Plasmodium vivax sporozoites

Plasmodium vivax and drug resistance

Whilst our understanding of drug resistant Plasmodium falciparum is quite well understood, the extent and nature of resistance in Plasmodium vivax parasites is for the most part unknown.

Plasmodium vivax infects 19-50 million people with malaria each year. Most of these cases occur in the Asia Pacific region where more than 2.2 billion people are at risk of infection. Since 1960, only five countries in the Asia Pacific have been certified free from malaria: Taiwan (1965), Australia (1981), Singapore (1982), Maldives (1984), Brunei (1987).

Other areas are making major progress to reduce the burden of malaria. This is due to increased political commitment, better access to diagnostics, effective malaria treatments and bed nets. As a result 16 countries in the Asia Pacific have publically stated their goal to eliminate malaria from the region by 2030.

Plasmodium vivax – a greater challenge to eliminate

P. vivax malaria has not been a priority for national malaria control programmes in the past. These have instead focused on the more pathogenic and deadly falciparum malaria. Malaria related deaths have declined over the last decade, mostly due to a reduction in falciparum malaria. However, this decline has often coincided with an increased number of P. vivax malaria cases.

Several factors contribute to this impact.  P. vivax can be difficult to detect since it usually circulates at low levels in the blood. It can be present and infectious to the mosquito vectors, even when the person shows no symptoms. P. vivax can also to lie dormant in a person’s liver, reawakening weeks to months after the first infection to cause relapses of symptomatic malaria.

In many places, the usual chloroquine treatment is no longer effective because of drug resistant P. vivax. This results in treatment failures and relapses. These recurrent episodes of P. vivax can cause severe anaemia and contribute to the sickness and death associated with vivax malaria [1-3]. The number of relapses and the frequency differ significantly by region. See the WWARN Primaquine Literature Review for more information.

Achieving the radical cure

Any treatment of vivax malaria requires a combination of drugs active against the blood stages of the parasite and the dormant liver stages. Primaquine is a commonly used malaria treatment and is currently the only licensed drug that targets the liver stage of the malaria lifecycle. However, widespread use of primaquine is limited by glucose-6-phosphate dehydrogenase (G6PD)(link is external) deficiency. This is one of the most common genetic conditions in people. It can be found in up to 40 per cent of some populations.  People with less than 10 per cent of normal enzyme activity are at risk of their red blood cells rupturing.

There is a lack of available and reliable diagnostics to determine this enzyme deficiency, concerns over drug toxicity, and the misperceived benign nature of P. vivax infection. This means that healthcare providers prescribe primaquine erratically even when it's recommended in national policy.  These are very high barriers to the control and elimination of P. vivax.

Emerging strains of drug resistant Plasmodium vivax

Although drug resistance has forced most malaria endemic countries to abandon chloroquine treatment for P. falciparum malaria, chloroquine remains the go-to treatment for P. vivax. This strategy is now under threat from the emergence and spread of chloroquine resistant P. vivax[4,5]. P. vivax has also developed drug resistance to sulfadoxine-pyrimethamine (SP) and potentially other antimalarial drugs such as mefloquine.

However, because it is difficult to diagnose resistant strains, strategies to detect and track drug resistant P. vivax are limited [6]. Researchers are making significant progess in developing clinical trials protocols and drug susceptibility testing. They are also trying to uncover the mechanisms behind chloroquine resistant P. vivax. Understanding these processes will greatly improve global monitoring of chloroquine resistance.

For a comprehensive review of drug resistant P. vivax see the Chloroquine Resistant Plasmodium vivax Review.

Related websites:

References:

  1. Anstey NM, Douglas NM, Poespoprodjo JR, Price RN (2012) Plasmodium vivax: clinical spectrum, risk factors and pathogenesis. Adv Parasitol 80: 151-201.
  2. Price RN, Douglas NM, Anstey NM (2009) New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistance. Curr Opin Infect Dis 22: 430-435.
  3. Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, et al. (2007) Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77: 79-87.
  4. Rieckmann KH, Davis DR, Hutton DC (1989) Plasmodium vivax resistance to chloroquine? Lancet 2: 1183-1184.
  5. Baird JK, Basri H, Purnomo, Bangs MJ, Subianto B, et al. (1991) Resistance to chloroquine by Plasmodium vivax in Irian Jaya, Indonesia. Am J Trop Med Hyg 44: 547-552.
  6. Price RN, Auburn S, Marfurt J, Cheng Q (2012) Phenotypic and genotypic characterisation of drug-resistant Plasmodium vivax. Trends Parasitol 28: 522-529.