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1.
Rev Med Suisse ; 16(693): 978-983, 2020 May 13.
Artigo em Francês | MEDLINE | ID: mdl-32401437

RESUMO

Long-term travelers are particularly exposed to malaria. It is essential to inform them about this risk, the recognition of the symptoms of the disease and the need for prompt treatment. Addressing any fears of travelers and answering their questions improve therapeutic adherence. Personal protective measures (repellents, mosquito nets) are fundamental and safe to reduce exposure to the vector of the disease. Depending on the individual risk of malaria and the special vulnerability of the traveler, short-term or prolonged chemoprophylaxis and/or emergency self-treatment and a rapid diagnostic test for malaria may be offered.


Assuntos
Antimaláricos/administração & dosagem , Educação em Saúde , Malária/prevenção & controle , Doença Relacionada a Viagens , Animais , Antimaláricos/uso terapêutico , Quimioprevenção , Diagnóstico Precoce , Humanos , Malária/diagnóstico , Malária/tratamento farmacológico , Mosquiteiros , Mosquitos Vetores , Prevenção Secundária
2.
Emerg Microbes Infect ; 9(1): 830-832, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32338155

RESUMO

The current pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls urgently for effective therapies. Anti-malarial medicine chloroquine (CQ) and particularly its chemical analogue hydroxychloroquine (HCQ) have been recommended as promising candidate therapeutics that are now under either compassionate off-label use or clinical trials for the treatment of COVID-19 patients. However, there are public concerns and disputes about both the safety and efficacy of CQ and HCQ for this new application. Given the fact that for decades HCQ has been approved as an immunomodulatory drug for the long term treatment of chronic rheumatic diseases, as experienced rheumatologists, we would like to share our thoughts in this regard and trigger a brainstorm among clinical care providers for exchanging their diverse opinions on this urgent topic.


Assuntos
Antimaláricos , Antirreumáticos , Antivirais , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina , Pneumonia Viral/tratamento farmacológico , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Comunicação Interdisciplinar , Pandemias , Pneumonia Viral/epidemiologia , Reumatologistas
3.
Lancet ; 395(10233): 1361-1373, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334702

RESUMO

BACKGROUND: In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia). METHODS: We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400. FINDINGS: Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8-48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0-53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0-45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7-57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2-44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5-61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16-0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16-0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10-0·68], p=0·006). No serious adverse events were reported. INTERPRETATION: In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria. FUNDING: Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/métodos , Controle de Mosquitos , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina/administração & dosagem , Análise por Conglomerados , Humanos , Malária Falciparum/epidemiologia , Controle de Mosquitos/métodos , Namíbia/epidemiologia , Plasmodium falciparum , Estudos Soroepidemiológicos
4.
Lancet ; 395(10233): 1345-1360, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32171078

RESUMO

BACKGROUND: Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance. METHODS: In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2-65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non-falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin-piperaquine or dihydroartemisinin-piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate-mefloquine or dihydroartemisinin-piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether-lumefantrine or artemether-lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov, NCT02453308, and is complete. FINDINGS: Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin-piperaquine (183 [17%]), dihydroartemisinin-piperaquine plus mefloquine (269 [24%]), artesunate-mefloquine (73 [7%]), artemether-lumefantrine (289 [26%]), or artemether-lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin-piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin-piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p<0·0001). Efficacy of dihydroartemisinin-piperaquine plus mefloquine in the three sites in Myanmar was 91% (42 of 46; 95% CI 79 to 98) versus 100% (42 of 42; 95% CI 92 to 100) after dihydroartemisinin-piperaquine (risk difference 9%, 95% CI 1 to 17; p=0·12). The 42-day PCR corrected efficacy of dihydroartemisinin-piperaquine plus mefloquine (96% [68 of 71; 95% CI 88 to 99]) was non-inferior to that of artesunate-mefloquine (95% [69 of 73; 95% CI 87 to 99]) in three sites in Cambodia (risk difference 1%; 95% CI -6 to 8; p=1·00). The overall 42-day PCR-corrected efficacy of artemether-lumefantrine plus amodiaquine (98% [281 of 286; 95% CI 97 to 99]) was similar to that of artemether-lumefantrine (97% [279 of 289; 95% CI 94 to 98]; risk difference 2%, 95% CI -1 to 4; p=0·30). Both TACTs were well tolerated, although early vomiting (within 1 h) was more frequent after dihydroartemisinin-piperaquine plus mefloquine (30 [3·8%] of 794) than after dihydroartemisinin-piperaquine (eight [1·5%] of 543; p=0·012). Vomiting after artemether-lumefantrine plus amodiaquine (22 [1·3%] of 1703) and artemether-lumefantrine (11 [0·6%] of 1721) was infrequent. Adding amodiaquine to artemether-lumefantrine extended the electrocardiogram corrected QT interval (mean increase at 52 h compared with baseline of 8·8 ms [SD 18·6] vs 0·9 ms [16·1]; p<0·01) but adding mefloquine to dihydroartemisinin-piperaquine did not (mean increase of 22·1 ms [SD 19·2] for dihydroartemisinin-piperaquine vs 20·8 ms [SD 17·8] for dihydroartemisinin-piperaquine plus mefloquine; p=0·50). INTERPRETATION: Dihydroartemisinin-piperaquine plus mefloquine and artemether-lumefantrine plus amodiaquine TACTs are efficacious, well tolerated, and safe treatments of uncomplicated P falciparum malaria, including in areas with artemisinin and ACT partner-drug resistance. FUNDING: UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and US National Institutes of Health.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Adolescente , Adulto , Amodiaquina/administração & dosagem , Amodiaquina/uso terapêutico , Antraquinonas/administração & dosagem , Antraquinonas/uso terapêutico , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina/administração & dosagem , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/administração & dosagem , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Mefloquina/administração & dosagem , Mefloquina/uso terapêutico , Plasmodium falciparum/efeitos dos fármacos , Reação em Cadeia da Polimerase , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Resultado do Tratamento , Adulto Jovem
6.
BMC Infect Dis ; 19(1): 1025, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795967

RESUMO

BACKGROUND: Treatment for severe malaria must be prompt with effective parenteral antimalarial drugs for at least 24 h to achieve fast parasite clearance, and when the patient can tolerate oral therapy, treatment should be completed with effective artemisinin based combination therapy (ACT) for complete parasite clearance and to prevent recrudescence. We evaluated piperaquine concentration and malaria treatment outcomes among Ugandan children treated for severe malaria with intravenous artesunate (AS) or quinine (QN) plus dihydroartemisinin-piperaquine (DP), in Tororo District Hospital in Eastern Uganda. METHODS: Capillary blood piperaquine concentration data were obtained from a randomized clinical trial whose objective was to evaluate parasite clearance, 42-day parasitological treatment outcomes and safety, following treatment of severe malaria with intravenous AS or QN, plus artemether-lumefantrine or DP among children in Tororo District Hospital, in Eastern Uganda. RESULTS: Piperaquine concentration data from 150 participants who received DP were analyzed. Participants with unadjusted treatment failure had lower median day 7 capillary piperaquine concentration than those with treatment success (34.7 (IQR) (17.9-49.1) vs 66.7 (IQR) (41.8-81.9), p < 0.001), and lower than the recommended day 7 cut off level of 57 ng/mL. There was no difference in median capillary piperaquine concentrations among participants with re-infection and recrudescence (35.3 (IQR) (17.9-55.2) vs 34.8 (IQR) (18.1-45.1), p = 0.847). The risk of treatment failure was two times higher among children with low (< 57 ng/mL) day 7 capillary piperaquine concentration (relative risk: 2.1 CI 1.4-3.1), p < 0.001) compared to children with high day 7 capillary piperaquine concentrations (> 57 ng/mL). CONCLUSION: Considering the low day 7 concentrations of piperaquine reported in the patients studied here, we suggest to adopt the recently recommended higher dose of DP in young children or a prolonged 5-day dosing in children living in malaria endemic areas who have suffered an initial episode of severe malaria in order to achieve adequate drug exposures for effective post-treatment prophylactic effects. TRIAL REGISTRATION: The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Artesunato/uso terapêutico , Malária Falciparum/tratamento farmacológico , Quinina/uso terapêutico , Quinolinas/sangue , Quinolinas/uso terapêutico , Administração Intravenosa , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Artesunato/administração & dosagem , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Malária Falciparum/parasitologia , Masculino , Concentração Osmolar , Plasmodium falciparum/isolamento & purificação , Quinina/administração & dosagem , Quinolinas/administração & dosagem , Recidiva , Resultado do Tratamento , Uganda
7.
Malar J ; 18(1): 428, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852499

RESUMO

BACKGROUND: Sample size calculations for cluster randomized trials are a recognized methodological challenge for malaria research in pre-elimination settings. Positively correlated responses from the participants in the same cluster are a key feature in the estimated sample size required for a cluster randomized trial. The degree of correlation is measured by the intracluster correlation coefficient (ICC) where a higher coefficient suggests a closer correlation hence less heterogeneity within clusters but more heterogeneity between clusters. METHODS: Data on uPCR-detected Plasmodium falciparum and Plasmodium vivax infections from a recent cluster randomized trial which aimed at interrupting malaria transmission through mass drug administrations were used to calculate the ICCs for prevalence and incidence of Plasmodium infections. The trial was conducted in four countries in the Greater Mekong Subregion, Laos, Myanmar, Vietnam and Cambodia. Exact and simulation approaches were used to estimate ICC values for both the prevalence and the incidence of parasitaemia. In addition, the latent variable approach to estimate ICCs for the prevalence was utilized. RESULTS: The ICCs for prevalence ranged between 0.001 and 0.082 for all countries. The ICC from the combined 16 villages in the Greater Mekong Subregion were 0.26 and 0.21 for P. falciparum and P. vivax respectively. The ICCs for incidence of parasitaemia ranged between 0.002 and 0.075 for Myanmar, Cambodia and Vietnam. There were very high ICCs for incidence in the range of 0.701 to 0.806 in Laos during follow-up. CONCLUSION: ICC estimates can help researchers when designing malaria cluster randomized trials. A high variability in ICCs and hence sample size requirements between study sites was observed. Realistic sample size estimates for cluster randomized malaria trials in the Greater Mekong Subregion have to assume high between cluster heterogeneity and ICCs. This work focused on uPCR-detected infections; there remains a need to develop more ICC references for trials designed around prevalence and incidence of clinical outcomes. Adequately powered trials are critical to estimate the benefit of interventions to malaria in a reliable and reproducible fashion. TRIAL REGISTRATION: ClinicalTrials.govNCT01872702. Registered 7 June 2013. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT01872702.


Assuntos
Antimaláricos/administração & dosagem , Malária Falciparum/prevenção & controle , Malária Vivax/prevenção & controle , Administração Massiva de Medicamentos/estatística & dados numéricos , Camboja/epidemiologia , Humanos , Incidência , Laos/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Mianmar/epidemiologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium vivax/efeitos dos fármacos , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Vietnã/epidemiologia
8.
Malar J ; 18(1): 439, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864358

RESUMO

BACKGROUND: A total dose of chloroquine of 25 mg/kg is recommended by the World Health Organization (WHO) to treat malaria by Plasmodium vivax. In several endemic areas, including the Brazilian Amazon basin, anti-malarial drugs are dispensed in small plastic bags at a dosing regimen based on age. This practice can lead to suboptimal dosing of the drug, which can impact treatment outcomes. The aim of the present study was to estimate the extent of sub-dosing of chloroquine in children and adolescents with vivax malaria using an age-based dose regimen, in addition to investigating the influence of age on the plasma concentrations of chloroquine and desethylchloroquine. METHODS: A study of cases was conducted with male patients with a confirmed infection by P. vivax, ages 2 to 14 years, using a combined regimen of chloroquine and primaquine. Height, weight and body surface area were determined at admission on the study. The total dose of chloroquine administered was estimated based on the weight and on the body surface area of the study patients. Chloroquine and desethylchloroquine were measured on Day 7 in each patient included in the study by a high-performance liquid chromatographic method with fluorescence detection. RESULTS: A total of 81 patients were enrolled and completed the study. The median age was 9 years (2-14 years). All patients presented negative blood smears at 42 days follow-up. The total dose of chloroquine ranged from 13.1 to 38.1 mg/kg. The percentage of patients with a total dose of the drug below 25 mg/kg ranged from 29.4 to 63.6%. The total dose of chloroquine administered based on BSA ranged from 387 to 1079 mg/m2, increasing with age. Plasma chloroquine concentrations ranged from 107 to 420 ng/ml, increasing with age. For desethylchloroquine, the plasma concentrations ranged from 167 to 390 ng/ml, with similar values among age-groups. CONCLUSION: The data demonstrated the widespread exposure of children and adolescents to suboptimal doses of chloroquine in the endemic area investigated.


Assuntos
Antimaláricos/administração & dosagem , Cloroquina/administração & dosagem , Malária Vivax/prevenção & controle , Adolescente , Brasil , Criança , Pré-Escolar , Cloroquina/análogos & derivados , Cloroquina/sangue , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Humanos , Masculino , Plasmodium vivax/efeitos dos fármacos
9.
Malar J ; 18(1): 438, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864376

RESUMO

BACKGROUND: The Democratic Republic of the Congo adopted the strategy of using, at the community level, a dose of rectal artesunate as a pre-referral treatment for severe malaria amongst children under 5 years who could not quickly reach a health care facility and take oral medication. However, the adherence to referral advice after the integration of this strategy and the acceptability of the strategy were unknown. METHODS: To assess adherence by the mothers/caretakers of children under 5 years to referral advice provided by the community health workers after pre-referral treatment of severe malaria with rectal artesunate, the authors conducted a noninferiority community trial with a pre- and post-intervention design in 63 (pre-intervention) and 51 (post-intervention) community care sites in 4 provinces (Kasaï-Oriental, Kasaï-Central, Lomami, Lualaba) from August 2014 through June 2016. The pre- and post-intervention surveys targets 387 mothers of children under 5 years and 63 community health workers and 346 mothers and 41 community health workers, respectively. A 15% margin was considered for noninferiority analyses due to the expected decrease in adherence to referral advice after the introduction of the new intervention. RESULTS: The mothers acknowledged that the rectal route was often used (60.7%), and medicines given rectally were considered more effective (63.6%) and easy to administer (69.7%). The acceptability of pre-referral rectal artesunate was relatively high: 79.4% (95% CI 75.4-83.3) among mothers, 90.3% (95% CI 82.3-96.8) among community health workers, and 97.8% (95% CI 93.3-100) among nurses. Adherence to referral advice at post-intervention [84.3% (95% CI 80.6-88.1)] was non-inferior to pre-intervention adherence [94.1% (95% CI 91.7-96.4)]. CONCLUSIONS: The integration of pre-referral rectal artesunate for severe malaria into the community care site in the DR Congo is feasible and acceptable. It positively affected adherence to referral advice. However, more health education is needed for parents of children under 5 years and community health workers.


Assuntos
Antimaláricos/administração & dosagem , Artesunato/administração & dosagem , Cuidadores/estatística & dados numéricos , Mães/estatística & dados numéricos , Profilaxia Pré-Exposição/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Administração Retal , Adulto , Pré-Escolar , República Democrática do Congo , Feminino , Humanos , Lactente , Recém-Nascido , Malária/prevenção & controle , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
PLoS Negl Trop Dis ; 13(11): e0007890, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31751347

RESUMO

Recent outbreaks of the Ebola virus (EBOV) have focused attention on the dire need for antivirals to treat these patients. We identified pyronaridine tetraphosphate as a potential candidate as it is an approved drug in the European Union which is currently used in combination with artesunate as a treatment for malaria (EC50 between 420 nM-1.14 µM against EBOV in HeLa cells). Range-finding studies in mice directed us to a single 75 mg/kg i.p. dose 1 hr after infection which resulted in 100% survival and statistically significantly reduced viremia at study day 3 from a lethal challenge with mouse-adapted EBOV (maEBOV). Further, an EBOV window study suggested we could dose pyronaridine 2 or 24 hrs post-exposure to result in similar efficacy. Analysis of cytokine and chemokine panels suggests that pyronaridine may act as an immunomodulator during an EBOV infection. Our studies with pyronaridine clearly demonstrate potential utility for its repurposing as an antiviral against EBOV and merits further study in larger animal models with the added benefit of already being used as a treatment against malaria.


Assuntos
Antimaláricos/administração & dosagem , Antivirais/administração & dosagem , Doença pelo Vírus Ebola/prevenção & controle , Naftiridinas/administração & dosagem , Animais , Antimaláricos/efeitos adversos , Antimaláricos/farmacocinética , Antivirais/efeitos adversos , Antivirais/farmacocinética , Citocinas/imunologia , Reposicionamento de Medicamentos , Ebolavirus/efeitos dos fármacos , Ebolavirus/genética , Ebolavirus/fisiologia , Feminino , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Naftiridinas/efeitos adversos , Naftiridinas/farmacocinética
11.
Pan Afr Med J ; 34: 16, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31762885

RESUMO

Introduction: Do health facilities (HF) have basic resources needed to manage malaria? The purpose of our study was to analyze the operational capacity (OC) of first-line health facilities in Ivory Coast in the management of malaria. Methods: SARA methodology was used to conduct a descriptive cross-sectional study from 10 to 30 July 2016. The operational capacity in the management showed an average availability of 9 identification tracers divided in 3 areas: (i) staff and guidelines; (ii) capacity of diagnosis; (iii) drugs and products. This operational capacity was assessed through the calculation of an index and then compared with the health facilities according to the management authority and the geographical area using Chi-square test with p-values α fixed at 0.05. Results: Out of 818 HFs, 651(79.6%) were in the public sector and 487(59.5%) were located in the rural area. The operational capacity of first line health facilities was 74.5%. This OC was higher in the public sector (81.3%) than in the private sector (48.8%) (p < 10-3) as well as in the rural area (82.7%) compared to the urban area (62.9%) (p < 10-3). Conclusion: In 2016, first line health facilities in Ivory Coast had basic resources needed to manage malaria. It is necessary to focus on the need to strengthen health facility services in addition to prevention.


Assuntos
Assistência à Saúde/organização & administração , Instalações de Saúde/estatística & dados numéricos , Malária/terapia , Antimaláricos/administração & dosagem , Costa do Marfim , Estudos Transversais , Humanos , Setor Privado/estatística & dados numéricos , Setor Público/estatística & dados numéricos
12.
Pan Afr Med J ; 33: 186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565146

RESUMO

Introduction: Acute gastroenteritis (AGE) is a leading cause of mortality in children in developing countries. Management of AGE consumes medical resources, including antibiotics and intra-venous fluids, but factors affecting resource utilization in the management of AGE are under-studied. We hope to identify clinical predictors of resource utilization in AGE. Methods: We performed a retrospective chart review of patients 1-60 months of age admitted to a tertiary hospital in Northern Ghana between January 2013 and December 2014 with an admitting diagnosis of AGE. We collected data on patient demographics, presenting symptoms, and subsequent management. Our primary outcome was prolonged hospital length of stay, defined as >4 days. Secondary outcomes included other measures of resource utilization, such as use of antibiotics, antimalarials and intravenous fluids. Demographic and clinical characteristics were compared between groups with Pearson chi square test for categorical variables and ANOVA for continuous variables. Multivariable logistic regression modeling for each outcome included all variables found to be significant in the bivariate analysis. Results: We reviewed charts for 473 patients admitted for AGE during this timeframe. 264 (56%) were male, median age was 12 months. 448 (95%) received antibiotics, 396 (84%) received antimalarials and 365 (77.2%) received intravenous fluids. 167 (35.3%) had prolonged LOS >4 days. Following multiple logistic regression analysis, clinical features associated with prolonged LOS included fever duration (OR 2.87, 95% CI 2.28-3.61 per 1-day increase), mild (OR 2.39, 95% CI 1.12-5.08) or moderate (OR 3.13, 95% CI 1.57-6.21) dehydration (compared to none) and symptom duration (OR 1.13, 95% CI 1.01-1.27 per 1-day increase). Conclusion: Dehydration and duration of symptoms prior to presentation predict prolonged hospital LOS in young children with AGE in Northern Ghana.


Assuntos
Desidratação/terapia , Gastroenterite/terapia , Hospitalização/estatística & dados numéricos , Doença Aguda , Antibacterianos/administração & dosagem , Antimaláricos/administração & dosagem , Pré-Escolar , Desidratação/epidemiologia , Feminino , Febre/epidemiologia , Hidratação/estatística & dados numéricos , Gana , Recursos em Saúde/estatística & dados numéricos , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária
13.
PLoS Med ; 16(10): e1002928, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31584960

RESUMO

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. METHODS AND FINDINGS: Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. CONCLUSIONS: In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis.


Assuntos
Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina/administração & dosagem , Artemisininas/administração & dosagem , Malária Vivax/tratamento farmacológico , Primaquina/administração & dosagem , Quinolinas/administração & dosagem , Humanos , Malária Vivax/diagnóstico , Plasmodium vivax , Recidiva , Risco , Resultado do Tratamento
14.
BMC Infect Dis ; 19(1): 920, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664924

RESUMO

BACKGROUND: The only licensed malaria vaccine, RTS,S/AS01, has been developed for morbidity-control in young children. The potential impact on transmission of deploying such anti-infective vaccines to wider age ranges, possibly with co-administration of antimalarial treatment, is unknown. Combinations of existing malaria interventions is becoming increasingly important as evidence mounts that progress on reducing malaria incidence is stalling and threatened by resistance. METHODS: Malaria transmission and intervention dynamics were simulated using OpenMalaria, an individual-based simulation model of malaria transmission, by considering a seasonal transmission setting and by varying epidemiological and setting parameters such as transmission intensity, case management, intervention types and intervention coverages. Chemopreventive drugs and anti-infective vaccine efficacy profiles were based on previous studies in which model parameters were fitted to clinical trial data. These intervention properties were used to evaluate the potential of seasonal mass applications of preventative anti-infective malaria vaccines, alone or in combination with chemoprevention, to reduce malaria transmission, prevent resurgence, and/or reach transmission interruption. RESULTS: Deploying a vaccine to all ages on its own is a less effective intervention strategy compared to chemoprevention alone. However, vaccines combined with drugs are likely to achieve dramatic prevalence reductions and in few settings, transmission interruption. The combined mass intervention will result in lower prevalence following the intervention compared to chemoprevention alone and will increase chances of interruption of transmission resulting from a synergistic effect between both interventions. The combination of vaccine and drug increases the time before transmission resurges after mass interventions cease compared to mass treatment alone. Deploying vaccines and drugs together requires fewer rounds of mass intervention and fewer years of intervention to achieve the same public health impact as chemoprevention alone. CONCLUSIONS: Through simulations we identified a previously unidentified value of deploying vaccines with drugs, namely the greatest benefit will be in preventing and delaying transmission resurgence for longer periods than with other human targeted interventions. This is suggesting a potential role for deploying vaccines alongside drugs in transmission foci as part of surveillance-response strategies.


Assuntos
Antimaláricos/administração & dosagem , Vacinas Antimaláricas/administração & dosagem , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Vacinação em Massa , Modelos Teóricos , Estações do Ano , Adulto , Quimioprevenção/métodos , Criança , Pré-Escolar , Transmissão de Doença Infecciosa/prevenção & controle , Quimioterapia Combinada , Humanos , Lactente , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/imunologia , Prevalência
15.
Malar J ; 18(1): 302, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477117

RESUMO

BACKGROUND: Infection during pregnancy with Plasmodium falciparum is associated with maternal anaemia and adverse birth outcomes including low birth weight (LBW). Studies using polymerase chain reaction (PCR) techniques indicate that at least half of all infections in maternal venous blood are missed by light microscopy or rapid diagnostic tests. The impact of these subpatent infections on maternal and birth outcomes remains unclear. METHODS: In a cohort of women co-enrolled in a clinical trial of intermittent treatment with sulfadoxine-pyrimethamine (SP) plus azithromycin for the prevention of LBW (< 2500 g) in Papua New Guinea (PNG), P. falciparum infection status at antenatal enrolment and delivery was assessed by routine light microscopy and real-time quantitative PCR. The impact of infection status at enrolment and delivery on adverse birth outcomes and maternal haemoglobin at delivery was assessed using logistic and linear regression models adjusting for potential confounders. Together with insecticide-treated bed nets, women had received up to 3 monthly intermittent preventive treatments with SP plus azithromycin or a single clearance treatment with SP plus chloroquine. RESULTS: A total of 9.8% (214/2190) of women had P. falciparum (mono-infection or mixed infection with Plasmodium vivax) detected in venous blood at antenatal enrolment at 14-26 weeks' gestation. 4.7% of women had microscopic, and 5.1% submicroscopic P. falciparum infection. At delivery (n = 1936), 1.5% and 2.0% of women had submicroscopic and microscopic P. falciparum detected in peripheral blood, respectively. Submicroscopic P. falciparum infections at enrolment or at delivery in peripheral or placental blood were not associated with maternal anaemia or adverse birth outcomes such as LBW. Microscopic P. falciparum infection at antenatal enrolment was associated with anaemia at delivery (adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI] 1.09, 3.67; P = 0.025). Peripheral microscopic P. falciparum infection at delivery was associated with LBW (aOR 2.75, 95% CI 1.27; 5.94, P = 0.010) and preterm birth (aOR 6.58, 95% CI 2.46, 17.62; P < 0.001). CONCLUSIONS: A substantial proportion of P. falciparum infections in pregnant women in PNG were submicroscopic. Microscopic, but not submicroscopic, infections were associated with adverse outcomes in women receiving malaria preventive treatment and insecticide-treated bed nets. Current malaria prevention policies that combine insecticide-treated bed nets, intermittent preventive treatment and prompt treatment of symptomatic infections appear to be appropriate for the management of malaria in pregnancy in settings like PNG.


Assuntos
Anemia/parasitologia , Recém-Nascido de Baixo Peso , Malária Falciparum/sangue , Malária Falciparum/complicações , Complicações Infecciosas na Gravidez/parasitologia , Adulto , Antibacterianos/administração & dosagem , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Infecções Assintomáticas , Azitromicina/administração & dosagem , Feminino , Hemoglobina A/análise , Humanos , Recém-Nascido , Malária Falciparum/prevenção & controle , Papua Nova Guiné , Plasmodium falciparum/genética , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Estudos Prospectivos , Pirimetamina/administração & dosagem , Sulfadoxina/administração & dosagem , Adulto Jovem
16.
Pan Afr Med J ; 33: 127, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31558926

RESUMO

Introduction: Low birth weight (LBW) is an important predictor of newborn survival and development. Given its pathophysiology, malaria is presumed to be one of the risk factors for low birth weight. This study aims to determine the association between malaria in pregnant women (PW) and LBW (weight < 2500 g). Methods: We conducted a case-control analytical study based on the administration of a questionnaire and an observation chart. We calculated the crude odds ratio (OR) and the adjusted odds ratio to determine this association. Logistic regression was applied to recognize the variables which act as determinants of the issue under discussion. Results: This study involved 156 women (78 cases and 78 controls). The prevalence of LBW was 12.32% (105/852); 41.02% (64/156) of women had had malaria during pregnancy and 42.14% of parturients had received three doses of IPT (intermittent preventive treatment). A significant association between malaria and LBW emerged. Crude odds ratio= 3.75 [P = 0.0001 (p < 0.05)] and adjusted OR = 2.82 [P = 0.01 (p < 0.05)] were calculated taking into account the various confusion factors. Conclusion: Malaria during pregnancy is a factor increasing the risk of LBW. Efforts should be made to improve IPT coverage and the use of long lasting impregnated mosquito nets in order to prevent malaria during pregnancy.


Assuntos
Antimaláricos/administração & dosagem , Peso ao Nascer , Malária/complicações , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Camarões , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Modelos Logísticos , Malária/epidemiologia , Malária/prevenção & controle , Gravidez , Complicações Parasitárias na Gravidez/prevenção & controle , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
17.
Pan Afr Med J ; 33: 152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558949

RESUMO

Introduction: Access to free diagnoses and treatments has been shown to be a major determinant in malaria control. The Cameroon government launched in 2011 and 2014 the exemption of the under-fives' simple and severe malaria treatment policy to increase access to health care and reduce inequality, so as to reduce the mortality related to malaria among the under-fives. This study assessed the effect of providing free malaria treatment in the Buea health district. Methods: This retrospective and cross sectional study was carried out in the Buea health district. Aggregated monthly data from (2008-2010) before and (2012-2014) after the implementation of free malaria treatment was compared, to assess the attributable outcomes of free treatment. A semi-structure questionnaire was also used to assess barriers faced in providing free malaria treatment services by health care workers. Data was collected using a semi-structure questionnaire and a data review summary sheet. The data was analysed using Epi-Info 7, Excel and SPSS (Statistical Package for the Social Sciences) version 20.0 for Windows. All statistical tests were performed at 95% confidence interval (significance level of 0.05). Results: Increase utilisation of health care; as general and malaria related consultations (by 5.7% (p=0.001) witnessed an increase after the implementation of free malaria treatment services. Severe malaria hospitalisation also increased, indicating that most caregivers used the health facility when complications had already set in, which could have led to no significant reduction in mortality due to malaria among under-five children (4.4%, p=0.533). Conclusion: Utilisation of health care increased; as consultation and morbidity rate increased after the implementation of free malaria treatment services. Communication strategy should therefore be strengthened so as to better disseminate information, so as to enhance the effectiveness of the program. There is the need to make a large-scale study to assess the impact of subsidized malaria treatment.


Assuntos
Antimaláricos/administração & dosagem , Política de Saúde , Acesso aos Serviços de Saúde/economia , Malária/tratamento farmacológico , Antimaláricos/economia , Camarões , Cuidadores/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Financiamento Governamental/economia , Hospitalização/estatística & dados numéricos , Humanos , Malária/economia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Socioeconômicos , Inquéritos e Questionários
18.
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
19.
Pan Afr Med J ; 33: 97, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31489075

RESUMO

Libman-Sacks endocarditis is a rare cardiac manifestation systemic lupus erythematosus, in which there is a sterile vegetation in the heart valves. There is a significant risk of infective endocarditis. Our patient was a 38 year old woman with persistent fever from two months with inflammatory polyarthralgia, fixed at the wrists and ankles. She was febrile at 39 ° C, had a mitral systolic murmur 2/6 and painful swelling of the wrists and ankles. We have objectified an inflammatory syndrome, blood cultures were negative. The dosage of anti-nuclear antibody was positive with a mottled appearance, as well as anti-DNA antibodies. The Doppler echocardiography had objectified vegetations in the mitral and aortic valves. Clinical, biological and morphological improvements were obtained after antibiotic and corticosteroid combination. We can conclude that Libman-Sacks endocarditis evolution is favorable in the absence of an associated antiphospholipid syndrome (APS). Always fear in all cases a surinfection. The treatment is based on the combination antibiotic-corticosteroid-synthetic antimalarial.


Assuntos
Anticorpos Antinucleares/imunologia , Endocardite/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Corticosteroides/administração & dosagem , Adulto , Antibacterianos/administração & dosagem , Antimaláricos/administração & dosagem , Ecocardiografia Doppler/métodos , Endocardite/etiologia , Endocardite/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Superinfecção/diagnóstico
20.
Pan Afr Med J ; 33: 101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489079

RESUMO

Introduction: Despite the effectiveness of intermittent preventive treatment in pregnancy using sulphadoxine-pyrimethamine (IPTp-SP), the uptake and coverage in southwest Nigeria are low. We assessed the factors influencing utilisation of IPTp-SP. Methods: A multistage sampling technique was used to select 400 pregnant women from six primary healthcare centers in Oyo State. Data on socio-demographic characteristics, knowledge, attitude towards IPTp-SP and its utilisation were obtained using a semi-structured questionnaire. Data were analyzed using SPSS software. Focus group discussions (FGD) and key informant interviews (KII) were held for pregnant women and healthcare workers and analysed thematically. Results: Mean age of respondents was 27.2 (SD ± 5.5) years. Mean gestational age was 29.5 weeks (SD ± 5.4). Overall, 320 (80.0%) took SP, of which 152 (47.5%) took 2 doses and 112 (35.0%) took under directly observed therapy (DOT). We found that early booking for ANC, more than two visits to ANC (adjusted odds ratio (aOR) = 5.6; 95% CI: 1.2 - 26.6), good knowledge on IPTp (aOR = 9.3; 95% CI: 5.4 - 16.0), positive attitude towards IPTp (aOR = 2.1; 95% CI: 1.5 - 2.9) and being employed (aOR = 1.4; 95% CI: 1.1 - 1.7) were factors associated with IPTp-SP utilisation. The FGD and KII revealed that IPTp-SP drugs were mostly taken at home due to stock out. Conclusion: Late ANC booking with stock out of IPTp-SP drugs was responsible for its low utilisation. There is need to encourage pregnant women to book early for ANC. Adherence to the practice of DOT scheme is recommended to improve IPTp-SP utilisation.


Assuntos
Antimaláricos/administração & dosagem , Malária/prevenção & controle , Complicações Parasitárias na Gravidez/prevenção & controle , Pirimetamina/administração & dosagem , Sulfadoxina/administração & dosagem , Adulto , Terapia Diretamente Observada , Combinação de Medicamentos , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Nigéria , Gravidez , Cuidado Pré-Natal/métodos , Atenção Primária à Saúde/métodos , Inquéritos e Questionários , Adulto Jovem
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