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J C Reeder

Publications and source records attributed to J C Reeder.

34 records · Page 2Linked to original sources
PubMed1996

Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea.

Plasmodium falciparum isolates from 24 Papua New Guinean patients with symptomatic malaria were tested for susceptibility to pyrimethamine and cycloguanil. Thirteen isolates were sensitive to both agents and the remainder exhibited varying degrees of resistance. No isolates were found to be resistant to one agent yet sensitive to the other and a positive correlation suggesting cross-resistance was found. Parasite DNA extracted from the patients' stained blood slides was amplified and sequenced to examine point mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase genes (DHPS) associated with antifolate resistance. All resistant isolates possessed mutations in the DHFR gene at codon 108, the majority changing from Ser to Asn, but one isolate from Ser to Thr, a change not previously reported in field isolates. A second mutation of the DHFR gene at Cys-59 to Arg was present in isolates with higher level resistance, but not exclusively so. Sequencing the DHPS gene, as a predictor of sulfadoxine resistance, revealed only one example that was different from DHPS alleles of sensitive isolates.

Animals↗
PubMed1995

Chondroitin sulfate A is a cell surface receptor for Plasmodium falciparum-infected erythrocytes.

Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors mediating adherence have been identified, but the process of adherence in vivo is poorly understood. We investigated the role of carbohydrate ligands in adherence, and we identified chondroitin sulfate (CS) as a specific receptor for P. falciparum-infected erythrocytes. Parasitized cells bound to Chinese hamster ovary (CHO) cells and C32 melanoma cells in a chondroitin sulfate-dependent manner, whereas glycosylation mutants lacking chondroitin sulfate A (CSA) supported little or no binding. Chondroitinase treatment of wild-type CHO cells reduced binding by up to 90%. Soluble CSA inhibited binding to CHO cells by 99.2 +/- 0.2% at 10 mg/ml and by 72.5 +/- 3.8% at 1 mg/ml, whereas a range of other glycosaminoglycans such as heparan sulfate had no effect. Parasite lines selected for increased binding to CHO cells and most patient isolates bound specifically to immobilized CSA. We conclude that P. falciparum can express or expose proteins at the surface of the infected erythrocyte that mediate specific binding to CSA. This mechanism of adherence may contribute to the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the capacity to bind specifically to cell-associated or immobilized CS.

Animals↗
PubMed1994

Sulfated glycoconjugates as disrupters of Plasmodium falciparum erythrocyte rosettes.

Some strains of Plasmodium falciparum form erythrocyte rosettes that are believed to result from a lectin interaction between malaria-infected and uninfected erythrocytes. The sulfated glycoconjugate heparin and certain heparin derivatives have been observed to disrupt rosettes. To investigate this interaction further, we have studied the effects of four sulfated glycoconjugates on 15 fresh isolates of P. falciparum from Papua New Guinea. A broader range of sulfated glycoconjugates has been tested against a laboratory strain. A concentration of 1,000 micrograms/ml of dextran sulfate (molecular weight [MW] 500,000) was the most potent disrupter of rosettes. Fucoidan, heparin, and dextran sulfate (MW 5,000) were of decreasing effectiveness in 14 of 15 fresh isolates. The same relationship was true for the laboratory strain. Pentosan polysulfate and sulfatide also disrupted rosettes; chondroitin sulfates A, B, and C and keratan sulfate gave either minimal or no rosette disruption. Thus, some sulfated glycoconjugates are potent disrupters of P. falciparum erythrocyte rosettes. Sulfated glycoconjugates that are potent disrupters of P. falciparum rosettes may prove useful in identifying ligands involved in rosette formation.

Animals↗
PubMed1994

Diversity of agglutinating phenotype, cytoadherence, and rosette-forming characteristics of Plasmodium falciparum isolates from Papua New Guinean children.

The relationship between antigenic variation, cytoadherence, rosette formation, and the pathogenesis of malaria has led to great interest in the diversity of these properties in Plasmodium falciparum isolates from different communities. In this study, we extend previous investigations by delineating the spectrum of agglutinating phenotypes, adherence to C32 melanoma cells, human umbilical vein endothelial cells (HUVEC), CD36, and intracellular adhesion molecule-1 (ICAM-1), and rosette-forming ability of a group of 20 P. falciparum isolates from Papua New Guinean children. Agglutination phenotypes were determined by using both the children's convalescent serum and a panel of adult immune sera. The wide range of variant antigenic types in the community was demonstrated by the failure of the agglutination assays to identify any two isolates with the same agglutinating phenotype in this, the largest study of its kind. Comparison of agglutination profiles from fresh and cryopreserved isolates demonstrated the general acceptability of cryopreservation before testing, but cautioned that some isolates may undergo selection and phenotypic change during the process. Nineteen isolates were able to bind to at least one of the four ligands studied and showed marked variation in both avidity and specificity of binding. The purified proteins ICAM-1 and CD36 proved to be the most useful assay ligands for investigating field isolates, with 18 isolates binding to at least one protein and 14 to both. No correlation was found between the binding of isolates to any two ligands nor between the binding of a standardized inoculum and the level of the patient's presenting parasitemia. All isolates from the study group were found to form rosettes (at a mean rate of 14.6% of cultured trophozoites involved in rosettes). A lack of correlation between rosette formation and CD36 binding suggests that the previously reported role of CD36 as a rosette formation receptor may not be important for isolates from Papua New Guinea.

Agglutination Tests↗
PubMed1992

The development of rural laboratory services in Papua New Guinea.

The health service of Papua New Guinea is targeted at village level primary health care, through aid posts and health centres. There is an increasing demand for providing these facilities with basic diagnostic laboratory services at the health centre level. To accomplish this, an inservice training program has been established to train existing health workers in specific laboratory skills. A management support scheme has also been instigated to ensure that the most effective use is made of these laboratory-trained staff. This has created a team of rural laboratory workers to support the clinical management of patients in rural locations throughout Papua New Guinea.

Community Health Services↗
PubMed1992

A quality assurance for rural laboratories: a report on a trial distribution in Momase Region, Papua New Guinea.

The strengthening of laboratory services in rural health centres is an important component of the Papua New Guinea National Health Plan. As part of the management support scheme for these services a National Quality Assurance Scheme has been formulated to monitor their technical performance. A trial distribution of quality assurance specimens to 44 laboratories in the Momase Region was met with enthusiastic response and encouraging results. The trial will be used as a model for a nation-wide distribution.

Community Health Services↗
PubMed1991

Identification, and susceptibility to seven antimicrobial agents, of 61 gram-negative anaerobic rods from periodontal pockets.

Sixty-one cultures of Gram-negative anaerobic rods were isolated from deep periodontal pockets of patients with rapidly progressive periodontitis. Isolates were speciated as Bacteroides gingivalis (18 isolates), Bacteroides intermedius (8), Bacteroides oris (1), Bacteroides gracilis (17) and Fusobacterium nucleatum (17). Their susceptibilities, to seven antimicrobial agents, were determined in vitro using a plate dilution technique. Amoxycillin and amoxycillin with clavulanic acid were active against all isolates (MIC less than 1 mg/l) and proved the most effective agents tested. F. nucleatum and B. gracilis showed resistance to erythromycin; F. nucleatum had MIC values ranging from 0.03 mg/l up to 128 mg/l when tested with this, least effective agent. Metronidazole was effective against all isolates except for a few strains of B. gracilis (MIC less than 4 mg/l). Tetracycline hydrochloride and minocycline were active against all isolates except for a few strains of B. gracilis (MIC less than 2 mg/l with both minocycline and tetracycline hydrochloride). Penicillin proved less effective than amoxycillin with regard to inhibition of B. gracilis.

Amoxicillin↗
PubMed1991

Improved detection of Candida albicans in a blood-culture model.

Human blood reduced the numbers of colony-forming units (cfu) of Candida albicans in a blood-culture model so that the detection time was increased by 12 h. Reduction in cfu was accompanied not by reduction in cell mass but by observable clumping of cultures, which was attributable to a heat-stable serum component. The action of the latter component could be negated if the medium were supplemented by a combination of trypsin, 2-phenyl ethanol, liquoid and Tween 80, when a statistically significant improvement was noted in minimum detection time for C. albicans growing in blood-culture medium.

Candida albicans↗
PubMed1990

Comparison of three-compartment Petri dishes and individual plates for routine culture of vaginal swabs.

Recovery of aerobes and facultative anaerobes from 200 consecutive randomly selected high vaginal swabs was evaluated using three-compartment Petri dishes containing Sabouraud, dextrose agar, GC selective agar, and chocolate agar. The method was compared with the traditional method using individual Petri dishes. The two methods produced comparable results both in terms and quantities of organisms recovered from the specimens. As three-compartment Petri dishes use less agar, save time in culturing specimens, yet still maintain the same standard of culture, they provide a more economical alternative to the traditional method for routine culture of vaginal swabs.

Bacteriological Techniques↗
PubMed1989

The improved recovery of Candida albicans from fluid culture media.

This study compares the mean generation time (MGT) and lag period of the growth of Candida albicans in four blood culture media, under a variety of conditions of incubation. The media compared were Bactec 6B, brain-heart infusion, malt extract broth and Sabourauds liquid medium. All four media were incubated under the eight possible permutations of the following conditions: 37 degrees C or 30 degrees C, vented or unvented, unshaken or constantly shaken. Then, using the incubation conditions found to be most favourable, minimum detection times for C. albicans were compared in the four media. The combination of incubation of the cultures at 37 degrees C, venting and constant-shaking, produced the fastest generation time with the minimum lag period. Of the media, Bactec 6B medium had the shortest lag period under these conditions while brain-heart infusion had the lowest MGT overall. Sabourauds liquid medium, which resulted in the most favourable combination of generation time and lag period, proved superior to the other media for the recovery of C. albicans.

Blood↗
PubMed1985

Indifferent streptococci in normal and purulent eyes of neonates.

The incidence of indifferent streptococci in the eyes of neonates less than 6 days old was investigated. The isolation of indifferent streptococci was significantly higher in infants with sticky eyes. Speciation using a shortened identification scheme was carried out on isolates; Streptococcus mitior and Streptococcus sanguis were the most common species in both purulent and non-infected eyes. Streptococcus mutans, a species not normally found in edentulous infants, comprised 14% of indifferent streptoccoi from neonates with sticky eyes but only 1% of those from infants with non-purulent eyes. It is suggested that the role of indifferent streptococci in neonatal conjunctivitis will be resolved only if speciation is performed.

Conjunctiva↗
PubMedDate not supplied

Mutations in the pfmdr1, dhfr and dhps genes of Plasmodium falciparum are associated with in-vivo drug resistance in West Papua, Indonesia.

This study (conducted in 1996-99) examines the association of mutations in pfmdr1, dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes of Plasmodium falciparum with in-vivo drug resistance in West Papua, Indonesia. Initially, 85 patients infected with P. falciparum were treated with chloroquine, of whom 21 were cleared of parasites, 49 had parasitaemias classified as RI, RII or RIII resistance and 1 patient had recrudescent parasitaemia. Fansidar (pyrimethamine-sulfadoxine) was the second-line treatment and 18 patients were cleared of parasites and 31 had continuing infections classified as RI, RII or RIII resistance and 1 patient had recrudescent parasitaemia. The pfmdr1, dhfr and dhps genes were examined for mutations previously shown to be associated with resistance to these drugs. In this study, mutations in pfmdr1 were associated with chloroquine resistance and mutations in both dhfr and dhps were associated with Fansidar resistance in vivo. Interestingly, Gly-437 in dhps along with Arg-59/Asn-108 in dhfr were associated with RI, RII and RIII resistance whereas Glu-540 was highly associated with only RII and RIII Fansidar resistance. This finding supports the hypothesis that the molecular basis of RI, RII and RIII Fansidar resistance involves an accumulation of mutations in both dhfr and dhps. These results suggest that mutations in both dhfr and dhps genes are a good predictor of potential Fansidar treatment failure.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Reduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community study.

A prospective community study in a highly malaria endemic area of Papua New Guinea found that infection with multiple Plasmodium falciparum genotypes was an indicator of lowered risk of subsequent clinical attack. The results suggest that concurrent or very recent infections provide protection from superinfecting parasites. The finding of an association between reduced risk of clinical malaria and infection with parasites of merozoite surface protein 1 (MSP-1) type RO33 or MSP-2 type 3D7 further suggests that the concomitant immunity is, at least in part, a consequence of a response to these major merozoite surface proteins.

Adolescent↗
PubMedDate not supplied

Malaria in pregnancy: getting to grips with a sticky problem.

In malaria-endemic areas, by young adulthood people have developed functional immunity to malaria. However, during pregnancy this immunity is breached and infection occurs, leading to increased risks for mother and child. In the past this effect has been attributed to nonspecific immunosuppression, but recent research has revealed a specific pathogenic mechanism, involving the adherence of rare parasite variants to the placenta. This commentary explores the current state of research in this area and proposes a model of immune evasion and placental colonization. This model points the way to the development of future therapeutic interventions.

Female↗
PubMedDate not supplied

Towards a malaria vaccine for Papua New Guinea.

Malaria is a major problem in Papua New Guinea, where it accounts for a high proportion of sickness and death. In addition to the human suffering, malaria also puts severe stress on the health services, and may directly hinder economic growth. A malaria vaccine would be the best, most cost-effective and safest public health measure to reduce the burden of malaria. Though considerable technical challenges are present, much natural and scientific evidence suggests a vaccine is achievable. Through the malaria vaccine program at the Papua New Guinea Institute of Medical Research, Papua New Guinea is playing a significant role in the global effort to develop a malaria vaccine, and ensuring that the malaria patterns of the Asia-Pacific region figure strongly in vaccine development strategies. Discussed here are some of the major issues to be considered as we work towards a malaria vaccine for Papua New Guinea.

Developing Countries↗