Mapping lymphatic filariasis in Loa loa endemic health districts naïve for ivermectin mass administration and situated in the forested zone of Cameroon.

BACKGROUND: The control of lymphatic filariasis (LF) caused by Wuchereria bancrofti in the Central African Region has been hampered by the presence of Loa loa due to severe adverse events that arise in the treatment with ivermectin. The immunochromatographic test (ICT) cards used for mapping LF demonstrated cross-reactivity with L. loa and posed the problem of delineating the LF map. To verify LF endemicity in forest areas of Cameroon where mass drug administration (MDA) has not been ongoing, we used the recently developed strategy that combined serology, microscopy and molecular techniques. METHODS: This study was carried out in 124 communities in 31 health districts (HDs) where L. loa is present. At least 125 persons per site were screened. Diurnal blood samples were investigated for circulating filarial antigen (CFA) by FTS and for L. loa microfilariae (mf) using TBF. FTS positive individuals were further subjected to night blood collection for detecting W. bancrofti. qPCR was used to detect DNA of the parasites. RESULTS: Overall, 14,446 individuals took part in this study, 233 participants tested positive with FTS in 29 HDs, with positivity rates ranging from 0.0 to 8.2%. No W. bancrofti mf was found in the night blood of any individuals but L. loa mf were found in both day and night blood of participants who were FTS positive. Also, qPCR revealed that no W. bancrofti but L.loa DNA was found with dry bloodspot. Positive FTS results were strongly associated with high L. loa mf load. Similarly, a strong positive association was observed between FTS positivity and L loa prevalence. CONCLUSIONS: Using a combination of parasitological and molecular tools, we were unable to find evidence of W. bancrofti presence in the 31 HDs, but L. loa instead. Therefore, LF is not endemic and LF MDA is not required in these districts.

Implications for annual retesting after a test-and-not-treat strategy for onchocerciasis elimination in areas co-endemic with Loa loa infection: an observational cohort study.

BACKGROUND: A test-and-not-treat (TaNT) strategy has been developed to prevent people with high concentrations of circulating Loa loa microfilariae (>20 000 microfilariae per mL) developing serious adverse events after ivermectin treatment during mass drug administration to eliminate onchocerciasis. An important question related to cost and programmatic issues is whether annual retesting is required for everyone. We therefore aimed to investigate changes in L loa microfilarial densities during TaNT campaigns run 18 months apart. METHODS: In this observational cohort study, we assessed the participants of two TaNT campaigns for onchocerciasis. These campaigns, which were run by a research team, together with personnel from the Ministry of Health and community health workers, were done in six health areas (in 89 communities) in Okola health district (Cameroon); the first campaign was run between Aug 10, and Oct 29, 2015, and the second was run between March 7, and May 26, 2017. All individuals aged 5 years and older were invited to be screened for Loa loa microfilaraemia before being offered ivermectin (unless contraindicated). L loa microfilarial density was measured at the point of care using the LoaScope. All those with a L loa microfilarial density of 20 000 microfilariae per mL or less were offered treatment; in the first 2 weeks of the 2015 campaign, a higher exclusion threshold of 26 000 microfilariae per mL or less was used. At both rounds of the intervention, participants were registered with a paper form, in which personal information were collected. In 2017, we also recorded whether each individual reported participation in the 2015 campaign. The primary outcome, assessed in all participants, was whether L loa microfilarial density was above or below the exclusion threshold (ie, the criteria that guided the decision to treat). FINDINGS: In the 2015 TaNT campaign, 26 415 people were censused versus 29 587 people in the 2017 TaNT campaign. All individuals aged 5 years and older without other contraindications to treatment (22 842 people in 2015 and 25 421 people in 2017) were invited to be screened for L loa microfilaraemia before being offered ivermectin. In 2015, 16 182 individuals were examined with the LoaScope, versus 18 697 individuals in the same communities in 2017. 344 (2·1%) individuals were excluded from ivermectin treatment because of a high L loa microfilarial density in 2015, versus 283 (1·5%) individuals in 2017 (p<0·0001). Records from 2017 could be matched to those from 2015 for 6983 individuals (43·2% of the 2015 participants). In this cohort, in 2017, 6981 (>99·9%) of 6983 individuals treated with ivermectin in 2015 had L loa microfilariae density below the level associated with neurological serious adverse events. INTERPRETATION: Individuals treated with ivermectin do not need to be retested for L loa microfilaraemia before the next treatment, provided that they can be re-identified. This adjusted approach will enable substantial cost savings and facilitate reaching programmatic goals for elimination of onchocerciasis in areas that are co-endemic for loiasis. FUNDING: Bill & Melinda Gates Foundation, Division of Intramural Research (National Institute of Allergy and Infectious Diseases, US National Institutes of Health).

Loa loa Microfilariae in Skin Snips: Consequences for Onchocerciasis Monitoring and Evaluation in L. loa-Endemic Areas.

The specificity of skin snips for onchocerciasis diagnoses is considered to be almost 100%. Our molecular methods revealed that microfilariae emerging from skin snips collected from highly microfilaremic Loa loa-infected individuals were largely misidentified as Onchocerca volvulus. This has important implications for onchocerciasis diagnostic testing in Loa-endemic areas.

Prevalence and intensity of Loa loa infection over twenty-three years in three communities of the Mbalmayo health district (Central Cameroon).

BACKGROUND: Loiasis is a vector-borne parasitic disease due to Loa loa and transmitted to humans by tabanids of the genus Chrysops. Loiasis has been historically considered as the second or third most common reason for medical consultation after malaria, and a recent study has reported an excess mortality associated with the infection. However, the clinical impact of this filarial disease is yet to be elucidated, and it is still considered a benign disease eliciting very little attention. As a consequence of post-treatment severe adverse events occurring in individuals harboring very high Loa microfilarial loads, ivermectin is not recommended in onchocerciasis hypo-endemic areas that are co-endemic for loiasis. Without treatment, it is likely that the transmission of the disease and the morbidity associated with the infection will increase over time. This study aimed at investigating the long-term trends in prevalence and intensity of Loa loa infection in an area where no mass anti-filarial treatment has ever been distributed. METHODS: A cross-sectional survey was conducted in three communities of the Mbalmayo health district (Central Cameroon). All volunteers, males and females aged five years and above, underwent daytime calibrated thick blood smears (CTBS) to search for L. loa microfilariae (mf). A structured questionnaire was administered to assess the history of both loiasis related clinical signs and migration of enrollees. RESULTS: The prevalence of loiasis was 27.3% (95% CI: 22.3-32.9) in the three surveyed communities, with a mean mf density of 1922.7 (sd: 6623.2) mf/mL. Loa loa infection rate was higher amongst females than in males (p = 0.0001) and was positively associated with age of (OR = 1.018; p = 0.007). The intensity of infection was higher among males than in females (p < 0.0001), and displayed a convex in form trends with age groups. The follow up over 23 years revealed that both the rate and intensity of infection were similar to baseline. CONCLUSIONS: The prevalence and intensity of Loa loa infection 23 years on is stable over time, indicating that this filarial disease might be noncumulative as regarded till now.

In Southern Nigeria Loa loa Blood Microfilaria Density is Very Low Even in Areas with High Prevalence of Loiasis: Results of a Survey Using the New LoaScope Technology.

Ivermectin treatment can cause central nervous system adverse events (CNS-AEs) in persons with very high-density Loa loa microfilaremia (≥ 30,000 mf/mL blood). Hypoendemic onchocerciasis areas where L. loa is endemic have been excluded from ivermectin mass drug administration programs (MDA) because of the concern for CNS AEs. The rapid assessment procedure for L. loa (RAPLOA) is a questionnaire survey to assess history of eye worm. If ≥ 40% of respondents report eye worm, this correlates with ≥ 2% prevalence of very high-density loiasis microfilaremia, posing an unacceptable risk of CNS-AEs after MDA. In 2016, we conducted a L. loa study in 110 ivermectin-naïve, suspected onchocerciasis hypoendemic villages in southern Nigeria. In previous RAPLOA surveys these villages had prevalences between 10% and 67%. We examined 10,605 residents using the LoaScope, a cell phone-based imaging device for rapidly determining the microfilaria (mf) density of L. loa infections. The mean L. loa village mf prevalence was 6.3% (range 0-29%) and the mean individual mf count among positives was 326 mf/mL. The maximum individual mf count was only 11,429 mf/mL, and among 2,748 persons sampled from the 28 villages with ≥ 40% RAPLOA, the ≥ 2% threshold of very high Loa mf density could be excluded with high statistical confidence (P < 0.01). These findings indicate that ivermectin MDA can be delivered in this area with extremely low risk of L. loa-related CNS-AEs. We also concluded that in Nigeria the RAPLOA survey methodology is not predictive of ≥ 2% prevalence of very high-density L. loa microfilaremia.

Case Report: Probable Case of Spontaneous Encephalopathy Due to Loiasis and Dramatic Reduction of Loa loa Microfilariaemia with Prolonged Repeated Courses of Albendazole.

Loiasis is a vector-borne parasitic disease caused by the filarial nematode Loa loa and transmitted by the tabanid vectors from the genus Chrysops. Loa loa infection is associated with clinical manifestations such as pruritus, migratory transient edema, passage of adult worm in the bulbar conjunctiva, retinal damage, glomerular damage, albuminuria, pleural effusion, hydrocele, and endomyocardial fibrosis. Data reporting the occurrence of spontaneous encephalopathy associated with loiasis are very scanty. Severe adverse events occurring post-ivermectin administered in the framework of the fight against onchocerciasis and/or lymphatic filariasis in loiasis co-endemic areas have been closely associated with very high L. loa microfilariaemia. Different regimens have been used to lower L. loa microfilariaemia before definitive treatment, and many discrepancies have been reported. We report the case of a patient who was admitted to a health facility and hospitalized for 34 days for altered consciousness, blurred vision, headache, and chills. After other potential diagnoses were eliminated, the patient was confirmed with encephalopathy due to loiasis and referred to the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT). On admission at CRFilMT, the patient was harboring 28,700 microfilariae per milliliter of blood (mf/mL), and after four 21-day courses of 400 mg daily albendazole, the L. loa microfilariaemia lowered to 5,060 mf/mL. The patient was then treated with ivermectin 3 mg and a total clearance of microfilariae was observed, with satisfactory clinical evolution and no adverse event. This case study further confirmed that albendazole is effective against L. loa, but might necessitate a longer course.

Edema de Calabar en una niña guineana: loasis / Guinean child with Calabar swelling: Loiasis

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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.

Development and validation of an Onchocerca ochengi microfilarial hamster model for onchocerciasis drug screens.

BACKGROUND: Onchocerciasis, caused by the parasitic nematode, Onchocerca volvulus afflicts some 37 million people worldwide, and is the second leading infectious cause of blindness globally. The only currently recommended drug for treatment of the disease, ivermectin, is only microfilaricidal and has serious adverse effects in individuals co-infected with high loads of Loa loa microfilariae (mf), prompting the search for new and better drugs. Onchocerciasis drug discovery studies have so far been based on in vivo models using Onchocerca species which are not the closest to O. volvulus, and which may therefore, not adequately mimic the natural infection in humans. Therefore, this study was carried out to develop a better drug screening model for onchocerciasis, based on the use of cow-derived O. ochengi, the closest known relative of O. volvulus. METHODS: Mf of O. ochengi were injected subcutaneously at the nape of Syrian hamsters (Mesocricetus auratus) and BALB/c mice. The skin, and especially the earlobes of the animals were examined for mf 15-31 days after infection. For selected model validation, the hamsters were treated with ivermectin at 150 or 600 µg/kg body weight and examined 30 days after infection for mf. For L. loa studies in hamsters, isolated mf were injected intraperitoneally and animal organs were examined on day 26 for mf. RESULTS: The Syrian hamsters were found to be the more permissive to O. ochengi mf as fully viable mf were recovered from them on day 30, compared to BALB/c mice where such mf were recovered on day 15, but not 30. However, both animals were not permissive to L. loa mf even by day 15. Interestingly, more than 50 % of the total O. ochengi mf recovered were from the earlobes. The number of mf injected was directly proportional to the number recovered. Ivermectin at both concentrations tested completely eliminated the O. ochengi mf from the hamsters. CONCLUSION: This study reveals the Syrian hamster as an appropriate small animal model for screening of novel compounds against O. ochengi, the closest known relative of O. volvulus.

Regulation of global gene expression in human Loa loa infection is a function of chronicity.

BACKGROUND: Human filarial infection is characterized by downregulated parasite-antigen specific T cell responses but distinct differences exist between patients with longstanding infection (endemics) and those who acquired infection through temporary residency or visits to filarial-endemic regions (expatriates). METHODS AND FINDINGS: To characterize mechanisms underlying differences in T cells, analysis of global gene expression using human spotted microarrays was conducted on CD4(+) and CD8(+) T cells from microfilaremic Loa loa-infected endemic and expatriate patients. Assessment of unstimulated cells showed overexpression of genes linked to inflammation and caspase-associated cell death, particularly in endemics, and enrichment of the Th1/Th2 canonical pathway in endemic CD4(+) cells. However, pathways within CD8(+) unstimulated cells were most significantly enriched in both patient groups. Antigen (Ag)-driven gene expression was assessed to microfilarial Ag (MfAg) and to the nonparasite Ag streptolysin O (SLO). For MfAg-driven cells, the number of genes differing significantly from unstimulated cells was greater in endemics compared to expatriates (p<0.0001). Functional analysis showed a differential increase in genes associated with NFkB (both groups) and caspase activation (endemics). While the expatriate response to MfAg was primarily a CD4(+) pro-inflammatory one, the endemic response included CD4(+) and CD8(+) cells and was linked to insulin signaling, histone complexes, and ubiquitination. Unlike the enrichment of canonical pathways in CD8(+) unstimulated cells, both groups showed pathway enrichment in CD4(+) cells to MfAg. Contrasting with the divergent responses to MfAg seen between endemics and expatriates, the CD4(+) response to SLO was similar; however, CD8(+) cells differed strongly in the nature and numbers (156 [endemics] vs 36 [expatriates]) of genes with differential expression. CONCLUSIONS: These data suggest several important pathways are responsible for the different outcomes seen among filarial-infected patients with varying levels of chronicity and imply an important role for CD8(+) cells in some of the global changes seen with lifelong exposure.

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.

Meningoencefalitis por Loa loa secundaria a tratamiento con mebendazol / Loa loa meningoencephalitis secondary to treatment with mebendazol

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Loiasis / No disponible

La loiasis es producida por el nematodo Loa loa, endémica en África Central y parte de África Occidental. Es transmitida por la picadura de moscas hembras del género Chrysops. Se calcula entre 3 y 13 millones de personas infectadas. Aunque la mortalidad asociada a la infección por Loa loa es baja, produce una morbilidad importante y es causa frecuente de consulta médica en las zonas endémicas. La manifestación más frecuente es el edema de Calabar, dicho edema es migratorio, no doloroso, y es producido por el paso de la filaria adulta por el tejido celular subcutáneo. Otra manifestación clínica es el paso de la filaria adulta por la conjuntiva ocular, siendo visible su desplazamiento entre la conjuntiva y la esclera ocular. El diagnóstico etiológico se establece con la demostración de microfilarias en sangre periférica, con periodicidad diurna. La PCR y la serología son otras herramientas diagnósticas. El diagnóstico diferencial de las microfilarias se debe de hacer con las otras microfilarias sanguíneas y la Onchocerca volvulus, que a veces aparece en sangre de forma ocasional. A nivel clínico, se debe diferenciar el edema de Calabar del producido por otras filariosis, gnathostomiasiso triquinosis. El tratamiento consiste en la administración de Dietilcarbamacina. El conocer las zonas geográficas de mayor prevalencia de Loa loa es útil al tratar la oncocercosis, ya que la ivermectina puede producir efectos indeseables graves a los pacientes que presenten cifras altas de microfilarias de Loa loa en sangre periférica (AU)

The loiasis is produced by the nematode Loa loa, endemic in Central Africa and part of Western Africa. It is transmitted by species of Chrysops flies. One calculates between 3 and 13 million infected people. Although the mortality associated to the infection by Loa loa is low, produces an important morbidity and is frequent cause of medical consultation in the endemic zones. The most frequent manifestation is Calabar swellings, this edema is migratory, non painful, and is produced by the passage of filaria adult by the subcutaneous cellular weave. Another clinical manifestation is the passage of filaria adult by the conjunctive, being visible its displacement between conjunctive and the ocular sclera. The aetiology diagnosis settles down with the demonstration of microfilarias in peripheral blood, with diurnal regularity. The PCR and the serology are other diagnostic tools. The diagnosis differential of the microfilarias is due to do with the other sanguineous microfilarias and the Onchocerca volvulus that same times appear in blood of occasional form. At clinical level, Calabar swellings is due to differentiate from the produced one by other filariosis, gnathostomiasis or trichinosis. The treatment consists of the administration of Dietil carbamacina. Knowing the geographiczones greater prevalence of Loa loa is useful when treatment the oncocercosis, since the ivermectina can produce serious undesirable effects to the patients who present high numbers of microfilarias of Loa loa in peripheral blood (AU)

Loiasis. Aproximación a una forma de parasitosis ocular / Loiasis. Approach to a form of ocular parasitosis

Caso clínico: Presentamos el caso de un camerunés que refiere la presencia de un gusano en ambos ojos de forma intermitente desde hace 5 años. El examen biomicroscópico reveló la existencia de un gusano reptante subconjuntival. El análisis microbiológico tras su extracción quirúrgica confirmó que se trataba de una forma adulta de Loa-Loa. Discusión: La loiasis es una enfermedad parasitaria endémica en África. El reconocimiento de la enfermedad tiene interés debido al incremento de la emigración africana hacia España

Case report: We present the case of a man from Cameroon who was referred because of the presenceof a worm in both eyes, intermittently, over afive-year period. Slit-lamp examination revealed a creeping worm under the conjunctiva. Its surgical removal enabled microbiologic confirmation of amature form of Loa-Loa. Discussion: Loiasis is a parasitic disease endemic in Africa. Because of the increase of African emigration to Spain, the possibility of this condition must be considered in Spain

Tumor de mama de origen parasitario / Tumour of the breast from parasite origin

Paciente de 18 años de edad, natural de Guinea, que acudea la consulta presentando una gran tumoración en la mama izquierdaque ocupa los dos cuadrantes externos. Se realizanmamografías, ecografía y resonancia magnética, mostrandoun gran granuloma de 12 centímetros, sin observar calcificacionesy localizando una larva adulta en el interior del mismo.Se practica una punción aspiración con aguja fina (PAAF)de la tumoración, observando filarias del tipo Loa Loa. Trasrecibir tratamiento con Dietilcarbamazina e Ivermectin es intervenidarealizando una tumorectomía amplia, quedando lapaciente asintomática

An eighteen years old patient, from Guinea, who comes toour clinic with a large tumour in the left breast that includesthe two external quadrants. A mammography, an ecographand a magnetic nuclear resonance are made showing a largegranuloma of 12 centimetres, without calcifications andwatching the adult larva on the inside of granuloma.A PAAF is practised on the tumour, watching the parasite(Loa Loa filaria). After receiving treatment with Dietilcarbamazinaand Ivermectin, the patient undergoes a large lumpectomy,the patient is now asymptomatic

[Current possibilities in the control of Loa Loa filariasis]. / Possibilités actuelles de lutte contre la filariose à Loa loa.

Loa loa is currently considered as a major pathogen in man. The clinical repercussions of this filariasis have been clearly established and treatment is considered essential. Ivermectin, administered alone or with diethylcarbamazine presents interesting therapeutic possibilities. The review of vector control methods show that trapping is the only effective measure of protection. In order to reduce the endemicity of loaiasis, mass treatment with ivermectin could be envisaged immediately. However, the development of this filariasis is directly related to the development of the Central African forest region.

Survival of Loa loa following transplantation from drills (Mandrillus leucophaeus) into jirds (Meriones unguiculatus): parasitology and pathology.

Two drills infected with Loa loa maintained a microfilaraemia for four and a half years ranging from less than 1 mf/100 microliters to 1150 mf/100 microliters. No significant tissue reactions to the adult worms were seen at autopsy. Adult worms were transplanted into the peritoneal cavities of naive jirds when a persistent microfilaraemia first developed by 17 days. Retransplantation of adult worms into naive jirds produced a microfilaraemia and microfilariae in the peritoneal cavities of three out of five animals. These three animals were all negative for circulating parasites by eight and a half months. The tissue reactions to the worms in the jirds are described, including a granulomatous response surrounding adults and a myositis involving microfilariae.