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Biomedical subjects

K C Kain

Publications and source records attributed to K C Kain.

At least 73 records · Page 4Linked to original sources
PubMed1996

Failure of combined chloroquine and high-dose primaquine therapy for Plasmodium vivax malaria acquired in Guyana, South America.

The presence of chloroquine-resistant Plasmodium vivax malaria in the New World has been suspected but not confirmed. We report the cases of three patients who acquired vivax malaria in Guyana, South America, and for whom standard chloroquine therapy (25 mg/kg) failed despite therapeutic blood levels. The optimal treatment of chloroquine-resistant P. vivax malaria is unknown, but recent studies suggest that a combination of chloroquine (25 mg/kg) and high-dose primaquine (2.5 mg/kg over 48 hours) is effective therapy. Two of our patients had recurrences of P. vivax malaria 6-8 weeks after receiving directly observed therapy with this combination. These cases confirm the presence of chloroquine-resistant P. vivax in Guyana and emphasize the need for better treatment regimens for chloroquine-resistant and primaquine-resistant P. vivax malaria.

Adult↗
PubMed1996

Molecular analysis of strains of Plasmodium vivax from paired primary and relapse infections.

Relapse infections are an important obstacle to the successful treatment and control of Plasmodium vivax malaria, but the molecular basis of relapse remains poorly understood. To provide insight into the molecular mechanisms of relapse, paired primary and relapse isolates of P. vivax were subjected to single-strand conformational polymorphism (SSCP) and sequence analysis of the circumsporozoite and merozoite surface protein 1 genes. All unrelated isolates were unique by both SSCP and sequence analysis, but 5 of 6 relapse isolates were identical to or were clones of their matched primary isolates. These results indicate that most relapses are caused by the same parasite populations that circulate during the primary infection and do not arise from a genetically distinct subpopulation.

Adult↗
PubMed1995

Concurrent falciparum malaria and Salmonella bacteremia in travelers: report of two cases.

Fever in travelers or immigrants from the tropics is an increasingly common problem facing physicians in urban centers of North America. Malaria and typhoid fever are endemic in developing countries and affect millions of people annually. An association between falciparum malaria and salmonella bacteremia has been noted for many years, although the underlying mechanisms have not been fully elucidated. We report on two travelers with falciparum malaria and concomitant salmonella bacteremia and review the possible mechanisms that may explain this association.

Adult↗
PubMed1995

A recombinant cysteine-rich section of the Entamoeba histolytica galactose-inhibitable lectin is efficacious as a subunit vaccine in the gerbil model of amebic liver abscess.

The 170-kDa subunit of the galactose-inhibitable adherence lectin of Entamoeba histolytica mediates attachment to colonic mucins and host cells. The DNA fragment encoding the 170-kDa subunit was produced by polymerase chain reaction (PCR) and divided into four sections by restriction endonucleases. The third section (designated LC3, base pairs 2273-3397) encodes a cysteine-rich fusion protein that was recognized by adherence-inhibitory anti-lectin monoclonal antibodies and serum antibodies from 95% of subjects with amebic liver abscess. Immunization of gerbils with purified recombinant LC3-encoded protein (10 micrograms) with Titermax adjuvant elicited a high-titer serum anti-LC3 IgG antibody response and protective immunity against intrahepatic challenge with 0.5 x 10(6) virulent axenic trophozoites (strain HM1:IMSS; 71% vaccine efficacy, P < .01). In summary, a recombinant cysteine-rich portion of the 170-kDa lectin subunit was highly antigenic, immunogenic, and effective as a subunit vaccine in an experimental animal model of amebic liver abscess.

Animals↗
PubMed1995

Chemotherapy and prevention of drug-resistant malaria.

Drug-resistant falciparum and vivax malaria will continue to be an increasing problem. The incidence of drug-resistant malaria has been increasing at a rate that exceeds new drug development. Plasmodium falciparum has rapidly developed resistance to new synthetic antimalarials, including mefloquine and halofantrine. P. vivax malaria resistant to chloroquine and primaquine is now widespread in parts of Oceania; the optimal therapy for this infection is unknown. At present, a combination of qinghaosu derivatives and mefloquine appears to be the most active drug regimen against multidrug-resistant falciparum malaria from Southeast Asia. However, qinghaosu compounds are not yet licensed and widely available. The capacity of P. falciparum to rapidly develop drug resistance and the growing evidence that other plasmodia can evolve resistance suggests that within the next 10 years, we face the real prospect of untreatable malaria. Ultimately, control of malaria may require more creative approaches than additional inhibitory drugs. These might include: the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerase), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against both asexual and sexual stages in order to block both the pathophysiology and transmission of disease.

Antimalarials↗
PubMed1994

Comparative test of DNA probes for detection of Plasmodium vivax circumsporozoite protein polymorphs VK 247 and VK 210.

Oligonucleotide probes specific to the characteristic repeat sequences of two alleles of the circumsporozoite protein gene of Plasmodium vivax (VK 210 and VK 247) were selected, synthesized, and tested on matched blood and sporozoite DNA amplified by polymerase chain reaction from 182 cases naturally acquired in Thailand. Probe results were compared to those of circumsporozoite phenotype-specific ELISAs used to evaluate sporozoites from the same cases. There was a 96% agreement between probe results for blood and for sporozoites. Although there was also a nearly complete agreement between probe and ELISA results for cases producing only VK 210 or VK 247 sporozoites, the probes detected 45% more mixed infections than did the ELISAs when used to test specimens from western and southern Thailand; there was no discrepancy when mixed cases from Cambodia were tested. Examination of Southern blots from ambiguous mixed cases demonstrated the presence of both genes, suggesting suppression of VK 247 in some mixed cases to numbers below those detectable by the ELISA.

Adult↗
PubMed1994

Qualitative and semiquantitative polymerase chain reaction to predict Plasmodium falciparum treatment failure.

Multidrug-resistant falciparum malaria is increasing in most malaria-endemic areas. Rapid methods for predicting treatment failure would aid management and control of drug-resistant infections. In this study, Plasmodium falciparum DNA clearance was examined by qualitative and semiquantitative polymerase chain reaction (PCR). Thai patients with acute falciparum malaria were prospectively followed by light microscopy and by PCR of P. falciparum DNA eluted from filter paper blood samples. A 206-bp P. falciparum sequence was amplified and detected radiometrically and by high-performance liquid chromatography. Clearance of P. falciparum DNA was significantly delayed in treatment failures compared with that in successfully treated patients (P = .02). Semiquantitative PCR levels did not drop to < 50% of pretreatment levels until day 3 or later in treatment failures compared with day 1 or earlier for successfully treated parasitemia-matched controls (P = .005). These results suggest that qualitative and semiquantitative PCR may be useful as a method for monitoring response to therapy.

Adolescent↗
PubMed1994

Failure to detect a Plasmodium vivax-like malaria parasite in globally collected blood samples.

Two variants of the circumsporozoite (CS) protein of Plasmodium vivax (VK210 and VK247) have been identified. Recently, a putative third CS variant of P. vivax, referred to as causing P. vivax-like malaria, has been reported from Papua New Guinea. The objective of this study was to confirm and extend findings on the global distribution of the P. vivax-like parasite. Blood samples were obtained from 126 untreated patients with P. vivax infection acquired in Central America, South America, Africa, Southeast Asia, and the Indian subcontinent. The P. vivax CS gene was amplified by polymerase chain reaction and hybridized with probes specific for the VK210, VK247, and P. vivax-like CS variants. All samples were positive for VK210, VK247, or both. No sample was positive for P. vivax-like DNA. Therefore, the existence of a third variant of P. vivax cannot be confirmed in the geographic areas studied.

Africa↗
PubMed1993

Evidence for two-stage binding by the 175-kD erythrocyte binding antigen of Plasmodium falciparum.

Plasmodium falciparum malaria merozoites invade human erythrocytes bearing sialic acid in a multistage process involving the sialic acid-dependent binding of a malaria molecule, the 175-kD erythrocyte binding antigen (EBA-175). We show here that after the initial interaction of EBA-175 with its sialic acid-containing erythrocyte determinant, endogenous proteases can cleave EBA-175 to 65-kD fragment(s), whose binding to erythrocytes is sialic acid independent. A 65-kD fragment was immunoprecipitated by antibodies against peptides between residues 354 and 1061 but not beyond residue 1062. Binding experiments utilizing combinations of native protein, expression-PCR-synthesized EBA-175 polypeptides, peptide synthesis, and antibodies, demonstrated that sialic acid-independent binding could be further mapped to a small (about 40-amino acid) homologous part of the dimorphic allelic region of EBA-175, residues 898-938 (Camp strain numbering). These data support a two-step binding hypothesis and are discussed in relation to the formation of a junction between the merozoite and the erythrocyte, and the finding that after the interaction of some viruses with specific cellular receptors, they undergo conformational changes or cleavage permitting membrane fusion with the host cell.

Amino Acid Sequence↗
PubMed1993

Expression polymerase chain reaction for the in vitro synthesis and epitope mapping of autoantigen. Application to the human thyrotropin receptor.

The clinical applicability of a newly described polymerase chain reaction directed protein expression system was assessed for the in vitro synthesis and partial epitope mapping of large radiolabeled human thyrotropin receptor (hTSH-R) protein segments. PCR amplification of targeted regions within the hTSH-R cDNA followed by in vitro transcription and translation permitted rapid synthesis of protein segments ranging in size from 18 to 62 kDa. Initial epitope mapping was directed at a 52 amino acid segment unique to the hTSH-R compared to otherwise homologous glycoprotein hormone receptors. Sera from Graves' disease patients known to have autoantibodies against the hTSH-R were used to immunoprecipitate two protein fragments differing only by the presence of the unique region in the larger fragment (E5) but not in the smaller fragment (E4). Dense precipitation bands were obtained using Graves' sera to immunoprecipitate E5 whereas little or no specific immunoprecipitation of E4 occurred. Normal sera gave only weak immunoprecipitation bands of E5. The technique provides significant advantages over conventional cloning methods and should have general applicability in the study of other protein targets of autoimmune disease.

Amino Acid Sequence↗
PubMed1993

Two alleles of the 175-kilodalton Plasmodium falciparum erythrocyte binding antigen.

EBA-175, erythrocyte binding antigen 175, is a 175-kDa antigen of Plasmodium falciparum which has been shown to be involved in the recognition of erythrocytes by merozoites and may be involved in the process of erythrocyte invasion. Invasion of erythrocytes by Camp strain merozoites is inhibited by pre-treatment of red blood cells by EBA-175 from the heterologous strain, FCR-3. The sequence of the Camp strain has been published and we report here the sequence of the FCR-3 strain. The sequences are nearly identical except for a 423-bp segment in the FCR-3 strain, F-segment, that is not found in the Camp strain and a 342-bp segment, C-segment, present in the Camp strain but not in the FCR-3 strain. The locations of these two segments are different in Camp and FCR-3 EBA-175 genes and there is little DNA or amino acid sequence homology between them. The essentially dimorphic alleles, F-segment and C-segment, are conserved in all isolates examined to date. Evidence of genetic cross-over between the FCR-3 and the Camp EBA-175 genes was not observed in the analysis of a limited number of wild isolates. The continued study of the biological relevance of these sequence divergences in EBA-175 may further elucidate the sequence of events resulting in merozoite invasion of erythrocytes.

Alleles↗
PubMed1993

Clinical spectrum of nonmenstrual toxic shock syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses.

To further characterize the clinical spectrum of nonmenstrual toxic shock syndrome (NMTSS), we constrasted and compared the clinical and laboratory features of 24 patients with NMTSS with those of 21 patients with menstrual TSS (MTSS), using univariate and stepwise discriminant analyses. In contrast to patients with MTSS, those with NMTSS comprised a heterogeneous group with varying host factors and clinical presentations. The NMTSS group differed from the MTSS group in terms of the frequency of prior antimicrobial treatment (46% vs. 16%; P = .05), the rate of nosocomial acquisition (65% vs. 0; P = .0001), and the time of onset of fever and rash in relation to the initial symptoms (P = .005 and .03, respectively, with earlier onset in the NMTSS group). In addition, NMTSS patients experienced more frequent renal and CNS complications and less frequent musculoskeletal involvement (P = .07 in all three cases). Stepwise discriminant analysis identified four variables (delayed onset of TSS symptoms after precipitating injury or event, more frequent CNS manifestations, less frequent musculoskeletal involvement, and higher degree of anemia) differentiating NMTSS patients from MTSS produced TSS toxin 1 (TSST-1) with comparable frequency (62% vs. 84%; P = .2), but production of staphylococcal enterotoxin A (SEA) was less common in NMTSS than in MTSS (33% vs. 74%; P = .01). Furthermore, MTSS-associated isolates more commonly coexpressed TSST-1 and SEA than did NMTSS-associated isolates (68% vs. 28%; P = .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Detection of Plasmodium vivax by polymerase chain reaction in a field study.

Detection and typing of Plasmodium vivax by the polymerase chain reaction (PCR) was evaluated in a prospective blinded comparative field study in Thailand. PCR amplification of the circumsporozoite (CS) gene was compared with microscopy for the detection of P. vivax in blood samples from 174 Thai Rangers and 50 malaria-free Bangkok residents. For PCR analysis, filter paper specimens collected by finger prick were randomly processed and blindly interpreted for the presence of the CS gene of P. vivax. The VK210 and VK247 CS variants of P. vivax were detected by specific fluorescein or radiolabeled oligoprobes. Autoradiography with 32P-labeled probes and enhanced chemoluminescent detection with fluorescein-labeled probes identified 91% and 96%, respectively, of 119 microscopically confirmed infections; both systems detected < 100 parasites/microL. Compared with microscopy, the specificity of PCR and radiometric or enhanced chemoluminescent detection was 96% and 90%, respectively. The ease of collection and transport of filter-paper specimens combined with the sensitive and specific detection of allelic genes of P. vivax by PCR suggests that this method may prove to be a valuable tool for epidemiologic and heterogeneity studies of P. vivax.

Animals↗