Explore the vast range of titles available.

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. 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. 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). 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. Drugs for Neglected Diseases initiative.

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.

Echocardiography is crucial for diagnosis and management of cardiac diseases. Existing reference values may not be applicable to rural African populations due ethnicity related variability and limited data. This study aimed to establish reference values for echocardiographic parameters in a rural population. We assessed echocardiographic parameters in the adult population ( ≥ 18 years) from rural areas endemic for loiasis in the Republic of Congo. Reference values were established using participants with normal BMI, no hypertension/diabetes, and no significant echocardiographic abnormalities. Statistical analyses included comparisons by sex and age group. This study of 422 participants revealed significant variations in echocardiographic parameters across age and sex groups. Left ventricular dimensions and mass were larger in males, while left ventricular ejection fraction was higher in females. Left atrial dimensions, including area and volume, increased with age. Right ventricular dimensions also exhibited sex and age-related differences, with males generally showing larger dimensions. The prevalence of echocardiographic abnormalities varied significantly compared to reference values from other populations. This study provides age- and sex-stratified reference values for echocardiographic parameters in a rural population endemic for loiasis, highlighting the need for population-specific reference values and a standardized approach to their establishment to improve comparability across studies. The authors assessed echocardiographic parameters in adults from rural areas endemic for loiasis in the Republic of Congo. They report significant differences in the Congolese adults from existing standard measurements, which highlights need for population-specific reference values and a standardized approach to their establishment to improve comparability across studies.

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. 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. 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.

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% (p<0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p<0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p<0.001), 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.

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.

Individuals with high Loa loa microfilarial densities (MFD) risk serious adverse events (SAEs) following ivermectin treatment. A single dose of levamisole (LEV) induces a temporary, progressive MFD decrease. This double-blind, randomized, placebo-controlled trial evaluated the safety and efficacy of 3-day and 5-day LEV regimens for the treatment of loiasis in the Republic of the Congo. Participants were randomly assigned to receive placebo (PLA), LEV-3, or LEV-5. Safety was assessed by the occurrence of SAEs and the frequency and severity of AEs. Efficacy was measured by changes in Loa loa MFD. No SAEs were reported, and AE severity was comparable across treatment arms. On day 5, MFD reductions were greater in the LEV-3 and LEV-5 groups compared to PLA ( −1.6%, 29.3%, and 51.4%, respectively; P  < 0.001). By day 7, a higher proportion of participants achieved ≥40% MFD reduction in the LEV-5 group (44.4%) compared to LEV-3 (34.6%) and PLA (8.3%) ( P  = 0.051). Post hoc contrasts confirmed significantly greater MFD reduction with LEV-5 versus LEV-3. These findings suggest that a 5-day LEV regimen is safe and moderately effective for reducing L. loa MFD and may represent a promising alternative for individualised management in loiasis-endemic areas, particularly where onchocerciasis is hypoendemic and coendemic with loiasis. Trial registration: NCT06252961. Loiasis poses significant treatment challenges, particularly in regions where onchocerciasis is hypoendemic and coendemic. Here, the authors demonstrate that a 5-day levamisole regimen is safe and more effective than shorter treatments in reducing Loa loa microfilarial densities, offering an alternative approach for managing loiasis in affected areas.

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.

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.

Loa loa filariasis, a parasitic infection endemic to Central Africa, is a common cause of medical consultation in this region. To evaluate the quality of life (QoL) of individuals living in loiasis-endemic areas, we enrolled 991 subjects (one-third being microfilaremic) from the general population of a rural area in the Republic of Congo. QoL and disability were assessed using WHODAS 2.0 12-items and EQ-5D-5L questionnaires. We collected data on the number of eye worm (Ew) and Calabar swelling episodes experienced throughout their lives, as well as individual L. loa microfilarial densities and information on infections with soil-transmitted helminthiasis. Individuals with a history of Ew had a nearly doubled risk of experiencing at least moderate disability (score >25/100) (adjusted Odds-Ratio = 1.77 (95%CI [1.05-2.99], p = 0.033), compared to those without such a history. Those with more than 10 episodes of Ew during their lifetime had a 28% increase in overall disability as measured by WHODAS. No other variable related to loiasis (Calabar swelling frequency, L. loa microfilarial density and positivity to L. loa antibody rapid test) was associated with the various scores. Additionally, infection with Trichuris trichiura was associated with worse anxiety score (adjusted incidence risk ratio = 1.22 (95% CI [1.06-1.39], p = 0.004)). The impact of loiasis on daily QoL appears to be primarily due to adult worms rather than microfilarial density. Indeed, our findings strongly suggest that the number of Ew episodes, likely reflecting the cumulative burden of adult worms, is the main correlate of worse QoL scores. These episodes seem to affect multiple dimensions of functioning, with notable impact on mobility, pain, anxiety, and daily activities. In contrast, microfilariae would primarily induce organ dysfunction. Further studies are needed to better understand the respective clinical impacts of adult worms and L. loa microfilariae.