Evaluation of coagulation and platelet activation state and function in heartworm-infected dogs.

BACKGROUND: Enhanced platelet responses have been demonstrated in heartworm-infected (HWI) dogs; however, the cause and clinical implications of altered platelet function have not been fully elucidated. OBJECTIVE: This study evaluated platelet function in HWI dogs. METHODS: Anticoagulated whole blood collected from eight HWI and eight uninfected dogs was evaluated using turbidometric platelet aggregometry, a platelet function analyzer (PFA-100), a total thrombus analysis system (T-TAS), tissue factor-activated and tissue plasminogen activator modified thromboelastography (TF- and tPA-TEG), CBC, von Willebrand Factor activity, and fibrinogen concentrations. Platelet activation state and the presence of reticulated platelets were assessed via flow cytometric expression of P-selection (CD-62P) and thiazole orange staining. RESULTS: Platelet aggregation responses to adenosine diphosphate (ADP, 10 µM) or collagen (20 µg/mL), PFA-100 closure times, and T-TAS occlusion times did not differ between groups. TEG values TF-R, tPA-R, TF-K, and TF-LY60 were decreased (P = .025, P = .047, P = .038, P = .025) and TF-MA, tPA-MA, TF-G, tPA-G and TF-alpha angle were increased (P < .04) in HWI dogs. HWI dogs had higher fibrinogen concentrations (465.6 ± 161 mg/dL vs 284.5 ± 38 mg/dL, P = .008) and eosinophil counts (0.686 ± 0.27 × 103/µL vs 0.267 ± 0.20 × 103/µL, P = .003). There was no difference in hematocrit, activation state, or percent of reticulated platelets. Non-activated reticulated platelets exhibited higher CD62P expression compared with mature platelets. CONCLUSIONS: Chronic canine heartworm disease was accompanied by hypercoagulability, hyperfibrinogenemia, and decreased fibrinolysis. Enhanced platelet activation was not identified in this group of HWI dogs.

Frequency of Dirofilaria immitis infection in blood donor dogs of the Rio de Janeiro state.

Dirofilariasis, a parasitic disease caused by the nematode Dirofilaria immitis, commonly known as heartworm, primarily inhabits the pulmonary artery and right heart of dogs and other animals. The disease is transmitted through diptera, predominantly from the Culex, Aedes, and Anopheles genera. Dirofilariasis is cosmopolitan in nature, endemic in coastal regions and tropical climates. Factors such as temperature, humidity, vector density, and the presence of definitive hosts significantly contribute to the spread of this parasitic disease. In the state of Rio de Janeiro, a prevalence of 58.6% of D. immitis infected animals has been recorded in municipalities like Niterói. Given that blood transfusions are routine clinical procedures and blood bags are not always accurately evaluated, an investigation into D. immitis infection in blood donor dogs from the metropolitan region of Rio de Janeiro was conducted. A total of 1044 blood donor dog files from a blood bank in Niterói, RJ, collected from January 2019 to December 2022, were analyzed. These samples, originating from kennels in various municipalities in the Metropolitan Region, were tested for the presence of microfilariae through direct examination using tubes and microhematocrit evaluated in optical microscopy. Additionally, the search for antigens was conducted using the enzyme-linked immunosorbent assay technique. Out of the 1044 records evaluated, 17.8% (186/1044) were positive for heartworm infection, with 2% (21/1044) samples positive for microfilariae and 14.8% (154/1044) positive for D. immitis antigens. The high prevalence rate indicates that canine D. immitis infection remains prevalent in the state of Rio de Janeiro, necessitating effective guidelines for prescribing preventive medications by veterinarians and an increase in epidemiological surveillance in the region.

A dirofilariose é uma parasitose determinada pelo nematóide Dirofilaria immitis, que tem como habitat artéria pulmonar e coração direito de canídeos e outros animais, sendo por isso conhecido popularmente como verme do coração. A transmissão da parasitose ocorre por meio de dípteros principalmente dos gêneros Culex, Aedes e Anopheles. A dirofilariose é considerada cosmopolita, sendo endêmica em regiões litorâneas e de clima tropical. A temperatura, a umidade, a densidade de vetores e a presença de hospedeiros definitivos são considerados os principais fatores que contribuem para a propagação da parasitose. No estado do Rio de Janeiro, alguns municípios como Niterói, já foi registrada uma prevalência de 58.6% de animais infectados por D. immitis. Como as transfusões de sangue são procedimentos clínicos rotineiros e as bolsas de sangue nem sempre são avaliadas corretamente, decidiu-se investigar a infecção por D. immitis em cães doadores de sangue da região metropolitana do estado do Rio de Janeiro. Foram analisados 1044 prontuários de cães doadores de sangue de um banco de sangue localizado em Niterói, RJ, obtidos no período de janeiro de 2019 a dezembro de 2022. As amostras foram provenientes de canis localizados em diferentes municípios da Região Metropolitana, e testadas para presença de microfilárias por meio de exame direto utilizando-se tubos e microhematócrito avaliados em microscopia óptica e através da realização da pesquisa de antígenos utilizando-se a técnica de ELISA. Das 1044 fichas avaliadas, 17.8% (186/1044) das amostras foram positivas para infecção pelo verme do coração, sendo 2% (21/1044) positivas para presença de microfilárias e 14.75% (154/1044) positivas para presença de antígenos de D. immitis. A alta taxa de prevalência encontrada permite concluir que a infecção canina por D. immitis ainda apresenta alta prevalência no estado do Rio de Janeiro, exigindo orientações efetivas para a prescrição de medicamentos preventivos por médicos veterinários e aumento da vigilância epidemiológica na região.

Motile microfilaria captured by fluorescent microscopy and the unmasking of eosinophilia following treatment.

A 24-year-old patient from Cameroon presented to our hospital because of a foreign structure in her left eye. To our knowledge, for the first time, fluorescent microscopy revealed motile microfilariae, and the diagnosis of loiasis was established. Despite substantial microfilaremia, eosinophilia only unmasked after the initiation of antiparasitic therapy.

[Reliability evaluation in rural Congo of the calibrated blood smear technique to assess Loa loa microfilaremia level]. / Évaluation en milieu rural au Congo de la fiabilité de la méthode de la goutte épaisse calibrée pour évaluer le niveau de la microfilarémie à Loa loa.

Background-Rationale: The diagnosis of Loa loa microfilaremia consists in the observation, using a microscope, of microfilariae in a sample of peripheral blood spread on a slide and subsequently stained (the "blood smear technique"). The accurate quantification of Loa loa microfilaremia is important because the choice of the first intention treatment depends on the patient's microfilaremia: severe adverse events can occur in individuals with high microfilarial densities when treated with ivermectin or diethylcarbamazine, the latter drug being the only one which can definitively cure the infection. However, despite the widespread usage of this technique and its role in guiding clinical management of the patient, estimates of its reliability remain scarce. Materials and methods: We evaluated the reliability (reproducibility and repeatability) of blood smear technique using several sets of 10 L. loo-positive slides, randomly selected, and considered the results with regard to regulatory requirements. The slides had been prepared as part of a clinical trial conducted in Sibiti, Republic of Congo, a region where loiasis is endemic. Results: The estimated and acceptable coefficients of repeatability (NB: the lower, the better) were 13.6% and 16.0%, respectively. The estimated and acceptable coefficients of intermediate reliability (reproducibility) were 15.1% and 22.5%, respectively. The poorest coefficient of intermediate reliability was 19.5% when the tested parameter was related to the technician who performed the readings (10.7% when the reading day was changed). The inter-technician coefficient of variation assessed using 1876 L. loo-positive slides was 13.2%. The coefficient of inter-technician variation considered acceptable was estimated at 18.6%. Discussion-Conclusion. All estimated coefficients of variability were lower than the calculated acceptable coefficients suggesting reliability of the technique, although the lack of laboratory references precludes any conclusion on the quality of this diagnosis. It is imperative to implement a quality system and standardization of procedures for the diagnosis of L. loo microfilaremia, both in endemic countries and in the rest of the world, where the demand for diagnosis has been increasing for years.

Safety of Simparica Trio® (sarolaner, pyrantel, moxidectin) in heartworm-infected dogs.

BACKGROUND: Assessment of the safety of heartworm preventatives in dogs with pre-existing patent heartworm (Dirofilaria immitis) infections is necessary because rapid adult worm and microfilarial death can lead to severe clinical complications, including thromboembolism and anaphylactic shock in dogs. The aim of this study was to determine the clinical safety of Simparica Trio® (sarolaner, pyrantel, moxidectin) in heartworm-infected dogs and the degree of microfilaricidal and adulticidal activity of three consecutive monthly treatments of Simparica Trio. METHODS: Twenty-four laboratory Beagle dogs were implanted with 10 male and 10 female D. immitis (ZoeKY isolate), and once infection was patent, they were randomized equally among three groups to receive no treatment, 1× or 3× the maximum recommended label dose of Simparica Trio. Dogs in the treated groups received Simparica Trio on days 0, 28 and 56. In-life assessments included body weight, physical examinations, clinical observations, daily general health observations, a quantitative estimate of food consumption and blood collections for pharmacokinetic (PK) analysis, microfilariae (MF) counts and D. immitis antigen testing. At the end of the study the heart, lungs and pleural and peritoneal cavities were examined for adult D. immitis worms. RESULTS: Simparica Trio was generally well tolerated. Emesis occurred at low frequency in all groups including control. Abnormal stool occurred occasionally in the 1× and 3× groups throughout the 3-month study. Fever (> 104 °F/40 °C) was recorded in one 1× and one 3× dog 1 day after the first dose and resolved by the following day. No severe hypersensitivity reactions occurred. The mean number of circulating microfilariae (MF) counts in the control group increased from 12,000/ml at study start (Day 0) to > 20,000/ml at Day 28 and remained > 20,000/ml for the duration of the study. The least squares means of circulating MF were reduced by 69.8% on Day 1 and 97.4% on Day 7 for the 1× group and remained at > 99% lower than the control group for the remainder of the study. Similarly, least squares means of circulating MF were reduced by 85.3% on Day 1 and 93.9% on Day 7 for the 3× group and remained > 98% lower than the control group for the remainder of the study. At the end of the study, the mean number of implanted adult worms recovered was < 10 per sex in all groups with 90%, 85% and 75% of live adult heartworms recovered in control, 1× and 3× treatment groups, respectively. Low numbers of dead adult worms were recovered in 1× and 3×, with none in control. Following each dose, the moxidectin and sarolaner AUC and Cmax had close to dose proportional increases. CONCLUSIONS: This study demonstrated that Simparica Trio (sarolaner, pyrantel, moxidectin) was well tolerated when administered to heartworm-positive dogs at 1× and 3× the maximum recommended dose at 28-day intervals for 3 consecutive months. Simparica Trio significantly reduced microfilaria counts in both treatment groups, without significant clinical consequences. At the doses administered, Simparica Trio had minor adulticidal activity but resulted in no clinical sequelae.

Factors associated with the periodicity of Loa loa microfilaremia in the Republic of the Congo.

BACKGROUND: Loa loa microfilariae circulate in the peripheral blood of human hosts following a diurnal periodicity, with maximal microfilaremia levels generally observed between 10:00 am and 3:00 pm. Few studies have assessed factors potentially associated with this periodicity. METHODS: Microfilaremia data were collected repeatedly between 9:00 am and 8:00 pm from 13 individuals in the Republic of the Congo. Using local polynomial regression (LOESS), we determined the best models representing the dynamics of microfilaremia over this period. In a second step, using cosinor models, we evaluated the influence of sex, age, and body temperature on the periodicity of L. loa microfilaremia in blood. RESULTS: All subjects reached their maximum microfilaremia between 10:00 am and 4:00 pm. Individual microfilaremia showed different patterns between individuals, and some clearly showed multiple peaks within a day. LOESS provided a good fit to the observed data. Without adjustment, the maximum microfilarial density was reached around 11:00 am. Adjustment revealed three distinct modes of microfilaremia, occurring around 10:00 am, 1:00 pm, and 4:00 pm. Cosinor models also provided good fit to our data. After adjustment on body temperature, the L. loa microfilaremia fluctuation amplitude decreased significantly from 1684.8 to 310.6 microfilariae(mf)/ml and the predicted peak was estimated at 12:02 pm. CONCLUSIONS: We characterized the periodicity of L. loa microfilaremia mathematically with two different approaches: cosinor models and LOESS regression. Both models suggest that body temperature plays a role in the variation in microfilaremia within a day. Further studies are needed to identify individual co-factors affecting microfilaremia.

Dirofilaria repens microfilaremia in humans: Case description and literature review.

INTRODUCTION: Dirofilaria repens is a vector-borne filaroid helminth of carnivorous animals, primarily domesticated dogs. Humans are considered to be accidental hosts in which D. repens rarely reach sexual maturity but induce local inflammation, mainly in subcutaneous and ocular tissues. METHODS: In the current study, we present the detection of multiple adults of D. repens, endosymbiont Wolbachia sp. and microfilariae by molecular analysis in peripheral tissues and bloodstream of a human host. A subsequent meta-analysis of published literature identified 21 cases of human infection with adult D. repens producing microfilariae. RESULTS: Within the study population, there were 13 (59.09%) males, eight (36.36%) females and, in one (4.55%) case, sex was not reported. A total of 11 (50.00%) cases had subcutaneous dirofilariasis, six (27.27%) had ocular dirofiliariasis, with single cases (4.55% each) of genital, mammary, lymphatic and a combination of subcutaneous and pulmonary dirofilariasis described. In one (4.55%) case, the primary anatomical site of adult D. repens could not be found. D. repens microfilariae were detected in the local tissue (local microfilariasis) in 11 (50.00%) cases and the peripheral blood (microfilaremia) in 11 (50.50%) cases. Final identification of D. repens microfilariae was based on morphological detection in 14 (63.64%) cases, and molecular detection in eight (36.36%) cases. CONCLUSION: The results of this study suggest that humans may act as a final host for D. repens, however its role as a source of D. repens infection is less clear.

Molecular characterization and genetic diversity of Loa loa parasites responsible of a long-delayed filarial infection in an immigrant patient inhabited in Paris.

A 21-year-old young boy who lived alone since one year and a half ago in Paris was referred due to severe vertigo. He is originally from Ivory Coast but lived from 2011 to 2017 in Douala city in west of Cameroon. Beside vertigo, he complained from headache, sudden abdominal pain and edema in both left and right forearms for about two years. General examination demonstrated a healthy condition with no subcutaneous nodules and swelling on any other part of the body, not splenomegaly or lymphadenopathy. Moreover, the eyes were normal with clear lens. Blood count analysis revealed a hypereosinophilia (2670*106/L, N: <500*106/L). A couple of direct and May-Grunwald-Giemsa stained smears, analyzed by microscopy revealed the semitransparent cylindrical worms with almost 300 µm length and 45 µm width identified as Loa loa. The identity of the worm was then confirmed by bidirectional sequencing of 450 bp fragment of internal transcribed spacer 1 (ITS1-rDNA). Based on Neighbor-Joining phylogenetic tree, our isolate was clustered tightly with other few Loa species from Gabon in the same clade. No hybrid was observed among processed sequences since all species groups were discriminated separately. In the current case, he was originally from Ivory Coast but absence of medical and epidemiological evidences as well as the residency of our patient for 6 years in Cameroon made us suspicious that the patient has been most likely infected by L. loa worms in this country. The patient was treated by a couple of ivermectin (200 µg/kg for 3 days) and diethylcarbamazine (3 mg/kg, 2 times per day for 4 weeks) and a favorable evolution was observed within few weeks. Regarding at least one year and a half interval between the probable Loa loa infection in Cameroon and diagnosis, Loa loa worms are competent to persist in the human host for several years. Consequently, the clinicians should be aware of this parasitosis among the travelers or immigrants coming from endemic regions in Africa.

Lymphatic filariasis elimination endgame in an urban Indian setting: the roles of surveillance and residual microfilaremia after mass drug administration.

BACKGROUND: To secure the gains of lymphatic filariasis (LF) elimination programs, attention is needed to the 'residual microfilaremia phase', in which high-risk populations may be crucial. The present study documents the impact of mass drug administration (MDA) in the urban Indian setting of Surat City, with high rates of in-migration. METHODS: Epidemiological assessment included National Filaria Control Program (NFCP) and World Health Organization recommended routine and pre-MDA microfilaremia surveys respectively. Routine filaria surveys were conducted around the year in approximately 2000-4000 people per month, while pre-MDA surveys were carried out annually among approximately 4000 people from four fixed and four random sites. In 2016, Transmission Assessment Survey (TAS) was done in primary school children. The outcomes were microfilaremia (Mf) and antigen prevalence; more specifically, microfilaremia according to place of birth, in pre-MDA and routine night blood smears (NBS) collected from 2008 to 2015. Prevalence ratios and confidence intervals were calculated. RESULTS: A total of 25 480 pre-MDA and 306 198 routine NBS were examined during the study. In 2008, the Mf prevalence in the routine survey was 63/18 814 (0.33%), declining to 23/39 717 (0.06%) in 2016. Pre-MDA surveys showed a similar decrease from 47/4184 (1.1%) in 2008 to 12/4042 (0.3%) in 2015. In those born outside Surat, microfilaremia decreased below transmission thresholds, but remained more than treble that of the remainder of the population, in both the pre-MDA surveys [prevalence ratio: 3.17, 95% confidence interval (CI): 1.15-8.72], and the routine surveys (3.31, 95% CI: 1.47-7.48). Though the TAS results indicated that MDA endpoints had been reached, sub-group analysis identified that 90% of antigenemic children were from families of high-risk groups. CONCLUSIONS: Extensive long-term epidemiological monitoring suggests that all the urban population, including high-risk groups, have benefitted from the ELF program. To prevent re-establishment of infection in large urban areas with unsanitary conditions conducive to filarial vector breeding, there is need to identify residual microfilaremia by customized surveys in addition to pre-MDA monitoring and TAS. The present findings can be used to develop strategies to prioritize screening, surveillance and plan treatment of high-risk groups after achieving MDA endpoints.

Slithering Through the Bone Marrow: Loiasis in a Patient With Human T-Cell Leukemia Virus-1-Associated Adult T-Cell Lymphoma.

Loiasis is a filarial disease endemic to areas of Central and West Africa. We present a case of Loa loa microfilaremia in a patient with HTLV-1-related adult T-cell lymphoma. This case may suggest the possible role of cellular immunity in controlling microfilaria burden.

Case Studies of Severe Microfilaremia in Four Dogs Naturally Infected With Dirofilaria repens as the Primary Disease or a Disease Complicating Factor.

Subcutaneous dirofilariosis in dogs, caused by Dirofilaria repens, is an underdiagnosed disease, now recognized for its zoonotic potential, and growing distribution and prevalence across Europe and Asia. Our understanding of the pathogenicity in human and canine host remains unclear, but case reports suggest that microfilariae (Mf) as well as adult D. repens may directly cause internal organs damage or may be a factor complicating the course of other ailments. The purpose of the study was to report high Mf in dogs and to discuss potential relevance with co-morbidity. Our data from a modified Knott's test performed on 62 infected dogs indicate that the median Mf count in D. repens infections is 675 Mf/ml and we consider microfilaremia above 10,000 Mf/ml as high intensity. This collection of case reports discusses 4 cases of high intensity D. repens microfilaremia in companion dogs; one presenting pathology from a very high intensity of adult D. repens with post-treatment complications, and 3 dogs in which high microfilaremia was detected incidentally during the management of other primary illnesses. To our knowledge this report describes the highest D. repens microfilaremia ever detected in a dog, at 178,000 Mf/ml. The issue of high microfilaremic infections in dogs is poorly studied and there is growing need to identify the presentation and understand the mechanisms of associated pathogenesis in the host-parasite relationship.

Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania.

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1-6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.

Imported loiasis in France: a retrospective analysis of 167 cases with comparison between sub-Saharan and non sub-Saharan African patients.

BACKGROUND: Imported loiasis is a rare cause of consultation at the return of stay in central Africa, which often poses difficult diagnostic and therapeutic questions to practitioners especially those who are unaccustomed to tropical medicine. These difficulties can lead to risks for the patients especially if inappropriate treatment is given. Large series of imported loiasis are scarce. METHODS: We retrospectively studied the data including outcome in patients diagnosed with imported loiasis between 1993 and 2013 in the Paris area on the basis of a parasitological diagnosis (microfilaremia > 1/ml and/or serologic tests). We compared sub-Saharan and non sub-Saharan African patients. RESULTS: Of the 177 identified cases, 167 could be analysed. Sex ratio was 1, mean age 41 years and 83% were sub-Saharan Africans. Cameroon was the main country of exposure (62%). Incubation time may be long (up to 18 months). Of the 167 cases, 57% presented with characteristic symptoms (Calabar swellings, creeping dermatitis, eyeworm) whereas 43% were diagnosed fortuitously. Microfilaremia was evidenced in 105 patients (63%), and specific antibodies in 53%. Compared to sub-Saharan Africans, other patients were presenting less frequently with eyeworm migration and microfilaremia whereas they had higher eosinophilia and positive serology. Prevalence of Calabar swellings was not significantly different between the two groups. Cure rates were 52% with ivermectin alone, and 77% with ivermectin followed by diethylcarbamazine. No severe adverse event was reported. CONCLUSIONS: Presentation of imported loiasis varies according to ethnicity. A systematic screening should be recommended in patients with potential exposure in endemic country. Treatment with ivermectin followed by diethylcarbamazine could be a valuable option.

Unusual feline Dirofilaria immitis infection: a case report / Infecção incomum por Dirofilaria immitis em felino: relato de caso

Abstract Cats are less susceptible to Dirofilaria immitis infection than dogs. Although rare, the feline disease can be fatal even with low parasitic loads. The infection is often asymptomatic or has non-specific symptoms that are mainly associated with the death of immature worms. Microfilaremia is rare and transient. Normally, microfilaremia, when present, lasts for not more than 33 days. This study describes a feline case presenting with non-specific clinical signs and prolonged microfilaremia. Case: a random bred cat infected by feline leukemia virus (FeLV) that was found to be microfilaremic by chance. The infection was detected by the presence of microfilariae in a blood smear and was confirmed by antigen test (SNAP Feline Triple Test, Idexx®) and echocardiogram.

Resumo Gatos são menos susceptíveis à infecção por Dirofilaria immitis do que cães. Apesar de rara, a doença nos gatos pode ser fatal mesmo com baixas cargas parasitárias. Muitas vezes, a doença é assintomática ou apresenta sintomas inespecíficos, principalmente associados com a morte de formas parasitárias imaturas. Microfilaremia é rara e transitória. Normalmente, quando ocorre microfilaremia, ela permanece por, no máximo, 33 dias. Este estudo descreve o caso de um felino que apresentava sinais inespecíficos e microfilaremia prolongada: um gato sem raça definida, portador de infecção pelo vírus da leucemia felina (FeLV) que foi diagnosticado como microfilaremico ao acaso. A infecção foi detectada pela presença de microfilárias em esfregaço sanguíneo e, posteriormente, confirmada pelo teste de antígenos (SNAP Feline Triple Test, Idexx®) e por ecocardiograma.

Atypical Clinical Manifestations of Loiasis and Their Relevance for Endemic Populations.

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.

Evaluation of the effect of mass drug administration against lymphatic filariasis in three health districts and public health implications: study of 12 epidemiological surveillance sites in Burkina Faso.

The implementation of mass drug administration (MDA) campaigns of albendazole (400 mg) and ivermectin (150-200 µm/kg) since 2001 has helped to change the epidemiological profile of lymphatic filariasis (LF) in many health districts in Burkina Faso. From 2002 to 2016, 14 rounds of MDA have taken place in the Central East zone, with therapeutic coverage exceeding 65%. The objective of the current study was to evaluate the impact of MDA in the fight against LF at 12 sentinel and spot-check sites. This descriptive cross-sectional study surveyed subjects aged 5 years and older between April and July 2017 at these 12 sites. The blood smear performed on nocturnal samples was used to diagnose Wuchereria bancrofti infection. The study included 4364 subjects. Their mean age was 20.55 years with a standard deviation of 14.22 and a range of 5 to 96 years. The overall prevalence of microfilaremia was 0.62% (27/4364), with rates exceeding 1% at three (3) sites. The average microfilaremia density was 106 µf/mL. The overall prevalence of morbidity was low (0.91%), predominantly lymphedema (0.60%). The MDA strategy has helped to reduce the prevalence of LF significantly in Burkina Faso, but some outbreaks still have microfilarial prevalence greater than 1%. Continuation of the additional 2-year strategy with improved adherence to treatment and vector control would help break LF transmission.

Lymphatic filariasis transmission in Rufiji District, southeastern Tanzania: infection status of the human population and mosquito vectors after twelve rounds of mass drug administration.

BACKGROUND: Control of lymphatic filariasis (LF) in most of the sub-Saharan African countries is based on annual mass drug administration (MDA) using a combination of ivermectin and albendazole. Monitoring the impact of this intervention is crucial for measuring the success of the LF elimination programmes. This study assessed the status of LF infection in Rufiji district, southeastern Tanzania after twelve rounds of MDA. METHODS: Community members aged between 10 and 79 years were examined for Wuchereria bancrofti circulating filarial antigens (CFA) using immunochromatographic test cards (ICTs) and antigen-positive individuals were screened for microfilaraemia. All study participants were examined for clinical manifestation of LF and interviewed for drug uptake during MDA rounds. Filarial mosquito vectors were collected indoor and outdoor and examined for infection with W. bancrofti using a microscope and quantitative real-time polymerase chain reaction (qPCR) techniques. RESULTS: Out of 854 participants tested, nine (1.1%) were positive for CFA and one (0.1%) was found to be microfilaraemic. The prevalence of hydrocele and elephantiasis was 4.8% and 2.9%, respectively. Surveyed drug uptake rates were high, with 70.5% of the respondents reporting having swallowed the drugs in the 2014 MDA round (about seven months before this study). Further, 82.7% of the respondents reported having swallowed the drugs at least once since the inception of MDA programme in 2000. Of the 1054 filarial vectors caught indoors and dissected to detect W. bancrofti infection none was found to be infected. Moreover, analysis by qPCR of 1092 pools of gravid Culex quinquefasciatus collected outdoors resulted in an estimated infection rate of 0.1%. None of the filarial vectors tested with qPCR were found to be infective. CONCLUSION: Analysis of indices of LF infection in the human population and filarial mosquito vectors indicated a substantial decline in the prevalence of LF and other transmission indices, suggesting that local transmission was extremely low if occurring at all in the study areas. We, therefore, recommend a formal transmission assessment survey (TAS) to be conducted in the study areas to make an informed decision on whether Rufiji District satisfied WHO criteria for stopping MDA.

Dirofilaria repens Nematode Infection with Microfilaremia in Traveler Returning to Belgium from Senegal.

We report human infection with a Dirofilaria repens nematode likely acquired in Senegal. An adult worm was extracted from the right conjunctiva of the case-patient, and blood microfilariae were detected, which led to an initial misdiagnosis of loiasis. We also observed the complete life cycle of a D. repens nematode in this patient.

Imported Infections with Mansonella perstans Nematodes, Italy.

We report 74 patients in Italy infected with Mansonella perstans nematodes, a poorly described filarial parasite. M. perstans nematodes should be included in the differential diagnosis for patients with eosinophilia from disease-endemic countries. Serologic analysis is useful for screening, and testing for microfilaremia in peripheral blood should be performed for parasite-positive patients.

Seasonality and circadian variation of microfilaremia in dogs experimentally infected with Dirofilaria immitis.

Periodicity, the cyclical rise and fall in microfilaria (mff) numbers in the peripheral blood over time, is observed in many filarial infections. It is correlated with the necessity for these larval stages to be ingested by the blood feeding vector before they can be transmitted to a new vertebrate host. Microfilariae of the dog heartworm Dirofilaria immitis have been described to show periodicity, but the circadian pattern does not seem to be consistent. Most publications describe the lowest mff-concentrations in the peripheral blood in the early morning, while the highest counts occurred either in the afternoon, in the late evening or shortly after midnight. Sixteen dogs were experimentally infected with D. immitis isolates originating from Italy (one isolate, 14 dogs), and the USA (two isolates, one dog each). The dogs were housed indoors with a natural light source (windows) and heating that prevented temperature-drops below 20°C during winter. When patency was reached, blood samples were collected at weekly and monthly intervals over a period of up to 3 years, and at given hours of the day (morning, noon, evening) for the duration of one year in order to determine seasonal, as well as daily variations of microfilaremia. Despite the fact that the dogs were kept indoors, there was an apparent seasonality of the D. immitis-microfilaremia, with peaks in summer and 5-49-times lower counts in winter. This difference was statistically significant and the ratio remained constant over the years, regardless of the fact that the mff-counts increased from the first to the second year of patency. Since the temperature was kept constantly in a range between 20 to 26°C (with some single outliners in both directions) the climatic conditions may not explain this observation. Therefore, day length may be the most obvious reason for the seasonality in the given study set-up. Interestingly, the Italian D. immitis-isolate lost seasonality after three passages of experimental infections in dogs. The circadian cycle of mff in the peripheral blood varied considerably between dogs and season. There was no consistent or apparent pattern, which led to the conclusion that many individual factors seem to influence the appearance of mff in the peripheral blood, even, or especially, under standardized environmental conditions.