RARE DISEASE
Loiasis
Loiasis
Loiasis
Drug discovery
0
drugs
With orphan designations
Overview
Loiasis, caused by the Loa loa filarial nematode, is transmitted by day-biting Chrysops flies in West/Central Africa. Clinical features include transient Calabar swellings (hypersensitivity-driven angioedema) and subconjunctival migration of adult worms. Diagnosis relies on blood smears (daytime microfilaremia) or visualization of worms. Treatment requires careful risk stratification due to encephalopathy risks in high microfilarial loads (>8,000/mL), with diethylcarbamazine (DEC) as first-line therapy. Coinfection with onchocerciasis necessitates caution to avoid Mazzotti reactions [1][6][10][19].
Burden
Associated with 14.5% mortality risk in microfilaremic individuals and reduced life expectancy (median survival: 39 vs. 58.5 years in non-infected) [9][17].
Annual healthcare costs average $58/patient in Gabon, with productivity losses from chronic symptoms (arthralgia, fatigue) and traditional treatment reliance [4][12].
Complicates mass drug administration for other filarial diseases (e.g., onchocerciasis) due to ivermectin contraindications [5][6].
Therapies
DEC (8–10 mg/kg/day for 21 days): Effective against microfilariae and adults; contraindicated in onchocerciasis coinfection [1][19].
Albendazole (200 mg BID for 21 days): Used for DEC-refractory cases or pre-treatment to reduce microfilarial density [3][19].
Apheresis: Critical for severe microfilaremia (≥8,000/mL) to mitigate fatal encephalopathy risks before DEC [1][19].
Categories: rare infectious diseases
Research Papers
194 drug discovery papers about Loiasis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
194 drug discovery papers about Loiasis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-04-25 | Clinical characteristics and treatments of imported loiasis patients with microfilaraemia diagnosed in France, 2000-2022.
Loiasis has been associated with increased morbidity and mortality, particularly in cases of high microfilarial density. Treatment depends on initial microfilaraemia (Mf) and relies on ivermectin (IVM), diethylcarbamazine (DEC) or albendazole (ALB), all associated with serious adverse events. Our objective was to describe the clinical characteristics, management and outcomes of patients diagnosed with loiasis and Mf in France. We conducted a multicenter retrospective study including patients with loiasis and Mf diagnosed and treated in France between 2000 and 2022, with at least one follow-up evaluation. We collected clinical and biological data, including Mf kinetics, for each treatment episode. A total of 150 patients (181 treatment episodes) were included across 27 centers. Median age was 35 years, and most patients presented symptoms (75.3%). Median Mf was 500 mf/ml; for 74% of episodes, baseline Mf below 2000 mf/ml, while 8% had baseline Mf above 8000 mf/ml. Twelve different treatment schemes were identified, the most common being a single dose of IVM (39%). Adverse events occurred in 12% of episodes, including one fatal event. On last follow-up visit, 9.3% of patients still experienced symptoms, 24.7% exhibited persistent Mf, and 19.3% had persistent blood eosinophilia, patients treated with stand-alone IVM experienced worse outcomes (18%, 72% and 39%, respectively). In France, loiasis treatment is inconsistent and frequently relies on inadequate options, including IVM monotherapy, which lacks therapeutic efficacy, and carries safety concerns. Our findings highlight real-world practices and indicates that better training is needed for practitioners treating patients with loiasis.
2026-01-20 | Assessment of the efficacy and safety of two albendazole regimens for the treatment of hypermicrofilaraemic loiasis in adults in Woleu-Ntem Province, Gabon: A phase IIb single-blind randomised controlled trial.
Loa (L.) loa hypermicrofilaraemia (≥ 8,000 mf/mL) increases the risk of severe adverse events during mass ivermectin administration for onchocerciasis control. Albendazole has been proposed as a potential alternative for reducing microfilaraemia prior to ivermectin administration. This prospective study was conducted in northern Gabon from November 2021 to April 2022. Individuals infected with L. loa were screened and allocated to three groups: two treatment arms receiving 400 mg or 800 mg of albendazole daily for 30 days among hypermicrofilaraemic participants, and a group with microfilaraemia < 8,000 mf/mL. Clinical symptoms and parasitological data were collected on Days 0, 2, 7, 14, and 30. A total of 70 participants were enrolled: 16 in the 400 mg group, 16 in the 800 mg group, and 38 in the group with microfilaraemia below 8,000 mf/mL. Itching was the most frequently reported adverse event. By Day 30, no participants in the group with microfilaraemia below 8,000 mf/mL presented with clinical symptoms. Microfilaraemia significantly decreased in all groups (p < 0.01). After 30 days, over 70.0% of patients treated with albendazole had microfilaraemia < 8,000 mf/mL. There was no significant difference in efficacy between the two albendazole regimens. Daily administration of 400 mg albendazole for 30 days effectively reduces microfilarial loads in patients with L. loa hypermicrofilaraemia and is well tolerated and safe. This pre-treatment regimen may reduce the risk of adverse events associated with ivermectin administration. Further research is needed to evaluate the long-term persistence of microfilarial suppression.
2026-01-07 | Ocular filariasis manifesting as an orbital cellulitis and conjunctival nodule: a case report.
Filariasis is a parasitic infection that mostly involves the skin and ocular surface, although all layers of the eye and orbit can be affected. We report a case of a 42-year-old woman with Loa loa infection manifesting as a sequential bilateral forehead Calabar swelling, severe orbital cellulitis and thereafter mimicking a conjunctival tumor. Anterior segment optical coherence tomography helped to differentiate between a neoplasm and the filarial worm and show typical features such as longitudinal and cross-sections of the parasite. The worm was surgically removed and microbiologists confirmed the diagnosis of a subconjunctival Loa loa infection. The patient was successfully treated with diethylcarbamazine (DEC) and ivermectin without adverse events. Parasitic orbital cellulitis is rarely reported and this case highlights the importance of considering loiasis in unexplained orbital cellulitis in patients with hypereosinophilia and a history of residence in endemic areas.
2025-12-11 | Loa loa Encephalopathy Following Treatment With Benzimidazole Derivatives: A Systematic Review.
Loiasis, a filarial vector-borne disease, is common in rural West and Central Africa. Benzimidazole derivatives albendazole and mebendazole are recommended as alternative treatments due to their perceived safety in hypermicrofilaremic patients. There is growing evidence that benzimidazoles might also lead to Loa loa-associated encephalopathy. In this systematic review we analyzed all available evidence of benzimidazole-associated encephalopathy. Literature was systematically searched in PubMed, Google Scholar, and WHO-VigiBase®, including conference abstracts and consultation of experts. Six potential cases of benzimidazole-associated encephalopathy, including 2 fatalities, were identified among microfilaremic loiasis patients. Due to the limited global use of prolonged benzimidazole regimens for loiasis, the number of encephalopathy cases identified raises significant safety concerns, challenging the rationale of their use. Further research on mechanisms and safer alternative regimens is urgently needed.
2025-12-11 | Activity of antifilarial drugs on microfilaremia in the treatment of loiasis: a systematic review.
Loiasis, caused by the nematode/filaria Loa loa, presents a major health burden in Central and West Africa. Despite the growing recognition of loiasis' medical significance, current antifilarial drugs remain inadequate in terms of efficacy and safety, particularly for individuals with hypermicrofilaremia. This systematic review aims to evaluate the efficacy of antifilarial treatment regimens for reducing L. loa microfilaremia and provide guidance on treatment strategies. A systematic review was conducted to evaluate the efficacy of antifilarial treatment regimens on reducing L. loa microfilaremia. Data on the percentage reduction of microfilaremia from baseline to nadir were extracted for each treatment regimen. A total of 27 studies were included in the review, with treatment regimens involving albendazole (ALB), mebendazole (MBZ), ivermectin (IVM), diethylcarbamazine (DEC), levamisole, imatinib, and moxidectin, among others. ALB and MBZ showed dose- and duration-dependent efficacy, with extended treatment leading to up to a 98-100% microfilaremia reduction. IVM showed a dose-dependent effect, with single doses of 200-400 µg/kg reducing microfilaremia by 88-92%. DEC exhibited high efficacy, achieving up to a 100% microfilaremia reduction. Antifilarial drug efficacy against L. loa microfilaremia varies by dosage and treatment duration, with IVM and DEC demonstrating rapid, high efficacy but presenting safety concerns for hypermicrofilaremic individuals. ALB and MBZ show efficacy with extended treatment but are slower acting. Further research is needed to optimize treatment regimens and assess clinical outcomes beyond microfilaremia reduction.
antibodies
2022-10-14 | The Host–Helminth Interface as a Rich Resource for Novel Drug Targets
The evolutionary arms races underlying all host–helminth associations have resulted in intricate negotiations enabling a successful infection. At the host–parasite interface, a continuous dialogue takes place, where a plethora of molecules are exchanged, with crucial consequences on the outcome of the infection. This molecular exchange appears to be a rich source of potential therapeutic targets. Here, we present what recent research has brought to light on this topic for helminths, focusing on filarial nematodes.
2020-09-07 | A Randomized, Placebo-controlled, Double-blind Pilot Study of Single-dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa loa Infection.
Diethylcarbamazine citrate (DEC) treatment of loiasis is complicated by adverse reactions that are correlated with the number of circulating microfilariae (mf). The cause of these reactions is unknown, but they are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation.To explore the role of IL-5 driven eosinophilia in post-DEC reactions, 8 adults with confirmed loiasis and <5000 mf/mL blood were enrolled in a randomized, double-blind, placebo-controlled trial of the humanized anti-IL-5 antibody, reslizumab, (1.0 mg/kg IV) administered 3 to 7 days prior to initiation of DEC treatment (9 mg/kg/day for 21 days). The primary endpoint was the reduction in absolute eosinophil count (AEC) during the first week of DEC treatment.Baseline characteristics were comparable between the two groups. Single dose reslizumab lowered the AEC by 77% prior to initiation of DEC therapy (vs. 12% in the placebo group, P < .05). More importantly, AEC remained below baseline in the first week of DEC treatment in all subjects who received reslizumab and in none of the placebo subjects. Mf clearance occurred within 2 days of initiation of DEC in all 7 mf-positive subjects. Mild to moderate adverse events were seen in all 8 subjects and were not significantly different between the groups.In summary, although reslizumab was able to blunt peripheral eosinophilia post-DEC treatment in subjects with loiasis and had no effect on microfilarial clearance, the reduction in AEC appeared to have been insufficient to prevent post-treatment AEs.
2016-09-01 | A diagnostic challenge: Eosinophilia of unknown etiology
Approximately 100 million people suffer from filarial diseases including lymphatic filariasis (elephantiasis), onchocerciasis (river blindness) and loiasis. These diseases are amongst the most devastating of the neglected tropical diseases in terms of social and economic impact. Moreover, many infection-induced immune mechanisms in the host, their relationship to disease-related symptoms and the development of pathology within the site of infection remain unclear. To improve on current drug therapies or vaccines, further studies are necessary to decipher the mechanisms behind filaria-driven immune responses and pathology development, and thus the rodent model of Litomosoides sigmodontis can be used to unravel host-filaria interactions. Interestingly, BALB/c mice develop a patent state (release of microfilariae, the transmission life-stage, into the periphery) when exposed to L. sigmodontis. Thus, using this model, we determined levels of host inflammation and pathology development during a L. sigmodontis infection in vivo for the first known time. Our study reveals that after 30 days p.i., inflammation and pathology began to develop in infected wild type BALB/c mice between the lung and diaphragm, close to the site of infection – the thoracic cavity. Interestingly, infected IL-4Rα/IL-5−/− BALB/c mice had accentuated inflammation of the pleural lung and pleural diaphragm, and higher parasite burdens. Corresponding to the pleural inflammation, levels of IP-10, MIP-1α, MIP-1β, MIP-2 and RANTES were significantly elevated in the thoracic cavity fluid of infected IL-4Rα/IL-5−/− mice compared with wild type controls. Moreover, upon L. sigmodontis antigen stimulation, IFN-γ and IL-17A secretions by cells isolated from draining lymph nodes of IL-4Rα/IL-5−/− mice were significantly elevated, whereas secretion of IL-5, IL-13 and IL-10 was reduced. Elevated filaria-specific IFN-γ secretion was also observed in spleen-derived CD4+ T cell co-cultures from IL-4Rα/IL-5−/− mice. In summary, this study unravels the essential role of IL-4/IL-5 signalling in controlling immunity against filarial infections and demonstrates the requirement of this pathway for the host to control ensuing pathology and inflammation.
2016-02-17 | Identification and Validation of Loa loa Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays.
Immunoassays are currently needed to quantify Loa loa microfilariae (mf). To address this need, we have conducted proteomic and bioinformatic analyses of proteins present in the urine of a Loa mf-infected patient and used this information to identify putative biomarkers produced by L. loa mf. In total, 70 of the 15,444 described putative L. loa proteins were identified. Of these 70, 18 were L. loa mf specific, and 2 of these 18 (LOAG_16297 and LOAG_17808) were biologically immunogenic. We developed novel reverse luciferase immunoprecipitation system (LIPS) immunoassays to quantify these 2 proteins in individual plasma samples. Levels of these 2 proteins in microfilaremic L. loa-infected patients were positively correlated to mf densities in the corresponding blood samples (r = 0.71 and P < 0.0001 for LOAG_16297 and r = 0.61 and P = 0.0002 for LOAG_17808). For LOAG_16297, the levels in plasma were significantly higher in Loa-infected (geometric mean [GM], 0.045 µg/ml) than in uninfected (P < 0.0001), Wuchereria bancrofti-infected (P = 0.0005), and Onchocerca volvulus-infected (P < 0.0001) individuals, whereas for LOAG_17808 protein, they were not significantly different between Loa-infected (GM, 0.123 µg/ml) and uninfected (P = 0.06) and W. bancrofti-infected (P = 0.32) individuals. Moreover, only LOAG_16297 showed clear discriminative ability between L. loa and the other potentially coendemic filariae. Indeed, the specificity of the LOAG_16297 reverse LIPS assay was 96% (with a sensitivity of 77%). Thus, LOAG_16297 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of L. loa mf densities.Loa loa, the causative agent of loiasis, is a parasitic nematode transmitted to humans by the tabanid Chrysops fly. Some individuals infected with L. loa microfilariae (mf) in high densities are known to experience post-ivermectin severe adverse events (SAEs [encephalopathy, coma, or death]). Thus, ivermectin-based mass drug administration (MDA) programs for onchocerciasis and for lymphatic filariasis control have been interrupted in parts of Africa where these filarial infections coexist with L. loa. To allow for implementation of MDA for onchocerciasis and lymphatic filariasis, tools that can accurately identify people at risk of developing post-ivermectin SAEs are needed. Our study, using host-based proteomics in combination with novel immunoassays, identified a single Loa-specific antigen (LOAG_16297) that can be used as a biomarker for the prediction of L. loa mf levels in the blood of infected patients. Therefore, the use of such biomarker could be important in the point-of-care assessment of L. loa mf densities.
gene therapies
2024-08-26 | Variability of Loa loa microfilarial counts in successive blood smears and its potential implication in drug-related serious adverse events
Background: The standard method to diagnose Loa loa infection and quantify microfilarial density (MFD) is the microscopic examination of calibrated thick blood smears (TBS). In 1950, it was noticed that successive L. loa MFDs from a single capillary puncture could exhibit up to 20% variation. Although loiasis treatment allocation is based on MFD to prevent serious adverse events (SAE), data on this variability are scarce. There are also no guidelines supporting the collection and analysis of one or two TBS. Methods: We assessed the variability of two successive L. loa MFDs (MFD1 and MFD2), collected from 255 patients. We analyzed the influence of sex, age, weight, heart rate, arterial pressure, body temperature, and sampling time on MFD variability, as well as variability’s impact on MFD thresholds relevant to loiasis treatment protocols. Results: 63% (1145/1826) of TBS pairs exhibited an MFD2 increase, while only 37% (681/1826) exhibited a decrease. MFD2 were on average 28% higher than MFD1. These variations drove a total of 333 (17.4%) MFD class changes according to loiasis treatment protocol, including 210 (11.3%) class increases. TBS sampled from subjects with lower MFD (1-1 000 mf/mL), lower MAP (55-80 mmHg) and sampled at an earlier hour (10:00-10:59 am) were more subject to MFD2 variability in a multivariate analysis. The MFD relative change was not constant over time for a given person. Conclusions: We observed a trend towards an increase in MFD2 with an important variability between samples that may impact loiasis treatment allocation. We suggest that systematically sampling at least two successive TBSs might allow better MFD assessments to prevent posttreatment SAEs. Further studies are needed to verify this variability in larger samples as well as confirm the potential explanatory variables identified.
2021-07-19 | Genome editing as control tool for filarial infections.
Human filarial infections are vector-borne nematode infections, which include lymphatic filariasis, onchocerciasis, loiasis, and mansonella filariasis. With a high prevalence in developing countries, filarial infections are responsible for some of the most debilitating morbidities and a vicious cycle of poverty and disease. Global initiatives set to eradicate these infections include community mass treatments, vector control, provision of care for morbidity, and search for vaccines. However, there are growing challenges associated with mass treatments, vector control, and antifilarial vaccine development. With the emergence of genome editing tools and successful applications in other infectious diseases, the integration of genetic editing techniques in future control strategies for filarial infections would offer the best option for eliminating filarial infections. In this review, we briefly discuss the mechanisms of the three main genetic editing techniques and explore the potential applications of these powerful tools to control filarial infections.
proteins
2026-07-13 |
Literature search strategy.
Background Loiasis is a filarial disease caused by Loa loa, endemic to Central and West Africa. Cases are observed in migrants and occasionally travellers. Its diagnosis may be difficult due to the unspecific clinical picture and the high percentage of people who do not have microscopically detectable circulating microfilariae. We performed a landscape analysis of the laboratory-based diagnostic techniques available for loiasis and of their estimated sensitivity and specificity. Methods We performed a systematic review of cross-sectional, cohort, case-control, diagnostic accuracy, and clinical trial studies published in PubMed, EMBASE, and CENTRAL (searched on March 26th 2025), applying diagnostic assays for human loiasis. When possible, a proportional meta-analysis was performed by estimating sensitivity and specificity separately against eligible reference tests (direct assays or presence of “eyeworm” or their composite or latent class analysis) for each technique category (microscopy of thick smears or concentrated blood, PCR-based or LAMP-based molecular assay, and ELISA-based or rapid -RDT- serological assays). A random-effects model with the DerSimonian-Laird approach was applied. Study quality was evaluated using the Newcastle–Ottawa Scale. Results Ninety-nine publications were included in the landscape analysis and 27 were also eligible for performance assessment. Microscopy was applied in 91/99 (91.9%) studies, PCR-based techniques in 29/99 (29.3%), LAMP in 4/99 (4.0%), and serological assays in 19/99 (19.2%). Within techniques categories, characteristics were highly heterogeneous. Sensitivities ranged from 75.0-98.3% for thick blood smears, 48.2-99.9% for blood concentration techniques, 80.6-98.4% for PCR-based techniques, 88.5-98.1% for LAMP-based techniques, 81.9-90.5% for ELISA seroassays, and 43.6-88.0% for RDTs. Cross-reactivity of L. loa-specific seroassays with M. perstans and other parasitoses was limited (<10%). Conclusions Assays for the diagnosis of loiasis are not standardized. ELISA-based serology and possibly PCR-based methods may be appropriate for screening. Microscopy must be performed even in case of negativity on screening when epidemiological or clinical factors suggestive of loiasis are present to plan safe treatment.
2026-02-23 | The economic burden of loiasis: A comprehensive cost-of-illness analysis of regionally representative, individual-level data from rural Gabon.
Loiasis is a vector-borne filarial infection endemic to parts of sub-Saharan Africa. It disproportionally affects economically disadvantaged communities in rural, forested regions. To better understand the economic burden of loiasis, we conducted a comprehensive cost-of-illness study in an endemic region of Gabon, with the aim of quantifying the financial costs incurred by individuals infected with the disease from a societal perspective. We conducted a cross-sectional survey in 2023 in rural Gabon. Study participants took part in diagnostic testing for loiasis and were interviewed based on a standardized questionnaire covering a wide range of medical and non-medical costs. Participants reporting eye worm migration or harboring loiasis microfilariae were defined as loiasis positive. Various cost estimates were derived by creating a synthetic control group by means of entropy-balancing and then applying generalized linear models (GLM) for the study region. We show that the average annual costs directly attributable to loiasis amount to 39.94 USD per individual per year. Average cost estimates are primarily driven by indirect costs and direct non-medical costs. We further show that in the rarer cases that individuals seek treatment at formal or informal healthcare providers for loiasis-specific symptoms, costs from the patient's perspective can be excessively high and amount to about 43 percent of the average monthly per capita income in the study region.
2026-02-20 | Design and analysis of randomized clinical trials for onchocerciasis, loiasis and mansonellosis: A systematic review.
The design and analysis of randomized clinical trials (RCTs) in filarial diseases such as onchocerciasis, loiasis, and mansonellosis pose unique statistical challenges, including skewed endpoints and limited sample sizes. This systematic review summarizes design and analysis approaches of RCTs conducted in these diseases with a focus on the statistical methodology. A systematic search was conducted in PubMed and four trial registries to identify RCTs investigating treatments for onchocerciasis, loiasis, and mansonellosis published or registered between 2000 and 2024. We excluded studies focusing on new methods or pharmacokinetics, short reports, and Phase I trials. Forty-four studies met the inclusion/exclusion criteria (23 for onchocerciasis, 16 for loiasis, and 5 for mansonellosis), information was retrieved from the registries, the manuscripts and/or the study protocol. As primary efficacy endpoints, for onchocerciasis studies qualitative endpoints dominated, while quantitative endpoints were more frequently observed for loiasis and mansonellosis. The most frequently reported hypothesis tests for the primary endpoint were the Mann-Whitney U and the chi-squared tests. We found considerable heterogeneity between trials - not only in study-specific parameters such as the number of arms, type of blinding or control group - but also in design parameters or attributes that could be standardized within each disease across studies with similar objectives, such as the primary endpoint, length of follow-up, the analysis method and the primary analysis population. Several trials were well-planned with detailed information provided in either the manuscript or the registry. However, for some trials, information was sparse or incomplete, indicating a need for more structured and transparent reporting. Adopting established frameworks such as CONSORT and ICH E9 (R1) estimand approach would enhance transparency and better align trial objectives, analyses, and reported conclusions.
2025-11-27 | Female Loa loa worm polyinfection in human hosts.
Loiasis is widespread in Central Africa. Some acute symptoms are associated with high Loa loa microfilaraemia, but the relation between the latter and the adult worm burden infecting an individual with loiasis is still unclear. This study aims to determine whether polyinfection by several reproductive female worms could be assessed using genetic variation in the mitochondrial genome of microfilariae. Microfilariae were collected from the individuals' blood. An optimization of the DNA extraction method that provides enough genetic material and minimization of human host contamination was the first step of the study. Extracted DNA was sequenced using the Illumina platform. Genetic variation in the mitochondrial genome was assessed by identifying polymorphic Single Nucleotide Polymorphisms (SNPs) and estimating the number of haplotypes. Dedicated DNA extraction kits yielded more DNA extracted (mean: 530 ng; SD = 211) from dried blood smears than the in-house chloroform-isoamyl method (mean: 102.5 ng; SD = 118). Filtering the slide elution and venous blood with 5 µm pore size microfilters improved parasite DNA mapping rates (54.64-79.65%). Analysis of polymorphism in the microfilariae mitochondrial genome from three individuals revealed 50, 207 and 332 polymorphic SNPs, respectively. A total of 7 to 20 mitochondrial DNA haplotypes were identified, representing the minimum number of fertile female worms. This study presents the first approach to estimating the L. loa female worm burden and highlights female parent polyinfection in individuals with loiasis.
2024-10-25 | A rare case of loiasis clinically manifested 9 years after the last epidemiological exposure
A 37-year-old Cameroonian patient, residing in Italy for the past nine years without returning to his home country, showed up at the Emergency Department of Cittadella Hospital with acute hyperemia of the conjunctival tissue, tearing, itching, headache in the right hemisphere and transient edema at ankles and wrists. A foreign body suspected to be a parasite was detected while migrating through his right eye. However, primary identification of the worm was hindered due to partial damage during surgical removal. The laboratory team based on the patient’s history and clinical manifestation, suspected blood infection due to microfi- lariae species and collected a blood sample at 12 pm. Microfilariae of Loa loa were identified in May Grunwald- Giemsa (MGG) staining (count of 270 microfilariae/mL) from a K2-EDTA blood sample. Identification of the microfilariae was based on morphological features, patient country of origin, and periodicity of the life cycle of the parasite.
small molecules
2026-04-25 | Clinical characteristics and treatments of imported loiasis patients with microfilaraemia diagnosed in France, 2000-2022.
Loiasis has been associated with increased morbidity and mortality, particularly in cases of high microfilarial density. Treatment depends on initial microfilaraemia (Mf) and relies on ivermectin (IVM), diethylcarbamazine (DEC) or albendazole (ALB), all associated with serious adverse events. Our objective was to describe the clinical characteristics, management and outcomes of patients diagnosed with loiasis and Mf in France. We conducted a multicenter retrospective study including patients with loiasis and Mf diagnosed and treated in France between 2000 and 2022, with at least one follow-up evaluation. We collected clinical and biological data, including Mf kinetics, for each treatment episode. A total of 150 patients (181 treatment episodes) were included across 27 centers. Median age was 35 years, and most patients presented symptoms (75.3%). Median Mf was 500 mf/ml; for 74% of episodes, baseline Mf below 2000 mf/ml, while 8% had baseline Mf above 8000 mf/ml. Twelve different treatment schemes were identified, the most common being a single dose of IVM (39%). Adverse events occurred in 12% of episodes, including one fatal event. On last follow-up visit, 9.3% of patients still experienced symptoms, 24.7% exhibited persistent Mf, and 19.3% had persistent blood eosinophilia, patients treated with stand-alone IVM experienced worse outcomes (18%, 72% and 39%, respectively). In France, loiasis treatment is inconsistent and frequently relies on inadequate options, including IVM monotherapy, which lacks therapeutic efficacy, and carries safety concerns. Our findings highlight real-world practices and indicates that better training is needed for practitioners treating patients with loiasis.
2026-01-20 | Assessment of the efficacy and safety of two albendazole regimens for the treatment of hypermicrofilaraemic loiasis in adults in Woleu-Ntem Province, Gabon: A phase IIb single-blind randomised controlled trial.
Loa (L.) loa hypermicrofilaraemia (≥ 8,000 mf/mL) increases the risk of severe adverse events during mass ivermectin administration for onchocerciasis control. Albendazole has been proposed as a potential alternative for reducing microfilaraemia prior to ivermectin administration. This prospective study was conducted in northern Gabon from November 2021 to April 2022. Individuals infected with L. loa were screened and allocated to three groups: two treatment arms receiving 400 mg or 800 mg of albendazole daily for 30 days among hypermicrofilaraemic participants, and a group with microfilaraemia < 8,000 mf/mL. Clinical symptoms and parasitological data were collected on Days 0, 2, 7, 14, and 30. A total of 70 participants were enrolled: 16 in the 400 mg group, 16 in the 800 mg group, and 38 in the group with microfilaraemia below 8,000 mf/mL. Itching was the most frequently reported adverse event. By Day 30, no participants in the group with microfilaraemia below 8,000 mf/mL presented with clinical symptoms. Microfilaraemia significantly decreased in all groups (p < 0.01). After 30 days, over 70.0% of patients treated with albendazole had microfilaraemia < 8,000 mf/mL. There was no significant difference in efficacy between the two albendazole regimens. Daily administration of 400 mg albendazole for 30 days effectively reduces microfilarial loads in patients with L. loa hypermicrofilaraemia and is well tolerated and safe. This pre-treatment regimen may reduce the risk of adverse events associated with ivermectin administration. Further research is needed to evaluate the long-term persistence of microfilarial suppression.
2026-01-07 | Ocular filariasis manifesting as an orbital cellulitis and conjunctival nodule: a case report.
Filariasis is a parasitic infection that mostly involves the skin and ocular surface, although all layers of the eye and orbit can be affected. We report a case of a 42-year-old woman with Loa loa infection manifesting as a sequential bilateral forehead Calabar swelling, severe orbital cellulitis and thereafter mimicking a conjunctival tumor. Anterior segment optical coherence tomography helped to differentiate between a neoplasm and the filarial worm and show typical features such as longitudinal and cross-sections of the parasite. The worm was surgically removed and microbiologists confirmed the diagnosis of a subconjunctival Loa loa infection. The patient was successfully treated with diethylcarbamazine (DEC) and ivermectin without adverse events. Parasitic orbital cellulitis is rarely reported and this case highlights the importance of considering loiasis in unexplained orbital cellulitis in patients with hypereosinophilia and a history of residence in endemic areas.
2025-12-11 | Loa loa Encephalopathy Following Treatment With Benzimidazole Derivatives: A Systematic Review.
Loiasis, a filarial vector-borne disease, is common in rural West and Central Africa. Benzimidazole derivatives albendazole and mebendazole are recommended as alternative treatments due to their perceived safety in hypermicrofilaremic patients. There is growing evidence that benzimidazoles might also lead to Loa loa-associated encephalopathy. In this systematic review we analyzed all available evidence of benzimidazole-associated encephalopathy. Literature was systematically searched in PubMed, Google Scholar, and WHO-VigiBase®, including conference abstracts and consultation of experts. Six potential cases of benzimidazole-associated encephalopathy, including 2 fatalities, were identified among microfilaremic loiasis patients. Due to the limited global use of prolonged benzimidazole regimens for loiasis, the number of encephalopathy cases identified raises significant safety concerns, challenging the rationale of their use. Further research on mechanisms and safer alternative regimens is urgently needed.
2025-12-11 | Activity of antifilarial drugs on microfilaremia in the treatment of loiasis: a systematic review.
Loiasis, caused by the nematode/filaria Loa loa, presents a major health burden in Central and West Africa. Despite the growing recognition of loiasis' medical significance, current antifilarial drugs remain inadequate in terms of efficacy and safety, particularly for individuals with hypermicrofilaremia. This systematic review aims to evaluate the efficacy of antifilarial treatment regimens for reducing L. loa microfilaremia and provide guidance on treatment strategies. A systematic review was conducted to evaluate the efficacy of antifilarial treatment regimens on reducing L. loa microfilaremia. Data on the percentage reduction of microfilaremia from baseline to nadir were extracted for each treatment regimen. A total of 27 studies were included in the review, with treatment regimens involving albendazole (ALB), mebendazole (MBZ), ivermectin (IVM), diethylcarbamazine (DEC), levamisole, imatinib, and moxidectin, among others. ALB and MBZ showed dose- and duration-dependent efficacy, with extended treatment leading to up to a 98-100% microfilaremia reduction. IVM showed a dose-dependent effect, with single doses of 200-400 µg/kg reducing microfilaremia by 88-92%. DEC exhibited high efficacy, achieving up to a 100% microfilaremia reduction. Antifilarial drug efficacy against L. loa microfilaremia varies by dosage and treatment duration, with IVM and DEC demonstrating rapid, high efficacy but presenting safety concerns for hypermicrofilaremic individuals. ALB and MBZ show efficacy with extended treatment but are slower acting. Further research is needed to optimize treatment regimens and assess clinical outcomes beyond microfilaremia reduction.
antibodies
2022-10-14 | The Host–Helminth Interface as a Rich Resource for Novel Drug Targets
The evolutionary arms races underlying all host–helminth associations have resulted in intricate negotiations enabling a successful infection. At the host–parasite interface, a continuous dialogue takes place, where a plethora of molecules are exchanged, with crucial consequences on the outcome of the infection. This molecular exchange appears to be a rich source of potential therapeutic targets. Here, we present what recent research has brought to light on this topic for helminths, focusing on filarial nematodes.
2020-09-07 | A Randomized, Placebo-controlled, Double-blind Pilot Study of Single-dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa loa Infection.
Diethylcarbamazine citrate (DEC) treatment of loiasis is complicated by adverse reactions that are correlated with the number of circulating microfilariae (mf). The cause of these reactions is unknown, but they are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation.To explore the role of IL-5 driven eosinophilia in post-DEC reactions, 8 adults with confirmed loiasis and <5000 mf/mL blood were enrolled in a randomized, double-blind, placebo-controlled trial of the humanized anti-IL-5 antibody, reslizumab, (1.0 mg/kg IV) administered 3 to 7 days prior to initiation of DEC treatment (9 mg/kg/day for 21 days). The primary endpoint was the reduction in absolute eosinophil count (AEC) during the first week of DEC treatment.Baseline characteristics were comparable between the two groups. Single dose reslizumab lowered the AEC by 77% prior to initiation of DEC therapy (vs. 12% in the placebo group, P < .05). More importantly, AEC remained below baseline in the first week of DEC treatment in all subjects who received reslizumab and in none of the placebo subjects. Mf clearance occurred within 2 days of initiation of DEC in all 7 mf-positive subjects. Mild to moderate adverse events were seen in all 8 subjects and were not significantly different between the groups.In summary, although reslizumab was able to blunt peripheral eosinophilia post-DEC treatment in subjects with loiasis and had no effect on microfilarial clearance, the reduction in AEC appeared to have been insufficient to prevent post-treatment AEs.
2016-09-01 | A diagnostic challenge: Eosinophilia of unknown etiology
Approximately 100 million people suffer from filarial diseases including lymphatic filariasis (elephantiasis), onchocerciasis (river blindness) and loiasis. These diseases are amongst the most devastating of the neglected tropical diseases in terms of social and economic impact. Moreover, many infection-induced immune mechanisms in the host, their relationship to disease-related symptoms and the development of pathology within the site of infection remain unclear. To improve on current drug therapies or vaccines, further studies are necessary to decipher the mechanisms behind filaria-driven immune responses and pathology development, and thus the rodent model of Litomosoides sigmodontis can be used to unravel host-filaria interactions. Interestingly, BALB/c mice develop a patent state (release of microfilariae, the transmission life-stage, into the periphery) when exposed to L. sigmodontis. Thus, using this model, we determined levels of host inflammation and pathology development during a L. sigmodontis infection in vivo for the first known time. Our study reveals that after 30 days p.i., inflammation and pathology began to develop in infected wild type BALB/c mice between the lung and diaphragm, close to the site of infection – the thoracic cavity. Interestingly, infected IL-4Rα/IL-5−/− BALB/c mice had accentuated inflammation of the pleural lung and pleural diaphragm, and higher parasite burdens. Corresponding to the pleural inflammation, levels of IP-10, MIP-1α, MIP-1β, MIP-2 and RANTES were significantly elevated in the thoracic cavity fluid of infected IL-4Rα/IL-5−/− mice compared with wild type controls. Moreover, upon L. sigmodontis antigen stimulation, IFN-γ and IL-17A secretions by cells isolated from draining lymph nodes of IL-4Rα/IL-5−/− mice were significantly elevated, whereas secretion of IL-5, IL-13 and IL-10 was reduced. Elevated filaria-specific IFN-γ secretion was also observed in spleen-derived CD4+ T cell co-cultures from IL-4Rα/IL-5−/− mice. In summary, this study unravels the essential role of IL-4/IL-5 signalling in controlling immunity against filarial infections and demonstrates the requirement of this pathway for the host to control ensuing pathology and inflammation.
2016-02-17 | Identification and Validation of Loa loa Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays.
Immunoassays are currently needed to quantify Loa loa microfilariae (mf). To address this need, we have conducted proteomic and bioinformatic analyses of proteins present in the urine of a Loa mf-infected patient and used this information to identify putative biomarkers produced by L. loa mf. In total, 70 of the 15,444 described putative L. loa proteins were identified. Of these 70, 18 were L. loa mf specific, and 2 of these 18 (LOAG_16297 and LOAG_17808) were biologically immunogenic. We developed novel reverse luciferase immunoprecipitation system (LIPS) immunoassays to quantify these 2 proteins in individual plasma samples. Levels of these 2 proteins in microfilaremic L. loa-infected patients were positively correlated to mf densities in the corresponding blood samples (r = 0.71 and P < 0.0001 for LOAG_16297 and r = 0.61 and P = 0.0002 for LOAG_17808). For LOAG_16297, the levels in plasma were significantly higher in Loa-infected (geometric mean [GM], 0.045 µg/ml) than in uninfected (P < 0.0001), Wuchereria bancrofti-infected (P = 0.0005), and Onchocerca volvulus-infected (P < 0.0001) individuals, whereas for LOAG_17808 protein, they were not significantly different between Loa-infected (GM, 0.123 µg/ml) and uninfected (P = 0.06) and W. bancrofti-infected (P = 0.32) individuals. Moreover, only LOAG_16297 showed clear discriminative ability between L. loa and the other potentially coendemic filariae. Indeed, the specificity of the LOAG_16297 reverse LIPS assay was 96% (with a sensitivity of 77%). Thus, LOAG_16297 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of L. loa mf densities.Loa loa, the causative agent of loiasis, is a parasitic nematode transmitted to humans by the tabanid Chrysops fly. Some individuals infected with L. loa microfilariae (mf) in high densities are known to experience post-ivermectin severe adverse events (SAEs [encephalopathy, coma, or death]). Thus, ivermectin-based mass drug administration (MDA) programs for onchocerciasis and for lymphatic filariasis control have been interrupted in parts of Africa where these filarial infections coexist with L. loa. To allow for implementation of MDA for onchocerciasis and lymphatic filariasis, tools that can accurately identify people at risk of developing post-ivermectin SAEs are needed. Our study, using host-based proteomics in combination with novel immunoassays, identified a single Loa-specific antigen (LOAG_16297) that can be used as a biomarker for the prediction of L. loa mf levels in the blood of infected patients. Therefore, the use of such biomarker could be important in the point-of-care assessment of L. loa mf densities.
gene therapies
2024-08-26 | Variability of Loa loa microfilarial counts in successive blood smears and its potential implication in drug-related serious adverse events
Background: The standard method to diagnose Loa loa infection and quantify microfilarial density (MFD) is the microscopic examination of calibrated thick blood smears (TBS). In 1950, it was noticed that successive L. loa MFDs from a single capillary puncture could exhibit up to 20% variation. Although loiasis treatment allocation is based on MFD to prevent serious adverse events (SAE), data on this variability are scarce. There are also no guidelines supporting the collection and analysis of one or two TBS. Methods: We assessed the variability of two successive L. loa MFDs (MFD1 and MFD2), collected from 255 patients. We analyzed the influence of sex, age, weight, heart rate, arterial pressure, body temperature, and sampling time on MFD variability, as well as variability’s impact on MFD thresholds relevant to loiasis treatment protocols. Results: 63% (1145/1826) of TBS pairs exhibited an MFD2 increase, while only 37% (681/1826) exhibited a decrease. MFD2 were on average 28% higher than MFD1. These variations drove a total of 333 (17.4%) MFD class changes according to loiasis treatment protocol, including 210 (11.3%) class increases. TBS sampled from subjects with lower MFD (1-1 000 mf/mL), lower MAP (55-80 mmHg) and sampled at an earlier hour (10:00-10:59 am) were more subject to MFD2 variability in a multivariate analysis. The MFD relative change was not constant over time for a given person. Conclusions: We observed a trend towards an increase in MFD2 with an important variability between samples that may impact loiasis treatment allocation. We suggest that systematically sampling at least two successive TBSs might allow better MFD assessments to prevent posttreatment SAEs. Further studies are needed to verify this variability in larger samples as well as confirm the potential explanatory variables identified.
2021-07-19 | Genome editing as control tool for filarial infections.
Human filarial infections are vector-borne nematode infections, which include lymphatic filariasis, onchocerciasis, loiasis, and mansonella filariasis. With a high prevalence in developing countries, filarial infections are responsible for some of the most debilitating morbidities and a vicious cycle of poverty and disease. Global initiatives set to eradicate these infections include community mass treatments, vector control, provision of care for morbidity, and search for vaccines. However, there are growing challenges associated with mass treatments, vector control, and antifilarial vaccine development. With the emergence of genome editing tools and successful applications in other infectious diseases, the integration of genetic editing techniques in future control strategies for filarial infections would offer the best option for eliminating filarial infections. In this review, we briefly discuss the mechanisms of the three main genetic editing techniques and explore the potential applications of these powerful tools to control filarial infections.
proteins
2026-07-13 |
Literature search strategy.
Background Loiasis is a filarial disease caused by Loa loa, endemic to Central and West Africa. Cases are observed in migrants and occasionally travellers. Its diagnosis may be difficult due to the unspecific clinical picture and the high percentage of people who do not have microscopically detectable circulating microfilariae. We performed a landscape analysis of the laboratory-based diagnostic techniques available for loiasis and of their estimated sensitivity and specificity. Methods We performed a systematic review of cross-sectional, cohort, case-control, diagnostic accuracy, and clinical trial studies published in PubMed, EMBASE, and CENTRAL (searched on March 26th 2025), applying diagnostic assays for human loiasis. When possible, a proportional meta-analysis was performed by estimating sensitivity and specificity separately against eligible reference tests (direct assays or presence of “eyeworm” or their composite or latent class analysis) for each technique category (microscopy of thick smears or concentrated blood, PCR-based or LAMP-based molecular assay, and ELISA-based or rapid -RDT- serological assays). A random-effects model with the DerSimonian-Laird approach was applied. Study quality was evaluated using the Newcastle–Ottawa Scale. Results Ninety-nine publications were included in the landscape analysis and 27 were also eligible for performance assessment. Microscopy was applied in 91/99 (91.9%) studies, PCR-based techniques in 29/99 (29.3%), LAMP in 4/99 (4.0%), and serological assays in 19/99 (19.2%). Within techniques categories, characteristics were highly heterogeneous. Sensitivities ranged from 75.0-98.3% for thick blood smears, 48.2-99.9% for blood concentration techniques, 80.6-98.4% for PCR-based techniques, 88.5-98.1% for LAMP-based techniques, 81.9-90.5% for ELISA seroassays, and 43.6-88.0% for RDTs. Cross-reactivity of L. loa-specific seroassays with M. perstans and other parasitoses was limited (<10%). Conclusions Assays for the diagnosis of loiasis are not standardized. ELISA-based serology and possibly PCR-based methods may be appropriate for screening. Microscopy must be performed even in case of negativity on screening when epidemiological or clinical factors suggestive of loiasis are present to plan safe treatment.
2026-02-23 | The economic burden of loiasis: A comprehensive cost-of-illness analysis of regionally representative, individual-level data from rural Gabon.
Loiasis is a vector-borne filarial infection endemic to parts of sub-Saharan Africa. It disproportionally affects economically disadvantaged communities in rural, forested regions. To better understand the economic burden of loiasis, we conducted a comprehensive cost-of-illness study in an endemic region of Gabon, with the aim of quantifying the financial costs incurred by individuals infected with the disease from a societal perspective. We conducted a cross-sectional survey in 2023 in rural Gabon. Study participants took part in diagnostic testing for loiasis and were interviewed based on a standardized questionnaire covering a wide range of medical and non-medical costs. Participants reporting eye worm migration or harboring loiasis microfilariae were defined as loiasis positive. Various cost estimates were derived by creating a synthetic control group by means of entropy-balancing and then applying generalized linear models (GLM) for the study region. We show that the average annual costs directly attributable to loiasis amount to 39.94 USD per individual per year. Average cost estimates are primarily driven by indirect costs and direct non-medical costs. We further show that in the rarer cases that individuals seek treatment at formal or informal healthcare providers for loiasis-specific symptoms, costs from the patient's perspective can be excessively high and amount to about 43 percent of the average monthly per capita income in the study region.
2026-02-20 | Design and analysis of randomized clinical trials for onchocerciasis, loiasis and mansonellosis: A systematic review.
The design and analysis of randomized clinical trials (RCTs) in filarial diseases such as onchocerciasis, loiasis, and mansonellosis pose unique statistical challenges, including skewed endpoints and limited sample sizes. This systematic review summarizes design and analysis approaches of RCTs conducted in these diseases with a focus on the statistical methodology. A systematic search was conducted in PubMed and four trial registries to identify RCTs investigating treatments for onchocerciasis, loiasis, and mansonellosis published or registered between 2000 and 2024. We excluded studies focusing on new methods or pharmacokinetics, short reports, and Phase I trials. Forty-four studies met the inclusion/exclusion criteria (23 for onchocerciasis, 16 for loiasis, and 5 for mansonellosis), information was retrieved from the registries, the manuscripts and/or the study protocol. As primary efficacy endpoints, for onchocerciasis studies qualitative endpoints dominated, while quantitative endpoints were more frequently observed for loiasis and mansonellosis. The most frequently reported hypothesis tests for the primary endpoint were the Mann-Whitney U and the chi-squared tests. We found considerable heterogeneity between trials - not only in study-specific parameters such as the number of arms, type of blinding or control group - but also in design parameters or attributes that could be standardized within each disease across studies with similar objectives, such as the primary endpoint, length of follow-up, the analysis method and the primary analysis population. Several trials were well-planned with detailed information provided in either the manuscript or the registry. However, for some trials, information was sparse or incomplete, indicating a need for more structured and transparent reporting. Adopting established frameworks such as CONSORT and ICH E9 (R1) estimand approach would enhance transparency and better align trial objectives, analyses, and reported conclusions.
2025-11-27 | Female Loa loa worm polyinfection in human hosts.
Loiasis is widespread in Central Africa. Some acute symptoms are associated with high Loa loa microfilaraemia, but the relation between the latter and the adult worm burden infecting an individual with loiasis is still unclear. This study aims to determine whether polyinfection by several reproductive female worms could be assessed using genetic variation in the mitochondrial genome of microfilariae. Microfilariae were collected from the individuals' blood. An optimization of the DNA extraction method that provides enough genetic material and minimization of human host contamination was the first step of the study. Extracted DNA was sequenced using the Illumina platform. Genetic variation in the mitochondrial genome was assessed by identifying polymorphic Single Nucleotide Polymorphisms (SNPs) and estimating the number of haplotypes. Dedicated DNA extraction kits yielded more DNA extracted (mean: 530 ng; SD = 211) from dried blood smears than the in-house chloroform-isoamyl method (mean: 102.5 ng; SD = 118). Filtering the slide elution and venous blood with 5 µm pore size microfilters improved parasite DNA mapping rates (54.64-79.65%). Analysis of polymorphism in the microfilariae mitochondrial genome from three individuals revealed 50, 207 and 332 polymorphic SNPs, respectively. A total of 7 to 20 mitochondrial DNA haplotypes were identified, representing the minimum number of fertile female worms. This study presents the first approach to estimating the L. loa female worm burden and highlights female parent polyinfection in individuals with loiasis.
2024-10-25 | A rare case of loiasis clinically manifested 9 years after the last epidemiological exposure
A 37-year-old Cameroonian patient, residing in Italy for the past nine years without returning to his home country, showed up at the Emergency Department of Cittadella Hospital with acute hyperemia of the conjunctival tissue, tearing, itching, headache in the right hemisphere and transient edema at ankles and wrists. A foreign body suspected to be a parasite was detected while migrating through his right eye. However, primary identification of the worm was hindered due to partial damage during surgical removal. The laboratory team based on the patient’s history and clinical manifestation, suspected blood infection due to microfi- lariae species and collected a blood sample at 12 pm. Microfilariae of Loa loa were identified in May Grunwald- Giemsa (MGG) staining (count of 270 microfilariae/mL) from a K2-EDTA blood sample. Identification of the microfilariae was based on morphological features, patient country of origin, and periodicity of the life cycle of the parasite.
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