Archive for March 2011
Chhean Nariddh Moeun profiles Ta Sanh Health Centre’s microscopist Tith Phanny.
In this remote village in Samlaut district where Hollywood actress Angelina Jolie adopted a Cambodian boy, pregnant women come to Ta Sanh Health Center to give birth to their babies or get their pregnancy checked. Other patients come here to get their blood tests and treatment for malaria, TB or HIV/AIDS.
However, many of them have one thing in common: the health centre worker who sees and treats them is the same person. And that person is nobody other than Tith Phanny.
As a former Khmer Rouge medic, Phanny says she had been trained as a midwife, a microscopist, and to provide blood tests and treatment for malaria, TB and HIV/AIDS.
Phanny, who thinks she is 50 minus or plus a year or two, reckons that she has helped several hundred women deliver their babies since she became a midwife in the early 1990s.
She says that she remembers helping deliver a baby for a pregnant woman who came to Ta Sanh Health Center 18 years ago. The baby was born as a healthy girl and grew up in the village near the Cambodian-Thai border once controlled by the Khmer Rouge.
“Some babies of the women I helped with their childbirth in the past have grown up, got married and come to deliver their own babies,” she proudly talks of the two generations of mothers she has helped.
Due to the lack of health workers, Phanny says she had learned her different medical skills from her hands-on experience working with various Khmer Rouge medics during the civil war in Cambodia.
She was assigned to do various things, including taking care of wounded soldiers and treating malaria patients who she thinks sometimes outnumbered the wounded…
Back then, she says she was assigned to do various things, including taking care of wounded soldiers and treating malaria patients who she thinks sometimes outnumbered the wounded.
Phanny says it was her own tragic past that had encouraged her to determine to help others. While living in a children’s mobile unit in Kandal province under the Khmer Rouge, she says she was separated from her family when the Vietnamese forces defeated the Khmer Rouge in 1979.
She says she had to follow others to the Thai border, where the fighting was very tense. In the 1980s, she says she was wounded twice — first in her head by shrapnel from a rocket fired by the Vietnamese and second when she stepped on a landmine and lost her right toe.
Miraculously, she survived the two incidents. Yet, it was not the end of her ordeal.
Phanny says she almost died several times from the scourge of malaria in the 1990s. She says she once went into a deep coma and had to receive successive intravenous drips several months before she regained her consciousness and recovered.
In 1996, the Khmer Rouge struck a deal with the government to end the war. It was the first time Phanny says she could enjoy peace after more than two decades of civil war and fighting.
After the Khmer Rouge was reintegrated into the Cambodian society, Phanny says she was sent to Phnom Penh and Battambang province for one month each to attend formal training in midwifery.
However, Phanny says she still juggles between different jobs at the Ta Sanh Health Center, from midwifery to microscopy, to blood tests and treatments for malaria, TB and HIV/AIDS.
She is indeed a busy woman. As Phanny is working on her microscope in the laboratory, she receives an urgent call to help deliver a baby for a woman.
“I run back and forth from the laboratory to the delivery room,” she says, adding she stays at the health center seven days a week.
Dr. Pov Pheng, deputy Chief of Ta Sanh Health Center, speaks highly of Phanny.
“She is very active,” he says, “She is very diligent in her work.”
Despite the hard work, Dr. Pheng says Phanny and other health workers at his hospital receive the same monthly salary of about $70. Yet, he says the amount is almost ten times more, compared to 10 years ago when they were paid only about eight dollars per month.
Regardless of the money she gets, Phanny never complains about her job.
“I am here 24 hours [a day],” she says, “I am always busy [but] I am happy with the work.”
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.
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?
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)  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.
 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.
CONTAINMENT recently spoke to Dr. Robert Newman, Director of WHO’s Global Malaria Program, who was on a field visit to Pailin in Western Cambodia.
There is a long history in malaria control efforts. What’s different now and how has the landscape changed?
Obviously the big issue here right now is the emergence of resistance to artemisinins and this is not just an issue along the Cambodian – Thailand border, but is also a global issue. We rely very heavily on artemisinin-based combination therapies or ACTs and artemisinin is the key ingredient in that combination.
And the stakes are very high because right now we do not have other drugs in the development pipeline that are likely to reach markets before five years, the earliest. And that is an optimistic projection.
So it is really critical that we bring all forces together to try and preserve the efficacy of these valuable medicines.
Here in Western Cambodia we have an extraordinary effort made by the Cambodian National Malaria Control Program and their counterpart program in Thailand to contain the spread of these resistant parasites. The efforts here, I think, have been groundbreaking in their comprehensiveness. Some of the approaches that have been taken are also novel and pioneering.
The Cambodian government has banned the sale of monotherapies. Do you think there should be a similar ban regionally within the Association of Southeast Asian Nations or ASEAN?
Absolutely. I think we all agree now at this point that the use of oral artemisinin monotherapies is probably the single greatest factor for the spread of artemisinin-resistant parasites. In 2007 there was a World Health Assembly resolution that called for a halt in the marketing and use of these compounds.
The worst 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]…
While there has been some forward movement in the number of countries that have complied both in terms of shutting down the manufacturer, marketing of these drugs and to some extent in their use, we still have to go some way. This is such an urgent issue. The time to do that is now.
We need all countries, globally – particularly here in the Greater Mekong sub-region and ASEAN to ensure that these dangerous medicines are removed immediately from the market place.
What are the differences between containment and elimination; elimination and eradication?
Containment would mean in this context that we take these resistant parasites and don’t let them spread outside the area where they have been identified. So at this point the confirmed areas are along the Thai-Cambodian border, although there are other areas in the Greater Mekong sub-region where we have suspicion of their emergence.
Elimination would mean that we would actually be able to eliminate all of the parasites. That is a very difficult thing to document. Obviously, if we are able to eliminate these resistant parasites then the risk of their spread is essentially gone.
The term elimination is more generally used to refer to the reduction at the country level of local transmission of malaria to zero. So usually we talk of eliminating malaria at a country level.
Eradication is reserved for the global incidence of malaria going to down to zero. And that’s for all plasmodium species and not just for falciparum. That obviously remains the ultimate public health goal, although I believe that will take 40 or more years to achieve. It would require the development of new transformative tools that we do not have, yet.
What’s the worst case scenario for MDR-falciparum malaria?
The worst 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].
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.
Right now we have resistance to artemisinins, but artemisinin-based combination therapies (ACTs) still remain efficacious. That is a very important message.
But 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.
As you know we still have more than 700,000 estimated deaths a year in Africa from malaria. We rely entirely on ACTs for the treatment of falciparum malaria. If we were to lose those medicines in Africa, that would be a catastrophe. This is precisely what the extraordinary efforts in the Containment Project, here, in the Greater Mekong sub-region are trying to prevent.