CONTAINMENT

contain + eliminate = no parasite

Day 3+ves in Ta Sanh, Western Cambodia

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Throughout the year for rice cultivation and agricultural activities villagers stay overnight in temporary shelters. Pix WHO/Sonny Krishnan

The drive to Ou Nonoung village in Western Cambodia’s Ta Sanh district is not for the faint-hearted. The almost 45 degree climbs and the steep plunges on the dirt track certainly calls for skilled driving of the 4-WD.

One wrong turn and the vehicle could turn turtle. One wrong detour into the bush and the 4-WD could set off one of the hundreds of unexploded ordinances in the soft dirt – a stark reminder of the war-torn years that almost sent Cambodia back to the Dark Ages.

Ou Nonoung village, in the foothills just below the Cardamom Mountains, lies at the fringe of the forests. In this ’old village’ that goes back to the dark Khmer Rouge-era, villagers have their farms in forest clearings. Throughout the year for rice cultivation and agricultural activities they stay overnight in temporary shelters. These movements in relation to agricultural activities have been identified as risk factors associated with malaria infection.

In these harsh conditions, village malaria workers or VMWs play a crucial role in the early detection and treatment of the killer falciparum malaria. But developments lately have been disturbing.

A warning on the presence of land mines around Ou Nonoung village.

Records from the Ou Nonoung VMW between September 2010 to February 2011 indicate that six villagers had tested positive for falciparum malaria. The results were from rapid diagnostic tests (RDTs). And out of the six Pf positive cases, three still had plasmodium parasites in their blood after a three-day course of treatment with dihydroartemisinin-piperaquine – the artemisinin combination therapy for uncomplicated falciparum malaria currently used along the Thai-Cambodian border.

The Day Three positive cases were verified by microscopy in the Ta Sanh district health center, from blood slides prepared by the VMW from the patients’ blood samples after the three-day course of treatment.

Though the Pf positive cases are relatively small due to active interventions in the Bill & Melinda Gates-funded Containment Project, the presence of Day Three positive patients is a cause for concern.

WHO’s ‘Guidelines for the treatment of malaria’ indicate that: “To eliminate at least 90 percent of the parasitaemia, a three-day course of the artemisinin is required to cover up to three post-treatment asexual cycles of the parasite. This ensures that only about 10 percent of the parasitamia is present for clearance by the partner medicine, thus reducing the potential for development of resistance.” This is the rationale for using dihydroartemisinin and its partner drug piperaquine that is available as a co-formulated tablet.

Host immunity and splenic function are important contributors to parasite clearance after artemisinin treatment. Reduction in herd immunity, perhaps resulting from reduced transmission, could decrease parasite clearance in Cambodia


The question asked is that if symptoms persist 3-14 days after initiation of drug therapy in accordance with the recommended treatment regimen, is that an indication of resistance?

A village malaria worker making a blood slide after doing a rapid diagnostic test. Pix WHO/ Sonny Krishnan

In a recent interview with CONTAINMENT, in Pailin in western Cambodia, Dr. Robert Newman, WHO’s Global Malaria Program director, warns of a worse case scenario.

“The worse case would be the spread of the delay in clearance of the [plasmodium] parasites. Right now we are finding an increase in the percentage of patients who are still positive on Day 3. That will be the hallmark of this problem [of resistance],” said Dr. Newman.

Added Dr. Newman: “If that were to continue to worsen, artemisinins would become less and less efficacious. It would then take longer and longer for patients to clear [plasmodium parasites in their blood], and we could get to the point of truly having failures to ACTs.”

But Dr. Newman clarified that though there is resistance to artemisinins, artemisinin-based combination therapies (ACTs) still remain efficacious. “That is a very important message,” he stressed.

But he issued a stark warning. “If that situation worsens, if were to lose ACTs, and if it spreads to the shores of Africa, we could have a public health catastrophe.”

Acknowledging that there is slow clearance rate in Western Cambodia, Anderson, et al. (2010) [1] ask whether slow clearance rate results from parasite, host, or other factors specific to the population in that part of the country.

Writing in the ‘The Journal of Infectious Diseases’, quoting previous studies on the comparison of parasites in Western Cambodia to that in the western part of Thailand along the Thai-Myanmar border, the authors point out that: “ Parasites with slow clearance rate after ACT do not show increased resistance to artemisinin compounds with conventional in vitro testing compared with parasites from western Thailand, which show rapid clearance rate.”

The authors offer several explanations for slow clearance rates.

“Host immunity and splenic function are important contributors to parasite clearance after artemisinin treatment. Reduction in herd immunity, perhaps resulting from reduced transmission, could decrease parasite clearance in Cambodia,” they write.


[1] Anderson, T., Nair. S., Nkhoma, S., Williams, J., Imwong, M., Yi, P., Socheat, D., Das, D., Chotivanich,K., Day, N., White,N., Dondorp, A. 2010, “High heritability of malaria parasite clearance rate indicates a genetic basis for Artemisinin resistance in Western Cambodia”, The Journal of Infectious Diseases, vol. 201, no. 9, pp. 1326 – 1330.

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3 Responses

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  1. […] parasites. Right now we are finding an increase in the percentage of patients who are still positive on Day 3. That will be the hallmark of this problem [of […]

  2. […] Consortium is pioneering a Day 3 positive alert system in Ta Sanh district, western Cambodia, using mobile phone and web-based technology to facilitate response in real-time. […]

  3. […] Melinda Gates Foundation-funded CONTAINMENT Project, is pioneering a Day 3 positive alert system in Ta Sanh district, western Cambodia, using mobile phone and web-based technology (including FrontlineSMS) to […]


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