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Cytophilic antibodies to Plasmodium falciparum glutamate rich protein are associated with malaria protection in an area of holoendemic transmission.

BACKGROUND: Several studies conducted in areas of medium or low malaria transmission intensity have found associations between malaria immunity and plasma antibody levels to glutamate rich protein (GLURP). This study was conducted to analyse if a similar relationship could be documented in an area of intense malaria transmission. METHODS: A six month longitudinal study was conducted in an area of holoendemic malaria transmission in north-eastern Tanzania, where the incidence of febrile malaria decreased sharply by the age of three years, and anaemia constituted a significant part of the malaria disease burden. Plasma antibodies to glutamate rich protein (GLURP) were analysed and related with protection against malaria morbidity in models correcting for the effect of age. RESULTS: The risk of febrile malaria episodes was reduced significantly in children with measurable anti-GLURP IgG1 antibodies at enrollment [adjusted odds ratio: 0.39 (95% CI: 0.15, 0.99); P = 0.047]. Interestingly, there was an inverse relationship between the plasma anti-GLURP IgG1 and IgG3 levels and the levels of parasitaemia at enrollment. However, anti-GLURP IgG2 and IgG4 levels were not associated with reduction in parasite density. Similarly, antibody levels were not associated with haemoglobin levels or anaemia risk. CONCLUSION: Cytophilic IgG1 and IgG3 antibodies against R0-GLURP may contribute to the control of parasite multiplication and reduction in febrile malaria incidence in children living in an area of intense malaria transmission.

Adolescent↗

Epidemiological characterization of Plasmodium falciparum in the Republic of Cabo Verde: implications for potential large-scale re-emergence of malaria.

BACKGROUND: Malaria has come near eradication at archipelago of Cabo Verde in 1970. Infections are now only observed in Santiago, where outbreaks occur. In these islands, malaria is considered by the international community as being of limited risk and, therefore, no prophylaxis is recommended. Since the understanding of factors that determine malaria outbreaks are crucial for controlling the disease, the present study aimed to investigate if the malaria infections observed in Santiago Island are maintained in isolated foci and in asymptomatic individuals. METHODS: The occurrence of asymptomatic carriers in villages with history of malaria as well as the level of exposure of these populations were investigated using PCR and serological analyses. RESULTS: Results indicate that malaria is maintained as asymptomatic and sub-patent infections and that the majority of the circulating parasite populations harbour chloroquine-resistant mutations. CONCLUSION: These observations highlight the alarming prospect of malaria to become a serious public health problem and underscore the need for a tighter surveillance.

Animals↗

Epidemiological distribution of Plasmodium falciparum drug resistance in Brazil and its relevance to the treatment and control of malaria.

With the use of a simple formulary, filled by health agents was established a monitoring programme for responses of P. falciparum to the antimalarial drugs. This monitoring programme is emphasized for the knowledge of the epidemiology of the drug resistance and the control of malaria falciparum in Amazon Basin where occurs more than 95% of Brazilian malaria cases every year. It was demonstrated that still now 4-aminoquinolines have a great importance for the mortality control in areas where just SUCAM (National Health Foundation--Health Ministry) agents are present without any medical assistance. The results obtained permitted the simplification of malaria treatment in Brazil. Important conclusions were established in the field of malaria drug resistance.

Animals↗

Clinical trials of Plasmodium falciparum erythrocytic stage vaccines.

Efficacy trials for malaria blood-stage vaccines are currently underway in several field sites. Numerous issues surround the design and execution of such trials, and there are many opportunities for failure that have little to do with the vaccines per se. This review highlights some of the key issues to be considered by investigators designing such trials, including those that are unique to trials for erythrocytic stage vaccines.

Adolescent↗

Association of interferon-gamma responses to pre-erythrocytic stage vaccine candidate antigens of Plasmodium falciparum in young Kenyan children with improved hemoglobin levels: XV. Asembo Bay Cohort Project.

Previous studies in animal models have revealed an association between interferon-gamma (IFN-gamma), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-gamma can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-gamma and lymphocyte proliferative responses to previously defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic stage antigens in 107 children six months to two years old from a community-based birth cohort in western Kenya. We found that IFN-gamma positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN-gamma non-responders, suggesting that IFN-gamma immune responses to these pre-erythrocytic antigens were associated with protection against malarial anemia. Children who responded by lymphocyte proliferation had a significantly longer time to first documented malaria parasitemia after birth; however, there was no correlation between the presence of lymphocyte proliferative response and higher Hb levels. We propose that IFN-gamma production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.

Anemia↗

Surveillance of in vivo resistance of Plasmodium falciparum to antimalarial drugs from 1992 to 1999 in Malabo (Equatorial Guinea).

From 1992-1999, we have assessed the therapeutic efficacy of three malaria treatment regimens (chloroquine 25 mg/kg over three days, pyrimethamine/sulfadoxine 1.25/25 mg/kg in one dose, and quinine 25-30 mg/kg daily in three oral doses over a four-, five-, or seven-day period) in 1,189 children under age 10 at Malabo Regional Hospital in Equatorial Guinea. Of those children, 958 were followed up clinically and parasitologically for 14 days. With chloroquine, the failure rate varied from 55% in 1996 to 40% in 1999; the early treatment failure rate increased progressively over the years, from 6% in 1992 to 30% in 1999. With pyrimethamine/sulfadoxine, the failure rate varied from 0% in 1996 to 16% in 1995. The short quinine treatment regimens used in 1992 and 1993 (4 and 5 days, respectively) resulted in significantly higher failure rates (19% and 22%, respectively) than the 7d regimen (3-5.5%). We conclude that: a) failure rates for chloroquine are in the change period (> 25%), and urgent action is needed; b) pyrimethamine/ sulfadoxine failure rates are in the alert period (6-15%), and surveillance must be continued; and c) quinine failure rates are in the grace period (< 6%), so quinine can be recommended.

Animals↗

[Resistance to chloroquine and cycloguanil of Plasmodium falciparum in patients arriving in France after travel in Africa without chemoprophylaxis].

The in vitro susceptibility of chloroquine and the genomic profile of dihydrofolate reductase (DHFR) codon 108 was determined against african isolates of P. falciparum (Pf) from imported malaria cases without previous drug intake by an isotopic microtest or PCR + RFLP. Pf resistance to chloroquine or to the DHFR inhibitor was present in 49% and 46% of isolates, respectively. Pf drug resistance was more frequent in permanent than in seasonal malarial transmission areas and chloroquine plus DHFR resistance reached 28% in years 1995-97. Updating the guidelines for the prevention of malaria in travellers to Africa is necessary.

Africa↗

Detection of glutamate dehydrogenase enzyme activity in Plasmodium falciparum infection.

We describe the separation of an active glutamate dehydrogenase [GDH (NADP+)] enzyme from the plasma of patients with P. falciparum infection using columns of sepharose anti-GDH (NADP+) of Proteus spp. The activity of this enzyme was also detected in P. falciparum culture supernatant. The parasitic origin of this enzyme was suggested by western blot analysis using anti-P. falciparum culture supernatant and anti-whole parasite antibodies. The differential inhibition of the P. falciparum GDH (NADP+) indicates that some epitopes recognised by the antibodies in both preparations may be different. The determination of P. falciparum GDH (NADP+) activity could be developed into a specific technique for the diagnosis of falciparum malaria.

Animals↗

Immune regulation of protection and pathogenesis in Plasmodium falciparum malaria.

The immune mechanisms whereby malaria parasites are eliminated by the human host or how they may avoid the immune response are poorly understood. Individuals living in malaria-endemic areas gradually acquire immunity. It is well established that this immunity involves both cell-mediated and humoral mechanisms and that T cells are the major regulators in both these events. The existence of functionally distinct P. falciparum-specific CD4+ T-cell subsets in humans has been shown in several studies. However, in contrast to what is the case in murine models there is no definitive link between the activation of various T cells and the course of human P. falciparum blood-stage infection. In the present paper we will review recent findings which illustrate how the balance between functionally different T-cell subsets affects the development of malaria immunity but also may contribute to its pathogenicity. An example of the latter is the deposition of IgE-containing immune complexes in small vessels, probably leading to local overproduction of tumor-necrosis factor (TNF), a pathogenic factor in malaria.

Animals↗

Improvement of growth of Plasmodium falciparum fresh clinical isolates by using an established serum-free medium, GIT.

In the present study, we have tried to establish continuous cultures of fresh clinical isolates of P. falciparum by using a serum-free medium, GIT. To examine the ability of GIT to support the parasite growth, the growth of various P. falciparum isolates including two laboratory strains of P. falciparum, FCR3 and K1 was compared in both of GIT and RPMI 1640 medium supplemented by 10% human serum (RPMI-HS). Growth rates of various P. falciparum expressed as fold increases were compared in GIT and RPMI-HS, and the maximum growth rates of P. falciparum were 72 in GIT and 35 in RPMI-HS during the culture for 8 days. Growth rate of the clinical isolates varied individually in both culture media, with average growth rates of parasites being 15.9 in GIT and 8.8 in RPMI-HS, respectively (not significant). Growth rates of FCR3 and K1 strains were 28.0 and 6.6 in GIT, and 10 and 7.5 in RPMI-HS. After 30 days culture of P. falciparum in GIT, 9 of 12 clinical isolates still continuously propagated but other three isolates disappeared. Despite variation of the P. falciparum isolates in their abilities to multiply in GIT, our experiments suggested that GIT is useful for culture of fresh clinical isolates of P. falciparum that are derived from geographically distinct areas as well as laboratory strains used commonly in laboratory research.

Animals↗