A systematic review and meta-analysis of all available case-control studies on the relationship between onchocerciasis and epilepsy. Because age and level of onchocerciasis endemicity in the area of ...residence are major determinants for infection, an additional analysis was performed, restricted to studies achieving control of these confounding factors.
Medical databases, the "African Neurology Database, Institute of Neuroepidemiology and Tropical Neurology, Limoges," reference lists of relevant articles, commercial search engines, up to May 2012.
We searched for studies examining infection status with Onchocerca volvulus in persons with epilepsy (PWE) and without epilepsy (PWOE) providing data suitable for the calculation of pooled odds ratios (ORp) and/or standardized mean differences (SMD) using random-effects models.
Eleven studies providing data of qualitative skin biopsies for diagnosis of onchocerciasis were identified. Combined analysis on the total sample of 876 PWE and 4712 PWOE resulted in an ORp of 2.49 (95% confidence interval (95%CI): 1.61-3.86, p<0.001). When this analysis was restricted to those studies achieving control for age, residence and sex (367 PWE, 624 PWOE), an ORp of 1.29 (95% CI: 0.93-1.79; p = 0.139) was found. Presence of nodules for diagnosis of onchocerciasis was analyzed in four studies (225 PWE, 189 PWOE; ORp 1.74; 95%CI: 0.94-3.20; p<0.076), including two studies of the restricted analysis (106 PWE, 106 PWOE; ORp 2.81; 95%CI: 1.57-5.00; p<0.001). One study examined quantitative microfilariae counts in patients without preceding microfilaricidal treatment and demonstrated significantly higher counts in PWE than in PWOE.
Our results strengthen the hypothesis that, in onchocerciasis foci, epilepsy and infection with O. volvulus are associated. Analysis of indicators giving information on infection intensity, namely nodule palpation and quantitative microfilaria count in untreated patients, support the hypothesis that intensity of infection with O. volvulus is involved in the etiology of epilepsy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background The burden of loiasis has received limited attention and loiasis is still considered a benign condition. To assess whether loiasis bears any excess mortality, we did a ...retrospective cohort study in Cameroon. Methods In 2001, 3627 individuals living in 28 villages were examined for Loa loa infection. In 2016, these villages were revisited and the vital status was determined for 3301 individuals (91%). The data were analysed at community level to assess the relation between the level of L loa infection in 2001 and standardised mortality rates (SMRs), and at individual level to assess the excess mortality relative to the 2001 microfilaraemia and to calculate the population-attributable fraction of mortality associated with L loa microfilaraemia. Findings 915 deaths occurred during the follow-up time (mean time of 12·5 years IQR 10·2–14·9) between April, 2001, and March 22, 2016. Crude mortality rate was 20·3 deaths per 1000 person-years. SMRs increased by 4·1% when the proportion of participants infected with greater than 30 000 microfilariae per mL increased by 1% (p=0·030). People aged older than 25 years with greater than 30 000 microfilariae per mL in 2001 died significantly earlier than did amicrofilaraemic people (time ratio 0·67, 95% CI 0·48–0·95, p=0·024). The population-attributable fraction of mortality associated with presence of L loa microfilaraemia was 14·5% (95% CI 6·5–21·8, p=0·001). Interpretation High-grade L loa microfilaraemia is associated with an increased mortality risk, suggesting that loiasis is not a benign condition and merits more attention because of its effect on onchocerciasis and lymphatic control strategies. Loiasis should be considered for inclusion in the WHO's list of neglected tropical diseases. Funding Drugs for Neglected Diseases initiative.
Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert ...selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.
Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.
This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis ...(LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow. Methodology/Principal findings We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo with moderately high prevalences for LF and hookworm infections. MDA with albendazole was provided every six months from June 2014 to December 2017 with treatment coverages of the eligible population (all greater than or equal to 2 year of age) that ranged between 56% and 88%. No adverse effects were reported during the trial. Evaluation at 48 months, (i.e. 6 months after the 8.sup.th round of MDA), showed that W. bancrofti microfilaremia (Mf) prevalence in the study communities had decreased between 2014 to 2018 from 12% to 0.9% (p0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p0.001), from 14.0% to 1.6% and 4.1% to 2.9%, respectively. Hookworm and Ascaris infection intensities were reduced by 93% (p = 0.02) and 57% (p = 0.03), respectively. In contrast, Trichuris infection intensity was not significantly reduced by MDA (p = 0.61) over this time period. Conclusion/Significance These results provide strong evidence that semiannual MDA with albendazole alone is a safe and effective strategy for LF elimination in Central Africa. Community MDA also had a major impact on STH infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of ...multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques.
Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon.
Multiple doses of ivermectin have a partial macrofilaricidal and a modest permanent sterilizing effect after 4 or more consecutive treatments, even at routine MDA doses (150 µg/kg) and frequencies (annual). The life expectancy of adult O. volvulus is reduced by approximately 50% and 70% after 3 years of annual or 3-monthly (quarterly) exposures to ivermectin.
Our quantification of macrofilaricidal and sterilizing effects of ivermectin should be incorporated into transmission models to inform onchocerciasis elimination efforts in Africa and residual foci in Latin America. It also provides a framework to assess macrofilaricidal candidate drugs currently under development.
Background Neglected Tropical Diseases amenable to Preventive Chemotherapy (PC-NTDs) affect the poorest populations around the world, especially in Africa. Scientific information on the distribution ...and level of endemicity of these diseases in the Republic of the Congo (RoC) is scarce in the published literature. We sought to collect all available epidemiological data on PC-NTDs in the RoC to document the historical and current situation and identify challenges in reaching the elimination of NTDs. Methods We searched Medline and Horizon databases for studies published until to July 4.sup.th, 2019, on onchocerciasis, lymphatic filariasis, soil-transmitted helminth infections, schistosomiasis, and trachoma in the RoC. Unpublished reports were also reviewed. We included all epidemiological studies containing community data and excluded case reports. Location, prevalence data, and dates of the studies were extracted. Principal findings We identified 933 records, of which 56 met the inclusion criteria. The articles published before 1960 mainly concerned onchocerciasis and schistosomiasis. Despite a low number over the studied period, since 2005 there has been a steady increase in the number of publications. Most of the studies were cross-sectional and conducted in the general population. Trachoma is endemic in the Sangha and Likouala departments (prevalence of trachomatous inflammation-follicular > 5% in some villages), and further mapping is essential to properly assess the burden of this disease in the country. While the prevalence of soil-transmitted helminths is still high (over 20%) in a large part of Congo, cases of lymphatic filariasis (based on Wuchereria bancrofti antigenaemia and/or microfilaraemia) and onchocerciasis are becoming rare and very focused. To achieve the elimination of PC-NTDs, further intervention is required. Conclusions Except for trachoma, whose epidemiological situation should be better evaluated, PC-NTDs are endemic in the RoC, and actions to control them have been taken by health authorities. To eliminate PC-NTDs, which are still present in some locations, new mapping surveys are needed, and increased investment in scientific research should be encouraged in the country.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown that the drug's ...pharmacologically active metabolite, albendazole sulfoxide, is characterised by substantial inter-individual pharmacokinetic variation. This variation might have implications for the efficacy of albendazole treatment, but current understanding of the factors associated with this variation remains incomplete. Methodology/Principal findings We carried out a systematic review to identify references containing temporally disaggregated data on the plasma concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer albendazole sulfoxide pharmacokinetic parameters and relate them to characteristics of the groups being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole sulfoxide pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. Age was significantly associated with variation in albendazole sulfoxide systemic availability and peak plasma concentration achieved; as well as the clearance rate (related to the half-life) after adjusting for variation in dosage due to differences in body weight between children and adults. Receipt of a fatty meal prior to treatment was associated with increased albendazole sulfoxide systemic availability (and by extension, peak plasma concentration and total albendazole sulfoxide exposure following the dose). Parasitic infection (particularly echinococcosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteristics to uninfected ones. Conclusions/Significance These results highlight the extensive inter-individual variation that characterises albendazole sulfoxide pharmacokinetics and provide insight into some of the factors associated with this variation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little information is available on the effect of ivermectin on the third- and fourth-stage larvae of Onchocerca volvulus. To assess a possible prophylactic effect of ivermectin on this parasite, we ...compared the effects of different ivermectin regimens on the acquisition of onchocercal nodules.
We analyzed data from a controlled randomized clinical trial of ivermectin conducted in the Mbam Valley (Cameroon) between 1994 and 1998 in a cohort of onchocerciasis infected individuals. The number of nodules that appeared between the start and the end of the clinical trial was analyzed, using ANOVA and multivariable Poisson regressions, between four treatment arms: 150 µg/kg annually, 800 µg/kg annually, 150 µg/kg 3-monthly, and 800 µg/kg 3-monthly.
The mean number of nodules that appeared during the trial was reduced by 17.7% in subjects treated 3-monthly compared to those treated annually (regardless of the dose). Poisson regression model, adjusting on subject's age and weight, initial number of nodules and intensity of O. volvulus infection in his village of residence, confirmed that the incidence of new nodules was reduced in 3-monthly treatment arms compared to annually treatment arms, and that the dosage of ivermectin does not seem to influence this effect. Furthermore, the number of newly acquired nodules was positively associated with the initial number of nodules. Analysis of disappearance of nodules did not show any significant difference between the treatment groups.
To our knowledge, these results suggest for the first time in humans, that ivermectin has a partial prophylactic effect on O. volvulus. Three-monthly treatment seems more effective than annual treatment to prevent the appearance of nodules.
The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first ...geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions.
Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson's correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2-90%) in 1975.
This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Loa loa filariasis (loiasis) is still considered a relatively benign disease. However, recent epidemiologic data suggest increased mortality and morbidity in L. loa infected individuals. We aimed to ...examine whether the density of L. loa microfilariae (mfs) in the blood is associated with cardiovascular disease.
Using a point-of-care device (pOpmètre), we conducted a cross-sectional study to assess arterial stiffness and peripheral arterial disease (PAD) in 991 individuals living in a loiasis-endemic rural area in the Republic of the Congo. Microfilaremic individuals were matched for age, sex and village of residence with 2 amicrofilaremic subjects. We analyzed markers of arterial stiffness (Pulse-Wave Velocity, PWV), PAD (Ankle-Brachial Index, ABI) and cardiovascular health (Pulse Pressure, PP). The analysis considered parasitological results (L. loa microfilarial density MFD, soil-transmitted helminths infection, asymptomatic malaria and onchocerciasis), sociodemographic characteristics and known cardiovascular risk factors (body mass index, smoking status, creatininemia, blood pressure).
Among the individuals included in the analysis, 192/982 (19.5%) and 137/976 (14.0%) had a PWV or an ABI considered out of range, respectively. Out of range PWV was associated with younger age, high mean arterial pressure and high L. loa MFD. Compared to amicrofilaremic subjects, those with more than 10,000 mfs/mL were 2.17 times more likely to have an out of range PWV (p = 0.00). Factors significantly associated with PAD were older age, low pulse rate, low body mass index, smoking, and L. loa microfilaremia. Factors significantly associated with an elevation of PP were older age, female sex, high average blood pressure, low pulse rate and L. loa microfilaremia.
A potential link between high L. loa microfilaremia and cardiovascular health deterioration is suggested. Further studies are required to confirm and explore this association.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
