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Fulltext Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti

Ahmad NA, Mancini MV, Ant TH, Martinez J, Kamarul GMR, Nazni WA, et al.

Philos Trans R Soc Lond B Biol Sci, 2021 Feb 15;376(1818):20190809.
PMID: 33357050 DOI: 10.1098/rstb.2019.0809

Aedes aegypti mosquitoes carrying the wAlbB Wolbachia strain show a reduced capacity to transmit dengue virus. wAlbB has been introduced into wild Ae. aegypti populations in several field sites in Kuala Lumpur, Malaysia, where it has persisted at high frequency for more than 2 years and significantly reduced dengue incidence. Although these encouraging results indicate that wAlbB releases can be an effective dengue control strategy, the long-term success depends on wAlbB maintaining high population frequencies and virus transmission inhibition, and both could be compromised by Wolbachia-host coevolution in the field. Here, wAlbB-carrying Ae. aegypti collected from the field 20 months after the cessation of releases showed no reduction in Wolbachia density or tissue distribution changes compared to a wAlbB laboratory colony. The wAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collected wAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands. These results indicate that wAlbB continues to inhibit currently circulating strains of dengue in field populations of Ae. aegypti, and provides additional support for the continued scale-up of Wolbachia wAlbB releases for dengue control. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.

Matched MeSH terms: Wolbachia/genetics*
Fulltext Anti-Wolbachia therapy for onchocerciasis & lymphatic filariasis: Current perspectives

Wan Sulaiman WA, Kamtchum-Tatuene J, Mohamed MH, Ramachandran V, Ching SM, Sazlly Lim SM, et al.

Indian J Med Res, 2019 06;149(6):706-714.
PMID: 31496523 DOI: 10.4103/ijmr.IJMR_454_17

Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.

Matched MeSH terms: Wolbachia/drug effects; Wolbachia/pathogenicity*
Acanthocheilonema delicata n. sp. (Nematoda: Filarioidea) from Japanese badgers (Meles anakuma): description, molecular identification, and Wolbachia screening

Uni S, Bain O, Suzuki K, Agatsuma T, Harada M, Motokawa M, et al.

Parasitol Int, 2013 Feb;62(1):14-23.
PMID: 22926421 DOI: 10.1016/j.parint.2012.08.004

Acanthocheilonema delicata n. sp. (Filarioidea: Onchocercidae: Onchocercinae) is described based on adult filarioids and microfilariae obtained from subcutaneous connective tissues and skin, respectively, of Japanese badgers (Meles anakuma) in Wakayama Prefecture, Japan. No endemic species of the genus had been found in Japan. Recently, some filarioids (e.g., Acanthocheilonema reconditum, Dirofilaria spp., and Onchocerca spp.) have come to light as causative agents of zoonosis worldwide. The new species was readily distinguished from its congeners by morphologic characteristics such as body length, body width, esophagus length, spicule length, and the length of microfilariae. Based on the molecular data of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene, A. delicata n. sp. was included in the clade of the genus Acanthocheilonema but differed from two other congeneric species available for study, A. viteae and A. reconditum. Acanthocheilonema delicata n. sp. did not harbor Wolbachia. It is likely that the fauna of filarioids from mammals on the Japanese islands is characterized by a high level of endemicity.

Matched MeSH terms: Wolbachia/physiology*
Fulltext Antifilarial activity of caffeic acid phenethyl ester on Brugia pahangi in vitro and in vivo

Al-Abd NM, Nor ZM, Junaid QO, Mansor M, Hasan MS, Kassim M

Pathog Glob Health, 2017 Oct;111(7):388-394.
PMID: 29065795 DOI: 10.1080/20477724.2017.1380946

Lymphatic filariasis (LF) is a vector borne disease caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi and B. timori, which are transmitted by mosquitoes. Current therapeutics to treat LF are mainly microfilarcidal, and lack activity against adult worms. This set back, poses a challenge for the control and elimination of filariasis. Thus, in this study the activities of caffeic acid phenethyl ester (CAPE) against the filarial worm B. pahangi and its bacterial endosymbiont, Wolbachia were evaluated. Different concentrations (2, 5, 10, 15, 20 μg/ml) of CAPE were used to assess its effects on motility, viability and microfilarial (mf) production of B. pahangi in vitro. Anti-Wolbachial activity of CAPE was measured in worms by quantification of Wolbachial wsp gene copy number using real-time polymerase chain reaction. Our findings show that CAPE was found to significantly reduce adult worm motility, viability, and mf release both in vitro and in vivo. 20 μg/ml of CAPE halts the release of mf in vitro by day 6 of post treatment. Also, the number of adult worms recovered in vivo were reduced significantly during and after treatment with 50 mg/kg of CAPE relative to control drugs, diethylcarbamazine and doxycycline. Real time PCR based on the Wolbachia ftsZ gene revealed a significant reduction in Wolbachia copy number upon treatment. Anti-Wolbachia and antifilarial properties of CAPE require further investigation as an alternative strategy to treat LF.

Matched MeSH terms: Wolbachia/drug effects
Fulltext Antifilarial and Antibiotic Activities of Methanolic Extracts of Melaleuca cajuputi Flowers

Al-Abd NM, Nor ZM, Mansor M, Hasan MS, Kassim M

Korean J Parasitol, 2016 Jun;54(3):273-80.
PMID: 27417081 DOI: 10.3347/kjp.2016.54.3.273

We evaluated the activity of methanolic extracts of Melaleuca cajuputi flowers against the filarial worm Brugia pahangi and its bacterial endosymbiont Wolbachia. Anti-Wolbachia activity was measured in worms and in Aedes albopictus Aa23 cells by PCR, electron microscopy, and other biological assays. In particular, microfilarial release, worm motility, and viability were determined. M. cajuputi flower extracts were found to significantly reduce Wolbachia endosymbionts in Aa23 cells, Wolbachia surface protein, and microfilarial release, as well as the viability and motility of adult worms. Anti-Wolbachia activity was further confirmed by observation of degraded and phagocytized Wolbachia in worms treated with the flower extracts. The data provided in vitro and in vivo evidence that M. cajuputi flower extracts inhibit Wolbachia, an activity that may be exploited as an alternative strategy to treat human lymphatic filariasis.

Matched MeSH terms: Wolbachia/drug effects*
Fulltext Voltage-sensitive sodium channel (Vssc) mutations associated with pyrethroid insecticide resistance in Aedes aegypti (L.) from two districts of Jeddah, Kingdom of Saudi Arabia: baseline information for a Wolbachia release program

Endersby-Harshman NM, Ali A, Alhumrani B, Alkuriji MA, Al-Fageeh MB, Al-Malik A, et al.

Parasit Vectors, 2021 Jul 12;14(1):361.
PMID: 34247634 DOI: 10.1186/s13071-021-04867-3

BACKGROUND: Dengue suppression often relies on control of the mosquito vector, Aedes aegypti, through applications of insecticides of which the pyrethroid group has played a dominant role. Insecticide resistance is prevalent in Ae. aegypti around the world, and the resulting reduction of insecticide efficacy is likely to exacerbate the impact of dengue. Dengue has been a public health problem in Saudi Arabia, particularly in Jeddah, since its discovery there in the 1990s, and insecticide use for vector control is widespread throughout the city. An alternative approach to insecticide use, based on blocking dengue transmission in mosquitoes by the endosymbiont Wolbachia, is being trialed in Jeddah following the success of this approach in Australia and Malaysia. Knowledge of insecticide resistance status of mosquito populations in Jeddah is a prerequisite for establishing a Wolbachia-based dengue control program as releases of Wolbachia mosquitoes succeed when resistance status of the release population is similar to that of the wild population.
METHODS: WHO resistance bioassays of mosquitoes with deltamethrin, permethrin and DDT were used in conjunction with TaqMan® SNP Genotyping Assays to characterize mutation profiles of Ae. aegypti.
RESULTS: Screening of the voltage-sensitive sodium channel (Vssc), the pyrethroid target site, revealed mutations at codons 989, 1016 and 1534 in Ae. aegypti from two districts of Jeddah. The triple mutant homozygote (1016G/1534C/989P) was confirmed from Al Safa and Al Rawabi. Bioassays with pyrethroids (Type I and II) and DDT showed that mosquitoes were resistant to each of these compounds based on WHO definitions. An association between Vssc mutations and resistance was established for the Type II pyrethroid, deltamethrin, with one genotype (989P/1016G/1534F) conferring a survival advantage over two others (989S/1016V/1534C and the triple heterozygote). An indication of synergism of Type I pyrethroid activity with piperonyl butoxide suggests that detoxification by cytochrome P450s accounts for some of the pyrethroid resistance response in Ae. aegypti populations from Jeddah.
CONCLUSIONS: The results provide a baseline for monitoring and management of resistance as well as knowledge of Vssc genotype frequencies required in Wolbachia release populations to ensure homogeneity with the target field population. Vssc mutation haplotypes observed show some similarity with those from Ae. aegypti in southeast Asia and the Indo-Pacific, but the presence of the triple mutant haplotype in three genotypes indicates that the species in this region may have a unique population history.

Matched MeSH terms: Wolbachia/physiology*
Fulltext Pathology of lymphatic filariasis

Mak JW

International e-Journal of Science, Medicine & Education, 2012;6 Suppl:S80-86.
MyJurnal

Developing and adult worms of the human lymphatic filarial parasites (Wuchereria bancrofti,
Brugia malayi, and Brugia timori) are located mainly in the lymphatic system and occasionally in aberrant sites like subcutaneous and conjunctival cysts. Lymphatic
pathology ranging from dilatation of lymphatic channels and lymphangiectasia are detected on ultrasonography in apparently healthy, amicrofilaraemic, but filarial antigen positive individuals in endemic areas. Microfilariae are distributed in various organs and may be associated with immune mediated pathology at these sites; tropical pulmonary eosinophilia is characterized by intense immune mediated destruction of microfilariae in the lung parenchyma. In the spleen and other sites, nodular granulomatous lesions can occur where microfilariae are trapped and destroyed. The finding of Wolbachia endosymbionts in all stages of lymphatic filarial parasites has provided new insight on the adverse reactions
associated with anti-filarial chemotherapy. Inflammatory molecules mainly lipopolysaccharide (LPS)-like molecules released from endosymbionts on death of the
parasites are largely responsible for the adverse reactions encountered during anti-filarial chemotherapy. Prenatal tolerance or sensitization to parasite derived molecules can immune-modulate and contribute to both pathology and susceptibility/resistance to infection. Pathological responses thus depend not only on exposure to filarial antigens/infection, but also on host-parasiteendosymbiont factors and to intervention with antifilarial treatment. Treatment induced or host mediated death of parasites are associated with various grades of inflammatory response, in which eosinophils and LPS from endosymbionts play prominent roles, leading to death of the parasite, granulomatous formation, organization and fibrosis. The non-human primate (Presbytis spp.) model of
Brugia malayi developed for the tertiary screening of anti-filarial compounds has provided unique opportunities for the longitudinal study of the pathology associated with lymphatic filariasis. The pathology in this non-human primate model closely follows that seen in
human lymphatic filarial infections and correlates with clinical evidence of lymphatic pathology as detected with ultrasonography. These studies also show that successful treatment as detected by loss of motility and calcification of worms on ultrasonography is associated with reversal of early dilatations of lymphatic channels.

Matched MeSH terms: Wolbachia