RESUMEN
Primaquine (PQ) is the main drug used to eliminate dormant liver stages and prevent relapses in Plasmodium vivax malaria. It also has an effect on the gametocytes of Plasmodium falciparum; however, it is unclear to what extent PQ affects P. vivax gametocytes. PQ metabolism involves multiple enzymes, including the highly polymorphic CYP2D6 and the cytochrome P450 reductase (CPR). Since genetic variability can impact drug metabolism, we conducted an evaluation of the effect of CYP2D6 and CPR variants on PQ gametocytocidal activity in 100 subjects with P. vivax malaria. To determine gametocyte density, we measured the levels of pvs25 transcripts in samples taken before treatment (D0) and 72 hours after treatment (D3). Generalized estimating equations (GEEs) were used to examine the effects of enzyme variants on gametocyte densities, adjusting for potential confounding factors. Linear regression models were adjusted to explore the predictors of PQ blood levels measured on D3. Individuals with the CPR mutation showed a smaller decrease in gametocyte transcript levels on D3 compared to those without the mutation (P = 0.02, by GEE). Consistent with this, higher PQ blood levels on D3 were associated with a lower reduction in pvs25 transcripts. Based on our findings, the CPR variant plays a role in the persistence of gametocyte density in P. vivax malaria. Conceptually, our work points to pharmacogenetics as a non-negligible factor to define potential host reservoirs with the propensity to contribute to transmission in the first days of CQ-PQ treatment, particularly in settings and seasons of high Anopheles human-biting rates.
Asunto(s)
Antimaláricos , Artemisininas , Malaria Falciparum , Malaria Vivax , Malaria , Humanos , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Malaria Vivax/tratamiento farmacológico , Malaria Falciparum/tratamiento farmacológico , NADPH-Ferrihemoproteína Reductasa , Cloroquina/farmacología , Citocromo P-450 CYP2D6/genética , Artemisininas/farmacología , Primaquina/farmacología , Primaquina/uso terapéutico , Malaria/tratamiento farmacológico , Plasmodium falciparum , Plasmodium vivax/genéticaRESUMEN
BACKGROUND: Plasmodium species of non-human primates (NHP) are of great interest because they can naturally infect humans. Plasmodium simium, a parasite restricted to the Brazilian Atlantic Forest, was recently shown to cause a zoonotic outbreak in the state of Rio de Janeiro. The potential of NHP to act as reservoirs of Plasmodium infection presents a challenge for malaria elimination, as NHP will contribute to the persistence of the parasite. The aim of the current study was to identify and quantify gametocytes in NHP naturally-infected by P. simium. METHODS: Whole blood samples from 35 NHP were used in quantitative reverse transcription PCR (RT-qPCR) assays targeting 18S rRNA, Pss25 and Pss48/45 malaria parasite transcripts. Absolute quantification was performed in positive samples for 18S rRNA and Pss25 targets. Linear regression was used to compare the quantification cycle (Cq) and the Spearman's rank correlation coefficient was used to assess the correlation between the copy numbers of 18S rRNA and Pss25 transcripts. The number of gametocytes/µL was calculated by applying a conversion factor of 4.17 Pss25 transcript copies per gametocyte. RESULTS: Overall, 87.5% of the 26 samples, previously diagnosed as P. simium, were positive for 18S rRNA transcript amplification, of which 13 samples (62%) were positive for Pss25 transcript amplification and 7 samples (54%) were also positive for Pss48/45 transcript. A strong positive correlation was identified between the Cq of the 18S rRNA and Pss25 and between the Pss25 and Pss48/45 transcripts. The 18S rRNA and Pss25 transcripts had an average of 1665.88 and 3.07 copies/µL, respectively. A positive correlation was observed between the copy number of Pss25 and 18S rRNA transcripts. Almost all gametocyte carriers exhibited low numbers of gametocytes (< 1/µL), with only one howler monkey having 5.8 gametocytes/µL. CONCLUSIONS: For the first time, a molecular detection of P. simium gametocytes in the blood of naturally-infected brown howler monkeys (Alouatta guariba clamitans) was reported here, providing evidence that they are likely to be infectious and transmit P. simium infection, and, therefore, may act as a reservoir of malaria infection for humans in the Brazilian Atlantic Forest.
Asunto(s)
Malaria , Plasmodium , Animales , Humanos , ARN Ribosómico 18S/genética , Brasil/epidemiología , Plasmodium/genética , Malaria/epidemiología , Malaria/veterinaria , Malaria/parasitología , Primates/genética , Bosques , Plasmodium falciparum/genéticaRESUMEN
P48/45 is a conserved gametocyte antigen involved in Plasmodium parasite fertilization. A recombinant Plasmodium vivax P48/45 (Pvs48/45) protein expressed in Escherichia coli (E. coli) was highly antigenic and immunogenic in experimental animals and elicited specific transmission-blocking (TB) antibodies in a previous pilot study. Here, a similar Pvs48/45 gene was expressed in Chinese Hamster Ovary (CHO) cells and we compared its immunoreactivity with the E. coli product. Specific antibody titers were determined using plasma from Colombian individuals (n=227) living in endemic areas where both P. vivax and P. falciparum are prevalent and from Guatemala (n=54) where P. vivax is highly prevalent. In Colombia, plasma seroprevalence to CHO-rPvs48/45 protein was 46.3%, while for E. coli-rPvs48/45 protein was 36.1% (p<0.001). In Guatemala, the sero prevalence was 24.1% and 14.8% (p<0.001), respectively. Reactivity index (RI) against both proteins showed an age-dependent increase. IgG2 was the predominant subclass and the antibody avidity index evaluated by ELISA ranged between 4-6 mol/L. Ex vivo P. vivax mosquito direct membrane feeding assays (DMFA) performed in presence of study plasmas, displayed significant parasite transmission-blocking (TB), however, there was no direct correlation between antibody titers and oocysts transmission reduction activity (%TRA). Nevertheless, DMFA with CHO rPvs48/45 affinity purified IgG showed a dose response; 90.2% TRA at 100 µg/mL and 71.8% inhibition at 10 µg/mL. In conclusion, the CHO-rPvs48/45 protein was more immunoreactive in most of the malaria endemic places studied, and CHO-rPvs48/45 specific IgG showed functional activity, supporting further testing of the protein vaccine potential.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Enfermedades Endémicas , Escherichia coli/metabolismo , Inmunoglobulina G/sangre , Malaria Vivax/diagnóstico , Plasmodium vivax/inmunología , Pruebas Serológicas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Especificidad de Anticuerpos , Antígenos de Protozoos/genética , Antígenos de Protozoos/metabolismo , Células CHO , Niño , Colombia/epidemiología , Cricetulus , Escherichia coli/genética , Femenino , Guatemala/epidemiología , Humanos , Malaria Vivax/sangre , Malaria Vivax/epidemiología , Malaria Vivax/inmunología , Masculino , Persona de Mediana Edad , Plasmodium vivax/patogenicidad , Valor Predictivo de las Pruebas , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
In a Plasmodium vivax infection, it was shown a proportionally increased on gametocyte distribution within the bone marrow aspirant, suggesting a role of this organ as a reservoir for this parasite stage. Here, we evaluated the ex vivo cytoadhesive capacity of P. vivax gametocytes to bone marrow endothelial cells (HBMEC) and investigated the involvement of some receptors in the cytoadhesion process by using transfected CHO cells (CHO-ICAM1, CHO-CD36 and CHO-VCAM), wild type (CHO-K1) or deficient in heparan and chondroitin sulfate (CHO-745). Ex-vivo cytoadhesion assays were performed using a total of 44 P. vivax isolates enriched in gametocyte stages by Percoll gradient in the different cell lines. The majority of isolates (88.9%) were able to adhere to HBMEC monolayer. ICAM1 seemed to be the sole receptor significantly involved. CD-36 was the receptor with higher adhesion rate, despite no significance was noticed when compared to CHO-745. We demonstrated that gametocyte P. vivax adheres ex vivo to bone marrow endothelial cells. Moreover, P. vivax gametocytes display the ability to adhere to all CHO cells investigated, especially to CHO-ICAM1. These findings bring insights to the comprehension of the role of the bone marrow as a P. vivax reservoir and the potential impact on parasite transmission to the vector.
Asunto(s)
Plasmodium falciparum , Plasmodium vivax , Animales , Médula Ósea , Cricetinae , Cricetulus , Células Endoteliales , Plasmodium vivax/genéticaRESUMEN
The control and elimination of malaria caused by Plasmodium vivax both represent a great challenge due to the biological aspects of the species. Gametocytes are the forms responsible for the transmission of the parasite to the vector and the search for new strategies for blocking transmission are essential in a scenario of control and elimination The challenges in this search in regard to P. vivax mainly stem from the lack of a long-term culture and the limitation of studies of gametocytes. This study evaluated the viability and infectivity of P. vivax gametocytes in short-term culture. The samples enriched in gametocytes using Percoll (i), using magnetic-activated cell sorting (MACS®) (ii), and using non-enriched samples (iii) were evaluated. After the procedures, gametocytes were cultured in IMDM medium for up to 48 h. Cultured P. vivax gametocytes were viable and infectious for up to 48 h, however differences in viability and infectivity were observed in the samples after 12 h of culture in relation to 0 h. Percoll-enriched samples were shown to be viable in culture for longer intervals than those purified using MACS®. Gametocyte viability after enrichment procedures and short-term culture may provide new avenues in the development of methods for evaluating P. vivax TB.
Asunto(s)
Malaria Vivax , Malaria , Humanos , Plasmodium falciparum , Plasmodium vivaxRESUMEN
BACKGROUND Different strategies for improvement of malaria control and elimination are based on the blockage of malaria parasite transmission to the mosquito vector. These strategies include the drugs that target the plasmodial sexual stages in humans and the early developmental stages inside mosquitoes. OBJECTIVES Here we tested Malaria Box compounds in order to evaluate their activity against male and female gametocytes in Plasmodium berghei, mosquito infection in P. vivax and ookinete formation in both species. METHODS/FINDINGS The membrane feeding assay and the development of ookinetes by a 24 h ex vivo culture and the ookinete yield per 1000 erythrocytes were used to test transmission-blocking potential of the Malaria Box compounds in P. vivax. For P. berghei we used flow cytometry to evaluate male and female gametocyte time course and fluorescence microscopy to check the ookinete development. The two species used in this study showed similar results concerning the compounds' activity against gametocytes and ookinetes, which were different from those in P. falciparum. In addition, from the eight Malaria Box compounds tested in both species, compounds MMV665830, MMV665878 and MMV665941 were selected as a hit compounds due the high inhibition observed. CONCLUSION Our results showed that P. berghei is suitable as an initial screening system to test compounds against P. vivax.
Asunto(s)
Animales , Plasmodium berghei/efectos de los fármacos , Plasmodium vivax/efectos de los fármacos , Malaria Vivax/prevención & control , Mosquitos Vectores/parasitología , Malaria Vivax/tratamiento farmacológico , Malaria Vivax/transmisiónRESUMEN
Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.
Asunto(s)
Amino Alcoholes/farmacología , Antiprotozoarios/farmacología , Amino Alcoholes/síntesis química , Amino Alcoholes/química , Animales , Antiprotozoarios/síntesis química , Antiprotozoarios/química , Babesia/efectos de los fármacos , Babesia/crecimiento & desarrollo , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Modelos Animales de Enfermedad , Leishmania/efectos de los fármacos , Leishmania/crecimiento & desarrollo , Estadios del Ciclo de Vida/efectos de los fármacos , Ratones , Plasmodium/efectos de los fármacos , Plasmodium/crecimiento & desarrollo , Infecciones por Protozoos/tratamiento farmacológico , Infecciones por Protozoos/parasitología , Resultado del Tratamiento , Trypanosoma/efectos de los fármacos , Trypanosoma/crecimiento & desarrollo , Células VeroRESUMEN
Abstract A free-living, adult male maned wolf (Chrysocyon brachyurus) was referred to the Governador "Laudo Natel" - FCAV/Unesp veterinary hospital after being found with skin lesions and a fracture on the right pelvic limb, which had to be amputated due to compromised integrity. Around 20 days later, bilateral accentuated swollen on humerus-radius-ulna articulation was observed. The synovial liquid was drained and sent to the laboratory for synovial cytology with Rosenfeld staining that revealed predominantly degenerated neutrophils with karyolytic chromatin associated with intracellular inclusions suggestive of Hepatozoon sp. gametocytes. Blood and synovial liquid samples were submitted to molecular analysis, aiming to amplify the Hepatozoon spp. 18S rRNA gene fragment. Despite the positioning of the found Hepatozoon sequence together with Hepatozoon canis previously detected in domestic carnivores, the BLAST analysis showed only 98% identity with H. canis. To the best of the authors' knowledge, this is the first time a Hepatozoon was detected in the synovial liquid by clinical pathology and molecular analyses.
Resumo Um lobo guará (Chrysocyon brachyurus) adulto, macho, de vida livre foi encaminhado para atendimento no hospital veterinário Governador "Laudo Natel" - FCAV/Unesp após ser encontrado com lesões de pele e fratura em membro pélvico direito, sendo amputado devido a comprometimento da integridade do membro. Aproximadamente 20 dias após a chegada ao hospital, foi notado acentuado aumento de volume bilateral em região de articulação úmero-rádio-ulnar. O líquido sinovial foi drenado e enviado para análise citológica com coloração de Rosenfeld, revelando a presença de neutrófilos degenerados com cromatina cariolítica associados a inclusões intracelulares sugestivas de gametócitos de Hepatozoon sp. Amostras de sangue e líquido sinovial foram submetidas a análises moleculares visando amplificar um fragmento do gene 18S rRNA de Hepatozoon spp. Apesar da sequência de Hepatozoon detectada se posicionar filogeneticamente no mesmo clado que H. canis previamente detectado em carnívoros domésticos, o resultado da análise do BLAST mostrou somente 98% de identidade com H. canis. De acordo com o conhecimento dos autores, esta é a primeira vez que Hepatozoon foi detectado no líquido sinovial por meio de patologia clínica e análises moleculares.
Asunto(s)
Animales , Masculino , Infecciones por Protozoos/parasitología , Líquido Sinovial/parasitología , Apicomplexa/genética , Canidae/parasitología , Filogenia , Brasil , ARN Ribosómico 18S/genética , Apicomplexa/aislamiento & purificación , Hallazgos IncidentalesRESUMEN
BACKGROUND: The susceptibility of Anopheles albimanus and An. pseudopunctipennis to local Plasmodium vivax has been associated in southern Mexico with two ookinete surface proteins (Pvs25/28) polymorphism. Perhaps parasite population selection (i.e. adaptation to local vectors) contributes to this phenomenon. It is also possible that certain molecular interactions exist between P. vivax and each mosquito species independently of geographical origin. This study aimed to explore the susceptibility of An. albimanus and An. pseudopunctipennis (collected from different geographical sites) to P. vivax cspVk/Pvs25-130 haplotypes from southern Mexico. RESULTS: Of the 120 P. vivax-infected blood samples used to simultaneously feed An. albimanus and An. pseudopunctipennis mosquitoes originating from various geographical sites, 80 produced at least one infected mosquito species. Three parasite haplotypes were identified in infected blood: Vk210/Pvs25-A (12.5%), Vk210/Pvs25-B (20%) and Vk247/Pvs25-B (67.5%). Two parameters (the proportion of infected mosquitoes and number of oocysts/mosquito) showed a similar pattern for each mosquito species (independently of geographical origin). For An. albimanus mosquitoes (from the Pacific coast, Mexican gulf and Lacandon Forest lowlands), these two parameters were higher in specimens infected with P. vivax Vk210/Pvs25-A versus Vk210/Pvs25-B or Vk247/Pvs25-B (P < 0.001). For An. pseudopunctipennis mosquitoes (from the Pacific coast, northeast Mexico and east Guatemala foothills), the same two parameters were higher in specimens infected with Vk247/Pvs25-B or Vk210/Pvs25-B versus Vk210/Pvs25-A (P < 0.001). Higher infection rates were caused by Vk247/Pvs25-B than Vk210/Pvs25-B parasites in An. pseudopunctipennis (P = 0.011) and An. albimanus (P = 0.001). The greatest parasitaemia, gametocytaemia and microgamete formation was observed in Vk247/Pvs25-B infected blood, and each of these parameters correlated with each other and with the number of oocysts in An. pseudopunctipennis from the sympatric colony. CONCLUSIONS: Plasmodium vivax Vk247/Pvs25-B infections were the most prevalent, likely due to the higher parasitaemia produced in the susceptible vector (especially An. pseudopunctipennis). The analysis of mosquito-parasite interactions indicate that An. pseudopunctipennis and An. albimanus each have a unique pattern of transmitting genetic variants of P. vivax, and this is not dependent on geographical origin. The present findings highlight the importance of parasite genotyping to understand transmission dynamics and vectorial participation.
Asunto(s)
Anopheles/parasitología , Antígenos de Protozoos/genética , Variación Genética , Malaria Vivax/epidemiología , Mosquitos Vectores/parasitología , Plasmodium vivax/genética , Animales , Femenino , Geografía , Guatemala/epidemiología , Haplotipos , Humanos , Malaria Vivax/sangre , México/epidemiología , Fenotipo , Polimorfismo Genético , Proteínas Protozoarias/genéticaRESUMEN
A free-living, adult male maned wolf (Chrysocyon brachyurus) was referred to the Governador Laudo Natel FCAV/Unesp veterinary hospital after being found with skin lesions and a fracture on the right pelvic limb, which had to be amputated due to compromised integrity. Around 20 days later, bilateral accentuated swollen on humerus-radius-ulna articulation was observed. The synovial liquid was drained and sent to the laboratory for synovial cytology with Rosenfeld staining that revealed predominantly degenerated neutrophils with karyolytic chromatin associated with intracellular inclusions suggestive of Hepatozoon sp. gametocytes. Blood and synovial liquid samples were submitted to molecular analysis, aiming to amplify the Hepatozoon spp. 18S rRNA gene fragment. Despite the positioning of the found Hepatozoon sequence together with Hepatozoon canis previously detected in domestic carnivores, the BLAST analysis showed only 98% identity with H. canis. To the best of the authors knowledge, this is the first time a Hepatozoon was detected in the synovial liquid by clinical pathology and molecular analyses.(AU)
Um lobo guará (Chrysocyon brachyurus) adulto, macho, de vida livre foi encaminhado para atendimento no hospital veterinário Governador Laudo Natel FCAV/Unesp após ser encontrado com lesões de pele e fratura em membro pélvico direito, sendo amputado devido a comprometimento da integridade do membro. Aproximadamente 20 dias após a chegada ao hospital, foi notado acentuado aumento de volume bilateral em região de articulação úmero-rádio-ulnar. O líquido sinovial foi drenado e enviado para análise citológica com coloração de Rosenfeld, revelando a presença de neutrófilos degenerados com cromatina cariolítica associados a inclusões intracelulares sugestivas de gametócitos de Hepatozoon sp. Amostras de sangue e líquido sinovial foram submetidas a análises moleculares visando amplificar um fragmento do gene 18S rRNA de Hepatozoon spp. Apesar da sequência de Hepatozoon detectada se posicionar filogeneticamente no mesmo clado que H. canis previamente detectado em carnívoros domésticos, o resultado da análise do BLAST mostrou somente 98% de identidade com H. canis. De acordo com o conhecimento dos autores, esta é a primeira vez que Hepatozoon foi detectado no líquido sinovial por meio de patologia clínica e análises moleculares.(AU)
Asunto(s)
Animales , Canidae/microbiología , Eucoccidiida/microbiología , Líquido SinovialRESUMEN
BACKGROUND: Asymptomatic individuals are one of the major challenges for malaria elimination programs in endemic areas. In the absence of clinical symptoms and with a lower parasite density they constitute silent reservoirs considered important for maintaining transmission of human malaria. Studies from Brazil have shown that infected individuals may carry these parasites for long periods. RESULTS: Patients were selected from three periurban endemic areas of the city of Manaus, in the western Brazilian Amazon. Symptomatic and asymptomatic patients with positive thick blood smear and quantitative real-time PCR (qPCR) positive for Plasmodium vivax were invited to participate in the study. A standardised pvs25 gene amplification by qPCR was used for P. vivax gametocytes detection. Anopheles aquasalis were fed using membrane feeding assays (MFA) containing blood from malaria patients. Parasitemia of 42 symptomatic and 25 asymptomatic individuals was determined by microscopic examination of blood smears and qPCR. Parasitemia density and gametocyte density were assessed as determinants of infection rates and oocysts densities. A strong correlation between gametocyte densities (microscopy and molecular techniques) and mosquito infectivity (P < 0.001) and oocysts median numbers (P < 0.05) was found in both groups. The ability to infect mosquitoes was higher in the symptomatic group (41%), but infectivity in the asymptomatic group was also seen (1.42%). CONCLUSIONS: Although their infectivity to mosquitoes is relatively low, given the high prevalence of P. vivax asymptomatic carriers they are likely to play and important role in malaria transmission in the city of Manaus. The role of asymptomatic infections therefore needs to be considered in future malaria elimination programs in Brazil.
Asunto(s)
Anopheles/parasitología , Infecciones Asintomáticas/epidemiología , Malaria Vivax/epidemiología , Plasmodium vivax/fisiología , Adulto , Animales , Anopheles/genética , Anopheles/fisiología , Brasil/epidemiología , Estudios Transversales , Erradicación de la Enfermedad , Enfermedades Endémicas , Femenino , Humanos , Estadios del Ciclo de Vida/fisiología , Malaria Vivax/sangre , Malaria Vivax/parasitología , Malaria Vivax/transmisión , Masculino , Persona de Mediana Edad , Mosquitos Vectores/parasitología , Oocistos/fisiología , Plasmodium vivax/genética , Prevalencia , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Even though malaria incidence has decreased substantially in Guatemala since 2000, Guatemala remains one of the countries with the highest malaria transmission in Mesoamerica. Guatemala is committed to eliminating malaria as part of the initiative 'Elimination of Malaria in Mesoamerica and the Island of Hispaniola' (EMMIE); however, it is still in the control phase. During the past decade, the government strengthened malaria control activities including mass distribution of long-lasting insecticide-impregnated bed nets, early diagnosis and prompt treatment. This study aimed to determine the prevalence of malaria, including gametocytes, in three areas of Guatemala using active case detection (ACD) and quantitative polymerase chain reaction (qPCR). METHODS: Cross-sectional surveys were conducted in three departments with varying transmission intensities: Escuintla, Alta Verapaz and Zacapa. Blood samples from 706 volunteers were screened for malaria using microscopy and qPCR which was also used to determine the prevalence of gametocytes among infected individuals. Results were collected and analysed using REDCap and R Project, respectively. RESULTS: Malaria was diagnosed by microscopy in only 2.8 % (4/141) of the volunteers from Escuintla. By contrast, qPCR detected a prevalence of 7.1 % (10/141) in the same volunteers, 8.4 % (36/429) in Alta Verapaz, and 5.9 % (8/136) in Zacapa. Overall, 7.6 % (54/706) of the screened individuals were positive, with an average parasitaemia level of 40.2 parasites/µL (range 1-1133 parasites/µL) and 27.8 % carried mature gametocytes. Fifty-seven percent (31/54) of qPCR positive volunteers were asymptomatic and out of the 42.6 % of symptomatic individuals, only one had a positive microscopy result. CONCLUSIONS: This study found a considerable number of asymptomatic P. vivax infections that were mostly submicroscopic, of which, approximately one-quarter harboured mature gametocytes. This pattern is likely to contribute to maintaining transmission across the region. Robust surveillance systems, molecular diagnostic tests and tailored malaria detection activities for each endemic site may prove to be imperative in accelerating malaria elimination in Guatemala and possibly across all of Mesoamerica.
Asunto(s)
Erradicación de la Enfermedad , Transmisión de Enfermedad Infecciosa/prevención & control , Malaria/epidemiología , Malaria/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimaláricos/uso terapéutico , Sangre/parasitología , Niño , Preescolar , Estudios Transversales , Diagnóstico Precoz , Femenino , Guatemala/epidemiología , Humanos , Lactante , Recién Nacido , Malaria/diagnóstico , Malaria/transmisión , Masculino , Microscopía , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Control de Mosquitos/métodos , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Voluntarios , Adulto JovenRESUMEN
Antecedentes: Los esquizonticidas anti-Plasmodium falciparum reducen la gametocitemia, sin erradicarla; por ello, se adiciona primaquina (PQ). Esta se administra al terminar el esquizonticida: día 4; 0,75 mg/kg; dosis única (régimen estándar). Las artemisininas actúan sobre gametocitos inmaduros I-IV de P. falciparum; la PQ actúa (stages I-IV) of P. falciparum; PQ acts on mature sobre gametocitos maduros (estadio V). ¿Cuál es la eficacia antigametocitos de la combinación esquizonticida-PQ? Objetivo: Analizar la eficacia de PQ-régimen estándar contra gametocitos de P. falciparum, asociada al esquizonticida. Metodología:Revisión sistemática de los artículos hallados en Pubmed y Lilacs. Resultados y conclusiones: Ningún esquizonticida elimina totalmente los gametocitos en 6-7 días iniciales de tratamiento. La adición de PQ-régimen estándar tiene potente acción antigametocitos. Ninguna combinación esquizonticida-PQ tiene eficacia total en ese plazo. No conocemos cómo varía la eficacia antigametocitos de PQ dada los días 1 a 3, ni en dosis diferentes a la estándar, ni en múltiples dosis. [Carmona-Fonseca J, Arango EM. Primaquina, gametocitemia de Plasmodium falciparum y bloqueo de transmisión: ineficacia del actual régimen de dosificación. the current dosing scheme. MedUNAB 2012; 15:14-21].
Background: Anti-Plasmodium falciparum schizontocides decrease gametocytemia, not eliminate it; by this, he added primaquine (PQ). The PQ is administered after the treatment schizonticide: day 4; 0.75 mg/kg single dose (standard regimen). The artemisinins act on immature gametocytes (stages I-IV) of P. falciparum; PQ acts on mature gametocytes (stage V). What is the efficacy of the combination schizontocide-PQ against gametocytes? Objective: Analyze the effectiveness of PQ-standard regimen against gametocytes of P. falciparum, associated with schizonticide. Methodology: Systematic review of articles found in PubMed and Lilacs. Results and conclusions: No schizonticide completely eliminates the gametocytes in initial treatment 6-7 days. The addition of PQ-standard regimen has potent anti-gametocytes. No combination has efficacy schizonticide-PQ total in that period. We do not know how the efficiency varies anti-gametocytes of PQ given on days 1 to 3, or different from the standard dose or multiple doses. [Carmona-Fonseca J, Arango EM. Primaquine, Plasmodium falciparum gametocytemia and blocking transmission: inefficiency of the current dosing scheme. MedUNAB 2012; 15:14-21].
Asunto(s)
Plasmodium falciparum , Primaquina , Colombia , MalariaRESUMEN
Anaemia in falciparum malaria is associated with an increased risk of gametocyte carriage, but its effects on transmission have not been extensively evaluated in malarious children. Plasmodium falciparum gametocyte carriage, emergence, clearance, population sex ratios (SR) (defined as the proportion of gametocytes that are male), inbreeding rates and temporal changes in SR were evaluated in 840 malarious children. Gametocyte carriage pre-treatment was at a level of 8.1 percent. Anaemia at enrolment was an independent risk factor for gametocyte carriage post-treatment. The emergence of gametocytes seven days post-treatment was significantly more frequent in anaemic children (7/106 vs. 10/696, p = 0.002). In the initially detected gametocytes, the proportion of children with a male-biased SR (MBSR) (> 0.5) was significantly higher in anaemic children (6/7 vs. 3/10, p = 0.027). Pre-treatment SR and estimated inbreeding rates (proportion of a mother's daughters fertilised by her sons) were similar in anaemic and non-anaemic children. Pre-treatment SR became more female-biased in non-anaemic children following treatment. However, in anaemic children, SR became male-biased. Anaemia was shown to significantly increase gametocyte emergence and may significantly alter the SR of emerging gametocytes. If MBSR is more infective to mosquitoes at low gametocytaemia, then these findings may have significant implications for malaria control efforts in endemic settings where malaria-associated anaemia is common.