User login
Protocol could improve massive blood transfusion
An “early and aggressive” approach to massive blood transfusion can save lives in military combat zones and may provide the same benefit in civilian trauma care as well, according to an article published in the AANA Journal.
The article describes 2 patients who required massive transfusions due to multiple gunshot wounds sustained while in combat zones.
One patient received an inadequate amount of blood products and ultimately died.
But the other patient benefitted from a protocol change to ensure an adequate amount of blood products was delivered quickly.
David Gaskin, CRNA, of Huntsville Memorial Hospital in Texas, and his colleagues described these cases in the journal.
The authors noted that, while providing care in a combat zone, the transfusion of packed red blood cells (PRBC) and fresh frozen plasma (FFP) is performed in a 1:1 ratio. However, the packaging and thawing techniques of the plasma can delay the delivery of blood products and prevent a patient from receiving enough blood.
Another issue in a military environment is the challenge of effectively communicating with live donors on site, which can cause delays in obtaining fresh blood supplies. Both of these issues can have life-threatening consequences for patients.
This is what happened with the first patient described in the article. The 38-year-old man sustained multiple gunshot wounds to the left side of the chest, left side of the back, and flank.
The surgical team was unable to maintain a high ratio of PRBCs to plasma and to infuse an adequate quantity of fresh whole blood (FWB) into this patient. He received 26 units of PRBCs, 5 units of FFP, 3 units of FWB, and 1 unit of cryoprecipitate.
The patient experienced trauma-induced coagulopathy, acidosis, and hypothermia. He died within 2 hours of presentation.
Because of this death, the team identified and implemented a protocol to keep 4 FFP units thawed and ready for immediate use at all times. They also identified and prescreened additional blood donors and implemented a phone roster and base-wide overhead system to enable rapid notification of these donors.
The second patient described in the article benefitted from these changes. This 23-year-old male sustained a gunshot wound to the left lower aspect of the abdomen and multiple gunshot wounds to bilateral lower extremities.
The “early and aggressive” use of FWB and plasma provided the necessary endogenous clotting factors and platelets to promote hemostasis in this patient. He received 18 units of PRBCs, 18 units of FFP, 2 units of cryoprecipitate, and 24 units of FWB.
Gaskin and his colleagues said these results suggest that efforts to incorporate a similar resuscitation strategy into civilian practice may improve outcomes, but it warrants continued study. 
An “early and aggressive” approach to massive blood transfusion can save lives in military combat zones and may provide the same benefit in civilian trauma care as well, according to an article published in the AANA Journal.
The article describes 2 patients who required massive transfusions due to multiple gunshot wounds sustained while in combat zones.
One patient received an inadequate amount of blood products and ultimately died.
But the other patient benefitted from a protocol change to ensure an adequate amount of blood products was delivered quickly.
David Gaskin, CRNA, of Huntsville Memorial Hospital in Texas, and his colleagues described these cases in the journal.
The authors noted that, while providing care in a combat zone, the transfusion of packed red blood cells (PRBC) and fresh frozen plasma (FFP) is performed in a 1:1 ratio. However, the packaging and thawing techniques of the plasma can delay the delivery of blood products and prevent a patient from receiving enough blood.
Another issue in a military environment is the challenge of effectively communicating with live donors on site, which can cause delays in obtaining fresh blood supplies. Both of these issues can have life-threatening consequences for patients.
This is what happened with the first patient described in the article. The 38-year-old man sustained multiple gunshot wounds to the left side of the chest, left side of the back, and flank.
The surgical team was unable to maintain a high ratio of PRBCs to plasma and to infuse an adequate quantity of fresh whole blood (FWB) into this patient. He received 26 units of PRBCs, 5 units of FFP, 3 units of FWB, and 1 unit of cryoprecipitate.
The patient experienced trauma-induced coagulopathy, acidosis, and hypothermia. He died within 2 hours of presentation.
Because of this death, the team identified and implemented a protocol to keep 4 FFP units thawed and ready for immediate use at all times. They also identified and prescreened additional blood donors and implemented a phone roster and base-wide overhead system to enable rapid notification of these donors.
The second patient described in the article benefitted from these changes. This 23-year-old male sustained a gunshot wound to the left lower aspect of the abdomen and multiple gunshot wounds to bilateral lower extremities.
The “early and aggressive” use of FWB and plasma provided the necessary endogenous clotting factors and platelets to promote hemostasis in this patient. He received 18 units of PRBCs, 18 units of FFP, 2 units of cryoprecipitate, and 24 units of FWB.
Gaskin and his colleagues said these results suggest that efforts to incorporate a similar resuscitation strategy into civilian practice may improve outcomes, but it warrants continued study.
An “early and aggressive” approach to massive blood transfusion can save lives in military combat zones and may provide the same benefit in civilian trauma care as well, according to an article published in the AANA Journal.
The article describes 2 patients who required massive transfusions due to multiple gunshot wounds sustained while in combat zones.
One patient received an inadequate amount of blood products and ultimately died.
But the other patient benefitted from a protocol change to ensure an adequate amount of blood products was delivered quickly.
David Gaskin, CRNA, of Huntsville Memorial Hospital in Texas, and his colleagues described these cases in the journal.
The authors noted that, while providing care in a combat zone, the transfusion of packed red blood cells (PRBC) and fresh frozen plasma (FFP) is performed in a 1:1 ratio. However, the packaging and thawing techniques of the plasma can delay the delivery of blood products and prevent a patient from receiving enough blood.
Another issue in a military environment is the challenge of effectively communicating with live donors on site, which can cause delays in obtaining fresh blood supplies. Both of these issues can have life-threatening consequences for patients.
This is what happened with the first patient described in the article. The 38-year-old man sustained multiple gunshot wounds to the left side of the chest, left side of the back, and flank.
The surgical team was unable to maintain a high ratio of PRBCs to plasma and to infuse an adequate quantity of fresh whole blood (FWB) into this patient. He received 26 units of PRBCs, 5 units of FFP, 3 units of FWB, and 1 unit of cryoprecipitate.
The patient experienced trauma-induced coagulopathy, acidosis, and hypothermia. He died within 2 hours of presentation.
Because of this death, the team identified and implemented a protocol to keep 4 FFP units thawed and ready for immediate use at all times. They also identified and prescreened additional blood donors and implemented a phone roster and base-wide overhead system to enable rapid notification of these donors.
The second patient described in the article benefitted from these changes. This 23-year-old male sustained a gunshot wound to the left lower aspect of the abdomen and multiple gunshot wounds to bilateral lower extremities.
The “early and aggressive” use of FWB and plasma provided the necessary endogenous clotting factors and platelets to promote hemostasis in this patient. He received 18 units of PRBCs, 18 units of FFP, 2 units of cryoprecipitate, and 24 units of FWB.
Gaskin and his colleagues said these results suggest that efforts to incorporate a similar resuscitation strategy into civilian practice may improve outcomes, but it warrants continued study.
Drug can block malaria transmission, studies show
Image by Ute Frevert
and Margaret Shear
PHILADELPHIA—A drug used to treat multiple tropical diseases can also inhibit malaria transmission, according to a pair of studies presented at the ASTMH 64th Annual Meeting.
One study suggests the drug, ivermectin, can reduce the transmission of malaria caused by Plasmodium falciparum, the most prevalent malaria parasite in Africa.
The other study indicates that ivermectin can block the transmission of Plasmodium vivax parasites, which are common in Southeast Asia.
Kevin Kobylinski, PhD, of the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, presented results of the P vivax study as abstract 1283.
And Brian D. Foy, PhD, of Colorado State University in Fort Collins, presented results of the P falciparum trial as abstract LB-5237.
P falciparum malaria
Dr Foy and his colleagues are assessing the ability of ivermectin to block malaria transmission in 4 villages in Burkina Faso, Africa.
Lab studies have shown that when mosquitoes feed on the blood of people who have taken ivermectin, it interferes with the mosquitoes’ ability to transmit malaria parasites to humans. Sometimes, it kills the mosquitoes outright, but, more often, it weakens them and interferes with their digestive system so they eventually die in the harsh conditions of nature.
“Even if the mosquitoes don’t get enough ivermectin to directly kill them, we think a sublethal dose should be sufficiently toxic to reduce malaria transmission,” Dr Foy said.
But he noted that because the goal is to interrupt malaria transmission, the drug must be taken by a majority of the people in a town or village, who then pass it along to the mosquitoes.
For the last few months, most of the population in the 4 villages in Burkina Faso has been receiving a single dose of ivermectin every 3 weeks. Individuals who are not eligible to take the drug include children less than 90 cm tall, pregnant women, and newly breastfeeding women.
The measure of success is a reduction in malaria incidence among children younger than 5, most of whom will not actually take the drug. But this is the age group most at risk of serious illness and death from the disease.
Thus far, the researchers have observed a roughly 16% reduction in childhood malaria episodes.
“These are preliminary results, but we expect to see further reductions in malaria fevers as we continue with the trial, which is occurring during the rainy season when malaria transmission typically peaks,” Dr Foy said.
“The drop in malaria fevers we’re seeing with the ivermectin treatment is in addition to whatever is being achieved with insecticide-treated bednets, which are in widespread use in all of the villages participating in the study.”
P vivax malaria
Dr Kobylinski and his colleagues found that ivermectin can affect P vivax parasites as well. The researchers tested the drug’s potential to block malaria transmission by feeding blood meals containing ivermectin and P vivax parasites to Anopheles dirus mosquitoes, the predominant malaria vector in Southeast Asia.
Ivermectin effectively killed A dirus mosquitoes, and it inhibited the ability of any surviving mosquitoes to develop P vivax parasites.
Dr Kobylinski noted that malaria experts are considering combining ivermectin with other medications in mass drug administration (MDA) campaigns that would seek to stop the spread of drug-resistant parasites in Southeast Asia by eliminating malaria from the entire region.
He said ivermectin could help increase compliance with an MDA strategy in places like Thailand, where drug-resistant malaria is spreading but overall malaria infection rates are relatively low.
“There is a lot of interest in launching MDA campaigns to fight drug-resistant malaria in Southeast Asia, but it can be hard to convince someone to take malaria medications if they don’t have an active malaria infection,” Dr Kobylinski said.
“But if you put ivermectin into the mix, that could improve participation because many people recognize the benefits of taking ivermectin for more common problems, like scabies.”
About ivermectin
Over the last 3 decades, more than 1 billion doses of ivermectin have been distributed in Africa and Latin America in MDA campaigns that have reduced the burden of lymphatic filariasis, which causes elephantiasis, and onchocerciasis, the disease that causes river blindness.
Ivermectin can also kill several types of debilitating intestinal worms known as soil-transmitted helminths.
Earlier this month, the Nobel Prize in Physiology or Medicine was awarded to a pair of researchers who isolated the precursor of ivermectin, avermectin, from an organism discovered in a single soil sample collected in Japan in the 1970s.
Image by Ute Frevert
and Margaret Shear
PHILADELPHIA—A drug used to treat multiple tropical diseases can also inhibit malaria transmission, according to a pair of studies presented at the ASTMH 64th Annual Meeting.
One study suggests the drug, ivermectin, can reduce the transmission of malaria caused by Plasmodium falciparum, the most prevalent malaria parasite in Africa.
The other study indicates that ivermectin can block the transmission of Plasmodium vivax parasites, which are common in Southeast Asia.
Kevin Kobylinski, PhD, of the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, presented results of the P vivax study as abstract 1283.
And Brian D. Foy, PhD, of Colorado State University in Fort Collins, presented results of the P falciparum trial as abstract LB-5237.
P falciparum malaria
Dr Foy and his colleagues are assessing the ability of ivermectin to block malaria transmission in 4 villages in Burkina Faso, Africa.
Lab studies have shown that when mosquitoes feed on the blood of people who have taken ivermectin, it interferes with the mosquitoes’ ability to transmit malaria parasites to humans. Sometimes, it kills the mosquitoes outright, but, more often, it weakens them and interferes with their digestive system so they eventually die in the harsh conditions of nature.
“Even if the mosquitoes don’t get enough ivermectin to directly kill them, we think a sublethal dose should be sufficiently toxic to reduce malaria transmission,” Dr Foy said.
But he noted that because the goal is to interrupt malaria transmission, the drug must be taken by a majority of the people in a town or village, who then pass it along to the mosquitoes.
For the last few months, most of the population in the 4 villages in Burkina Faso has been receiving a single dose of ivermectin every 3 weeks. Individuals who are not eligible to take the drug include children less than 90 cm tall, pregnant women, and newly breastfeeding women.
The measure of success is a reduction in malaria incidence among children younger than 5, most of whom will not actually take the drug. But this is the age group most at risk of serious illness and death from the disease.
Thus far, the researchers have observed a roughly 16% reduction in childhood malaria episodes.
“These are preliminary results, but we expect to see further reductions in malaria fevers as we continue with the trial, which is occurring during the rainy season when malaria transmission typically peaks,” Dr Foy said.
“The drop in malaria fevers we’re seeing with the ivermectin treatment is in addition to whatever is being achieved with insecticide-treated bednets, which are in widespread use in all of the villages participating in the study.”
P vivax malaria
Dr Kobylinski and his colleagues found that ivermectin can affect P vivax parasites as well. The researchers tested the drug’s potential to block malaria transmission by feeding blood meals containing ivermectin and P vivax parasites to Anopheles dirus mosquitoes, the predominant malaria vector in Southeast Asia.
Ivermectin effectively killed A dirus mosquitoes, and it inhibited the ability of any surviving mosquitoes to develop P vivax parasites.
Dr Kobylinski noted that malaria experts are considering combining ivermectin with other medications in mass drug administration (MDA) campaigns that would seek to stop the spread of drug-resistant parasites in Southeast Asia by eliminating malaria from the entire region.
He said ivermectin could help increase compliance with an MDA strategy in places like Thailand, where drug-resistant malaria is spreading but overall malaria infection rates are relatively low.
“There is a lot of interest in launching MDA campaigns to fight drug-resistant malaria in Southeast Asia, but it can be hard to convince someone to take malaria medications if they don’t have an active malaria infection,” Dr Kobylinski said.
“But if you put ivermectin into the mix, that could improve participation because many people recognize the benefits of taking ivermectin for more common problems, like scabies.”
About ivermectin
Over the last 3 decades, more than 1 billion doses of ivermectin have been distributed in Africa and Latin America in MDA campaigns that have reduced the burden of lymphatic filariasis, which causes elephantiasis, and onchocerciasis, the disease that causes river blindness.
Ivermectin can also kill several types of debilitating intestinal worms known as soil-transmitted helminths.
Earlier this month, the Nobel Prize in Physiology or Medicine was awarded to a pair of researchers who isolated the precursor of ivermectin, avermectin, from an organism discovered in a single soil sample collected in Japan in the 1970s.
Image by Ute Frevert
and Margaret Shear
PHILADELPHIA—A drug used to treat multiple tropical diseases can also inhibit malaria transmission, according to a pair of studies presented at the ASTMH 64th Annual Meeting.
One study suggests the drug, ivermectin, can reduce the transmission of malaria caused by Plasmodium falciparum, the most prevalent malaria parasite in Africa.
The other study indicates that ivermectin can block the transmission of Plasmodium vivax parasites, which are common in Southeast Asia.
Kevin Kobylinski, PhD, of the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, presented results of the P vivax study as abstract 1283.
And Brian D. Foy, PhD, of Colorado State University in Fort Collins, presented results of the P falciparum trial as abstract LB-5237.
P falciparum malaria
Dr Foy and his colleagues are assessing the ability of ivermectin to block malaria transmission in 4 villages in Burkina Faso, Africa.
Lab studies have shown that when mosquitoes feed on the blood of people who have taken ivermectin, it interferes with the mosquitoes’ ability to transmit malaria parasites to humans. Sometimes, it kills the mosquitoes outright, but, more often, it weakens them and interferes with their digestive system so they eventually die in the harsh conditions of nature.
“Even if the mosquitoes don’t get enough ivermectin to directly kill them, we think a sublethal dose should be sufficiently toxic to reduce malaria transmission,” Dr Foy said.
But he noted that because the goal is to interrupt malaria transmission, the drug must be taken by a majority of the people in a town or village, who then pass it along to the mosquitoes.
For the last few months, most of the population in the 4 villages in Burkina Faso has been receiving a single dose of ivermectin every 3 weeks. Individuals who are not eligible to take the drug include children less than 90 cm tall, pregnant women, and newly breastfeeding women.
The measure of success is a reduction in malaria incidence among children younger than 5, most of whom will not actually take the drug. But this is the age group most at risk of serious illness and death from the disease.
Thus far, the researchers have observed a roughly 16% reduction in childhood malaria episodes.
“These are preliminary results, but we expect to see further reductions in malaria fevers as we continue with the trial, which is occurring during the rainy season when malaria transmission typically peaks,” Dr Foy said.
“The drop in malaria fevers we’re seeing with the ivermectin treatment is in addition to whatever is being achieved with insecticide-treated bednets, which are in widespread use in all of the villages participating in the study.”
P vivax malaria
Dr Kobylinski and his colleagues found that ivermectin can affect P vivax parasites as well. The researchers tested the drug’s potential to block malaria transmission by feeding blood meals containing ivermectin and P vivax parasites to Anopheles dirus mosquitoes, the predominant malaria vector in Southeast Asia.
Ivermectin effectively killed A dirus mosquitoes, and it inhibited the ability of any surviving mosquitoes to develop P vivax parasites.
Dr Kobylinski noted that malaria experts are considering combining ivermectin with other medications in mass drug administration (MDA) campaigns that would seek to stop the spread of drug-resistant parasites in Southeast Asia by eliminating malaria from the entire region.
He said ivermectin could help increase compliance with an MDA strategy in places like Thailand, where drug-resistant malaria is spreading but overall malaria infection rates are relatively low.
“There is a lot of interest in launching MDA campaigns to fight drug-resistant malaria in Southeast Asia, but it can be hard to convince someone to take malaria medications if they don’t have an active malaria infection,” Dr Kobylinski said.
“But if you put ivermectin into the mix, that could improve participation because many people recognize the benefits of taking ivermectin for more common problems, like scabies.”
About ivermectin
Over the last 3 decades, more than 1 billion doses of ivermectin have been distributed in Africa and Latin America in MDA campaigns that have reduced the burden of lymphatic filariasis, which causes elephantiasis, and onchocerciasis, the disease that causes river blindness.
Ivermectin can also kill several types of debilitating intestinal worms known as soil-transmitted helminths.
Earlier this month, the Nobel Prize in Physiology or Medicine was awarded to a pair of researchers who isolated the precursor of ivermectin, avermectin, from an organism discovered in a single soil sample collected in Japan in the 1970s.
Cancer care in Latin America
patient and her father
Photo by Rhoda Baer
Despite progress made in cancer care in Latin America in the last 2 years, substantial barriers remain to ensure optimal clinical management, according to a report commissioned by The Lancet Oncology.
The report, an update from a report published in 2013, details a number of improvements in cancer care in Latin America, either specifically related to cancer or to general healthcare initiatives that will also benefit cancer patients.
However, the updated report also suggests that major changes are needed in many areas to increase the standard of cancer care in Latin America.
Progress made
According to the report, progress has been made in the following areas.
The proportion of people in Latin America affiliated with any kind of health insurance program grew from 46% to 60% between 2008 and 2013.
For 2014, the World Health Organization (WHO) reported an 8% increase in the number of countries (60% of the whole region) with a National Cancer Plan. The following countries have newly adopted plans: Suriname, Ecuador, Dominican Republic, Trinidad and Tobago, Puerto Rico, Peru, El Salvador, and Colombia.
In addition, Latin America—most notably, Brazil and Argentina—has begun to address the shortage of cancer specialists.
Brazil has shown an increase of 77% in oncologists since 2011 (from 1457 to 2577). Concurrently, the number of hematologists has also increased by 40% (from 1420 in 2011 to 1985 in 2015), and that of radiotherapists by 12% (from 444 in 2011 to 497 in 2015). These rises are in the context of an 11% increase in cancer cases in Brazil (from 518,000 new cases in 2012 to 576,000 in 2014).
Many countries across Latin America have signed on to the Global Action Plan for the Prevention and Control of Non-Communicable Diseases 2013-2020, endorsed by the WHO, which aims to achieve a 25% reduction in premature mortality from non-communicable diseases (including cancer) by 2025.
The Colombian Ministry of Health and Social Protection has expanded its social insurance program to cover all types of cancer.
Since January 2014, the administration of chemotherapy and radiation treatments is free of charge in Uruguay.
The Atlas of Palliative Care was published in Latin America, which revealed a growth of more than 400% in the number of palliative services since 2006.
Room for improvement
The report indicates that the following issues are still problems in Latin America.
Compared with high-income countries, Latin America in 2015 remains behind in terms of public expenditure on health and cancer care.
Argentina and Mexico spend around 6% of their gross national product on healthcare, compared to 9% for the UK, 11% for Germany, and 17% for the US, which reflects a gap between Latin American and other countries not only proportionately but also in terms of absolute dollars. Only Brazil, at 9%, is close to the proportion spent in high-income countries.
In Latin America, only Brazil, Cuba, Costa Rica, and Uruguay are considered to have integration of social security and public insurance, and only Brazil, Cuba, and Costa Rica can be judged to have universal healthcare.
Many countries still have no specific training in palliative care (including Bolivia, El Salvador, Honduras, and Nicaragua).
Additionally, data from 2002 showed that Latin America accounted for less than 1% of the world’s opioid drug consumption for pain relief. Consumption of strong opioids still lags behind developed countries today, with no Latin American country exceeding 15 mg/capita per year.
Under-implementation of new technologies has not improved substantially since the previous Lancet Oncology Commission in 2013. There are a few exceptions, however, such as PET scanning technology improvements in Uruguay.
Pharmaceutical trials for expensive new anticancer therapies are largely unhelpful to most patients in Latin America. Patients participating in trials of expensive new anticancer therapies sometimes cannot complete treatment once their trial ends, and the trials often do not lead to approval in these regions.
There are often geographical disparities where most cancer specialists are located in major hospitals in big cities, requiring patients from rural and remote areas to travel far distances to these hospitals for cancer care.
In addition, waiting times in these centers can be unacceptably long, with reports from Mexico and Brazil describing median waiting times of 7 months or more for patients with breast cancer from symptomatic presentation to initial treatment.
Better cancer registries are desperately needed in all Latin American countries to more accurately quantify the cancer burden in the region and the resources required to combat it, according to the report.
patient and her father
Photo by Rhoda Baer
Despite progress made in cancer care in Latin America in the last 2 years, substantial barriers remain to ensure optimal clinical management, according to a report commissioned by The Lancet Oncology.
The report, an update from a report published in 2013, details a number of improvements in cancer care in Latin America, either specifically related to cancer or to general healthcare initiatives that will also benefit cancer patients.
However, the updated report also suggests that major changes are needed in many areas to increase the standard of cancer care in Latin America.
Progress made
According to the report, progress has been made in the following areas.
The proportion of people in Latin America affiliated with any kind of health insurance program grew from 46% to 60% between 2008 and 2013.
For 2014, the World Health Organization (WHO) reported an 8% increase in the number of countries (60% of the whole region) with a National Cancer Plan. The following countries have newly adopted plans: Suriname, Ecuador, Dominican Republic, Trinidad and Tobago, Puerto Rico, Peru, El Salvador, and Colombia.
In addition, Latin America—most notably, Brazil and Argentina—has begun to address the shortage of cancer specialists.
Brazil has shown an increase of 77% in oncologists since 2011 (from 1457 to 2577). Concurrently, the number of hematologists has also increased by 40% (from 1420 in 2011 to 1985 in 2015), and that of radiotherapists by 12% (from 444 in 2011 to 497 in 2015). These rises are in the context of an 11% increase in cancer cases in Brazil (from 518,000 new cases in 2012 to 576,000 in 2014).
Many countries across Latin America have signed on to the Global Action Plan for the Prevention and Control of Non-Communicable Diseases 2013-2020, endorsed by the WHO, which aims to achieve a 25% reduction in premature mortality from non-communicable diseases (including cancer) by 2025.
The Colombian Ministry of Health and Social Protection has expanded its social insurance program to cover all types of cancer.
Since January 2014, the administration of chemotherapy and radiation treatments is free of charge in Uruguay.
The Atlas of Palliative Care was published in Latin America, which revealed a growth of more than 400% in the number of palliative services since 2006.
Room for improvement
The report indicates that the following issues are still problems in Latin America.
Compared with high-income countries, Latin America in 2015 remains behind in terms of public expenditure on health and cancer care.
Argentina and Mexico spend around 6% of their gross national product on healthcare, compared to 9% for the UK, 11% for Germany, and 17% for the US, which reflects a gap between Latin American and other countries not only proportionately but also in terms of absolute dollars. Only Brazil, at 9%, is close to the proportion spent in high-income countries.
In Latin America, only Brazil, Cuba, Costa Rica, and Uruguay are considered to have integration of social security and public insurance, and only Brazil, Cuba, and Costa Rica can be judged to have universal healthcare.
Many countries still have no specific training in palliative care (including Bolivia, El Salvador, Honduras, and Nicaragua).
Additionally, data from 2002 showed that Latin America accounted for less than 1% of the world’s opioid drug consumption for pain relief. Consumption of strong opioids still lags behind developed countries today, with no Latin American country exceeding 15 mg/capita per year.
Under-implementation of new technologies has not improved substantially since the previous Lancet Oncology Commission in 2013. There are a few exceptions, however, such as PET scanning technology improvements in Uruguay.
Pharmaceutical trials for expensive new anticancer therapies are largely unhelpful to most patients in Latin America. Patients participating in trials of expensive new anticancer therapies sometimes cannot complete treatment once their trial ends, and the trials often do not lead to approval in these regions.
There are often geographical disparities where most cancer specialists are located in major hospitals in big cities, requiring patients from rural and remote areas to travel far distances to these hospitals for cancer care.
In addition, waiting times in these centers can be unacceptably long, with reports from Mexico and Brazil describing median waiting times of 7 months or more for patients with breast cancer from symptomatic presentation to initial treatment.
Better cancer registries are desperately needed in all Latin American countries to more accurately quantify the cancer burden in the region and the resources required to combat it, according to the report.
patient and her father
Photo by Rhoda Baer
Despite progress made in cancer care in Latin America in the last 2 years, substantial barriers remain to ensure optimal clinical management, according to a report commissioned by The Lancet Oncology.
The report, an update from a report published in 2013, details a number of improvements in cancer care in Latin America, either specifically related to cancer or to general healthcare initiatives that will also benefit cancer patients.
However, the updated report also suggests that major changes are needed in many areas to increase the standard of cancer care in Latin America.
Progress made
According to the report, progress has been made in the following areas.
The proportion of people in Latin America affiliated with any kind of health insurance program grew from 46% to 60% between 2008 and 2013.
For 2014, the World Health Organization (WHO) reported an 8% increase in the number of countries (60% of the whole region) with a National Cancer Plan. The following countries have newly adopted plans: Suriname, Ecuador, Dominican Republic, Trinidad and Tobago, Puerto Rico, Peru, El Salvador, and Colombia.
In addition, Latin America—most notably, Brazil and Argentina—has begun to address the shortage of cancer specialists.
Brazil has shown an increase of 77% in oncologists since 2011 (from 1457 to 2577). Concurrently, the number of hematologists has also increased by 40% (from 1420 in 2011 to 1985 in 2015), and that of radiotherapists by 12% (from 444 in 2011 to 497 in 2015). These rises are in the context of an 11% increase in cancer cases in Brazil (from 518,000 new cases in 2012 to 576,000 in 2014).
Many countries across Latin America have signed on to the Global Action Plan for the Prevention and Control of Non-Communicable Diseases 2013-2020, endorsed by the WHO, which aims to achieve a 25% reduction in premature mortality from non-communicable diseases (including cancer) by 2025.
The Colombian Ministry of Health and Social Protection has expanded its social insurance program to cover all types of cancer.
Since January 2014, the administration of chemotherapy and radiation treatments is free of charge in Uruguay.
The Atlas of Palliative Care was published in Latin America, which revealed a growth of more than 400% in the number of palliative services since 2006.
Room for improvement
The report indicates that the following issues are still problems in Latin America.
Compared with high-income countries, Latin America in 2015 remains behind in terms of public expenditure on health and cancer care.
Argentina and Mexico spend around 6% of their gross national product on healthcare, compared to 9% for the UK, 11% for Germany, and 17% for the US, which reflects a gap between Latin American and other countries not only proportionately but also in terms of absolute dollars. Only Brazil, at 9%, is close to the proportion spent in high-income countries.
In Latin America, only Brazil, Cuba, Costa Rica, and Uruguay are considered to have integration of social security and public insurance, and only Brazil, Cuba, and Costa Rica can be judged to have universal healthcare.
Many countries still have no specific training in palliative care (including Bolivia, El Salvador, Honduras, and Nicaragua).
Additionally, data from 2002 showed that Latin America accounted for less than 1% of the world’s opioid drug consumption for pain relief. Consumption of strong opioids still lags behind developed countries today, with no Latin American country exceeding 15 mg/capita per year.
Under-implementation of new technologies has not improved substantially since the previous Lancet Oncology Commission in 2013. There are a few exceptions, however, such as PET scanning technology improvements in Uruguay.
Pharmaceutical trials for expensive new anticancer therapies are largely unhelpful to most patients in Latin America. Patients participating in trials of expensive new anticancer therapies sometimes cannot complete treatment once their trial ends, and the trials often do not lead to approval in these regions.
There are often geographical disparities where most cancer specialists are located in major hospitals in big cities, requiring patients from rural and remote areas to travel far distances to these hospitals for cancer care.
In addition, waiting times in these centers can be unacceptably long, with reports from Mexico and Brazil describing median waiting times of 7 months or more for patients with breast cancer from symptomatic presentation to initial treatment.
Better cancer registries are desperately needed in all Latin American countries to more accurately quantify the cancer burden in the region and the resources required to combat it, according to the report.
Gene may be key to fighting sepsis
with a multi-pipettor
Photo courtesy of Stuart Hay/
Australian National University
Scientists have identified a gene that could potentially aid the development of new treatments for sepsis.
The team knew that sepsis occurs when lipopolysaccharides (LPS) on the surface of some bacteria infiltrate cells, triggering an immune response that causes the cells to self-destruct.
However, it was unclear exactly how this happens. That is, until the team found the protein gasdermin D plays a critical role in the pathway to sepsis.
“This finding is a key that could potentially unlock our ability to shut down this killer disease before it gets to a life-threatening stage,” said Chris Goodnow, PhD, of The Australian National University in Canberra.
Dr Goodnow and his colleagues described their discovery in Nature.
The scientists found that gasdermin D usually exists in cells in an inactive form.
But when the LPS molecules enter cells, they trigger caspase-11 to lop off the protective chemical cap of gasdermin D. This, in turn, prompts the cells to self-destruct.
The team said this suggests gasdermin D is a critical target of
caspase-11 and a key mediator of the host response against Gram-negative
bacteria.
To identify the source of this discovery, the scientists screened thousands of genes. In a little over a year, they isolated the gene that produces gasdermin D.
Lead study author Nobuhiko Kayagaki, PhD, of Genentech in San Francisco, California, said this work could have implications beyond sepsis.
“The identification of gasdermin D can give us a better understanding not only of lethal sepsis, but also of multiple other inflammatory diseases,” he said.
with a multi-pipettor
Photo courtesy of Stuart Hay/
Australian National University
Scientists have identified a gene that could potentially aid the development of new treatments for sepsis.
The team knew that sepsis occurs when lipopolysaccharides (LPS) on the surface of some bacteria infiltrate cells, triggering an immune response that causes the cells to self-destruct.
However, it was unclear exactly how this happens. That is, until the team found the protein gasdermin D plays a critical role in the pathway to sepsis.
“This finding is a key that could potentially unlock our ability to shut down this killer disease before it gets to a life-threatening stage,” said Chris Goodnow, PhD, of The Australian National University in Canberra.
Dr Goodnow and his colleagues described their discovery in Nature.
The scientists found that gasdermin D usually exists in cells in an inactive form.
But when the LPS molecules enter cells, they trigger caspase-11 to lop off the protective chemical cap of gasdermin D. This, in turn, prompts the cells to self-destruct.
The team said this suggests gasdermin D is a critical target of
caspase-11 and a key mediator of the host response against Gram-negative
bacteria.
To identify the source of this discovery, the scientists screened thousands of genes. In a little over a year, they isolated the gene that produces gasdermin D.
Lead study author Nobuhiko Kayagaki, PhD, of Genentech in San Francisco, California, said this work could have implications beyond sepsis.
“The identification of gasdermin D can give us a better understanding not only of lethal sepsis, but also of multiple other inflammatory diseases,” he said.
with a multi-pipettor
Photo courtesy of Stuart Hay/
Australian National University
Scientists have identified a gene that could potentially aid the development of new treatments for sepsis.
The team knew that sepsis occurs when lipopolysaccharides (LPS) on the surface of some bacteria infiltrate cells, triggering an immune response that causes the cells to self-destruct.
However, it was unclear exactly how this happens. That is, until the team found the protein gasdermin D plays a critical role in the pathway to sepsis.
“This finding is a key that could potentially unlock our ability to shut down this killer disease before it gets to a life-threatening stage,” said Chris Goodnow, PhD, of The Australian National University in Canberra.
Dr Goodnow and his colleagues described their discovery in Nature.
The scientists found that gasdermin D usually exists in cells in an inactive form.
But when the LPS molecules enter cells, they trigger caspase-11 to lop off the protective chemical cap of gasdermin D. This, in turn, prompts the cells to self-destruct.
The team said this suggests gasdermin D is a critical target of
caspase-11 and a key mediator of the host response against Gram-negative
bacteria.
To identify the source of this discovery, the scientists screened thousands of genes. In a little over a year, they isolated the gene that produces gasdermin D.
Lead study author Nobuhiko Kayagaki, PhD, of Genentech in San Francisco, California, said this work could have implications beyond sepsis.
“The identification of gasdermin D can give us a better understanding not only of lethal sepsis, but also of multiple other inflammatory diseases,” he said.
How a cancer diagnosis affects income
receiving treatment
Photo by Rhoda Baer
A new study indicates that when American adults are diagnosed with
cancer, they experience significant decreases in the probability of
working, in the number of hours they work, and correspondingly, in their
incomes.
Additionally, these effects appear to be more pronounced among men than women.
Anna Zajacova, PhD, of the University of Wyoming in Laramie, and her colleagues reported these findings in Cancer.
The researchers analyzed data from the Panel Study of Income Dynamics, a nationally representative, prospective, population-based, observational study with individual and family level economic information. The data spanned the period from 1999 to 2009.
The team used models to estimate the impact of cancer on employment, hours worked, individual income, and total family income.
The results showed that, after a cancer diagnosis, the probability of a patient being employed dropped by almost 10 percentage points, and hours worked declined by up to 200 hours, or about 5 weeks of full-time work, in the first year.
Annual labor market earnings dropped almost 40% within 2 years of diagnosis, and they remained lower than before diagnosis. Total family income declined by 20%, although it recovered within 4 years of cancer diagnosis.
These effects were primarily driven by losses among male cancer survivors. For women diagnosed with cancer, the losses were largely not statistically significant.
“Fifteen million American adults are cancer survivors, and American families need economic support while they are dealing with the rigors of cancer treatment,” Dr Zajacova said.
“Our paper suggests that families where an adult—especially a working-age male—is diagnosed with cancer suffer short-term and long-term declines in their economic well-being. We need to improve workplace and insurance safety nets so families can focus on dealing with the cancer treatment rather than deal with the financial and employment fallout.”
receiving treatment
Photo by Rhoda Baer
A new study indicates that when American adults are diagnosed with
cancer, they experience significant decreases in the probability of
working, in the number of hours they work, and correspondingly, in their
incomes.
Additionally, these effects appear to be more pronounced among men than women.
Anna Zajacova, PhD, of the University of Wyoming in Laramie, and her colleagues reported these findings in Cancer.
The researchers analyzed data from the Panel Study of Income Dynamics, a nationally representative, prospective, population-based, observational study with individual and family level economic information. The data spanned the period from 1999 to 2009.
The team used models to estimate the impact of cancer on employment, hours worked, individual income, and total family income.
The results showed that, after a cancer diagnosis, the probability of a patient being employed dropped by almost 10 percentage points, and hours worked declined by up to 200 hours, or about 5 weeks of full-time work, in the first year.
Annual labor market earnings dropped almost 40% within 2 years of diagnosis, and they remained lower than before diagnosis. Total family income declined by 20%, although it recovered within 4 years of cancer diagnosis.
These effects were primarily driven by losses among male cancer survivors. For women diagnosed with cancer, the losses were largely not statistically significant.
“Fifteen million American adults are cancer survivors, and American families need economic support while they are dealing with the rigors of cancer treatment,” Dr Zajacova said.
“Our paper suggests that families where an adult—especially a working-age male—is diagnosed with cancer suffer short-term and long-term declines in their economic well-being. We need to improve workplace and insurance safety nets so families can focus on dealing with the cancer treatment rather than deal with the financial and employment fallout.”
receiving treatment
Photo by Rhoda Baer
A new study indicates that when American adults are diagnosed with
cancer, they experience significant decreases in the probability of
working, in the number of hours they work, and correspondingly, in their
incomes.
Additionally, these effects appear to be more pronounced among men than women.
Anna Zajacova, PhD, of the University of Wyoming in Laramie, and her colleagues reported these findings in Cancer.
The researchers analyzed data from the Panel Study of Income Dynamics, a nationally representative, prospective, population-based, observational study with individual and family level economic information. The data spanned the period from 1999 to 2009.
The team used models to estimate the impact of cancer on employment, hours worked, individual income, and total family income.
The results showed that, after a cancer diagnosis, the probability of a patient being employed dropped by almost 10 percentage points, and hours worked declined by up to 200 hours, or about 5 weeks of full-time work, in the first year.
Annual labor market earnings dropped almost 40% within 2 years of diagnosis, and they remained lower than before diagnosis. Total family income declined by 20%, although it recovered within 4 years of cancer diagnosis.
These effects were primarily driven by losses among male cancer survivors. For women diagnosed with cancer, the losses were largely not statistically significant.
“Fifteen million American adults are cancer survivors, and American families need economic support while they are dealing with the rigors of cancer treatment,” Dr Zajacova said.
“Our paper suggests that families where an adult—especially a working-age male—is diagnosed with cancer suffer short-term and long-term declines in their economic well-being. We need to improve workplace and insurance safety nets so families can focus on dealing with the cancer treatment rather than deal with the financial and employment fallout.”
WHO recommends pilot projects for malaria vaccine
a malaria-endemic region
Photo by Sarah Mattison
More testing is needed before the malaria vaccine candidate RTS,S/AS01 (Mosquirix) can be put into widespread use, according to a pair of World Health Organization (WHO) advisory committees.
The WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Committee (MPAC) are recommending that RTS,S be introduced in 3 to 5 pilot projects to determine the best way to deliver the vaccine to young children.
The issue, according to the committees, is that the vaccine must be administered in 4 doses and therefore requires repeat contact with the healthcare system.
The first 3 doses are given 1 month apart, and the last dose is given 18 months later. Without the fourth dose, children in a phase 3 study of RTS,S had no overall reduction in severe malaria.
So SAGE and MPAC want to be sure this vaccination schedule is feasible.
“The question about how the malaria vaccine may best be delivered still needs to be answered,” said Jon S. Abramson, chair of SAGE. “After detailed assessment of all the evidence, we recommended that this question is best addressed by having 3 to 5 large pilot implementation projects.”
This could delay widespread implementation of RTS,S for 3 to 5 years. Alternatively, if it is not possible to deliver all 4 doses of RTS,S consistently, Abramson said the vaccine may not be used at all.
RTS,S is being assessed as a complementary malaria control tool that could potentially be added to—but not replace—the core package of proven malaria preventive, diagnostic, and treatment measures.
The vaccine acts against Plasmodium falciparum, the most deadly malaria parasite globally and the most prevalent in Africa.
In a phase 3 trial, young children who received 4 doses of RTS,S had a 36% reduction in the number of clinical episodes of malaria at 4 years. Infants who received 4 doses of RTS,S had a 26% reduction in the number of clinical malaria episodes over 3 years.
Children had a significantly lower incidence of severe malaria only if they received all 4 doses of RTS,S. The vaccine did not confer the same benefit in infants, regardless of the doses given.
Results of a subsequent study suggested that genetic variation influences the vaccine’s ability to ward off malaria in young children but not in infants.
RTS,S was recently granted a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) via Article 58 of Regulation No 726/2004.
This allows the CHMP, in cooperation with the WHO, to give a scientific opinion on a medicinal product intended for markets outside the European Union. This assessment requires products to meet the same standards as products intended for use in the European Union.
Once the CHMP issued a positive opinion of RTS,S, the WHO began formulating a policy recommendation on use of the vaccine in national immunization programs. RTS,S must pass the WHO pre-qualification process and be approved by national regulatory authorities before it can be used in such programs.
a malaria-endemic region
Photo by Sarah Mattison
More testing is needed before the malaria vaccine candidate RTS,S/AS01 (Mosquirix) can be put into widespread use, according to a pair of World Health Organization (WHO) advisory committees.
The WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Committee (MPAC) are recommending that RTS,S be introduced in 3 to 5 pilot projects to determine the best way to deliver the vaccine to young children.
The issue, according to the committees, is that the vaccine must be administered in 4 doses and therefore requires repeat contact with the healthcare system.
The first 3 doses are given 1 month apart, and the last dose is given 18 months later. Without the fourth dose, children in a phase 3 study of RTS,S had no overall reduction in severe malaria.
So SAGE and MPAC want to be sure this vaccination schedule is feasible.
“The question about how the malaria vaccine may best be delivered still needs to be answered,” said Jon S. Abramson, chair of SAGE. “After detailed assessment of all the evidence, we recommended that this question is best addressed by having 3 to 5 large pilot implementation projects.”
This could delay widespread implementation of RTS,S for 3 to 5 years. Alternatively, if it is not possible to deliver all 4 doses of RTS,S consistently, Abramson said the vaccine may not be used at all.
RTS,S is being assessed as a complementary malaria control tool that could potentially be added to—but not replace—the core package of proven malaria preventive, diagnostic, and treatment measures.
The vaccine acts against Plasmodium falciparum, the most deadly malaria parasite globally and the most prevalent in Africa.
In a phase 3 trial, young children who received 4 doses of RTS,S had a 36% reduction in the number of clinical episodes of malaria at 4 years. Infants who received 4 doses of RTS,S had a 26% reduction in the number of clinical malaria episodes over 3 years.
Children had a significantly lower incidence of severe malaria only if they received all 4 doses of RTS,S. The vaccine did not confer the same benefit in infants, regardless of the doses given.
Results of a subsequent study suggested that genetic variation influences the vaccine’s ability to ward off malaria in young children but not in infants.
RTS,S was recently granted a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) via Article 58 of Regulation No 726/2004.
This allows the CHMP, in cooperation with the WHO, to give a scientific opinion on a medicinal product intended for markets outside the European Union. This assessment requires products to meet the same standards as products intended for use in the European Union.
Once the CHMP issued a positive opinion of RTS,S, the WHO began formulating a policy recommendation on use of the vaccine in national immunization programs. RTS,S must pass the WHO pre-qualification process and be approved by national regulatory authorities before it can be used in such programs.
a malaria-endemic region
Photo by Sarah Mattison
More testing is needed before the malaria vaccine candidate RTS,S/AS01 (Mosquirix) can be put into widespread use, according to a pair of World Health Organization (WHO) advisory committees.
The WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Committee (MPAC) are recommending that RTS,S be introduced in 3 to 5 pilot projects to determine the best way to deliver the vaccine to young children.
The issue, according to the committees, is that the vaccine must be administered in 4 doses and therefore requires repeat contact with the healthcare system.
The first 3 doses are given 1 month apart, and the last dose is given 18 months later. Without the fourth dose, children in a phase 3 study of RTS,S had no overall reduction in severe malaria.
So SAGE and MPAC want to be sure this vaccination schedule is feasible.
“The question about how the malaria vaccine may best be delivered still needs to be answered,” said Jon S. Abramson, chair of SAGE. “After detailed assessment of all the evidence, we recommended that this question is best addressed by having 3 to 5 large pilot implementation projects.”
This could delay widespread implementation of RTS,S for 3 to 5 years. Alternatively, if it is not possible to deliver all 4 doses of RTS,S consistently, Abramson said the vaccine may not be used at all.
RTS,S is being assessed as a complementary malaria control tool that could potentially be added to—but not replace—the core package of proven malaria preventive, diagnostic, and treatment measures.
The vaccine acts against Plasmodium falciparum, the most deadly malaria parasite globally and the most prevalent in Africa.
In a phase 3 trial, young children who received 4 doses of RTS,S had a 36% reduction in the number of clinical episodes of malaria at 4 years. Infants who received 4 doses of RTS,S had a 26% reduction in the number of clinical malaria episodes over 3 years.
Children had a significantly lower incidence of severe malaria only if they received all 4 doses of RTS,S. The vaccine did not confer the same benefit in infants, regardless of the doses given.
Results of a subsequent study suggested that genetic variation influences the vaccine’s ability to ward off malaria in young children but not in infants.
RTS,S was recently granted a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) via Article 58 of Regulation No 726/2004.
This allows the CHMP, in cooperation with the WHO, to give a scientific opinion on a medicinal product intended for markets outside the European Union. This assessment requires products to meet the same standards as products intended for use in the European Union.
Once the CHMP issued a positive opinion of RTS,S, the WHO began formulating a policy recommendation on use of the vaccine in national immunization programs. RTS,S must pass the WHO pre-qualification process and be approved by national regulatory authorities before it can be used in such programs.
Genetic variation influences effect of malaria vaccine candidate
Photo by Caitlin Kleiboer
Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.
Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.
The variation did not appear to affect the vaccine’s efficacy for infants.
Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.
RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.
The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.
RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.
With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.
The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.
The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.
The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.
The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.
Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).
The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.
Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.
“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”
RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.
The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.
The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.
Photo by Caitlin Kleiboer
Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.
Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.
The variation did not appear to affect the vaccine’s efficacy for infants.
Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.
RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.
The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.
RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.
With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.
The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.
The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.
The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.
The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.
Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).
The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.
Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.
“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”
RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.
The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.
The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.
Photo by Caitlin Kleiboer
Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.
Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.
The variation did not appear to affect the vaccine’s efficacy for infants.
Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.
RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.
The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.
RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.
With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.
The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.
The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.
The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.
The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.
Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).
The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.
Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.
“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”
RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.
The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.
The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.
‘Room for improvement’ in animal research
Photo by Aaron Logan
A study of animal-based research published over the last 70 years suggests that scientists could have done more to reduce the risk of bias.
A group of researchers examined a few thousand published studies conducted in animals and found that, most of the time, scientists did not employ 4 measures believed to reduce the risk of bias: randomization, blinded assessment of outcome, a conflict of interest statement, and sample size calculation.
“I don’t believe for a moment that scientists set out to do anything other than excellent research, but what this work shows is that there is considerable room for improvement,” said Malcolm Macleod, PhD, of the University of Edinburgh in the UK.
Dr Macleod and his colleagues conducted this research and reported their findings in PLOS Biology.
The team first looked at a random sample of 146 in vivo studies published between 1941 and 2012. Randomization was reported in 20% of the publications in which it would have been appropriate.
Three percent of the publications reported blinding, 10% reported a conflict of interest statement, and none reported a sample size calculation.
Next, the researchers looked at 2671 studies published between 1992 and 2012 that reported drug efficacy in 8 disease models. Randomization was reported in 25% of publications, blinding in 30%, sample size calculation in 0.7%, and a statement of potential conflict of interest in 12%.
However, there were significant increases in 3 of these measures over time. The use of randomization increased from 14% in 1992 to 42% in 2011 (P<0.001), blinding increased from 16% to 39% (P<0.001), and a statement of possible conflict of interest increased from 2% to 35% (P<0.001).
The reporting of a sample size calculation did not change significantly and actually decreased from 2% to 1%.
Dr Macleod and his colleagues also used this dataset to determine whether a journal’s impact factor (a commonly used but disputed measure of journal “quality”)
played a role in the use of the 4 risk-of-bias measures.
The median journal impact factor was significantly higher (P<0.001) for studies reporting a potential conflict of interest, but it was significantly lower in studies reporting randomization (P=0.001). There was no significant difference for the other 2 measures.
Finally, the researchers examined bias in animal studies from the UK’s top 5 universities (according to the
2008 Research Assessment Exercise).
Of 1028 studies published in 2009 and 2010, 14% reported randomization, 17% reported blinding, 10% reported inclusion or exclusion criteria or both, and 1% reported a sample size calculation. Only 1 publication reported using all 4 of these measures.
Dr Macleod and his colleagues concluded that, although this study had its limitations, the results suggest room for improvement in in vivo research.
Photo by Aaron Logan
A study of animal-based research published over the last 70 years suggests that scientists could have done more to reduce the risk of bias.
A group of researchers examined a few thousand published studies conducted in animals and found that, most of the time, scientists did not employ 4 measures believed to reduce the risk of bias: randomization, blinded assessment of outcome, a conflict of interest statement, and sample size calculation.
“I don’t believe for a moment that scientists set out to do anything other than excellent research, but what this work shows is that there is considerable room for improvement,” said Malcolm Macleod, PhD, of the University of Edinburgh in the UK.
Dr Macleod and his colleagues conducted this research and reported their findings in PLOS Biology.
The team first looked at a random sample of 146 in vivo studies published between 1941 and 2012. Randomization was reported in 20% of the publications in which it would have been appropriate.
Three percent of the publications reported blinding, 10% reported a conflict of interest statement, and none reported a sample size calculation.
Next, the researchers looked at 2671 studies published between 1992 and 2012 that reported drug efficacy in 8 disease models. Randomization was reported in 25% of publications, blinding in 30%, sample size calculation in 0.7%, and a statement of potential conflict of interest in 12%.
However, there were significant increases in 3 of these measures over time. The use of randomization increased from 14% in 1992 to 42% in 2011 (P<0.001), blinding increased from 16% to 39% (P<0.001), and a statement of possible conflict of interest increased from 2% to 35% (P<0.001).
The reporting of a sample size calculation did not change significantly and actually decreased from 2% to 1%.
Dr Macleod and his colleagues also used this dataset to determine whether a journal’s impact factor (a commonly used but disputed measure of journal “quality”)
played a role in the use of the 4 risk-of-bias measures.
The median journal impact factor was significantly higher (P<0.001) for studies reporting a potential conflict of interest, but it was significantly lower in studies reporting randomization (P=0.001). There was no significant difference for the other 2 measures.
Finally, the researchers examined bias in animal studies from the UK’s top 5 universities (according to the
2008 Research Assessment Exercise).
Of 1028 studies published in 2009 and 2010, 14% reported randomization, 17% reported blinding, 10% reported inclusion or exclusion criteria or both, and 1% reported a sample size calculation. Only 1 publication reported using all 4 of these measures.
Dr Macleod and his colleagues concluded that, although this study had its limitations, the results suggest room for improvement in in vivo research.
Photo by Aaron Logan
A study of animal-based research published over the last 70 years suggests that scientists could have done more to reduce the risk of bias.
A group of researchers examined a few thousand published studies conducted in animals and found that, most of the time, scientists did not employ 4 measures believed to reduce the risk of bias: randomization, blinded assessment of outcome, a conflict of interest statement, and sample size calculation.
“I don’t believe for a moment that scientists set out to do anything other than excellent research, but what this work shows is that there is considerable room for improvement,” said Malcolm Macleod, PhD, of the University of Edinburgh in the UK.
Dr Macleod and his colleagues conducted this research and reported their findings in PLOS Biology.
The team first looked at a random sample of 146 in vivo studies published between 1941 and 2012. Randomization was reported in 20% of the publications in which it would have been appropriate.
Three percent of the publications reported blinding, 10% reported a conflict of interest statement, and none reported a sample size calculation.
Next, the researchers looked at 2671 studies published between 1992 and 2012 that reported drug efficacy in 8 disease models. Randomization was reported in 25% of publications, blinding in 30%, sample size calculation in 0.7%, and a statement of potential conflict of interest in 12%.
However, there were significant increases in 3 of these measures over time. The use of randomization increased from 14% in 1992 to 42% in 2011 (P<0.001), blinding increased from 16% to 39% (P<0.001), and a statement of possible conflict of interest increased from 2% to 35% (P<0.001).
The reporting of a sample size calculation did not change significantly and actually decreased from 2% to 1%.
Dr Macleod and his colleagues also used this dataset to determine whether a journal’s impact factor (a commonly used but disputed measure of journal “quality”)
played a role in the use of the 4 risk-of-bias measures.
The median journal impact factor was significantly higher (P<0.001) for studies reporting a potential conflict of interest, but it was significantly lower in studies reporting randomization (P=0.001). There was no significant difference for the other 2 measures.
Finally, the researchers examined bias in animal studies from the UK’s top 5 universities (according to the
2008 Research Assessment Exercise).
Of 1028 studies published in 2009 and 2010, 14% reported randomization, 17% reported blinding, 10% reported inclusion or exclusion criteria or both, and 1% reported a sample size calculation. Only 1 publication reported using all 4 of these measures.
Dr Macleod and his colleagues concluded that, although this study had its limitations, the results suggest room for improvement in in vivo research.
HSC finding may have range of implications
Image by Matthias Zepper
Murine research has provided new insight into the functionality of hematopoietic stem cells (HSCs).
Investigators found that a full complement of mini-chromosome maintenance (MCM) proteins is required to preserve HSC functionality and the proper differentiation and maturation of erythrocytes.
Downregulation of the gene MCM3 during embryonic development caused replication stress in hematopoietic progenitors and led to fetal anemia.
In adult mice, downregulation of MCM3 reduced life expectancy and promoted lymphomagenesis.
The investigators therefore believe that therapies designed to modulate replication stress could fight aging, anemia, and hematopoietic malignancies.
This research was published in Nature Communications.
A previous study revealed that replication stress drives the functional decline of HSCs that occurs with age. With the new study, investigators have managed to replicate this phenomenon in mouse embryos.
The team did this by reducing levels of MCM3, one of the components of the MCM complex that is responsible for separating the strands of the DNA double helix during replication. Cells need to maintain high levels of MCM during DNA replication or they experience replication stress.
“When we reduce the levels of the MCM3 gene in the entire organism, we observe that replication stress especially affects the stem cells that give rise to the other blood cells and, in particular, the red blood cell precursors,” explained study author Juan Méndez, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain.
“In adult organisms, the production and maturation of red blood cells takes place in the bone marrow, but, during embryonic development, it occurs mainly in the fetal liver. In animals with MCM3 deficiency, the stem cells of the fetal liver are deteriorated, and the embryos develop a severe form of anemia that prevents them from being born.”
“We could say that replication stress turns fetal stem cells, which should be in perfect working order, into very old cells. We have verified this finding in transplantation experiments, where fetal cells with replication stress were unable to adequately reconstitute the blood system in the recipient animals.”
However, the investigators managed to prevent embryonic lethality and reduce anemia by increasing the levels of another gene, CHK1.
“CHK1 is one of the genes responsible for protecting cells from replication stress,” Dr Méndez noted. “It supervises DNA replication. When something goes wrong, CHK1 slows down or halts cell division until the problem has been resolved.”
Embryos that were subjected to replication stress (due to loss of MCM3) but had higher levels of CHK1 showed less pronounced anemia. Four of every 10 embryos developed normally and completed their gestation.
The investigators said an interesting implication of this work is that the type of anemia caused by replication stress is very similar to the aplastic anemia that arises in patients receiving chemotherapy or radiation therapy.
Therefore, the team believes these results could aid the development of novel therapies for aplastic anemia.
Image by Matthias Zepper
Murine research has provided new insight into the functionality of hematopoietic stem cells (HSCs).
Investigators found that a full complement of mini-chromosome maintenance (MCM) proteins is required to preserve HSC functionality and the proper differentiation and maturation of erythrocytes.
Downregulation of the gene MCM3 during embryonic development caused replication stress in hematopoietic progenitors and led to fetal anemia.
In adult mice, downregulation of MCM3 reduced life expectancy and promoted lymphomagenesis.
The investigators therefore believe that therapies designed to modulate replication stress could fight aging, anemia, and hematopoietic malignancies.
This research was published in Nature Communications.
A previous study revealed that replication stress drives the functional decline of HSCs that occurs with age. With the new study, investigators have managed to replicate this phenomenon in mouse embryos.
The team did this by reducing levels of MCM3, one of the components of the MCM complex that is responsible for separating the strands of the DNA double helix during replication. Cells need to maintain high levels of MCM during DNA replication or they experience replication stress.
“When we reduce the levels of the MCM3 gene in the entire organism, we observe that replication stress especially affects the stem cells that give rise to the other blood cells and, in particular, the red blood cell precursors,” explained study author Juan Méndez, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain.
“In adult organisms, the production and maturation of red blood cells takes place in the bone marrow, but, during embryonic development, it occurs mainly in the fetal liver. In animals with MCM3 deficiency, the stem cells of the fetal liver are deteriorated, and the embryos develop a severe form of anemia that prevents them from being born.”
“We could say that replication stress turns fetal stem cells, which should be in perfect working order, into very old cells. We have verified this finding in transplantation experiments, where fetal cells with replication stress were unable to adequately reconstitute the blood system in the recipient animals.”
However, the investigators managed to prevent embryonic lethality and reduce anemia by increasing the levels of another gene, CHK1.
“CHK1 is one of the genes responsible for protecting cells from replication stress,” Dr Méndez noted. “It supervises DNA replication. When something goes wrong, CHK1 slows down or halts cell division until the problem has been resolved.”
Embryos that were subjected to replication stress (due to loss of MCM3) but had higher levels of CHK1 showed less pronounced anemia. Four of every 10 embryos developed normally and completed their gestation.
The investigators said an interesting implication of this work is that the type of anemia caused by replication stress is very similar to the aplastic anemia that arises in patients receiving chemotherapy or radiation therapy.
Therefore, the team believes these results could aid the development of novel therapies for aplastic anemia.
Image by Matthias Zepper
Murine research has provided new insight into the functionality of hematopoietic stem cells (HSCs).
Investigators found that a full complement of mini-chromosome maintenance (MCM) proteins is required to preserve HSC functionality and the proper differentiation and maturation of erythrocytes.
Downregulation of the gene MCM3 during embryonic development caused replication stress in hematopoietic progenitors and led to fetal anemia.
In adult mice, downregulation of MCM3 reduced life expectancy and promoted lymphomagenesis.
The investigators therefore believe that therapies designed to modulate replication stress could fight aging, anemia, and hematopoietic malignancies.
This research was published in Nature Communications.
A previous study revealed that replication stress drives the functional decline of HSCs that occurs with age. With the new study, investigators have managed to replicate this phenomenon in mouse embryos.
The team did this by reducing levels of MCM3, one of the components of the MCM complex that is responsible for separating the strands of the DNA double helix during replication. Cells need to maintain high levels of MCM during DNA replication or they experience replication stress.
“When we reduce the levels of the MCM3 gene in the entire organism, we observe that replication stress especially affects the stem cells that give rise to the other blood cells and, in particular, the red blood cell precursors,” explained study author Juan Méndez, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain.
“In adult organisms, the production and maturation of red blood cells takes place in the bone marrow, but, during embryonic development, it occurs mainly in the fetal liver. In animals with MCM3 deficiency, the stem cells of the fetal liver are deteriorated, and the embryos develop a severe form of anemia that prevents them from being born.”
“We could say that replication stress turns fetal stem cells, which should be in perfect working order, into very old cells. We have verified this finding in transplantation experiments, where fetal cells with replication stress were unable to adequately reconstitute the blood system in the recipient animals.”
However, the investigators managed to prevent embryonic lethality and reduce anemia by increasing the levels of another gene, CHK1.
“CHK1 is one of the genes responsible for protecting cells from replication stress,” Dr Méndez noted. “It supervises DNA replication. When something goes wrong, CHK1 slows down or halts cell division until the problem has been resolved.”
Embryos that were subjected to replication stress (due to loss of MCM3) but had higher levels of CHK1 showed less pronounced anemia. Four of every 10 embryos developed normally and completed their gestation.
The investigators said an interesting implication of this work is that the type of anemia caused by replication stress is very similar to the aplastic anemia that arises in patients receiving chemotherapy or radiation therapy.
Therefore, the team believes these results could aid the development of novel therapies for aplastic anemia.
Drug-resistant malaria could spread to Africa, team says
of Plasmodium falciparum
Image by Mae Melvin/CDC
New research indicates that drug-resistant forms of the malaria parasite Plasmodium falciparum can infect the Anopheles coluzzii mosquito (formerly Anopheles gambiae M form), which is the main transmitter of malaria in Africa.
The discovery suggests that Africa is more at risk for drug-resistant malaria infections than researchers previously thought, and this could further compromise efforts to prevent and eliminate the disease.
Rick Fairhurst, MD, PhD, of the National Institute of Allergy and Infectious Diseases in Rockville, Maryland, and his colleagues reported the discovery in Nature Communications.
The team noted that P falciparum parasites that are resistant to artemisinin, the main drug used to treat malaria, have been rapidly spreading in parts of Southeast Asia.
Malaria experts are concerned that artemisinin-resistant parasites could spread to Africa. However, there were no scientific indications to suggest these parasites could infect A coluzzii mosquitoes—until now.
Dr Fairhurst and his colleagues investigated the transmission potential of these parasites in 3 mosquito species—A coluzzii and the Southeast Asian mosquito species Anopheles dirus and Anopheles minimus.
The researchers evaluated whether these mosquitoes became infected after feeding on blood containing any of 6 artemisinin-resistant parasite strains and 3 artemisinin-sensitive parasite strains previously isolated from malaria patients in Cambodia.
The team found parasites in the mosquitoes’ midguts and salivary glands in almost all cases, showing that the artemisinin-resistant and artemisinin-sensitive Cambodian parasites can infect a variety of mosquito species.
The researchers also discovered a shared genetic background among artemisinin-resistant parasites that may enable them to infect diverse mosquito species by evading the insects’ immune systems.
This study did not show that infected mosquitoes can effectively transmit the disease to humans. However, the results support the idea that artemisinin-resistant parasites could potentially spread beyond Cambodia and to Africa, the researchers said.
They plan to investigate other potential genetic determinants of parasite infection in mosquitoes and further examine which Anopheles species from Cambodia are naturally transmitting artemisinin-resistant parasites in the wild.
of Plasmodium falciparum
Image by Mae Melvin/CDC
New research indicates that drug-resistant forms of the malaria parasite Plasmodium falciparum can infect the Anopheles coluzzii mosquito (formerly Anopheles gambiae M form), which is the main transmitter of malaria in Africa.
The discovery suggests that Africa is more at risk for drug-resistant malaria infections than researchers previously thought, and this could further compromise efforts to prevent and eliminate the disease.
Rick Fairhurst, MD, PhD, of the National Institute of Allergy and Infectious Diseases in Rockville, Maryland, and his colleagues reported the discovery in Nature Communications.
The team noted that P falciparum parasites that are resistant to artemisinin, the main drug used to treat malaria, have been rapidly spreading in parts of Southeast Asia.
Malaria experts are concerned that artemisinin-resistant parasites could spread to Africa. However, there were no scientific indications to suggest these parasites could infect A coluzzii mosquitoes—until now.
Dr Fairhurst and his colleagues investigated the transmission potential of these parasites in 3 mosquito species—A coluzzii and the Southeast Asian mosquito species Anopheles dirus and Anopheles minimus.
The researchers evaluated whether these mosquitoes became infected after feeding on blood containing any of 6 artemisinin-resistant parasite strains and 3 artemisinin-sensitive parasite strains previously isolated from malaria patients in Cambodia.
The team found parasites in the mosquitoes’ midguts and salivary glands in almost all cases, showing that the artemisinin-resistant and artemisinin-sensitive Cambodian parasites can infect a variety of mosquito species.
The researchers also discovered a shared genetic background among artemisinin-resistant parasites that may enable them to infect diverse mosquito species by evading the insects’ immune systems.
This study did not show that infected mosquitoes can effectively transmit the disease to humans. However, the results support the idea that artemisinin-resistant parasites could potentially spread beyond Cambodia and to Africa, the researchers said.
They plan to investigate other potential genetic determinants of parasite infection in mosquitoes and further examine which Anopheles species from Cambodia are naturally transmitting artemisinin-resistant parasites in the wild.
of Plasmodium falciparum
Image by Mae Melvin/CDC
New research indicates that drug-resistant forms of the malaria parasite Plasmodium falciparum can infect the Anopheles coluzzii mosquito (formerly Anopheles gambiae M form), which is the main transmitter of malaria in Africa.
The discovery suggests that Africa is more at risk for drug-resistant malaria infections than researchers previously thought, and this could further compromise efforts to prevent and eliminate the disease.
Rick Fairhurst, MD, PhD, of the National Institute of Allergy and Infectious Diseases in Rockville, Maryland, and his colleagues reported the discovery in Nature Communications.
The team noted that P falciparum parasites that are resistant to artemisinin, the main drug used to treat malaria, have been rapidly spreading in parts of Southeast Asia.
Malaria experts are concerned that artemisinin-resistant parasites could spread to Africa. However, there were no scientific indications to suggest these parasites could infect A coluzzii mosquitoes—until now.
Dr Fairhurst and his colleagues investigated the transmission potential of these parasites in 3 mosquito species—A coluzzii and the Southeast Asian mosquito species Anopheles dirus and Anopheles minimus.
The researchers evaluated whether these mosquitoes became infected after feeding on blood containing any of 6 artemisinin-resistant parasite strains and 3 artemisinin-sensitive parasite strains previously isolated from malaria patients in Cambodia.
The team found parasites in the mosquitoes’ midguts and salivary glands in almost all cases, showing that the artemisinin-resistant and artemisinin-sensitive Cambodian parasites can infect a variety of mosquito species.
The researchers also discovered a shared genetic background among artemisinin-resistant parasites that may enable them to infect diverse mosquito species by evading the insects’ immune systems.
This study did not show that infected mosquitoes can effectively transmit the disease to humans. However, the results support the idea that artemisinin-resistant parasites could potentially spread beyond Cambodia and to Africa, the researchers said.
They plan to investigate other potential genetic determinants of parasite infection in mosquitoes and further examine which Anopheles species from Cambodia are naturally transmitting artemisinin-resistant parasites in the wild.