Spread of multidrug-resistant Plasmodium falciparum malaria and predictors of treatment failures in Vietnam

2019 ◽  
Author(s):  
Minh Cuong Duong ◽  
Oanh Kieu Nguyet Pham ◽  
Phong Thanh Nguyen ◽  
Van Vinh Chau Nguyen ◽  
Phu Hoan Nguyen
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Early Treatment ◽  
Molecular Technique ◽  
Drug Resistant ◽  
Early Treatment Failure ◽  
Central Highland ◽  
Late Treatment

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. We examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 95%CI 55.1%-64.4%) of patient acquired P. falciparum infection of whom 21.9% (95%CI 17.1%-27.4%) had severe malaria, while 10.2% (95%CI 6.8%-14.5%) and 19.2% (95%CI 14.7%-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. ETF was 6.8% among patients referred from Binh Phuoc province and Central Highland, 11.3% from other areas in Vietnam, and 6.9% from Africa. LTF was 16.2% among patients from Binh Phuoc province and Central Highland, 22.6% from other areas in Vietnam, and 27.6% from Africa. Most patients (98.5%) recovered completely. Having severe malaria was a predictor of ETF (AOR 4.42, 95%CI 1.85-10.61, P = 0.001). No predictor of LTF was identified.Conclusion P. falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. Parenteral artesunate and an oral partner drug should be concurrently used for severe malaria to reduce the risk for ETF. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam which are known as nonendemic areas of antimalarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies. Key words: Plasmodium falciparum; severe malaria; early treatment failure; late treatment failure; Vietnam

scholarly journals Predictors of treatment failures of Plasmodium falciparum malaria in Vietnam: a 4-year single-center retrospective study

2020 ◽  
Author(s):  
Minh Cuong Duong ◽  
Oanh Kieu Nguyet Pham ◽  
Phong Thanh Nguyen ◽  
Chau Van Vinh Nguyen ◽  
Phu Hoan Nguyen
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Control Strategies ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Technique ◽  
Drug Resistant ◽  
Public Health Burden ◽  
Central Highland

Abstract BackgroundDrug-resistant falciparum malaria is an increasing public health burden. We examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. MethodsMedical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcomes. ResultsMore than half (59.8%, CI 55.1%-64.4%) of patient acquired P. falciparum infection of whom 21.9% (CI 17.1%-27.4%) had severe malaria, while 7.2% (CI 4.6%-10.9%) and 19.2% (CI 14.7%-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. ETF was 4.7% among patients referred from Binh Phuoc province and Central Highland, 12.9% from other areas in Vietnam, and 6.9% from Africa. LTF was 16.2% among patients from Binh Phuoc province and Central Highland, 22.6% from other areas in Vietnam, and 27.6% from Africa. Most patients (98.5%) recovered completely. Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55-19.02, P < 0.001). No predictor of LTF was identified.ConclusionP. falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam which are known as nonendemic areas of antimalarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

scholarly journals Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single‐centre retrospective study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Minh Cuong Duong ◽  
Oanh Kieu Nguyet Pham ◽  
Phong Thanh Nguyen ◽  
Van Vinh Chau Nguyen ◽  
Phu Hoan Nguyen
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Control Strategies ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Technique ◽  
Drug Resistant ◽  
Public Health Burden

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified. Conclusions Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

scholarly journals Double Mutation in thepfmdr1Gene Is Associated with Emergence of Chloroquine-Resistant Plasmodium falciparum Malaria in Eastern India

2014 ◽  
Vol 58 (10) ◽  
pp. 5909-5915 ◽  
Author(s):  
Sabyasachi Das ◽  
Santanu Kar Mahapatra ◽  
Satyajit Tripathy ◽  
Sourav Chattopadhyay ◽  
Sandeep Kumar Dash ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Early Treatment ◽  
Chloroquine Resistance ◽  
Major Public Health Problem ◽  
Early Treatment Failure ◽  
Double Mutation ◽  
Chloroquine Treatment ◽  
Late Treatment

ABSTRACTMalaria is a major public health problem in tropical and subtropical countries, including India. This study elucidates the cause of chloroquine treatment failure (forPlasmodium falciparuminfection) before the introduction of artemisinin combination therapy. One hundred twenty-six patients were randomized to chloroquine treatment, and the therapeutic efficacy was monitored from days 1 to 28. Anin vitrosusceptibility test was performed with all isolates. Parasitic DNA was isolated, followed by PCR and restriction digestion of different codons of thepfcrtgene (codons 72 to 76) and thepfmdr1gene (N86Y, Y184F, S1034C, N1042D, and D1246Y). Finally, sequencing was done to confirm the mutations. Forty-three (34.13%) early treatment failure cases and 16 (12.69%) late treatment failure cases were observed after chloroquine treatment.In vitrochloroquine resistance was found in 103 isolates (81.75%). Twenty-six (60.47%) early treatment failure cases and 6 (37.5%) late treatment failure cases were associated with the CVMNK-YYSNYallele (the underlined amino acids are those that were mutated). Moreover, the CVIEK-YYSNYallele was found in 8 early treatment failure (18.60%) and 2 late treatment failure (12.5%) cases. The presence of the wild-typepfcrt(CVMNK) andpfmdr1(YYSNY) double mutant allele in chloroquine-nonresponsive cases was quite uncommon.In vivochloroquine treatment failure andin vitrochloroquine resistance were strongly correlated with the CVMNK-YYSNYand CVIEK-YYSNYhaplotypes (P< 0.01).

scholarly journals How often do symptoms return after unsuccessful drug treatment for malaria? A systematic review and meta-analysis

2020 ◽  
Author(s):  
Rida Mumtaz ◽  
Lucy C. Okell ◽  
Joseph D. Challenger
Keyword(s):  
Clinical Trials ◽  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Meta Analysis ◽  
Positive Association ◽  
Bayesian Regression ◽  
Drug Resistant ◽  
Study Results ◽  
Late Treatment ◽  
Number Of Treatment

Background In clinical trials of therapies for uncomplicated Plasmodium falciparum, there are usually some patients who fail treatment even in the absence of drug resistance. Treatment failures are categorised as "clinical" or "parasitological" failures, the latter indicating that recrudescence of the infection has occurred without inducing the return of symptoms. Asymptomatic treatment failure has public health implications for continued malaria transmission and may be important for the spread of drug-resistant malaria. As the number of treatment failures in an individual trial is often low, it is difficult to assess how commonplace asymptomatic treatment failure is, and with what factors it is associated. Methods A systematic literature review was carried out on clinical trials of artemether-lumefantrine (AL) in patients seeking treatment for symptomatic uncomplicated falciparum malaria, and information on symptoms during treatment failure was recorded. Only treatment failures examined by polymerase chain reaction (PCR) were included, so as to exclude reinfections. Using a multivariable Bayesian regression model, we explored factors potentially explaining the proportion of recrudescent infections which are symptomatic across the trials included in our study. Results Across 60 published trials including 9137 malaria patients we found that 40.8% (95% CIs [35.9-45.8%]) of late treatment failures were symptomatic. We found a positive association between transmission intensity and the observed proportion of treatment failures that were asymptomatic. We also found that symptoms were more likely to return in trials that only enrolled children aged < 72 months (odds ratio =1.62, 95% CIs [1.01,2.59]). However, 84 studies had to be excluded from our analysis, as treatment failures were not specified as symptomatic or asymptomatic. Conclusions AL, the most widely used treatment for uncomplicated Plasmodium falciparum in Africa, remains a highly efficacious drug in most endemic countries. However in the small proportion of patients where AL does not clear parasitaemia, the majority of patients do not develop symptoms again and thus would be unlikely to seek another course of treatment. This continued asymptomatic parasite carriage in patients who have been treated may have implications for drug-resistant parasites being introduced into high-transmissions settings.

Early treatment failure in severe malaria resulting from abnormally low plasma quinine concentrations

2006 ◽  
Vol 100 (2) ◽  
pp. 184-186 ◽  
Author(s):  
Paul N. Newton ◽  
Steven Ward ◽  
Brian J. Angus ◽  
Wirongrong Chierakul ◽  
Arjen Dondorp ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Severe Malaria ◽  
Early Treatment ◽  
Early Treatment Failure

scholarly journals Efikasi Obat Kloroquine, Kina, Artesunate-SP, Artesunate-Amodiaquine, Artesunate-Lumafentrin pada Anak Malaria Falciparum di BLU RSUP Prof. Dr. RD. Kandou Manado

Sari Pediatri ◽  
2016 ◽  
Vol 10 (6) ◽  
pp. 417
Author(s):  
Suryadi Nicolaas Napoleon Tatura
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Early Treatment ◽  
Early Treatment Failure ◽  
Negative Rate ◽  
Kaplan Meier

Latar belakang. Malaria falciparum masih merupakan salah satu penyebab utama kematian dan kesakitan pada anak-anak dan orang dewasa di negara-negara tropis. Di Indonesia, dilaporkan Plasmodium falciparum telsh resisten terhadap obat – obat anti malaria, terutama kemungkinan terjadi early treatment failure (ETF).Tujuan. Untuk mengetahui efikasi dan early treatment failure (ETF) obat anti malaria (OAM) yaitu kloroquin (CQ), kina, artesunat-SP(AS-SP), dan artesunate-amodiaquin(AS-AQ) serta artesunate- lumafentrin(AS-L) pada anak dengan malaria falciparum.Metode. Penelitian deskriptif retrospektif� �� � � � � � � � � � � . Populasi adalah bayi dan anak usia 1 bulan-14 tahun yang terdiagnosis dengan malaria falciparum dan mendapat OAM. Data diperoleh dari rekam medis Bagian Anak BLU RSUP Prof Dr. RD. Kandou Manado sejak Maret 2007 sampai Maret 2009. Data dikelompokkan berdasarkan jenis obat anti malaria yang digunakan oleh pasien selama 3 hari (3x24jam), kemudian dinilai waktu bebas parasit dalam darah pasien serta ETF. Hitung parasit menggunakan metode semikuantitatif. Data dianalis dengan metode Kaplan-Meier menggunakan SPSS 17.Hasil. Efikasi obat anti malaria dalam 3 hari sebagai berikut, AS-L 100%, AS-SP 100%, AS-AQ 97%, CQ 85%, dan kina 81%. Terdapat ETF obat kina 19%, CQ 15% dan AS-AQ 3%. Parasite negative rate dalam 24 jam AS-SP 0,6, AS-L 0,6, AS-AQ 0,89, Kina 0,35 dan CQ 0,54.Kesimpulan. Artesunate-lumafentrin dan artesunate-SP merupakan obat anti malaria falciparum pilihan. Artesunate-amodiaquine sangat baik menurunkan angka parasit dalam 24 jam I. Telah terjadi ETF pada kloroquine, kina dan arteunate-amodiaquine.

scholarly journals Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study

2018 ◽  
Vol 5 (2) ◽  
Author(s):  
Maroun Sfeir ◽  
Marissa Walsh ◽  
Rossana Rosa ◽  
Laura Aragon ◽  
Sze Yan Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Renal Disease ◽  
Treatment Failure ◽  
Retrospective Cohort Study ◽  
Early Treatment ◽  
Retrospective Cohort ◽  
Positive Culture ◽  
Mycobacterium Abscessus ◽  
Early Treatment Failure

Abstract Background Infections caused by Mycobacterium abscessus group strains are usually resistant to multiple antimicrobials and challenging to treat worldwide. We describe the risk factors, treatment, and clinical outcomes of patients in 2 large academic medical centers in the United States. Methods A retrospective cohort study of hospitalized adults with a positive culture for M. abscessus in Miami, Florida (January 1, 2011, to December 31, 2014). Demographics, comorbidities, the source of infection, antimicrobial susceptibilities, and clinical outcomes were analyzed. Early treatment failure was defined as death and/or infection relapse characterized either by persistent positive culture for M. abscessus within 12 weeks of treatment initiation and/or lack of radiographic improvement. Results One hundred eight patients were analyzed. The mean age was 50.81 ± 21.03 years, 57 (52.8%) were females, and 41 (38%) Hispanics. Eleven (10.2%) had end-stage renal disease, 34 (31.5%) were on immunosuppressive therapy, and 40% had chronic lung disease. Fifty-nine organisms (54.6%) were isolated in respiratory sources, 21 (19.4%) in blood, 10 (9.2%) skin and soft tissue, and 9 (8.3%) intra-abdominal. Antimicrobial susceptibility reports were available for 64 (59.3%) of the patients. Most of the isolates were susceptible to clarithromycin, amikacin, and tigecycline (93.8%, 93.8%, and 89.1%, respectively). None of the isolates were susceptible to trimethoprim/sulfamethoxazole, and only 1 (1.6%) was susceptible to ciprofloxacin. Thirty-six (33.3%) patients early failed treatment; of those, 17 (15.7%) died while hospitalized. On multivariate analysis, risk factors significantly associated with early treatment failure were disseminated infection (odds ratio [OR], 11.79; 95% confidence interval [CI], 1.53–81.69; P = .04), acute kidney injury (OR, 6.55; 95% CI, 2.4–31.25; P = .018), organ transplantation (OR, 2.37; 95% CI, 2.7–23.1; P = .005), immunosuppressive therapy (OR, 2.81; 95% CI, 1.6–21.4; P = .002), intravenous amikacin treatment (OR, 4.1; 95% CI, 0.9–21; P = .04), clarithromycin resistance (OR,79.5; 95% CI, 6.2–3717.1, P &lt; .001), and presence of prosthetic device (OR, 5.43; 95% CI, 1.57–18.81; P = .008). Receiving macrolide treatment was found to be protective against early treatment failure (OR, 0.13; 95% CI, 0.002–1.8; P = .04). Conclusions Our cohort of 108 M. abscessus complex isolates in Miami, Florida, showed an in-hospital mortality of 15.7%. Most infections were respiratory. Clarithromycin and amikacin were the most likely agents to be susceptible in vitro. Resistance to fluoroquinolone and trimethoprim/sulfamethoxazole was highly common. Macrolide resistance, immunosuppression, and renal disease were significantly associated with early treatment failure.

scholarly journals Predictors of recurrence, early treatment failure and death from Staphylococcus aureus bacteraemia: Observational analyses within the ARREST trial

2019 ◽  
Vol 79 (4) ◽  
pp. 332-340 ◽  
Author(s):  
Alexander Szubert ◽  
Sarah Lou Bailey ◽  
Graham S. Cooke ◽  
Tim Peto ◽  
Martin J. Llewelyn ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Early Treatment ◽  
Early Treatment Failure ◽  
Predictors Of Recurrence
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