[show abstract][hide abstract] ABSTRACT: Global efforts to eliminate lymphatic filariasis are based on the annual mass administration of antifilarial drugs to reduce the microfilaria reservoir available to the mosquito vector. Insecticide-treated bed nets are being widely used in areas in which filariasis and malaria are coendemic.
We studied five villages in which five annual mass administrations of antifilarial drugs, which were completed in 1998, reduced the transmission of Wuchereria bancrofti, one of the nematodes that cause lymphatic filariasis. A total of 21,899 anopheles mosquitoes were collected for 26 months before and 11 to 36 months after bed nets treated with long-lasting insecticide were distributed in 2009. We evaluated the status of filarial infection and the presence of W. bancrofti DNA in anopheline mosquitoes before and after the introduction of insecticide-treated bed nets. We then used a model of population dynamics to estimate the probabilities of transmission cessation.
Village-specific rates of bites from anopheline mosquitoes ranged from 6.4 to 61.3 bites per person per day before the bed-net distribution and from 1.1 to 9.4 bites for 11 months after distribution (P<0.001). During the same period, the rate of detection of W. bancrofti in anopheline mosquitoes decreased from 1.8% to 0.4% (P=0.005), and the rate of detection of filarial DNA decreased from 19.4% to 14.9% (P=0.13). The annual transmission potential was 5 to 325 infective larvae inoculated per person per year before the bed-net distribution and 0 after the distribution. Among all five villages with a prevalence of microfilariae of 2 to 38%, the probability of transmission cessation increased from less than 1.0% before the bed-net distribution to a range of 4.9 to 95% in the 11 months after distribution.
Vector control with insecticide-treated bed nets is a valuable tool for W. bancrofti elimination in areas in which anopheline mosquitoes transmit the parasite. (Funded by the U.S. Public Health Service and the National Institutes of Health.).
New England Journal of Medicine 08/2013; 369(8):745-53. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Wuchereria bancrofti (Wb) is the primary causative agent of lymphatic filariasis (LF). Our studies of LF in Papua New Guinea (PNG) have shown that it is possible to reduce the prevalence of Wb in humans and mosquitoes through mass drug administration (MDA; diethylcarbamazine with/without ivermectin). While MDAs in the Dreikikir region through 1998 significantly reduced prevalence of Wb infection, parasites continue to be transmitted in the area.
We sequenced the Wb mitochondrial Cytochrome Oxidase 1 (CO1) gene from 16 people infected with Wb. Patients were selected from 7 villages encompassing both high and moderate annual transmission potentials (ATP). We collected genetic data with the objectives to (i) document contemporary levels of genetic diversity and (ii) distinguish between populations of parasites and hosts across the study area.
We discovered 109 unique haplotypes currently segregating in the Wb parasite population, with one common haplotype present in 15 out of 16 infections. We found that parasite diversity was similar among people residing within the same village and clustered within transmission zones. For example, in the high transmission area, diversity tended to be more similar between neighboring villages, while in the moderate transmission area, diversity tended to be less similar.
In the Dreikikir region of PNG there are currently high levels of genetic diversity in populations of Wb. High levels of genetic diversity may complicate future MDAs in this region and the presence of dominant haplotypes will require adjustments to current elimination strategies.
[show abstract][hide abstract] ABSTRACT: The relationship between mosquito vectors and lymphatic filariasis (LF) parasites can result in a range of transmission outcomes. Anophelines are generally characterized as poor vectors due to an inability to support development at low densities. However, it is important to understand the potential for transmission in natural vectors to maximize the success of elimination efforts. Primary vectors in Papua New Guinea (n = 1209) were dissected following exposure to microfilaremic blood (range 8-233 mf/20 µl). We examined density dependent and species-specific parasite prevalence, intensity and yield, barriers to parasite development as well as impacts on mosquito survival. We observed strikingly different parasite prevalence and yield among closely related species. Prevalence of infective stage larvae (L3s) ranged from 4.2% to 23.7% in An. punctulatus, 24.5% to 68.6% in An. farauti s.s. and 61.9% to 100% in An. hinesorum at low and high density exposures, respectively. Injection experiments revealed the greatest barrier to parasite development involved passage from the midgut into the hemocoel. The ratio of L3 to ingested mf at low densities was higher in An. hinesorum (yield = 1.0) and An. farauti s.s. (yield = 0.5) than has been reported in other anopheline vectors. There was a negative relationship between mosquito survival and bloodmeal mf density. In An. farauti s.s., increased parasite yield and survival at low densities suggest greater competence at low microfilaremias. In Papua New Guinea the likelihood of transmission will be strongly influenced by vector composition and changes in the mf reservoir as a result of elimination efforts. Global elimination efforts will be strengthened by the knowledge of transmission potential in the context of current control measures.
[show abstract][hide abstract] ABSTRACT: Anopheles punctulatus sibling species (An. punctulatus s.s., Anopheles koliensis, and Anopheles farauti species complex [eight cryptic species]) are principal vectors of malaria and filariasis in the Southwest Pacific. Given significant effort to reduce malaria and filariasis transmission through insecticide-treated net distribution in the region, effective strategies to monitor evolution of insecticide resistance among An. punctulatus sibling species is essential. Mutations in the voltage-gated sodium channel (VGSC) gene have been associated with knock-down resistance (kdr) to pyrethroids and DDT in malarious regions. By examining VGSC sequence polymorphism we developed a multiplex assay to differentiate wild-type versus kdr alleles and query intron-based polymorphisms that enable simultaneous species identification. A survey including mosquitoes from seven Papua New Guinea Provinces detected no kdr alleles in any An. punctulatus species. Absence of VGSC sequence introgression between species and evidence of geographic separation within species suggests that kdr must be monitored in each An. punctulatus species independently.
The American journal of tropical medicine and hygiene 01/2012; 86(1):140-51. · 2.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Malaria and filariasis are transmitted in the Southwest Pacific region by Anopheles punctulatus sibling species including An. punctulatus, An. koliensis, the An. farauti complex 1-8 (includes An. hinesorum [An. farauti 2], An. torresiensis [An. farauti 3]). Distinguishing these species from each other requires molecular diagnostic methods. We developed a multiplex polymerase chain reaction (PCR)-based assay specific for known species-specific nucleotide differences in the internal transcribed spacer 2 region and identified the five species most frequently implicated in transmitting disease (An. punctulatus, An. koliensis, An. farauti 1, An. hinesorum, and An. farauti 4). A set of 340 individual mosquitoes obtained from seven Papua New Guinea provinces representing a variety of habitats were analyzed by using this multiplex assay. Concordance between molecular and morphological diagnosis was 56.4% for An. punctulatus, 85.3% for An. koliensis, and 88.9% for An. farauti. Among 158 mosquitoes morphologically designated as An. farauti, 33 were re-classified by PCR as An. punctulatus, 4 as An. koliensis, 26 as An. farauti 1, 49 as An. hinesorum, and 46 as An. farauti 4. Misclassification results from variable coloration of the proboscis and overlap of An. punctulatus, An. koliensis, the An. farauti 4. This multiplex technology enables further mosquito strain identification and simultaneous detection of microbial pathogens.
The American journal of tropical medicine and hygiene 01/2011; 84(1):166-73. · 2.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: The development of insecticide resistance has compromised mosquito control efforts in many parts of the world. Papua New Guinea (PNG) has a long history of dichlorodiphenyltrichloroethane (DDT) use and currently distributes pyrethroid-treated nets for malaria control. This study is the first to investigate the status of pyrethroid resistance in the Anopheles punctulatus group, the major malaria and filariasis vectors of PNG. The study used World Health Organization standard susceptibility bioassays to detect knockdown phenotypes and a novel nested polymerase chain reaction to detect the knockdown resistant (kdr) allele in these vectors. Our results show 100% susceptibility to pyrethroids in all populations surveyed and an absence of the kdr allele.
The American journal of tropical medicine and hygiene 12/2010; 83(6):1259-61. · 2.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Four major malaria-causing Plasmodium spp. and lymphatic filariasis-causing Wuchereria bancrofti are co-endemic in many tropical and sub-tropical regions. Among molecular diagnostic assays, multiplex polymerase chain reaction (PCR)-based assays for the simultaneous detection of DNAs from these parasite species are currently available only for P. falciparum and W. bancrofti or P. vivax and W. bancrofti. Using a post-PCR oligonucleotide ligation detection reaction-fluorescent microsphere assay (LDR-FMA), we developed a multiplex assay that has the capability to simultaneously detect all four Plasmodium spp. and W. bancrofti infections in blood samples. Compared with microfilarial positivity in the blood, the LDR-FMA assay is highly concordant (91%), sensitive (86%), and specific (94%), and has high reproducibility for Plasmodium spp. (85-93%) and W. bancrofti (90%) diagnoses. The development of this assay for the simultaneous diagnosis of multiple parasitic infections enables efficient screening of large numbers of human blood and mosquito samples from co-endemic areas.
The American journal of tropical medicine and hygiene 06/2010; 82(6):1030-3. · 2.53 Impact Factor