Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparum malaria during an epidemic in Central Java, Indonesia

A recent malaria epidemic in the Menoreh Hills of Central Java has increased concern about the re-emergence of endemic malaria on Java, which threatens the island's 120 million residents. A 28-day, in-vivo test of the efficacy of treatment of malaria with antimalarial drugs was conducted among 16 7 villagers in the Menoreh Hills. The treatments investigated, chloroquine (CQ) and sulfadoxine pyrimethamine (SP), constitute, respectively, the first- and second-line treatments for uncomplicated malaria in Indonesia. The prevalence of malaria among 1389 residents screened prior to enrollment was 33%. Treatment outcomes were assessed by microscopical diagnoses, PCR-based confirmation of the diagnoses, measurement of the whole-blood concentrations of CQ and desethylchloroquine (DCQ), and identification of the Plasmodium falciparum genotypes. The 28-day cumulative incidences of therapeutic failure for CQ and SP were, respectively, 47% (N = 36) and 22% (N = 50) in the treatment of P. falciparum, and 18% (N = 77) and 67% (N = 6) in the treatment of P. vivax. Chloroquine was thus an ineffective therapy for P. falciparum malaria, and the presence of CQ-resistant P. vivax and SP-resistant P. falciparum will further compromise efforts to control resurgent malaria on Java.

Comparison of tafenoquine (WR238605) and primaquine in the post-exposure (terminal) prophylaxis of vivax malaria) in Australian Defence Force personnel

On return from duty in North Solomons Province (including Bougainville Island), Papua New Guinea, 586 Australian Defence Force personnel received either primaquine (14-d) or tafenoquine (3-d) post-exposure malaria prophylaxis. Within 12 months, 6 of the 214 volunteers receiving primaquine and 7 of 378 receiving tafenoquine had developed vivax malaria. Overall, volunteers preferred the shorter course of tafenoquine.

Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay

To determine which species and populations of Anopheles transmit malaria in any given situation, immunological assays for malaria sporozoite antigen can replace traditional microscopical examination of freshly dissected Anopheles. We developed a wicking assay for use with mosquitoes that identifies the presence or absence of specific peptide epitopes of circumsporozoite (CS) protein of Plasmodium falciparum and two strains of Plasmodium vivax (variants 210 and 247). The resulting assay (VecTest(TM) Malaria) is a rapid, one-step procedure using a 'dipstick' test strip capable of detecting and distinguishing between P. falciparum and P. vivax infections in mosquitoes. The objective of the present study was to test the efficacy, sensitivity, stability and field-user acceptability of this wicking dipstick assay. In collaboration with 16 test centres world-wide, we evaluated more than 40 000 units of this assay, comparing it to the standard CS ELISA. The 'VecTest(TM) Malaria' was found to show 92% sensitivity and 98.1% specificity, with 97.8% accuracy overall. In accelerated storage tests, the dipsticks remained stable for >15 weeks in dry conditions up to 45degreesC and in humid conditions up to 37degreesC. Evidently, this quick and easy dipstick test performs at an acceptable level of reliability and offers practical advantages for field workers needing to make rapid surveys of malaria vectors.

Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum

Background The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such cell-mediated immunity was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. Methods We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. Findings After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. Interpretation People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine.

Distributional profiles of homologous open reading frames among bacterial phyla: implications for vertical and lateral transmission

If open reading frames (ORFs) have been transmitted primarily by vertical descent, the distributional profile of orthologues of each ORF should be congruent with the organismal tree or a subtree thereof. Distributional patterns not reconciled parsimoniously with tree-like descent and loss are prima facie evidence of lateral gene transfer. Herein, a rigorous criterion for recognizing ORF distributions is described and implemented; it does not require the inference of phylogenetic trees, nor does it assume any specific tree. Because lineage-specific differences in rates of sequence change can also generate unexpected distributional patterns, rate artefacts, were controlled for by requiring pairwise matches between ORFs to exceed a rigorous inclusion threshold, but absence of a match was assessed against a more-permissive exclusion threshold. Applying this dual-threshold criterion to cross-domain and cross-phylum distributional patterns for ORFs in 23 bacterial genomes, a relative abundance of ORFs was observed that find a match in exactly seven other bacterial phyla; 94-99% of these ORFs also find matches among the Archaea and/or Eukarya. In the larger (and some smaller) bacterial genomes, ORFs that find matches in exactly one other bacterial phylum are also relatively abundant, but fewer of these have non-bacterial homologues; most of their matches within the Bacteria are to the Proteobacteria and/or Firmicutes, which cannot be sister lineages to all bacteria. ORFs that are neither distributed universally among the Bacteria, nor necessarily shared with topologically adjacent lineages, are preferentially enriched in large bacterial genomes.

Immunity to asexual blood stage malaria and vaccine approaches

The development of a malaria vaccine seems to be a definite possibility despite the fact that even individuals with a life time of endemic exposure do not develop sterile immunity. An effective malaria vaccine would be invaluable in preventing malaria-associated deaths in endemic areas, especially amongst children less than 5 years of age and pregnant women. This review discusses our current understanding of immunity against the asexual blood stage of malaria - the stage that is responsible for the symptoms of the disease - and approaches to the design of an asexual blood stage vaccine.

Adapting immunity with subunit vaccines: case studies with group A Streptococcus and malaria

Although vaccines have widely been regarded as the most cost-effective way to improve public health, for some organisms new technological advances in vaccine design and delivery, incurring additional developmental costs, will be essential. These organisms are typically those for which natural immunity is either slow to develop or does not develop at all. Clearly, such organisms have evolved strategies to evade immune responses and innovative approaches will be required to induce a type of immune response which is both different to that which develops naturally and is effective. This article describes some approaches to develop vaccines for two such organisms (malaria parasites and Streptococcus pyogenes (group A Streptococcus)) that are associated with widespread mortality and morbidity, mostly in the poorest countries of the world. At this stage, the challenges are primarily scientific, but if these hurdles are surmounted then the challenges will become financial ones - developing much needed vaccines for people least able to afford them. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.

Prospects for a vaccine against malaria [Commentary]

No Abstract

Characterization of microsatellite loci in Anopheles flavirostris, the principal malaria vector in the Philippines

Microsatellites were isolated and characterized from Anopheles flavirostris, the principal malaria vector in the Philippines. Fifty of the 150 positive clones sequenced contained mostly dinucleotide microsatellites and only 16 had trinucleotide repeats. We designed primers from the unique sequences flanking 18 microsatellite loci. Of these, 11 loci produced successful amplification and revealed high levels of polymorphism; 86 alleles were detected with allele number ranging from 2 to 16 at each locus. The high allelic variability will make these microsatellite loci very useful for taxonomic and population genetic studies.

The coincidence of thrips and dispersed pollen in PNRSV-infected stonefruit orchards - a precondition for thrips-mediated transmission via infected pollen

Recent laboratory studies have demonstrated that Prunus necrotic ringspot virus (PNRSV) (family Bromoviridae) can be readily transmitted when thrips and virus-bearing pollen are placed together on to test plants. For this transmission mechanism to result in stonefruit tree infection in the field, PNRSV-bearing pollen must be deposited onto surfaces of stonefruit trees on which thrips also occur. In a previous paper, we demonstrated that almost all pollen in a PNRSV-infected Japanese plum orchard in southeastern Queensland was deposited onto flowers, whereas few grains occurred on leaves and none on stems. Here, we present results of our investigation of thrips species composition, distribution and abundance on stonefruit trees in the same study area as our previous pollen deposition study. We collected a total of 2010 adult thrips from 13 orchards during the 1989, 1991 and 1992 flowering seasons of which all but 14 were in the suborder Terebrantia. Most (97.4%) terebrantian thrips were of three species, Thrips imaginis, Thrips australis and Thrips tabaci. Thrips tabaci as well as species mixtures that included T imaginis, T australis and T tabaci have been shown to transmit PNRSV via infected pollen in laboratory tests. Adult thrips were frequently collected from flowers but rarely from leaves and never from stems. Large and significant differences in numbers of T imaginis, T australis and T tabaci adults in flowers occurred among orchards and between seasons. No factor was conclusively related to thrips numbers but flowers of late-flowering stonefruit varieties tended to hold more thrips than those of early-flowering varieties. Our results indicate that the common thrips species present on stonefruit trees in the Granite Belt are also ones previously shown to transmit PNRSV via infected pollen in the laboratory and that these thrips are concentrated in stonefruit flowers where most stonefruit pollen is deposited. These results contribute to mounting circumstantial evidence that stonefruit flowers may be inoculated with PNRSV via an interaction of thrips with virus-bearing pollen and that this transmission mechanism may be an important cause of new tree infections in the field.

Occlusable corneas in toadfishes: light transmission, movement and ultrastruture of pigment during light- and dark-adaptation

The toadfishes Tetractenos hamiltoni and Torquigener pleurogramma (Tetraodontidae) possess occlusable yellow corneas. We examine the light transmission and location of the yellow/orange pigment throughout the cornea, the temporal properties of pigment migration and the ultrastructure of the pigmented processes during light- and dark-adaptation. Each species was dark-adapted during the day and light-adapted during the night and then exposed to either sun illumination or darkness for different lengths of time (0-70 min). Movement of corneal pigment could be induced in both species regardless of time of day or night. The pigment was able to migrate in a dorsal or ventral direction and changed from minimal to maximal pigmentation within 60 min. Three types of transmission curves were found with varying degrees of transmission in the 400-500 nm waveband, indicating that the pigment distribution is not uniform across the cornea; some areas of the cornea transmit near UV light, while others absorb blue light. The gradual change of the transmission characteristics in different areas of the cornea indicates the presence of different concentrations of a single type of pigment. Ultrastructural examination of the corneas showed that the layer containing the pigment is situated within the scleral cornea either surrounding (T. pleurogramma) or abutting (T. hamiltoni) an iridescent layer. Long sheet-like processes or chromatophores extending centrally from dorsal and ventral reservoirs are filled with pigment during the light-adapted state but empty in the dark-adapted state.