Drug-Resistant Malaria in Bangladesh: An in Vitro Assessment

Noedl, Harald; Faiz, MA; Yunus, Emran Bin; Rahman, Rezaur; Hossain, M Amir; Samad, Rasheda; Miller, R. Scott; Pang, Lorrin; Wongsrichanalai, Chansuda

doi:10.4269/ajtmh.2003.68.140

Cited by 35 publications

(26 citation statements)

References 7 publications

(7 reference statements)

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“…Although no in vitro resistance cut off values have been reported for artesunate, the EC values of individual isolates against the drug were very low, and fell within the range of EC50 values previously reported for sensitive isolates to the drug, or its active metabolite, dihydroartemisinin (Noedl et al, 2003;Woodrow et al, 2005;Pradines et al, 2006;Tinto et al, 2006).…”

Section: Fig 3 Relative Ec50 (Nm) Distribution Patterns Of Quinine supporting

confidence: 72%

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The in vitro Assessment of Drug Resistant Malaria In Makurdi, North Central Nigeria

Ikpa¹,

Ja²,

Imandeh³

et al. 2010

Science World Journal

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Multi-drug resistant malaria parasite strains have spread to new areas that were once free of such strains. This study evaluated the specific in vitro sensitivities of some standard antimalarial drugs, against Plasmodium falciparum isolates in Makurdi, North Central Nigeria. The standard schizonts growth inhibition assays was used to study the in vitro activities of quinine, artesunate, and amodiaquine against 146 isolates in children aged 2-14 years. 100 % of isolates were in vitro sensitive to quinine, geometric mean effective concentration (EC)50 = 241.55 nM, EC90 = 676.08 nM, and EC99 = 993.12 nM; and artesunate, EC50 = 1.05 nM, EC90 = 2.42 nM, and EC99 = 3.16 nM. 1.37 % of isolates were resistant to amodiaquine, EC50 = 22.08 nM, EC90 = 66.22 nM and EC99 = 100.23 nM. Significant in vitro cross resistance was found at EC50 values of quinine-amodiaquine drug pair (r = + 0.342, P < 0.05), but not quinine -artesunate (r = + 0.057, P > 0.05) or artesunateamodiaquine (r = + 0.088, P > 0.05). These results call for constant surveillance, to curb the spread of P. falciparum resistance to amodiaquine in Nigeria.

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Section: Fig 3 Relative Ec50 (Nm) Distribution Patterns Of Quinine supporting

confidence: 72%

“…have not yet been determined (Noedl et al, 2003), therefore the estimated EC values were reported as a baseline data for future comparison.…”

Section: Determination Of In Vitro Effective Concentration (Ec) Valuementioning

confidence: 99%

The in vitro Assessment of Drug Resistant Malaria In Makurdi, North Central Nigeria

Ikpa¹,

Ja²,

Imandeh³

et al. 2010

Science World Journal

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“…Increasing trend of resistance was observed against all antimalarials in use in Bangladesh. Even mefloquine, an antimalarial which was never used by NMCP, was available temporarily in the private sector also showed relatively high degree of resistance against Pf 9 . Several studies carried out to update the antimalarial drug regimen specially to identify a suitable first line drug, MSF-Holland (NGO) in collaboration with Government of Bangladesh carried out a study to measure the efficacy of several drug combinations including artemether plus lumefantrine (Coartem®).…”

Section: Discussionmentioning

confidence: 99%

An open randomized controlled trial to compare the efficacy of two fixed dose combinations of artemesinin based combinations for uncomplicated falciparum malaria in Bangladesh

Samad¹,

Rahman²,

Yunus³

et al. 2014

Bangladesh Med Res Counc Bull

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National Malaria Control Program (NMCP) of Bangladesh has introduced Artemisinin Based Combination (ACT), Coartem (R) (Artemether-Lumefantrine (AL), fixed dose combination, in the confirmed cases of uncomplicated P. falciparum malaria since 2004. Despite the reduction of mortality due to malaria, the development and spread of anti-malarial drug resistance wordwide posing a threat to the health services and will make it difficult to control malaria in Bangladesh in future. We need to have an alternative to Coartem which could be Artesunate-amodiaquine (AA) in a fixed dose combination (FDC), a cheaper altenative not yet evidenced to be effective and safe to our population. In this study we compared the efficacy and safety of Artemether + Lumefantrene (FDC, Coartem®) with Artesunate +Amodiaquine tablets (100/270 mg FDC) for the treatment of uncomplicated P. falciparum malaria in three high risk multi-drug resistant malaria prevalent areas of Bangladesh. It was an open label randomized controlled trial conducted between December 2008 and November 2009 in 4 upazillas in patients over the age 12 to 60 years diagnosed as a case of uncomplicated P.falciparum malaria. The outcome of the cases were measured as clinical response, parasitological response, defervescence time and parasite clearance time. Drug safety was assessed by comparing the adverse events. A total of 252 cases were randomized to receive Artesunate + Amodiaquine (AA group, 147 cases) and Artemether + Lumefantrene (AL group, 106 cases), one lost to follow up at day 28 in AA group. The distribution of the cases was comparable by age, sex and study sites. Treatment success' response was observed 100% in the AL group and AA group had 99%, two failures with AA were late treatment failures and the difference was not statistically significant (p>.1). The parasitological sensitive (S) response was observed in 97% of cases in AL group and 95% in the AA group, and was not a statistically significant difference. There was no significant difference in deffervescence time and parasite clearance time between two groups of cases. No serious adverse events were observed. The frequencies of minor adverse events were insignificantly different between the two treatment groups. The two ACT regimen, AA and AL had no significant difference in efficacy and safety for treatment of Uncomplicated Malaria in Bangladesh. However, there were few more failures with AA regimen compared to AL regimen, which was not statistically significant. Both these regimens can be used alternatively by the NMCP of Bangladesh as first-line treatment option.

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“…In vitro, parasites are considered to be chloroquine-resistant, the 50% inhibitory concentration (IC 50 ) of the drug is >160 nmol/L (51 µg/L) (Ringwald, 2005). Recent reports from areas where malaria is endemic documented that the majority of chloroquineresistant isolates of P. falciparum have IC 50 values <400 nmol/L (128 µg/L) (Bacon et al, 2007;Sibley and Ringwald, 2006;Hatabu et al, 2005;Borrmann et al, 2002;Moreno et al, 2001;Yang et al, 1997;Noedl et al, 2003). In contrast, typical trough levels are 80 to 125 nmol/L (25 to 40 µg/L).…”

Section: Status Of Resistancementioning

confidence: 99%

Is chloroquine making a comeback?

Saifi

Beg²,

Harrath³

et al. 2012

Afr. J. Pharm. Pharmacol.

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Malaria remains one of the leading causes of disease and death in the tropics, mainly of children under 5 years of age. Chloroquine began as a first-line antimalarial in 1946; it became the corner stone of antimalarial chemotherapy for the next 40 years. It is one of the least expensive antimalarials available and is still in widespread use. Chloroquine can be taken both as prophylactic and as a treatment. For decades, chloroquine was a remarkably effective, safe, and inexpensive antimalarial. Optimism about effectiveness of chloroquine led public health professionals to predict the eradication of malaria by 2000. Despite much research during the last 40 years, the exact mechanism by which the chloroquine kills the malaria parasite remains controversial. Biochemical analyses suggest that this class of compounds enter acidic vacuoles of host cells, where they inhibit the growth of parasites by forming a complex with haematin. Unfortunately, Plasmodium falciparum gradually became resistant to chloroquine. After first appearing in Southeast Asia and South America in the late 1950s, resistance spread throughout Africa by the 1980s. Resistance to chloroquine was slow to develop, taking almost 20 years, despite extensive use of the drug, suggesting that mutations in several genes were required to produce the resistance phenotype. The mechanism of chloroquine resistance also is uncertain. Similar to the artemisinin derivatives, prospects for long-term chloroquine efficacy will be enhanced if it can be used in combination, such as chloroquine-azithromycin. With the right dosage and combination, the prospects for a chloroquine comeback are good.

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Drug-Resistant Malaria in Bangladesh: An in Vitro Assessment

Cited by 35 publications

References 7 publications

The in vitro Assessment of Drug Resistant Malaria In Makurdi, North Central Nigeria

The in vitro Assessment of Drug Resistant Malaria In Makurdi, North Central Nigeria

An open randomized controlled trial to compare the efficacy of two fixed dose combinations of artemesinin based combinations for uncomplicated falciparum malaria in Bangladesh

Is chloroquine making a comeback?

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