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1.
Int Emerg Nurs ; 60: 101110, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34953438

RESUMO

BACKGROUND: Malaria is a life-threatening disease. Prior to the pandemic, over a million people annually from non-endemic, high income countries such as Europe and North America visited countries with a risk of malaria transmission. Emergency care nurses in non-endemic countries frequently encounter returning travellers, presenting with symptoms suggestive of malaria. While rapid diagnostic tests are used in countries with endemic malaria, in countries such as the United Kingdom diagnosis is undertaken by microscopy and three negative tests are required to exclude. QUESTION: Are rapid diagnostic tests effective for diagnosing imported malaria in non-endemic, high income countries? METHOD: A systematic review of published research (January 2009 - November 2020) comparing rapid diagnostic tests with microscopy. RESULTS: Fourteen studies were included, conducted in five countries with 14 different RDTs evaluated. Mean sensitivity and specificity for Plasmodium Falciparum was 91.8% and 97.7% and Plasmodium Vivax 81.6% and 99.2%. Higher sensitivities were related to higher parasite densities. CONCLUSIONS: International travel will return post-pandemic and rapid, accurate and cost-efficient tests will be required. The rapid diagnostic tests in these studies showed significant variation and were not as accurate as microscopy. Consequently, it cannot be recommended that rapid diagnostic tests replace the gold standard of microscopy. Further research is required.


Assuntos
Testes Diagnósticos de Rotina , Malária , Países Desenvolvidos , Humanos , Malária/diagnóstico , Plasmodium vivax , Sensibilidade e Especificidade
2.
Malar J ; 20(1): 483, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952581

RESUMO

BACKGROUND: Ethiopia is one of the few countries in Africa where Plasmodium vivax commonly co-exists with Plasmodium falciparum, and which accounts for ~ 40% of the total number of malaria infections in the country. Regardless of the growing evidence over many decades of decreasing sensitivity of this parasite to different anti-malarial drugs, there has been no comprehensive attempt made to systematically review and meta-analyse the efficacy of different anti-malarial drugs against P. vivax in the country. However, outlining the efficacy of available anti-malarial drugs against this parasite is essential to guide recommendations for the optimal therapeutic strategy to use in clinical practice. The aim of this study was to synthesize evidence on the efficacy of anti-malarial drugs against clinical P. vivax malaria in Ethiopia. METHODS: All potentially relevant, peer-reviewed articles accessible in PubMed, Scopus, Web of Science, and Clinical Trial.gov electronic databases were retrieved using a search strategy combining keywords and related database-specific subject terms. Randomized controlled trials (RCTs) and non-randomized trials aiming to investigate the efficacy of anti-malarial drugs against P. vivax were included in the review. Data were analysed using Review Manager Software. Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity. The funnel plot and Egger's test were used to examine risk of publication bias. RESULTS: Out of 1294 identified citations, 14 articles that presented data on 29 treatment options were included in the analysis. These studies enrolled 2144 clinical vivax malaria patients. The pooled estimate of in vivo efficacy of anti-malarial drugs against vivax malaria in Ethiopia was 97.91% (95% CI: 97.29-98.52%), with significant heterogeneity (I2 = 86%, p < 0.0001) and publication bias (Egger's test = -12.86, p < 0.001). Different anti-malarial drugs showed varied efficacies against vivax malaria. The duration of follow-up significantly affected the calculated efficacy of any given anti-malarial drug, with longer duration of the follow-up (42 days) associated with significantly lower efficacy than efficacy reported on day 28. Also, pooled PCR-corrected efficacy and efficacy estimated from altitudinally lower transmission settings were significantly higher than PCR-uncorrected efficacy that estimated for moderate transmission settings, respectively. CONCLUSION: The overall efficacy of anti-malarial drugs evaluated for the treatment of vivax malaria in Ethiopia was generally high, although there was wide-ranging degree of efficacy, which was affected by the treatment options, duration of follow-up, transmission intensity, and the confirmation procedures for recurrent parasitaemia. Regardless of evidence of sporadic efficacy reduction reported in the country, chloroquine (CQ), the first-line regimen in Ethiopia, remained highly efficacious, supporting its continuous utilization for confirmed P. vivax mono-infections. The addition of primaquine (PQ) to CQ is recommended, as this is the only approved way to provide radical cure, and thus ensure sustained efficacy and longer protection against P. vivax. Continuous surveillance of the efficacy of anti-malarial drugs and clinical trials to allow robust conclusions remains necessary to proactively act against possible emergence and spread of drug-resistant P. vivax in Ethiopia.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/prevenção & controle , Plasmodium vivax/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Etiópia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
3.
Malar J ; 20(1): 470, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930260

RESUMO

BACKGROUND: Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection. METHODS: This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated. RESULTS: The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566-27,815), 71,427 parasites/ml [IQR 33,236-180,213], and 34,840 parasites/ml (IQR 13,302-77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8-13.3), 14.8% (IQR 11.8-15.9) and 11.7% (IQR 8.9-14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5-21), 15 (IQR 7-22), and 8 (IQR 7-15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1-5.3), 7.2% (IQR 5.8-7.8), and 4.9% (IQR 3.7-6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006-0.06), 0.128% (IQR 0.068-0.616) and 0.022% (IQR 0.008-0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. CONCLUSION: Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.


Assuntos
Anemia/tratamento farmacológico , Antimaláricos/uso terapêutico , Eritrócitos/parasitologia , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Parasitemia/tratamento farmacológico , Adulto , Anemia/parasitologia , Feminino , Humanos , Malária Falciparum/complicações , Malária Falciparum/parasitologia , Malária Vivax/complicações , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Parasitemia/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium vivax/efeitos dos fármacos , Adulto Jovem
4.
Malar J ; 20(1): 479, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930278

RESUMO

BACKGROUND: Plasmodium vivax blood-stage relapses originating from re-activating hypnozoites are a major barrier for control and elimination of this disease. Radical cure is a form of therapy capable of addressing this problem. Recent clinical trials of radical cure have yielded efficacy estimates ranging from 65 to 94%, with substantial variation across trial sites. METHODS: An analysis of simulated trial data using a transmission model was performed to demonstrate that variation in efficacy estimates across trial sites can arise from differences in the conditions under which trials are conducted. RESULTS: The analysis revealed that differences in transmission intensity, heterogeneous exposure and relapse rate can yield efficacy estimates ranging as widely as 12-78%, despite simulating trial data under the uniform assumption that treatment had a 75% chance of clearing hypnozoites. A longer duration of prophylaxis leads to a greater measured efficacy, particularly at higher transmission intensities, making the comparison between the protection of different radical cure treatment regimens against relapse more challenging. Simulations show that vector control and parasite genotyping offer two potential means to yield more standardized efficacy estimates that better reflect prevention of relapse. CONCLUSIONS: Site-specific biases are likely to contribute to variation in efficacy estimates both within and across clinical trials. Future clinical trials can reduce site-specific biases by conducting trials in low-transmission settings where re-infections from mosquito bite are less common, by preventing re-infections using vector control measures, or by identifying and excluding likely re-infections that occur during follow-up, by using parasite genotyping methods.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Malária Vivax/prevenção & controle , Plasmodium vivax/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Geografia , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Adulto Jovem
5.
Malar J ; 20(1): 460, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895233

RESUMO

BACKGROUND: A detailed analysis of household and individual level Plasmodium infection patterns in two low-endemic districts of Meghalaya was undertaken to better understand the epidemiology of malaria in northeast India. METHODS: Socio-demographic and behavioural information from residents (aged 1-69 years) of households were collected through pre-tested, questionnaire conducted in 2018 and 2019. Blood samples collected from participants were tested for Plasmodium falciparum and/or Plasmodium vivax infection using rapid diagnostic test, microscopy and PCR. Plasma samples from a subset of participants were analysed for antibodies against thirteen P. falciparum and four P. vivax antigens. Associations between household and individual level risk factors, and Plasmodium infections were evaluated using multilevel logistic regression models. RESULTS: A total of 2753 individuals from 827 households were enrolled in 2018, and 834 individuals from 222 households were enrolled in 2019. Of them, 33 (1.2%) were positive by PCR for P. falciparum in 2018 and none were positive for P. vivax. In 2019, no PCR-positive individuals were detected. All, but one, infections were asymptomatic; all 33 infections were sub-microscopic. Reported history of malaria in the past 12 months (OR = 8.84) and history of travel in the past 14 days (OR = 10.06) were significantly associated with Plasmodium infection. A significant trend of increased seropositivity with age was noted for all 17 antigens. Although adults (≥ 18 years) consistently had the highest seropositivity rates, a sizeable proportion of under-five children were also found to be seropositive. Almost all individuals (99.4%) reported sleeping under an insecticide-treated bed-net, and household indoor residual spray coverage in the 12 months preceding the survey was low (23%). Most participants correctly identified common signs and symptoms of malaria, i.e., fever (96.4%), headache (71.2%), chills (83.2%) and body-ache (61.8%). Almost all participants (94.3%) used government-provided services for treatment of malaria. CONCLUSION: This study explored the epidemiology of malaria in two communities in Meghalaya, India, in the context of declining transmission. The presence of widespread asymptomatic infections and seropositivity among under-five children suggest that low-level Plasmodium transmission persists in this region. Implications of the study findings for malaria elimination efforts in low-transmission settings are discussed.


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Infecções Assintomáticas/epidemiologia , Estudos Transversais , Características da Família , Feminino , Humanos , Incidência , Índia/epidemiologia , Malária Falciparum/prevenção & controle , Malária Vivax/prevenção & controle , Masculino , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Fatores de Risco
6.
Front Cell Infect Microbiol ; 11: 738075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790586

RESUMO

Drug resistance in Plasmodium vivax may pose a challenge to malaria elimination. Previous studies have found that P. vivax has a decreased sensitivity to antimalarial drugs in some areas of the Greater Mekong Sub-region. This study aims to investigate the ex vivo drug susceptibilities of P. vivax isolates from the China-Myanmar border and genetic variations of resistance-related genes. A total of 46 P. vivax clinical isolates were assessed for ex vivo susceptibility to seven antimalarial drugs using the schizont maturation assay. The medians of IC50 (half-maximum inhibitory concentrations) for chloroquine, artesunate, and dihydroartemisinin from 46 parasite isolates were 96.48, 1.95, and 1.63 nM, respectively, while the medians of IC50 values for piperaquine, pyronaridine, mefloquine, and quinine from 39 parasite isolates were 19.60, 15.53, 16.38, and 26.04 nM, respectively. Sequence polymorphisms in pvmdr1 (P. vivax multidrug resistance-1), pvmrp1 (P. vivax multidrug resistance protein 1), pvdhfr (P. vivax dihydrofolate reductase), and pvdhps (P. vivax dihydropteroate synthase) were determined by PCR and sequencing. Pvmdr1 had 13 non-synonymous substitutions, of which, T908S and T958M were fixed, G698S (97.8%) and F1076L (93.5%) were highly prevalent, and other substitutions had relatively low prevalences. Pvmrp1 had three non-synonymous substitutions, with Y1393D being fixed, G1419A approaching fixation (97.8%), and V1478I being rare (2.2%). Several pvdhfr and pvdhps mutations were relatively frequent in the studied parasite population. The pvmdr1 G698S substitution was associated with a reduced sensitivity to chloroquine, artesunate, and dihydroartemisinin. This study suggests the possible emergence of P. vivax isolates resistant to certain antimalarial drugs at the China-Myanmar border, which demands continuous surveillance for drug resistance.


Assuntos
Preparações Farmacêuticas , Plasmodium vivax , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mianmar , Plasmodium vivax/genética , Proteínas de Protozoários/genética
7.
Korean J Parasitol ; 59(5): 507-512, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34724771

RESUMO

Since 1993, vivax malaria has been recognized as a public health burden in Korea. Despite of pan-governmental malaria-control efforts and the dramatic reduction in the burden of this disease over the last 10 years, vivax malaria has not been well controlled and has remained continuously endemic. We focused interviewed and examined the charts of 28 confirmed vivax malaria patients given malarial therapy for whom daily records were kept from Gimpo-si, Gyeonggido of Korea. Various epidemiological characteristics of vivax malaria, including the incubation period, medication used, and recurrence, and an evaluation of the parasitic characteristics from the focused interviews of patients from this region are described here. Most of the participants indicated the 3 most common symptoms of malaria (headache, chills and fever). Of the 28 cases, 2 experienced a second attack and there were 17 and 11 cases with short- and long-term incubation periods, respectively, yielding a short-term to long-term ratio of 1.5. Based on the parasitemia stages, most of the participants were tested at 5 to 7 days (11 cases) and 7 to 15 days (11 cases) after initial wave of asexual parasites. In conclusion, public health authorities should consider developing management measures to decrease the time lag for diagnosis and drafting unified and robust guidelines for drug use for malaria and drawing up unified and robust guidelines on the use of medication for malaria. It also suggests that routine monitoring, surveillance, and precise medical surveys in high-risk vivax malaria endemic areas are pivotal to controlling this persistent public disease and finally eliminating it from Korea.


Assuntos
Malária Vivax , Humanos , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Plasmodium vivax , República da Coreia/epidemiologia
8.
Korean J Parasitol ; 59(5): 513-518, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34724772

RESUMO

The incidence of vivax malaria in Korea was reduced to a low plateau. For successful elimination of vivax malaria, socio-behavioral changes in the communities are essential. This study aimed to figure out awareness of the inhabitants on the vivax malaria endemicity. The 407 participants including vivax malaria patients and uninfected inhabitants in Gimpo- and Paju-si, Gyeonggi-do, known as high-risk areas in Korea. We used a community-based study design and non-probability sampling method using primary data. Except for the perception about the public health facilities' capability to cope with anti-malaria programs, the 2 groups of participants shared the same level of awareness about public promotional and educational measures and opinions for malaria elimination from the community. Thus, our future goals for malaria prevention and elimination are to develop more active and well-organized community-based education and evaluation programs collaborating with the community healthcare authorities and local governments.


Assuntos
Malária Vivax , Malária , Anticorpos Antiprotozoários , Humanos , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Plasmodium vivax , República da Coreia/epidemiologia
9.
F1000Res ; 10: 779, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621515

RESUMO

Mixed infections with two or more species of Plasmodium are frequently reported due to vector factors, parasite factors (formation of hypnozoites) and host factors (residing in endemic areas, travel to endemic areas, inadequately treated previous infection, lack of compliance to therapy). Here we report a case of a 33-year-old Saudi female who had a significant travel history, and a peripheral blood smear (PBS) revealed mixed infection with P. falciparum and P. vivax. The case was successfully treated with a combination therapy of artemisinin and primaquine with follow up testing at three, seven, 14, and 28 days. Mixed malaria infections are especially reported in travelers to endemic areas. Hence, adequate diagnosis and appropriate treatment of the cases contributes majorly to preventing relapse and controlling the disease. Travel consultations should be given to all travelers before their trips to endemic countries.


Assuntos
Coinfecção , Malária Vivax , Adulto , Coinfecção/tratamento farmacológico , Feminino , Humanos , Malária Vivax/diagnóstico , Malária Vivax/tratamento farmacológico , Plasmodium falciparum , Plasmodium vivax , Centros de Atenção Terciária
11.
Malar J ; 20(1): 431, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717641

RESUMO

BACKGROUND: Although considerable success in reducing the incidence of malaria has been achieved in Brazil in recent years, an increase in the proportion of cases caused by the harder-to-eliminate Plasmodium vivax parasite can be noted. Recurrences in P. vivax malaria cases are due to new mosquito-bite infections, drug resistance or especially from relapses arising from hypnozoites. As such, new innovative surveillance strategies are needed. The aim of this study was to develop an infographic visualization tool to improve individual-level malaria surveillance focused on malaria elimination in the Brazilian Amazon. METHODS: Action Research methodology was employed to deal with the complex malaria surveillance problem in the Amazon region. Iterative cycles were used, totalling four cycles with a formal validation of an operational version of the Malaria Trigram tool at the end of the process. Further probabilistic data linkage was carried out so that information on the same patients could be linked, allowing for follow-up analysis since the official system was not planned in such way that includes this purpose. RESULTS: An infographic user interface was developed for the Malaria Trigram that incorporates all the visual and descriptive power of the Trigram concept. It is a multidimensional and interactive historical representation of malaria cases per patient over time and provides visual input to decision-makers on recurrences of malaria. CONCLUSIONS: The Malaria Trigram is aimed to help public health professionals and policy makers to recognise and analyse different types of patterns in malaria events, including recurrences and reinfections, based on the current Brazilian health surveillance system, the SIVEP-Malária system, with no additional primary data collection or change in the current process. By using the Malaria Trigram, it is possible to plan and coordinate interventions for malaria elimination that are integrated with other parallel actions in the Brazilian Amazon region, such as vector control management, effective drug and vaccine deployment strategies.


Assuntos
Visualização de Dados , Erradicação de Doenças/estatística & dados numéricos , Monitoramento Epidemiológico , Malária Vivax/prevenção & controle , Vigilância da População/métodos , Brasil , Humanos , Plasmodium vivax , Recidiva
12.
Braz J Biol ; 83: e247219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468526

RESUMO

Military conflicts have been significant obstacles in detecting and treating infectious disease diseases due to the diminished public health infrastructure, resulting in malaria endemicity. A variety of violent and destructive incidents were experienced by FATA (Federally Administered Tribal Areas). It was a struggle to pursue an epidemiological analysis due to continuing conflict and Talibanization. Clinical isolates were collected from Bajaur, Mohmand, Khyber, Orakzai agencies from May 2017 to May 2018. For Giemsa staining, full blood EDTA blood samples have been collected from symptomatic participants. Malaria-positive microscopy isolates were spotted on filter papers for future Plasmodial molecular detection by nested polymerase chain reaction (nPCR) of small subunit ribosomal ribonucleic acid (ssrRNA) genes specific primers. Since reconfirming the nPCR, a malariometric study of 762 patients found 679 positive malaria cases. Plasmodium vivax was 523 (77%), Plasmodium falciparum 121 (18%), 35 (5%) were with mixed-species infection (P. vivax plus P. falciparum), and 83 were declared negative by PCR. Among the five agencies of FATA, Khyber agency has the highest malaria incidence (19%) with followed by P. vivax (19%) and P. falciparum (4.1%). In contrast, Kurram has about (14%), including (10.8%) P. vivax and (2.7%) P. falciparum cases, the lowest malaria epidemiology. Surprisingly, no significant differences in the distribution of mixed-species infection among all five agencies. P. falciparum and P. vivax were two prevalent FATA malaria species in Pakistan's war-torn area. To overcome this rising incidence of malaria, this study recommends that initiating malaria awareness campaigns in school should be supported by public health agencies and malaria-related education locally, targeting children and parents alike.


Assuntos
Plasmodium , Criança , Humanos , Epidemiologia Molecular , Paquistão/epidemiologia , Plasmodium/genética , Plasmodium falciparum/genética , Plasmodium vivax/genética
13.
Malar J ; 20(1): 366, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503519

RESUMO

BACKGROUND: In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. METHODS: The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. RESULTS: The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day. CONCLUSION: The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.


Assuntos
Antimaláricos/administração & dosagem , Esquema de Medicação , Malária Vivax/prevenção & controle , Plasmodium vivax/efeitos dos fármacos , Primaquina/administração & dosagem , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Sci Rep ; 11(1): 17928, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504134

RESUMO

Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide. Among the species of Plasmodium causing human malaria, P. vivax is the second most prevalent and the most geographically widespread species. A major target of a pre-erythrocytic vaccine is the P. vivax circumsporozoite protein (PvCSP). In previous studies, we fused two recombinant proteins representing three allelic variants of PvCSP (VK210, VK247 and P. vivax-like) to the mumps virus nucleocapsid protein to enhance immune responses against PvCSP. The objective of the present study was to evaluate the protective efficacy of these recombinants in mice challenged with transgenic P. berghei parasites expressing PvCSP allelic variants. Formulations containing Poly (I:C) or Montanide ISA720 as adjuvants elicited high and long-lasting IgG antibody titers specific to each PvCSP allelic variant. Immunized mice were challenged with two existing chimeric P. berghei parasite lines expressing PvCSP-VK210 and PvCSP-VK247. We also developed a novel chimeric line expressing the third allelic variant, PvCSP-P. vivax-like, as a new murine immunization-challenge model. Our formulations conferred partial protection (significant delay in the time to reach 1% parasitemia) against challenge with the three chimeric parasites. Our results provide insights into the development of a vaccine targeting multiple strains of P. vivax.


Assuntos
Alelos , Imunidade Humoral , Vacinas Antimaláricas/imunologia , Malária Vivax/prevenção & controle , Plasmodium vivax/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Vacinação/métodos , Adjuvantes Imunológicos , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Feminino , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vacinas Antimaláricas/química , Malária Vivax/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Organismos Geneticamente Modificados , Plasmodium berghei/genética , Plasmodium berghei/imunologia , Plasmodium berghei/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas Recombinantes/imunologia
15.
Elife ; 102021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585667

RESUMO

Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia, remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study, we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses, and ex vivo assays. Patterns of clinical features, parasite burden, and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation, and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients' signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia, and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, particularly in the haematopoietic niche of bone marrow and spleen.


Assuntos
Malária Vivax/parasitologia , Parasitemia/parasitologia , Plasmodium vivax/fisiologia , Adulto , Biomassa , Feminino , Humanos , Malária Vivax/patologia , Malária Vivax/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Malar J ; 20(1): 377, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556130

RESUMO

BACKGROUND: Plasmodium spp. sporozoite rates in mosquitoes are used to better understand malaria transmission intensity, the relative importance of vector species and the impact of interventions. These rates are typically estimated using an enzyme-linked immunosorbent assay (ELISA) utilizing antibodies against the circumsporozoite protein of Plasmodium falciparum, Plasmodium vivax VK210 (P. vivax210) or P. vivax VK247 (P. vivax247), employing assays that were developed over three decades ago. The ELISA method requires a separate assay plate for each analyte tested and can be time consuming as well as requiring sample volumes not always available. The bead-based multiplex platform allows simultaneous measurement of multiple analytes and may improve the lower limit of detection for sporozoites. METHODS: Recombinant positive controls for P. falciparum, P. vivax210 and P. vivax247 and previously developed circumsporozoite (cs) ELISA antibodies were used to optimize conditions for the circumsporozoite multiplex bead assay (csMBA) and to determine the detection range of the csMBA. After optimizing assay conditions, known amounts of sporozoites were used to determine the lower limit of detection for the csELISA and csMBA and alternate cut-off measures were applied to demonstrate how cut-off criteria can impact lower limits of detection. Sporozoite rates from 1275 mosquitoes collected in Madagascar and 255 mosquitoes collected in Guinea were estimated and compared using the established csELISA and newly optimized csMBA. All mosquitoes were tested (initial test), and those that were positive were retested (retest). When sufficient sample volume remained, an aliquot of homogenate was boiled and retested (boiled retest), to denature any heat-unstable cross-reactive proteins. RESULTS: Following optimization of the csMBA, the lower limit of detection was 25 sporozoites per mosquito equivalent for P. falciparum, P. vivax210 and P. vivax247 whereas the lower limits of detection for csELISA were found to be 1400 sporozoites for P. falciparum, 425 for P. vivax210 and 1650 for P. vivax247. Combined sporozoite rates after re-testing of samples that initially tested positive for Madagascar mosquitoes by csELISA and csMBA were 1.4 and 10.3%, respectively, and for Guinea mosquitoes 2% by both assays. Boiling of samples followed by csMBA resulted in a decrease in the Madagascar sporozoite rate to 2.8-4.4% while the Guinea csMBA sporozoite rate remained at 2.0%. Using an alternative csMBA cut-off value of median fluorescence intensity (MFI) of 100 yielded a sporozoite rate after confirmational testing of 3.7% for Madagascar samples and 2.0% for Guinea samples. Whether using csMBA or csELISA, the following steps may help minimize false positives: specimens are appropriately stored and bisected anterior to the thorax-abdomen junction, aliquots of homogenate are boiled and retested following initial testing, and an appropriate cut-off value is determined. CONCLUSIONS: The csMBA is a cost-comparable and time saving alternative to the csELISA and may help eliminate false negatives due to a lower limit of detection, thus increasing sensitivity over the csELISA. The csMBA expands the potential analyses that can be done with a small volume of sample by allowing multiplex testing where analytes in addition to P. falciparum, P. vivax210 and P. vivax247 can be added following optimization.


Assuntos
Anopheles/parasitologia , Mosquitos Vetores/parasitologia , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Proteínas de Protozoários/isolamento & purificação , Esporozoítos/isolamento & purificação , Animais , Ensaio de Imunoadsorção Enzimática/métodos , Guiné , Madagáscar
17.
Malar J ; 20(1): 380, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563189

RESUMO

BACKGROUND: Globally, there are over 200 million cases of malaria annually and over 400,000 deaths. Early and accurate detection of low-density parasitaemia and asymptomatic individuals is key to achieving the World Health Organization (WHO) 2030 sustainable development goals of reducing malaria-related deaths by 90% and eradication in 35 countries. Current rapid diagnostic tests are neither sensitive nor specific enough to detect the low parasite concentrations in the blood of asymptomatic individuals. METHODS: Here, an imaging-based sensing technique, particle diffusometry (PD), is combined with loop mediated isothermal amplification (LAMP) on a smartphone-enabled device to detect low levels of parasitaemia often associated with asymptomatic malaria. After amplification, PD quantifies the Brownian motion of fluorescent nanoparticles in the solution during a 30 s video taken on the phone. The resulting diffusion coefficient is used to detect the presence of Plasmodium DNA amplicons. The coefficients of known negative samples are compared to positive samples using a one-way ANOVA post-hoc Dunnett's test for confirmation of amplification. RESULTS: As few as 3 parasite/µL of blood was detectable in 45 min without DNA extraction. Plasmodium falciparum parasites were detected from asymptomatic individuals' whole blood samples with 89% sensitivity and 100% specificity when compared to quantitative polymerase chain reaction (qPCR). CONCLUSIONS: PD-LAMP is of value for the detection of low density parasitaemia especially in areas where trained personnel may be scarce. The demonstration of this smartphone biosensor paired with the sensitivity of LAMP provides a proof of concept to achieve widespread asymptomatic malaria testing at the point of care.


Assuntos
Doenças Assintomáticas/epidemiologia , Testes Diagnósticos de Rotina/métodos , Malária Falciparum/diagnóstico , Malária Vivax/diagnóstico , Parasitemia/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito/normas , Smartphone/estatística & dados numéricos , Criança , Pré-Escolar , Humanos , Lactente , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Uganda
18.
Malar J ; 20(1): 372, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535130

RESUMO

BACKGROUND: Ethiopia embarked on combating malaria with an aim to eliminate malaria from low transmission districts by 2030. A continuous monitoring of malaria prevalence in areas under elimination settings is important to evaluate the status of malaria transmission and the effectiveness of the currently existing malaria intervention strategies. The aim of this study was to assess the prevalence of malaria and associated risk factors in selected areas of Dembiya district. METHODS: A cross-sectional parasitological and retrospective survey was conducted in the two localities of Dembiya District, selected based on their long standing history of implementing malaria prevention and elimination strategies. Thin and thick blood smears collected from 735 randomly selected individuals between October and December, 2018 were microscopically examined for malaria parasites. Six years (2012-2017) retrospective malaria data was collected from the medical records of the health centres. Structured questionnaires were prepared to collect information about the socio-economic data of the population. Logistic regression analysis was used to determine a key risk factor explaining the prevalence of malaria. The data were analysed using SPSS version 20 and p ≤ 0.05 were considered statistically significant. RESULTS: The 6-year retrospective malaria prevalence trend indicates an overall malaria prevalence of 22.4%, out of which Plasmodium falciparum was the dominant species. From a total of 735 slides examined for the presence of malaria parasites, 3.5% (n = 26) were positive for malaria parasites, in which P. falciparum was more prevalent (n = 17; 2.3%), Plasmodium vivax (n = 5; 0.7%), and mixed infections (n = 4; 0.5%). Males were 2.6 times more likely to be infected with malaria than females (AOR = 2.6; 95% CI 1.0, 6.4), and individuals with frequent outdoor activity were 16.4 times more vulnerable than individuals with limited outdoor activities (AOR = 16.4, 95% CI 1.8, 147.9). Furthermore, awareness about malaria transmission was significantly associated with the prevalence of malaria. CONCLUSIONS: Malaria is still a public health problem in Dembiya district irrespective of the past and existing vector control interventions. Therefore, the authorities should work on designing alternative intervention strategies targeting outdoor malaria transmission and improving community awareness about malaria transmission and control methods in the study area. For this, continuous monitoring of vectors' susceptibility, density, and behaviour is very important in such areas.


Assuntos
Coinfecção/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Coinfecção/parasitologia , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Malar J ; 20(1): 369, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535137

RESUMO

BACKGROUND: French Guiana (FG) is a French overseas territory where malaria is endemic. The current incidence rate is 0.74‰ inhabitants, and Plasmodium vivax is widely predominating even though Plasmodium falciparum is still present due to imported cases mainly from Africa. In FG, rapid diagnostic test (SD Malaria Ag P.f/Pan®) is based on the detection of pan-pLDH, PfHRP2, and PfHRP3 antigens, while in South America, the share of deletion of PfHRP2 gene is significantly increasing. Accordingly, the study questions the reliability of RDTs in the Amazonian context. METHODS: The study is retrospective. It is conducted over 4 years and analysed 12,880 rapid diagnostic tests (RDTs) compared to concomitant Blood Film Tests (BFTs) sampled for malaria diagnosis. RESULTS: The global assessment of the accuracy of SD Malaria Ag P.f/Pan® in the diagnostic of malaria shows both Positive and Negative Predictive Values (PPV and NPV) higher than 95%, except for PPV in the diagnosis of malaria to P. falciparum (88%). Overall, the concordance rate between RDT and BFT (positive/positive; negative/negative) was 99.5%. The PPV of the RDT in the follow-up of patients diagnosed with P. falciparum was the lowest during the first 28 days. The PPV of the RDT in the follow-up of patients diagnosed with P. vivax was the lowest during the first 21 days. The global sensitivity of SD Malaria Ag P.f/Pan® test was, on average, 96% (88.2-100) for P. falciparum and 93% (90.6-94.2) for P. vivax. The global specificity was 99.8% (99.5-100) for all included species. CONCLUSION: SD Malaria Ag P.f/Pan® is a reliable rapid test used for the first-line diagnosis in remote healthcare centres. The test results should be interpreted in the light of patient's recent medical history and the date of arrival to FG.


Assuntos
Testes Diagnósticos de Rotina/estatística & dados numéricos , Malária Falciparum/diagnóstico , Malária Vivax/diagnóstico , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Guiana Francesa , Reprodutibilidade dos Testes , Estudos Retrospectivos
20.
Malar J ; 20(1): 373, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535140

RESUMO

BACKGROUND: A key step to advancing the goal of malaria elimination in Viet Nam by 2030 is focusing limited resources for treatment and prevention to groups most at risk for malaria transmission. METHODS: To better understand risk factors for malaria transmission in central Viet Nam, a survey of 1000 malaria positive cases and 1000 malaria negative controls was conducted. Cases and controls were matched for age and gender and self-presented at commune health stations (CHS) in Binh Phuoc, Dak Nong and Dak Lak Provinces. Diagnoses were confirmed with microscopy, rapid diagnostic test and PCR. Participants were interviewed about 50 potential risk factors for malaria, which included information about occupation, forest visitation, travel, healthcare-seeking behaviour and prior use of anti-malaria interventions. Participants were enrolled by trained government health workers and the samples were analysed in Vietnamese government laboratories. Data were analysed by univariable, block-wise and multivariable logistic regression. RESULTS: Among cases, 61.8% had Plasmodium falciparum, 35.2% Plasmodium vivax and 3% mixed species infections. Median (IQR) age was 27 (21-36) years and 91.2% were male. Twenty-five risk factors were associated with being a case and eleven with being a control. Multivariable analysis found that malaria cases correlated with forest workers, recent forest visitation, longer duration of illness, having a recorded fever, number of malaria infections in the past year, having had prior malaria treatment and having previously visited a clinic. CONCLUSIONS: This study demonstrates the benefits of increased statistical power from matched controls in malaria surveillance studies, which allows identification of additional independent risk factors. It also illustrates an example of research partnership between academia and government to collect high quality data relevant to planning malaria elimination activities. Modifiable risk factors and implications of the findings for malaria elimination strategy are presented.


Assuntos
Coinfecção/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/fisiologia , Plasmodium vivax/fisiologia , Fatores de Risco , Vietnã/epidemiologia , Adulto Jovem
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