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Jefferson A. Vaughan

Bio: Jefferson A. Vaughan is an academic researcher from University of North Dakota. The author has contributed to research in topics: Population & Anopheles gambiae. The author has an hindex of 23, co-authored 53 publications receiving 1632 citations. Previous affiliations of Jefferson A. Vaughan include United States Department of the Army & Johns Hopkins University.


Papers
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Journal ArticleDOI
TL;DR: PCR appears to be a useful method for detecting Plasmodium parasites during active malaria surveillance in Thailand, and data indicated that the discrepancy between the two methods resulted from poor performance of microscopy at low parasite densities rather thanpoor performance of PCR.
Abstract: The main objective of this study was to compare the performance of nested PCR with expert microscopy as a means of detecting Plasmodium parasites during active malaria surveillance in western Thailand. The study was performed from May 2000 to April 2002 in the village of Kong Mong Tha, located in western Thailand. Plasmodium vivax (PV) and Plasmodium falciparum (PF) are the predominant parasite species in this village, followed by Plasmodium malariae (PM) and Plasmodium ovale (PO). Each month, fingerprick blood samples were taken from each participating individual and used to prepare thick and thin blood films and for PCR analysis. PCR was sensitive (96%) and specific (98%) for malaria at parasite densities ≥ 500/μl; however, only 18% (47/269) of P. falciparum- and 5% (20/390) of P. vivax-positive films had parasite densities this high. Performance of PCR decreased markedly at parasite densities <500/μl, with sensitivity of only 20% for P. falciparum and 24% for P. vivax at densities <100 parasites/μl. Although PCR performance appeared poor when compared to microscopy, data indicated that the discrepancy between the two methods resulted from poor performance of microscopy at low parasite densities rather than poor performance of PCR. These data are not unusual when the diagnostic method being evaluated is more sensitive than the reference method. PCR appears to be a useful method for detecting Plasmodium parasites during active malaria surveillance in Thailand.

177 citations

Journal ArticleDOI
TL;DR: This quantitative study indicates that the sporogony of cultured P. falciparum in laboratory-infected A. gambiae is an inefficient process and that the ookinete is the key transitional stage affecting the probability of vector infectivity.
Abstract: The population dynamics of cultured Plasmodium falciparum parasites was examined during their sporogonic development in Anopheles gambiae mosquitoes. Estimates of absolute densities were determined for each life stage, and life tables were constructed for each of 38 experimental infections. Macrogametocyte and ookinete mortalities contributed equally to the overall mortality. On average, there was a 40-fold decrease in parasite numbers in the transition from the macrogametocyte to the ookinete stage, a 69-fold decrease in the transition from ookinete to oocyst stages, and a total net decrease in parasite numbers from macrogametocyte to oocyst stage of 2,754-fold (i.e., multiplicative). There was no relationship between macrogametocyte and ookinete densities due to the inherent variability in fertility among different gametocyte cultures. There was a curvilinear relationship (r2 = 0.66) between ookinete and oocyst densities. Above a threshold of about 30 ookinetes/mosquito, the oocyst yield per ookinete became increasingly greater with increasing ookinete density. There was a linear relationship (r2 = 0.73) between oocyst and sporozoite densities, with an average of 663 salivary gland sporozoites produced per oocyst. Sporozoite production per oocyst was not affected by oocyst density and virtually all oocyst infections resulted in sporozoite infections of the salivery glands. This quantitative study indicates that the sporogony of cultured P. falciparum in laboratory-infected A. gambiae is an inefficient process and that the ookinete is the key transitional stage affecting the probability of vector infectivity.

141 citations

Journal ArticleDOI
TL;DR: The low but highly variable numbers of sporozoites transmitted in vitro by mosquitoes used in malaria vaccine challenge studies appears to be a reasonable simulation of natural sporozoite transmission.
Abstract: The frequency and numbers of Plasmodium falciparum sporozoites transmitted in vitro and corresponding sporozoite loads were determined for experimentally infected Anopheles gambiae and An. stephensi. Geometric mean (GM) sporozoite loads in three experiments ranged from 808 to 13, 905 for An. gambiae and from 6, 608 to 17, 702 for An. stephensi. A total of 44.1% of 68 infected An. gambiae and 49.2% of 63 infected An. stephensi transmitted sporozoites in vitro. The GM number of sporozoites transmitted was 4.5 for An. gambiae and 5.4 for An. stephensi. Overall, 86.9% of the mosquitoes transmitted from one to 25 sporozoites, and only 6.6% transmitted over 100 sporozoites (maximum = 369). Sporozoite loads were not a useful predictor of potential sporozoite transmission. Despite higher sporozoite loads, the numbers of sporozoites transmitted in vitro by the experimentally infected mosquitoes were similar to estimates obtained, using the same techniques, for naturally infected An. gambiae in western Kenya. The low but highly variable numbers of sporozoites transmitted in vitro by mosquitoes used in malaria vaccine challenge studies appears to be a reasonable simulation of natural sporozoite transmission.

115 citations

Journal ArticleDOI
TL;DR: Recent publications on the population dynamics of sporogony are reviewed, with special attention to the differences and similarities among the parasite-vector systems examined thus far.

96 citations

Journal ArticleDOI
TL;DR: The results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity.
Abstract: The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.

90 citations


Cited by
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Journal ArticleDOI
TL;DR: Calreticulin is a highly versatile lectin-like chaperone, and it participates during the synthesis of a variety of molecules, including ion channels, surface receptors, integrins and transporters.
Abstract: The endoplasmic reticulum (ER) plays a critical role in the synthesis and chaperoning of membrane-associated and secreted proteins. The membrane is also an important site of Ca(2+) storage and release. Calreticulin is a unique ER luminal resident protein. The protein affects many cellular functions, both in the ER lumen and outside of the ER environment. In the ER lumen, calreticulin performs two major functions: chaperoning and regulation of Ca(2+) homoeostasis. Calreticulin is a highly versatile lectin-like chaperone, and it participates during the synthesis of a variety of molecules, including ion channels, surface receptors, integrins and transporters. The protein also affects intracellular Ca(2+) homoeostasis by modulation of ER Ca(2+) storage and transport. Studies on the cell biology of calreticulin revealed that the ER membrane is a very dynamic intracellular compartment affecting many aspects of cell physiology.

767 citations

Journal ArticleDOI
10 Apr 2008-Nature
TL;DR: It is shown that holidays lead to a 20–29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults, as well as predicting the effect of school closure during a pandemic.
Abstract: The threat posed by the highly pathogenic H5N1 influenza virus requires public health authorities to prepare for a human pandemic. Although pre-pandemic vaccines and antiviral drugs might significantly reduce illness rates, their stockpiling is too expensive to be practical for many countries. Consequently, alternative control strategies, based on non-pharmaceutical interventions, are a potentially attractive policy option. School closure is the measure most often considered. The high social and economic costs of closing schools for months make it an expensive and therefore controversial policy, and the current absence of quantitative data on the role of schools during influenza epidemics means there is little consensus on the probable effectiveness of school closure in reducing the impact of a pandemic. Here, from the joint analysis of surveillance data and holiday timing in France, we quantify the role of schools in influenza epidemics and predict the effect of school closure during a pandemic. We show that holidays lead to a 20-29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults. Holidays prevent 16-18% of seasonal influenza cases (18-21% in children). By extrapolation, we find that prolonged school closure during a pandemic might reduce the cumulative number of cases by 13-17% (18-23% in children) and peak attack rates by up to 39-45% (47-52% in children). The impact of school closure would be reduced if it proved difficult to maintain low contact rates among children for a prolonged period.

656 citations

Journal ArticleDOI
TL;DR: How control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed are drawn together to show how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir.
Abstract: Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.

651 citations

Journal Article
02 Jan 2009-Science
TL;DR: Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units.
Abstract: Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.

576 citations

Journal ArticleDOI
TL;DR: Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself, which has important implications for the assessment of radical treatment efficacy and for malaria control and elimination.
Abstract: Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics P. vivax infections are characterized either by a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria control and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important implications for the assessment of radical treatment efficacy and for malaria control and elimination.

525 citations