Purification, characterization, and immunogenicity of a disulfide cross-linked Plasmodium vivax vaccine candidate antigen, merozoite surface protein 1, expressed in Escherichia coli.
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The Plasmodium vivax merozoite surface protein 1 (MSP-1) 42-kDa fragment (PvMSP-1 p42) is a promising vaccine candidate antigen against the blood stage of the malarial parasite. We have developed a process for the production of this vaccine target, keeping in mind its use in human volunteers. A novel strain, Origami(DE3), of Escherichia coli with mutations in the glutathione and thioredoxin reductase genes yielded 60% more soluble PvMSP-1 p42 than the conventional E. coli BL21(DE3) strain. Recombinant PvMSP-1 p42 was purified to > or = 99% purity with a rapid two-step protocol designed for easy scaling up. The final product had a low endotoxin content and was stable in its lyophilized form. PvMSP-1 p42 was found to have the predicted primary and tertiary structures and consisted of a single conformer containing one free cysteine, as predicted. The product was recognized by conformational monoclonal antibodies against P. vivax MSP-1. Immunogenicity studies of PvMSP-1 p42 were carried out with two strains of mice and the adjuvants Montanide ISA51 and Montanide ISA720. Both formulations were found to induce high levels of immunoglobulin G1 (IgG1), IgG2b, and IgG2a antibodies along with low levels of IgG3. Lymphocytes from animals in all the PvMSP-1 p42-immunized groups showed proliferative responses upon stimulation with PvMSP-1 p42; the cytokines interleukin 2 (IL-2), gamma interferon, IL-4, and IL-10 were detected in the culture supernatants. These results indicate that PvMSP-1 p42 in combination with both of the adjuvants elicited cellular and humoral responses in mice. (+info)
Diagnostic performance characteristics of rapid dipstick test for Plasmodium vivax malaria.
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We compared the diagnostic performance characteristics of newly developed method, the rapid dipstick test, which provides colorimetric determination by developing antibody to the lactate dehydrogenase enzyme of parasites, with conventional standard thick-blood film examination. For the rapid test, OptiMAL commercial kits were used. The results were also evaluated with clinical findings from patients. The parasites were determined by microscopic examination of thick-blood films from 81 patients with vivax malaria from southeastern Anatolia, Turkey. The OptiMAL test results were found to be negative in five patients who were diagnosed clinically and through thick-film testing as having vivax malaria. There was no false positivity observed with the OptiMAL test. We concluded that this rapid malaria test has a lower level of sensitivity than the classical thick-blood-film test for malaria, but that these methods have equal specificity. (+info)
Variants of the Plasmodium vivax circumsporozoite protein (VK210 and VK247) in Colombian isolates.
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Phenotypic diversity has been described in the central repeated region of the circumsporozoite protein (CSP) from Plasmodium vivax. Two sequences VK210 (common) and VK247 (variant) have been found widely distributed in P. vivax isolates from several malaria endemic areas around the world. A third protein variant called P. vivax-like showing a sequence similar to the simian parasite P. simioovale has also been described. Here, using an immunofluorescent test and specific monoclonal antibodies, we assessed the presence of two of these protein variants (VK210 and VK247) in laboratory produced sporozoite. Both sequences were found in parasite isolates coming from different geographic regions of Colombia. Interestingly, sporozoites carrying the VK247 sequence were more frequently produced in Anopheles albimanus than sporozoites with the VK210 sequence. This difference in sporozoites production was statistically significant (p <0.05, Kruskal-Wallis); not correlation was found with parameters as the total number of parasites or gametocytes in blood from human donors used to feed mosquitoes. Previous studies in the same region have shown a higher prevalence of anti-VK210 antibodies which in theory may suggest their role in blocking the development of sporozoites carrying the CSP VK210 sequence. (+info)
Clinical features of vivax malaria.
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Plasmodium vivax malaria reemerged in the Republic of Korea in 1993 near the Demilitarized Zone (DMZ). We reviewed clinical features of 101 symptomatic patients with vivax malaria. Of the patients, 77 patients (76.3%) were veterans who had served near the DMZ; their median age was 23 years. The duration of the minimum latent period was > 6 months in 66.2% (51 of 77) of the patients (median, 278 days). Tertian fever developed in 69 patients (68.3%). Severe thrombocytopenia with platelet counts < 60,000/microL was common (29.6% of patients). The parasite densities ranged 32-52,127 parasites per microliter of blood (geometric mean, 1,287). The only complication was a splenic rupture in one patient. All patients responded promptly to chloroquine therapy. Our data suggest that the clinical features of reemerging vivax malaria may be similar to those of Korean vivax malaria reported in the past. (+info)
Plasmodium vivax clinically resistant to chloroquine in Colombia.
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Chloroquine-resistant Plasmodium vivax has been the subject of numerous case reports and prospective studies from Oceania and Asia. In contrast, only case reports exist from the Americas. We performed a prospective study with 28-day follow-up of clinical responses to chloroquine in 2 P. vivax-endemic regions of Colombia. Three (11%) of 27 patients failed to respond to treatment with the standard regimen of chloroquine (1,500 mg of base over 3 days). One patient demonstrated RI resistance on Day 26; one patient demonstrated RI resistance due to recrudescence of blood stages on Day 11; and one patient demonstrated RII resistance of blood stages by never displaying clearing of peripheral parasitemia. All patients were successfully treated with primaquine, which has some blood stage efficacy against P. vivax, combined with a second course of chloroquine. Clinical resistance of P. vivax to chloroquine is present in Colombia and should be monitored in the Americas. (+info)
Plasmodium vivax polymorphism in a clinical drug trial.
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Data from a double-blind randomized clinical drug trial were analyzed to find the comparative responses of two antirelapse drugs, bulaquine and primaquine, against different relapsing forms of Plasmodium vivax infection. A 1-year follow-up study strongly suggests that the duration of preerythrocytic development of P. vivax is a polymorphic characteristic, exhibited by two strains of hypnozoites responsible for early and late manifestations after primary infection. Short-term relapses were significantly higher in the first half year than long-term relapses, and the reverse was true in the second half year. Clinical drug response data showed that the hypnozoites characterized for short-term relapse were not susceptible to either of the antirelapse drugs in the currently administered dose, whereas hypnozoites characterized for long incubation were significantly susceptible. (+info)
Prevention of sporogony of Plasmodium vivax in Anopheles dirus mosquitoes by transmission-blocking antimalarials.
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The sporontocidal activity of four dihydroacridine-diones (WR-233602, WR-243251, WR-250547, and WR-250548) and three fluoroquinolones (WR-279135, WR-279298, and WR-279288) was determined against naturally circulating isolates of Plasmodium vivax. Laboratory-reared Anopheles dirus mosquitoes were infected with P. vivax by feeding them on gametocytemic volunteers reporting to local malaria clinics in Kanchanaburi and Tak provinces, Thailand. Four days after the infectious feed, mosquitoes were re-fed on uninfected mice treated 90 minutes previously with a given drug at a dose of 100 mg base drug/kg mouse body weight. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. None of the fluoroquinolones exhibited sporontocidal activity against P. vivax, whereas all 4 dihydroacridine-diones affected sporogonic development to some degree. WR-233602 affected oocyst development, but had no impact on sporozoite production, WR-250548 affected oocyst development and had a limited effect on sporozoite production, and WR-243251 and WR-250547 had a marked impact on all phases of sporogony. These data demonstrate that experimental dihydroacridine-diones are capable of interrupting the sporogonic development of P. vivax. These compounds may be useful in preventing malaria transmission. (+info)
Severe acute renal failure in malaria.
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BACKGROUND: We have noticed a recent rise in the incidence and severity of acute renal failure (ARF) in malaria. AIM: To study the incidence, severity and outcome of ARF in malaria. SETTING AND DESIGN: It is a retrospective analysis of data of one year from a tertiary medical centre in a metropolitan city. MATERIALS AND METHODS: Patients with ARF and smear positive malaria were evaluated. STATISTICAL ANALYSIS: Results were expressed as mean, range and standard deviation. RESULTS: Out of 402 detected smear positive malaria, 24 had ARF. Eighteen were of the age group 21-40 years. Plasmodium falciparum (PF) was detected in 16, Plasmodium vivax in three, and mixed infection in five. Non-oliguric ARF was seen in 14. Eighteen showed severe ARF (Serum creatinine >5 mg%). Twenty-two patients needed dialysis. Prolonged ARF lasting for 2-6 weeks was seen in eight. Seventeen patients recovered completely, while seven showed fatal combination of disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), severe ARF and PF malaria. No response was seen to chloroquine and artesunate given alone and twenty patients required quinine. CONCLUSION: ARF necessitating dialysis was seen in 92% of patients with ARF in malaria. PF infection, severe ARF, DIC and ARDS were poor prognostic factors. Resistance was noted to both chloroquine and artesunate. (+info)