Heightened Transmission of Stable Malaria in an Isolated Population in the Highlands of Irian Jaya, Indonesia

Anthony, Ronald L.; Bangs, Michael J.; Hamzah, Nasir; Basri, Hasan; Purnomo, Purnomo; Subianto, Budi

doi:10.4269/ajtmh.1992.47.346

Cited by 37 publications

(22 citation statements)

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“…More common in sub-Saharan Africa and the southwest Pacific (3,5,6,12,38), P. malariae is also detected in Asia (7,11,13,14,21), the Middle East (1), and South and Central America (34,39). Responsible for quartan malaria, P. malariae is usually considered a benign pathogen compared to human sympatric P. falciparum and P. vivax.…”

Section: Discussionmentioning

confidence: 99%

Reduced Impact of Pyrimethamine Drug Pressure on Plasmodium malariae Dihydrofolate Reductase Gene

Khim

Kim

Bouchier

et al. 2012

Antimicrob Agents Chemother

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Molecular investigations performed following the emergence of sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum have allowed the identification of the dihydrofolate reductase (DHFR) enzyme as the target of pyrimethamine. Although clinical cases of Plasmodium malariae are not usually treated with antifolate therapy, incorrect diagnosis and the high frequency of undetected mixed infections has probably exposed non-P. falciparum parasites to antifolate therapy in many areas. In this context, we aimed to assess the worldwide genetic diversity of the P. malariae dhfr gene in 123 samples collected in Africa and Asia, areas with different histories of SP use. Among the 10 polymorphic sites found, we have observed 7 new mutations (K55E, S58R, S59A, F168S, N194S, D207G, and T221A), which led us to describe 6 new DHFR proteins. All isolates from African countries were classified as wild type, while new mutations and haplotypes were recognized as exclusive to Madagascar (except for the double mutations at nucleotides 341 and 342 [S114N] found in one Cambodian isolate). Among these nonsynonymous mutations, two were likely related to pyrimethamine resistance: S58R (corresponding to C59R in P. falciparum and S58R in Plasmodium vivax; observed in one Malagasy sample) and S114N (corresponding to S108N in P. falciparum and S117N in P. vivax; observed in three Cambodian samples). Currently, in many parts of the globe, the emergence and spread of malaria parasites resistant to various antimalarial drugs recommended by the international organizations remain major factors threatening control efforts (41). Among the five Plasmodium species that affect humans (40), resistant Plasmodium falciparum parasites were first selected by chloroquine (CQ), a highly effective, fast-acting, and inexpensive 4-aminoquinoline widely used for several decades, in Southeast Asia or South America (29,44) in the 1960s. CQ-resistant parasites of the other Plasmodium species emerged much later: in 1989 for Plasmodium vivax (Papua New Guinea) (32) and in 2002 for Plasmodium malariae (Indonesia) (26). Following the introduction of the sulfadoxinepyrimethamine combination (SP) to replace CQ as the first-line treatment for uncomplicated P. falciparum malaria, the same scenario was observed. SP-resistant P. falciparum parasites were first detected in the 1980s (9, 19). Molecular investigations, based on laboratory and field isolates, demonstrated later that the resistance of P. falciparum to pyrimethamine was mediated by specific point mutations in the dihydrofolate reductase gene (dhfr) (30, 31). Currently, it is assumed that pyrimethamine resistance is conferred by the stepwise selection of a series of nonsynonymous point mutations (codons 50, 51, 59, and 164) from the S108N single mutant allele (24). Parasites with the triple mutant allele (N51I C59R S108N) have markedly reduced in vitro susceptibility to pyrimethamine, and the presence of this allele in a P. falciparum-infected patient increases the risk of SP therapeutic failure (15). The ...

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Section: Discussionmentioning

confidence: 99%

Reduced Impact of Pyrimethamine Drug Pressure on Plasmodium malariae Dihydrofolate Reductase Gene

Khim

Kim

Bouchier

et al. 2012

Antimicrob Agents Chemother

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“…P. malariae infections are most common in sub-Saharan Africa and the southwest Pacific, where age-specific prevalence in mass blood surveys have exceeded 15-30% [2][3][4][5][6][7][8]. By contrast, when P. malariae has been detected in malaria-endemic regions of Asia [9][10][11][12], the Middle East [13], South America [14] and Central America [15], it is observed as an infrequent infection, with blood-smear light microscopy (LM) prevalence rarely exceeding 1-2%.…”

Section: Geographical Distributionmentioning

confidence: 99%

Plasmodium malariae and Plasmodium ovale – the ‘bashful’ malaria parasites

Müeller

Zimmerman

Reeder

2007

Trends in Parasitology

264

245

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Although Plasmodium malariae was first described as an infectious disease of humans by Golgi in 1886 and Plasmodium ovale identified by Stevens in 1922, there are still large gaps in our knowledge of the importance of these infections as causes of malaria in different parts of the world. They have traditionally been thought of as mild illnesses that are caused by rare and, in case of P. ovale, short-lived parasites. However, recent advances in sensitive PCR diagnosis are causing a re-evaluation of this assumption. Low-level infection seems to be common across malaria-endemic areas, often as complex mixed infections. The potential interactions of P. malariae and P. ovale with Plasmodium falciparum and Plasmodium vivax might explain some basic questions of malaria epidemiology, and understanding these interactions could have an important influence on the deployment of interventions such as malaria vaccines. Geographical distributionAlthough distribution of Plasmodium malariae infection is reported as being patchy, it has been observed in all major malaria-endemic regions of the world [1]. P. malariae infections are most common in sub-Saharan Africa and the southwest Pacific, where age-specific prevalence in mass blood surveys have exceeded 15-30% [2][3][4][5][6][7][8]. By contrast, when P. malariae has been detected in malaria-endemic regions of Asia [9][10][11][12], the Middle East [13], South America [14] and Central America [15], it is observed as an infrequent infection, with blood-smear light microscopy (LM) prevalence rarely exceeding 1-2%. Much higher levels of infection were, however, found in montagnard refugees from the Cambodian-Vietnamese border [16]. In South America, P. malariae is thought to be a zoonotic infection because the genetically identical Plasmodium brasilianum infects new-world monkeys [17] and both monkeys and humans in endemic areas show high levels of seropositivity to P. malariae and P. brasilianum antigens [18].Plasmodium ovale was thought to have a much more limited distribution, with endemic transmission traditionally described as being limited to areas of tropical Africa, New Guinea, the eastern parts of Indonesia and the Philippines [19,20]. Infections with P. ovale, however, have also been reported in the Middle East [13], the Indian subcontinent [21] and different parts of Southeast Asia [11,22,23]. In West Africa (and to a lesser extent Central Africa), age specific LM prevalence of >10% have been observed [3,6] places where P. ovale is observed, it is relatively uncommon and its prevalence (as detected by LM) rarely exceeds 3-5% [22,[24][25][26].Indepth descriptions of the epidemiology of both infections based upon LM data are, thus, restricted almost exclusively to highly endemic areas in Africa and the Southwest Pacific. Detailed epidemiological studies from South America and Asia are lacking. Variation in parasite prevalenceIn West Africa, P. malariae prevalence has been reported to peak at ages similar to those of P. falciparum (i.e. in children under ten years of...

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“…26 The characteristics of malaria transmission in the region were investigated by field workers from the United States Navy Medical Research Unit 2, Jakarta (NAMRU2) because of a reported dramatic increase in malaria deaths. 26 Briefly, this is a remote, isolated highland valley of Irian Jaya near the Papua New Guinea border. There are four major villages in the Oksibil subdistrict where the population of approximately 2,000 live.…”

Section: Methodsmentioning

confidence: 99%

“…Intense year-round transmission of malaria was recorded, with 34% of the population slide positive for malaria over five-point prevalence studies from May 1990 to July 1991. 26 From the just-mentioned survey of malaria in the Oksibil subdistrict, 26 a group of study participants were identified who gave informed consent for donation of repeated blood samples. These individuals were not selected for symptoms suggesting malaria, only for their willingness to continue to have blood samples taken.…”

Section: Methodsmentioning

confidence: 99%

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

Eisen

Saul²,

Fryauff³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Many of the asexual stage Plasmodium falciparum proteins that are the targets of host protective responses are markedly polymorphic. The full repertoire of diversity is not defined for any antigen. Most studies have focused on the genes encoding merozoite surface proteins 1 and 2 (MSP1, MSP2). We explored the extent of diversity of some of the less studied merozoite surface antigens and analyzed the degree of complexity of malaria field isolates by deriving nucleotide sequences of several antigens. We have determined the genotype of apical membrane antigen 1 (AMA1) in a group of 30 field samples, collected over 29 months, from individuals living in an area of intense malaria transmission in Irian Jaya, identifying 14 different alleles. AMA1 genotyping was combined with previously determined MSP2 typing. AMA1 had the greatest power in distinguishing between isolates but methodological problems, especially when mixed infections are present, suggest it is not an ideal typing target. MSP1, MSP3, and glutamate-rich protein genotypes were also determined from a smaller group of samples, and all results were combined to derive an extended antigenic haplotype. Within this subset of 10 patients, nine different genotypes could be discerned; however, five patients were all infected with the same strain. This strain was present in individuals from two separate villages and was still present 12 months later. This strain was predominant at the first time point but had disappeared at the fourth time point. This significant change in malaria genotypes could be due to strain-specific immunity developing in this population.

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Heightened Transmission of Stable Malaria in an Isolated Population in the Highlands of Irian Jaya, Indonesia

Cited by 37 publications

References 0 publications

Reduced Impact of Pyrimethamine Drug Pressure on Plasmodium malariae Dihydrofolate Reductase Gene

Reduced Impact of Pyrimethamine Drug Pressure on Plasmodium malariae Dihydrofolate Reductase Gene

Plasmodium malariae and Plasmodium ovale – the ‘bashful’ malaria parasites

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

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