scholarly journals In vivo and in vitro Plasmodium falciparum Resistance to Chloroquine, Amodiaquine and Quinine in the Brazilian Amazon

Author(s):  
Aluisio Augusto Cotrim SEGURADO ◽  
Silvia Maria DI SANTI ◽  
Mario SHIROMA

In order to study the chemoresistance of Plasmodium falciparum to commonly used antimalarial drugs in Brazil the authors have studied ten patients with falciparum malaria, acquired in the Brazilian Amazon region. Patients were submitted to in vivo study of drug sensitivity, after chemotherapy with either 4-aminoquinolines (chloroquine or amodiaquine) or quinine. Adequate drug absorption was confirmed by standard urine excretion tests for antimalarials. Eight patients could be followed up to 28 days. Among these in vivo resistance (R I and R II responses) was seen in all patients who received 4-amino-quinolines. One patient treated with quinine exhibited a R III response. Peripheral blood samples of the same patients were submitted to in vitro microtests for sensitivity to antimalarials. Out of nine successful tests, resistance to chloroquine and amodiaquine was found in 100% and resistance to quinine in 11.11% of isolates. Probit analysis of log dose-response was used to determine effective concentrations EC50, EC90 and EC99 to the studied drugs. Good correlation between in vivo and in vitro results was seen in six patients. The results emphasize high levels of P. falciparum resistance to 4- aminoquinolines and suggest an increase in resistance to quinine in the Brazilian Amazon region, reinforcing the need for continuous monitoring of drug sensitivity to adequate chemotherapy according to the most efficacious drug regimens

2002 ◽  
Vol 101 (2-3) ◽  
pp. 111-120 ◽  
Author(s):  
Paulo Afonso Nogueira ◽  
Gerhard Wunderlich ◽  
Mauro Shugiro Tada ◽  
Joana d’Arc Neves Costa ◽  
Maria José Menezes ◽  
...  

Acta Tropica ◽  
2008 ◽  
Vol 107 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Alexandre Lorenzetti ◽  
Patrícia Aparecida Fornazari ◽  
Ana Carolina Bonini-Domingos ◽  
Roberta de Souza Rodrigues Penhalbel ◽  
Érika Fugikaha ◽  
...  

2002 ◽  
Vol 66 (5) ◽  
pp. 461-466 ◽  
Author(s):  
Erika Martins Braga ◽  
Antoniana Ursine Krettli ◽  
Cristiane Guimarães Morais ◽  
Rosa Maria Barros ◽  
Maria Sĵnia Martins ◽  
...  

Author(s):  
Leandro Góes ◽  
Nathália Chamma-Siqueira ◽  
José Mário Peres ◽  
José Maria Nascimento ◽  
Suiane Valle ◽  
...  

Histidine-rich proteins 2 and 3 gene (pfhrp2 and pfhrp3) deletions affect the efficacy of rapid diagnostic tests (RDTs) based on the histidine-rich protein 2 (HRP2), compromising the correct identification of the Plasmodium falciparum species. Therefore, molecular surveillance is necessary for the investigation of the actual prevalence of this phenomenon and the extent of the disappearance of these genes in these areas and other South American countries, thus guiding national malaria control programs on the appropriate use of RDTs. This study aimed to evaluate the pfhrp2 and pfhrp3 gene deletion in P. falciparum in endemic areas of the Brazilian Amazon. Aliquots of DNA from the biorepository of the Laboratory of Basic Research in Malaria, Evandro Chagas Institute, with a positive diagnosis for P. falciparum infection as determined by microscopy and molecular assays, were included. Monoinfection was confirmed by nested-polymerase chain reaction assay, and DNA quality was assessed by amplification of the merozoite surface protein-2 gene (msp2). The pfhrp2 and pfhrp3 genes were amplified using primers for the region between exons 1 and 2 and for all extension of exon 2. Aliquots of DNA from 192 P. falciparum isolates were included in the study, with 68.7% (132/192) from the municipality of Cruzeiro do Sul (Acre) and 31.3% (60/192) from Manaus (Amazonas). Of this total, 82.8% (159/192) of the samples were considered of good quality. In the state of Acre, 71.7% (71/99) showed pfhrp2 gene deletion and 94.9% (94/99) showed pfhrp3 gene deletion, while in the state of Amazonas, 100.0% (60/60) of the samples showed pfhrp2 gene deletion and 98.3% (59/60) showed pfhrp3 gene deletion. Moreover, 79.8% (127/159) of isolates displayed gene deletion. Our findings confirm the presence of a parasite population with high frequencies of pfhrp2 and pfhrp3 gene deletions in the Brazilian Amazon region. This suggests reconsidering the use of HRP2-based RDTs in the Acre and Amazonas states and calls attention to the importance of molecular surveillance and mapping of pfhrp2/pfhrp3 deletions in this area and in other locations in the Amazon region to guarantee appropriate patient care, control and ultimately contribute to achieving P. falciparum malaria elimination.


2006 ◽  
Vol 22 (12) ◽  
pp. 2703-2711 ◽  
Author(s):  
Giselle Maria Rachid Viana ◽  
Ricardo Luís Dantas Machado ◽  
Vanja Sueli Pachiano Calvosa ◽  
Marinete Marins Póvoa

The objectives of this study were to investigate the molecular basis for Plasmodium falciparum resistance to chloroquine in isolates from the Brazilian Amazon and to identify polymorphisms in the pfmdr1 gene, codons 184, 1042, and 1246, the kappa and gamma regions of the cg2 gene, and the K76T mutation of the pfcrt gene, in order to calculate the distribution of polymorphism within each target gene, comparing samples from distinct geographic areas, using allele-specific polymerase chain reaction (PCR) for the pfmdr gene and PCR plus restriction fragment length polymorphism (RFLP) for the cg2 and pfcrt genes. The sample consisted of 40 human blood isolates, already collected and morphologically diagnosed as carriers of P. falciparum parasites, from four localities: Porto Velho in Rondonia State and Maraba, Itaituba, and Tailandia in Pará State. Distribution of P. falciparum in vitro chloroquine resistance in the isolates was 100% for pfmdr1, cg2 gamma region, and pfcrt, except for the polymorphism in the cg2 kappa region, which was not found.


Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).


Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Merricka C. Livingstone ◽  
Alexis A. Bitzer ◽  
Alish Giri ◽  
Kun Luo ◽  
Rajeshwer S. Sankhala ◽  
...  

AbstractPlasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.


2021 ◽  
Vol 9 (4) ◽  
pp. 743
Author(s):  
Blenda Gonçalves Cabral ◽  
Danielle Murici Brasiliense ◽  
Ismari Perini Furlaneto ◽  
Yan Corrêa Rodrigues ◽  
Karla Valéria Batista Lima

Surgical site infection (SSI) following caesarean section is associated with increased morbidity, mortality, and significant health care costs. This study evaluated the epidemiological, clinical, and microbiological features of Acinetobacter spp. in women with SSIs who have undergone caesarean section at a referral hospital in the Brazilian Amazon region. This study included 69 women with post-caesarean SSI by Acinetobacter spp. admitted to the hospital between January 2012 and May 2015. The 69 Acinetobacter isolates were subjected to molecular species identification, antimicrobial susceptibility testing, detection of carbapenemase-encoding genes, and genotyping. The main complications of post-caesarean SSI by Acinetobacter were inadequate and prolonged antibiotic therapy, sepsis, prolonged hospitalization, and re-suture procedures. A. baumannii, A. nosocomialis and A. colistiniresistens species were identified among the isolates. Carbapenem resistance was associated with OXA-23-producing A. baumannii isolates and IMP-1-producing A. nosocomialis isolate. Patients with multidrug-resistant A. baumannii infection showed worse clinical courses. Dissemination of persistent epidemic clones was observed, and the main clonal complexes (CC) for A. baumannii were CC231 and CC236 (Oxford scheme) and CC1 and CC15 (Pasteur scheme). This is the first report of a long-term Acinetobacter spp. outbreak in women who underwent caesarean section at a Brazilian hospital. This study demonstrates the impact of multidrug resistance on the clinical course of post-caesarean infections.


2001 ◽  
Vol 17 (suppl) ◽  
pp. S155-S164 ◽  
Author(s):  
Pedro F. C. Vasconcelos ◽  
Amélia P. A. Travassos da Rosa ◽  
Sueli G. Rodrigues ◽  
Elizabeth S. Travassos da Rosa ◽  
Nicolas Dégallier ◽  
...  

A total of 187 different species of arboviruses and other viruses in vertebrates were identified at the Evandro Chagas Institute (IEC) from 1954 to 1998, among more than 10,000 arbovirus strains isolated from humans, hematophagous insects, and wild and sentinel vertebrates. Despite intensive studies in the Brazilian Amazon region, especially in Pará State, very little is known about most of these viruses, except for information on date, time, source, and method of isolation, as well as their capacity to infect laboratory animals. This paper reviews ecological and epidemiological data and analyzes the impact of vector and host population changes on various viruses as a result of profound changes in the natural environment. Deforestation, mining, dam and highway construction, human colonization, and urbanization were the main manmade environmental changes associated with the emergence and/or reemergence of relevant arboviruses, including some known pathogens for humans.


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