, entailing 11.5% and 8.0% of the total score, respectively. Contribution of behavioural factors to the total score was highest in both sub-Saharan African countries. In particular, adjusted scores related to unhealthy dietary patterns were highest in South Africa (3.21) compared to Uganda (1.66) and Europe (1.09). Whereas, contribution of metabolic factors was highest in Europe (30.6%) compared with Uganda (20.8%) and South Africa (22.6%). Conclusion: The total risk score, subcomponents, categories, and their contribution to total score greatly vary across contexts, which could be due to disparities in risk burden and/or self-reporting bias in resource-limited settings. Therefore, primary preventive initiatives should identify risk factor burden across contexts and intervention activities need to be customized accordingly. Furthermore, contextualizing the risk assessment tool and evaluating its usefulness in different settings are recommended.

Correction: Dusabimana et al. Surveillance for Onchocerciasis-Associated Epilepsy and Ov16 IgG4 Testing of Children 6-10 Years Old Should Be Used to Identify Areas Where Onchocerciasis Elimination Programs Need Strengthening. Pathogens 2022, 11, 281.

There was an error in the original publication [...].

The Prevalence of Onchocerciasis-Associated Epilepsy in Mundri West and East Counties, South Sudan: A Door-to-Door Survey.

A two-phase survey of epilepsy was conducted in selected villages in Mundri West and East Counties (26 June-8 July, 2021), an onchocerciasis-endemic area in Western Equatoria State in South Sudan. In the first phase, households were visited by a trained research team to identify persons suspected to have epilepsy. In the second phase, persons suspected to have epilepsy were interviewed and examined by a clinician to confirm the diagnosis. A total of 364 households agreed to participate in the survey, amounting to 2588 individuals. The epilepsy screening questionnaire identified 91 (3.5%) persons with suspected epilepsy, of whom the diagnosis of epilepsy was confirmed by a clinician in 86 (94.5%). The overall prevalence of confirmed epilepsy was 3.3% (95% CI: 2.7-4.1%), and of nodding syndrome was 0.9% (95% CI: 0.6-1.4%). In 61 (16.8%) households there was at least one person with epilepsy. Only 1212 (46.9%) of 2583 people took ivermectin during the last distribution round in 2021. The annual epilepsy incidence was 77.3/100,000 (95% CI: 9.4-278.9/100,000) and the annual epilepsy mortality was 251.2/100,000 (95% CI: 133.8-428.7/100,000). In conclusion, a high prevalence and incidence of epilepsy was observed in villages in Mundri. Urgent action is needed to prevent children from developing onchocerciasis-associated epilepsy by strengthening the local onchocerciasis-elimination programme.

Surveillance for Onchocerciasis-Associated Epilepsy and OV16 IgG4 Testing of Children 6-10 Years Old Should Be Used to Identify Areas Where Onchocerciasis Elimination Programs Need Strengthening.

To eliminate onchocerciasis-associated morbidity, it is important to identify areas where there is still high ongoing Onchocerca volvulus transmission. Between 2015 and 2021, door-to-door surveys were conducted in onchocerciasis-endemic villages in Cameroon, the Democratic Republic of Congo (DRC), Nigeria, South Sudan, and Tanzania to determine epilepsy prevalence and incidence, type of epilepsy and ivermectin therapeutic coverage. Moreover, children aged between six and 10 years were tested for anti-Onchocerca antibodies using the Ov16 IgG4 rapid diagnostic test (RDT). A mixed-effect binary logistic regression analysis was used to assess significantly associated variables of Ov16 antibody seroprevalence. A high prevalence and incidence of epilepsy was found to be associated with a high Ov16 antibody seroprevalence among 6-10-year-old children, except in the Logo health zone, DRC. The low Ov16 antibody seroprevalence among young children in the Logo health zone, despite a high prevalence of epilepsy, may be explained by a recent decrease in O. volvulus transmission because of a decline in the Simulium vector population as a result of deforestation. In the Central African Republic, a new focus of O. volvulus transmission was detected based on the high Ov16 IgG4 seropositivity among children and the detecting of nodding syndrome cases, a phenotypic form of onchocerciasis-associated epilepsy (OAE). In conclusion, Ov16 IgG4 RDT testing of 6-10-year-old children is a cheap and rapid method to determine the level of ongoing O. volvulus transmission and to assess, together with surveillance for OAE, the performance of onchocerciasis elimination programs.

Impact of the COVID-19 pandemic on persons with epilepsy in Uganda: A descriptive cross-sectional study.

OBJECTIVE: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the disease course, lives, and psychosocial wellbeing of persons with epilepsy (PWE) in Uganda. METHODS: From April 2021 till May 2021, we carried out a descriptive cross-sectional study at four hospitals located in four regions of Uganda. PWE presenting at the study sites were offered a structured questionnaire in the local language. We used the PHQ-9 questionnaire to screen for depression and the GAD-7 to screen for anxiety. Univariate and multivariable logistic regression was used to investigate factors associated with anxiety and depression. RESULTS: A total of 370 responses were collected. The median age of the respondents was 20.5 years (IQR 15-29), and 51.9% were males. During the lockdown period, the seizure frequency increased in 87 (23.5%) PWE. Various forms of physical and psychological violence were inflicted upon 106 (28.6%) PWE. Fifty-eight (15.7%) screened positive for anxiety and 65 (17.6%) positive for depression. Both increased seizure frequency and experienced violence were associated with experiencing depression and anxiety. CONCLUSION: The COVID-19 pandemic and lockdown impacted seizure frequency and the psychosocial wellbeing of PWE in Uganda. Increased seizure frequency was associated with higher rates of anxiety and depression. This underlines the importance of continued follow-up of PWE and a low threshold to screen for depression, anxiety, and domestic violence.

Ivermectin treatment response in two rural villages with a high prevalence of onchocerciasis and epilepsy, Mahenge Tanzania.

Background: Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages. Objectives: We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE). Methods: Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment. Results: The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean microfilarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the microfilarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High microfilarial density at baseline was the only significant predictor associated with higher microfilarial density in the post-ivermectin skin snips. Conclusion: Our study reports a decrease in microfilarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge.

Ivermectin treatment response in two rural villages with a high prevalence of onchocerciasis and epilepsy, Mahenge Tanzania

Background: Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages. Objectives: We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE). Methods: Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment. Results: The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean micro filarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the micro filarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High micro filarial density at baseline was the only significant predictor associated with higher micro filarial density in the post-ivermectin skin snips. Conclusion: Our study reports a decrease in micro filarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge

No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy.

Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.

Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study.

Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated.

High Prevalence of Epilepsy in an Onchocerciasis-Endemic Area in Mvolo County, South Sudan: A Door-To-Door Survey.

In June 2020, a door-to-door household survey was conducted in Mvolo County, an onchocerciasis-endemic area in South Sudan. A total of 2357 households containing 15,699 individuals agreed to participate in the study. Of these, 5046 (32.1%, 95% CI: 31.4-32.9%) had skin itching and 445 (2.8%, 95% CI: 2.6-3.1%) were blind. An epilepsy screening questionnaire identified 813 (5.1%) persons suspected of having epilepsy. Of them, 804 (98.9%) were seen by a medical doctor, and in 798 (98.1%) the diagnosis of epilepsy was confirmed. The overall epilepsy prevalence was 50.8/1000 (95% CI: 47.6-54.4/1000), while the prevalence of nodding syndrome was 22.4/1000 (95% CI: 20.1-24.9/1000). Younger age, being male, skin itching, blindness, and living in a neighbourhood or village close to the Naam River were risk factors for epilepsy. The annual incidence of epilepsy was 82.8/100,000 (95% CI: 44.1-141.6/100,000). Among children 7-9 years old without epilepsy, 34% were Ov16 seropositive, suggesting high ongoing Onchocerca volvulus transmission, but only 41.9% of them took ivermectin during the last mass distribution. In conclusion, a high prevalence and incidence of epilepsy was observed in Mvolo, South Sudan. Strengthening of the onchocerciasis elimination programme is urgently needed in order to prevent epilepsy in this region.

Community perceptions and attitudes regarding epilepsy and disease cost after implementation of a community-based epilepsy treatment program in onchocerciasis-endemic communities in the Democratic Republic of Congo.

BACKGROUND: In October 2017, a community-based epilepsy treatment program (CBETP) was initiated in the Logo health zone (Ituri province, Democratic Republic of Congo), consisting mainly of community epilepsy education, provision of free antiepileptic drugs (AEDs), and monthly follow-up of persons with epilepsy (PWE). Prior to the implementation of the CBETP, qualitative research had revealed several misconceptions about the cause of epilepsy, major epilepsy-related stigma, and high economic cost for families of PWE mainly because of costly treatment by traditional healers. One year after the implementation of the CBETP, we assessed the perceived effect of this program on the community's perceptions and attitudes regarding epilepsy and on disease costs. METHODS: Focus group discussions (FGD) and semi-structured in-depth interviews (SSI) were conducted with different target groups. Additionally, the cost associated with epilepsy was evaluated using questionnaires administered to 74 PWE and/or their families. RESULTS: Nine FGDs and 16 SSIs were conducted. There was a notable shift in perceptions and attitudes, as most community members no longer believed that epilepsy is contagious, while acknowledging that this condition can be treated in local health centers. Persons with epilepsy and their family experienced less epilepsy-related stigma and consulted less frequently traditional healers; the latter showed a growing willingness to collaborate with health professionals in the management of PWE. The direct and indirect costs for families caring for a PWE decreased by 95.2% and 95.7%, respectively. CONCLUSION: The main perceived benefits of the CBETP were the decrease in misconceptions about epilepsy and epilepsy-related stigma. Families with PWE understood the benefit of seeking health care from trained health professionals rather than with traditional healers. The direct and indirect costs for families to take care of a PWE reduced considerably after the program. However, the cost-effectiveness and long-term sustainability of this approach remain to be assessed.

The epidemiology of tuberculosis-associated hyperglycemia in individuals newly screened for type 2 diabetes mellitus: systematic review and meta-analysis.

BACKGROUND: There is scarce evidence that tuberculosis (TB) can cause diabetes in those not previously known to be diabetic. Whilst the World Health Organization (WHO) recommends screening for Diabetes Mellitus (DM) at the onset of TB treatment, nevertheless, it remains to be elucidated which patients with TB-associated hyperglycemia are at higher risk for developing DM and stand to benefit from a more regular follow-up. This review aims to firstly quantify the reduction of newly detected hyperglycemia burden in TB patients who are on treatment over time; secondly, determine the burden of TB-associated hyperglycemia after follow-up, and thirdly, synthesize literature on risk factors for unresolved TB-associated hyperglycemia in previously undiagnosed individuals. METHODS: We searched PUBMED, EMBASE, SCOPUS, and Global Health for articles on TB-associated hyperglycemia up to September 30th, 2019. Search terms included Tuberculosis and hyperglycemia/DM, and insulin resistance. We appraised studies, extracted data, and conducted a meta-analysis to assess the change of the burden of hyperglycemia in prospective studies. The review is registered in the PROSPERO database (CRD42019118173). RESULTS: Eleven studies were included in the meta-analysis yielding a total of 677 (27,3%) of patients with newly detected hyperglycemia at baseline. The mean quality score of eligible studies using the Newcastle-Ottawa Quality Assessment Scale was 7.1 out of 9 (range 6-9). The pooled unresolved new cases of hyperglycemia at the end of follow up was 50% (95% CI: 36-64%) and the total pooled burden of hyperglycemia at 3-6 months of follow up was 11% (95% CI: 7-16%), with both estimates displaying a high heterogeneity, which remained significant after performing a sub-analysis by DM diagnostic method and 3 months of follow up. As only 2 studies explored risk factors for unresolved hyperglycemia, no meta-analysis was performed on risk factors. CONCLUSION: Our meta-analysis showed that although in half of the patients with newly observed hyperglycemia at baseline, it remained unresolved at a follow-up of 3 to 6 months, the total burden of hyperglycemia is slightly above 10%, 3 months after initiating TB treatment. Studies are warranted to assess whether risk factors including HIV positivity, smoking, and extensive pulmonary TB disease put patients at higher risk for DM.

OV16 Seroprevalence among Persons with Epilepsy in Onchocerciasis Endemic Regions: A Multi-Country Study.

There is growing epidemiological evidence that onchocerciasis may induce epilepsy. High prevalence of onchocerciasis has been reported in onchocerciasis-meso and hyper-endemic regions. We aimed to determine the OV16 antibody prevalence in persons with epilepsy (PWE) in four onchocerciasis-endemic regions. PWE were identified during studies in Mahenge area (Tanzania), Kitgum and Pader districts (Uganda), the Mbam and Sanaga river valleys (Cameroon), and the Logo health zone (Democratic Republic of Congo). Exposure to Onchocerca volvulus was assessed by testing PWE for OV16 IgG4 antibodies using a rapid diagnostic test. The OV16 seroprevalence among PWE in the four onchocerciasis-endemic study sites ranged from 35.2% to 59.7%. OV16 seroprevalence increased with age until the age of 39 years, after which it decreased drastically. Our study suggests that, in onchocerciasis-endemic regions, epilepsy in young people is often associated with onchocerciasis, while epilepsy in older persons seems unrelated to O. volvulus exposure.

Ivermectin Treatment Response in Onchocerca Volvulus Infected Persons with Epilepsy: A Three-Country Short Cohort Study.

Despite a long history of community-directed treatment with ivermectin (CDTI), a high ongoing Onchocerca volvulus transmission is observed in certain onchocerciasis-endemic regions in Africa with a high prevalence of epilepsy. We investigated factors associated with higher microfilarial (mf) density after ivermectin treatment. Skin snips were obtained from O. volvulus-infected persons with epilepsy before, and 3 to 5 months after ivermectin treatment. Participants were enrolled from 4 study sites: Maridi (South Sudan); Logo and Aketi (Democratic Republic of Congo); and Mahenge (Tanzania). Of the 329 participants, 105 (31.9%) had a post-treatment mf density >20% of the pre-treatment value. The percentage reduction in the geometric mean mf density ranged from 69.0% (5 months after treatment) to 89.4% (3 months after treatment). A higher pre-treatment mf density was associated with increased probability of a positive skin snip after ivermectin treatment (p = 0.016). For participants with persistent microfiladermia during follow-up, a higher number of previous CDTI rounds increased the odds of having a post-treatment mf density >20% of the pre-treatment value (p = 0.006). In conclusion, the high onchocerciasis transmission in the study sites may be due to initially high infection intensity in some individuals. Whether the decreasing effect of ivermectin with increasing years of CDTI results from sub-optimal response mechanisms warrants further research.

Comparison of Diagnostic Tests for Onchocerca volvulus in the Democratic Republic of Congo.

Onchocerciasis is diagnosed by detecting microfilariae in skin snips or by detecting OV16 IgG4 antibodies in blood by either enzyme linked immunosorbent assay (ELISA) or a rapid diagnostic test (RDT). Here, we compare the sensitivity and specificity of these three tests in persons with epilepsy living in an onchocerciasis endemic region in the Democratic Republic of Congo. Skin snips and blood samples were collected from 285 individuals for onchocerciasis diagnosis. Three tests were performed: the OV16 RDT (SD Bioline) and the OV16 ELISA both on serum samples, and microscopic detection of microfilariae in skin snips. The sensitivity and specificity of each test was calculated with the combined other tests as a reference. Microfilariae were present in 105 (36.8%) individuals, with a median of 18.5 (6.5-72.0) microfilariae/skin snip. The OV16 RDT and OV16 ELISA were positive in, respectively, 112 (39.3%) and 143 (50.2%) individuals. The OV16 ELISA had the highest sensitivity among the three tests (83%), followed by the OV16 RDT (74.8%) and the skin snip (71.4%). The OV16 RDT had a higher specificity (98.6%) compared to the OV16 ELISA (84.8%). Our study confirms the need to develop more sensitive tests to ensure the accurate detection of ongoing transmission before stopping elimination efforts.

Urinary N-acetyltyramine-O,ß-glucuronide in Persons with Onchocerciasis-Associated Epilepsy.

We investigated urinary N-acetyltyramine-O,ß-glucuronide (NATOG) levels as a biomarker for active Onchocerca volvulus infection in an onchocerciasis-endemic area in the Democratic Republic of Congo with a high epilepsy prevalence. Urinary NATOG was measured in non-epileptic men with and without O. volvulus infection, and in O. volvulus-infected persons with epilepsy (PWE). Urinary NATOG concentration was positively associated with microfilarial density (p < 0.001). The median urinary NATOG concentration was higher in PWE (3.67 µM) compared to men without epilepsy (1.74 µM), p = 0.017; and was higher in persons with severe (7.62 µM) compared to mild epilepsy (2.16 µM); p = 0.008. Non-epileptic participants with and without O. volvulus infection had similar NATOG levels (2.23 µM and 0.71 µM, p = 0.426). In a receiver operating characteristic curve analysis to investigate the diagnostic value of urinary NATOG, the area under the curve was 0.721 (95% CI: 0.633-0.797). Using the previously proposed cut-off value of 13 µM to distinguish between an active O. volvulus infection and an uninfected state, the sensitivity was 15.9% and the specificity 95.9%. In conclusion, an O. volvulus infection is associated with an increased urinary NATOG concentration, which correlates with the individual parasitic load. However, the NATOG concentration has a low discriminating power to differentiate between infected and uninfected individuals.

Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo.

BACKGROUND: There is anecdotal evidence that ivermectin may decrease seizure frequency in Onchocerca volvulus-infected persons with epilepsy (PWE). METHODS: In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy experiencing ≥2 seizures/month were randomly allocated to receive, over a one-year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs. Data was analyzed using multiple logistic regression. RESULTS: We enrolled 197 participants. In an intent-to-treat analysis (data from group 1 and 2 combined), seizure freedom was more likely among OIPWE treated with ivermectin thrice (OR: 5.087, 95% CI: 1.378-19.749; p = 0.018) and twice (OR: 2.471, 95% CI: 0.944-6.769; p = 0.075) than in those treated once. Similarly, >50% seizure reduction was more likely among those treated with ivermectin twice (OR: 4.469, 95% CI: 1.250-16.620) and thrice (OR: 2.693, 95% CI: 1.077-6.998). Absence of microfilariae during the last 4 months increased the odds of seizure freedom (p = 0.027). CONCLUSIONS: Increasing the number of ivermectin treatments was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures.

Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial.

INTRODUCTION: Recent findings from onchocerciasis-endemic foci uphold that increasing ivermectin coverage reduces the epilepsy incidence, and anecdotal evidence suggests seizure frequency reduction in persons with onchocerciasis-associated epilepsy, when treated with ivermectin. We conducted a randomized clinical trial to assess whether ivermectin treatment decreases seizure frequency. METHODS: A proof-of-concept randomized clinical trial was conducted in the Logo health zone in the Ituri province, Democratic Republic of Congo, to compare seizure frequencies in onchocerciasis-infected persons with epilepsy (PWE) randomized to one of two treatment arms: the anti-epileptic drug phenobarbital supplemented with ivermectin, versus phenobarbital alone. The primary endpoint was defined as the probability of being seizure-free at month 4. A secondary endpoint was defined as >50% reduction in seizure frequency at month 4, compared to baseline. Both endpoints were analyzed using multiple logistic regression. In longitudinal analysis, the probability of seizure freedom during the follow-up period was assessed for both treatment arms by fitting a logistic regression model using generalized estimating equations (GEE). RESULTS: Ninety PWE enrolled between October and November 2017 were eligible for analysis. A multiple logistic regression analysis showed a borderline association between ivermectin treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062). There was no significant difference in the probability of experiencing >50% reduction of the seizure frequency at month 4 between the two treatment arms. Also, treatment with ivermectin did not significantly increase the odds of being seizure-free during the individual follow-up visits. CONCLUSION: Whether ivermectin has an added value in reducing the frequency of seizures in PWE treated with AED remains to be determined. A larger study in persons with OAE on a stable AED regimen and in persons with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with OAE. TRIAL REGISTRATION: Registration: www.clinicaltrials.gov; NCT03052998.

Effect of Ivermectin Treatment on the Frequency of Seizures in Persons with Epilepsy Infected with Onchocerca volvulus.

A clinical trial performed in the Democratic Republic of Congo (DRC), among persons with epilepsy (PWE) infected with Onchocerca volvulus treated with anti-seizure medication suggested that ivermectin reduces the seizure frequency. We assessed the effect of ivermectin treatment on seizure frequency in PWE with and without anti-seizure medication in three onchocerciasis endemic areas (Maridi, South Sudan; Aketi, DRC; and Mahenge, Tanzania). Pre- and 3-5 months post-ivermectin microfilariae densities in skin snips and seizure frequency were assessed. After ivermectin, the median (IQR) percentage reduction in seizure frequency in the study sites ranged from 73.4% (26.0-90.0) to 100% (50.0-100.0). A negative binomial mixed model showed that ivermectin significantly reduced the seizure frequency, with a larger decrease in PWE with a high baseline seizure frequency. Mediation analysis showed that ivermectin reduced the seizure frequencies indirectly through reduction in microfilariae densities but also that ivermectin may have a direct anti-seizure effect. However, given the short half-life of ivermectin and the fact that ivermectin does not penetrate the healthy brain, such a direct anti-seizure effect is unlikely. A randomized controlled trial assessing the ivermectin effect in people infected with O. volvulus who are also PWE on a stable anti-seizure regimen may be needed to clarify the causal relationship between ivermectin and seizure frequency.

The epidemiology of intransient TB-induced hyperglycaemia in previously undiagnosed diabetes mellitus 2 individuals: a protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus (DM) is burgeoning as a global chronic health condition. Some studies suggest that tuberculosis (TB) can even cause diabetes in those not previously known to be diabetic, which as a corollary can add to the already heavy global DM burden. The World Health Organization (WHO) recommends screening for DM at the start of TB treatment; however, it remains to be elucidated which patients with TB-induced hyperglycaemia are at risk for developing DM and who would benefit from a more regular follow-up. This systematic review will aim to firstly synthesise literature on the irreversibility of TB-induced hyperglycaemia in individuals with previously undiagnosed type 2 diabetes mellitus and secondly to synthesise literature on risk factors for progression from TB-induced hyperglycaemia to overt DM in previously undiagnosed. METHODS: We will search for relevant studies in electronic databases such as PubMed, EMBASE, PROQUEST, and SCOPUS. Furthermore, references will be hand searched to identify other studies. A flow diagram will be drawn to identify the studies retrieved from each database. We will review all publications that include studies containing data on impaired glucose metabolism upon TB diagnosis, and the quality of all eligible studies will be assessed using the Newcastle-Ottawa Scale. We will further conduct a meta-analysis to pool estimates on the risk of progression of persistent hyperglycaemia to overt DM within this population group, as well as the risk factors for this progression. We will use a random effect model to assess heterogeneity, will carry out sensitivity analysis to explore the influence of a single study on the overall estimate, and will report our findings from our systematic review and meta-analysis according to PRISMA guidelines. Egger's test will be performed to explore the presence of selective reporting bias. If data allow, we will perform a subgroup/meta-regression analysis. Summary effects will be reported using odds ratio, hazard ratio, and relative risk ratios. Furthermore, any clinical, epidemiological, and public health research gaps we identify will be described in a research proposal.