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Chloroquine resistant Plasmodium falciparum infection from Lampung and South Sumatra, Indonesia

Pribadi W, Dakung LS, Gandahusada S, Daldyono

Southeast Asian J. Trop. Med. Public Health, 1981 Mar;12(1):69-73.
PMID: 7020096

A report was made of 4 cases of chloroquine resistant Plasmodium falciparum infections. The infections, detected in Jakarta, were imported from Kotabumi, Tanjung Karang, the Island of Pidada in the Lampung Province and from Pangkalpinang on the Island Bangka in the Province of South Sumatra. Treatment with courses of 1500 mg chloroquine base and with increased dosages up to 2250 mg base failed to cure the patients. The chloroquine sensitivity test in vitro was carried out in 3 patients, which showed that the Plasmodium falciparum strains were resistant to chloroquine at the R I level. The strains appeared to be similar to the Malaya Camp strain. In vivo observations revealed that the parasites were resistant at the R I level with a delayed recrudescence. The chloroquine resistant falciparum malaria cases, acquired in South Sumatra, may therefore be regarded as the first reported cases from a focus outside the already known two foci in Indonesia, namely East Kalimantan and Irian Jaya. It may be expected that chloroquine resistant Plasmodium falciparum will be encountered in other parts of Indonesia in the near future. The use of a combination of sulfadoxine and pyrimethamine should not be recommended in Indonesia because chloroquine is still considered the drug of choice against all malaria infections in Indonesia.

Matched MeSH terms: Chloroquine/therapeutic use*
Epidemiology of malaria in Malaysia

Rahman KM

Rev. Infect. Dis., 1982 9 1;4(5):985-91.
PMID: 6755616

Malaria is a major public health problem in Malaysia, particularly in peninsular Malaysia and the state of Sabah. An eradication program started in the states of Sabah and Sarawak in 1961 initially was remarkably successful. A similar but staged program was started in peninsular Malaysia in 1967 and was also quite successful. However, a marked upsurge in incidence in Sabah in 1975-1978 showed that malaria is still a major hazard. The disease leads to great economic losses in terms of the productivity of the labor force and the learning capacity of schoolchildren. The topography, the climate, and the migrations of the people due to increased economic activity are similar in peninsular Malaysia, Sabah, and Sarawak. However, the epidemiologic picture differs strikingly from area to area in terms of species of vectors, distribution of parasitic species, and resistance of Plasmodium falciparum to chloroquine. Likewise, the problems faced by the eradication or control programs in the three regions are dissimilar. Because solutions to only some of these problems are possible, the eradication of malaria in Malaysia is not likely in the near future. However, the situation offers an excellent opportunity for further studies of antimalaria measures.

Matched MeSH terms: Chloroquine/pharmacology
Fulltext Malaria in the Malaysian Army with particular reference to chemosuppressive use

Supramaniam V, Datta GC, Singam V, Singh J

Med J Malaysia, 1987 Mar;42(1):44-9.
PMID: 3323860

Malaria is the most important communicable disease in the field for the Malaysian soldier. His chief weapon is chemoprophylaxis. This was proguanil hydrochloride in the '50s, changed to Daraclor in 1962; since late 1985, Fansidar only is used. The incidence of malaria over the years has fluctuated widely and had its peak in 1977 at 29.7/1,000 soldiers and since then has shown a downward trend. Studies carried out to study the problem are noted briefly. Antimalarial discipline in the field, continued surveillance and integrated control measures in the base are emphasised in the fight against malaria.

Matched MeSH terms: Chloroquine/therapeutic use*
Studies on the resistance of malaria to chloroquine and to a combination of chloroquine and pyrimethamine in Peninsular Malaysia

Dondero TJ, Parsons RE, Ponnampalam JT

Trans R Soc Trop Med Hyg, 1976;70(2):145-8.
PMID: 785725

In vivo chloroquine resistance surveys, which allowed for detection of late recrudescing RI resistance, were conducted in three regions of Peninsular Malaysia, which were previously not recognized as having appreciable drug resistance. Among the 485 Plasmodium falciparum infections tested resistance rates ranged locally from 20% to 67% in those with parasitaemias over 1,000 per mm3, and 5% to 59% in all parasitaemias. The region found to have the most serious resistance was western Pahang. In one study a combination of chloroquine and pyrimethamine proved no more efficacious than chloroquine alone. Most of the resistance encountered was the late recrudescing RI type. There was no apparent correlation between drug resistance and Anopheles balabacensis as this species was not found despite intensive collections in two of the three main regions. There was no evidence of resistance among the 222 P. vivax and 35 P. malariae infections also tested.

Matched MeSH terms: Chloroquine/pharmacology*
Malaria--the British point of view

Drew R

Ann Intern Med, 1969 Jan;70(1):147-9.
PMID: 5763718
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*
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
Fulltext Studies on the relationship between fluorescent antibody response and ecology of malaria in Malaysia

Collins WE, Warren M, Skinner JC, Fredericks HJ

Bull World Health Organ, 1968;39(3):451-63.
PMID: 4882987

The fluorescent antibody (FA) technique was used to detect the presence of malarial antibody in populations living in 3 different ecological areas of Malaysia. Serum samples were tested using Plasmodium falciparum, P. vivax, P. malariae and P. fieldi antigens. An area of hyperendemic malaria had a good correlation between the antibody responses and active parasitaemias. The percentage and intensity of responses increased with the age of the individuals. In an area of hypoendemic malaria, each of 17 sites had ecological conditions which would favour or discourage the transmission of malaria. The reasons for high FA responses in some villages and low responses in others were readily apparent. The effect of even limited control programmes on the malarial ecology could be measured by an examination of the antibody responses. An aboriginal population receiving suppressive drugs had FA responses indicating both past experience and the effect of the drug programme.

Matched MeSH terms: Chloroquine/therapeutic use
DRUG-RESISTANT FALCIPARUM MALARIA FROM CAMBODIA AND MALAYA

CONTACOS PG, LUNN JS, COATNEY GR

Trans R Soc Trop Med Hyg, 1963 Nov;57:417-24.
PMID: 14081296
Matched MeSH terms: Chloroquine*
Barrier spraying at the Kelantan side of the Thai-Malaysia border

Huehne WH

J Trop Med Hyg, 1971 May;74(5):106-9.
PMID: 5580454
Matched MeSH terms: Chloroquine/therapeutic use
Experience with an insecticide-drug combination and observations on suppressive chloroquine-pyrimethamine treatment

Huehne WH

J Trop Med Hyg, 1971 May;74(5):110-6.
PMID: 4931687
Matched MeSH terms: Chloroquine/therapeutic use*
DRUG-RESISTANCE IN FALCIPARUM MALARIA IN SOUTH-EAST ASIA

SANDOSHAM AA, EYLES DE, MONTGOMERY R

Med J Malaysia, 1964 Mar;18:172-83.
PMID: 14157183
Matched MeSH terms: Chloroquine*
Intraspecific variation in Plasmodium falciparum

Aikawa M, Ward RA

Am J Trop Med Hyg, 1974 Jul;23(4):570-3.
PMID: 4367833
Matched MeSH terms: Chloroquine/pharmacology
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*
Effect of 7-day daily replacement of culture medium containing Eurycoma longifolia Jack constituents on the Malaysian Plasmodium falciparum isolates

Ang HH, Chan KL, Mak JW

J Ethnopharmacol, 1995 Dec 15;49(3):171-5.
PMID: 8824743 DOI: 0.1016/0378-8741(95)01321-0

Six Malaysian chloroquine-resistant Plasmodium falciparum isolates were cultured in vitro following the candle-jar method. Antimalarial evaluations of daily replacement of culture medium containing chloroquine and a semi-purified extract of Eurycoma longifolia Jack (containing 13 beta, 18-dihydroeurycomanol (1), eurycomanol-2-O-beta-D-glucopyranoside (2), eurycomanol (3) and eurycomanone (4)) were performed on 6-well plates at 37 degrees C for a week. Presence or absence of the parasites was determined microscopically on thin-film Giemsa-stained preparations. Results showed that the antimalarial activity of Eurycoma longifolia Jack was dose-dependent and reached a maximum of < 50% at 0.07-5.00 micrograms ml-1 after 1 day post-treatment. However, complete inhibitions were observed at 1.25-5.00 micrograms ml-1 extract after 3 days post-treatment and 0.62 and 0.31 micrograms ml-1 after 4 and 6 days post-treatment, respectively. Further results indicated that chloroquine exhibited total inhibition at concentrations > 2.50 and 0.62 micrograms ml-1 after 1 and 2 days post-treatment, respectively and at all concentrations after 3 days post-treatment.

Matched MeSH terms: Chloroquine/pharmacology
Antimalarial drug susceptibility of Plasmodium falciparum isolates from forest fringe dwelling aborigines (Orang Asli) of Peninsular Malaysia

Lambros C, Davis DR, Lewis GE

Am J Trop Med Hyg, 1989 Jul;41(1):3-8.
PMID: 2669543 DOI: 10.4269/ajtmh.1989.41.1.TM0410010003

The drug susceptibility of 70 isolates of Plasmodium falciparum to standard and experimental antimalarials was evaluated using a radioisotope microdilution method. All isolates were from forest fringe dwelling Orang Asli, the aborigines of Peninsular Malaysia. The geometric mean IC50 values were: chloroquine, 10 ng/ml; amodiaquine, 4.7 ng/ml; mefloquine, 2.8 ng/ml; quinine, 40.5 ng/ml; halofantrine, 1.5 ng/ml; enpiroline, 3 ng/ml; and pyrimethamine, 21 ng/ml. Four isolates exhibited decreased susceptibility to chloroquine (IC50 greater than 60 ng/ml), and one exhibited decreased susceptibility to quinine (IC50 = 161 ng/ml). Three isolates showed decreased susceptibility to mefloquine (IC50 = 10-11 ng/ml). The lack of drug pressure may account for the high prevalence of P. falciparum isolates susceptible to chloroquine.

Matched MeSH terms: Chloroquine/pharmacology
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
Effects of quinine and of chloroquine in vitro against a strain of chloroquine-resistant Plasmodium falciparum that displays a relative resistance to quinine in vivo

Rieckmann KH, McNamara JV, Powell RD

Mil Med, 1969 Sep;134(10):795-801.
PMID: 4987058
Matched MeSH terms: Chloroquine/pharmacology*
Fulltext Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial

Grigg MJ, William T, Menon J, Barber BE, Wilkes CS, Rajahram GS, et al.

Clin Infect Dis, 2016 Jun 01;62(11):1403-1411.
PMID: 27107287 DOI: 10.1093/cid/ciw121

BACKGROUND: Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown.
METHODS: A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan-Meier analysis.
RESULTS: From 2012 to 2014, 103 adults and children were enrolled. Treatment failure by day 28 was 61.1% (95% confidence interval [CI], 46.8-75.6) after CQ and 0% (95% CI, 0-.08) following AS-MQ (P < .001), of which 8.2% (95% CI, 2.5-9.6) were early treatment failures. All patients with treatment failure had therapeutic plasma CQ concentrations at day 7. Compared with CQ, AS-MQ was associated with faster parasite clearance (normalized clearance slope, 0.311 vs 0.127; P < .001) and fever clearance (mean, 19.0 vs 37.7 hours; P =001) and with lower risk of anemia at day 28 (odds ratio = 3.7; 95% CI, 1.5-9.3; P =005). Gametocytes were present at day 28 in 23.8% (10/42) of patients following CQ vs none with AS-MQ (P < .001). AS-MQ resulted in lower bed occupancy: 4037 vs 6510 days/1000 patients (incidence rate ratio 0.62; 95% CI, .60-.65; P < .001). One patient developed severe anemia not regarded as related to their AS-MQ treatment.
CONCLUSIONS: High-grade CQ-resistant P. vivax is prevalent in eastern Malaysia. AS-MQ is an efficacious ACT for all malaria species. Wider CQ-efficacy surveillance is needed in vivax-endemic regions with earlier replacement with ACT when treatment failure is detected.Clinical Trials Registration NCT01708876.

Matched MeSH terms: Chloroquine/pharmacology*
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*

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