BACKGROUND: The aim of this study was to evaluate the rates of parasitaemia clearance and the prevalence of treatment failure in patients with uncomplicated Plasmodium falciparum malaria treated with artemether-lumefantrine (AL), mefloquine (MQ), and atovaquone-proguanil (AP). METHOD: The retrospective descriptive study included adult patients with uncomplicated P. falciparum malaria treated at the University Hospital Bulovka in Prague from 2006 to 2019. Parasitaemia clearance was estimated using a linear regression model. RESULTS: The study included 72 patients with a median age of 33 years (IQR 27-45) and a male to female ratio of 3.2:1. Thirty-six patients (50.0%) were treated with AL, 27 (37.5%) with MQ and 9 (12.5%) with AP. The proportion of VFR and migrants was 22.2% with no significant differences among the three groups. The median time to the parasitaemia clearance was two days (IQR 2-3) in patients treated with AL versus four days in the MQ (IQR 3-4) and AP (IQR 3-4) groups, p < 0.001. The clearance rate constant was 3.3/hour (IQR 2.5-4.0) for AL, 1.6/hour (IQR 1.3-1.9) for MQ, and 1.9/hour (IQR 1.3-2.4) for AP, p < 0.001. Malaria recrudescence occurred in 5/36 (13.9%) patients treated with AL and in no patients treated with MQ or AP. CONCLUSIONS: The findings demonstrate the superior efficacy of AL compared to other oral antimalarials in early malaria treatment. However, we observed a higher rate of late treatment failure in patients treated with AL than previously reported. This issue warrants further investigation of possible dose adjustments, extended regimens, or alternative artemisinin-based combinations.

• MeSH
• Antimalarials * adverse effects   MeSH
• Artemether therapeutic use   MeSH
• Adult MeSH
• Ethanolamines therapeutic use   MeSH
• Drug Combinations MeSH
• Artemether, Lumefantrine Drug Combination therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Malaria * drug therapy   MeSH
• Mefloquine therapeutic use   adverse effects   MeSH
• Treatment Failure MeSH
• Plasmodium falciparum MeSH
• Retrospective Studies MeSH
• Malaria, Falciparum * drug therapy   epidemiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

• MeSH
• Antimalarials * adverse effects   MeSH
• Artemether therapeutic use   MeSH
• Quinine adverse effects   MeSH
• Ethanolamines therapeutic use   MeSH
• Drug Combinations MeSH
• Artemether, Lumefantrine Drug Combination therapeutic use   MeSH
• Humans MeSH
• Malaria * drug therapy   MeSH
• Stillbirth epidemiology   MeSH
• Prospective Studies MeSH
• Pregnancy Trimester, First MeSH
• Abortion, Spontaneous * MeSH
• Pregnancy MeSH
• Malaria, Falciparum * drug therapy   MeSH
• Pregnancy Outcome MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Systematic Review MeSH

This report presents the recommendations of the WHO Expert Committee responsible for updating the WHO Model List of Essential Medicines. The first part contains an update on the revised procedures for updating the Model List and the development of the WHO Essential Medicines Library. It continues to present a summary of the Committee\'s considerations and justifications for additions and changes to the 12th Model List, including its recommendation to add ten antiretroviral medicines. The annexes include the 12th WHO Model List of Essential Medicines in its usual presentation and, for the first time, in the five-level Anatomical Therapeutic Chemical (ATC) classification system.

• MeSH
• Child MeSH
• Drugs, Essential administration & dosage   MeSH
• Drug Information Services MeSH
• Drug Utilization MeSH
• Check Tag
• Child MeSH

• Conspectus
• Farmacie. Farmakologie
• NML Fields
• pediatrie
• farmacie a farmakologie
• farmacie a farmakologie
• NML Publication type
• publikace WHO

• MeSH
• Drugs, Essential standards   MeSH
• Drug Information Services MeSH
• Guidelines as Topic MeSH
• Drug Utilization MeSH
• Publication type
• Guideline MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• veřejné zdravotnictví
• farmacie a farmakologie
• farmacie a farmakologie
• NML Publication type
• publikace WHO

Malárie se vyskytuje ve většině tropických a subtropických oblastí s největším rizikem v subsaharské Africe. Infekce P. falciparum představuje u neimunních cestovatelů bez léčby smrtelnou infekci. Tato skutečnost je často opomíjena a přibývá turistů i českých pracovníků, kteří vyjíždí do vysoce rizikových oblastí bez řádné antimalarické profylaxe a bez dostatečných informací o závažnosti, klinických projevech, diagnostice a léčbě malárie. Infekce P. falciparum se může projevit i déle než jeden měsíc po návratu z rizikové oblasti, relapsy P. vivax a P. ovale i za řadu měsíců a let. Při horečnatém onemocnění během pobytu nebo po návratu z malarické oblasti je třeba infekci vyloučit vyšetřením obarvených krevních nátěrů (tlustá kapka, tenký nátěr). Léčba musí být zahájena ihned po diagnóze a probíhá většinou na infekčních odděleních a klinikách, jejichž seznam je dostupný na www.infekce.cz. Lékem volby nekomplikované infekce P. falciparum je kombinace artemeter/lumefantrin nebo atovachon/proguanil, meflochin či chinin se používají pouze při jejich nedostupnosti. Chlorochin je možné použít pouze u „non-falciparum“ infekcí, antirelapsová léčba primachinem se nasazuje u terciány vivax a ovale. Profylaxe malárie je založena na ochraně před sáním komárů (expoziční profylaxe) a v preventivním užívání antimalarik (antimalarická chemoprofylaxe) při vysokém riziku malárie. V ČR jsou k profylaxi dostupné atovachon/proguanil (Malarone) a doxycyklin. Patogeneze tropické malárie je komplexní soubor dějů vyvolaných produkcí parazitárních antigenů a shlukováním parazitovaných i neparazitovaných erytrocytů ve vnitřních orgánech. Klinický stav může vyústit v poruchy mikrocirkulace, hypoperfuzi orgánů, tkáňovou hypoxii a šokový stav s multiorgánovým selháním. Nejzávažnější komplikací je cerebrální (mozková) malárie, která se projevuje těžkou poruchou vědomí (sopor, koma). V patogenezi cerebrální malárie se uvažuje o vlivu sekvestrovaných parazitovaných erytrocytů a obstrukci mikrocirkulace či lokální produkci oxidu dusnatého, který se může uplatňovat jako falešný neurotransmiter, a tím vyvolávat encefalopatii. Lékem volby cerebrální malárie je i. v. artesunát, ale při jeho nedostupnosti v ČR se používá i. v. chinin v kombinaci s i. v. klindamycinem nebo doxycyklinem. Podpůrná léčba mozkové malárie a dalších komplikací při multiorgánovém selhání probíhá za využití všech dostupných a doporučovaných modalit podobně jako u jiných urgentních stavů.

Malaria is distribited in many tropical and subtropical regions, but the risk is highest in sub-Saharan Africa. If untreated, infection with P. falciparum is a fatal in non-immune travellers. This fact is often neglected, and there are increasing numbers of tourists as well as Czech workers who travel to high-risk areas without receiving appropriate antimalarial prophylaxis and sufficient information on the severity, clinical manifestations, diagnosis, and treatment of malaria. Infection with P. falciparum may manifest in more than one month after returning from a risk area, and P. vivax and P. ovale relapses occurring in months or even years. In the case of a febrile disease during a stay in or upon return from a malaria region, the infection has to be ruled out by examining stained blood smears (thick and think blood smear). Treatment must be initiated immediately after diagnosis and is typically provided at infectious diseases departments, a list of which is available at www.infekce.cz. The combination of artemether and lumefantrine or that of atovaquone and proguanil is the drug of choice in uncomplicated P. falciparum infection, with mefloquine or quinine being used only when the above are unavailable. Chloroquine can only be used in non-falciparum infections, and anti-relapse therapy with primaquine is indicated in tertian vivax and ovale malaria. Malaria prophylaxis is based on preventing mosquito bites (exposure prophylaxis) and a preventive use of antimalarial drugs (antimalarial chemoprophylaxis) when there is a high risk of malaria. In the Czech Republic, atovaquone/proguanil (Malarone) and doxycycline are available for prophylaxis. The pathogenesis of tropical malaria is a comprehensive set of processes caused by a production of parasitic antigens and accumulation of P. falciparum – infected and uninfected red blood cells in many organs. The clinical condition may result in impaired microcirculation, organ hypoperfusion, tissue hypoxia, and shock with multiple organ failure. Cerebral malaria is the most serious complication that is manifested by a severe disturbance of consciousness (sopor, coma). The following are thought to be implicated in the pathogenesis of cerebral malaria: an effect of sequestration of infected red blood cells and obstruction of microcirculatory or a local production of nitric oxide that can act as a false neurotransmitter, and thus induce encephalopathy. IV artesunate is the drug of choice in treating cerebral malaria; however, if unavailable in the Czech Republic, IV quinine in combination with IV clindamycin or doxycycline is used. Supportive treatment of cerebral malaria and other complications in multiple organ failure involves the use of all available and recommended modalities, similarly to other urgent conditions.

• MeSH
• Artesunate administration & dosage   therapeutic use   MeSH
• Quinine administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Malaria * diagnosis   epidemiology   complications   therapy   MeSH
• Malaria, Cerebral pathology   therapy   MeSH
• Plasmodium falciparum MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Chemical Actions and Uses MeSH
• Poisoning MeSH
• Pathology MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• patologie