Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients

2021 ◽  
Author(s):  
Camille Roussel ◽  
Papa Alioune Ndour ◽  
Eric Kendjo ◽  
Sébastien Larréché ◽  
Aida Taieb ◽  
...  
Keyword(s):  
Severe Malaria ◽  
First Trimester ◽  
Imported Malaria ◽  
World Health ◽  
Cardiac Events ◽  
Conduction Disorders ◽  
Drug Agency ◽  
First Trimester Of Pregnancy ◽  
Enzyme Elevation ◽  
Health Organization

Abstract Background Intravenous artesunate is the World Health Organization–recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. Methods We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011–2017) of a national program implemented by the French Drug Agency. Results Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate–delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. Conclusions Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

scholarly journals Clinical Features and Mortality Associated with Severe Malaria in Adults in Southern Mauritania

2020 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Boushab Mohamed Boushab ◽  
Mohamed Salem Ould Ahmedou Salem ◽  
Ali Ould Mohamed Salem Boukhary ◽  
Philippe Parola ◽  
Leonardo Basco
Keyword(s):  
Renal Failure ◽  
Respiratory Distress ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Clinical Features ◽  
Signs And Symptoms ◽  
Plasmodium Falciparum Malaria ◽  
Severe Anaemia ◽  
World Health ◽  
Health Organization

Severe malaria in adults is not well-studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (p < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, such as parenteral artesunate, is required to lower the mortality rate associated with severe malaria.

scholarly journals Preventing the re-establishment of malaria in Sri Lanka amidst the COVID-19 pandemic

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Prasad Ranaweera ◽  
Rajitha Wickremasinghe ◽  
Kamini Mendis
Keyword(s):  
Sri Lanka ◽  
Task Force ◽  
Health Sector ◽  
Police Department ◽  
Control Programme ◽  
Imported Malaria ◽  
World Health ◽  
Cumulative Number ◽  
Health Organization ◽  
Health Programmes

Abstract The COVID-19 pandemic has had a considerable impact on other health programmes in countries, including on malaria, and is currently under much discussion. As many countries are accelerating efforts to eliminate malaria or to prevent the re-establishment of malaria from recently eliminated countries, the COVID-19 pandemic has the potential to cause major interruptions to ongoing anti-malaria operations and risk jeopardizing the gains that have been made so far. Sri Lanka, having eliminated malaria in 2012, was certified by the World Health Organization as a malaria-free country in 2016 and now implements a rigorous programme to prevent its re-establishment owing to the high receptivity and vulnerability of the country to malaria. Sri Lanka has also dealt with the COVID-19 epidemic quite successfully limiting the cumulative number of infections and deaths through co-ordinated efforts between the health sector and other relevant sectors, namely the military, the Police Department, Departments of Airport and Aviation and Foreign Affairs, all of which have been deployed for the COVID-19 epidemic under the umbrella of a Presidential Task Force. The relevance of imported infections and the need for a multi-sectoral response are features common to both the control of the COVID-19 epidemic and the Prevention of Re-establishment (POR) programme for malaria. Sri Lanka’s malaria POR programme has, therefore, creatively integrated its activities with those of the COVID-19 control programme. Through highly coordinated operations the return to the country of Sri Lankan nationals stranded overseas by the COVID-19 pandemic, many from malaria endemic countries, are being monitored for malaria as well as COVID-19 in an integrated case surveillance system under quarantine conditions, to the success of both programmes. Twenty-three imported malaria cases were detected from February to October through 2773 microscopic blood examinations performed for malaria in quarantine centres, this number being not much different to the incidence of imported malaria during the same period last year. This experience highlights the importance of integrated case surveillance and the need for a highly coordinated multi-sectoral approach in dealing with emerging new infections. It also suggests that synergies between the COVID-19 epidemic control programme and other health programmes may be found and developed to the advantage of both.

P1591Cardiovascular toxicity of ibrutinib: a pharmacovigilance study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J E Salem ◽  
A Manouchehri ◽  
M arie Bretagne ◽  
B Lebrun Vignes ◽  
J D Groarke ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Kinase Inhibitor ◽  
World Health ◽  
Cardiac Events ◽  
Full Spectrum ◽  
Conduction Disorders ◽  
Hemorrhagic Events ◽  
Pharmacovigilance Database ◽  
Time To Onset ◽  
Ischemic Events

Abstract Importance Ibrutinib, a first in class Bruton tyrosine kinase inhibitor, has revolutionized treatment for several B-cell malignancies. However, early data suggested that ibrutinib was associated with supra-ventricular arrhythmias (SVA) and bleeding. Other types of cardiovascular adverse drug reactions (CV-ADR) induced by ibrutinib have been sporadically reported. Objective To determine the full spectrum of CV-ADR associated with ibrutinib and provide data concerning their clinical characteristics. Design An observational, retrospective, pharmacovigilance study Setting VigiBase, the World Health Organization's pharmacovigilance database. Main outcomes and measures A disproportionality analysis using reporting odds-ratios (ROR) and information component (IC). IC compares observed and expected values to find associations between drugs and ADR using disproportionate Bayesian reporting; IC025 (lower end of the IC 95% credibility interval) >0 is considered statistically significant. Exposures Exposure to ibrutinib versus entire database. Results Ibrutinib was associated with higher reporting of supraventricular arrhythmias (SVA; ROR: 23.1 [21.6–24.7]; IC025:3.97), central nervous system (CNS) hemorrhagic events (ROR: 3.7 [3.4–4.1]; IC025:1.63), heart failure (HF; ROR: 3.5 [3.1–3.8]; IC025:1.46), ventricular arrhythmias (VA; ROR: 4.7 [3.7–5.9]; IC025:0.96), conduction disorders (CD; ROR: 3.5 [2.7–4.6]; IC025:0.76), CNS ischemic events (ROR: 2.2 [2.0–2.5]; IC025:0.73) and hypertension (ROR: 1.7 [1.5–1.9]; IC025:0.4). CV-ADR occurred early after ibrutinib administration, as soon as after the first dose, with a shorter median time to onset of 27.5 days (IQR: 1–138.5 days) for CD (p<0.01, Kruskal-Wallis), as compared to CNS ischemic events (51 days; IQR: 17.5–160 days, p: 0.05 vs. CD), CNS hemorrhagic events (53.5 days; IQR: 20.3–183.3 days, p: 0.03 vs. CD), HF (54 days; IQR: 20–142.8 days, p: 0.05 vs. CD), VA (70 days; IQR: 28.5–152.5 days, p: 0.03 vs. CD), SVA (74 days; (IQR: 29.5–196.5 days, p: 0.0004 vs. CD) and hypertension (164 days; IQR: 20–274 days, p: 0.04 vs. CD). CV-ADR were associated with fatalities, with rates ranging from ∼10% (SVA and VA) to ∼20% (CNS events, HF and CD). More deaths occurred when SVA cases were associated with CNS hemorrhagic and/or ischemic events compared to their absence (15/52, 28.8% vs. 88/907, 9.7%, p<0.0001, respectively). Conclusions Severe and occasionally fatal cardiac events related to cardiac SVA, VA, CD, HF, hypertension, CNS hemorrhagic and ischemic events occur in patients exposed to ibrutinib. These events should be considered in patient care and in clinical trial designs.

scholarly journals SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3316
Author(s):  
Vincenzo Quagliariello ◽  
Annamaria Bonelli ◽  
Antonietta Caronna ◽  
Gabriele Conforti ◽  
Martina Iovine ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Patients ◽  
World Health ◽  
Fulminant Myocarditis ◽  
Cardiac Events ◽  
Risk Of Death ◽  
Cardiovascular Side Effects ◽  
Viral Illness ◽  
Health Organization ◽  
Gastro Intestinal Tract

The coronavirus disease-2019 (COVID-19) is a highly transmissible viral illness caused by SARS-CoV-2, which has been defined by the World Health Organization as a pandemic, considering its remarkable transmission speed worldwide. SARS-CoV-2 interacts with angiotensin-converting enzyme 2 and TMPRSS2, which is a serine protease both expressed in lungs, the gastro-intestinal tract, and cardiac myocytes. Patients with COVID-19 experienced adverse cardiac events (hypertension, venous thromboembolism, arrhythmia, myocardial injury, fulminant myocarditis), and patients with previous cardiovascular disease have a higher risk of death. Cancer patients are extremely vulnerable with a high risk of viral infection and more negative prognosis than healthy people, and the magnitude of effects depends on the type of cancer, recent chemotherapy, radiotherapy, or surgery and other concomitant comorbidities (diabetes, cardiovascular diseases, metabolic syndrome). Patients with active cancer or those treated with cardiotoxic therapies may have heart damages exacerbated by SARS-CoV-2 infection than non-cancer patients. We highlight the cardiovascular side effects of COVID-19 focusing on the main outcomes in cancer patients in updated perspective and retrospective studies. We focus on the main cardio-metabolic risk factors in non-cancer and cancer patients and provide recommendations aimed to reduce cardiovascular events, morbidity, and mortality.

scholarly journals Putative Cellular and Molecular Roles of Zika Virus in Fetal and Pediatric Neuropathologies

2018 ◽  
Vol 22 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Rajendra Gharbaran ◽  
Latchman Somenarain
Keyword(s):  
Zika Virus ◽  
Neural Progenitor Cells ◽  
First Trimester ◽  
Host Cells ◽  
World Health ◽  
Molecular Evidence ◽  
Innate Immune Responses ◽  
Selective Targeting ◽  
Health Organization ◽  
Productive Replication

Although the World Health Organization declared an end to the recent Zika virus (ZIKV) outbreak and its association with adverse fetal and pediatric outcome, on November 18, 2016, the virus still remains a severe public health threat. Laboratory experiments thus far supported the suspicions that ZIKV is a teratogenic agent. Evidence indicated that ZIKV infection cripples the host cells’ innate immune responses, allowing productive replication and potential dissemination of the virus. In addition, studies suggest potential transplacental passage of the virus and subsequent selective targeting of neural progenitor cells (NPCs). Depletion of NPCs by ZIKV is associated with restricted brain growth. And while microcephaly can result from infection at any gestational stages, the risk is greater during the first trimester. Although a number of recent studies revealed some of specific molecular and cellular roles of ZIKV proteins of this mosquito-borne flavivirus, the mechanisms by which it produces it suspected pathophysiological effects are not completely understood. Thus, this review highlights the cellular and molecular evidence that implicate ZIKV in fetal and pediatric neuropathologies.

scholarly journals Central venous catheter use in severe malaria: time to reconsider the World Health Organization guidelines?

2011 ◽  
Vol 10 (1) ◽  
Author(s):  
Josh Hanson ◽  
Sophia WK Lam ◽  
Sanjib Mohanty ◽  
Shamshul Alam ◽  
Md Mahtab Uddin Hasan ◽  
...  
Keyword(s):  
Central Venous Catheter ◽  
World Health Organization ◽  
Severe Malaria ◽  
Venous Catheter ◽  
World Health ◽  
Central Venous ◽  
The World ◽  
Health Organization

scholarly journals Teratogenicity of Artemether–Clindamycin Nanostructured Lipid Carriers in Rats

2016 ◽  
Vol 35 (4) ◽  
pp. 420-428 ◽  
Author(s):  
Soniya A. Jain ◽  
Madhavi Awale ◽  
Sulabha Pathak ◽  
Geeta Vanage ◽  
Vandana B. Patravale ◽  
...  
Keyword(s):  
Therapeutic Dose ◽  
Parasite Clearance ◽  
First Trimester ◽  
Nanostructured Lipid Carriers ◽  
World Health ◽  
Malaria During Pregnancy ◽  
Fetal Malformations ◽  
Nanolipid Carriers ◽  
Health Organization ◽  
In Pregnancy

Currently, artemisinin-based combination therapy is considered the best option in the treatment of malaria. However, toxicity of artemisinins limits their use in pregnancy. In the absence of sufficient toxicity data, the World Health Organization recommends that artemisinins are not to be used in the first trimester of pregnancy and can be used only in second and third trimesters, when other treatments are not available. We have recently observed that drugs loaded in nanolipid carriers are selectively taken up in Plasmodium-infected erythrocytes with a concomitant reduction in the dose required to cure animals. Thus, 20% of the therapeutic dose of artemether–clindamycin (ARM-CP) loaded in nanostructured lipid carriers (NLCs; mean particle size 55 ± 10 nm) resulted in complete parasite clearance and 100% survival of infected mice. Here, we investigate the teratogenicity of this formulation in rodents (dosing on alternate days from 6th day to 18th day of gestation; 12-15 animals/group). The teratogenicity of drug-free NLCs and artesunate–clindamycin (ARS-CP) solution was also evaluated. We found that the therapeutic dose of ARS-CP caused fetal resorptions (87.5% resorptions in 8 litters), suggesting its unsuitability for use in pregnancy. Artesunate–clindamycin NLCs at therapeutic doses also resulted in ∼90% fetal resorptions in 10 litters examined. However, postimplantation losses or fetal malformations were not observed at the dose of ARM-CP NLCs that was required for complete parasite clearance in preclinical trials (ie, 20% of the therapeutic dose). Our data suggest that the NLCs loaded with 20% of the therapeutic dose of ARM-CP may have potential in treating malaria during pregnancy.

scholarly journals Safety of Artemisinin Derivatives in the First Trimester of Pregnancy: A Controversial Story

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3505 ◽  
Author(s):  
Sarah D’Alessandro ◽  
Elena Menegola ◽  
Silvia Parapini ◽  
Donatella Taramelli ◽  
Nicoletta Basilico
Keyword(s):  
Congenital Malformation ◽  
Uncomplicated Malaria ◽  
Time Window ◽  
Artemisinin Combination Therapy ◽  
First Trimester ◽  
Experimental Models ◽  
World Health ◽  
Artemisinin Derivatives ◽  
Increased Risk ◽  
First Trimester Of Pregnancy

Artemisinin combination therapy (ACT) is recommended by the World Health Organization (WHO) as first line treatment for uncomplicated malaria both in adults and children. During pregnancy, ACT is considered safe only in the second and third trimester, since animal studies have demonstrated that artemisinin derivatives can cause foetal death and congenital malformation within a narrow time window in early embryogenesis. During this period, artemisinin derivatives induce defective embryonic erythropoiesis and vasculogenesis/angiogenesis in experimental models. However, clinical data on the safety profile of ACT in pregnant women have not shown an increased risk of miscarriage, stillbirth, or congenital malformation, nor low birth weight, associated with exposure to artemisinins in the first trimester. Although further studies are needed, the evidence collected up to now is prompting the WHO towards a change in the guidelines for the treatment of uncomplicated malaria, allowing the use of ACT also in the first trimester of pregnancy.

scholarly journals Study to assess knowledge attitude and practices of antenatal care among antenatal women attending outdoor clinic in tertiary care hospital

2018 ◽  
Vol 7 (5) ◽  
pp. 1754
Author(s):  
Neetu Ahirwar
Keyword(s):  
Antenatal Care ◽  
Tertiary Care ◽  
First Trimester ◽  
World Health ◽  
Control Group ◽  
Care Hospital ◽  
Indian Government ◽  
Attitudes And Practices ◽  
Gandhi Medical College ◽  
Health Organization

Background: Maternal mortality rate in India continues to be a national challenge despite of the various measures taken by the Indian government, Non profit organizations in and outside the country including the World Health Organization. To find out the gaps between the providers and beneficiaries we tried to find out what actually prevents our pregnant women to seek Regular Antenatal Care by evaluating their knowledge, attitudes and practices towards antenatal care.Methods: All antenatal women attending outpatient clinic of department of obstetrics and gynae Gandhi medical college Bhopal over a period of one year were included in the study. Study group was of unbooked antenatal women and control group consisted of booked women at the hospital. All subjects were given a predesigned, pretested questionnaire to fill in their local language and the data thus obtained was analysed statistically.Results: 86.16% subjects visited ANC clinic during first trimester, 66.33% knew correctly about frequency of antenatal visits, 97.50% knew about Tetanus immunization. Likewise, 78.33% had positive attitude towards antenatal checkups and early registration. Similarly, 70.4% took adequate antenatal care, 93.33% took iron folic acid tablets.Conclusions: Thus, the study shows that the knowledge, attitude and practice of antenatal care is good in the booked subject the same is not the case in unbooked subjects coming to the hospital with complications or being referred to the hospital.

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