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1.
MMWR Morb Mortal Wkly Rep ; 68(46): 1062-1068, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31751320

RESUMO

An estimated 219 million cases of malaria occurred worldwide in 2017, causing approximately 435,000 deaths (1). Malaria is caused by intraerythrocytic protozoa of the genus Plasmodium transmitted to humans through the bite of an infective Anopheles mosquito. Five Plasmodium species that regularly cause illness in humans are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi (2). The parasite first develops in the liver before infecting red blood cells. Travelers to areas with endemic malaria can prevent malaria by taking chemoprophylaxis. However, most antimalarials do not kill the liver stages of the parasite, including hypnozoites that cause relapses of disease caused by P. vivax or P. ovale. Therefore, patients with these relapsing species must be treated with two medications: one for the acute infection, and another to treat the hypnozoites (antirelapse therapy). Until recently, primaquine was the only drug available worldwide to kill hypnozoites. Tafenoquine, a long-acting 8-aminoquinoline drug related to primaquine, was approved by the Food and Drug Administration (FDA) on July 20, 2018, for antirelapse therapy (Krintafel) and August 8, 2018, for chemoprophylaxis (Arakoda) (3,4). This report reviews evidence for the efficacy and safety of tafenoquine and provides CDC guidance for clinicians who prescribe chemoprophylaxis for travelers to areas with endemic malaria and treat malaria.


Assuntos
Aminoquinolinas/uso terapêutico , Antimaláricos/uso terapêutico , Malária/prevenção & controle , Guias de Prática Clínica como Assunto , Prevenção Secundária , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicina de Viagem , Estados Unidos
2.
Georgian Med News ; (294): 109-113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687960

RESUMO

Malaria is a parasitic disease. It is one of blood infections caused by malaria plasmodia. The disease is transmitted to a human by a bite of a female mosquito of Anopheles genus. Local malaria transmission in Ukraine has not been registered since 1956, however, every year some imported cases occur. In 2017, 45 cases of malaria were imported to Ukraine: 80% of them were caused by P. falciparum. The aim of the research is to present a case of imported tropical malaria in a pregnant woman with the development of malaria coma. An unusual course of the illness made diagnoses difficult due to partial immunity of the patient caused by multiple previous invasions of malaria plasmodia. The diagnosis was confirmed by blood microscopy. A literature on epidemiology, clinical findings and current tropical malaria course has been scanned as well. In the presence of an appropriate epidemiological anamnesis, the patients with fever of unknown genesis should first of all be examined for malaria, the most socially significant tropical disease. It is necessary to define the type of malarial plasmodium by repeated blood parasitoscopy by a thick-blood film and blood smear coloured by Gimza-Romanovsky method. Doctors' vigilance against malaria allows preventing complicated forms and late relapses of this malignant invasion. The countries free of malaria can also face this problem and therefore they should be ready to diagnose and treat this disease effectively. The infectious diseases hospitals of Ukraine should be supplied with antimalarial drugs.


Assuntos
Coma/parasitologia , Malária/diagnóstico , Plasmodium/isolamento & purificação , Animais , Antimaláricos/uso terapêutico , Coma/etiologia , Feminino , Humanos , Malária/tratamento farmacológico , Gravidez , Gestantes , Viagem , Ucrânia
3.
Mikrobiyol Bul ; 53(4): 472-479, 2019 Oct.
Artigo em Turco | MEDLINE | ID: mdl-31709945

RESUMO

In spite of the fact that Plasmodium vivax is the leading causative agent of malaria in our country, imported malaria cases have been reported, recently. In this report, two malaria cases originated from sub-Saharan Africa, and their diagnostic and therapeutic approaches were aimed to be presented. First case, 45-year-old male, who has been working in Republic of Ghana, was admitted to Hacettepe University Hospitals Emergency Service with complaints of fever, sweating and shivering, after returning to Turkey. On admission, his general condition was fine and his physical examination revealed no pathological finding. After his admission, a fever episode occured and his blood tests revealed anemia, trombocytopenia and increased alkaline phosphatase level. Second case, 39-year-old-male admitted to the emergency service with the complaints of fever, shivering and myalgia. His physical examination revealed decreased breath sounds and splenomegaly, his laboratory tests resulted in pansitopenia and elevated liver enzymes. In the thick blood smears of the patients ring formed young trophozoites are detected and in the thin films multiple ring forms demonstrated in one erythrocyte with the absence of mature trophozoites and schizont forms, which were compatible with falciparum malaria. The rapid antigen test (Digamed, Belgium) of the second case found to be positive for both Plasmodium falciparum and P.vivax and this patient followed-up in intensive care unit due to his deterioration of general condition, respiratory distress, hematuria and change of consciousness. Neither cases were commenced on malaria prophylaxis. Both patients have been in countries which chloroquine resistance is commonly seen, they were treated with artemether/lumefantrine as current World Health Organization recommended. Targeting hypnozoites of P.vivax, primaquine was added to the therapy of the second patient. Both patients resulted in cure. In conclusion, while travelling to endemic countries, people should be informed about the importance of malaria prophylaxis and prophylaxis should be commenced immediately and continued appropriately. Additionally, malaria should always be considered in the differential diagnosis of high fever for the patients who admitted to the hospital with a travelling history to these countries.


Assuntos
Antimaláricos , Combinação Arteméter e Lumefantrina , Malária , Primaquina , Adulto , África ao Sul do Saara , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/tratamento farmacológico , Doenças Transmissíveis Importadas/parasitologia , Doenças Transmissíveis Importadas/prevenção & controle , Humanos , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/parasitologia , Malária/prevenção & controle , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum , Plasmodium vivax , Primaquina/uso terapêutico , Viagem , Resultado do Tratamento , Turquia
4.
BMC Public Health ; 19(1): 1467, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694607

RESUMO

BACKGROUND: Malaria and tetanus infections among pregnant women represent two major public health problems in sub-Saharan Africa. Optimum use of Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (IPTp-SP) and immunization against tetanus among pregnant women during antenatal care (ANC) visits are recommended strategies to prevent these issues. Despite these recommendations, many women in Africa remain deprived of these cost-effective and life-saving interventions. In this study, we aimed to examine the prevalence of women using these two services, and the association between women's uptake of IPTp-SP and tetanus toxoid (TT) with antenatal care use in Ivory Coast. METHODS: This study was based on the fifth round of Multiple Indicator Cluster Survey (MICS 5) conducted in Ivory Coast in 2016. Participants were 9583 women aged between 15 and 49 years. Outcomes were TT and Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). Data analysis was conducted using bivariate and multiple logistic regression. RESULTS: In this study, the prevalence of taking TT immunization and IPTp-SP drugs was 81.97 and 17.83% respectively. Of the participants who took these drugs at all, the prevalence of taking adequate doses of TT immunization was 78.75% and that of IPTp-SP was 35.46%. In the multivariable analysis model, higher age groups, 25-29 years (OR = 2.028, 95%CI = 1.120-3.669) were found to be positively associated with uptake of adequate doses of IPTp-SP drugs. Women who attended at least four ANC visits had higher odds of taking IPTp-SP drugs (OR = 1.656, 95%CI = 1.194-2.299) and TT immunization (OR = 2.347, 95%CI = 1.384-3.981), and also had higher odds of receiving adequate doses of IPTp-SP drugs (OR = 3.291, 95%CI = 2.157-5.020) and that of TT immunization (OR = 1.968, 95%CI = 1.398-2.771). The odds of taking IPTp-SP drugs were significantly higher among women with primary (OR = 2.504, 95%CI = 1.020-6.146) and secondary/higher education (OR = 3.298, 95%CI = 1.343-8.097) compared to those with no education. Also, women with higher parity had lower odds of taking TT immunization (OR = 0.218, 95%CI = 0.055-0.858) compared to those with lower parity. Findings from this study also revealed that the odds of taking adequate doses of IPTp-SP drugs were significantly lower among participants from Mandé du Nord ethnicity (OR = 0.378,95%CI = 0.145-0.983) compared to those from other ethnicities. CONCLUSION: In this study, uptake of IPTp-SP drugs was much lower than TT immunization. High number of ANC visits were found to be significantly associated with taking IPTp-SP drugs and TT immunization and also with that of taking them in adequate doses. Vaccination promotion is necessary to protect pregnant women and reduce adverse health outcomes among the newborn in Ivory Coast.


Assuntos
Antimaláricos/uso terapêutico , Malária/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal/estatística & dados numéricos , Toxoide Tetânico/uso terapêutico , Tétano/prevenção & controle , Adolescente , Adulto , Costa do Marfim , Combinação de Medicamentos , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Análise Multivariada , Gravidez , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Inquéritos e Questionários , Adulto Jovem
5.
BMC Public Health ; 19(1): 1294, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615478

RESUMO

BACKGROUND: The hematological changes following the initial drug regimen has been poorly understood in Thailand. This study was designed to determine the prevalence of malaria parasite recurrence and hematological alteration of patients during the initial drug regimen. METHODS: A retrospective study was conducted at Phop Phra Hospital, Tak Province, located in northwestern Thailand. All data from patients who were diagnosed with Plasmodium spp. infection - including types of Plasmodium spp., clinical characteristics, and hematological parameters - were retrieved and analyzed. RESULTS: The results demonstrated that during years 2012-2018, 95 out of 971 patients (9.78%) were infected with malaria two or more times. The gender, nationality, symptom of headache, type of Plasmodium spp., and career of each patient were associated with recurrence (P-value< 0.05). Among patients treated with malarial drug, the leukocyte count and red cell distribution width (RDW) were significantly changed when compared to untreated patients with recurrence (P-value< 0.05). CONCLUSION: This study indicated the high prevalence of malarial recurrence in Tak Province, Western Thailand, and its relationship to certain characteristics of individuals. Patients who were treated with antimalarial drugs exhibited leukocyte and RDW changes following the initial drug regimen. This data could be useful for prompt detection, treatment, and prevention of malarial recurrence in endemic areas of Thailand.


Assuntos
Antimaláricos/uso terapêutico , Índices de Eritrócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Malária/tratamento farmacológico , Malária/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Estudos Retrospectivos , Tailândia/epidemiologia , Resultado do Tratamento , Adulto Jovem
6.
BMC Infect Dis ; 19(1): 872, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640574

RESUMO

BACKGROUND: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. METHODS: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. RESULTS: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. CONCLUSIONS: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.


Assuntos
Antimaláricos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Adolescente , Adulto , Álcool Desidrogenase/genética , Cloroquina/uso terapêutico , Estudos Transversais , República Democrática do Congo/epidemiologia , Combinação de Medicamentos , Resistência a Medicamentos/genética , Frequência do Gene , Humanos , Estudos Longitudinais , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Mutação , Plasmodium falciparum/genética , Prevalência , Proteínas de Protozoários/genética , Pirimetamina/uso terapêutico , Análise Espaço-Temporal , Sulfadoxina/uso terapêutico , Adulto Jovem
7.
BMC Public Health ; 19(1): 1330, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640635

RESUMO

BACKGROUND: To reduce the under-five mortality (U5M), fine-gained spatial assessment of the effects of health interventions is critical because national averages can obscure important sub-national disparities. In turn, sub-national estimates can guide control programmes for spatial targeting. The purpose of our study is to quantify associations of interventions with U5M rate at national and sub-national scales in Uganda and to identify interventions associated with the largest reductions in U5M rate at the sub-national scale. METHODS: Spatially explicit data on U5M, interventions and sociodemographic indicators were obtained from the 2011 Uganda Demographic and Health Survey (DHS). Climatic data were extracted from remote sensing sources. Bayesian geostatistical Weibull proportional hazards models with spatially varying effects at sub-national scales were utilized to quantify associations between all-cause U5M and interventions at national and regional levels. Bayesian variable selection was employed to select the most important determinants of U5M. RESULTS: At the national level, interventions associated with the highest reduction in U5M were artemisinin-based combination therapy (hazard rate ratio (HRR) = 0.60; 95% Bayesian credible interval (BCI): 0.11, 0.79), initiation of breastfeeding within 1 h of birth (HR = 0.70; 95% BCI: 0.51, 0.86), intermittent preventive treatment (IPTp) (HRR = 0.74; 95% BCI: 0.67, 0.97) and access to insecticide-treated nets (ITN) (HRR = 0.75; 95% BCI: 0.63, 0.84). In Central 2, Mid-Western and South-West, largest reduction in U5M was associated with access to ITNs. In Mid-North and West-Nile, improved source of drinking water explained most of the U5M reduction. In North-East, improved sanitation facilities were associated with the highest decline in U5M. In Kampala and Mid-Eastern, IPTp had the largest associated with U5M. In Central1 and East-Central, oral rehydration solution and postnatal care were associated with highest decreases in U5M respectively. CONCLUSION: Sub-national estimates of the associations between U5M and interventions can guide control programmes for spatial targeting and accelerate progress towards mortality-related Sustainable Development Goals.


Assuntos
Serviços de Saúde da Criança/organização & administração , Mortalidade da Criança/tendências , Bem-Estar da Criança/estatística & dados numéricos , Determinantes Sociais da Saúde/estatística & dados numéricos , Antimaláricos/uso terapêutico , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Inseticidas/uso terapêutico , Modelos de Riscos Proporcionais , Fatores de Risco , Uganda
9.
Malar J ; 18(1): 349, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619243

RESUMO

BACKGROUND: The resistance of Plasmodium falciparum to artemisinin has been identified in Asia and some parts of Africa. The drug resistance of P. falciparum will be an obstacle to the successful elimination of malaria by 2025. Whole-genome sequencing of the artemisinin-resistant parasite line revealed mutations on the k13 gene associated with drug resistance in P. falciparum. To understand the artemisinin resistance of the imported P. falciparum cases from Africa, the mutations in the k13 gene in parasites from imported malaria cases in Guangxi Province were detected and the treatment efficiency of artesunate monotherapy was observed. METHODS: DNA was extracted from 319 blood samples from migrant workers with P. falciparum infection who returned to their hometown in Guangxi Province from Africa between 2014 and 2017. The k13-propeller gene was amplified by nested PCR, and sequencing, gene mutation frequency and geographic difference of imported P. falciparum cases were analysed by comparison with the wild-type strain. Of 319 patients, 158 were P. falciparum-infected and were treated with intravenous injection of artesunate and were observed, including the time of asexual stage clearance and the dose of artesunate used. RESULTS: Of the 319 P. falciparum samples, 12 samples had the k13-propeller mutation, and 11 point mutations were detected; 5 were non-synonymous mutations (T474I, A481T, A578S, V603E, G665S) and were not associated with artemisinin resistance. The clinical treatment observation showed that the median (IQR) dose of artesunate for peripheral blood parasite asexual stage clearance was 407.55 (360-510) mg, and the D3 parasite clearance rate was 70.25%, including the five k13-propeller mutations of P. falciparum. After 7 days of treatment, 98.73% of cases were cleared. Two cases were treated with artemisinin for 8 days with a 960-mg dose to completely clear the asexual parasite, but they did not have a mutation in the k13 gene. CONCLUSIONS: Five mutations of the k13-propeller gene in 319 P. falciparum samples from patients returning from Africa were identified. The frequency of the k13-propeller mutants was low, and the mutations were not strongly associated with artemisinin resistance. The median (IQR) dose of artesunate monotherapy in actual clinical treatment to remove asexual parasite stages was 407.55 (360-510) mg, equivalent to D3-D4. Some P. falciparum cases without a k13-propeller mutation showed obvious delayed clearance of the parasite from peripheral blood. Trial registration The diagnosis of malaria and the treatment of malaria-infected patients are the routine work of Centres for Disease Control and Prevention. Information on the patients was conveyed with the patient's approval, and the research aim, methods, risks and benefits of the study were explained in detail to the patients.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Artesunato/uso terapêutico , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , China , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Migrantes/estatística & dados numéricos
10.
Rev Med Liege ; 74(10): 503-507, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31609552

RESUMO

Malaria is a life-threatening infection which affects especially non-immune subjects including children under the age of 5. Imported malaria is a rare disease in Europe but, with the increasing number of travelers and people who are visiting friends or relatives, it is important not to neglect it. Severe malaria leads to many pediatric deaths in countries with limited resources. The treatment of choice is a parenteral antimalarial. For a long time, only quinine was used in that case. Based on strong studies conducted in Asia and Africa, WHO (World Health Organization) has recommended the use of artesunate as a first-line treatment for severe malaria in adults and children since 2010.The use of artesunate has shown a reduction in mortality rate in severe malaria. In Europe, there still are several barriers to the implementation of these recommendations, especially in terms of availability and cost. In pediatrics departments and adults, artesunate is the first-line treatment in severe malaria, although close monitoring is essential, especially at the hematological side, monitoring the development of delayed post-artesunate haemolytic anemia (PADH), a known side effect.


Assuntos
Antimaláricos , Artemisininas , Artesunato , Malária , Antimaláricos/uso terapêutico , Artesunato/uso terapêutico , Criança , Europa (Continente) , Humanos , Malária/tratamento farmacológico , Pediatria
11.
Malar J ; 18(1): 340, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590661

RESUMO

BACKGROUND: G6PD enzyme deficiency is a common enzymatic X-linked disorder. Deficiency of the G6PD enzyme can cause free radical-mediated oxidative damage to red blood cells, leading to premature haemolysis. Treatment of Plasmodium vivax malaria with primaquine poses a potential risk of mild to severe acute haemolytic anaemia in G6PD deficient people. In this study, the prevalence and distribution of G6PD mutations were investigated across broad areas of Ethiopia, and tested the association between G6PD genotype and phenotype with the goal to provide additional information relevant to the use of primaquine in malaria treatment. METHODS: This study examined G6PD mutations in exons 3-11 for 344 febrile patient samples collected from seven sites across Ethiopia. In addition, the G6PD enzyme level of 400 febrile patient samples from Southwestern Ethiopia was determined by the CareStart™ biosensor. The association between G6PD phenotype and genotype was examined by Fisher exact test on a subset of 184 samples. RESULTS: Mutations were observed at three positions of the G6PD gene. The most common G6PD mutation across all sites was A376G, which was detected in 21 of 344 (6.1%) febrile patients. Thirteen of them were homozygous and eight were heterozygous for this mutation. The G267+119C/T mutation was found in 4 (1.2%) individuals in South Ethiopia, but absent in other sites. The G1116A mutation was also found in 4 (1.2%) individuals from East and South Ethiopia. For the 400 samples in the south, 17 (4.25%) were shown to be G6PD-deficient. G6PD enzyme level was not significantly different by age or gender. Among a subset of 202 febrile patients who were diagnosed with malaria, 11 (5.45%) were G6PD-deficient. These 11 infected samples were diagnosed with Plasmodium vivax by microscopy. Parasitaemia was not significantly different between the G6PD-deficient and G6PD-normal infections. CONCLUSIONS: The prevalence of G6PD deficiency is modest among febrile patients in Ethiopia. G6PD deficiency testing is thus recommended before administrating primaquine for radical cure of P. vivax infected patients. The present study did not indicate a significant association between G6PD gene mutations and enzyme levels.


Assuntos
Antimaláricos/uso terapêutico , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Malária Vivax/prevenção & controle , Primaquina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/efeitos adversos , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Primaquina/efeitos adversos , Adulto Jovem
13.
Rev Soc Bras Med Trop ; 52: e20190163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618306

RESUMO

Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated malaria. Currently, there appears to be a downward trend in the efficacy of ACT in some parts of sub-Saharan Africa because some patients have been positive for Plasmodium parasite 3 days after artemether-lumefantrine treatment. We reported three cases of possible parasite resistance to artemether-lumefantrine therapy. All subjects had complete parasite clearance when treated with other antimalarial drugs. This observation necessitates the urgent need to re-evaluate artemether-lumefantrine medication in Nigeria since it is one of the most commonly used ACT drug.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Adulto , Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Adulto Jovem
14.
Malar J ; 18(1): 331, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31558149

RESUMO

BACKGROUND: Febrile children seen in malaria hypo-endemic settings, such as the Greater Accra region (GAR) of Ghana are more likely to be suffering from a non-malarial febrile illness compared to those seen in hyper-endemic settings. The need for prescribers to rely on malaria test results to guide treatment practices in the GAR is even greater. This study was designed to investigate the factors associated with inappropriate artemisinin-based combination therapy (ACT) prescription. METHODS: A survey was conducted in six health facilities in the region in 2015. Treatment practices for febrile outpatient department (OPD) patients were obtained from their records. Prescribers were interviewed and availability of malaria commodities were assessed. The primary outcome was the proportion of patients prescribed ACT inappropriately. Independent variables included patient age and access to care, prescriber factors (professional category, work experience, access to guidelines, exposure to training). Data were analysed using Stata at 95% CI (α-value of 0.05). Frequencies and means were used to describe the characteristics of patients and prescribers. To identify the predictors of inappropriate ACT prescription, regression analyses were performed accounting for clustering. RESULTS: Overall, 2519 febrile OPD records were analysed; 45.6% (n = 1149) were younger than 5 years. Only 40.0% of patients were tested. The proportion of patients who were prescribed ACT inappropriately was 76.4% (n = 791 of 1036). Of these 791 patients, 141 (17.8%) were prescribed anti-malarial injections. Patients seen in facilities with rapid diagnostic tests (RDT) in stock were less likely to be prescribed ACT inappropriately, (AOR: 0.04, 95% CI 0.01-0.14, p < 0.001) compared to those seen in facilities with RDT stock-outs. Prescribers who had been trained on malaria case management within the past year were 4 times more likely to prescribe ACT inappropriately compared to those who had not been trained (AOR: 4.1; 95% CI (1.5-11.6); p < 0.01). Patients seen by prescribers who had been supervised were 8 times more likely to be  prescribed ACT inappropriately. CONCLUSION: Inappropriate ACT prescription to OPD febrile cases was high. Training and supervision of health workers appears not to be yielding the desired outcomes. Further research is needed to understand this observation.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Febre/tratamento farmacológico , Febre/parasitologia , Prescrição Inadequada/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Febre/epidemiologia , Gana/epidemiologia , Pessoal de Saúde , Humanos , Lactente , Injeções , Malária/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Inquéritos e Questionários , Adulto Jovem
15.
Korean J Parasitol ; 57(4): 369-377, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31533403

RESUMO

Artemisinin-based combination therapy (ACT) resistance is widespread throughout the Greater Mekong Subregion. This raises concern over the antimalarial treatment in Thailand since it shares borders with Cambodia, Laos, and Myanmar where high ACT failure rates were reported. It is crucial to have information about the spread of ACT resistance for efficient planning and treatment. This study was to identify the molecular markers for antimalarial drug resistance: Pfkelch13 and Pfmdr1 mutations from 5 provinces of southern Thailand, from 2012 to 2017, of which 2 provinces on the Thai- Myanmar border (Chumphon and Ranong), one on Thai-Malaysia border (Yala) and 2 from non-border provinces (Phang Nga and Surat Thani). The results showed that C580Y mutation of Pfkelch13 was found mainly in the province on the Thai-Myanmar border. No mutations in the PfKelch13 gene were found in Surat Thani and Yala. The Pfmdr1 gene isolated from the Thai-Malaysia border was a different pattern from those found in other areas (100% N86Y) whereas wild type strain was present in Phang Nga. Our study indicated that the molecular markers of artemisinin resistance were spread in the provinces bordering along the Thai-Myanmar, and the pattern of Pfmdr1 mutations from the areas along the international border of Thailand differed from those of the non-border provinces. The information of the molecular markers from this study highlighted the recent spread of artemisinin resistant parasites from the endemic area, and the data will be useful for optimizing antimalarial treatment based on regional differences.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Marcadores Genéticos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/genética , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Sequência de Bases , DNA de Protozoário/química , Combinação de Medicamentos , Resistência a Medicamentos/genética , Genes MDR/genética , Humanos , Repetição Kelch/genética , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Mutação , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Reação em Cadeia da Polimerase , Tailândia
16.
Malar J ; 18(1): 319, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533729

RESUMO

BACKGROUND: Plasmodium falciparum, the deadliest causative agent of malaria, has high prevalence in Nigeria. Drug resistance causing failure of previously effective drugs has compromised anti-malarial treatment. On this basis, there is need for a proactive surveillance for resistance markers to the currently recommended artemisinin-based combination therapy (ACT), for early detection of resistance before it become widespread. METHODS: This study assessed anti-malarial resistance genes polymorphism in patients with uncomplicated P. falciparum malaria in Lagos, Nigeria. Sanger and Next Generation Sequencing (NGS) methods were used to screen for mutations in thirty-seven malaria positive blood samples targeting the P. falciparum chloroquine-resistance transporter (Pfcrt), P. falciparum multidrug-resistance 1 (Pfmdr1), and P. falciparum kelch 13 (Pfk13) genes, which have been previously associated with anti-malarial resistance. RESULTS: Expectedly, the NGS method was more proficient, detecting six Pfmdr1, seven Pfcrt and three Pfk13 mutations in the studied clinical isolates from Nigeria, a malaria endemic area. These mutations included rare Pfmdr1 mutations, N504K, N649D, F938Y and S967N, which were previously unreported. In addition, there was moderate prevalence of the K76T mutation (34.6%) associated with chloroquine and amodiaquine resistance, and high prevalence of the N86 wild type allele (92.3%) associated with lumefantrine resistance. CONCLUSION: Widespread circulation of mutations associated with resistance to current anti-malarial drugs could potentially limit effective malaria therapy in endemic populations.


Assuntos
Antimaláricos/uso terapêutico , Resistência a Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Nigéria/epidemiologia , Plasmodium falciparum/efeitos dos fármacos , Prevalência , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
17.
Malar J ; 18(1): 318, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533845

RESUMO

BACKGROUND: Intermittent preventive treatment (IPT) of malaria is recommended as policy for certain high-risk populations, but not currently for schoolchildren. A cluster-randomized trial was conducted to evaluate the effect of IPT with dihydroartemisinin-piperaquine (DP) on primary schoolchildren in Jinja, Uganda. Results of the impact of IPT of schoolchildren on community-level transmission have been reported previously. Here, secondary outcomes from a school-based survey are presented. METHODS: Eighty-four clusters (one primary school plus 100 households) were randomized to intervention and control (1:1 ratio). Participants from intervention schools received monthly IPT with DP for up to 6 rounds (June-December 2014). At endline (November-December 2014), randomly selected children from all 84 schools were surveyed (13 per school) and thick blood smears were done. Those with fever or history of fever were tested with rapid diagnostic tests (RDTs) for malaria. Haemoglobin was measured in every fifth participant. Outcome measures included prevalence of asexual parasites and gametocytes (by microscopy), and prevalence of anaemia. Prevalence outcomes were analysed using generalized linear Poisson models with log link function, incorporating a cluster-level random intercept and quantified using prevalence risk ratios. RESULTS: Among 23,280 students listed on the 42 intervention school registers, 10,079 (43.3%) aged 5-20 years were enrolled into the IPT intervention and received at least one dose of DP; of these, 9286 (92.1%) received at least one full (3-day) course. In total, 1092 children were enrolled into the final school survey (546 per arm) and had a thick blood smear done; of these, 255 had haemoglobin measured (129 intervention, 126 control). Children in the intervention arm were less likely to have asexual parasites (9.2% intervention vs 44.1% control, adjusted risk ratio [aRR] 0.22 [95% CI 0.16-0.30] p < 0.001), gametocytes (3.1% intervention vs 9.5% control, aRR 0.34 [95% CI 0.20-0.56] p < 0.001), fever (20.2% intervention vs 56.2% control, aRR 0.35 [95% CI 0.25-0.50] p < 0.001), or symptomatic malaria (5.1% intervention vs 35.7% control, aRR 0.14 [95% CI 0.08-0.26] p < 0.001). Prevalence of anaemia and mean haemoglobin were similar in both study arms. CONCLUSIONS: School-aged children are a major reservoir of malaria parasites. Delivering IPT to schoolchildren would benefit individual children and may reduce transmission. School-based IPT could help to intensify malaria control toward elimination, and should be considered for policies and programmes. Trial registration Clinicaltrials.gov (NCT02009215), Registered 11 December 2013. https://clinicaltrials.gov/ct2/show/NCT02009215.


Assuntos
Anemia/epidemiologia , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/prevenção & controle , Quinolinas/uso terapêutico , Adolescente , Criança , Pré-Escolar , Análise por Conglomerados , Combinação de Medicamentos , Feminino , Humanos , Malária/epidemiologia , Masculino , Prevalência , Estudantes , Uganda/epidemiologia
18.
Malar J ; 18(1): 307, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488139

RESUMO

BACKGROUND: While bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides, where humans or animals are treated with drugs that kill mosquitoes upon ingestion via blood meal, are therefore generating much interest. This work explores the conditions under which long-lasting systemic insecticides would have a substantial impact on transmission and burden. METHODS: Hypothetical long-lasting systemic insecticides with effective durations ranging from 14 to 90 days are simulated using an individual-based mathematical model of malaria transmission. The impact of systemic insecticides when used to complement existing vector control and drug campaigns is evaluated in three settings-a highly seasonal high-transmission setting, a near-elimination setting with seasonal travel to a high-risk area, and a near-elimination setting in southern Africa. RESULTS: At 60% coverage, a single round of long-lasting systemic insecticide with effective duration of at least 60 days, distributed at the start of the season alongside a seasonal malaria chemoprevention campaign in a high-transmission setting, results in further burden reduction of 30-90% depending on the sub-populations targeted. In a near-elimination setting where transmission is sustained by seasonal travel to a high-risk area, targeting high-risk travellers with systemic insecticide with effective duration of at least 30 days can result in likely elimination even if intervention coverage is as low as 50%. In near-elimination settings with robust vector control, the addition of a 14-day systemic insecticide alongside an anti-malarial in mass drug administration (MDA) campaigns can decrease the necessary MDA coverage from about 85% to the more easily achievable 65%. CONCLUSIONS: While further research into the safety profile of systemic insecticides is necessary before deployment, models predict that long-lasting systemic insecticides can play a critical role in reducing burden or eliminating malaria in a range of contexts with different target populations, existing malaria control methods, and transmission intensities. Continued investment in lengthening the duration of systemic insecticides and improving their safety profile is needed for this intervention to achieve its fullest potential.


Assuntos
Antimaláricos/uso terapêutico , Controle de Doenças Transmissíveis/métodos , Inseticidas/uso terapêutico , Malária/prevenção & controle , Controle de Mosquitos/métodos , Humanos , Modelos Teóricos , Nigéria , Zâmbia
19.
Malar J ; 18(1): 304, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481075

RESUMO

BACKGROUND: Studies of the association between malaria in pregnancy (MiP) and malaria during infancy have provided mixed results. A systematic review was conducted to evaluate available evidence on the impact of Plasmodium falciparum malaria infection during pregnancy, and intermittent preventive treatment of malaria during pregnancy (IPTp), on the risk of clinical malaria or parasitaemia during infancy. METHODS: MEDLINE, EMBASE, Global Health, and Malaria in Pregnancy Library databases were searched from inception to 22 May 2018 for articles published in English that reported on associations between MiP and malaria risk in infancy. Search terms included malaria, Plasmodium falciparum, pregnancy, placenta, maternal, prenatal, foetal, newborn, infant, child or offspring or preschool. Randomized controlled trials and prospective cohort studies, which followed infants for at least 6 months, were included if any of the following outcomes were reported: incidence of clinical malaria, prevalence of parasitaemia, and time to first episode of parasitaemia or clinical malaria. Substantial heterogeneity between studies precluded meta-analysis. Thus, a narrative synthesis of included studies was conducted. RESULTS: The search yielded 14 published studies, 10 prospective cohort studies and four randomized trials; all were conducted in sub-Saharan Africa. Infants born to mothers with parasitaemia during pregnancy were at higher risk of malaria in three of four studies that assessed this association. Placental malaria detected by microscopy or histology was associated with a higher risk of malaria during infancy in nine of 12 studies, but only one study adjusted for malaria transmission intensity. No statistically significant associations between the use of IPTp or different IPTp regimens and the risk of malaria during infancy were identified. CONCLUSION: Evidence of an association between MiP and IPTp and risk of malaria in infancy is limited and of variable quality. Most studies did not adequately adjust for malaria transmission intensity shared by mothers and their infants. Further research is needed to confirm or exclude an association between MiP and malaria in infancy. Randomized trials evaluating highly effective interventions aimed at preventing MiP, such as IPTp with dihydroartemisinin-piperaquine, may help to establish a causal association between MiP and malaria in infancy.


Assuntos
Malária Falciparum/epidemiologia , Parasitemia/epidemiologia , Plasmodium falciparum/fisiologia , Complicações Parasitárias na Gravidez/epidemiologia , Antimaláricos/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Malária Falciparum/parasitologia , Masculino , Parasitemia/parasitologia , Gravidez , Complicações Parasitárias na Gravidez/parasitologia , Risco
20.
Malar J ; 18(1): 267, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31477109

RESUMO

Parasite resistance against anti-malarial drugs is a major threat to the ongoing malaria control and elimination strategies. This is especially true since resistance to the currently recommended artemisinins and partner drugs has been confirmed in South East Asia (SEA) and new anti-malarial compounds are not expected to be available in the near future. Spread from SEA or independent emergence of artemisinin resistance in sub-Saharan Africa (SSA) could reverse the achievements in malaria control that have been attained in the past two decades and derail the ongoing elimination strategies. The current surveillance of clinical efficacy and resistance to anti-malarial drugs is based on efficacy trials to assess the clinical performance of anti-malarials, in vivo/ex vivo assessment of parasite susceptibility to anti-malarials and prevalence of known molecular markers of drug resistance. Whereas clinical efficacy trials are restricted by cost and the complex logistics of patient follow-up, molecular detection of genetic mutations associated with resistance or reduced susceptibility to anti-malarials is by contrast a simple and powerful tool for early detection and monitoring of the prevalence of resistant parasites at population level. This provides needed information before clinical failure emerges, allowing policy makers to anticipate problems and respond. The various methods previously used in detection of molecular markers of drug resistance share some limitations: low-throughput, and high costs per sample and demanding infrastructure. However, recent technological advances including next-generation sequencing (NGS) methodologies promise greatly increased throughput and reduced costs, essentially providing unprecedented potential to address different research and operational questions of relevance for drug policy. This review assesses the potential role of NGS to provide comprehensive information that could guide drug policies in malaria endemic countries and looks at the foreseeable challenges facing the establishment of NGS approaches for routine surveillance of parasite resistance to anti-malarials in SSA.


Assuntos
Antimaláricos/uso terapêutico , Controle de Doenças Transmissíveis/legislação & jurisprudência , Resistência a Medicamentos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Plasmodium falciparum/genética , Formulação de Políticas , África ao Sul do Saara , Controle de Doenças Transmissíveis/métodos , Quimioterapia Combinada , Saúde Global/legislação & jurisprudência , Saúde Global/normas , Legislação de Medicamentos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos
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