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Background: Endemic to Central Africa, loiasis, caused by the vector-borne worm Loa loa, affects approximately 10 million individuals. Clinical manifestations include transient angioedema (Calabar swellings), migration of the adult worm under the eye conjunctiva (eye worm) and less specific general symptoms. Loiasis presents a significant public health challenge because L. loa-infected individuals can develop serious adverse events after taking ivermectin, the drug used to combat onchocerciasis. In this context, alternative interventions and rigorous diagnostic approaches are needed. Diagnosing loiasis is challenging because its main clinical manifestations are sporadic and non-specific. The definitive diagnosis relies on identifying adult worms migrating beneath the conjunctiva, or microfilariae (pre-larvae) in blood smears. However, "occult loiasis" (infection without blood microfilariae) is frequent. Serological rapid antibody diagnostic tests (ARTs) can provide an alternative diagnostic method. We compared a novel ART simultaneously targeting onchocerciasis (IgG4 to Ov-16 and OvOC3261, test line 1) and loiasis (IgG4 to L1-SXP-1, test line 2), called IgG4-SXP-1 biplex test) to the already established Loa-ART (all IgG isotypes to Ll-SXP-1, called pan-IgG-SXP-1 test). Methodology: Blood samples underwent both ARTs, read qualitatively and semi-quantitatively. Additionally, blood smears, skin snips, Kato-Katz method for soil-transmitted helminthiases identification and eosinophilia measurements were performed. Questionnaires gathered demographic details and loiasis-related signs. ARTs performance was compared using specific loiasis-related signs and microfilaremia as references. Discordances between the two ARTs were investigated using logistic regression models. Principal findings: Out of 971 participants, 35.4% had L. loa microfilaremia, 71.9% had already experienced loiasis-related signs, 85.1% were positive in the pan-IgG-SXP-1 test and 79.4% were positive in the IgG4-SXP-1 biplex test. In the microfilariae-positive population, the sensitivity of the rapid tests was 87.4% for the pan-IgG-SXP-1 test and 88.6% for the prototype IgG4-SXP-1 biplex test. Sensitivity was similar for both ARTs when using eye worm or Calabar swelling as references, but diagnostic performance varied based on microfilaremia levels and occult loiasis. Overall, IgG4-SXP-1 biplex test demonstrated a sensitivity of 84.1% and specificity of 47.6% for loiasis compared to the pan-IgG-SXP-1 test, leading to a Kappa coefficient estimated at 0.27 ± 0.03 for the qualitative results of the 2 ARTs. In the group that tested positive with the Pan-IgG test but negative with the IgG4-specific test, there was a lower prevalence of STH infection (p = 0.008) and elevated eosinophilia (p<0.001) compared to the general tested population. Conclusion/Significance: The sensitivity of each test was good (84–85%) but the diagnostic agreement between the two ARTs was poor, suggesting that IgG and IgG4 antibody responses should be interpreted differently. The assessment of the innovative rapid diagnostic IgG4-SXP-1 biplex test, designed for onchocerciasis and loiasis, shows encouraging sensitivity but underlines the necessity for further in vitro assessment. Author summary: Loiasis, a disease caused by the parasite Loa loa impacting approximately 10 million people in Central Africa, causes transient angioedemas called Calabar swellings and eye worm episodes. Treatment is challenging, particularly in regions where onchocerciasis, another type of filariasis, is also prevalent. We tested a new kind of test that can detect both diseases at once and compared its performance with a previously available test for loiasis. We took blood samples from 971 people living in an area of Congo where loiasis is endemic. Out of the participants, 35.4% had L. loa pre-larvae in the blood–known as microfilariae, and 72.0% had experienced loiasis-related signs. The new test demonstrated promise in detecting the disease, albeit with some likelihood of false positives. Additionally, its performance varied according to the density of microfilariae in the blood. While the results exceeded expectations, further testing is essential to ensure its reliability. If validated, this test could prove instrumental in diagnosing both loiasis and onchocerciasis, offering a valuable tool for public health interventions in affected regions. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is an infectious neglected tropical disease caused by mosquito-borne nematodes such as Wuchereria bancrofti, Brugia malayi, and Brugia timori. Globally, LF affects 51 million people, with approximately 863 million at risk in 47 countries. In Kenya, filariasis is endemic along the entire coastal strip, and more recently, at the Kenya–Ugandan border. The World Health Organization (WHO) recommends mass drug administration to reduce disease transmission and morbidity. Monitoring the effectiveness of such interventions relies on robust surveillance, achieved through microscopic examination of microfilariae in nighttime blood, detection of circulating filarial antigens (CFA), and molecular xenomonitoring. We focused on molecular xenomonitoring along the Kenyan coast due to its noninvasive nature and the opportunity to identify new vectors. Methods: In 2022, mosquitoes were collected from Kilifi, Kwale, and Taita-Taveta counties located within the LF endemic region in Kenya. Subsequently, genomic deoxyribonucleic acid (gDNA) was extracted from these mosquitoes for speciation and analysis of Wuchereria bancrofti infection rates. The impact of sociodemographic and household attributes on infection rates was assessed using generalized estimating equations. Results: A total of 18,121 mosquitoes belonging to Culicinae (63.0%, n = 11,414) and Anophelinae (37.0%, n = 6707) subfamilies were collected. Morphological identification revealed that Anopheline mosquitoes were dominated by An. funestus (45.4%, n = 3045) and An. gambiae (42.8%, n = 2873). Wuchereria bancrofti infection rates were highest in Kilifi (35.4%; 95% CI 28.0–43.3%, n = 57/161) and lowest in Taita Taveta (5.3%; 95% CI 3.3–8.0%, n = 22/412). The major vectors incriminated are An. rivulorum, An. funestus sensu stricto, and An. arabiensis. Mosquitoes of the An. funestus complex were significantly associated with LF transmission (OR 18.0; 95% CI 1.80–180; p = 0.014). Additionally, a higher risk of transmission was observed outdoors (OR 1.74; 95% CI 1.08–2.82; p = 0.024) and in homesteads that owned livestock (OR 2.00; 95% CI 1.09–3.66; p = 0.025). Conclusions: In this study, we identified An. funestus s.l. sibling species, An. rivulorum and An. funestus s.s., as the primary vectors of lymphatic filariasis along the Kenyan coast. These findings also highlight that a significant portion of disease transmission potentially occurs outdoors where indoor-based vector control tools, including long-lasting insecticidal nets and indoor residual spray, may not be effective. Therefore, control measures targeting outdoor resting mosquitoes such as zooprophylaxis, larval source management, and attractive sugar baits may have potential for LF transmission reduction. [ABSTRACT FROM AUTHOR]

Background: Mapping, monitoring, and evaluation of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) rely on high-throughput diagnostics. While the WHO-recommended Filariasis Test Strip (FTS) is widely used to evaluate the programme, its use is limited by some technical and operational issues. We evaluated the performance characteristics of Q Filariasis Antigen Test (QFAT) compared to FTS for detecting Wuchereria bancrofti filarial antigen in the field. Methods: The QFAT and FTS kits were tested simultaneously for circulating filarial antigen (CFA) during an epidemiological monitoring survey (EMS) in two blocks of a filariasis endemic district in Karnataka, India, as a part of evaluation of the filariasis elimination programme with three drugs (Ivermectin, Diethylcarbamazine, and Albendazole-IDA). Blocks are considered as the evaluation unit as per the revised national guidelines. Two sentinel and one random site from each block with a sample size of 300 individuals aged ≥20 years were selected for the EMS. The field evaluation of the new kit was carried out in the four sentinel sites. Positive tests with either FTS or QFAT or both were tested for microfilaria (Mf) using night blood samples. The performance of the tests was compared in terms of sensitivity, specificity, and predictive values. The percentage agreement between the tests was verified using Cohen's kappa statistics (k), with a P value of less than 0.05 indicating statistical significance. Findings: A total of 1227 individuals were tested for CFA using both the QFAT and FTS tests. The QFAT test detected 299 positive individuals at the end of 10 minutes, while the FTS detected 310 positives. The QFAT showed high sensitivity (95.5%), specificity (99.7%), positive predictive value (99.0%), and negative predictive value (98.5%), and the results were in near perfect agreement with those of the FTS (k = 0.97, P <0.001) when the results were read at 10 minutes. There were 17 discordant results that were positive according to either one of the tests. Both antigen tests were positive for all 68 microfilaria-positive samples. None of the QFAT tests were invalid, while three FTS tests were invalid due to non-flow on the test pad. There was no cross-reactivity of the QFAT with Brugia malayi-positive samples (n = 5). The feedback from the technicians indicates that QFAT tests were easier to perform compared to FTS in the field. Conclusions: The Q filariasis antigen test is a promising tool for detecting the Wuchereria bancrofti antigen. The kits may be further validated for the review of Diagnostic Technical Advisory Group for Neglected Tropical Diseases (DTAG), to be recommended for the Global Programme to Eliminate Lymphatic Filariasis (GPELF). Author summary: Globally, lymphatic filariasis (LF) is targeted for elimination by 2030. Since its inception in 2000 until 2018, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has witnessed a 74% decline in people infected with LF. As we progress towards the elimination goal, more sensitive diagnostic tools are necessary for inclusion in the GPELF diagnostic portfolio. At present, the WHO recommended filariasis test strip (FTS) is extensively used to evaluate the LF elimination programme worldwide. However, FTS is documented to have certain drawbacks. As a part of a multicentric study, we evaluated the field performance of a new diagnostic kit that detects Wuchereria bancrofti filarial antigenemia. The new kit called the Q Filariasis Antigen Test (QFAT), field tested in an LF endemic area in India, had a sensitivity of 95.5% and a specificity of 99.7% compared to FTS, and both tests (FTS and QFAT) detected all W. bancrofti microfilaria-positive (100%) individuals. The Cohen's kappa of 0.97 suggested near-perfect agreement between the test results. The test was easy to perform and interpret in the field and required only 20 μL of capillary blood, and no invalid tests were reported. This study documented that the QFAT has comparable performance characteristics with the currently used FTS in field settings, suggesting it to be a promising diagnostic tool. The pooled analysis of performance characteristics from other geographic areas will enable a decision on its inclusion in the diagnostic portfolio of GPELF. [ABSTRACT FROM AUTHOR]

Background: Human onchocerciasis remains a public health problem in Ghana. Mass drug administration (MDA) with ivermectin (IVM) has reduced disease morbidity and prevalence, but the transmission of onchocerciasis remains ongoing in several endemic foci. We investigated parasite transmission in some endemic communities in Ghana that had received > 18 rounds of annual MDA with IVM and determined the species composition of black fly (Simulium damnosum) vectors in these areas. Methods: Adult female black flies were collected using human landing catches and identified as either forest or savanna species using morpho-taxonomic keys. The adult flies underwent dissection to determine their parity and detect any O. volvulus larvae, followed by the calculation of entomological indices. Simulium damnosum s.l. larvae were collected and preserved in freshly prepared Carnoy's fixative and were later used for cytotaxonomic studies. Results: A total of 9,983 adult flies were caught: 6,569 and 3,414 in the rainy and dry seasons respectively. Black fly biting activities over the study period showed bimodal or trimodal patterns. The highest monthly biting rate (MBR) of 10,578.75 bites/person/month was recorded in July in Beposo, while the highest monthly transmission potential of 100.69 infective bites/person/month was recorded in Asubende in August. Morphological analysis of 2,032 flies showed that 99.8% (2,028) of the flies were savanna species, with only 4 (0.2%) adult flies being of the forest species. Cytogenetic studies on 114 black fly larvae revealed three cytospecies (Simulium damnosum s.s., S. sirbanum and S. sanctipauli) in the study area. Conclusions: The present studies confirmed an ongoing transmission of onchocerciasis in the study communities except Abua-1. It also provides further information on biting behaviors and onchocerciasis transmission indices in the study communities. Further, our data confirmed the savanna species (S. damnosum s.s. and S. sirbanum) of the S.damnosum s.l. to be the major vectors of onchocerciasis in the study areas, with only an occasional influx of forest cytotypes. [ABSTRACT FROM AUTHOR]

Introduction: Epidemiological evidence suggests that Onchocerca volvulus is associated with epilepsy, although the exact pathophysiological mechanism is unknown. Mahenge is an endemic focus of onchocerciasis, with the longest-running ivermectin treatment intervention in Tanzania. We assessed the prevalence of onchocerciasis and epilepsy after 25 years of control using ivermectin. Methods: This was a population-based cross-sectional study in 34 villages in Mahenge in 2021. Community health workers conducted door-to-door household surveys to enumerate the population and screen for individuals suspected of epilepsy using a standardised questionnaire. Trained physicians confirmed epilepsy. Children aged 6–11 years were screened for onchocerciasis antibodies using the Ov16 rapid test. Villages were stratified into three altitude levels (low [<400], medium [400–950], and high [>950 meters above sea level]) as a proxy for rapids, which black flies favour for breeding sites. Incidence of epilepsy was estimated as a ratio of new cases in the year preceding the survey per 100,000 population. Results: 56,604 individuals (median age 20.2 years, 51.1% females) were surveyed. Onchocerciasis prevalence in children was 11.8% and was highest in villages at medium (21.7%) and lowest in low altitudes (3.2%), p<0.001. Self-reported use of ivermectin was 88.4%. Epilepsy prevalence was 21.1 (95%CI: 19.9–22.3) cases per 1000 persons and was highest in medium (29.5%) and lowest in the lowlands (12.7%). The odds ratio (OR) of having epilepsy was significantly higher in females (OR = 1.22, 95%CI: 1.08–1.38), middle altitudes (OR = 2.34 [95%CI: 2.04–2.68]), and in individuals positive for OV16 (OR = 1.98 [95%CI:1.57–2.50]). The incidence of epilepsy a year before the survey was 117 (95%CI: 99.7–160.4) cases per 100,000 person-years. Conclusion: Despite ivermectin use for 25 years, the prevalence of onchocerciasis and epilepsy remains high. It is crucial to strengthen bi-annual ivermectin treatment and initiate interventions targeting vectors to control onchocerciasis and epilepsy in the area. Author summary: Onchocerciasis is endemic in Mahenge, with epidemiological evidence that the parasite (Onchocerca volvulus) may be associated with epilepsy. The high burden of the disease in Mahenge led to the introduction of Community Directed Treatment with Ivermectin (CDTI) in 1997. Despite the long history of CDTI implementation in Mahenge, the persistent transmission of the parasite is still reported. A population-based cross-sectional study was conducted to establish the current prevalence of onchocerciasis and epilepsy 25 years after the start of the CDTI programme. The prevalence of epilepsy was 21.1 (95%CI: 19.9–22.3) cases per 1000 people. The incidence of epilepsy one year preceding the survey was 117 (95%CI: 99.7–160.4) per 100,000 person-years. Despite high self-reported coverage of ivermectin (88%), active onchocerciasis transmission was observed among children aged 6–11 years, and more than half of the individuals with epilepsy (54.1%) were serologically positive for onchocerciasis. The predictors for epilepsy were sex (female), age ≥ 10 years, being a resident of Mahenge for ≥20 years, especially in villages located at a medium altitude, and being onchocerciasis positive. Strengthening of processes to ensure bi-annual ivermectin treatment is recommended. [ABSTRACT FROM AUTHOR]

Background: Loiasis is a disease caused by the nematode Loa loa. Serious adverse events sometimes occur in people with heavy L. loa microfilaremia after ivermectin treatment. In regions of Central Africa where loiasis is endemic, this significantly impedes global elimination programs for lymphatic filariasis and onchocerciasis that use mass distribution of ivermectin. Improved diagnostic tests to identify individuals at increased risk of serious adverse events could facilitate efforts to eliminate lymphatic filariasis and onchocerciasis in this region. Methods and findings: We previously identified the L. loa protein Ll-Bhp-1 in loiasis patient sera. Here, we further characterize Ll-Bhp-1 and report development of an antigen capture ELISA to detect this antigen. This assay detected Ll-Bhp-1 in 74 of 116 (63.8%) loiasis patient sera. Ll-Bhp-1 levels were significantly correlated with L. loa microfilarial counts, and the sensitivity of the assay was highest for samples from people with high counts, (94% and 100% in people with ≥20,000 and ≥50,000 microfilaria per milliliter of blood, respectively). The antigen was not detected in 112 sera from people with other filarial infections, or in 34 control sera from the USA. Conclusions: This Ll-Bhp-1 antigen assay is specific for loiasis, and highly sensitive for identifying people with high L. loa microfilarial counts who are at increased risk for serious adverse events after ivermectin treatment. L. loa antigen detection has the potential to facilitate loiasis mapping efforts and programs to eliminate lymphatic filariasis and onchocerciasis in Central Africa. Author summary: Lymphatic filariasis and onchocerciasis are major neglected tropical diseases that have been targeted for elimination by the World Health Organization. Elimination campaigns for these infections using mass drug administration have had a huge impact in Africa. However, they face a major challenge in 11 countries in Central Africa where there is co-endemic loiasis, another filarial infection caused by the parasite Loa loa. The anti-filarial medication ivermectin that is used in elimination programs can cause serious and fatal adverse drug events in people with heavy loiasis infections, or high blood microfilarial counts. These programs would benefit from practical and affordable screening tests to detect people at high risk of adverse events from ivermectin. Furthermore, loiasis itself causes a variety of negative health outcomes and improved diagnostic tests would help control this infection. Here, we report the development of a sandwich immunoassay that detects the L. loa protein Ll-Bhp-1 in human serum samples. This assay is specific for L. loa infection and is highly sensitive in people with high microfilarial counts. Further work is needed to refine this prototype test and to determine whether antigen testing for loiasis can facilitate filarial eliminations efforts in Central Africa. [ABSTRACT FROM AUTHOR]

Background: Infection with the filarial nematode Loa loa, endemic in Central and Western Africa, has been associated with increased morbidity and mortality. A number of reports described the presence of spleen nodules, originating from degenerating microfilariae, in humans and animals infected with L. loa. The long-term consequences of this process on individuals chronically exposed to infection in terms of spleen function and possible link with excess mortality are unknown. The aim of this study was to evaluate the prevalence of focal spleen lesions, their evolution over time, and markers of spleen function, in individuals with L. loa infection living in highly endemic areas of Gabon. Methodology/principal findings: This was a cross-sectional study followed by a longitudinal study of the subset of individuals with spleen nodules. Two hundred sixteen participants from Ngounié and Moyen-Ogooué provinces of Gabon, reporting a history of eyeworm migration and/or Calabar swelling, were included. Participants were categorized into infected microfilaraemic with low (N = 74) and high (N = 10) microfilaraemia, and symptomatic amicrofilaraemic (N = 132), based on blood microscopy. Howell-Jolly bodies in erythrocytes, as indirect marker of spleen functional impairment, were within normal ranges. On ultrasound, no evident signs of spleen fibrosis or hypotrophy were observed. Multiple spleen hypoechoic centimetric macronodules were observed in 3/216 participants (1.4%), all with microfilaraemic L. loa infection (3.4% of microfilaraemics); macrondules disappeared at the 6-months follow-up examination in 2/3 individuals. Spleen hypoechoic micronodules, persisting at the 6-months follow-up, were detected in 3/216 participants (1.4%), who were all amicrofilaraemic. Conclusions/significance: Transitory spleen macronodules are present in a small but consistent proportion of individuals with microfilaraemic loiasis, appearing a rather benign phenomenon in terms of impact on spleen morphology and function. Their occurrence should be taken into consideration to avoid misdiagnosis and mistreatment. Prevalence and significance of spleen micronodular ultrasound patterns in the general population would be also worth evaluating. Author summary: Loa loa is a vector borne, filarial worm affecting an estimated 20 million people in Central and West Africa. Long considered a benign infection, more recently it has been associated with substantial morbidity and increased mortality in individuals with high L. loa microfilaraemia, prompted to reconsider the importance this infection and investigate the potential pathophysiological mechanisms. The spleen has a central role in the response to pathogens, including parasites; therefore, its dysfunction may lead to an increase in the risk and severity of infectious diseases, which might contribute to the observed excess mortality in hypermicrofilaremic loiasis. The presence of spleen centimetric nodules, originating from degradation of microfilariae, in humans and animals infected with L. loa, has been described, but the long-term consequences of this process on individuals chronically exposed to infection in terms of spleen function are unknown. In this study performed in individuals with L. loa infection living in highly endemic areas of Gabon, we found a prevalence of 3.4% spleen nodules in microfilaraemic participants, while no such lesions were observed in symptomatic amicrofilaraemic participants. Nodules were transitory and appeared to be a rather benign phenomenon in terms of impact on spleen morphology and function. [ABSTRACT FROM AUTHOR]

Background: Loiasis is a disease of relevance in endemic populations and there has been advocacy for its inclusion on the World Health Organization's neglected tropical diseases list. As loiasis-related healthcare-seeking behaviors and related costs are unknown, we aimed to evaluate these aspects in a population residing in an endemic region in Gabon. Methods: Data were collected during a community-based, cross-sectional study assessing the disease burden due to loiasis. Diagnostics for microfilaremia were performed and a history of eyeworm was obtained. In addition, a standardized questionnaire about type of healthcare resources and frequency of use, as well as respective associated costs was administered to each participant. Loiasis related healthcare-seeking behaviors were evaluated, and the associated monetary burden was estimated as a secondary outcome of the study. Findings: Individuals diagnosed with loiasis more frequently reported any healthcare-seeking (OR 1.52 (95%CI: 1.21–1.91)), self-medicating (OR 1.62 (1.26–2.08)), inability to work (OR 1.86 (1.47–2.35)), and consulting with traditional healers (logOdds 1.03 (0.52–1.53)), compared to loiasis negative individuals. The most frequently reported treatment for the eyeworm was traditional herbs. The estimated healthcare associated costs, per positive individual, was US-$ 58 (95% CI: 21–101) per year, which would correspond to 3.5% of the reported mean household income. Extrapolation to the rural population of Gabon (n = 204,000), resulted in an annual monetary burden estimate of US-$ 3,206,000 (1,150,000–5,577,000). Interpretation: Loiasis patients have demonstrated healthcare needs, often consulted traditional healers, and used traditional treatments for disease specific symptoms. Further, loiasis seems to be associated with substantial direct and indirect costs for individuals and thus may cause a relevant economic burden for endemic populations and economies of affected countries. Author summary: Loiasis has long been considered a negligible infection, however disease perception is changing as more data on significant disease-associated morbidity and mortality are being published. Still, many important aspects of the disease, such as the socioeconomic impact, are unknown. This study was part of a larger project on loiasis associated disease burden and aimed to evaluate healthcare seeking behaviors and estimate associated costs in individuals with loiasis living in a highly endemic region. We found that loiasis is associated with healthcare consultation, self-medicating, and sick leave. Self-medicating for treatment of disease specific symptoms was frequent. Traditional treatments and pain medication were most frequently used. Based on these data, we estimated loiasis related direct healthcare costs and indirect costs due to sickness, resulting in a monetary burden of US-$ 58 (95% CI: 21–101) per loiasis positive individual per year. Extrapolating these numbers to the rural population of Gabon (n = 204,000) would correspond to a monetary burden of US-$ 3,206,000 (95% CI: 1,150,000–5,577,000). Thus, loiasis is not only associated with morbidity and mortality but also with healthcare-seeking and may cause a relevant socioeconomic burden on affected populations. Therefore, considering loiasis a negligible disease is not appropriate anymore. [ABSTRACT FROM AUTHOR]

Background: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. Methodology/Principal findings: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1-hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. Conclusion/Significance: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions. Author summary: Lymphatic filariasis (LF) is a debilitating tropical disease caused by infection with parasitic filarial worms that are transmitted by mosquitoes. Long-term infection can lead to stigmatising chronic conditions like lymphoedema and elephantiasis. The World Health Organization initiated the global programme to eliminate lymphatic filariasis (GPELF) in 2000, focusing on mass drug administration (MDA) of anti-LF drugs to stop transmission in endemic countries. However, to monitor the success of this programme and to make informed decisions to stop costly MDA, it is crucial to have access to accurate and reliable rapid diagnostics. Here, we evaluated the performance of a new rapid antigen test called the Q Filariasis antigen test and compared it to the currently recommended filariasis test strip under field laboratory conditions in Samoa. This study showed that the new rapid test could be a suitable alternative to the currently recommended test for use in GPELF-related activities with more user-friendly features. [ABSTRACT FROM AUTHOR]

Background: Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China. Methods: The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected. Results: Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse. Conclusion: This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions. [ABSTRACT FROM AUTHOR]

Background In 2018, the US Food and Drug Administration approved the macrocylic lactone moxidectin (MOX) at 8 mg dosage for onchocerciasis treatment in individuals aged ≥12 years. Severe adverse reactions have occurred after ivermectin (IVM), also a macrocyclic lactone, in individuals with high Loa microfilarial density (MFD). This study compared the safety and efficacy of a 2 mg MOX dose and the standard 150 µg/kg IVM dose in individuals with low L loa MFD. Methods A double-blind, randomized, ivermectin-controlled trial of a 2 mg moxidectin dose was conducted in Cameroon between May and July 2022. It enrolled 72 adult men with L loa MFD between 5 and 1000 microfilariae/mL. Outcomes were occurrence of adverse events (AEs) and L loa MFD reduction rate during the first month off treatment. Results No serious or severe AEs occurred among the 36 MOX- or the 36 IVM-treated individuals. Forty-nine AEs occurred in the MOX arm versus 59 AEs in the IVM arm. Grade 2 AE incidence was higher among IVM- than MOX-treated participants (38.5% and 14.3%, respectively, P =.043). Median MFD reduction rates were significantly higher after IVM than MOX at day 3 (70.2% vs 48.5%), day 7 (76.4% vs 50.0%), and day 30 (79.8% vs 48.1%). Conclusions A single 2 mg MOX dose is as safe as 150 µg/kg IVM in patients with low L loa MFD. Further studies with higher MOX doses and in patients with higher MFD are warranted. Clinical Trials Registration NCT04049851. [ABSTRACT FROM AUTHOR]

We report the case of a 21-year-old Cameroonian woman residing in France for one year, who presented to our department with left eye discomfort and itching. Examination revealed a mobile translucent cord beneath the nasal-inferior conjunctiva, prompting suspicion of loaiasis. Anesthesia was administered for extraction, revealing a 31 mm male Loa loa. A positive microfilarial load, albeit low, confirmed the diagnosis and the diagnostic workup excluded other locations. Treatment with diethylcarbamazine was well-tolerated. This case highlights the importance of considering loaiasis in non-endemic regions and underscores the need for interdisciplinary collaboration in its diagnosis and management. [ABSTRACT FROM AUTHOR]

Ascaris spp. undergo extensive migration within the body before establishing patent infections in the small intestinal tract of humans and pigs. However, whether larval migration is critical for inducing efficient type 2 responses remains poorly understood. Therefore, we investigated systemic versus local adaptive immune responses along the hepato-tracheal migration of Ascaris suum during primary, single infections in conventionally raised pigs. Neither the initial invasion of gut tissue nor migration through the liver resulted in discernable Th2 cell responses. In contrast, lung-stage larvae elicited a Th2-biased pulmonary response, which declined after the larvae had left the lungs. In the small intestine, we observed an accumulation of Th2 cells upon the arrival of fourth-stage larvae (L4) to the small intestinal lumen. In parallel, we noticed robust and increasing Th1 responses in circulation, migration-affected organs, and draining lymph nodes. Phenotypic analysis of CD4+ T cells specifically recognizing A. suum antigens in the circulation and lung tissue of infected pigs confirmed that the majority of Ascaris-specific T cells produced IL-4 (Th2) and, to a much lesser extent, IL-4/IFN-g (Th2/1 hybrids) or IFN-g alone (Th1). These data demonstrate that lungstage but not the early liver-stage larvae lead to a locally restricted Th2 response. Significant Th2 cell accumulation in the small intestine occurs only when L4 complete the body migration. In addition, Th2 immunity seems to be hampered by the concurrent, nonspecific Th1 bias in growing pigs. Together, the late onset of Th2 immunity at the site of infection and the Th1-biased systemic immunity likely enable the establishment of intestinal infections by sufficiently large L4 stages and pre-adult worms, some of which resist expulsion mechanisms. [ABSTRACT FROM AUTHOR]

Background: More than 20 million people are infected with L. loa, and around 40 million live in high or intermediate-risk areas in West- and Central Africa. Although loiasis is associated with significant morbidity and excess mortality, little is known about the perception of loiasis by affected communities. This study assessed the knowledge, attitudes, and practices in the rural population of Sindara, Gabon, a region characterized by high loiasis prevalence. Methods: A community-based cross-sectional survey was conducted in Gabon between January and June 2022. During systematic door-to-door visits, randomly selected inhabitants were invited to participate in this questionnaire based survey. Venous blood was collected at midday from all participants for microscopic detection of filarial infection and clinical signs of loiasis were assessed. Results: A total of 150 participants were recruited, of which 66% were infected by L. loa. While almost everyone had some knowledge about L. loa, 72% of the participants understood that L. loa is a parasitic worm. The transmission of L. loa via the deer fly was known to only 21% of participants. The most frequently mentioned clinical symptoms attributed to loiasis were itching (84%), eye worm migration (59%), and conjunctivitis-like symptoms (53%). Participants who experienced migratory loiasis had better knowledge of loiasis and considered it as more serious. Traditional and herbal medicine was reported most often as an available treatment option (72%). While the formal healthcare sector was mentioned as the preferred treatment provider, 60% of the reported infections were treated by traditional medical practitioners. Conclusion: Loiasis is in general well known by this community residing in a region of high L. loa transmission. Important gaps in knowledge were discovered foremost regarding the mode of transmission. The available healthcare system does not seem to provide adequate management for loiasis. Author summary: Loiasis is a filarial disease highly prevalent in parts of Western- and Central Africa. For a long time, the disease has been considered to be a relatively benign condition, but recent studies have shown that loiasis causes significant morbidity and excess mortality. In the present study, we investigated the perception of loiasis in a highly affected community in rural Gabon to better understand the community perspective on this infectious disease. While L. loa as a disease is known to most inhabitants, the mode of transmission and prevention modalities are only poorly understood. This lack of knowledge leaves the communities with inadequate means to prevent onward transmission of this filarial disease. The contribution from media, schools and healthcare institutions in providing information about loiasis is inadequate, and the available healthcare system is insufficient to provide the necessary care for loiasis. A better understanding of loiasis by the affected communities is desirable to empower inhabitants of high-transmission regions to better protect themselves from loiasis. Improved understanding of the disease by the healthcare sector is necessary to improve the management of loiasis. [ABSTRACT FROM AUTHOR]

Background: Chronic infection by Loa loa remains an unsolved immunological paradox. Despite harboring subcutaneously migrating adult worms and often high densities of microfilariae, most patients experience only relatively mild symptoms, yet microfilaricidal treatment can trigger life-threatening inflammation. Here, we investigated innate cell populations hypothesized to play a role in these two faces of the disease, in an endemic population in Gabon. Methodology/Principal findings: We analyzed numbers and activation of eosinophils and basophils, as well as myeloid-derived suppressor cell (MDSC) subsets and associated circulating cytokine levels by flow cytometry in sex- and age-matched L. loa-uninfected (LL-), -amicrofilaraemic (MF-) and -microfilaraemic (MF+) individuals (n = 42), as well as microfilaraemic individuals treated with albendazole (n = 26). The percentage of eosinophils was lower in LL- (3.0%) than in the combined L. loa-infected population, but was similar in MF+ (13.1%) and MF- (12.3%). Upon treatment of MF+, eosinophilia increased from day 0 (17.2%) to day 14 (24.8%) and had decreased below baseline at day 168 (6.3%). Expression of the eosinophil activation marker CD123 followed the same pattern as the percentage of eosinophils, while the inverse was observed for CD193 and to some extent CD125. Circulating IL-5 levels after treatment followed the same pattern as eosinophil dynamics. Basophil numbers did not differ between infection states but increased after treatment of MF+. We did not observe differences in MDSC numbers between infection states or upon treatment. Conclusions/Significance: We demonstrate that both chronic infection and treatment of L. loa microfilaraemia are associated with eosinophil circulation and distinct phenotypical activation markers that might contribute to inflammatory pathways in this setting. In this first ever investigation into MDSC in L. loa infection, we found no evidence for their increased presence in chronic loiasis, suggesting that immunomodulation by L. loa is induced through other pathways. Author summary: Loiasis–also called African eye worm for its most pathognomonic feature–is a disease caused by the helminth Loa loa, affecting over ten million people in Central and West Africa. While L. loa seems to successfully evade an effective immune response in chronic infection, treatment can lead to severe inflammation upon rapid death of L. loa larvae in the blood. Here, we investigated different subsets of immune cells hypothesized to play a role in L. loa-mediated immune modulation in chronically infected individuals and upon treatment of individuals with circulating larvae. We found that eosinophils–an important cell population in the immune response to helminths–increase in numbers and are activated in both L. loa-infection and its treatment. Myeloid-derived suppressor cells can suppress immune responses in cancer and some other infectious diseases but have never been investigated in loiasis. We hypothesized that they are involved in immunosuppression by L. loa but found no evidence thereof. Better understanding of immunomodulation in chronic loiasis may ultimately improve the management of this neglected disease. [ABSTRACT FROM AUTHOR]

Background: The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is driven by the vector density, hence influencing the disease prevalence and intensity. Onchocerciasis is currently targeted for elimination using mass drug administration (MDA) of ivermectin, a potent microfilaricide. MDA in Cameroon began in 1987 in the Vina Valley, an endemic cross-border area with Chad, known for high vector densities and precontrol endemicity. Evaluations in 2008–2010 in this area showed ongoing transmission, while border areas in Chad were close to interrupting transmission. This study aimed to evaluate transmission in this area after several rounds of MDA since the last evaluation surveys. Methods: Black flies were collected by human landing catches at seven border sites in Cameroon, twice a week, from August 2021 to March 2022. A fraction of the flies was dissected for parity assessment and identification of Onchocerca larval stages. The transmission indices were estimated. Black fly larvae were also collected from the breeding sites at the fly catching sites and identified to species level by cytotaxonomy. Results: A total of 14,303 female flies were collected, and 6918 were dissected. Of these, 4421 (64.0%) were parous. The total biting rates were high, reaching up to 16,407 bites/person/study period, and transmission potential (third-stage larvae (L3) from head/all L3) were 367/702, 146/506, 51/55, 20/32, 0/3, 0/0, and 0/0 infective larvae/person, respectively, for Mbere-Tchad, Babidan, Hajam/V5, Gor, Djeing, Touboro, and Koinderi. Infectivity rates (L3 from head) were 16.00, 12.75, 5.15, and 4.07 infective females (L3H)/1000 parous flies for Haijam, Mbere-Tchad, Babidan, and Gor, respectively. These values exceed the World Health Organization (WHO) thresholds of ≤ 20 annual transmission potential (ATP) or < 1 infective female/1000 parous females. The major vectors identified were Simulium damnosum sensu stricto, S. squamosum, and for the first time in the area, S. yahense. Conclusions: More than 20 years of MDA has not eliminated onchocerciasis in the study area; hence, this area is a potential source of reintroduction of onchocerciasis in Chad and would require alternative treatment strategies. Many factors such as MDA efficiency, effectiveness of ivermectin, and cytospecies composition may be contributing to transmission persistence. [ABSTRACT FROM AUTHOR]

Brugia malayi and B. pahangi, potential zoonotic pathogens transmitted by mosquitoes, are believed to primarily infect dogs and cats as reservoir hosts. Although previous studies have indicated nematode infections in lions, particularly in zoo environments where human contact with these reservoirs is possible, limited documentation exists regarding Brugia sp. infections in lions in Thailand. This study aims to investigate a case of Brugia infection in a lion from a zoo in Thailand. The blood sample was collected and examined from a female lion, using staining methods to morphologically identify microfilaria at the genus level. Subsequently, the PCR was employed targeting specific genes, including mitochondrial 12S rDNA, 18S rDNA, cytochrome oxidase I (COI) and Wolbachia surface protein (wsp), to confirm the species of the filarial nematode parasite. The genetic sequencing results revealed a high similarity (99-100%) to B. malayi for the 12S rDNA, 18S rDNA, COI and wsp genes. Phylogenetic analysis based on nucleotide sequences from the 12S rDNA, 18S rDNA, COI and wsp genes showed that the sequences from this study belong to different clusters. This marks the inaugural documentation of molecular identification of Brugia infection in a lion, signifying that lions could function as reservoirs for this parasite and present a potential public health risk in the region. Our research underscores the effectiveness of molecular techniques and phylogenetic analysis in discerning and comprehending the evolution of filarial parasites. Additionally, it emphasizes the significance of these methods in enhancing the diagnosis, control, and prevention of zoonotic filarial nematode infections. [ABSTRACT FROM AUTHOR]

Filariasis, a neglected tropical disease caused by roundworms, is a significant public health concern in many tropical countries. Microscopic examination of blood samples can detect and differentiate parasite species, but it is time consuming and requires expert microscopists, a resource that is not always available. In this context, artificial intelligence (AI) can assist in the diagnosis of this disease by automatically detecting and differentiating microfilariae. In line with the target product profile for lymphatic filariasis as defined by the World Health Organization, we developed an edge AI system running on a smartphone whose camera is aligned with the ocular of an optical microscope that detects and differentiates filarias species in real time without the internet connection. Our object detection algorithm that uses the Single-Shot Detection (SSD) MobileNet V2 detection model was developed with 115 cases, 85 cases with 1903 fields of view and 3342 labels for model training, and 30 cases with 484 fields of view and 873 labels for model validation before clinical validation, is able to detect microfilarias at 10x magnification and distinguishes four species of them at 40x magnification: Loa loa, Mansonella perstans, Wuchereria bancrofti, and Brugia malayi. We validated our augmented microscopy system in the clinical environment by replicating the diagnostic workflow encompassed examinations at 10x and 40x with the assistance of the AI models analyzing 18 samples with the AI running on a middle range smartphone. It achieved an overall precision of 94.14%, recall of 91.90% and F1 score of 93.01% for the screening algorithm and 95.46%, 97.81% and 96.62% for the species differentiation algorithm respectively. This innovative solution has the potential to support filariasis diagnosis and monitoring, particularly in resource-limited settings where access to expert technicians and laboratory equipment is scarce. Author summary: Filariasis is a common tropical infectious disease. Depending on the parasite, it causes lymphoedema, elephantiasis, itching, blindness, etc. It is estimated that more than 1 billion people require preventive chemotherapy to stop the spread of this infection. The diagnosis of this disease is made through microscopical examination of a blood smear by a human expert, which is not always available. In this study we propose an edge Artificial Intelligence (AI) system that detects and quantifies four species of microfilariae (Loa loa, Mansonella perstans, Wuchereria bancrofti and Brugia malayi) using the camera of a smartphone attached to an optical microscope with a 3D printed adapter. The system works in real time and does not need internet connectivity as the AI models are run locally in a medium range smartphone. We have replicated the diagnostic workflow that is typically performed by an expert microscopist augmented by the support of the AI system. [ABSTRACT FROM AUTHOR]

A recent article in PLoS Neglected Tropical Diseases discusses the potential of artificial intelligence (AI) in the diagnosis and surveillance of filariasis, a group of parasitic diseases. The authors describe a computer vision platform that uses a neural network to analyze microscopic images of blood smears and identify different species of filariae. The app has shown good overall performance, with high precision and recall rates for most species. However, there are some limitations, such as a small dataset and the need for a 3D printer for the cellphone-microscope adaptor. Despite these shortcomings, the technology shows promise for the future of filariasis diagnosis. [Extracted from the article]

Objectives: The potential impact of cumulative community-directed treatment with ivermectin (CDTI) on epilepsy epidemiology in Mvolo County, South Sudan, an onchocerciasis-endemic area with high epilepsy prevalence, was investigated. Annual CDTI was introduced in 2002 in Mvolo, with interruptions in 2016 and 2020. Methods: Comprehensive house-to-house surveys in Mvolo (June 2020 and 2022) identified cases of epilepsy, including probable nodding syndrome (pNS). Community workers screened households in selected sites for suspected epilepsy, and medical doctors confirmed the diagnosis and determined the year of seizure onset. The incidence of epilepsy, including pNS, was analysed using 95% confidence intervals (CIs). Data on ivermectin intake and onchocerciasis-associated manifestations (itching and blindness) were collected. Results: The surveys covered 15,755 (2020) and 15,092 (2022) individuals, identifying 809 (5.2%, 95% CI: 4.8–5.5%) and 672 (4.5%, 95% CI: 4.1–4.8%) epilepsy cases, respectively. Each survey reported that a third of the surveyed population experienced skin itching, and 3% were blind. Epilepsy incidence per 100,000 person-years gradually declined, from 326.5 (95% CI: 266.8–399.1) in 2013–2015 to 96.6 (95% CI: 65.5–141.7) in 2019–2021. Similarly, pNS incidence per 100,000 person-years decreased from 151.7 (95% CI: 112.7–203.4) to 27.0 (95% CI: 12.5–55.5). Coverage of CDTI was suboptimal, reaching only 64.0% of participants in 2019 and falling to 24.1% in 2021 following an interruption in 2020 due to COVID-19 restrictions. Additionally, while 99.4% of cases had active epilepsy in 2022, less than a quarter of these had access to antiseizure medication. Conclusions: The observed decrease in epilepsy incidence despite suboptimal CDTI coverage highlights the potential impact of onchocerciasis control efforts and underscores the need to strengthen these efforts in Mvolo County and across South Sudan. As a proactive measure, Mvolo and neighbouring counties are transitioning to biannual CDTI. Furthermore, the substantial epilepsy treatment gap in Mvolo should be addressed. Author summary: In areas where many people have onchocerciasis, a parasitic infection spread by female blackflies, there is often a high occurrence of epilepsy. The latter includes nodding syndrome (NS), a type of epilepsy where the head repeatedly drops forward. This is the case in Mvolo County, South Sudan. Our study examined how the annual intake of ivermectin, a drug that prevents onchocerciasis, impacted the occurrence of new epilepsy cases, including NS, in the county. In June 2020, we visited selected sites and screened 15,480 individuals for epilepsy, with confirmation of diagnosis by a medical professional. This exercise was repeated in June 2022 with 15,092 individuals. We found fewer new epilepsy and probable NS cases after introducing annual ivermectin treatment. Still, not all eligible community members received the treatment, with 64% of participants reporting taking ivermectin in 2019 and only 24% in 2021. Our research further corroborates that ivermectin intake at the community level can help reduce the high number of epilepsy and NS cases in regions where onchocerciasis is found. Consequently, it is imperative that individuals at risk for onchocerciasis, particularly those within the 5–18-year-old age group, who are most susceptible to developing onchocerciasis-associated epilepsy, have access to annual ivermectin. [ABSTRACT FROM AUTHOR]

Background: In Ethiopia, Onchocerciasis is a prevalent neglected tropical disease, currently targeted for elimination with mass drug administration and community behavioral changes towards sustained control and eventual elimination. This study aimed to elucidate the awareness, perceptions and practices of endemic communities in Jimma Zone, Ethiopia. Methods and materials: Community-based cross-sectional study triangulated with qualitative method was conducted from October-November, 2021. A multistage sampling was employed and data were collected using a pre-tested interviewer-administered structured questionnaire. Logistic regression was used to identify the predictors of comprehensive knowledge and preventive practice. Adjusted odds ratios were calculated at 95% confidence interval (CI) and considered significant with a p-value of <0.05. Kruskal-Whallis and Mann-whitney tests were used to compare median risk perception score by socio-demographic factors. Qualitative data were collected through focus group discussions and key informant interviews and transcribed verbatim. Then the data were coded, categorized, and themes were developed. Result: The overall prevalence of adequate comprehensive knowledge was 48.8% (95% CI: 44.9, 52.3), high risk perception was 18.7% (95%CI15.9, 21.4) and preventive practice was 46.9%(95%CI:(43.3,50.4). High risk perception[AOR = 1.95 95%CI: (1.32, 2.89] was statistically significant with comprehensive knowledge, likewise knowledge of mode of transmission [AOR = 2.64 95% CI: (1.44, 4.85)], knowledge of consequences [AOR = 2.12 95%CI: (1.21, 3.72)] and knowledge of preventive measures [AOR = 15.65,95%CI:(10.1, 24.2)] were statistically significant with preventive practice. The median risk perception was varied significantly between the groups by educational status, study district and age category. Qualitative evidence showed that there were great community knowledge gap about the disease. Conclusion: Community knowledge, perceptions, and practices are unacceptably low. Risk perception was significantly associated with comprehensive knowledge, likewise knowledge of mode of transmission, consequences and preventive measures were significantly associated with preventive practice. This implies knowledge is a key component of effective prevention strategies as it is a necessary condition for the behavior change. Author summary: Onchocerciasis is a common neglected tropical disease with serious consequences in Ethiopia. Mass drug administration and behavioral changes in the community are being used for its control and eventual eradication, but community awareness, perceptions, and practices are still underreported. This study examined community knowledge, perceptions and preventive practices towards Onchocerciasis using mixed method in Jimma, Ethiopia. The finding revealed that, most of the respondents were familiar with Onchocerciasis, despite some confusions and misinterpretations around it. In these communities where Onchocerciasis is endemic, correct perceptions and proper understanding of this disease was inadequate and the level of risk perception towards Onchocerciasis was quite low. On the other hand, more than half of the participants did not practice Onchocerciasis recommended preventive measures and lack adequate knowledge of it. Furthermore, participants who were knowledgeable about the mode of transmission, its consequences and preventive measures were more likely to practice its preventive measures. Thus, our findings highlight the need for strengthening context-specific and tailored behavior change communications by integrating it into routine Onchocerciasis control and elimination program. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine performance indicators of thick blood smears of 50 µl (TBS-50), following the Standards for the Reporting of Diagnostic Accuracy Studies–Bayesian Latent Class Model (STARD-BLCM) guidelines. TBS-50 was compared with two common parasitological techniques—direct examination of 10 µl blood and a leukoconcentration of 5 ml—for the diagnosis of microfilaremic loiasis. Methods: The study population was recruited among patients of the Department of Parasitology-Mycology-Tropical Medicine over a period of 1 year. Age, sex, symptoms, and eosinophilia variables were recorded from laboratory registers and medical files. Direct examination of 10 µl of blood, TBS-50, and the leukoconcentration technique with 5 ml of blood were performed for each patient. The classical formula and BLCM were used to determine the diagnostic accuracy of the three techniques as well as the prevalence of microfilaremic loiasis. Three models were built within the framework of BLCM—the BLCM model I and alternative models II and III—for sensitivity analysis. Results: In total, 191 patients consented to be included. The direct blood examination and TBS-50 yielded comparable qualitative and quantitative results. Hence, they are reported together. The prevalence of Loa loa microfilaremia was 9.4% (95% CI 5.7–14.5; n = 18/191) with direct blood examination/TBS-50 and 12.6% [8.2–18.1] (n = 24/191) for leukoconcentration. Comparing TBS-50 with the leukoconcentration method using the classical formula, the sensitivity was 75.0% [53.3–90.2], specificity was 100.0% [97.8–100.0], the positive predictive value was 100.0% [81.5–100.0], and the negative predictive value was 96.5% [92.6–98.7]. The prevalence of microfilaremic loiasis was estimated at 9.7% [6.2–13.7] using BLCM model I. The outputs of BLCM model I showed sensitivity of 78.9% [65.3–90.3], specificity of 100.0% [99.3–100.0], a positive predictive value of 99.1% [87.2–100.0], and a negative predictive value of 93.0% [87.3–97.7] for direct blood examination/TBS-50. Conclusions: TBS-50 demonstrates low sensitivity relative to two other techniques. In one in five cases, the result will be falsely declared negative using these methods. However, this method can be deployed with limited funds. [ABSTRACT FROM AUTHOR]

Background: After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no eye involvement, DEC + ivermectin + albendazole treatment a few months after ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naïve individuals with ≥ 10 SmfD after 8 mg moxidectin (n = 978) or 150 µg/kg ivermectin (n = 494) treatment. Methods: We analyzed the data from 1463 participants with both eyes evaluated using six (0, 1–5, 6–10, 11–20, 21–40, > 40) mfAC and three pre-treatment (< 20, 20 to < 50, ≥ 50) and post-treatment (0, > 0–5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs. Results: Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096–2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27–5.749 and 1.619, 95% CI 0.80–3.280, respectively). Conclusions: The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals. [ABSTRACT FROM AUTHOR]

Background: Filarial worms are important vector-borne pathogens of a large range of animal hosts, including humans, and are responsible for numerous debilitating neglected tropical diseases such as, lymphatic filariasis caused by Wuchereria bancrofti and Brugia spp., as well as loiasis caused by Loa loa. Moreover, some emerging or difficult-to-eliminate filarioid pathogens are zoonotic using animals like canines as reservoir hosts, for example Dirofilaria sp. 'hongkongensis'. Diagnosis of filariasis through commonly available methods, like microscopy, can be challenging as microfilaremia may wane below the limit of detection. In contrast, conventional PCR methods are more sensitive and specific but may show limited ability to detect coinfections as well as emerging and/or novel pathogens. Use of deep-sequencing technologies obviate these challenges, providing sensitive detection of entire parasite communities, whilst also being better suited for the characterisation of rare or novel pathogens. Therefore, we developed a novel long-read metabarcoding assay for deep-sequencing the filarial nematode cytochrome c oxidase subunit I gene on Oxford Nanopore Technologies' (ONT) MinION™ sequencer. We assessed the overall performance of our assay using kappa statistics to compare it to commonly used diagnostic methods for filarial worm detection, such as conventional PCR (cPCR) with Sanger sequencing and the microscopy-based modified Knott's test (MKT). Results: We confirmed our metabarcoding assay can characterise filarial parasites from a diverse range of genera, including, Breinlia, Brugia, Cercopithifilaria, Dipetalonema, Dirofilaria, Onchocerca, Setaria, Stephanofilaria and Wuchereria. We demonstrated proof-of-concept for this assay by using blood samples from Sri Lankan dogs, whereby we identified infections with the filarioids Acanthocheilonema reconditum, Brugia sp. Sri Lanka genotype and zoonotic Dirofilaria sp. 'hongkongensis'. When compared to traditionally used diagnostics, such as the MKT and cPCR with Sanger sequencing, we identified an additional filarioid species and over 15% more mono- and coinfections. Conclusions: Our developed metabarcoding assay may show broad applicability for the metabarcoding and diagnosis of the full spectrum of filarioids from a wide range of animal hosts, including mammals and vectors, whilst the utilisation of ONT' small and portable MinION™ means that such methods could be deployed for field use. [ABSTRACT FROM AUTHOR]

Background: 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. Methodology: 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). Principal findings: 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. Conclusion: A potential link between high L. loa microfilaremia and cardiovascular health deterioration is suggested. Further studies are required to confirm and explore this association. Author summary: Recent epidemiologic data suggested an increased mortality and morbidity in individuals harboring high densities of Loa loa microfilariae in the blood, underscoring the importance of studies on the possible reasons for this excess mortality. This cross-sectional study assessed arterial stiffness and cardiovascular health markers using a point-of-care device (pOpmètre) among 991 sex-, age- and residency-matched individuals living in rural forested areas of Congo. Analyses included known cardiovascular risk factors (body mass index, smoking, blood pressure, creatininemia) and parasitological covariates (onchocerciasis, asymptomatic malaria, soil-transmitted helminths and Loa loa microfilaremia). People with microfilaremia were more likely to have levels of cardiovascular markers indicating arterial stiffness and deteriorated cardiovascular health, compared with those without microfilaremia. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository. Methodology: We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment. Principle findings: We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and morbidity outcomes measured with other diagnostics, from participants followed for adverse event outcomes only or recruited after initial intervention. Conclusions: The LF treatment study landscape is heterogeneous, but the abundance of studies and related IPD suggest that establishing a global data repository to facilitate IPD meta-analyses would be feasible and useful to address unresolved questions on variation in treatment outcomes across geographies, demographics and in underrepresented groups. New studies using more standardized approaches should be initiated to address the scarcity and inconsistency of data on morbidity management. Author summary: Lymphatic filariasis (LF) is a debilitating parasitic disease that the World Health Organization (WHO) has earmarked for elimination by 2030 through a combination of mass distribution of anti-parasitic medicines and disease management approaches. Great strides have been made towards the elimination of LF as a public health problem, but nearly 900 million people still require treatment every year. In recent years, new combinations of medicines have been shown to improve the treatment of LF, yet there remain substantial gaps in understanding of apparent variability in treatment success and on the best treatment and management approaches to alleviate chronic morbidity. Some of these questions could be addressed through the development of a LF global data platform, which would enable pooled analyses of all available individual participant data. Here, we present the results of a systematic literature review of the LF treatment study landscape. We estimate the abundance of individual data on treatment of infection and morbidity and describe the characteristics of the studies and participants that have generated these data. We argue that collating and curating these data into a data LF platform could help to fill gaps in understanding of the best ways to treat infection and disease and enhance prospects of eliminating LF by 2030. [ABSTRACT FROM AUTHOR]

Introduction: Lymphatic filariasis is a neglected tropical disease (NTD) caused by microscopic worms that live only in the human lymphatic system. Physical environmental factors play a role in preventing filariasis, especially the presence of breeding places and contact with mosquitoes. The aim of this study was to describe agent, vector, and physical environment risk factors such as bed net usage and sewerage conditions for lymphatic filariasis in developing countries. Discussion: This study was conducted using the narrative literature review method. The main sources for this study were articles from Google Scholar, Research Gate, PubMed, Springer, Scopus, and DOAJ databases with the criteria published between 2012 and 2022, observational studies including cross-sectional, casecontrol, and cohort designs, open access, and articles were organized according to STROBE guidelines. Out of the 100 articles identified, only 14 articles fulfilled the predetermined criteria after undergoing screening and removal of duplicate articles. The study was carried out in a group of developing country, including India, Myanmar, Indonesia, Nigeria, Ethiopia, Democratic Republic of Congo, Republic of Congo, Zambia, and United Republic of Tanzania. Wuchereria bancrofti is the most common agent of lymphatic filariasis. Culex and Anopheles are the vectors. The presence of bed nets and sewerage conditions were physical environment risk factors for lymphatic filariasis in developing countries. Conclusion: The use of mosquito nets or insect repellent at night can prevent lymphatic filariasis. In addition, open drains should be cleaned regularly to prevent them from becoming breeding sites for mosquito as vectors. [ABSTRACT FROM AUTHOR]

Background: Loiasis is endemic in the northern and western part of the Republic of Congo. Between 2004 and 2010, surveys were conducted, using the RAPLOA method, in all departments of the Republic of Congo to assess the distribution of loiasis. Prior to 2004, only two parasitological surveys on loiasis had been conducted in Congo and mainly in the Department of Lékoumou, in the southwestern of the country. In 2019, we conducted a parasitological survey in this same department, more than 30 years after the first surveys. Methods: The study was conducted in 21 villages. Loa loa and Mansonella perstans microfilaremia levels were quantified using 50 µl calibrated blood smears. Results: A total of 2444 individuals were examined. The median age of the screened individuals was 43 (interquartile range: 30–57, range: 18–91) years old. The overall prevalences of L. loa and M. perstans microfilaremia were 20.0% [95% confidence intervals (CI) 18.0–21.6%] and 1.0% (95% CI 0.6–1.4%) respectively. The proportion of individuals with a microfilarial density of L. loa > 8000 mf/ml and > 30,000 mf/ml were 5.1% (95% CI 4.3–6.1%) and 1.1% (95% CI 0.8–1.7%), respectively. The overall community microfilarial load was 3.4 mf/ml. Conclusions: Prevalences and intensities of L. loa infection remained generally stable between the late 1980s and 2019 in the Lékoumou Department. In contrast, parasitological indicators for M. perstans have declined sharply in the intervening years for an unknown reason. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prevalence of substandard products, a quality study based on the United States Pharmacopeia (USP) standards was conducted on the veterinary medicinal product ivermectin. Methods: From September 2020 to January 2021, a cross-sectional quality analysis was carried out on 19 samples of pharmaceutical products. These samples were obtained from all veterinary retail outlets in Addis Ababa, Ethiopia. The analysis included organoleptic assessment for packaging-related information and physical appearance, as well as high-performance liquid chromatography (HPLC)- based physicochemical analysis for identity, assay, packaging uniformity, and HLB ratio. The procedures followed were in accordance with the USP recommendations. The quality analysis took place at the national veterinary drug quality test center. Results: The quality analysis has revealed the presence of substandard products for uniformity of packaging (15.8%), API assay (15.8%), and filling to a volume (16.67%). However, both sampled products demonstrated the expected API, recommended physical appearance, and consistent packaging information. The prevalence ratio values for all H1B1a/(H1B1a+H1B1b) chemical species were greater than 0.95. Conclusion: The findings from this study clearly indicate the alarming presence of substandard veterinary pharmaceutical products. This highlights the need for strengthening the regulatory surveillance system. [ABSTRACT FROM AUTHOR]

Background: Reducing contact between humans and black flies can lead to interruption of onchocerciasis transmission. The Esperanza Window Trap (EWT) has been shown to be an effective tool for reducing black fly densities. Several shape-based improvements to this trapping system have been made to optimise its effectiveness, but optimisation of this trapping system has been based most often on the shape of the trap, collection in areas of high black fly density and the addition of attractants, without considering transmission potentials and parity rates. This study aims to investigate the differences in biting rates and transmission potential between three catch points along a transect to guide the choice of EWT placement. Methods: Monthly black fly collection was carried out over a 1-year study period using the human landing method at three catch points along a transect from the riverside toward the centre of two first-line villages (Biatsota and Bayomen), in the Mbam valley in Cameroon. All female black flies caught were counted and dissected, and entomological indicators were computed and compared between the catch points and villages. Results: A total of 80,732 black flies were caught, of which 57,517 were dissected; of the latter, 2743 (4.8%) were parous and 44 (1.6%) were infective. Regarding the distance to the river, a vector density gradient was observed, with the highest annual biting rates being recorded at the riverside. The highest annual transmission potentials were also recorded at the riverside (165 vs 255 infective larvae/man/year in Bayomen and Biatsota, respectively). Overall, the highest parity rates were recorded at the riverside in Biatsota (5.1%) where various human activities are frequent and at the centre of Bayomen village (6.3%). Conclusion: The results of this study reveal that entomological parameters were the highest at the riverside catch sites and indicate that riverside locations should be prioritised for EWTs or other trapping systems to achieve optimal performance in onchocerciasis control. [ABSTRACT FROM AUTHOR]

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Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA. This article is part of the theme issue 'Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'. [ABSTRACT FROM AUTHOR]

This prospective, cross-sectional study was conducted from April 3 to July 20, 2023, at the Paul MOUKAMBI Regional Hospital of Koula-Moutou. Blood samples taken from participants were used to diagnose Loa loa filariasis by direct optical microscopy and leucoconcentration. A questionnaire was used to collect data, which were entered into an Excel 2016 spreadsheet and exported to R software version 3.6.1. Univariate analysis, followed by multivariate analysis using logistic regression, yielded crude and adjusted Odds-Ratios. Within a 95% confidence interval, results were considered statistically significant at p ≤ 0.05. A total of 300 participants, with a mean age of 26.7 ± 17.45 years, took part in the study. A prevalence of Loa loa filariasis of 14% (95% CI: [0.10. 0.18]) was reported. After univariate analysis, multivariate logistic regression adjustment of this prevalence according to the different variables indicated that being female (adjusted OR = 56.9, 95% CI: [1.71; 1893,] p =0.024*) was the only significant risk factor for Loa loa filariasis in this study. Systematic epidemiological surveillance is needed to protect elderly women from Loa loa filariasis in Gabon. [ABSTRACT FROM AUTHOR]

Mass drug administration programs targeting filarial infections depend on diagnostic tools that are sensitive and specific. The coendemicity of Loa loa with other filarial species often hampers the control programs. LL2634 was identified as the most promising target among several highly repeated targets, with sensitivity between 500 ag and 1 fg of genomic DNA. Using DNA from infected individuals, LL2643 quantitative polymerase chain reaction (qPCR) was positive in all individuals. LL2643 was detected in plasma-derived circulating cell-free DNA (ccfDNA) from 48 of 53 microfilariae-positive patients. Detection of ccfDNA in urine was possible, but it occurred rarely among those tested. Importantly, LL2643 ccfDNA became undetectable within 1 month following diethylcarbamazine (DEC) treatment and remained negative for at least a year. LL2643 offers a more sensitive and specific target for detection of L. loa infection and would be easily configurable to a point-of-contact assay. Clinical Trials Registration. NCT00001230 and NCT00090662. [ABSTRACT FROM AUTHOR]

More than half a century has passed since the introduction of the National Filariasis Control Program; however, as of 2023, lymphatic filariasis (LF) still prevails globally, particularly in the tropical and subtropical regions, posing a substantial challenge to the objective of worldwide elimination. LF is affecting human beings and its economically important livestock leading to a crucial contributor to morbidities and disabilities. The current scenario has been blowing up alarms of attention to develop potent therapeutics and strategies having efficiency against the adult stage of filarial nematodes. In this context, the exploration of a suitable drug target that ensures lethality to macro and microfilariae is now our first goal to achieve. Apoptosis has been the potential target across all three stages of filarial nematodes viz. oocytes, microfilariae (mf) and adults resulting in filarial death after receiving the signal from the reactive oxygen species (ROS) and executed through intrinsic and extrinsic pathways. Hence, it is considered a leading target for developing antifilarial drugs. Herein, we have shown the efficacy of several natural and synthetic compounds/nanoformulations in triggering the apoptotic death of filarial parasites with little or no toxicity to the host body system. [ABSTRACT FROM AUTHOR]

Four species of the Mansonella genus infect millions of people across sub-Saharan Africa and Central and South America. Most infections are asymptomatic, but mansonellosis can be associated with nonspecific clinical manifestations such as fever, headache, arthralgia, and ocular lesions (M. ozzardi); pruritus, arthralgia, abdominal pain, angioedema, skin rash, and fatigue (M. perstans and perhaps Mansonella sp. 'DEUX'); and pruritic dermatitis and chronic lymphadenitis (M. perstans). We searched the PubMed and SciELO databases for publications on mansonelliasis in English, Spanish, Portuguese, or French that appeared until 1 May 2023. Literature data show that anthelmintics – single-dose ivermectin for M. ozzardi, repeated doses of mebendazole alone or in combination with diethylcarbamazine (DEC) for M. perstans, and DEC alone for M. streptocerca – are effective against microfilariae. Antibiotics that target Wolbachia endosymbionts, such as doxycycline, are likely to kill adult worms of most, if not all, Mansonella species, but the currently recommended 6-week regimen is relatively impractical. New anthelmintics and shorter antibiotic regimens (e.g. with rifampin) have shown promise in experimental filarial infections and may proceed to clinical trials. We recommend that human infections with Mansonella species be treated, regardless of any apparent clinical manifestations. We argue that mansonellosis, despite being widely considered a benign infection, may represent a direct or indirect cause of significant morbidity that remains poorly characterized at present. [ABSTRACT FROM AUTHOR]

Background: There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based treatment regimens to reduce Loa loa microfilaraemia in Gabon. Methods: Eligible adult patients with L. loa microfilaraemia between 5,000 and 50,000 microfilariae/ml were randomized to either a control or one of three intervention groups (1:2:2:2 allocation ratio) consisting of three-week twice daily 400mg oral albendazole followed by 1) no treatment, 2) two further weeks of twice daily 400mg albendazole, or 3) a single dose of ivermectin in this open label randomized assessor blinded controlled clinical trial. The primary outcome was the proportion of participants with L. loa microfilaraemia ≤ 100 mf/ml at Day 168. Results: In the efficacy-population of 42 patients 0 (0%; control group), 1 (9%; 3-week albendazole), 5 (39%; 5-weeks albendazole) and 2 (22%; 3-week albendazole plus single dose ivermectin) participants met the primary outcome of microfilaraemia below 100/ml at day 168. A 80–90% reduction of microfilaraemia was observed in the active treatment groups. Conclusion: The 5-week regimen of albendazole or a 3-week regimen of albendazole followed by ivermectin were most efficacious to reduce microfilaraemia. All therapeutic regimens were well tolerated and safe. Trial registration: Trial registered at the Pan-African Clinical Trials Registry: PACTR201807197019027. Author summary: To date there is a lack of safe treatment options to be used for the control of Loa loa transmission in highly endemic regions. This study assessed the parasitological efficacy of albendazole alone (three or five weeks regimen) or albendazole (three weeks regimen) with a single dose of ivermectin for the reduction of microfilaraemia in adult patients in Gabon. This proof of concept study showed highest efficacy of about 90% reduction of microfilaraemia when albendazole was given twice daily for five weeks or albendazole was administered twice daily for three weeks followed by single dose ivermectin. As there were no safety concerns these findings indicate that albendazole based treatment regimens may in principle be useful for implementation in population-based control programs. To overcome the problem associated with prolonged oral treatment regimens new injectable drug formulations with extended release of active substances may be considered to facilitate implementation of such control programs. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a debilitating and painful neglected tropical disease and is one of the leading causes of permanent disability. In many countries, the intersection of gender with various social stratifiers has influenced exposure to LF and ultimately impacting the disease burden and its elimination. This study aimed to explore the influence of gender and its intersection with other social stratifiers for the prevention and care seeking behavior of LF in Nepal. Methods: This study employed qualitative research methods: in-depth interviews (IDIs) and focus group discussions (FGDs) for data collection in Bardiya, Nepal. A total of 22 IDIs (11 male, 11 female) and 2 FGDs (1 male and 1 female) were conducted with the community people between January and March 2020. The participants were purposively selected to represent different social stratifiers including age, sex, ethnicity, occupation. The data collected were analyzed using a thematic framework approach with use of intersectional gender analysis matrix. Results: The study findings revealed that men spend more time outside their household compared to women while fulfilling their roles and responsibilities, largely determined by societal expectations and gender norms. This resulted in limited access to preventive health services for men, as they often missed annual mass drug administration programme in their community and limited access to preventive methods. Further traditional occupation, specific to particular ethnicity, influenced the vulnerability to LF for certain ethnic groups. The ability to prevent exposure varied among individuals. Although women made decisions regarding the use of protective methods, it was influenced by patriarchal and gender norms. They often felt a responsibility to take care and priorities males and other family members when resources are limited. The intersectionality of gender with other social stratifiers such as marital status, ethnicity, and geographical areas influenced individual's ability to access information related to LF and care seeking. Conclusions: Overall, the findings emphasized how access to resources, division of work, norms and values and decision-making power alone and its interaction with various social stratifiers shaped peoples' vulnerability to disease, ability to prevent exposure and response to illness. [ABSTRACT FROM AUTHOR]

Nodding syndrome (NS) is a phenotypic presentation of onchocerciasis-associated epilepsy (OAE). OAE is an important public health problem in areas with high ongoing Onchocerca volvulus transmission. OAE, including NS, is preventable by strengthening onchocerciasis elimination programs. The presence of tau in OAE postmortem brains could be the consequence of neuroinflammation directly or indirectly induced by O. volvulus. Omics research is needed to investigate whether O. volvulus worms contain a neurotropic virus. [ABSTRACT FROM AUTHOR]

Trombiculosis is a parasitic skin disease caused by larvae of mites from the family Trombiculidae (chiggers). In general, larvae provoke dermatitis. Kepkatrombicula desaleri Methlagl, 1928 is one of species involved in the etiology of animal trombiculosis, detected in European goats. The aim of the present study was to detect the species of trombiculid mites infesting goats and to recommend appropriate means for control of provoked disease. The study included total of 141 goats from two flocks in the Kalugerovo village, Pazardzhik district, Bulgaria. All infested goats from the first flock were treated with ivermectin, and those from the second flock - with cypermethrin. The identification of larvae showed their affiliation to the K. desaleri Methlagl, 1928 species. In the first flock, 15 infected goats were detected (17%) vs 7 (13%) in the second flock. The mites were detected on eyelids, medial eye angles, nose and ears as orangered papules. Neither squamae nor crusts were found in the skin adjacent to chiggers' location, and goats did not show any clinical signs. The treatment with ivermectin was ineffective, and spraying with cypermethrin resulted in reduced motility and rapid death of 100% of mites only several minutes after the treatment. The mites infected only animals with dark haircoat regardless of their age and sex. [ABSTRACT FROM AUTHOR]

Onchocerciasis, the second leading infectious cause of blindness, afflicts approximately 21 million people globally. Its control is limited to the use of the microfilaricidal drugs, ivermectin and moxidectin. Both drugs are unable to kill the adult worms which can survive for up to 15 years in patients, justifying the urgent need for potent and novel macrofilaricides that kill adult worms. The development of such drugs has been hindered by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo. This study assessed the survival of O. ochengi female worms and their embryos over time in two laboratory rodents: gerbils and hamsters and tested using "proof-of-concept" studies, whether known macrofilaricidal drugs can kill these worms. Animals were surgically implanted with mechanical or collagenase-liberated O. ochengi worm masses, and necropsied at various time points to test for survival. Recovered worm masses were assessed for viability by biochemical analysis (MTT/formazan assay) or fecundity (embryogram). Flubendazole (FBZ) administered at 20 mg/kg body weight was used to validate both rodent models. By day 26 post-implantation of 15 worm masses, a median of 7.00 (4.00–10.00) was recovered from hamsters, and 2.50 (2.00–4.00) from gerbils. Worm masses recovered from gerbils were mostly disintegrated or fragmented, with significantly higher fragmentation observed with collagenase-liberated worm masses. FBZ had no significant effect on the number of worm masses recovered, but enhanced embryo degradation in gerbils and reduced worm mass viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. ochengi. The hamsters appeared to maintain the worms longer, compared to gerbils. [ABSTRACT FROM AUTHOR]

A 17-year-old asymptomatic male from The Gambia presented for a routine health examination after migration to Spain. Laboratory diagnosis confirmed the presence of Loa loa microfilariae. This unusual finding emphasizes the importance of screening in newly arrived migrants and the need of an extended anamnesis including migratory route and previous travels. [ABSTRACT FROM AUTHOR]

Background: Nodding syndrome (NS) has been consistently associated with onchocerciasis. Nevertheless, a positive association between NS and a Mansonella perstans infection was found in South Sudan. We aimed to determine whether the latter parasite could be a risk factor for NS in Mahenge. Methods: Cases of epilepsy were identified in villages affected by NS in Mahenge, Tanzania, and matched with controls without epilepsy of the same sex, age and village. We examined blood films of cases and controls to identify M. perstans infections. The participants were also asked for sociodemographic and epilepsy information, examined for palpable onchocercal nodules and onchocerciasis-related skin lesions and tested for anti-Onchocerca volvulus antibodies (Ov16 IgG4) by ELISA. Clinical characteristics of cases and controls, O. volvulus exposure status and relevant sociodemographic variables were assessed by a conditional logistic regression model for NS and epilepsy status matched for age, sex and village. Results: A total of 113 epilepsy cases and 132 controls were enrolled, of which, respectively, 56 (49.6%) and 64 (48.5%) were men. The median age in cases and controls was 28.0 (IQR: 22.0–35.0) and 27.0 (IQR: 21.0–33.3) years. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria and 106 (93.8%) had onchocerciasis-associated epilepsy (OAE). M. perstans infection was absent in all participants, while Ov16 seroprevalence was positively associated with probable NS (odds ratio (OR): 5.05, 95%CI: 1.79–14.27) and overall epilepsy (OR: 2.03, 95%CI: 1–07–3.86). Moreover, onchocerciasis-related skin manifestations were only found in the cases (n = 7, p = 0.0040), including persons with probable NS (n = 4, p = 0.0033). Residing longer in the village and having a family history of seizures were positively correlated with Ov16 status and made persons at higher odds for epilepsy, including probable NS. Conclusion: In contrast to O. volvulus, M. perstans is most likely not endemic to Mahenge and, therefore, cannot be a co-factor for NS in the area. Hence, this filaria is unlikely to be the primary and sole causal factor in the development of NS. The main risk factor for NS remains onchocerciasis. Author summary: Nodding syndrome (NS) is a rare and severe form of epilepsy that mainly affects children. The syndrome has only been found in onchocerciasis-endemic areas, and epidemiological studies suggest that it may be one of the forms of onchocerciasis-associated epilepsy caused by the parasite Onchocerca volvulus. Nevertheless, other causes have been considered, such as an infection with Mansonella perstans. To identify a main causal factor for NS, it needs to be present in all sites where the syndrome is found. Hence, our team explored 113 people with epilepsy and 132 healthy controls in Mahenge, Tanzania, to determine if M. perstans could be behind the epidemic of NS in the area. Over a third of the epilepsy cases in the study met the criteria for probable NS. None of the participants was diagnosed with an M. perstans infection. However, those exposed to onchocerciasis and with onchocerciasis-associated skin lesions were more likely to have epilepsy, including probable NS. In conclusion, onchocerciasis remains the most likely main risk factor for NS. [ABSTRACT FROM AUTHOR]

Background: Individuals with high Loa loa microfilarial densities are at risk of developing severe encephalopathy after administration of antiparasitic drugs. Apart from this finding, loiasis is considered benign with no effect on brain function. However, recent epidemiological data suggest an increased mortality and morbidity in L. loa infected individuals, underscoring the importance of studies on the possible neurological morbidity associated with loiasis. Methodology: Using MoCA tests and neurological ultrasounds, we conducted a cross-sectional study to assess cognitive alteration in a population living in a rural area endemic for loiasis in the Republic of Congo. Fifty individuals with high microfilarial densities (MFD) were matched on sex, age and residency with 50 individuals with low MFD and 50 amicrofilaremic subjects. Analyses focused on individuals with MoCA scores indicating an altered cognition (i.e. < 23/30) and on the total MoCA score according to Loa loa MFD, sociodemographic characteristics and neurological ultrasound results. Principal findings: MoCA scores were very low in the studied population (mean of 15.6/30). Individuals with more than 15,000 microfilariae per milliliter of blood (mean predicted score:14.0/30) are more than twenty times more likely to have an altered cognition, compared to individuals with no microfilaremia (mean predicted score: 16.3/30). Years of schooling were strongly associated with better MoCA results. Extracranial and intracranial atheroma were not associated with L. loa MFD. Conclusion/significance: Loaisis microfilaremia is probably involved in cognitive impairment, especially when the MFD are high. These results highlight the urgent need to better understand loaisis-induced morbidity. Further studies investigating neurological morbidity of loiasis are needed. Author summary: Individuals with high Loa loa blood microfilarial densities are at risk of developing a serious encephalopathy after administration of antiparasitic drugs. Apart from this major inconvenience, L. loa filariasis (loiasis) is considered a benign disease, with no effect on brain function. However, recent epidemiological data suggest an increased mortality and morbidity in L. loa infected individuals, underscoring the importance of studies on the possible neurological morbidity associated with loiasis. This cross-sectional study assessed cognition using MoCA tests (Montreal Cognitive assessments, a tool for early detection of mild cognitive impairment) and neurological ultrasound among 143 matched individuals with either no microfilaremia, low microfilaremia or high microfilaremia. People with high microfilaremia were more than twenty times more likely to have an altered cognition, compared to individuals with no microfilaremia. [ABSTRACT FROM AUTHOR]

Background: Life-style metabolic diseases are steadily rising, not only in developed countries, but also in low- and middle-income countries, presenting a global health problem. Metabolic disorders like type 2 diabetes and cardiovascular diseases are among the ten leading causes of death defined by the WHO in 2019. Results from animal and observational human studies suggest a connection between the decline in human helminth infections and rise of life-style-associated metabolic diseases in developing regions. This trial was designed to investigate filarial infections and their impact on metabolic diseases in Cameroon. We hypothesize that the induction of regulatory immune responses during filarial infection reduces obesity-induced low-grade inflammatory immune responses and thereby improves metabolic parameters, whereas anthelmintic treatment abolishes this protective effect. Methods/design: Participants infected with Mansonella perstans, Onchocerca volvulus and/or Loa loa being lean (BMI <25), overweight (BMI >25 and <30) or clinically obese (BMI ≥30) from Littoral regions of Cameroon will be evaluated for their parasitological, immunological, metabolic and biochemical profile before and after treatment of their parasitic infections. Anthropomorphic measurements and a detailed questionnaire will complement our analysis. The investigation will assess blood immune cell populations, serum adipokines and cytokines that could be influenced by the parasite infection and/or metabolic diseases. Further, parameters like blood glucose, homeostatic model assessment of insulin resistance (HOMA-IR), circulating lipids and circulating makers of liver function will be monitored. Parameters will be assessed before treatment, 12 and 18 months after treatment. Conclusion: The focus of this study is to obtain a comprehensive metabolic profile of the participants in rural areas of Cameroon and to investigate the relationship between filarial immunomodulation and metabolic diseases. This study will elucidate the effect of anti-filarial treatment on the metabolic and immunological parameters that partake in the development of insulin resistance, narrowing in on a potential protective effect of filarial infections on metabolic diseases. Trial registration: doi.org/10.1186/ISRCTN43845142, ISRCTN43845142 February 2020 Trial title Effects of filarial parasite infection on type 2 diabetes Issue date: 27.10.22, V.1. [ABSTRACT FROM AUTHOR]