[Case report: Two patients with eye worm and recurrent swelling of the extremities].

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.

Increasing evidence of low lymphatic filariasis prevalence in high risk Loa loa areas in Central and West Africa: a literature review.

In West and Central Africa, there is a need to establish the prevalence of Wuchereria bancrofti in areas that are co-endemic for Loa loa, in order to implement the appropriate strategies to scale-up interventions for the elimination of lymphatic filariasis (LF). Due to the risk of severe adverse events (SAEs) to ivermectin in individuals with high L. loa microfilaraemia, the current strategy recommended by the World Health Organization (WHO) is twice yearly mass drug administration (MDA) with albendazole, supplemented by vector control targeting the Anopheles vectors. Defining W. bancrofti prevalence in areas co-endemic with L. loa is complicated by the cross-reactivity of rapid diagnostic immunochromatographic card tests (ICT), widely used for LF mapping, in individuals with high L. loa microfilaraemia. This has probably resulted in the overestimation of LF prevalence, triggering the implementation of MDA strategies, which may be unnecessary and wasteful of the limited resources for elimination programme implementation. Here we review the literature and present historical evidence, which uniformly highlight low or no prevalence of W. bancrofti infection and/or clinical LF cases across five Central African countries, in more than 30 different geographical areas covering 280 individual sites and > 22,000 individuals tested within high risk L. loa areas. This highlights the very limited information available on LF prevalence in L. loa areas, and potentially has major policy implications, which could shift the focus towards revised mapping criteria to verify low or no W. bancrofti prevalence in high risk L. loa areas. In this situation, revising the current WHO strategy from MDA, to focus more on ensuring high and effective vector control, through insecticide treated/long-lasting impregnated bednets (ITNs/LLINs), integration of point-of-care test-and-treat options into health systems, and consolidating closer links with the malaria control programme may be a more effective and appropriate use of the limited resources and drug donations available for LF elimination.

The Population Biology and Transmission Dynamics of Loa loa.

Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions.

Loa loa vectors Chrysops spp.: perspectives on research, distribution, bionomics, and implications for elimination of lymphatic filariasis and onchocerciasis.

BACKGROUND: Loiasis is a filarial disease caused Loa loa. The main vectors are Chrysops silacea and C. dimidiata which are confined to the tropical rainforests of Central and West Africa. Loiasis is a mild disease, but individuals with high microfilaria loads may suffer from severe adverse events if treated with ivermectin during mass drug administration campaigns for the elimination of lymphatic filariasis and onchocerciasis. This poses significant challenges for elimination programmes and alternative interventions are required in L. loa co-endemic areas. The control of Chrysops has not been considered as a viable cost-effective intervention; we reviewed the current knowledge of Chrysops vectors to assess the potential for control as well as identified areas for future research. RESULTS: We identified 89 primary published documents on the two main L. loa vectors C. silacea and C dimidiata. These were collated into a database summarising the publication, field and laboratory procedures, species distributions, ecology, habitats and methods of vector control. The majority of articles were from the 1950-1960s. Field studies conducted in Cameroon, Democratic Republic of Congo, Equatorial Guinea, Nigeria and Sudan highlighted that C. silacea is the most important and widespread vector. This species breeds in muddy streams or swampy areas of forests or plantations, descends from forest canopies to feed on humans during the day, is more readily adapted to human dwellings and attracted to wood fires. Main vector targeted measures proposed to impact on L. loa transmission included personal repellents, household screening, indoor residual spraying, community-based environmental management, adulticiding and larviciding. CONCLUSIONS: This is the first comprehensive review of the major L. loa vectors for several decades. It highlights key vector transmission characteristics that may be targeted for vector control providing insights into the potential for integrated vector management, with multiple diseases being targeted simultaneously, with shared human and financial resources and multiple impact. Integrated vector management programmes for filarial infections, especially in low transmission areas of onchocerciasis, require innovative approaches and alternative strategies if the elimination targets established by the World Health Organization are to be achieved.

Loiasis in US Traveler Returning from Bioko Island, Equatorial Guinea, 2016.

The filarial parasite Loa loa overlaps geographically with Onchocera volvulus and Wuchereria bancrofti filariae in central Africa. Accurate information regarding this overlap is critical to elimination programs targeting O. volvulus and W. bancrofti. We describe a case of loiasis in a traveler returning from Bioko Island, Equatorial Guinea, a location heretofore unknown for L. loa transmission.

Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes.

Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodes Brugia, Wuchereria and Loa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83-99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25-22 million years ago (Myr ago) involving the Brugia/Wuchereria lineage and >20-17 Myr ago involving the Loa lineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity.

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon.

BACKGROUND: Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. METHODS: A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999-2000. RESULTS: There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999-2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. CONCLUSION: The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is an indication that the risk of occurrence of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time.

Occurrence and distribution of Chrysops species in Akamkpa community of Cross River State, Nigeria.

Chrysops species have been recognized for its role as vectors in the transmission of human loiasis in Nigeria. This investigation was aimed at studying the occurrence and distribution of Chrysops species in Akamkpa community, Cross River State. Two fly boys were used as human baits in the collection of adult Chrysops from each of the various villages in Akamkpa community, cross river state, Nigeria. Two species of Chrysops were identified. Chrysops dimidiata recorded significantly higher prevalence of 69.7% than Chrysops silacea 30.3% in all the sampling sites (p<0.05). Out of the 1299 Chrysops species caught in the entire study, the highest prevalence was reported during the late rainy season 916 (70.5%), while the least prevalence of 137 (10.6%) was reported during the late dry season (p<0.05). Two biting peaks 9-10 am and 3-4 pm were identified for Chrysops at all the sampling sites. Fly abundance was found to be higher in the morning hours than in the afternoon. The knowledge of the occurrence and distribution of Chrysops vectors will aid in the ongoing control program for human loiasis in Nigeria and the neighbouring countries where the vectors exist.

[Loa loa filariasis in Italy: review of the literature with a clinical report]. / Filariasi da Loa loa in Italia: revisione della letteratura e descrizione di un caso.

We present the case of an asymptomatic Loa loa disease in a 28-year-old Nigerian man living in Italy for 5 years. The man was admitted to our clinic for an occasional identification of hypereosinophilia (white blood cell count 5440/mmc, eosinophil 42%) and the presence of microfilaria at an hemoscopic evaluation. The diagnosis was made by testing the diurnal peripheral blood that showed a parasitaemia of 7000 microfilia/mL. The patient was treated with ivermectin 12 mg on the first day followed by albendazole 400 mg every 12 hours for 21 days with a reduction but no negativization of the parasitaemia and no collateral effect. Filariasis should be considered in all patients who come from or have stayed in endemic areas or who present alterations in the leukocyte formula, including hypereosinophilia, or some unexplainable allergic disorders. The lab diagnosis can be conducted through a hemoscopic test or directly with the identification of the adult worm, whereas the parasitaemia can be evaluated only through a hemoscopic test. The therapy can be non-conclusive or carried out with difficulty as finding diethylcarbamazine may be a hard task or potentially fatal anaphylactic reactions may occur.

Loiasis: the individual factors associated with the presence of microfilaraemia.

No microfilariae are detectable in a significant percentage of those infected with the filarial worm Loa loa. While the probability of an infected individual becoming microfilaraemic is known to increase with age, the mechanisms underlying this trend are not well understood. Epidemiological data from an endemic village in central Cameroon were therefore explored, in an attempt to determine if, after taking into account any history of filaricidal treatment, the presence of Loa microfilaraemia in an individual was related to his/her gender, age, and/or exposure to the human-infective larvae of the parasite. An index of exposure, based on the monthly transmission potentials of the Chrysops in each of the main types of vegetation in a village and on the activity schedule of each inhabitant of the village, was developed. The results of the data analysis confirm that the acquisition of microfilaraemia is gender-dependent (males generally being more likely to be microfilaraemic than females), and indicate that, in males, a high level of exposure to infective larvae determines the shift from amicrofilaraemic to microfilaraemic status. They also indicate that filaricidal treatments have a long-lasting suppressive effect on Loa microfilaraemia, an observation that may have important implications for any strategy to limit the risk of Loa-associated encephalopathy following ivermectin treatment.

Importation of seven cases of an unusual helminthic infection into Singapore and assessment of the risk of local transmission.

Singapore remains vulnerable to the introduction of infectious diseases from other countries due to the high traffic of migrant labour and other visitors. We describe seven cases of migrant workers from West Africa who entered Singapore carrying loaisis, a helminthic infection. The clinical presentation, treatment using single dose ivermectin, potential for transmission, and the need for screening of this infection in Singapore are discussed.

[Ocular involvement in systemic Loa-Loa filariasis. Case report and review of the literature]. / Okuläre Beteiligung bei systemischer Loa-Loa-Infektion. Fallbericht und Literaturübersicht.

BACKGROUND: Within the last few years there is more and more evidence for nonspecific ocular symptoms caused by "exotic" pathogens. We herewith report another case of such an infection to underline the increasing importance and diagnostic relevance even of rare diseases. PATIENT: A 35-year-old female German patient presented with recurrent left retrobulbar "feeling of pressure" after a 6-month-stay in Central Africa 5 years ago. In addition, she reported on repeated swelling of the skin and joints of her hands and arms. Multiple ophthalmologic and rheumatologic investigations had been carried out without diagnostic results. Her ophthalmologist referred her with the presumed diagnosis of a subconjunctival worm. RESULTS: Slit-lamp biomicroscopy confirmed the original suspicion, and after topical anesthesia a female Loa-Loa worm was easily removed with forceps through a conjunctival incision. The general examination showed symptoms of systemic infection (calabar swelling, eosinophilia). Classification and initiation of treatment with diethylcarbamazine and mebendazole were carried out by the University Institute of Parasitology. CONCLUSION: Loa-Loa is a parasitic infection endemic in the tropical rain forests of Western, Central, and Eastern Africa. It is transmitted by the Chrysops fly. An increasing number of oculosystemic infections in non-African patients with Loa-Loa are being published. Therefore, any patient with an unclassifiable eye affection should also be investigated for those rare pathogens.

Potential vectors of loiasis and other tabanids on the island of Bioko, Equatorial Guinea.

The biting flies Chrysops dimidiatus Wulp and C.silaceus Austen (Diptera: Tabanidae), vectors of Loa loa (Cobbold) (Nematoda: Onchocercidae) on the African mainland, were found to be widespread on the island of Bioko (Equatorial Guinea) during 1996-2001. These tabanids were particularly prevalent in the southern part of Bioko, indicating potential transmission of loiasis on the island. The only other tabanids previously recorded on Bioko, Tabanus argenteus Surcouf (from 1915) and Haematopota near heptagramma Speiser (from 1933), were also collected. The possibility of loiasis being endemic on Bioko contra-indicates ivermectin treatment of onchocerciasis cases, due to risks of adverse side-effects.

Expression of filarial-specific IgG subclasses under different transmission intensities in a region endemic for loiasis.

Specific IgG subclasses were investigated in two villages (Okoumbi and Ndjokaye) in southeast Gabon with different Loa loa transmission intensities of approximately 9,000 and 1,300 infective larvae (L3) per person per year, respectively. IgG subclasses were measured by an enzyme-linked immunosorbent assay (ELISA) using extracts of L. loa L3, microfilariae (MF), or adult worms. Levels of L3-specific IgG3 were significantly higher in the village with low transmission (Ndjokaye) (P = 0.006). In contrast, MF-specific IgG2 was significantly higher in Okoumbi than in Ndjokaye (P = 0.0009). In the high-transmission village (Okoumbi), levels of both MF- and adult-specific IgG4 were significantly increased in MF carriers compared with amicrofilaremic subjects (P = 0.0015 and P = 0.003, respectively), while levels of L3- and MF-specific IgG1 were significantly higher in amicrofilaremic individuals compared with MF carriers (P = 0.04 and P = 0.03, respectively). Furthermore, among microfilaremic individuals, the level of the specific IgG1 subclass was much lower in Okoumbi than in Ndjokaye (P = 0.036). These results suggest that the expression of antigen-specific IgG3 and IgG2 is more likely to vary with transmission intensity, whereas antigen-specific IgG4 and IgG1 varies with adult worm and MF burden.

Chrysops silacea biting densities and transmission potential in an endemic area of human loiasis in south-west Cameroon.

We studied the biting densities of Chrysops silacea and the transmission of loiasis over 1 year in a regenerated forest in the south-west province of Cameroon. A total of 3015 flies caught near a wood fire at ground level during rainy and dry seasons were identified morphologically and 1975 caught during the rainy season were dissected to determine their physiological age and infection rate. The prevalence of microfilaraemia in the human population in the study area was determined using the thick blood smear method. Chrysops silacea was the only species caught. The daily and seasonal biting cycle of C. silacea showed two peaks of activities, 9-11 a.m. and 2-4 p.m. The biting cycles of parous and nulliparous flies showed the same trends, but the density of nulliparous flies biting at all time of the day was 2-3 times higher. Chrysops silacea biting density was high during the rainy season (9.06 +/- 6.88 flies/man/h) and lowest during the dry season (0.44 +/- 0.75 flies/man/h). An infection rate of 1.72% and a monthly morning and afternoon transmission potentials of 120769.11 and 139016.64 infective head L3/man were observed, respectively, in the rainy season. Even though few Chrysops carried Loa loa infective larvae (0.7%), their parasite load was high, giving a high level of transmission of L. loa in the area. A total of 20.37% of the people examined for blood microfilariae were positive. These results suggest that the study area is an active focus of loiasis transmission.

Transmission intensity affects both antigen-specific and nonspecific T-cell proliferative responses in Loa loa infection.

T-cell proliferative responses were studied in two villages in Gabon with different levels of Loa loa transmission. The first village (Okoumbi) had an annual transmission potential (ATP) of approximately 9,000 infective larvae (L3)/person/year (high transmission village), while the second village (Ndjokaye) had an ATP of approximately 1,000 L3/person/year (low transmission village). Proliferation and cytokine assays were performed on peripheral blood mononuclear cells (PBMC) from individuals aged 18 years and over using either mitogens (concanavalin A or phytohemagglutinin), antigens (purified protein derivative [PPD], irrelevant antigen), or soluble extracts of L3, microfilariae, or adult L. loa. PBMC from individuals in the low transmission village responded better to stimulation with adult antigen and to PPD than did PBMC from individuals in the high transmission village (P = 0.0031 and P = 0.0012, respectively). These data suggest that high levels of transmission of L. loa depress both specific and nonspecific T-cell proliferative responses in infected humans.

[Entomologic study of loaiasis transmission in the Lekie area (Cameroon)]. / Etude entomologique sur la transmission de la loase dans de département de la Lékié (Cameroun).

A number of cases of Loa encephalopathy have been recorded after ivermectin treatment in the Lekie Division, an area of degraded forest located in central Cameroon. An entomological study was carried out in a village of this region between May 1999 and April 2000 to determine whether the high microfilarial loads of Loa found in the population, which can exceed 10,000 microfilariae per ml of blood, were related to high densities of vector populations. The Chrysops collected at 10 catching stations, using hand nets, by persons standing by a wood fire, were dissected to evaluate their level of infection with Loa. The vectorial densities were three-fold higher in the forest stations than in those located near the habitations (2307 and 725 bites per man per year, respectively). These values are lower than those reported from similar studies in Cameroon, Congo and Gabon. Measurement of Chrysops densities does not seem to be an appropriate tool to evaluate the level of endemicity of loiasis, and to delineate the areas where there is a risk of post-ivermectin Loa encephalopathies.

Density and dispersal of the loaiasis vector Chrysops dimidiata in southern Cameroon.

By mark-release-recapture experiments, we assessed the density of loaisis vectors, Chrysops dimidiata Wulp plus some Chrysops silacea Austen (Diptera: Tabanidae) and estimated their range of flight in the secondary forest of southern Cameroon. In 1993, the release point was at the centre of the study area and recapture points were at 1,100 m radius. In 1994, releases were on the periphery of the study area and recapture sites were 400-8,000 m from the release points. Results were concordant and showed Chrysops female densities of 785-3,682 flies/ km2. The theoretical flight range was < 6,000 m, with a maximum distance of 4,500 m observed. These results are considered promising for the use of vector control methods against loaiasis.