ArticleLiterature Review

Loa la does it deserve to be neglected?

Authors:
  • Institute of Tropical Medicine, Tuebingen
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Abstract

More than 10 million people in western and central Africa are estimated to be infected with Loa loa filarial nematodes. Like most other infectious diseases, L loa filariasis (loiasis) covers a wide range of symptoms. Severe complications have been reported; however, most observations are anecdotal, typically in travellers. The widespread use of filaricidal drugs within eradication programmes of Onchocerca volvulus and Wuchereria bancrofti led to the observation that concomitant L loa infection increases the risk of severe treatment-associated, life-threatening complications. Initiatives were therefore launched to map the risk of loiasis. Insight about the epidemiology of L loa has advanced notably; however, its effect on the individual as well as on the community level has not been well studied. In the absence of appropriate studies, L loa is commonly judged a harmless nematode, and loiasis as a separate entity does not belong to the list of neglected tropical diseases to be controlled or eradicated in worldwide campaigns. We advocate reorientation of research efforts towards a patient-centric view of loiasis and, as a first step, to establish the disease burden in disability-adjusted life-years of this chronic infection, and to answer the question of whether loiasis should be included in future control programmes.

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... While it is known that loiasis causes various manifestations, including signs and symptoms of a rather "allergic type" and varying degrees of immune-activation, these effects have been described to be more predominant in travelers and short term residents than in residents of endemic regions with chronic infections [10,11]. However, knowledge on disease outcomes in individuals living in endemic regions is scarce and improved understanding of the disease in this patient population is now increasingly warranted [8-10, 19,[22][23][24][25][26]. ...
... On the other hand, it is not known how long after a reported eye worm migration an individual remains actively infected. While it would be possible that the parasite died shortly after appearing as an eye worm, based on clinical reports it is estimated that adult L. loa filaria can live more than 15 years in the host [23]. Combining these factors, it becomes evident that history of eye worm is an imprecise diagnostic feature and does not allow to differentiate active from past infection. ...
... Further, the here provided findings were described in a large group of individuals who are likely to be re-exposed and chronically infected over several years. This underlines the significant clinical and hematological impact of loiasis, and refute once more the notion of loiasis being an inconspicuous, asymptomatic infection [1,7,[12][13][14]19,23,37]. Contrarily, loiasis apparently shares important similarities to other filarial diseases, for which the respective infection states leading to various disease outcomes have long been acknowledged [34,35]. ...
Article
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Background Loiasis–a filarial disease endemic in Central and West Africa–is increasingly recognized as significant individual and public health concern. While the understanding of the disease characteristics remains limited, significant morbidity and excess mortality have been demonstrated. Here, we characterize clinical and hematological findings in a large cohort from Gabon. Methods Loiasis-related clinical manifestations and microfilaremia, hemoglobin and differential blood counts were recorded prospectively during a cross-sectional survey. For analysis, participants were categorized into distinct infection states by the diagnostic criteria of eye worm history and microfilaremia. Results Analysis of data from 1,232 individuals showed that occurrence of clinical and hematological findings differed significantly between the infection states. Eye worm positivity was associated with a wide range of clinical manifestations while microfilaremia by itself was not. Loa loa infection was associated with presence of eosinophilia and absolute eosinophil counts were associated with extent of microfilaremia (p-adj. = 0.012, ß-estimate:0.17[0.04–0.31]). Conclusions Loiasis is a complex disease, causing different disease manifestations in patients from endemic regions. The consequences for the affected individuals or populations as well as the pathophysiological consequences of correlating eosinophilia are largely unknown. High-quality research on loiasis should be fostered to improve patient care and understanding of the disease.
... The parasite is transmitted to humans by Tabanid flies of the genus Chrysops and affects between 3 and 13 million people in the west and central regions of Africa [1]. Human loiasis is known to be endemic in eleven countries, including Angola, Chad, the Democratic Republic of the Congo, Cameroon, the Central African Republic, Equatorial Guinea, Ethiopia, Gabon, Nigeria, Republic of Congo and Sudan [2]. The main specific clinical manifestations include subcutaneous edema (Calabar swelling) and pruritus. ...
... Rarely, loiasis can cause damage in other organs [3]; although, a high Loa loa microfilaremia has been recently associated with an increased mortality risk [4]. Despite this, loiasis has been largely neglected as a public health problem in Africa and, even to date, the disease does not appear on the World Health Organization's (WHO) list of neglected tropical diseases (NTD) [2]. Loiasis actually appear in the WHO-ESPEN (Expanded Special Project for Elimination of NTDs) program [5]. ...
... Several studies have already demonstrated the efficacy of using PCR-based methods and LAMP assays for the detection of infectious agents-including parasites, viruses and bacteria-in combination with simple DNA extraction methods from DBS [35,38,39]. Regarding this, Chelex-100 resin-based DNA extraction methods are among the most widely used because these procedures are simple, rapid, economic, involve no organic solvents and do not require multiple tube transfers avoiding excessive handling [2,38,[40][41][42][43]. ...
Article
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Loiasis, caused by the filarial nematode Loa loa, is endemic in Central and West Africa. Loa loa has been associated with severe adverse reactions in high Loa-infected individuals receiving ivermectin during mass drug administration programs for the control of onchocerciasis and lymphatic filariasis. Diagnosis of loiasis still depends on microscopy in blood samples, but this is not effective for large-scale surveys. New diagnostics methods for loiasis are urgently needed. Previously, we developed a colorimetric high-sensitive and species-specific LAMP for Loa loa DNA detection. Here, we evaluate it in a set of 100 field-collected clinical samples stored as dried blood spots. In addition, Loa loa-LAMP was also evaluated in real-time testing and compared with microscopy and a specific PCR/nested PCR. A simple saponin/Chelex-based method was used to extract DNA. Colorimetric and real-time LAMP assays detected more samples with microscopy-confirmed Loa loa and Loa loa/Mansonella perstans mixed infections than PCR/nested-PCR. Samples with the highest Loa loa microfilariae counts were amplified faster in real-time LAMP assays. Our Loa loa-LAMP could be a promising molecular tool for the easy, rapid and accurate screening of patients for loiasis in endemic areas with low-resource settings. The real-time testing (feasible in a handheld device) could be very useful to rule out high-microfilariae loads in infected patients.
... Regarding mansonellosis little is known on its impact on population morbidity and mortality, however, this might be explained by the relatively lesser attention that it receives in comparison to other tropical diseases. Diagnosis of the infection is established by detection of parasites in biological specimen [5][6][7]. Most commonly microfilariae are microscopically determined in blood samples. ...
... Most commonly microfilariae are microscopically determined in blood samples. While for L. loa a circadian periodicity has been described with highest microfilariae densities around noon, no circadian periodicity is known for M. perstans [5][6][7][8]. ...
... Furthermore, in individual case management when infection by a filarial blood parasite is suspected it is recommended to withdraw venous blood of larger quantities (i.e. several milliliters) for microfilariae detection at different days [7,18]. Yet, it was the objective of this study to investigate CAP-VEN differences in microfilaraemia and a potentially resulting differential odds for microfilaraemia-detection. For that it was important to investigate equal sample volumes of CAP and VEN blood in order to enable a fair comparison. ...
Article
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Background Loa loa and Mansonella perstans-the causative agents of loiasis and mansonellosis-are vector-borne filarial parasites co-endemic in sub-Saharan Africa. Diagnosis of both infections is usually established by microscopic analysis of blood samples. It was recently established that the odds for detecting Plasmodium spp. is higher in capillary (CAP) blood than in venous (VEN) blood. In analogy to this finding this analysis evaluates potential differences in microfilaraemia of L. loa and M. perstans in samples of CAP and VEN blood.Methods Recruitment took place between 2015 and 2019 at the CERMEL in Lambaréné, Gabon and its surrounding villages. Persons of all ages presenting to diagnostic services of the research center around noon were invited to participate in the study. A thick smear of each 10 microliters of CAP and VEN blood was prepared and analysed by a minimum of two independent microscopists. Differences of log2-transformed CAP and VEN microfilaraemia were computed and expressed as percentages. Furthermore, odds ratios for paired data were computed to quantify the odds to detect microfilariae in CAP blood versus in VEN blood.ResultsA total of 713 participants were recruited among whom 52% were below 30 years of age, 27% between 30-59 years of age and 21% above 60 years of age. Male-female ratio was 0.84. Among 152 participants with microscopically-confirmed L. loa infection median (IQR) microfilaraemia was 3,650 (275-11,100) per milliliter blood in CAP blood and 2,775 (200-8,875) in VEN blood (p
... Loa loa is a common filarial parasite in Western and Central Africa which infects an estimated ten million people or more [1]. Loiasis, the infection caused by this parasite, is asymptomatic in most people infected [2]. ...
... Currently, it is estimated that greater than 10 million people are infected with Loa loa [1]. Endemic areas encompass much of Western and Central Africa with the highest prevalence of disease being in Cameroon, Gabon, Equitorial Guinea, Congo, and the Central African Republic [5]. ...
... The microfilaria presence in the serum follows a diurnal curve, with a high density between 10 : 00 and 16 : 00 [3]. Blood drawn outside this window may yield a false negative result [1]. It is interesting to note that our patient was found to have microfilaria in blood drawn at 20 : 00. ...
Article
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Purpose. To report a case of ocular involvement of Loa loa parasite. Observations. We present a rare case report of a Loiasis diagnosed in the United States from a patient presenting with subcutaneous migration of an adult worm within an eyelid who was found to have systemic disease with microfilaria in his blood. This is the second report in the United States and the eighth case in published literature worldwide. Conclusions and Importance. Due to the relatively mild disease course, Loiasis is relatively ignored in public health in low resource health districts. Understandably, the focus of public health in endemic areas must focus on basic health needs like malnutrition and diseases that entail a greater disease burden. As globalization has increased the amount of trade of physical goods, the effect of immigration also has implications for the spread of infectious disease. Medical practitioners in the United States should be aware of endemic diseases from foreign lands.
... The filarial helminth Loa loa and its characteristic manifestations of eye worm migration and Calabar swelling have been described in the literature for centuries. 1,2 Currently it is estimated that more than 10 million people are infected with L loa in central Africa and parts of west Africa, including highly endemic regions with historic eye worm prevalence of more than 60%. 1 L loa is transmitted by diurnal tabanid Chrysops spp flies and can cause extremely high blood micro filaria counts in the human host. During mass drug adminis tration programmes, these hypermicrofilaraemic patients were found to be at risk of developing serious adverse events when treated with certain anthelmintic drugs. ...
... 4,5 However, loiasis itself has attracted little interest for clinical research or control programmes. 1 The few existing reports on the clinical syndrome caused by L loa in endemic populations indicate substantial mor bidity with this infection. [6][7][8][9] Furthermore, severe organ damage has been attributed to loiasis, although thought to be rare, 9,10 and loiasis was described to be a major reason for medical consultation in endemic areas. 2 Importantly, a recent retrospective study revealed excess mortality in loiasis patients with high microfilaria loads. ...
... Thus, a formal burden of disease assessment from endemic areas is warranted. 1,9,11,12 Disabilityadjusted life years (DALYs), which take morbidity and mortality into account, are an established metric used to assess the impact of diseases and rank public health priorities in affected populations. 13 So far, no burden of disease assessment based on purposely collected field data has been done for loiasis. ...
Article
Background Loiasis is a highly prevalent helminth infection found in distinct regions of sub-Saharan Africa. The disease has been considered to be of minor clinical significance, but this belief is being increasingly challenged by recent evidence. We aimed to prospectively quantify the overall burden of disease caused by loiasis in an endemic region of Gabon, using disability-adjusted life years (DALYs). Methods We did a cross-sectional survey during 2017 and 2018 in rural Gabon. Volunteers underwent diagnostic tests for loiasis and were given a standardised questionnaire on symptoms. Participants reporting eye worm migration or harbouring Loa loa microfilariae were defined as loiasis positive. Morbidity-based DALYs associated with loiasis were estimated for the rural population of Gabon. Findings Between Sept 1, 2017 and May 31, 2018, 1235 participants residing in 38 villages in the Gabonese departments of Tsamba-Magotsi and Ogooué et des Lacs were screened. 626 (50·8%) of 1232 eligible participants had loiasis. 520 (42·2%) of 1232 participants reported eye worm migration. 478 (93·9%) of 509 individuals with eye worm migration also reported associated pain, and 397 (78·6%) of 505 reported vision disturbances. After correcting for age and sex, loiasis was significantly associated with a variety of symptoms, including transient painful oedema (adjusted odds ratio 1·76 [95% CI 1·37–2·26]) and arthralgia (1·30 [1·01–1·69]). Application of attributable fractions of correlating symptoms resulted in 412·9 (95% CI 273·9–567·7) morbidity-based DALYs per 100 000 people in rural Gabon. Interpretation Loiasis, with the pathognomonic sign of eye worm migration, appears to not be benign, but severely impeding to affected individuals. Furthermore, loiasis is associated with substantial morbidity, comparable to that of other neglected tropical parasitic diseases. These findings call for reconsideration of L loa as a relevant pathogen in affected populations, with a need for more concerted research and control of these infections. Funding Federal Ministry of Science, Research and Economy of Austria, and the European Union. Résumé Contexte La loase est une helminthiase très répandue que l’on retrouve dans des régions distinctes de l'Afrique subsaharienne. Longtemps considérée comme d’une importance clinique mineure, cette croyance est de plus en plus remise en cause. Étant donné que la plupart des travaux sur l'impact de la loase sur la santé sont anecdotiques, nous avons conduit la première étude plus précisément dans une région endémique, afin de quantifier de manière prospective le fardeau de la maladie à l’aide de l’espérance de vie corrigée de l’incapacité ou ‘’DALY’’ (Disability Adjusted Life Years – coûts par années de vie ajustées sur l'incapacité). Méthodes Au cours d’une enquête transversale, réalisée au Gabon en 2017 et 2018, des volontaires ont été soumis à des tests de diagnostic et ont répondu à un questionnaire standardisé sur les symptômes. Les participants rapportant la migration d’un ver oculaire et/ou l’hébergement de microfilaires Loa loa, étaient considérés comme des cas de loase. Le système de mesure ‘’DALY ‘’ a été calculé pour la population rurale du Gabon. Résultats Sur 1232 participants, 626 étaient des cas de loase (51%). Après correction de l'âge et le sexe, la loase était significativement associée à une variété de symptômes, notamment un œdème douloureux transitoire (OR ajustée 1 · 76 [1·37-2·26]) et une arthralgie (OR ajustée 1·30 [1·01-1·69]), entre autres. Des antécédents de migrations oculaires du ver ont été rapportés par 42% (520/1232) de tous les participants, dont 94% (478/509) y ont associé des douleurs et 79% (397/505) des troubles de la vision. L'application de fractions attribuables de symptômes relatifs résultent en 412·9 (273·9-567·7) morbidités selon la mesure DALY pour 100 000 habitants dans les régions rurales du Gabon. Interprétation Globalement, la loase a été associée à une variété de symptômes. Le signe pathognomonique de la migration oculaire du ver n’est pas bénin mais plutôt gravement incapacitant. Par conséquent, la loase est associée à une morbidité importante, comparable à d'autres maladies parasitaires tropicales négligées. Ces résultats invitent à une reconsidération de L. loa en tant que pathogène pertinent chez les populations affectées, avec un besoin de recherche et de contrôle plus concertés.
... Ef sníklafjöldinn er mikill eða óþekktur, er maelt með að gefa fyrst meðferð með albendazóli í þrjár vikur eins og gert var í tilfelli 1. 10 Sá annmarki er þó á meðferðinni að albendazól hefur minni virkni en DEC, það drepur aðeins fullorðna orma, en hefur minni aukaverkanir. 1 Hugsanlegt er að endurkoma einkenna í tilfelli 2 skýrist af því að albendazól hefur takmarkaða virkni gegn forlirfur (microfilariae) L. loa. Oftast er ekki fýsilegt að fjarlaegja orminn vegna þess hversu hreyfanlegur hann er, en með því móti faest þó nákvaem greining. ...
... Ekkert bóluefni er til, en talið er að mikil notkun á ivermektíni til að útrýma árblindu hafi átt sinn þátt í að draga úr útbreiðslu sýkingarinnar. 1 Einnig má íhuga lyfjagjöf með DEC, 300 mg vikulega, ef til daemis er um að raeða Vesturlandabúa sem starfa tímabundið á svaeðum þar sem sýkingin er útbreidd. ...
... Lóasýking er ekki talin til vanraektra hitabeltissjúkdóma af Alþjóðaheilbrigðisstofnuninni, 11 en nýlegar rannsóknir benda þó til að sýkingunni fylgi aukin dánartíðni 12 og lagt hefur verið til að sjúkdómurinn verði talinn til þessara sjúkdóma. 1 Með auknum ferðalögum má gera ráð fyrir að sýkingar af ýmsum toga sem faestir íslenskir laeknar þekkja nema af afspurn muni í vaxandi maeli koma til þeirra kasta. 13 Vert er að hafa slíka sjúkdóma í huga hjá sjúklingum með ódaemigerð og þrálát einkenni eins og í fyrra tilfelli okkar. ...
Article
We report two cases of Loa loa (eye worm) infection in Iceland; the former in a 35-year-old woman born in Africa but living in Iceland for several years; the latter in a 31-year- old woman who had traveled in Africa. Both women sought medical attention due to discomfort in one eye. On exami-nation a worm was noted in both cases, moving under the conjunctiva, 3 cm in length and 0.5 mm in diameter. Both patients also had symptoms from the extremities; episodic swelling and itching in the former case, and muscle pain in the latter. Both patients were diagnosed with loiasis with Calabar swellings of the extremities and were successfully treated with albendazole and diethylcarbamazine. Increased awareness is needed for infections which previously have been rare in the Nordics.
... A diagnostic kit can be used to detect MRSA specific antibodies in serum samples Metzger and Mordmüller, 2014). Multi-epitope peptides may be used to improve diagnostic kit accuracy, and antigen-based immunoassays are required for rapid point-of-care detection of MRSA. ...
... Multi-epitope peptides may be used to improve diagnostic kit accuracy, and antigen-based immunoassays are required for rapid point-of-care detection of MRSA. However, limited biomarker-based diagnostic techniques for MRSA have made it to the point-of-care (Akue et al., 2018;Metzger and Mordmüller, 2014). Consequently, this study sought to develop a diagnostic multi-epitope construct that is as accurate, specific, and efficient as possible. ...
Article
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Background: Methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA) remains a significant clinical and epidemiological pathogen in hospital settings and in the community world-wide. The resistance to methicillin in Staphylococcus aureus is mediated by the mecA gene, which encodes penicillin-binding protein 2a (PBP2A). Rapid patient screening for MRSA is essential for infection control procedures in order to possibly enhance the outcomes of infected patients. In this study, we utilized PBP2A to predict and create a novel synthetic protein with multiple immunodominant B cell epitopes for rapid diagnosis of MRSA using an in-silico approach. Methods: Seven putative PBP2A peptides were used to analyze the protein’s primary, secondary, and tertiary structures (BepiPred). The B cell construct was then evaluated using I-TASSER server, and physicochemical properties, and homology modeling of the 3 D structure of the protein were obtained. Results: In silico analyses revealed regions with high immunogenicity. Altogether, 19 consented epitopes were selected for the in-silico succession; three consented epitopes from ALJ10988.1, three from ORN56903.1, three from AFJ06714.1, one from AEO00772.1, three from WP_000721309.1, three from WP_057521704.1, and three from WP_063851348.1. The constructs have an average length of 503 amino acids, molecular weight of 55,151.78, instability index of 41.44, theoretical PI of 9.28 and a C score −1.50. In addition, the parameters that were examined indicated the newly multi-epitope construct could potentially serve as a theoretical framework for the development of a MRSA diagnostic kit. Conclusions: Overall, we have developed an antigen-based multi-epitope peptide for the rapid and accurate diagnosis of MRSA infection through an in-silico approach, acceptable in terms of antigenicity, physicochemical properties, structural stability and strong immunogenicity.
... Loa loa is a vector-borne filarial parasite affecting estimated 10 million people in West-Central Africa, with a limited geographical distribution: Angola, Cameroon, Central African Republic, Chad, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Nigeria, Republic of Congo and South Sudan. 1 The diagnosis of loiasis can be elusive, and its treatment is not standardized. 2,3 Infection may be asymptomatic or cause non-specific manifestations; specific signs, Calabar swelling and subconjunctival parasite migration, are inconstant. 1 Diagnosis relies on identification of circulating microfilariae. ...
... 2,3 Infection may be asymptomatic or cause non-specific manifestations; specific signs, Calabar swelling and subconjunctival parasite migration, are inconstant. 1 Diagnosis relies on identification of circulating microfilariae. These are 230-250 μm long, with colourless sheath in Giemsa-stained preparations, and nuclei extending to the tip of the tail. ...
Article
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In the absence of pathognomonic signs, the diagnosis of filarial infections relies on geographical exposure and morphology of microfilariae, which requires expertise. We present a case of loiasis in a patient not reporting exposure in areas of known Loa loa endemicity, whose diagnosis was achieved by molecular analysis of microfilariae.
... Parmi ces derniers, la prévalence la plus élevée (e.g. zones hyperendémiques) est observée au Gabon et en Guinée équatoriale, où elle peut dépasser 40 % dans les enquêtes de terrain [7]. Cependant, l'infection à Loa loa ne figure pas à l'heure actuelle dans la liste des maladies tropicales négligées établie par l'Organisation mondiale de la santé (OMS). ...
... Pourtant plusieurs études de terrain évaluant l'impact clinique et socio-économique dans les populations en zones d'hyperendémie, notamment au Gabon [8], réfutent cette caractérisation de maladie bénigne et tendent à prouver son impact clinico-socio-économique largement sous-estimé. L'inclusion de la loaose dans la liste des maladies tropicales négligées par l'OMS apparaît comme une étape nécessaire afin de mieux faire connaître cette filariose et stimuler la recherche sur cette parasitose afin d'en améliorer le contrôle en Afrique centrale et de l'Ouest [7,8]. ...
Article
Résumé La loaose est endémique dans plusieurs pays d’Afrique sub-saharienne. En France, elle reste une pathologie d’importation peu fréquente, diagnostiquée chez des patients de retour d’une zone d’endémie, souvent après plusieurs années d’évolution. Si la migration sous-conjonctivale et l’œdème de Calabar sont les manifestations cliniques les plus caractéristiques, des localisations inhabituelles, sont possibles. Ce cas clinique décrit un cas de loaose chez une patiente de 17 ans présentant une migration sous-conjonctivale et sous-palpébrale typique qui, au décours du traitement anti-parasitaire, expulsera un ver adulte par effraction du sillon gingivo-dentaire supérieur droit. Cette observation singulière permet de rappeler l’épidémiologie et les outils du diagnostic de cette parasitose.
... An estimated 10 million people are infected with L. loa in the 10 endemic countries of West Africa 1 and more than 114 million with M. perstans, mostly in sub-Saharan Africa. 2 Despite classical manifestations of loiasis having been reported as a major driver for people seeking medical advice in endemic areas, this infection has long been regarded as a benign condition. 1 Only recently has high L. loa microfilaremia been associated with an increased mortality risk, prompting reconsideration of the importance this parasitosis. 3 Infection with M. perstans is considered one of the most prevalent human parasitosis in Africa, but clear definition of symptoms and quantification of associated health consequences are still lacking. ...
... In our study, no appearance of specific symptoms and no new or increasing mf/mL, eosinophil counts, or antibody SI clearly indicating relapse were observed, likely due to the adoption, in our center, of a treatment schedule with plausible high macrofilaricidal effect. 1,24,25 When re-treatment was decided for patients in our cohort, a posttreatment rise in eosinophil counts and antibody SI was observed in some but not all occasions. Interestingly, in two patients (#7 and #10), a rise in these laboratory parameters could be observed after one re-treatment (at T2 and T15, . ...
Article
Infections due to Loa loa and Mansonella perstans are common yet elusive neglected filariases. Parasitological cure after treatment is very difficult to assess, as adult parasites are not accessible. Therefore, outside transmission areas, patients require a long follow-up period to ascertain the therapeutic outcome, which is impractical for non-sedentary populations such as migrants. We studied the change over time of microfilaremia, eosinophil counts, and antifilarial antibodies tested with a commercial ELISA test (Bordier Affinity Products, Crissier, Switzerland), in a retrospective cohort of patients with confirmed L. loa and M. perstans infections, to evaluate the role of serology in clinical practice. After treatment, all 22 eligible patients diagnosed in our center between 2015 and 2017 reached amicrofilaremia, with microfilarial counts decreasing sharply within 2 months. Paralleling eosinophil counts, antibodies decreased in all patients, 36% of whom reached sero-reversion or near-sero-reversion in < 20 months. These findings suggest that positive serology is not just residual from a past infection, and may be used for diagnosis even when microfilaremia is negative or cannot be performed. Interestingly, antibodies and eosinophil counts increased following some, but not all, re-treatment courses. If the rise in these parameters reflects death of macrofilariae, caution is required in interpreting high eosinophil counts and antibody titers shortly after treatment, as these may reflect no need for further treatment. To optimize patients' management, it is now pivotal to ascertain the interval between treatment and macrofilarial death and therefore whether re-treatments are required for complete clearance of parasites.
... Les infections par Loa loa sont restreintes aux forêts tropicales d'Afrique de l'Ouest et du Centre ou elles représentent au moins 10 millions de cas [23,[31][32][33] . Dans ces zones, de nombreux cas de co-infection avec O. volvulus, W. bancrofti et/ou M. perstans sont décrits [22,31,34,35] . ...
... Les infections par Loa loa sont restreintes aux forêts tropicales d'Afrique de l'Ouest et du Centre ou elles représentent au moins 10 millions de cas [23,[31][32][33] . Dans ces zones, de nombreux cas de co-infection avec O. volvulus, W. bancrofti et/ou M. perstans sont décrits [22,31,34,35] . ...
Thesis
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Les filaires sont des nématodes parasites transmis à des vertébrés par des arthropodes hématophages. Les espèces filariennes qui s'installent dans les cavités cœlomiques, les vaisseaux lymphatiques ou des tissus conjonctifs ont leurs stades infestants (ou L3) qui migrent via le système lymphatique après leur inoculation dans la peau. En utilisant le modèle murin avec la filaire Litomosoides sigmodontis dont les adultes résident dans la cavité pleurale, deux phases d'interaction des filaires avec les poumons des souris BALB/c sont décrites 1) lors de la migration des L3 de la peau à la cavité pleurale ; 2) pendant la phase patente de l’infection quand les adultes pondent des microfilaires dans la cavité pleurale. Dans la 1ère phase les L3 rejoignent le système sanguin pulmonaire puis traversent les poumons pour entrer dans la cavité pleurale. Ce passage induit une pathologie aigue transitoire: tout d'abord des hémorragies consécutives à la rupture des capillaires pulmonaires, accompagnées d'une augmentation du nombre de neutrophiles pulmonaires et de la libération transitoire d'IL-1β et des alarmines IL-33 et S100A9 dans la cavité pleurale. Le S100A9 semble faciliter la survie des filaires, soit par un effet anti-inflammatoire soit en facilitant la migration des L3. Les neutrophiles peuvent libérer des NETS en réponse aux L3. Dans les jours suivant l'infection, une réponse régulatrice se met en place dans les poumons, avec le recrutement de macrophages et d'éosinophiles, la production d'IL-4, de CCL2 et d'IL9, ainsi que la baisse d'expression de molécules inflammatoires. La formation des granulomes est également observée dans le tissu pulmonaire. Le passage des L3 induit aussi une inflammation des vaisseaux sanguins pulmonaires chez les souris C57BL/6 seulement. Lors de la phase patente de l'infection, 40% des souris ne développent pas de microfilarémie sanguine. La comparaison des réponses des souris microfilarienne et amicrofilarienne montre une exacerbation de l'inflammation pleurale induite par les microfilaires. De plus, les souris microfilarémiques développent une pathologie pulmonaire dépendant des microfilaires consistant en la fibrose de la plèvre viscérale, une accumulation périvasculaire de macrophages et une inflammation bronchoalvéolaire (production de mucus et éosinophilie). Le contrôle des filaires (adultes et microfilaires), mais aussi la mise en place de la pathologie sont dépendantes de l'IL-5 et de l'IL-4R.
... [11][12][13] It is endemic to West and Central Africa. [11][12][13][14][15][16][17] In non-endemic regions, loiasis is diagnosed in immigrants or returning travelers. 18,19 Clinical diagnosis is often based on history and clinical manifestations and is confirmed by demonstrating microfilariae in peripheral blood usually accompanied by eosinophilia. ...
... The patient had eosinophilia but lacked any specific symptoms attributable to loiasis. 11,[14][15][16][17]19 Those that are asymptomatic but microfilaremic are at an increased risk for morbidity and mortality. 16 Some patients with loiasis remain amicrofilaremic, 29 which led to the development of PCR-based tests that are not available for clinical use. ...
Article
A 63-year-old woman who migrated from Nigeria to the United States was found to have an elevated total serum protein, anemia, and eosinophilia. Serum protein electrophoresis (SPEP) and serum protein immunofixation electrophoresis (SPIFE) demonstrated monoclonal IgG κ restricted bands (IgG 3,820 mg/dL; κ/λ ratio 4.47), indicative of monoclonal gammopathy of unknown significance (MGUS). A rapid diagnostic test (RDT) for malaria was positive for Plasmodium falciparum (BinaxNOW®). Giemsa-stained blood smears were negative for malarial parasites, however, Loa loa microfilariae were identified. Reverse transcription polymerase chain reaction for P. falciparum, Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax yielded a negative result. She was treated for loiasis with diethylcarbamazine and received no malaria medication. Treatment resulted in a resolution of the microfilaremia and eosinophilia, a negative RDT for malaria, and marked reduction in the monoclonal gammopathy. This is the first reported human case of MGUS associated with loiasis and its resolution after antiparasitic treatment.
... Loiasis is a highly neglected infectious disease caused by the filarial nematode Loa loa typically manifesting as a migrating eye worm under the bulbar conjunctiva or transient peripheral oedemas. L. loa is endemic in West and Central Africa [1,2] with more than 10 million persons infected and 30 million at risk of infection [3]. For a long time loiasis has been considered an infection with limited clinical importance easily tolerated by infected individuals in endemic regions [4,5]. ...
Article
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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.
... It is transmitted to humans mainly through the bite of adult female Chrysops silacea and Chrysops dimidiata gadflies [1]. It is geographically distributed in the west and central region of the African continent, where >10 million people are estimated to be infected [2]. Pathognomonic manifestations of the disease are Calabar swelling and the presence of the adult worm on the surface of the eye, although most people infected with L loa are asymptomatic [1]. ...
Article
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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.
... However, this came at a huge compliance cost requiring twice or four times ivermectin treatment per year for at least a decade. Other setbacks to the sole reliance on ivermectin are: it is only microfilaricidal (Katabarwa et al. 2011), induces life-threatening complications in onchocerciasis individuals with concomitant Loa loa infection (Gardon et al. 1997;Metzger and Mordmüller 2014), and possible resistance may have emerged in some areas in Ghana and Cameroon (Bourguinat et al. 2007;Osei-Atweneboana et al. 2011). This indicates a limitation of the drug to completely break the transmission cycle especially in hyperendemic foci. ...
Article
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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.
... 2,3 The first line anti-parasitic medication like diethylcarbamazine (DEC) to kill both microfilaria and macrofilaria, 4,5 and the second line treatment include albendazole or ivermectin, both have limited efficacy on adult worms. 6 Oral steroid may be used in combination with anti-parasitic drug to reduce inflammation and allergic reaction to parasite and adverse effects of anti-parasitic medication. 1,3 Here, we attempt to report a rare case of atypical presentation of living parasite in the eyelid. ...
Article
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To report a rare case of living parasite in the eyelid. This case report was done in a tertiary care eye hospital in Bangladesh. We evaluated the patient thoroughly. CT scan of the orbit and histopathology were helped to diagnose the case. Per operative video recording, preoperative and postoperative photograph was documented properly. : A young boy presented with gradual swelling in the right upper eyelid. Clinically a firm mass was found in the right upper eyelid. CT Scan of the orbit revealed a cystic lesion in the eyelid. A live worm was extracted from the right upper eyelid. Parasitic lesion may be occurred in the eyelid. Ophthalmologist should be aware of the atypical presentation of the eyelid.
... 22 L. loa has been neglected because the impact on mortality was considered to be low. 24 However, in the past 20 years, L. loa was found to be a major obstacle in the implementation of mass drug administration programs for Onchocerca volvulus and lymphatic filariasis in co-endemic areas, since hypermicrofilaremic L. loa may induce fatal side effects including death when DEC or ivermectin, the drug used for mass chemotherapy, is applied. 25,26 Albeit in experimental conditions, 27-29 endangered species of primates are receptive to L. loa. ...
Article
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Roland Dieki,1,2 Edouard Nsi-Emvo,2 Jean Paul Akue1 1Department of Parasitology, International Centre of Medical Research of Franceville, Franceville, Gabon; 2Department of Chemistry, Université des Sciences et Techniques de Masuku (USTM), Franceville, GabonCorrespondence: Jean Paul Akue, Department of Parasitology, International Centre of Medical Research of Franceville, Franceville, BP 769, Gabon, Email jpakue@yahoo.frAbstract: Loa loa loiasis was considered an anecdotal disease 30 years ago. Its spread in Equatorial Africa and the side effects associated with mass drug administration programs against filariasis in co-endemic areas have drawn the attention of the international research community. Progress in research conducted to date has provided insight into the immunobiology of this parasite. An interesting finding reported in several studies is that 70% of individuals with loiasis do not carry microfilariae in their blood, and 30% are microfilaremic, suggesting the involvement of several immunological mechanisms, as shown by elevated specific IgG4 and IgE levels signifying a potential cross-linking mechanism between the two isotypes via L. loa antigen to prevent allergy. A mechanism of anergy in the appearance of microfilariae in the peripheral blood results in immunological unresponsiveness in individuals with microfilariae. There is an interaction between other pathogens (parasites, bacteria, viruses) in individuals co-infected with L. loa. The strong antigen cross-reactivity between L. loa and lymphatic filarial worms warrants a re-evaluation of the distribution of the latter in co-endemic regions. The mechanism of concomitant immunity observed in the elimination of microfilariae or infective larvae (third-stage larvae, L3) may be used for the conception of an immunoprophylactic strategy.Keywords: Loa loa, diagnostics, immune anergy, immune evasion, cross-reactivity
... The disease is limited to forested areas of western and central Africa, and it is especially common in Cameroon, eastern Nigeria, and Congo (6). More than 10 million people are estimated to be infected worldwide (7). There are two major clinical presentations, the first being adult worm migration under the bulbar conjunctiva (eyeworm) and the second a characteristic transient and migratory edema known as Calabar swelling, which is caused by its wanderings and is usually seen on the extremities (8,9). ...
Article
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Filariasis is a parasitic disease caused by infection with roundworms of the Filarioidea superfamily. Depending on the species of roundworm, the disease can present itself in one of three forms. It can affect the lymphatic system, the subcutaneous tissue, or serous cavities. We present the case of a male patient from central Europe with a subcutaneous manifestation similar to filariasis. Laboratory findings showed eosinophilia and elevated levels of IgE antibodies, and histological examination of skin biopsy material showed granulation tissue with lymphoid and plasma cell infiltration. When the lesion was examined under a microscope following an excision, live wormlike parasites about 3.5 cm long were detected. Such parasitic infections are usually encountered in tropical regions and sometimes reported in travelers returning from endemic countries. Our patient, however, had never left Europe, which is what makes this case so interesting.
... Infections with the filarial nematodes Loa loa and Mansonella perstans are among the most neglected filarial infections. L. loa is endemic in 11 countries of Central and West Africa and loiasis is estimated to affect about 20 million people (Metzger and Mordmüller, 2014;Molyneux, 2009). M. perstans infection is widespread in more than 30 countries of sub-Saharan Africa, while sporadic cases have been reported in Latin America, mostly in the Caribbean and along the Atlantic coast. ...
Article
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Infections with the filarial nematodes Loa loa and Mansonella perstans are among the most neglected filarial infections. L. loa is endemic in 11 countries of Central and West Africa and loiasis is estimated to affect about 20 million people. M. perstans infection is widespread in more than 30 countries of sub-Saharan Africa. Due to the difficulty in diagnosing loiasis and M. perstans mansonellosis on a clinical basis, the diagnosis of infection with L. loa and M. perstans relies on laboratory techniques. Definitive diagnosis is based on the detection, identification, and quantification of circulating microfilariae (mf) by microscopy of concentrated blood. However, this is impractical for screening purposes as it requires expert laboratory personnel, considerable blood manipulation, and is time consuming, especially for the final issue of negative result reports, which are very common in the population visited outside endemic areas. The aim of the current work is the preliminary evaluation of the performance of the in-house real-time PCR described by Ta and colleagues compared to the routine microscopic approach for the screening of filarial infections in the clinical setting outside endemic areas, using samples from patients accessing the dedicated outpatient clinics for migrants and travelers of a reference centre for tropical diseases in Northern Italy.
... Occasionally, adult worms will migrate to the eye and can be observed grossly in the conjunctiva (5). Diethylcarbamazine is the treatment of choice and is known to be effective at eradicating both microfilariae and adult worms but must be used with caution (6). There is significant risk of fatal encephalopathy in patients treated with DEC if the microfilarial load is high (Ͼ8,000 microfilariae per ml) in peripheral blood (https://www .cdc.gov/parasites/loiasis/health_professionals/index.html#tx). ...
... Loiasis or African eye worm is a vector-borne disease caused by a parasitic nematode, Loa loa, transmitted by a tabanid belonging to the genus Chrysops that colonizes forested areas of West and Central Africa, considered as high-risk for loiasis, where over 14 million people currently reside [1,2]. Infection with L. loa manifests itself in human populations by pruritus and two main clinical signs, the migration of adult worms under the bulbar conjunctiva, and migratory edema commonly known as Calabar swelling. ...
Article
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Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. IVM-based preventive chemotherapies (PCs), so-called community-directed treatment with ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. A cross-sectional study was conducted in the Yabassi Health District where CDTI have been implemented since 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf). The prevalence of loiasis was 3.7% (95% CI: 2.2-6.2), significantly lower than its baseline prevalence (12.4%; 95% CI: 10.1-15.2; Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline microfilarial density (mean = 839.3 mf/mL; SD = 6447.1; max = 130,840; Wilcoxon W = 179,904.5; p < 0.0001). This study revealed that the endemicity level of loiasis was significantly low compared to its baseline value, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.
... Loiasis or African eye worm is a vector-borne disease caused by a parasitic nematode, Loa loa, transmitted by a tabanid belonging to the genus Chrysops that colonizes forested areas of West and Central Africa, considered as high-risk for loiasis, where over 14 million people currently reside [1][2]. Infection with L. loa manifests itself in human populations by pruritus and two main clinical signs, the migration of adult worms under the bulbar conjunctiva, and migratory edema among which, the Calabar swelling. ...
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Background Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. IVM-based preventive chemotherapies (PC), so-called Community-Directed Treatment with Ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. Because of the geographic overlap of onchocerciasis and loiasis in Central Africa, one would have expected similar trend for loiasis in co-endemic settings. Surprisingly, a recent study revealed that L. loa entomological indices remained almost unchanged after 13 years of CDTI to fight onchocerciasis. This study then aimed to assess whether parasitological indicators of L. loa infection follow the same trends than the previously described entomological indices. A cross-sectional study was conducted in six communities of the Yabassi Health District where CDTI have been implemented since ~ 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf), then prevalence and intensity of infection were compared to baseline data. Results A total of 376 individuals (55.9% female), aged 5 to 89 years old, were enrolled in this study. The prevalence of loiasis was 3.7% (95% CI: 2.2–6.2), significantly lower than its baseline (12.4%; 95% CI: 10.1–15.2) (Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (Mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline (Mean = 839.3 mf/mL; SD = 6447.1; max = 130,840) (Wilcoxon W = 179904.5; p < 0.0001). Conclusions This study revealed that the prevalence and intensity of L. loa infection were significantly low compared to their baselines, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.
... Introduction Loiasis, the disease caused by the infection with the filarial nematode Loa loa, is transmitted through the bite of tabanid flies of the genus Chrysops. It is endemic in Central and West Africa where, according to the most recent estimates, about 10 million people are infected [1]. ...
Article
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Loiasis, caused by the filarial nematode Loa loa, is endemic in Central and West Africa where about 10 million people are infected. There is a scarcity of convenient, commercial diagnostics for L. loa. Microscopy requires trained personnel and has low sensitivity, while the serodiagnosis is currently not standardized. Individual case management is also important in non-endemic countries to treat migrants, expatriates and tourists. We retrospectively compared the performance of a Loa Antibody Rapid Test (RDT) and a commercial ELISA pan-filarial test on 170 patients, 65 with loiasis [8 with eyeworm, 29 with positive microfilaremia, 28 with neither microfilaremia nor history of eyeworm but eosinophilia and history of Calabar swelling (occult loiasis)], 95 with other common parasitic infections and no previous exposure to L. loa (37 with M. perstans, 1 with Brugia sp., 18 with strongyloidiasis, 20 with schistosomiasis, 5 with hookworm, 4 with Ascaris lumbricoides infection, 10 with hyper-reactive malarial splenomegaly), and 10 uninfected controls. The sensitivity of the RDT and of the ELISA were 93.8% (61/65) and 90.8% (59/65), respectively. For the RDT, most of the cross-reactions were observed in patients with M. perstans: 7/37 (18.9%), followed by 1/10 (10%) with hyper-reactive malarial splenomegaly and 1/20 (5%) with schistosomiasis. None of the 27 subjects infected with intestinal nematodes was found positive at this test. The ELISA is meant to be a pan-filarial assay, and reacted extensively with cases of M. perstans (95%), as expected, and also in 11/18 (61.1%) patients with strongyloidiasis and in 3/5 (60%) with hookworm infection. The RDT and the ELISA are both highly sensitive for the diagnosis of loiasis. The main difference lies in the extent of cross-reactivity with other parasites. Considering that the RDT is specifically meant for Loa loa infection, and its high sensitivity, this test could be a useful tool for the diagnosis of occult loiasis.
... We estimate that by 2025 there will be more than 6 million L. loa microfilaremic cases remaining that may require treatment for loiasis infection. Loa loa may cause more harm than commonly suggested; infection can lead to various severe complications, including cardiac fibrosis, encephalopathy (in the absence of treatment), pulmonary infiltrates, neurological and psychiatric disorders, and excess mortality [33,34]. We predict that by 2025, 684 000 people living in nonendemic areas for onchocerciasis will be L. loa hypermicrofilaremic, justifying additional investments in research and drug development for treating L. loa infection. ...
... Loiasis, also called the "African eye worm", affects between 3 and 13 million individuals living in west and central regions of Africa [1,2]. The endemic countries are Angola, Chad, Democratic Republic of the Congo, Cameroon, Central African Republic, Equatorial Guinea, Gabon, Nigeria, Republic of Congo, and South Sudan [3]. In endemic areas, loiasis is often regarded as benign, and the infection is so common that little effort has been made to assess the frequency of its clinical manifestations and the efficacy of the various treatments used [4,5]. ...
Article
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Abstract Background Loiasis is an uncommon and poorly understood parasitic disease outside endemic areas of Africa. The aim of this study was to describe the clinical and biological patterns and treatment of imported loiasis by sub-Saharan migrants diagnosed in Madrid, Spain. Methods A retrospective study was conducted with sub-Saharan immigrants seen at the Tropical Medicine Unit of the Carlos III Hospital in Madrid, Spain, a reference center, over 19 years. Categorical variables were expressed as frequency counts and percentages. Continuous variables were expressed as the mean and standard deviation (SD) or median and interquartile range (IQR: Q3–Q1). Chi-square tests were used to assess the association between categorical variables. The measured outcomes were expressed as the odds ratio (OR) with a 95% confidential interval. Continuous variables were compared by Student’s t-tests or Mann-Whitney U tests. Binary logistic regression models were used. P
... This will be especially true in communities bearing high microfilarial burdens, as severe manifestations of loiasis occur at higher frequencies in heavily infected individuals. We advocate that large-scale, community-wide (and ideally longitudinal) studies be conducted in endemic regions to ascertain the true prevalence of atypical loiasis manifestations and the association between infection intensity and morbimortality to better understand the clinical and public health burden of loiasis in its own right and not merely as an impediment to the control of other filarial diseases [37]. ...
Article
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Background Loiasis is mostly considered a relatively benign infection when compared with other filarial and parasitic diseases, with Calabar swellings and eyeworm being the most common signs. Yet, there are numerous reports in the literature of more serious sequelae. Establishing the relationship between infection and disease is a crucial first step toward estimating the burden of loiasis. Methods We conducted a systematic review of case reports containing 329 individuals and detailing clinical manifestations of loiasis with a focus on nonclassical, atypical presentations. Results Results indicate a high proportion (47%) of atypical presentations in the case reports identified, encompassing a wide range of cardiac, respiratory, gastrointestinal, renal, neurological, ophthalmological, and dermatological pathologies. Individuals with high microfilarial densities and residing in an endemic country were at greater risk of suffering from atypical manifestations. Conclusions Our findings have important implications for understanding the clinical spectrum of conditions associated with Loa loa infection, which extends well beyond the classical eyeworm and Calabar swellings. As case reports may overestimate the true rate of atypical manifestations in endemic populations, large-scale, longitudinal clinico-epidemiological studies will be required to refine our estimates and demonstrate causality between loiasis and the breadth of clinical manifestations reported. Even if the rates of atypical presentations were found to be lower, given that residents of loiasis-endemic areas are both numerous and the group most at risk of severe atypical manifestations, our conclusions support the recognition of loiasis as a significant public health burden across Central Africa.
... We detected sequences related to a variety of filarial nematodes in order Spirurida, including W. bancrofti, D. immitis, Brugia timori, Elaeophora elaphi, and Loa loa (Table 4 and Supplementary Table S1). D. immitis is a common filarial parasite in dogs, whereas three of the other species, W. bancrofti, B. timori, and L. loa, are human filarial parasites [21,22] and E. elaphi has only been reported as a parasite in red deer (Cervus elaphus) in Spain [23]. These facts indicate that the sequences with the highest similarity to human and deer filarial parasites may have originated from D. immitis, but were misclassified. ...
... L oiasis (tropical eye worm) is a parasitic helminth disease affecting ~13-15 million people in forested areas of Central and West Africa 1,2 . The disease is transmitted by bloodfeeding Chrysops tabanid flies carrying the causative agent, the filarial worm Loa loa. ...
Article
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Elimination of the helminth disease, river blindness, remains challenging due to ivermectin treatment-associated adverse reactions in loiasis co-infected patients. Here, we address a deficit in preclinical research tools for filarial translational research by developing Loa loa mouse infection models. We demonstrate that adult Loa loa worms in subcutaneous tissues, circulating microfilariae (mf) and presence of filarial biomarkers in sera occur following experimental infections of lymphopenic mice deficient in interleukin (IL)-2/7 gamma-chain signaling. A microfilaraemic infection model is also achievable, utilizing immune-competent or -deficient mice infused with purified Loa mf. Ivermectin but not benzimidazole treatments induce rapid decline (>90%) in parasitaemias in microfilaraemic mice. We identify up-regulation of inflammatory markers associated with allergic type-2 immune responses and eosinophilia post-ivermectin treatment. Thus, we provide validation of murine research models to identify loiasis biomarkers, to counter-screen candidate river blindness cures and to interrogate the inflammatory etiology of loiasis ivermectin-associated adverse reactions.
... Albeit rarely, loiasis can cause damage to other organs [2]. Loiasis had been considered as a benign disease until a retrospective study recently demonstrated an excess of mortality in patients with high microfilaremia [3], and advocated more studies on this disease [4]. Currently three drugs may be used for the treatment of loiasis: diethylcarbamazine (DEC), ivermectin (IVM) and albendazole (ALB). ...
Article
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Background Loa loa infection is endemic in limited areas of West-Central Africa. Loiasis has been associated with excess mortality, but clinical studies on its treatment are scant, particularly outside endemic areas, due to the rarity of cases diagnosed. Methodology/Principal findings With this retrospective TropNet (European Network for Tropical Medicine and Travel Health) study, we aimed at outlining the treatment schedules followed by different reference centers for tropical medicine across Europe. We gathered information about 238 cases of loiasis, 165 of which had follow up data. The regimens followed by the different centers were heterogeneous. The drugs most frequently administered were: diethylcarbamazine alone (74/165, 45.1%), ivermectin alone (41/165, 25%), albendazole + ivermectin (21/164, 11.6%), ivermectin + diethylcarbamazine (16/165, 9.7%). Conclusions/Significance The management of loiasis substantially differs across specialized travel clinics in Europe. These discrepancies could be due to different local protocols as well as to (un)availability of the drugs. An harmonization of clinical protocols for the treatment of loiasis would be suggested across reference centers for tropical medicine in Europe.
... Loa loa causes a chronic infection in humans that is characterized by two clinical features which are migration of adult worms across the sub-conjunctiva and Calabar swelling, (localized angioedema found predominantly on the extremities). It is transmitted by species of horse-flies (Chrysops spp.), most commonly Chrysops dimidiata and C. silacea which inhabit the forest areas of West and Central Africa, extending to the Ethiopian border [15]. Loiasis affects more than 40% of people with an estimate of 14.4 million people at risk of becoming infected [16]. ...
Chapter
This chapter defines the group of parasitic worms, which belong to the main groups of trematodes, cestodes, nematodes, pentastomids, acanthocephalans and leeches. Important species of respective groups are each described under the headlines name, geographic distribution, biology/morphology, symptoms of disease, diagnosis, pathway of infection, prophylaxis, incubation period, prepatent period, patency, chemotherapy and further reading.
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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 microfilarias. 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.
Article
Loiasis is a parasitic infection caused by the filarial nematode Loa loa within endemic regions of West and Central Africa. These regions include areas co-endemic for other nematode infections. Although loiasis is rarely seen in the United States (US), primary care providers who regularly see refugees from endemic areas should be aware of its clinical presentation, diagnostic work-up, and initial management. Given the challenges of diagnosing loiasis, especially in low prevalence settings, we present cases of four family members, two of whom were diagnosed with loiasis, and discuss an approach to screening populations from endemic regions during their initial Refugee Health Examination upon arrival to the US.
Article
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Background: Onchocerciasis (river blindness) caused by the filarial worm Onchocerca volvulus is a neglected tropical disease that affects the skin and eyes of humans. Mass drug administration with ivermectin (IVM) to control the disease often suffers from severe adverse events in individuals co-injected with high loads of Loa loa microfilariae (mf). Thus loiasis animal models for counter-screening of compounds effective against onchocerciasis are needed, as are the corresponding onchocerciasis screening models. The repertoire of such models is highly limiting. Therefore, this study was aimed at developing and validating mf immunocompetent small animal models to increase tools for onchocerciasis drug discovery. Methodology/principal findings: O. ochengi mf from cattle skin and L. loa mf from human blood were used to infect BALB/c mice and Mongolian gerbils, and IVM was used for model validation. O. ochengi mf were given subcutaneously to both rodents while L. loa mf were administered intravenously to mice and intraperitoneally to gerbils. IVM was given orally. In an 8-day model of O. ochengi mf in BALB/c mice, treatment with IVM depleted all mf in the mice, unlike the controls. Also, in a 2.5-day model of L. loa mf in BALB/c, IVM significantly reduced mf in treated mice compared to the untreated. Furthermore, the gerbils were very susceptible to O. ochengi mf and IVM eradicated all mf in the treated animals. In the peritoneal L. loa mf gerbil model, IVM reduced mf motility in treated animals compared to the controls. In a 30-day gerbil co-injection model, IVM treatment cleared all O. ochengi mf and reduced motility of L. loa mf. Both mf survived for up to 50 days in a gerbil co-injection model. Conclusions/significance: We have developed two immunocompetent small animal models for onchocerciasis and loiasis that can be used for microfilaricide discovery and to counter-screen onchocerciasis macrofilarides.
Article
ZUSAMMENFASSUNG Rund 10–15 Mio. Menschen in Zentral- und Westafrika sind mit der Filarie Loa loa infiziert. Obwohl die assoziierte Krankheitslast vergleichbar mit wichtigen Tropenkrankheiten wie der Schistosomiasis ist, gilt die Loaisis bisher als extrem vernachlässigte Tropenerkrankung. Parasitologisch wird differenziert zwischen der mikrofilariämen Loiasis, bei der die Mikrofilarien mittels Mikroskopie im Blutausstrich nachgewiesen werden, und der okkulten Loiasis, die nur bei entsprechender Exposition durch typische Symptome diagnostiziert werden kann. Pathognomonische Symptome sind die Wanderung des adulten Wurms in der Konjunktiva („afrikanischer Augenwurm“) sowie die transiente Calabar-Schwellung. Die Therapie der Loaisis stellt vor allem in Endemiegebieten oft eine große Herausforderung dar. Potenziell schwere Nebenwirkungen der verfügbaren Medikamente sowie das hohe Risiko einer Reinfektion führen meist dazu, dass L. loa-Patient*innen in den Endemiegebieten keine Therapie erhalten.
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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 mired by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo . This study assessed the survival of O. change 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 enzyme-liberated O. change female worms, and sacrificed at various time points to test for survival. Recovered worms 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, 58.6 ± 7.5% female worms were recovered from hamsters, and 20 ± 3.5% from gerbils. Those recovered from gerbils were mostly disintegrated or fragmented, with significantly higher fragmentation observed with enzymatically-liberated worms. FBZ had no significant effect on the number worms recovered, but enhanced embryo degradation in gerbils and reduced worm viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. change . The hamsters appeared to maintain the worms longer, compared to gerbils.
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Loa loa is a filarial nematode responsible for loiasis, endemic to West-Central Africa south of the Sahara and transmitted by flies. This study reports a case of L. loa in the vitreous cavity of the eye of a young patient, along with an in-depth literature review. A 22-year-old woman from Cameroon who migrated from Cameroon to Italy was referred to the Emergency Ophthalmology Department at Policlinico di Bari in July 2021 with the presence of a moving parasite in the subconjunctiva of the left eye. A recent onset of a papular lesion on the dorsal surface of the right wrist and a nodular lesion in the scapular region were detected. L. loa filariasis was diagnosed based on anamnestic data, clinical and paraclinical signs, and a parasitological test confirming the presence of microfilariae in two blood samples collected in the morning of two different days. Because of the unavailability of diethylcarbamazine (DEC), albendazole (ALB) 200 mg twice daily was administered for 21 days. A mild exacerbation of pruritus occurred during treatment, but resolved with the use of an antihistamine. A single dose of 12 mg ivermectin was prescribed at the end of the treatment with albendazole. Unlike other endemic parasite infections, L. loa is not included in the Global Program to Eliminate Lymphatic Filariasis, because it is not mentioned in the WHO and CDC list of neglected tropical diseases. This can result in an overall risk of lack of attention and studies on loiasis, with lack of data on global burden of the disease.
Article
Loiasis, also called African eye worm, is not currently on WHO's list of priority neglected tropical diseases, even though the risk that individuals with high Loa loa microfilarial densities will develop potentially fatal encephalopathy when they take ivermectin has complicated efforts to use mass drug administration for onchocerciasis (river blindness) and lymphatic filariasis control in co-endemic areas. At least 10 million residents of central and west Africa are thought to have loiasis, which causes painful and itchy subcutaneous oedema, arthralgia, and discomfort when adult helminths that are 3–7 cm in length are present under the conjunctiva of the eye. High levels of microfilaraemia are associated with renal, cardiac, neurological, and other sequelae, and an increased risk of death. The public health burden of loiasis could be greatly reduced with expanded use of diagnostic tests, anthelmintic treatment, and control of the Chrysops spp (tabanid flies) vectors that transmit the parasite. Loiasis should be added to the next revision of the WHO neglected tropical disease priority list, not merely because its inclusion will support the elimination of other skin and subcutaneous neglected tropical diseases, but also because of the complications caused by loiasis itself.
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Loa loa microfilariae were found on thick blood smears (TBSs) from 8 of 300 (2.7%) residents of Bioko Island, Equatorial Guinea, during a Plasmodium falciparum sporozoite malaria vaccine clinical trial. Only one subject was found to have microfilaraemia on his first exam; parasites were not discovered in the other seven until subsequent TBSs were performed, at times many weeks into the study. All infected individuals were asymptomatic, and were offered treatment with diethylcarbamazine, per national guidelines. L. loa microfilaraemia complicated the enrolment or continued participation of these eight trial subjects, and only one was able to complete all study procedures. If ruling out loiasis is deemed to be important during clinical trials, tests that are more sensitive than TBSs should be performed.
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Loiasis, the infection with the vector-borne filarial nematode Loa loa, is widely distributed in central and west Africa. Long considered a rather benign infection, recently loiasis with high microfilarial burden was associated with increased mortality risk. Eyeworm and Calabar swelling are pathognomonic signs of the infection, but other atypical, non-specific manifestations can also occur. For instance, splenic nodules have been seldom reported. In this Grand Round, we report two cases of loiasis in migrants who presented with spleen nodules, which could be followed up over time (up to 27 months) with multiple imaging techniques until their resolution. We comment on the clinical implications of these observations, including differential diagnosis with similar imaging findings, and critically review the evidence of spleen involvement in loiasis and other filarial infections.
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Background Regular and comprehensive epidemiological surveys of the filarial nematodes Mansonella perstans and Loa loa in children, adolescents and adults living across Bioko Island, Equatorial Guinea are lacking. We aimed to demonstrate that blood retained on malaria rapid diagnostic tests, commonly deployed for malaria surveys, could be used as a source of nucleic acids for molecular based detection of M . perstans and L . loa . We wanted to determine the positivity rate and distribution of filarial nematodes across different age groups and geographical areas as well as to understand level of co-infections with malaria in an asymptomatic population. Methodology M . perstans , L . loa and Plasmodium spp. parasites were monitored by qPCR in a cross-sectional study using DNA extracted from a subset malaria rapid diagnostic tests (mRDTs) collected during the annual malaria indicator survey conducted on Bioko Island in 2018. Principal findings We identified DNA specific for the two filarial nematodes investigated among 8.2% (263) of the 3214 RDTs screened. Positivity rates of M . perstans and L . loa were 6.6% and 1.5%, respectively. M . perstans infection were more prominent in male (10.5%) compared to female (3.9%) survey participants. M . perstans parasite density and positivity rate was higher among older people and the population living in rural areas. The socio-economic status of participants strongly influenced the infection rate with people belonging to the lowest socio-economic quintile more than 3 and 5 times more likely to be L . loa and M . perstans infected, respectively. No increased risk of being co-infected with Plasmodium spp. parasites was observed among the different age groups. Conclusions/Significance We found otherwise asymptomatic individuals were infected with M . perstans and L . loa . Our study demonstrates that employing mRDTs probed with blood for malaria testing represents a promising, future tool to preserve and ship NAs at room temperature to laboratories for molecular, high-throughput diagnosis and genotyping of blood-dwelling nematode filarial infections. Using this approach, asymptomatic populations can be reached and surveyed for infectious diseases beyond malaria.
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Case Report An otherwise healthy young patient, born and raised in Yaounde (Cameroon), currently living in Switzerland for 7 years (since 2014), was referred to the tropical medicine consultation of the University Hospitals of Geneva (Switzerland) by her general practitioner to investigate an asymptomatic eosinophilia of 1.22 G/l. The patient did not travel outside Europe in the last 7 years. She recalls a history of “eye worm “in Cameroon, possibly treated with unknown topic treatment. She does not remember any Calabar swelling in the past nor other medical problems. Filaria antibodies were found positive (enzyme-linked immunosorbent assay 0.96 optical density, reference < 0.5; immunofluorescent antibody test 1:320, reference < 1:160) and the circulating filarial antigen was negative. Schistosoma spp. and Strongyloides stercoralis serologies were also done and both came out negative. Because of the high suspicion of Loa loa infection, a diurnal search of microfilariae was realized. Direct microscopic observation (Video, available as Supplementary data at JTM online) found viable microfilariae, and the stained blood smear confirmed Loa loa species (839 mf/ml).(Figure 1).
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The novel coronavirus disease 2019 (COVID-19) is one of the worst global health crises of this generation. The core of this pandemic is the rapid transmissibility of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, its high morbidity and mortality, and the presence of infectious asymptomatic carriers. As a result, COVID-19 has dominated this year's headlines and commanded significant research attention. As we consider SARS-CoV-2 and the COVID-19 pandemic, it is essential that scientists, governments, the media, and the general population also come to grips with the everyday cost of parasitic diseases. Plasmodium (malaria), schistosomes, filarial worms, hookworms, Ascaris, whipworms, and other protozoan and metazoan parasites take a tremendous toll on local communities. Yet, because most of these diseases are no longer endemic to developed countries, their research and intervention are not funded at levels that are proportional to their global morbidity and mortality. The scientific and public health communities must indeed vigorously fight SARS-CoV-2 and COVID-19, but while doing so and beyond, it will be essential to demonstrate steadfast resolve toward understanding and combating the parasitic diseases that for centuries have haunted humankind.
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Objective: Ocular loasis refers to ocular conditions such as pain and redness caused by the movement of the Loa loa nematode through the subconjuctival space of the eye. It is a tropical disease that is very rarely seen in North America. We report the case of a 32-year-old male who was recently diagnosed with ocular loasis in the Midwestern region of the United States. Methods: He presented to the emergency department with left eye pain after seeing a “worm in his eye” the previous night. He had emigrated from Cameroon 7 years prior. Anterior segment examination revealed a translucent, motile worm in the subconjunctival space of his left eye. Results: Prior to the patient’s scheduled follow-up for surgical removal of the worm, it migrated into the lower eyelid subdermal space. Serum testing confirmed the presence of Loa loa microfilariae at a concentration of >17,000 mf/mL. Conclusion: The patient was treated at the National Institute of Health (NIH) with pheresis followed by diethylcarbamazine and reported symptomatic improvement 1 month after treatment. This case report demonstrates the importance of being able to recognize and properly manage vector-borne parasites in nonendemic areas due to increased travel and climate change.
Chapter
The cutaneous filariae are transmitted by biting insects. Some, such as Onchocerca volvulus , are transmitted by Simulium flies and can cause debilitating conditions such as visual impairment and disfiguring skin conditions. The Mansonella infections are transmitted either by Simulium flies or biting midges (genus Culicoides ), but consequences of infections are general mild. Loa loa is transmitted by the bite of the Chrysops fly. Loaisis is manifest by adult worms periodically passing beneath the sclera and by subcutaneous swellings, usually of the forearm. Onchocerciasis, or river blindness, historically occurred in 34 countries in Africa, Yemen, and Latin America. It is estimated that 18 million people are infected, and 87 million at risk of infection. Most are in Africa. Mass treatment with ivermectin has now greatly lessened the ocular burden of infection.
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Loiasis is a vector-borne parasitic disease caused by the filarial Loa loa (L. loa). Definitive diagnosis can be done by identifying and counting microfilariae in the peripheral blood by microscopy and with L.loa-specific PCR. An additional diagnostic method is the detection of L.loa-specific antibodies. Accurate methods are needed to automate quantification of microfilaria (mf) in peripheral blood. Indeed, the treatment procedure depends on the microfilarial L. loa load in blood. We report the first documented use of flow cytometry as a new method to count microfilaraemia in peripheral blood from a patient with L. loa infection. The diagnosis of loiasis was strongly suspected based on clinical presentation and rapidly confirmed by identifying typical features of L. loa in the peripheral blood. This diagnosis was achieved by flow cytometry using a specific fluorescence pattern for microfilaraemia count. The current report highlights the potential of flow cytometry to assess microfilarial L. loa load from a patient with loiasis infection.
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We describe the outcomes of 16 cases of imported loiasis in Italy. Patients had microfilaremia <20,000/mL and were treated with high-dose albendazole for 28 days and a single dose of ivermectin. This combination might be an effective treatment option in nonendemic areas, when diethylcarbamazine, the drug of choice, is not available.
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Interest in filariasis has found a new impetus now that neglected tropical diseases have their own journal. However, some of the advances published in renowned international journals have completely ignored previous publications on the subject, particularly those in languages other than English. The rapid assessment procedure for loiasis and the mapping of lymphatic filariasis provide two perfect illustrations of this. This problem may seem a bit outdated, given that all "good authors" now publish exclusively in English. It certainly is outdated for most areas of medicine. But, surely, this should not be the case for neglected tropical diseases, for which certain long-standing findings are every bit as important as what may be presented as new discoveries. One possibility would be for certain journals, such as PLOS Neglected Tropical Diseases, to include a specific heading permitting the publication in English of older studies that initially appeared in a language other than English. The texts would be English versions respecting the entirety of the original text. Submission should be accompanied by a presentation of the problem, with details and explanatory comments, with submission at the initiative of the authors of the former article in question or their students or sympathizers.
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The filarial parasites Loa loa and Mansonnella perstans are endemic in the central and western African forest block. Loa loa is pathogenic and represents a major obstacle to the control of co-endemic filariae because its treatment can cause fatal complications such as encephalitis. 4392 individuals aged over 15 years were studied both by direct examination and a concentration technique. The overall prevalence rates were 22.4% for Loa loa microfilaremia, 10.2% for M. perstans microfilaremia, and 3.2% for mixed infection. The prevalence of both filariae was higher in the forest ecosystem than in savannah and lakeland (p<0.0001). The intensity of microfilariae (mf) was also higher in the forest ecosystem for both parasites. The prevalence and intensity of microfilaria were both influenced by age and gender. Correlations were found between the prevalence and intensity of Loa loa microfilariae (r = 0.215 p = 0.036), and between the prevalence of Loa loa and the prevalence of individuals with microfilaria >8000 mf/ml (r = 0.624; p<0.0001) and microfilariae >30 000 mf/ml (r = 0.319, p = 0.002). In contrast, the prevalence of pruritis and Calabar swellings correlated negatively with the prevalence of Loa loa microfilaria (r = -0.219, p = 0.032; r = -0.220; p = 0.031, respectively). Pruritis, Calabar swellings and eye worm were not associated with L. loa mf intensity (r = -0.144, p = 0.162; r-0.061, p = 0.558; and r = 0.051, p = 0.624, respectively), or with the prevalence or intensity of M. perstans microfilariae. This map of the distribution of filariae in Gabon should prove helpful for control programs. Our findings confirm the spatial uniformity of the relationship between parasitological indices. Clinical manifestations point to a relationship between filariae and allergy.
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Loiasis is a major obstacle to ivermectin treatment for onchocerciasis control and lymphatic filariasis elimination in central Africa. In communities with a high level of loiasis endemicity, there is a significant risk of severe adverse reactions to ivermectin treatment. Information on the geographic distribution of loiasis in Africa is urgently needed but available information is limited. The African Programme for Onchocerciasis Control (APOC) undertook large scale mapping of loiasis in 11 potentially endemic countries using a rapid assessment procedure for loiasis (RAPLOA) that uses a simple questionnaire on the history of eye worm. RAPLOA surveys were done in a spatial sample of 4798 villages covering an area of 2500×3000 km centred on the heartland of loiasis in Africa. The surveys showed high risk levels of loiasis in 10 countries where an estimated 14.4 million people live in high risk areas. There was a strong spatial correlation among RAPLOA data, and kriging was used to produce spatially smoothed contour maps of the interpolated prevalence of eye worm and the predictive probability that the prevalence exceeds 40%. The contour map of eye worm prevalence provides the first global map of loiasis based on actual survey data. It shows a clear distribution with two zones of hyper endemicity, large areas that are free of loiasis and several borderline or intermediate zones. The surveys detected several previously unknown hyperendemic foci, clarified the distribution of loiasis in the Central African Republic and large parts of the Republic of Congo and the Democratic Republic of Congo for which hardly any information was available, and confirmed known loiasis foci. The new maps of the prevalence of eye worm and the probability that the prevalence exceeds the risk threshold of 40% provide critical information for ivermectin treatment programs among millions of people in Africa.
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Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Loa loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Loa mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs.
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Onchocerciasis can be effectively controlled by annual mass treatment with ivermectin in endemic communities. However, in communities that are endemic for loiasis there may be significant risk of severe adverse reactions after ivermectin treatment. Planning of control requires therefore mapping of these two infections using rapid assessment tools developed for each disease. These tools were initially implemented independently till the feasibility of combining them was demonstrated. This paper reports the results of integrated mapping in four epidemiological zones in the Democratic Republic of Congo and its implications on operational decision-making on ivermectin treatment. Rapid assessment surveys were conducted between 2004 and 2005 using both rapid epidemiological mapping of onchocerciasis (REMO) and rapid assessment procedure for loiasis (RAPLOA). The survey results were subjected to a spatial analysis in order to generate for each of the two diseases maps of the estimated prevalence of infection throughout the four zones. Surveys were undertaken in 788 villages where 25,754 males were examined for palpable onchocercal nodules and 62,407 people were interviewed for history of eye worm. The results showed major differences in the geographic distribution of the two diseases. Loiasis was highly endemic in some areas, where special precautions were required, but not in others where routine ivermectin treatment could proceed. Integrated rapid mapping of onchocerciasis and loiasis reduces both time and cost of surveys and greatly facilitates operational decision-making on ivermectin treatment in areas where loiasis might be co-endemic.
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Background: The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. Methods: A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 microg/kg) at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events. Results: One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia and all embryonic stages in utero. Notably, the viability of female adult worms was significantly reduced in doxycycline treated groups and the macrofilaricidal and sterilising activity was unaffected by the addition of ivermectin. Treatment with doxycycline was well tolerated and the incidence of adverse event to doxycycline or ivermectin did not significantly deviate between treatment groups. Conclusions: A six-week course of doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. Therefore, further trials are warranted to assess the safety and efficacy of doxycycline-based interventions to treat onchocerciasis in individuals at risk of serious adverse reactions to standard treatments due to the co-occurrence of high intensities of L. loa parasitaemias. The development of an anti-wolbachial treatment regime compatible with MDA control programmes could offer an alternative to the control of onchocerciasis in areas of co-endemicity with loiasis and at risk of severe adverse reactions to ivermectin. Trial registration: Controlled-Trials.com ISRCTN48118452.
Article
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Severe side effects following ivermectin treatment of onchocerciasis in areas of co-endemicity with loaisis have been an impediment for the work of the African Programme for Onchocerciasis Control (APOC) in forested regions of several countries. Doxycycline has been shown to be effective in the treatment of onchocerciasis and has the added advantages of killing adult Onchocerca volvulus but neither adult Loa loa nor their microfilariae. This drug therefore offers great potential for the treatment of onchocerciasis in areas of co-endemicity with loiasis. The limitation of use of this drug is the duration of treatment that may pose a potential problem with therapeutic coverage and compliance with treatment. To benefit from the advantages that doxycycline offers in the treatment of onchocerciasis, it will be necessary to establish an effective distribution system that can access remote communities. This study assessed the feasibility of a large-scale distribution of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis using a community-directed approach. The study was carried out in 5 health areas co-endemic for Onchocerca volvulus and Loa loa which had no prior experience of the Community Directed Treatment with Ivermectin (CDTI). The community-directed delivery process was introduced using a cascade mechanism from the central health system that passed through the regional health delegation, health district and the health areas. Community health implementers (CHIs) were trained to deliver doxycycline to community members and, under the supervision of the health system, to monitor and document drug intake and side effects. The community members adhered massively to the process. Of the 21355 individuals counted, 17519 were eligible for treatment and 12936 were treated with doxycycline; giving a therapeutic coverage of eligible population of 73.8%. Of the 12936 who started the treatment, 97.5% complied by the end of six weeks. No serious side effect was registered during the six week treatment. This study indicates that when empowered the community health implementers can successfully deliver doxycycline for six weeks for the treatment of onchocerciasis in areas of co-endemicity with loiasis. The therapeutic coverage and the compliance treatment rate achieved in this study coupled to the known efficacy of doxycycline on O. volvulus, are indicators that the strategy involving the mass administration of doxycycline can be used to control onchocerciasis in those areas of co-endemicity with loiasis where ivermectin may be contraindicated.
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Onchocerciasis is an endemic disease in Ondo state, Nigeria. Community directed distribution of ivermectin is currently on-going in some local government areas of the state. Randomly selected persons (2331 males and 2469 females) were interviewed using a modified rapid assessment procedure for Loa loa (RAPLOA) to assess community directed treatment with ivermectin. The retrospective study evaluated the coverage, impacts and adverse reactions to the drug treatment. A questionnaire was administered by house-to-house visit in six local government areas, implementing community directed treatment with ivermectin (CDTI) in this bioclimatic zone. A total of 2,398 respondents were reported to have participated in the treatment. The overall ivermectin coverage of 49.96% was recorded (range 0-52% in different communities). Adverse reactions from ivermectin administration were experienced in 38% of individuals. Diverse adverse reactions experienced included predominantly itching (18.50%); oedema, especially of the face and the limbs (8.2%); rashes (3.4%) and body weakness (2.4%). Expulsion of intestinal worms occurred in 0.96% of the respondents. The occurrence of adverse reactions in relation to age categories was statistically significant. Neither fatal nor severe adverse reactions were reported by respondents. Significantly, despite experienced adverse reactions, continued participation, acceptability and compliance to ivermectin treatment was expressed by the various communities. This attitude is in consonance with the African Programme for Onchocerciasis Control (APOC) objectives. Rev. Biol.
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In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic. Ivermectin (at 150 micrograms/kg) was given to 17877 people living in the Lékié area of Cameroon. 50 microL samples of capillary blood were taken during the daytime before treatment from all adults (aged > or = 15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model. 20 patients (0-11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2-3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio > 1000) for loads above 50000 microfilariae/mL. Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.
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Several cases of encephalopathy recorded in Cameroon since 1991 were in patients with very high, coincident, Loa loa microfilaraemias who had been treated with ivermectin for onchocerciasis. There was thus an urgent need to identify those areas where loiasis is hyperendemic, and where specific monitoring procedures should be developed if large-scale ivermectin treatment of onchocerciasis is to be implemented. In the present review, the available data on Loa endemicity are detailed and maps showing the prevalence of Loa microfilaraemia throughout the area endemic for the infection are presented. By superimposing these maps on those which show where onchocerciasis is meso- or hyper-endemic, it is now possible to identify several areas, in south-eastern Nigeria, southern and central Cameroon, the south of the Central African Republic, Equatorial Guinea, Gabon, and the north and west of the Democratic Republic of the Congo (ex-Zaire), where ivermectin treatment, although indicated, is most likely to lead to adverse reactions because of L. loa infections. Additional surveys, to delineate the areas highly infected with L. loa more accurately, are required.
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Over the past nine years, more than 12 million people exposed to Onchocerca volvulus infection have received at least one dose of ivermectin, almost all without serious adverse reactions. Since 1991, however, several cases with neurologic manifestations, including coma, have been reported after ivermectin treatment of persons infected with O. volvulus who also had concomitant Loa loa infection with very high microfilaremia (> 50,000 microfilariae/ml of blood). In 1995, four criteria were established to define probable cases of Loa encephalopathy temporally related to treatment with ivermectin (PLERI). The present paper describes three PLERI cases recorded in Cameroon and compares them with two others reported previously. Disorders of consciousness began 3-4 days after treatment. The objective neurologic signs were variable. The conditions improved favorably in three patients who benefited from early hospitalization and good nursing; their disorders of consciousness lasted only 2-3 days; the results of clinical examination became normal after one month and electroencephalographic abnormalities disappeared after 5-7 months. Conversely, late diagnosis and delay in proper management in two others probably led to worsening of the condition and to fatal outcome related to the usual complications of coma. In addition to these cases, patients w with high Loa microfilaremia also developed milder neurologic manifestations causing functional impairment lasting for at least one week after treatment. Before launching mass ivermectin distribution programs to control onchocerciasis in central Africa, communities in which the intensity of concomitant L. loa microfilaremia is high need to be identified, and specific educational measures and monitoring strategies should be developed and applied before they are treated.
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Although diethylcarbamazine is curative in ∼60% of patients who acquire loiasis as long-term visitors to an endemic area, some individuals continue to have signs and symptoms of infection despite multiple courses of diethylcarbamazine. On the basis of a study of albendazole treatment of loiasis in microfilaremic patients that suggested a macrofilaricidal effect of the drug, we treated three patients who had symptomatic loiasis refractory to more than four courses of diethylcarbamazine with albendazole. At the time of treatment, all patients had persistent symptoms despite decreasing titers of antifilarial antibodies and normal eosinophil counts. Symptoms resolved in all three patients following albendazole therapy. In one patient, nonspecific symptoms recurred 2 years later, but unlike her symptoms before albendazole therapy, they were not accompanied by the appearance of subcutaneous nodules containing adult worms. The other two patients have been symptom-free in the 8 years after albendazole treatment. In summary, albendazole may be useful for the treatment of loiasis when diethylcarbamazine is ineffective or cannot be used.
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The problem of Loa-encephalopathy, which may occur after ivermectin treatment of patients harbouring high Loa microfilarial loads, might be solved if one could find a treatment regimen bringing about a significant but progressive decrease in the Loa microfilaraemia. A trial was performed in Central Cameroon, whose aim was to follow up for 10 months, and to compare the changes in the Loa microfilarial loads in two groups of patients, one treated with a single dose (600 mg) of albendazole (Alben, SmithKline Beecham) given with fatty food, and the other treated with mebendazole (100 mg, twice a day, generic tablets) at a fasting state. The microfilarial loads remained stable in the mebendazole group, whereas a significant decrease in microfilaraemia was recorded in the albendazole group (initial median load: 230 microfilariae per 50 microliters; median load ten months after: 84 microfilariae per 50 microliters). This should encourage further trials to evaluate the effects and the safety of two- or three-day albendazole regimens in patients infected with Loa loa.
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Background The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the question whether elimination of infection or eradication of onchocerciasis can be achieved using this strategy of critical importance. This study was undertaken to explore this issue. Methods An empirical approach was adopted in which a comprehensive analysis was undertaken of available data on the impact of more than a decade of ivermectin treatment on onchocerciasis infection and transmission. Relevant entomological and epidemiological data from 14 river basins in the OCP and one basin in Cameroon were reviewed. Areas were distinguished by frequency of treatment (6-monthly or annually), endemicity level and additional control measures such as vector control. Assessment of results were in terms of epidemiological and entomological parameters, and as a measure of inputs, therapeutic and geographical coverage rates were used. Results In all of the river basins studied, ivermectin treatment sharply reduced prevalence and intensity of infection. Significant transmission, however, is still ongoing in some basins after 10–12 years of ivermectin treatment. In other basins, transmission may have been interrupted, but this needs to be confirmed by in-depth evaluations. In one mesoendemic basin, where 20 rounds of four-monthly treatment reduced prevalence of infection to levels as low as 2–3%, there was significant recrudescence of infection within a few years after interruption of treatment. Conclusions Ivermectin treatment has been very successful in eliminating onchocerciasis as a public health problem. However, the results presented in this paper make it almost certain that repeated ivermectin mass treatment will not lead to the elimination of transmission of onchocerciasis from West Africa. Data on 6-monthly treatments are not sufficient to draw definitive conclusions.
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Background Many filarial nematodes harbour Wolbachia endobacteria. These endobacteria are transmitted vertically from one generation to the next. In several filarial species that have been studied to date they are obligatory symbionts of their hosts. Elimination of the endobacteria by antibiotics interrupts the embryogenesis and hence the production of microfilariae. The medical implication of this being that the use of doxycycline for the treatment of human onchocerciasis and bancroftian filariasis leads to elimination of the Wolbachia and hence sterilisation of the female worms. Wolbachia play a role in the immunopathology of patients and may contribute to side effects seen after antifilarial chemotherapy. In several studies Wolbachia were not observed in Loa loa. Since these results have been doubted, and because of the medical significance, several independent methods were applied to search for Wolbachia in L. loa. Methods Loa loa and Onchocerca volvulus were studied by electron microscopy, histology with silver staining, and immunohistology using antibodies against WSP, Wolbachia aspartate aminotransferase, and heat shock protein 60. The results achieved with L. loa and O. volvulus were compared. Searching for Wolbachia, genes were amplified by PCR coding for the bacterial 16S rDNA, the FTSZ cell division protein, and WSP. Results No Wolbachia endobacteria were discovered by immunohistology in 13 male and 14 female L. loa worms and in numerous L. loa microfilariae. In contrast, endobacteria were found in large numbers in O. volvulus and 14 other filaria species. No intracellular bacteria were seen in electron micrographs of oocytes and young morulae of L. loa in contrast to O. volvulus. In agreement with these results, Wolbachia DNA was not detected by PCR in three male and six female L. loa worms and in two microfilariae samples of L. loa. Conclusions Loa loa do not harbour obligatory symbiotic Wolbachia endobacteria in essential numbers to enable their efficient vertical transmission or to play a role in production of microfilariae. Exclusively, the filariae cause the immunopathology of loiasis is patients and the adverse side effects after antifilarial chemotherapy. Doxycycline cannot be used to cure loiais but it probably does not represent a risk for L. loa patients when administered to patients with co-infections of onchocerciasis.
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Background The majority of filarial nematode species are host to Wolbachia bacterial endosymbionts, although a few including Acanthocheilonema viteae, Onchocerca flexuosa and Setaria equina have been shown to be free of infection. Comparisons of species with and without symbionts can provide important information on the role of Wolbachia symbiosis in the biology of the nematode hosts and the contribution of the bacteria to the development of disease. Previous studies by electron microscopy and PCR have failed to detect intracellular bacterial infection in Loa loa. Here we use molecular and immunohistological techniques to confirm this finding. Methods We have used a combination of PCR amplification of bacterial genes (16S ribosomal DNA [rDNA], ftsZ and Wolbachia surface protein [WSP]) on samples of L. loa adults, third-stage larvae (L3) and microfilariae (mf) and immunohistology on L. loa adults and mf derived from human volunteers to determine the presence or absence of Wolbachia endosymbionts. Samples used in the PCR analysis included 5 adult female worms, 4 adult male worms, 5 mf samples and 2 samples of L3. The quality and purity of nematode DNA was tested by PCR amplification of nematode 5S rDNA and with diagnostic primers from the target species and used to confirm the absence of contamination from Onchocerca sp., Mansonella perstans, M. streptocerca and Wuchereria bancrofti. Immunohistology was carried out by light and electron microscopy on L. loa adults and mf and sections were probed with rabbit antibodies raised to recombinant Brugia malayi Wolbachia WSP. Samples from nematodes known to be infected with Wolbachia (O. volvulus, O. ochengi, Litomosoides sigmodontis and B. malayi) were used as positive controls and A. viteae as a negative control. Results Single PCR analysis using primer sets for the bacterial genes 16S rDNA, ftsZ, and WSP were negative for all DNA samples from L. loa. Positive PCR reactions were obtained from DNA samples derived from species known to be infected with Wolbachia, which confirmed the suitability of the primers and PCR conditions. The quality and purity of nematode DNA samples was verified by PCR amplification of 5S rDNA and with nematode diagnostic primers. Additional analysis by 'long PCR' failed to produce any further evidence for Wolbachia symbiosis. Immunohistology of L. loa adults and mf confirmed the results of the PCR with no evidence for Wolbachia symbiosis. Conclusion DNA analysis and immunohistology provided no evidence for Wolbachia symbiosis in L. loa.
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Of the 207 Serious Adverse Events (SAEs) following treatment with Mectizan® (ivermectin, Merck, Sharpe & Dohme) that were reported from 1989 to 2001 through the passive SAE surveillance system required of all onchocerciasis mass treatment programs, 65 were cases of 'Probable' or 'Possible' Loa loa Encephalopathy temporally Related to treatment with Mectizan® (PLERM). A retrospective analysis of these 65 PLERM cases revealed that 97% were from southern Cameroon, 85% were male and 93% were being treated with ivermectin for the first time. The mean time to onset of symptoms was 1.7 days (95% CI: 1.3, 2.2) but the mean time to receiving medical attention after the onset of symptoms was 2.0 days (95% CI: 1.5, 2.6). Hospitalization was reported in 53 cases with a mean duration of 27.5 days (95% CI: 13.3, 41.6, n = 35). Clinical outcome was reported in 34 cases: 64.7% recovered fully, 11.8% had partial neurologic deficit and 23.5% died. For the 32 cases where quantitative L. loa data were reported, the arithmetic means with 95% confidence intervals were for 1) peripheral blood: pre-treatment – 164,250 mf/ml (79,537, 248,963; n = 4); post-treatment within 1 month – 3926 mf/ml (2,128, 5,725; n = 21) and within 5 to 6 months – 7800 mf/ml (3417, 12,183; n = 7); and for 2) cerebrospinal fluid: 32 mf/ml (7, 37; n = 10) within 1 month post-treatment. Pending further research on practical methods to exclude individuals with high intensity L. loa infection from onchocerciasis mass treatment programs, more emphasis should be placed on surveillance and monitoring to ensure early recognition, referral and management of SAEs, during the first 2 years when majority of the population is presumably naïve to ivermectin.
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This report reviews information on Serious Adverse Events (SAE), mainly Loa-encephalopathy, following treatment with ivermectin (Mectizan®, Merck, Sharpe & Dohme) for control of onchocerciasis carried out by the African Programme for Onchocerciasis Control (APOC), in areas where heavy microfilarial infections with Loa loa are co-endemic with Onchocerca volvulus infections. It also endeavours to define the information and research needed to understand, prevent, and manage cases of Loa-encephalopathy.
Article
Several cases of encephalopathy recorded in Cameroon since 1991 were in patients with very high, coincident, Loa loa microfilaraemias who had been treated with ivermectin for onchocerciasis. There was thus an urgent need to identify those areas where loiasis is hyperendemic, and where specific monitoring procedures should be developed if large-scale ivermectin treatment of onchocerciasis is to be implemented. In the present review, the available data on Loa endemicity are detailed and maps showing the prevalence of Loa microfilaraemia throughout the area endemic for the infection are presented. By superimposing these maps on those which show where onchocerciasis is meso- or hyper-endemic, it is now possible to identify several areas, in south-eastern Nigeria, southern and central Cameroon, the south of the Central African Republic, Equatorial Guinea, Gabon, and the north and west of the Democratic Republic of the Congo (ex-Zaire), where ivermectin treatment, although indicated, is most likely to lead to adverse reactions because of L. loa infections. Additional surveys, to delineate the areas highly infected with L. loa more accurately, are required.
Article
A case of retinal hemorrhages with special features and degradation of the general condition is reported in a 27-year-old female patient, following the ingestion of ivermectin for the treatment of onchocerciasis. The patient was infested by both Onchocerca volvulus and Loa loa. A bilateral peripheral temporal location of the retinal lesions was observed. The role of L. loa microfilarial load in the occurrence of the retinal lesions as well as the transient character of the lesions are discussed, based on the clinical observation and with reference to the literature. The authors call for setting up a rapid therapeutic system to take care of serious adverse reactions following treatment with ivermectin in areas with a high prevalence of L. loa infestation.
Loiasis is endemic in the tropical rain forest of Central and some parts of West Africa and is transmitted by the insect vector Chrysops silacea and Chrysops dimidiata. Loa loa infestation causes local inflammation due to migrating adult worms in the subcutis (Calabar swelling) and in the conjunctivae (eye worm). The diagnosis is made by the demonstration of circulating blood microfilariae, the larvae of the adult worms. Since the density of the microfilariae is very low, they can only be identified by concentration methods, such as hemofiltration. During treatment with the specific antiparasitic drug (diethylcarbamazine, DEC), side effects such as allergic reactions due to the rapid disruption of circulating microfilariae may occur. Those symptoms are aggravated in patients with a high number of larvae, leading to meningo-encephalomyelitis or even death.1Since microfilariae accumulate in the buffy coat during leukocytapheresis,2 it was thought that this technique might be a suitable tool to reduce the parasite load and to bypass the side effects of specific drug treatment. Muylle et al. achieved apheresis of microfilariae in two patients with Loa loa infestation by using a Haemonetics, M-300 blood processor.3 The authors studied two patients with an excessive microfilarial count in the peripheral blood of up to 9/μL and achieved a high enrichment by discontinuous-flow centrifugation. A similar observation was reported by Saeed et al. later on. 4 We have studied two patients with loiasis and report the results of microfilarial apheresis using a continuous-flow IBM/Cobe cell separator.
Article
A nested polymerase chain reaction (nested PCR) assay, targeted on the repeat 3 region (15r3) of the gene coding for a Loaloa 15 kD polyprotein, was developed to detect L. loa infection. The assay has a sensitivity of 95% and is 100% specific with regard to sympatric filarial parasites: Mansonella perstans, Onchocerca volvulus and Wuchereria bancrofti. In this field study in a mixed filarial (L. loa and M. perstans) endemic region of Gabon, 157 L. loa amicrofilaraemic blood samples (AMF; diagnosed by leucoconcentration followed by standard microscopic examination) from the residents from four villages were screened by the 15r3-nested PCR assay. The assay detected 106 occult infected subjects among the 157 AMF individuals (68%), including 59 of 87 adults (68%) and 47 of 70 children (67%). In each village the prevalence of occult infection was, respectively, 38%, 52%, 79% and 80% for Moyabi, Djoutou, N'djokaye and Okoumbi. The annual transmission potential (ATP) of loiasis has been estimated to be 250 infective larvae (L 3) per man per year for Moyabi and Djoutou, 1800 for N'djokaye and 43000 L3/man/year for Okoumbi. This implies a correlation between occult infection of loiasis and the intensity of transmission. By contrast, the prevalence of L. loa microfilariae was 21% for Okoumbi, 22% for N'djokaye and 19% for Djoutou and Moyabi. These results show that the prevalence of loiasis in this region of Gabon is higher than previously described by standard microscopic examination and that the application of this assay will be significant in the development of control strategies for loiasis.
Article
Among the two cases of loiasis published in this issue,1,2 one particularly deserves to be commented on because it is atypical in some respects.1 The patient was an expatriate who had an upper eyelid swelling from which a nematode was extracted. During the preceding 2 years, he had had transient swellings at various sites of the head, and at referral his eosinophilia was normal and no microfilaria (mf) was found in his blood. No serologic or polymerase chain reaction (PCR) assays were performed on blood samples. The parasite removed has not been examined morphologically to seek classical characteristics of adult Loa loa (cuticle with numerous, randomly arranged, smooth, round bosses); but the real‐time PCR assay performed on a piece of the worm demonstrated unambiguously that it was a L loa specimen. The first interesting point in this case is that the patient reported to have visited sub‐Saharan Africa only once for a business trip, 20 years before the extraction of the worm. Unlike Onchocerca volvulus or Wuchereria bancrofti (the most pathogenic human filariae), the average lifespan of adult L loa has never been evaluated. However, it is known that the parasite can live more than 10 years,3 the record reported so far being 17 years.4 The possibility that the patient presented in this report had been infected elsewhere than in Africa could be considered: experimental infections using monkey models have shown that at least one American Chrysops species supports the development of L loa up to the infective stage, and could thus theoretically retransmit the parasite locally after having taken a bloodmeal on an infected individual.5 However, this is rather unlikely (as stated by Orihel and Lowrie,5 no report exists of Loa establishment in America, even at the height of the slave trade) and … Corresponding Author: Michel Boussinesq, MD, PhD, Unite Mixte Internationale 233, Institut de Recherche pour le Developpement, 911 avenue Agropolis, BP 64501, F‐34394 Montpellier Cedex 5, France. E‐mail: michel.boussinesq{at}ird.fr
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The high prevalence neglected tropical diseases (NTDs) exhibit a global disease burden that exceeds malaria, tuberculosis, and other better known global health conditions; they also represent a potent force in trapping the world's poorest people in poverty. Through extremely low cost national programs of disease mapping and mass drug administration (MDA) for the seven most common NTDs, integrated NTD control and elimination efforts are now in place in more than 14 countries through the support of the United States Agency for International Development (USAID), the British Department for International Development (DFID), and the Global Network for NTDs and its partners. The World Health Organization (WHO) estimates that in 2008 some 670 million people in 75 countries received NTD treatments through these and other sponsored programs. With continued successes the next decade could witness the global elimination of blinding trachoma, human Africa trypanosomiasis (HAT), lymphatic filariasis (LF), onchocerciasis, trachoma, and leprosy as public health problems, in addition to the eradication of dracunculiasis. For other high prevalence NTDs, including hookworm infection, schistosomiasis, Chagas disease and leishmaniasis, new drugs and vaccines may still be required. Increasingly it is recognized that the high prevalence NTDs exhibit extensive geographic overlap and polyparasitism is commonly found throughout the world's low income countries. Therefore, global elimination will also require integrated packages of drugs together with vaccine-linked chemotherapy. Ultimately, the global elimination of the high prevalence NTDs will require continued large-scale support from the U.S. Government and selected European governments, however, the emerging market economies, such as Brazil, China, India, Mexico, and Nigeria, and wealthy countries in the Middle East will also have to substantially contribute.
Article
Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i.e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti-allergic treatment. This type of drug-induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature.