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[Diagnosis and Treatment of the First Imported Case of Plasmodium knowlesi Infection in China]

Pan B, Pei FQ, Ruan CW, Lin RX, Cen YZ, Liu MR, et al.

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 2016 12;34(6):513-6.
PMID: 30141606

Objective: To diagnose and treat the first imported active case of Plasmodium knowlesi infection in China.
Methods: The clinical information of the patient was collected. Microscopy of blood smear was conducted after Giemsa staining. Genomic DNA was extracted from blood, and PCR was conducted to amplify rDNA. The PCR products were sequenced and analyzed with BLAST
Results: The patient returned from a one-week tour in a tropical rain forest in Malaysia. The first disease attack occurred in Guangzhou on Oct. 16, 2014, with fever, shivering and sweating. The patient was initially diagnosed as malaria and hospitalized on Oct. 26, 2014. Microscopic observation revealed typical forms of P. knowlesi in blood smear. The red blood cells became enlarged, with big trophozoites appearing as a ring with dual cores and dark brown malaria pigment. The trophozoites were slightly bigger and thicker than P. falciparum. The schizont had 6-8 merozoites, with obvious brown malaria pigment. PCR resulted in a specific band of 1 099 bp. BLAST analysis showed that the sequence of the PCR product was 99% homologous to P. knowlesi (acession No. AM910985.1, L07560.1 and AY580317.1). The patient was diagnosed as P. knowlesi infection, and was then given an 8-day treatment with chloroquine and primaquine, together with dihydroartemisinin piperaquine phosphate tablet. The patient was discharged after recovery on Oct. 28, 2014.
Conclusion: According to the clinical symptoms, epidemiological history and laboratory test, the patient has been confirmed as P. knowlesi infection. It may also be the first active case of knowlesi malaria reported in China.

Matched MeSH terms: Chloroquine
Fulltext Malacca leaf ethanolic extract (Phyllanthus emblica) as a hepatoprotector of the liver of mice (Mus musculus) infected with Plasmodium berghei

Asmilia N, Aliza D, Fahrimal Y, Abrar M, Ashary S

Vet World, 2020 Jul;13(7):1457-1461.
PMID: 32848324 DOI: 10.14202/vetworld.2020.1457-1461

Background and Aim: Although existing research confirms the antiparasitic effect of the Malacca plant against Plasmodium, its effect on the liver, one of the target organs of Plasmodium has not been investigated. Therefore, this study was conducted to explore the potential of the ethanolic extract of Malacca (Phyllanthus emblica) leaves in preventing liver damage in mice (Mus musculus) caused by Plasmodium berghei infection.
Materials and Methods: This study was conducted using the livers of 18 mice fixed in 10% neutral-buffered formalin. A completely randomized design with a unidirectional pattern comprising six treatments was used in this study, with each treatment consisting of three replications. Treatment 0 was the negative control group infected with P. berghei, treatment 1 was the positive control group infected with P. berghei followed by chloroquine administration at a dose of 5 mg/kg BW, and treatments 2, 3, 4, and 5 were groups infected with P. berghei and administered Malacca leaf ethanolic extracts at doses of 100, 300, 600, and 1200 mg/kg BW, respectively. The extracts were administered orally using a gastric tube for 4 consecutive days. Mice were sacrificed on the 7th day and livers were collected for histopathological examination.
Results: Histopathological examination of the livers of mice infected with P. berghei demonstrated the presence of hemosiderin, hydropic degeneration, fat degeneration, necrosis, and megalocytosis. However, all these histopathological changes were reduced in the livers of P. berghei-infected mice treated with various doses of Malacca leaf ethanolic extract. The differences between the treatments were found be statistically significant (p<0.05).
Conclusion: Ethanolic extract of Malacca leaves has the potential to protect against liver damage in mice infected with P. berghei. The dose of 600 mg/kg BW was found to be the most effective compared with the doses of 100, 300, and 1200 mg/kg BW.

Matched MeSH terms: Chloroquine
Fulltext Suppression of Plasmodium berghei parasitemia by LiCl in an animal infection model

Nurul Aiezzah Z, Noor E, Hasidah MS

Trop Biomed, 2010 Dec;27(3):624-31.
PMID: 21399604 MyJurnal

Malaria, caused by the Plasmodium parasite is still a health problem worldwide due to resistance of the pathogen to current anti-malarials. The search for new anti-malarial agents has become more crucial with the emergence of chloroquine-resistant Plasmodium falciparum strains. Protein kinases such as mitogen-activated protein kinase (MAPK), MAPK kinase, cyclin-dependent kinase (CDK) and glycogen synthase kinase- 3(GSK-3) of parasitic protozoa are potential drug targets. GSK-3 is an enzyme that plays a vital role in multiple cellular processes, and has been linked to pathogenesis of several diseases such as type II diabetes and Alzheimer's disease. In the present study, the antiplasmodial property of LiCl, a known GSK-3 inhibitor, was evaluated in vivo for its antimalarial effect against mice infected with Plasmodium berghei. Infected ICR mice were intraperitoneally administered with LiCl for four consecutive days before (prophylactic test) and after (suppressive test) inoculation of P. berghei-parasitised erythrocytes. Results from the suppressive test (post-infection LiCl treatment) showed inhibition of erythrocytic parasitemia development by 62.06%, 85.67% and 85.18% as compared to nontreated controls for the 100 mg/kg, 300 mg/kg and 600 mg/kg dosages respectively. Both 300 mg/kg and 600 mg/kg LiCl showed similar significant (P<0.05) suppressive values to that obtained with chloroquine-treated mice (86% suppression). The prophylactic test indicated a significantly (P<0.05) high protective effect on mice pre-treated with LiCl with suppression levels relatively comparable to chloroquine (84.07% and 86.26% suppression for the 300 mg/kg and 600 mg/kg LiCl dosages respectively versus 92.86% suppression by chloroquine). In both the suppressive and prophylactic tests, LiCl-treated animals survived longer than their non-treated counterparts. Mortality of the non-treated mice was 100% within 6 to 7 days of parasite inoculation whereas mice administered with LiCl survived beyond 9 days. Healthy non-infected mice administered with 600 mg/ kg LiCl for four consecutive days also showed decreased mortality compared to animals receiving lower doses of LiCl; three of the seven mice intraperitoneally injected with the former dose of LiCl did not survive more than 24 h after administration of LiCl whereas animals given the lower LiCl doses survived beyond four days of LiCl administration. To date, no direct evidence of anti-malarial activity in vivo or in vitro has been reported for LiCl. Evidence of anti-plasmodial activity of lithium in a mouse infection model is presented in this study.

Matched MeSH terms: Chloroquine/administration & dosage
Fulltext Antimalarial properties of Goniothalamin in combination with chloroquine against Plasmodium yoelii and Plasmodium berghei growth in mice

Mohd Ridzuan MA, Ruenruetai U, Noor Rain A, Khozirah S, Zakiah I

Trop Biomed, 2006 Dec;23(2):140-6.
PMID: 17322815 MyJurnal

Malaria is a disease which is still endemic and has become a disastrous scourge because of the emergence of antimalarial drug resistant Plasmodium falciparum. A new approach in addressing this is in developing a combination drug. This study is to show the enhancement of antimalarial properties, when single compound, goniothalamin combine with standard drug, chloroquine. Based on 4 Day Test, percentage of parasite growth on treated infected mice were determined. Oral treatment with 1 mg/kg BW of chloroquine on experimental mice suppressed 70% and 76.7% of both Plasmodium yoelii and Plasmodium berghei, respectively. The infection of P. berghei in mice was inhibited less than 50% by goniothalamin individual treatment at all doses in this study. About 27.8% and 18.5% inhibition of infection were observed in P. yoelii infected mice treated with 30 mg/kg and 60 mg/kg of goniothalamin respectively and the suppression exceed more than 50% at higher doses (90 and 120 mg/kg). Combination of 1 mg/kg chloroquine with either 30 mg/kg or 60 mg/kg of goniothalamin decreased the parasitemia of P. yoelii infected mice more than 90% and prolong the survival up to 100% after treatment. Similar treatment to P. berghei infected mice only shows about 60% reduction of parasitemia. The study findings showed that antimalarial property of goniothalamin was enhanced by combination with chloroquine at lower dose of each drug.

Matched MeSH terms: Chloroquine/administration & dosage; Chloroquine/pharmacology*
Episodic positive selection in the Cam734 haplotype and low prevalence of the A144F mutation in Plasmodium falciparum chloroquine resistance transporter gene among Thai isolates

Buppan P, Seethamchai S, Kuamsab N, Jongwutiwes S, Putaporntip C

Trop Biomed, 2018 Dec 01;35(4):861-871.
PMID: 33601836

Chloroquine resistance transporter of Plasmodium falciparum (PfCRT) is a food vacuolar transmembrane protein that mediates susceptibility of the parasite to chloroquine. A mutation at K76T of the Pfcrt gene is a key determinant for chloroquine resistance phenotype. In the absence of drug pressure, in vitro growth rate of chloroquine-resistance parasites was outcompeted by wild-type parasites unless intragenic compensatory mutations occurred. Chloroquine-resistant P. falciparum bearing the Cam734 haplotype known to circulate in endemic areas of Cambodia bordering Thailand contains 9 mutations in Pfcrt and exhibits both chloroquine resistance and comparable growth rate to the chloroquine-sensitive 3D7 strain. To analyze the evolution of the Cam734 haplotype, codon-based analysis was performed by using the mixed effects model of evolution (MEME), branch-site random effects likelihood (BR-REL) and other related methods. Results revealed that the Cam734 haplotype has evolved distinctively from other known mutant haplotypes including the most common Dd2 haplotype in Southeast Asia. Evidence of episodic positive selection was detected at codon 144, characterized by c.[430G>T; 431C>T] (p.A144F), known to be indispensable for both chloroquine resistance and restoration of growth rate of the parasites. To survey the prevalence of mutations at codons 76 and 144 in Pfcrt among Thai isolates, restriction fragment analysis of 548 P. falciparum isolates collected from six endemic provinces of Thailand during 1991 and 2016 was performed. The 144F Pfcrt mutant was detected in 7 (1.28%) isolates. All Thai isolates analyzed herein harbored a mutation at codon 76 whilst the wild-type parasite was not found. The low prevalence of isolates bearing the mutation 144F in PfCRT could imply little or lack of survival advantage of this mutant in endemic areas of Thailand where the wild-type parasites seem to be absent or extremely rare.

Matched MeSH terms: Chloroquine
Progression of malaria induced pathogenicity during chloroquine therapy

Zaid OI, Abd Majid R, Sidek HM, Noor SM, Abd Rachman-Isnadi MF, Bello RO, et al.

Trop Biomed, 2020 Mar 01;37(1):29-49.
PMID: 33612716

Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to eradicate malaria This study aims at investigating the impact of treatment failure with chloroquine on the progression of the disease-induced histo-pathogenic and immunogenic outcomes. To achieve this, Rane's protocol with modifications was applied on a model of Plasmodium berghei ANKA infected ICR mice to determine the dose response curve of chloroquine and to screen the treatment impact on the disease progression. Chloroquine was given at 1, 5, 10, 15 and 20 mg/kg once the parasitemia reached to 20-30% (the experimental initiation point). During the subsequent days, the mice were monitored for changes in the clinical signs, hematology parameters and the progress of the parasitemia until the parasitemia reached to 60-70% (the experimental termination point) or up to 10 days after chloroquine administration in case of achieving a complete eradication of the parasite. At the end, the mice were exsanguinated and their blood and organs were collected for the biochemistry and the histology study. A complete eradication of the parasite was achieved at 20 mg/kg while recrudescence was observed at the lower doses. At 1 mg/kg, the parasite growth was comparable to that of the positive control. The histo-pathogenic and immunogenic changes were stronger in the groups that experienced recrudescence (at 5 and 10 mg/kg). All in all, the study highlights the possibility of having a worsened clinical condition when chloroquine is given at its sub-therapeutic doses during malaria treatment.

Matched MeSH terms: Chloroquine/administration & dosage*; Chloroquine/therapeutic use
Potential of repurposing chloroquine as an adjunct therapy for melioidosis based on a murine model of Burkholderia pseudomallei infection

Ganesan N, Embi N, Hasidah MS

Trop Biomed, 2020 Jun 01;37(2):303-317.
PMID: 33612800

Burkholderia pseudomallei is the etiologic agent of melioidosis, a major cause of community-acquired pneumonia and sepsis in the endemic areas. The overall mortality of patients with severe melioidosis remains high due to severe sepsis attributed to overwhelming inflammatory cytokine response in spite of recommended antibiotic therapy. It is crucial that therapeutic approaches beyond just effective antibiotic treatment such as adjunct therapy be considered to mitigate the dysregulated inflammatory signaling and augment host defenses. In an acute B. pseudomallei infection model, we have previously demonstrated that treatment with anti-malarial drug, chloroquine, modulated inflammatory cytokine levels and increased animal survivability via Akt-mediated inhibition of glycogen synthase kinase-3β (GSK3β). GSK3β is a downstream effector molecule within the phosphatidylinositol 3-kinase (PI3K)/ Akt axis which plays a pivotal role in regulating the production of pro- and anti-inflammatory cytokines. Here we evaluate the effect of chloroquine treatment in combination with a subtherapeutic dose of the antibiotic doxycycline on animal survivability, cytokine levels and phosphorylation states of GSK3β (Ser9) in a murine model of acute melioidosis infection to investigate whether chloroquine could be used as an adjunct therapy along with doxycycline for the treatment of melioidosis. Our findings revealed that 50 mg/kg b.w. chloroquine treatment together with a dose of 20 mg/kg b.w. doxycycline improved survivability (100%) of mice infected with 3 X LD50 of B. pseudomallei and significantly (P<0.05) lowered the bacterial loads in spleen, liver and blood compared to controls. B. pseudomallei-infected mice subjected to adjunct treatment with chloroquine and doxycycline significantly (P<0.05) reduced serum levels of pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) but increased levels of antiinflammatory cytokines (IL-4 and IL-10). Western blot analysis demonstrated that the intensities of pGSK3β (Ser9) in liver samples from mice treated with chloroquine and doxycycline combination were significantly (P<0.05) higher suggesting that the adjunct treatment resulted in significant inhibition of GSK3β. Taken together the bacteriostatic action of doxycycline coupled with the cytokine-modulating effect of chloroquine gave full protection to B. pseudomallei-infected mice and involved inhibition of GSK3β. Findings from the present study using B. pseudomallei-infected BALB/c mice suggest that chloroquine is a plausible candidate for repurposing as adjunct therapy to treat acute B. pseudomallei infection.

Matched MeSH terms: Chloroquine/therapeutic use*
Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes

Safar HF, Ali AH, Zakaria NH, Kamal N, Hassan NI, Agustar HK, et al.

Trop Biomed, 2022 Dec 01;39(4):552-558.
PMID: 36602215 DOI: 10.47665/tb.39.4.011

Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

Matched MeSH terms: Chloroquine
Polymorphism in the pvcrt-o and pvmdr-1 genes of Plasmodium vivax associated with a better prognosis for malaria

Alves-Junior ER, Dombroski TCD, Nakazato L, Dutra V, Neves-Costa JD, Katsuragawa TH, et al.

Trop Biomed, 2022 Sep 01;39(3):421-427.
PMID: 36214439 DOI: 10.47665/tb.39.3.012

The early molecular identification of strains of Plasmodium vivax that have a worse prognosis is important to stratify the risk of complications and choice of conduct made by medical teams. Thus, the aim of the present study was to associate the presence of polymorphisms in the pvmdr-1 and pvcrt-o resistance genes of P. vivax in patients with better or worse prognosis. This cross-sectional epidemiological study was conducted based on data obtained from the records of 120 patients diagnosed with malaria in the Brazilian Amazon. The T958M and F1076L mutations of the pvmdr-1 gene had a frequency of 3.3 and 4.2%, respectively, and primo-infected patients had a 17 times greater chance of being infected with protozoa with the T958M mutation compared to patients with previous episodes. Regarding pvcrt-o, the C393T and T786C polymorphisms had a frequency of 14.2 and 3.3%, respectively, and self-declared white patients had a 3.1 times greater chance of being infected with protozoa with the C393T polymorphism. In addition, patients with this pvcrt-o polymorphism had lower concentrations of C-reactive protein, indicating a better prognosis. These data present clues of genetic indicators useful for assessing the virulence of the parasite and the prognosis of patients with vivax malaria.

Matched MeSH terms: Chloroquine/therapeutic use
The superior efficacy of chloroquine over buparvaquone in reducing the chronic cerebral Toxoplasma gondii cysts load and improving the ultrastructural pathology in an immunocompromised murine model

Fahmy MEA, Abdel-Aal AA, Hassan SI, Shalaby MA, Esmat M, Abdel Shafi IR, et al.

Trop Biomed, 2023 Mar 01;40(1):115-123.
PMID: 37356011 DOI: 10.47665/tb.40.1.018

Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 - 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.

Matched MeSH terms: Chloroquine/pharmacology; Chloroquine/therapeutic use
Nephropathy in Malaria

Wolthuis FH

Trop Geogr Med, 1968 Mar;20(1):21-7.
PMID: 4868143
Matched MeSH terms: Chloroquine/therapeutic use
Opisthorchis viverrini (Poirier, 1886) a trematode parasite of man in West Malaysia

Bisseru B, Chong LK

Trop Geogr Med, 1969 Jun;21(2):138-46.
PMID: 5816416
Matched MeSH terms: Chloroquine/therapeutic use
The Treatment of Plasmodium knowlesi Malaria

Barber BE, Grigg MJ, William T, Yeo TW, Anstey NM

Trends Parasitol, 2017 03;33(3):242-253.
PMID: 27707609 DOI: 10.1016/j.pt.2016.09.002

Plasmodium knowlesi occurs across Southeast Asia and is the most common cause of malaria in Malaysia. High parasitaemias can develop rapidly, and the risk of severe disease in adults is at least as high as in falciparum malaria. Prompt initiation of effective treatment is therefore essential. Intravenous artesunate is highly effective in severe knowlesi malaria and in those with moderately high parasitaemia but otherwise uncomplicated disease. Both chloroquine and artemisinin-combination therapy (ACT) are highly effective for uncomplicated knowlesi malaria, with faster parasite clearance times and lower anaemia rates with ACT. Given the difficulties with microscope diagnosis of P. knowlesi, a unified treatment strategy of ACT for all Plasmodium species is recommended in coendemic regions.

Matched MeSH terms: Chloroquine/therapeutic use*
Efficacy and safety of chloroquine for treatment in patients with uncomplicated Plasmodium vivax infections in endemic countries

Naing C, Aung K, Win DK, Wah MJ

Trans R Soc Trop Med Hyg, 2010 Nov;104(11):695-705.
PMID: 20850161 DOI: 10.1016/j.trstmh.2010.08.009

Chloroquine (CQ) is a relatively inexpensive drug for treatment of malaria. If efficacy of CQ is still assumed, then it should be indicated in malaria treatment policies as the drug of choice for uncomplicated Plasmodium vivax malaria in endemic countries with resource constraints. The objective of this review is to summarize the existing evidence on the relative efficacy and safety of CQ in treating patients with uncomplicated P. vivax malaria in endemic countries. We searched online data bases (PUBMED, MEDLINE, EMBASE, The Cochrane Library) and the reference lists of the retrieved articles. Fifteen randomized controlled trials (n=6215) assessing the relative efficacy and safety of CQ for treatment of uncomplicated P. vivax malaria were included. CQ monotherapy was compared to CQ plus primaquine (PQ), artemisinin/artemether, artemisinin based combination therapy, quinine, CQ plus tafenoquine, chlorguanil plus dapsone, azithromycin, or placebo. Treatment efficacy was not significantly different between the CQ monotherapy group and that of the CQ with PQ 14 day group at 28 day follow-up (55/711, 7.7% vs 35/712, 4.9%; P=0.16). Evidence from the trials identified for this review draw a fairly clear conclusion about the relative efficacy and safety of CQ for treating uncomplicated P. vivax malaria infection. However, further research in this field with well powered, randomized, non-inferiority design, using the standardized protocol is needed.

Matched MeSH terms: Chloroquine/therapeutic use*
Plasmodium falciparum: increased proportion of severe resistance (RII and RIII) to chloroquine and high rate of resistance to sulfadoxine-pyrimethamine in Peninsular Malaysia after two decades

Lokman Hakim S, Sharifah Roohi SW, Zurkurnai Y, Noor Rain A, Mansor SM, Palmer K, et al.

Trans R Soc Trop Med Hyg, 1996 5 1;90(3):294-7.
PMID: 8758083

Uncomplicated falciparum malaria patients were randomly assigned to receive either 25 mg/kg chloroquine (CHL) over 3 d or a statim dose of 25 mg/kg sulfadoxine (SDX) plus 1.25 mg/kg pyrimethamine (PYR). Patients were followed up for 28 d and the parasite response graded according to World Health Organization criteria. Overall resistance to CHL was 63.3% and 47.4% to SDX/PYR. RI, RII and RIII rates were 9.1%, 42.4% and 12.1% for CHL and 10.5%, 21.1% and 15.8% for SDX/PYR, respectively. Degree and rates of resistance to CHL were significantly correlated with pre-treatment parasite density, but not those to SDX/PYR. Plasma CHL and SDX/PYR levels were within the reported ranges and were not significantly different in patients with sensitive and resistant responses.

Matched MeSH terms: Chloroquine/blood; Chloroquine/therapeutic use*
Assessment of the association between three pfmdr1 point mutations and chloroquine resistance in vitro of Malaysian Plasmodium falciparum isolates

Cox-Singh J, Singh B, Alias A, Abdullah MS

Trans R Soc Trop Med Hyg, 1995 7 1;89(4):436-7.
PMID: 7570891
Matched MeSH terms: Chloroquine*
A study of the sensitivity of Plasmodium falciparum to chloroquine and mefloquine using the in vitro microtechnique in Peninsular Malaysia

Ho KB, Mak JW, Ramadas M

Trans R Soc Trop Med Hyg, 1987;81(2):257-9.
PMID: 3303483

Plasmodium falciparum drug sensitivities to chloroquine and mefloquine were assessed with WHO in vitro microtechnique test kits in 5 localities near the border with Thailand in Peninsular Malaysia. 105 of 113 (92.9%) parasite isolates were successfully tested and 103 (98.1%) showed resistance to chloroquine with parasite growth even at greater than or equal to 5.7 pmol of the drug. All these isolates were sensitive to mefloquine, parasite growth being inhibited at less than or equal to 11.3 pmol of the drug.

Matched MeSH terms: Chloroquine/pharmacology*
Doxycycline in the treatment of falciparum malaria among aborigine children in West Malaysia

Ponnampalam JT

Trans R Soc Trop Med Hyg, 1981;75(3):372-7.
PMID: 7034311

Doxycycline in a single dose was found to be a valuable drug in the treatment of chloroquine-resistant falciparum malaria. It was less effective in a single daily dose of 4 mg/kg body-weight for four days, when it cured only five out of nine patients, while a dosage of 4 mg/kg body-weight for seven days cured 23 out of 26 patients.

Matched MeSH terms: Chloroquine/therapeutic use
Chemosuppression of malaria by the triple combination mefloquine/sulfadoxine/pyrimethamine: a field trial in an endemic area in Malaysia

Navaratnam V, Mohamad M, Hussain S, Kumar A, Jamaludin A, Sulaiman I, et al.

Trans R Soc Trop Med Hyg, 1989 11 1;83(6):755-9.
PMID: 2694509

Malaria, particularly that due to chloroquine-resistant Plasmodium falciparum, which requires management with antimalarial drugs capable of protecting against multiresistant strains, has emerged in Malaysia. A study was carried out to assess the efficacy and tolerability of 2 dosages of mefloquine/sulfadoxine/pyrimethamine (MSP; RO 13-5112) compared to Fansidar in a malaria endemic area. 914 subjects in 3 random groups were studied. Occurrence of malaria was assessed both clinically as well as by blood films. Plasma drug levels were also measured. The results showed that the low dose of MSP was completely effective in suppressing parasitaemia. 2.7% of the study population reported adverse drug reactions, the lowest incidence being in subjects on the low dose; their blood chemical profiles were also the least affected. The plasma levels of pyrimethamine and sulfadoxine achieved in the low dose group were slightly higher than expected, but there was no significant difference in bioavailability. The study showed that, for chemoprophylaxis, a low dose of MSP provided effective protection with minimal side effects.

Matched MeSH terms: Chloroquine/therapeutic use
Prophylactic and sporontocidal treatment of chloroquine resistant Plasmodium falciparum from Malaya

Clyde DF, DuPont HL, Miller RM, McCarthy VC

Trans R Soc Trop Med Hyg, 1970;64(6):834-8.
PMID: 4924648
Matched MeSH terms: Chloroquine/therapeutic use*

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