Large-scale purification and characterization of malaria vaccine candidate antigen Pvs25H for use in clinical trials.

The budding yeast Saccharomyces cerevisiae has been used to express the recombinant protein Pvs25H, currently the only candidate transmission-blocking vaccine against Plasmodium vivax malaria. This molecule contains four epidermal growth factor-like domains and is expressed as at least two stable monomeric forms with different physicochemical properties. Pvs25H-A is apparently homogeneous and seems to have a correct disulfide bond structure.

Developments in a methodology for the design of engineered invert traps in combined sewer systems.

Sediments within sewers can have a significant effect on the operation of the sewer system and on the surrounding natural and urban environment. One possible method for the management of sewer sediments is the use of slotted invert traps. Although invert traps can be used to selectively trap only inorganic bedload material, little is known with regard to the design of these structures.

Fine sediment retention in storage chambers: an assessment of time-dependent effects.

The optimisation of the design of a storage chamber is generally based upon some measure of the chamber's sedimentation efficiency. In the UK, chambers that minimise the deposition of fine sediments are preferred. Previous laboratory and CFD-based studies to measure efficiency have focused on steady flow conditions.

Aotus New World monkeys: model for studying malaria-induced anemia.

Falciparum malaria is a major cause of disease and death in African children and pregnant women, primarily due to severe anemia. We studied anemia in vaccinated Aotus monkeys during a second infection where the animals were considered to be semi-immune. Most animals had extremely low or undetectable levels of parasitemia; in some, anemia did not develop and reticulocytemia remained unchanged; in others, moderate to severe anemia developed with inappropriately low reticulocytemia indicating bone marrow dysfunction.

The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling.

Recrudescing Plasmodium falciparum parasitaemia is attributed to the switching of PfEMP1, a variant antigen family encoded by the var gene repertoire, and the host's immune response. We have developed a mathematical model which incorporates var gene switching, and variant specific, non-variant specific and non-specific immunity. By conducting a sensitivity analysis of the model we have defined the parameter limits which produce chronic and recrudescing infections.

Development of response timing and direction selectivity in cat visual thalamus and cortex.

Single-unit recordings were made in the dorsal lateral geniculate nucleus (LGN) and visual cortex of kittens that were 4-13 weeks of age. Responses to visual stimuli were analyzed to determine the relationship between two related facets of the behaviors of the cells: direction selectivity (DS) and timing. DS depends on timing differences within the receptive field.

A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea.

The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites.

Short day lengths augment stress-induced leukocyte trafficking and stress-induced enhancement of skin immune function.

Environmental conditions influence the onset and severity of infection and disease. Stressful conditions during winter may weaken immune function and further compromise survival by means of hypothermia, starvation, or shock. To test the hypothesis that animals may use photoperiod to anticipate the onset of seasonal stressors and adjust immune function, we evaluated glucocorticoids and the distribution of blood leukocytes in Siberian hamsters (Phodopus sungorus) exposed to long day lengths (i.

The effect of extended in-sewer storage on wastewater treatment plant performance.

A project funded by UKWIR is under way in the UK to develop a relatively simple methodology whereby the effects of the introduction of extended in-sewer storage at CSOs on downstream sewerage and treatment can be assessed. Recent legislation (UK and European) has compelled many sewer system operators to introduce systems which increase in-sewer retention times, and also retain more flow and load within sewer networks. The project has reviewed existing knowledge about the interaction between in-sewer flow and treatment plants, together with available models.

Treatment of tinea pedis with a single pulse of itraconazole.

An open-design, prospective, non-comparative study was conducted to evaluate the efficacy and safety of itraconazole in the treatment of tinea pedis (interdigital-type, hyperkeratotic-type and the combination of both). Treatment consisted of one pulse of itraconazole, meaning that each patient received 400 mg/day for one week. Clinical and mycologic control examinations were performed at baseline and at the end of treatment; follow-up visits took place at 30 and 60 days after the last medication administration.

Merozoite surface protein 3 and protection against malaria in Aotus nancymai monkeys.

A blood-stage vaccine based on Plasmodium falciparum merozoite surface protein 3 (MSP3) was tested for efficacy in a primate model. Aotus nancymai monkeys were vaccinated with yeast-expressed MSP3 before a lethal challenge with Plasmodium falciparum parasites. Five of 7 control monkeys had acute infections and required treatment to control parasitemia.

Progress and challenges for malaria vaccines.

Malaria causes much physical and economic hardship in tropical regions, particularly in communities where medical care is rudimentary. Should a vaccine be developed, it is the residents of these areas that stand to benefit the most. But the vaccine, which has been promised to be 'just round the corner' for many years, remains elusive.

Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections.

A deterministic mathematical model which predicts the probability of developing a new drug-resistant parasite population within the human host is reported. The model incorporates the host's specific antibody response to PfEMP1, and also investigates the influence of chemotherapy on the probability of developing a viable drug-resistant parasite population within the host. Results indicate that early treatment, and a high antibody threshold coupled with a long lag time between antibody stimulation and activity, are risk factors which increase the likelihood of developing a viable drug-resistant parasite population.

Successful treatment of AIDS-related disseminated cutaneous sporotrichosis with itraconazole.

Sporotrichosis is a chronic granulomatous mycosis caused by a dimorphic fungus, Sporothrix schenckii. The most common manifestations of infection are lymphocutaneous and fixed-cutaneous types. In the case of immunosuppressed patients, and particularly in patients with acquired immune deficiency syndrome (AIDS), it occurs as disseminated cutaneous disease.

A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum.

Two strains of transgenic mice have been generated that secrete into their milk a malaria vaccine candidate, the 42-kDa C-terminal portion of Plasmodium falciparum merozoite surface protein 1 (MSP1(42)). One strain secretes an MSP1(42) with an amino acid sequence homologous to that of the FVO parasite line, the other an MSP1(42) where two putative N-linked glycosylation sites in the FVO sequence have been removed. Both forms of MSP1(42) were purified from whole milk to greater than 91% homogeneity at high yields.

Antibodies to Plasmodium vivax transmission-blocking vaccine candidate antigens Pvs25 and Pvs28 do not show synergism.

Transmission-blocking vaccines against malaria parasites target molecules expressed by sexual stage parasites to elicit antibodies that prevent the infection of the mosquito vector. Pvs25 and Pvs28, expressed on the surface of ookinetes, are potential candidates for such a vaccine and induce antibodies that block the infectivity of Plasmodium vivax in immunized animals. To improve the ability to induce transmission-blocking antibodies, Pvs25 and Pvs28 were produced as a single fusion protein by the yeast Saccharomyces cerevisiae.

The sequence of a 200 kb portion of a Plasmodium vivax chromosome reveals a high degree of conservation with Plasmodium falciparum chromosome 3.

Within a 199,866 base pair (bp) portion of a Plasmodium vivax chromosome we identified a conserved linkage group consisting of at least 41 genes homologous to Plasmodium falciparum genes located on chromosome 3. There were no P. vivax homologues of the P.

Diagnosis of malaria in a remote area of the Philippines: comparison of techniques and their acceptance by health workers and the community.

Objective: To compare the efficacies of remote symptom-based diagnosis of malaria, rapid diagnostic tests and microscopy in an area of low endemicity in the Philippines.

Methods: In Trial I, 350 symptomatic patients were tested within their villages using malaria Plasmodium falciparum (Pf)/Plasmodium vivax (Pv) immunochromatographic tests (ICT tests) and blood films stored and read under local conditions. The slides were later restained and read.

Chromoblastomycosis: clinical and mycologic experience of 51 cases.

This is a study of 51 cases of chromoblastomycosis detected in a 17-year period, all of which were clinically and mycologically proven by direct examinations, cultures and biopsies. The therapeutic results of the various treatments used are reported. Most cases were males (36 of 51; 70%), the mean age was 35 years and farmers predominated (74%); the most frequent lesions were in the lower limbs (54%).

Mutation rates in the dihydrofolate reductase gene of Plasmodium falciparum.

A new method has been established to define the limits on a spontaneous mutation rate for a gene in Plasmodium falciparum. The method combines mathematical modelling and large-scale in vitro culturing and calculates the difference in mutant frequencies at 2 separate time-points. We measured the mutation rate at 2 positions in the dihydrofolate reductase (DHFR) gene of 3D7, a pyrimethamine-sensitive line of P.

Modeling factors influencing malaria incidence in Myanmar.

This is a documentary study to determine factors influencing malaria incidence in Myanmar. The period of study covered was from 1989 to 1998 using time series data. Multiple regression analysis was performed on the dependent variable, yearly incidence of malaria in Myanmar, with hypothesized independent variables including variables related to epidemiology, demography, service and socioeconomic status.

Prenatal RHD gene determination and dosage analysis by PCR: clinical evaluation.

Background: Use of the polymerase chain reaction (PCR) for detection of the RHD gene can measure the RHD gene status for unborn babies at risk for hemolytic disease of the newborn (HDN). The occurrence of D gene variants has led to errors in prenatal typing. Previous reports have highlighted the danger of assigning a positive fetus as negative, resulting in intrauterine fetal deaths.