The study assessed artemether-lumefantrine + primaquine as a treatment option against P. vivax. Chloroquine and primaquine have been used worldwide against P. vivax as first-line drugs since 1946 and 1950 respectively. Reports from South-American countries such as Colombia and Brazil
[20, 21] on decreasing chloroquine efficacy against P. vivax and a change of drug policies from chloroquine to ACT for vivax infections in four countries (Solomon Islands, Vanuatu, PNG and Papua (Indonesia))
, led to the question for an alternative treatment option in Guyana. So far only a few studies have examined artemether-lumefantrine as a treatment option for P. vivax and even less studies looked at artemether-lumefantrine and primaquine.
All patients in the study cleared parasites on day 1, which makes artemether-lumefantrine an efficacious alternative for chloroquine in the treatment of vivax malaria. No severe side effects or adverse events were observed, similar to other studies, which show a good safety profile for artemether-lumefantrine alone
[28–31] and for artemether-lumefantrine in combination with primaquine
, when used for P. vivax infections. Drug interactions between the two drugs seem to be unlikely
Two patients (2.7%) presented with parasitological failure at day 28. In one of those patients P. vivax was PCR-confirmed at day 28, with negative PCRs on day 7, 14 and 21. It can be assumed that the new parasitaemia derived from relapse, rather than recrudescence, although a new infection or a recrudescence cannot be ruled out completely since there is no evidence that genotyping of P. vivax parasites may help to distinguish these events
. Frequent relapses with artemether-lumefantrine have been described, due to the short half-life of lumefantrine
. However, a combination with a longer-acting partner drug, such as piperaquine would only delay the P. vivax relapse, but not prevent it. Lumefantrine on the other hand is less likely to induce resistance compared to long half-life drugs as chloroquine or piperaquine
. In a situation, where primaquine can be administered in a safe and compliant manner, primaquine is the ideal drug for preventing relapse. However, a concerning rate of 24.5% resistance to primaquine has been described in Brazil
, which could be one reason for the two treatment failures, observed in the study. Another reason might be a poor compliance to the unsupervised primaquine treatment.
With recent reports clearly demonstrating severe P. vivax infections resembling the course of malign P. falciparum infections
[36, 37] the application of a sufficient therapy has to be ensured. Therefore the continuing surveillance of chloroquine efficacy is of great importance. Studying the history of anti-malarial drug resistance development worldwide, it is not hard to predict that we also will encounter frequent treatment failures due to chloroquine in the upcoming years in South America.
A drawback to this study is that only eight patients could be screened for pvmdr1 single-nucleotide polymorphism and no mutations in codon Y976F were found. Low parasitaemia and sub-optimal sample storage conditions might partly explain the poor usefulness of the PCR method with these samples, while it usually works well with many other blood spot samples. No conclusions can be drawn on any resistance associated with pvmdr1 polymorphism. One out of the two patients with treatment failure was tested for Y976F mutation, but was wild type. In total, 90% of the study participants were male. In Guyana, malaria affects many more males than females at a ratio of almost 4:1 (males 78.2% and females 21.8%). This reflects the fact, that the migrant populations, primarily miners, are by far the most affected group. In addition to that all women aged 12 to 26 were excluded, in order to avoid potential pregnant study participants. 60% of all reported malaria cases occur in the Amerindian population, to which 16.2% of the study participants belong
A switch of drug policies in Guyana to artemether-lumefantrine + primaquine for P. vivax infections would establish a common treatment for both circulating Plasmodium species, which are P. falciparum and P. vivax. Artemether-lumefantrine is highly effective against P. falciparum in Guyana, based on a study conducted in 2007/2008 (National Malaria Control Program, unpublished data). A common treatment could result in a number of advantages. Reports from Thailand and Indonesia detected up to 23% of P. falciparum infections being wrongly diagnosed as P. vivax, leading to inappropriate treatment with chloroquine
[39, 40]. ACT has also shown to clear P. vivax more quickly than chloroquine
. Treating P. falciparum with artemether-lumefantrine + primaquine would have the advantage of also treating potential dormant P. vivax hypnozoites, which are thought to become activated due to P. falciparum infections, thereby explaining the high number of vivax infections after P. falciparum treatment
Keeping chloroquine in the market, could lead to its administration against P. falciparum in the private sector. Disadvantages of a common treatment will be the higher price for ACT as well as a decreased impetus for laboratories and hospitals in performing a correct plasmodium species diagnostic. The prescription of primaquine to all malaria cases without prior testing for G6PD deficiency presents a potential risk for severe haemolytic anaemia in G6PD-deficient patients, although G6PD deficiency is an infrequent trait in Guyana.