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Concept: Microfilaria

28

Abstract An examination was made of Giemsa-stained microfilariae in thin blood films from dogs naturally or experimentally infected with Dirofilaria immitis or Dirofilaria repens. The blood was from 9 dogs infected with D. immitis and 9 dogs infected with D. repens. Measurements (total length, length of cephalic space, anterior end to nerve ring and last body nucleus, and nucleus-free tail tip) were made on 2 to 6 microfilariae from each dog using digitally captured images and imaging software. The microfilariae of D. repens were significantly (p<0.001) greater in all measured dimensions except for the length of the cephalic space which was significantly shorter (p<0.001) than that of D. immitis. The cephalic space of D. repens was characterized by being short and routinely being terminated by a distinct pair of nuclei that were separate from the remaining somatic nuclei of the microfilaria. The cephalic space of the smaller microfilaria of D. immitis is longer and does not have the distinct nuclei separated from the somatic column nuclei near the anterior end. The character of the cephalic space seems to be a criterion that could be routinely used for the easy differentiation of these two microfilariae in stained blood films.

Concepts: Function, Vector space, Units of measurement, IMAGE, Dog, Dirofilaria immitis, Dirofilaria, Microfilaria

19

Parasitic helminths cause debilitating diseases that affect millions of people in primarily low-resource settings. Efforts to eliminate onchocerciasis and lymphatic filariasis in Central Africa through mass drug administration have been suspended because of ivermectin-associated serious adverse events, including death, in patients infected with the filarial parasite Loa loa. To safely administer ivermectin for onchocerciasis or lymphatic filariasis in regions co-endemic with L. loa, a strategy termed “test and (not) treat” has been proposed whereby those with high levels of L. loa microfilariae (>30,000/ml) that put them at risk for life-threatening serious adverse events are identified and excluded from mass drug administration. To enable this, we developed a mobile phone-based video microscope that automatically quantifies L. loa microfilariae in whole blood loaded directly into a small glass capillary from a fingerprick without the need for conventional sample preparation or staining. This point-of-care device automatically captures and analyzes videos of microfilarial motion in whole blood using motorized sample scanning and onboard motion detection, minimizing input from health care workers and providing a quantification of microfilariae per milliliter of whole blood in under 2 min. To validate performance and usability of the mobile phone microscope, we tested 33 potentially Loa-infected patients in Cameroon and confirmed that automated counts correlated with manual thick smear counts (94% specificity; 100% sensitivity). Use of this technology to exclude patients from ivermectin-based treatment at the point of care in Loa-endemic regions would allow resumption/expansion of mass drug administration programs for onchocerciasis and lymphatic filariasis in Central Africa.

Concepts: Malaria, Parasitism, Parasitic diseases, Filariasis, Neglected diseases, Ivermectin, Microfilaria, Loa loa filariasis

18

Elimination of filariasis requires a macrofilaricide treatment that can be delivered within a 7-day period. Here we have identified a synergy between the anthelmintic albendazole (ABZ) and drugs depleting the filarial endosymbiont Wolbachia, a proven macrofilaricide target, which reduces treatment from several weeks to 7 days in preclinical models. ABZ had negligible effects on Wolbachia but synergized with minocycline or rifampicin (RIF) to deplete symbionts, block embryogenesis, and stop microfilariae production. Greater than 99% Wolbachia depletion following 7-day combination of RIF+ABZ also led to accelerated macrofilaricidal activity. Thus, we provide preclinical proof-of-concept of treatment shortening using antibiotic+ABZ combinations to deliver anti-Wolbachia sterilizing and macrofilaricidal effects. Our data are of immediate public health importance as RIF+ABZ are registered drugs and thus immediately implementable to deliver a 1-wk macrofilaricide. They also suggest that novel, more potent anti-Wolbachia drugs under development may be capable of delivering further treatment shortening, to days rather than weeks, if combined with benzimidazoles.

Concepts: Ozone depletion, Diethylcarbamazine, Filariasis, Microfilaria

10

Understanding vector-parasite interactions is increasingly important as we move towards the endpoint goals set by the Global Programme for the Elimination of Lymphatic Filariasis (GPELF), as interaction dynamics may change with reduced transmission pressure. Elimination models used to predict programmatic endpoints include parameters for vector-specific transmission dynamics, despite the fact that our knowledge of the host-seeking behaviour of filariasis infected mosquitoes is lacking. We observed a dynamic, stage-specific and density dependent change in Aedes aegypti behaviour towards host cues when exposed to Brugia malayi filarial parasites. Infected mosquitoes exhibited reduced activation and flight towards a host during the period of larval development (L1/L2), transitioning to a 5 fold increase in activation and flight towards a host when infective stage larvae (L3) were present (p < 0.001). In uninfected control mosquitoes, we observed a reduction in convergence towards a host during the same period. Furthermore, this behaviour was density dependent with non-activated mosquitoes harbouring a greater burden of L1 and L2 larvae while activated mosquitoes harboured a greater number of L3 (p < 0.001). Reductions in fecundity were also density-dependent, and extended to mosquitoes that were exposed to microfilariae but did not support larval development.

Concepts: Malaria, Mosquito, Aedes, Vector, Diethylcarbamazine, Filariasis, Brugia timori, Microfilaria

2

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.

Concepts: Malaria, Parasitic diseases, Filariasis, Neglected diseases, Ivermectin, Microfilaria, Loa loa filariasis, Deer fly

0

Filariasis is a major public health problem in tropical countries like India. Despite the large number of people at risk, detection of eggs with or without larva (microfilaria) on fine-needle aspiration cytology is very unusual, especially in an uncommon site or incidentally detected in clinically unsuspected cases of filariasis with the absence of microfilariae in the peripheral blood. A 19-year-old male presented with swelling over medial aspect of left arm (just above the elbow), with no other specific signs and symptoms. Fine needle aspiration cytology revealed an adult gravid female filarial worm in a background of reactive lymphoid cells and lymphohistiocytic clusters. We report a case with elaborate fine needle aspiration cytology findings of filarial worm infestation with unusual presentation of isolated epitrochlear lymph node involvement in a clinically unsuspected case and recommend clinicians and pathologists to consider a high index of suspicion for such infections at uncommon sites especially in endemic territories, as early diagnosis and treatment prevent the more severe manifestations of disease.

Concepts: Malaria, Pathology, Lymphatic system, Needle aspiration biopsy, Lymph, Filariasis, Tropical disease, Microfilaria

0

Post-mass drug administration (MDA) surveillance during the lymphatic filariasis (LF) elimination program in Sri Lanka, revealed the re-emergence of brugian filariasis after four decades. This study was done with the objectives of investigating the epidemiology and age-specific vulnerability to infection. Surveillance was done using night blood smears (NBS) and the Brugia rapid test (BRT), to detect microfilaria (MF) and anti-Brugia IgG4 antibodies in blood samples collected from an age-stratified population enrolled from two high-risk study areas (SA)s, Pubudugama and Wedamulla in the Gampaha District. The periodicity of the re-emergent Brugia spp. was characterized by quantitative estimation of MF in blood collected periodically over 24 h using nucleopore-membrane filtration method.

Concepts: Immune system, Sri Lanka, Filariasis, Brugia timori, Colombo, Microfilaria, Western Province, Sri Lanka, Bandaranaike International Airport

0

Parasitic nematodes have evolved powerful immunomodulatory molecules to enable their survival in immunocompetent hosts by subverting immune responses and minimizing pathological processes. One filarial molecule known to counteract host immune responses by inducing IL-10 and regulatory macrophages in mice is filarial cystatin. During a patent filarial infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive. The microfilarial larval stage was formerly shown to induce human regulatory monocytes and macrophages. Thus, here we aim was to determine how filarial cystatin of the human pathogenic filaria Brugia malayi (BmCPI-2) contributes to immune hyporesponsiveness in human monocytes and macrophages elicited by microfilaria. For this purpose, filarial cystatin was depleted from microfilarial lysate (Mf). Detecting the immunomodulatory potential of cystatin-depleted Mf revealed that IL-10, but not IL-8 and IL-6 induction in monocytes and macrophages is dependent on the presence of cystatin. In addition, the Mf-induced expression of the regulatory surface markers PD-L1 and PD-L2 in human monocytes, but not in macrophages, is dependent on cystatin. While Mf-treated monocytes result in decreased CD4+ T-cell proliferation in a co-culture assay, stimulation of T-cells with human monocytes treated with cystatin-depleted Mf lead to a restoration of CD4+ T-cell proliferation. Moreover, IL-10 induction by cystatin within Mf was dependent on p38 and ERK in macrophages, but independent of the ERK pathway in monocytes. These findings indicate that filarial nematodes differentially trigger and exploit various signaling pathways to induce immunomodulation in different myeloid cell subsets.

Concepts: Immune system, White blood cell, Immunology, Diethylcarbamazine, Filariasis, Brugia timori, Wuchereria bancrofti, Microfilaria

0

Microfilaria is a major public health problem in tropical and subtropical countries and is an endemic problem in India. Wuchereria bancrofti is the commonest filarial infection. In some lesions, microfilariae and adult filarial worm have been incidentally detected in fine-needle aspirates.

Concepts: Malaria, Nematodes, Diethylcarbamazine, Filariasis, Tropical disease, Wuchereria bancrofti, Microfilaria, Insect-borne diseases

0

Concern is growing regarding the prospects of achieving the global elimination of lymphatic filariasis (LF) by 2020. Apart from operational difficulties, evidence is emerging which points to unique challenges that could confound achieving LF elimination as extinction targets draw near. Diethylcarbamazine (DEC)-medicated salt may overcome these complex challenges posed by the endgame phase of parasite elimination. We calibrated LF transmission models using Bayesian data-model assimilation techniques to baseline and follow-up infection data from 11 communities that underwent DEC salt medication. The fitted models were used to assess the utility of DEC salt treatment for achieving LF elimination, in comparison with other current and proposed drug regimens, during the endgame phase. DEC-medicated salt consistently reduced microfilaria (mf) prevalence from 1% mf to site-specific elimination thresholds more quickly than the other investigated treatments. The application of DEC salt generally required less than one year to achieve site-specific LF elimination, while annual and biannual MDA options required significantly longer durations to achieve the same task. The use of DEC-medicated salt also lowered between-site variance in extinction timelines, especially when combined with vector control. These results indicate that the implementation of DEC-medicated salt, where feasible, can overcome endgame challenges facing LF elimination programs.

Concepts: Diethylcarbamazine, Filariasis, Microfilaria