The co-existence of Plasmodium: sidelights from falciparum and vivax malaria in Thailand

doi:10.1016/j.pt.2004.05.004

Trends in Parasitology

Volume 20, Issue 7, 1 July 2004, Pages 333-339

https://doi.org/10.1016/j.pt.2004.05.004 Get rights and content

Abstract

It is rare to find human populations exposed to a single malaria parasite species – in most endemic areas, at least three Plasmodium species co-exist. Here, we briefly review mixed species infection in malaria, and discuss apparently disparate clinical and epidemiological observations of Plasmodium falciparum and Plasmodium vivax, now equally prevalent in Thailand, which suggest that an ‘entente cordiale’ between these two species might be beneficial both to parasites and humans. If this were the case, the influence of changes in the parasite formula in endemic areas on the burden of malaria would become an important element of study.

Section snippets

Out of sight…

Mixed species infections have been a relatively neglected field during the prolific early investigations on malaria. This was due, in part, to the debate on the existence of different Plasmodium species of humans. In the 1890s, Italian malariologists split these parasites into three species, whereas Alphonse Laveran championed the idea that they all belonged to a single species – the ‘unicity’ theory – with the parasites merely changing morphologically. The debate was finally laid to rest in

An emerging interest

Over the past decade, interest in the question of mixed-species Plasmodium infections has revived. This has been sparked by the introduction of sensitive molecular tools of detection, and sustained by the realization by a growing number of researchers that Plasmodium species other than P. falciparum are worthy of study. The first conference entirely devoted to P. vivax (‘Vivax Malaria Research: 2002 and Beyond’, convened by the Multilateral Initiative on Malaria in February 2002 in Bangkok,

A natural experiment

Clinical and epidemiological observations in Thailand, more than in any other endemic setting, have brought malaria mixed infections to the attention of malariologists. Thailand is particularly well suited to provide insights on interactions between Plasmodium species for several reasons. Thailand boasts excellent country-wide epidemiological surveillance and hosts several continuously monitored sites. Data are available for numerous patients recruited for drug efficacy studies who have been

Beneficial associations

The Shoklo camp on the Thai–Myanmar border in western Thailand, where Karen populations displaced by armed conflict took refuge since 1984, has provided an excellent setting for detailed long-term epidemiological and clinical observations of malaria. However, malaria epidemiology at this site and at that time is unlikely to be representative of the rest of Thailand, and patient recruitment in the early 1990s was coincident with the peak crisis of mefloquine resistance and the first efforts to

Too many mixed infections

The levels of mixed infections recorded in Shoklo contrast sharply with those recorded for the rest of the country. Indeed, P. falciparum and P. vivax were found together only in 0.3–0.7% of the total positive blood smears recorded in Thailand [51]. If this were the true prevalence of mixed species infections, then any interactions between the species would have minimal impact on public health. However, there are compelling indications that the higher levels of mixed infection recorded in

Mixed perspectives

Two immediate conclusions can be drawn from the observations made in Thailand and elsewhere: (i) mixed-species malaria infections are common; and (ii) they are likely to have an impact on the morbidity and epidemiology of malaria. The growing trend to include non-P. falciparum infections in the analysis of epidemiological and clinical data is providing glimpses of interesting associations with mixed infections in other areas where the different species are prevalent such as Papua New Guinea [73]

References (77)

M.J Miller
Observations on the natural history of malaria in the semi-resistant West African
Trans. R. Soc. Trop. Med. Hyg.
(1958)
A Voller et al.
Immunological studies on simian malaria parasites. IV. Heterologous superinfection of monkeys with chronic Plasmodium knowlesi infections
Trans. R. Soc. Trop. Med. Hyg.
(1969)
M Yoeli et al.
The course of simultaneously inoculated, concomitant infections with Plasmodium vinckei and Plasmodium berghei in white mice
Trans. R. Soc. Trop. Med. Hyg.
(1970)
G Snounou
Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections
Mol. Biochem. Parasitol.
(1993)
G Snounou
High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction
Mol. Biochem. Parasitol.
(1993)
G Snounou
The importance of sensitive detection of malaria parasites in the human and insect hosts in epidemiological studies, as shown by the analysis of field samples from Guinea Bissau
Trans. R. Soc. Trop. Med. Hyg.
(1993)
J Black
Mixed infections with Plasmodium falciparum and P. malariae and fever in malaria
Lancet
(1994)
K Maitland
Plasmodium vivax and Plasmodium falciparum: biological interactions and the possibility of cross-species immunity
Parasitol. Today
(1997)
M.C Bruce et al.
Cross-species regulation of malaria parasitaemia in the human host
Curr. Opin. Microbiol.
(2002)
M.C Bruce et al.
Cross-species regulation of Plasmodium parasitemia in semi-immune children from Papua New Guinea
Trends Parasitol.
(2003)

M Mayxay

Mixed species malaria infections in humans

Trends Parasitol.

(2004)

D.P Mason

The blood-stage dynamics of mixed Plasmodium malariae–Plasmodium falciparum infections

J. Theor. Biol.

(1999)

K Congpuong

Sensitivity of Plasmodium vivax to chloroquine in Sa Kaeo Province, Thailand

Acta Trop.

(2002)

C Luxemburger

The epidemiology of malaria in a Karen population on the western border of Thailand

Trans. R. Soc. Trop. Med. Hyg.

(1996)

C Luxemburger

The epidemiology of severe malaria in an area of low transmission in Thailand

Trans. R. Soc. Trop. Med. Hyg.

(1997)

R.N Price

Artesunate/mefloquine treatment of multi-drug resistant falciparum malaria

Trans. R. Soc. Trop. Med. Hyg.

(1997)

R.E.L Paul

Genetic analysis of Plasmodium falciparum infections on the north-western border of Thailand

Trans. R. Soc. Trop. Med. Hyg.

(1999)

S Looareesuwan

High rate of Plasmodium vivax relapse following treatment of falciparum malaria in Thailand

Lancet

(1987)

A.E Brown

Demonstration by the polymerase chain reaction of mixed Plasmodium falciparum and P. vivax infections undetected by conventional microscopy

Trans. R. Soc. Trop. Med. Hyg.

(1992)

N Siripoon

Cryptic Plasmodium falciparum parasites in clinical P. vivax blood samples from Thailand

Trans. R. Soc. Trop. Med. Hyg.

(2002)

N.J White

The assessment of antimalarial drug efficacy

Trends Parasitol.

(2002)

J.F Trape

Impact of chloroquine resistance on malaria mortality

C.R. Acad. Sci. III

(1998)

R.W Snow

The past, present and future of childhood malaria mortality in Africa

Trends Parasitol.

(2001)

G.R Coatney

Simian malarias in man: facts, implications, and predictions

Am. J. Trop. Med. Hyg.

(1968)

D Antic

Experimentelle reproduktion der malaria

Arch. Schif. U. Trop. Hyg.

(1925)

A Plehn

Immunisierung gegen malaria

Bft. Z. Arch. Schif. U. Trop. Hyg.

(1926)

M.F Boyd et al.

Simultaneous inoculation with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

(1937)

M.F Boyd et al.

Vernal vivax activity in persons simultaneously inoculated with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

(1938)

B Mayne et al.

Antagonism between species of malaria parasites in induced mixed infections (Preliminary note)

Pub. Health Rep.

(1938)

M.F Boyd

Consecutive inoculations with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

(1939)

W.C Earle

Observations on the course of naturally acquired malaria in Puerto Rico

Puerto Rico J. Pub. Health Trop. Med.

(1939)

E.J Pampana et al.

Studi di epidemiologia malarica in Sardegna

Riv. Malariol.

(1940)

R.B Hill

Observations on the course of malaria in children in an endemic region

Am. J. Trop. Med.

(1943)

K.M Cobban

Malaria in the partially immune adult Nigerian

J. Trop. Med. Hyg.

(1960)

L.J Bruce-Chwatt

A longitudinal survey of natural malaria infection in a group of West African adults. Part I

West Afr. Med. J.

(1963)

L.J Bruce-Chwatt

A longitudinal survey of natural malaria infection in a group of West African adults. Part II

West Afr. Med. J.

(1963)

W.E Collins et al.

A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum in patients previously infected with heterologous species of Plasmodium: effect on development of parasitologic and clinical immunity

Am. J. Trop. Med. Hyg.

(1999)

F.E McKenzie

Plasmodium malariae infection boosts Plasmodium falciparum gametocyte production

Am. J. Trop. Med. Hyg.

(2002)

Cited by (106)

Differential diagnosis of Plasmodium falciparum and Plasmodium vivax in mixed infection by colorimetric nanogold probes
2021, Analytical Biochemistry
Malaria is an infectious disease reported mostly in the tropical region. The most severe human malaria is Plasmodium falciparum since it can cause cerebral malaria. Therefore, the presence of P. falciparum either in single or mixed infection needs accurate diagnosis. In some mixed infections, the presence of P. falciparum may be cryptic which cannot be detected by microscopic examination. The molecular diagnosis is required in these cases. Many methods based on amplification of malaria parasite genes have been developed but most of them need sophisticated instruments. Here, we created a colorimetric method using probe immobilized gold nanoparticles (AuNPs) to detect the malaria parasite gene. Color changes rely on salt-induced aggregation of AuNPs in the presence or absence of DNA hybridization. Color changes could be observed either by a naked eye or UV–vis spectrophotometer. By this approach, single infection by the most common malaria parasite, P. falciparum or P. vivax could be differentially identified. Mixed infection of these two malaria species could also be clearly diagnosed including cases of cryptic P. falciparum. The novel nanogold based molecular malaria diagnosis is sensitive, specific, rapid and cheap ($0.94). The prepared nanogold malaria probes are stable for up to 3 months indicating their filed application in remote areas.
Primaquine for Plasmodium vivax radical cure: What we do not know and why it matters
2021, International Journal for Parasitology: Drugs and Drug Resistance
Plasmodium vivax radical cure requires the administration of a blood schizonticide for killing blood-stage parasites and the addition of a drug able to kill hypnozoites, the dormant parasite stages residing in the liver of infected patients. All drugs used clinically for killing hypnozoites are 8-aminoquinolines and among them, primaquine has been at the forefront of P. vivax case management for decades. We discuss here the possible factors that could lead to the emergence and selection of P. vivax primaquine resistant parasites and emphasize on how a better understanding of the mechanisms underlying primaquine treatment and hypnozoite biology is needed to prevent this catastrophic scenario from happening.
Structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase-dihydropteroate synthase from Plasmodium vivax sheds light on drug resistance
2018, Journal of Biological Chemistry
The genomes of the malaria-causing Plasmodium parasites encode a protein fused of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and dihydropteroate synthase (DHPS) domains that catalyze sequential reactions in the folate biosynthetic pathway. Whereas higher organisms derive folate from their diet and lack the enzymes for its synthesis, most eubacteria and a number of lower eukaryotes including malaria parasites synthesize tetrahydrofolate via DHPS. Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) HPPK–DHPSs are currently targets of drugs like sulfadoxine (SDX). The SDX effectiveness as an antimalarial drug is increasingly diminished by the rise and spread of drug-resistant mutations. Here, we present the crystal structure of PvHPPK–DHPS in complex with four substrates/analogs, revealing the bifunctional PvHPPK–DHPS architecture in an unprecedented state of enzymatic activation. SDX's effect on HPPK–DHPS is due to 4-amino benzoic acid (pABA) mimicry, and the PvHPPK–DHPS structure sheds light on the SDX-binding cavity, as well as on mutations that effect SDX potency. We mapped five dominant drug resistance mutations in PvHPPK–DHPS: S382A, A383G, K512E/D, A553G, and V585A, most of which occur individually or in clusters proximal to the pABA-binding site. We found that these resistance mutations subtly alter the intricate enzyme/pABA/SDX interactions such that DHPS affinity for pABA is diminished only moderately, but its affinity for SDX is changed substantially. In conclusion, the PvHPPK–DHPS structure rationalizes and unravels the structural bases for SDX resistance mutations and highlights architectural features in HPPK–DHPSs from malaria parasites that can form the basis for developing next-generation anti-folate agents to combat malaria parasites.
Interactions between tafenoquine and artemisinin-combination therapy partner drug in asexual and sexual stage Plasmodium falciparum
2017, International Journal for Parasitology: Drugs and Drug Resistance
Citation Excerpt :
Other drugs such as TFQ, MFQ, LMF, and PPQ have a higher bioavailability when taken with food (Crockett and Kain, 2007; Nguyen et al., 2008). With regard to mixed infections, P. falciparum and P. vivax mixed infections have been reported to show differences in severity, onset of one or the other, and the number of gametocytes etc. compared to single infections (Price et al., 1999; Snounou and White, 2004). In addition, TFQ Cmax may be variable depending on cytochrome P450 metabolism and gender, with women displaying higher plasma concentrations than men (Edstein et al., 2007; Vuong et al., 2015).
The 8-aminoquinoline tafenoquine (TFQ), a primaquine derivative, is currently in late-stage clinical development for the radical cure of P. vivax. Here drug interactions between TFQ and chloroquine and six artemisinin-combination therapy (ACT) partner drugs in P. falciparum asexual stages and gametocytes were investigated. TFQ was mostly synergistic with the ACT-partner drugs in asexual parasites regardless of genetic backgrounds. However, at fixed ratios of 1:3, 1:1 and 3:1, TFQ only interacted synergistically with naphthoquine, pyronaridine and piperaquine in gametocytes. This study indicated that TFQ and ACT-partner drugs will likely have increased potency against asexual stages of the malaria parasites, whereas some drugs may interfere with each other against the P. falciparum gametocytes.
Mathematical models of Plasmodium vivax transmission: A scoping review
2024, PLoS Computational Biology
Surveillance of drug resistance molecular markers in Plasmodium vivax before and after introduction of dihydroartemisinin and piperaquine in Thailand: 2009–2019
2023, Parasitology Research

View all citing articles on Scopus

View full text

Trends in Parasitology

Vivax series:The co-existence of Plasmodium: sidelights from falciparum and vivax malaria in Thailand

Abstract

Section snippets

Out of sight…

An emerging interest

A natural experiment

Beneficial associations

Too many mixed infections

Mixed perspectives

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Mol. Biochem. Parasitol.

Mol. Biochem. Parasitol.

Trans. R. Soc. Trop. Med. Hyg.

Lancet

Parasitol. Today

Curr. Opin. Microbiol.

Trends Parasitol.

Trends Parasitol.

J. Theor. Biol.

Acta Trop.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Lancet

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Trends Parasitol.

C.R. Acad. Sci. III

Trends Parasitol.

Simian malarias in man: facts, implications, and predictions

Am. J. Trop. Med. Hyg.

Experimentelle reproduktion der malaria

Arch. Schif. U. Trop. Hyg.

Immunisierung gegen malaria

Bft. Z. Arch. Schif. U. Trop. Hyg.

Simultaneous inoculation with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

Vernal vivax activity in persons simultaneously inoculated with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

Antagonism between species of malaria parasites in induced mixed infections (Preliminary note)

Pub. Health Rep.

Consecutive inoculations with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

Observations on the course of naturally acquired malaria in Puerto Rico

Puerto Rico J. Pub. Health Trop. Med.

Studi di epidemiologia malarica in Sardegna

Riv. Malariol.

Observations on the course of malaria in children in an endemic region

Am. J. Trop. Med.

Malaria in the partially immune adult Nigerian

J. Trop. Med. Hyg.

A longitudinal survey of natural malaria infection in a group of West African adults. Part I

West Afr. Med. J.

A longitudinal survey of natural malaria infection in a group of West African adults. Part II

West Afr. Med. J.

A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum in patients previously infected with heterologous species of Plasmodium: effect on development of parasitologic and clinical immunity

Am. J. Trop. Med. Hyg.

Plasmodium malariae infection boosts Plasmodium falciparum gametocyte production

Am. J. Trop. Med. Hyg.

Vivax series:
The co-existence of Plasmodium: sidelights from falciparum and vivax malaria in Thailand