This week’s learning goal was the pathophysiology of our selected disease. Instead of focusing on the life cycle of malaria which includes the vector stages, I chose an article that concentrated on the two broad categories of severe malaria manifestations: metabolic and neurological complications.
While anemia (due to RBC destruction and reduced RBC production as a result of cytokine-mediated suppression of erythrogenesis), hypoglycemia, and renal failure (more common in adults) require urgent treatment, Planche and Krishna found that cerebral malaria and lactic acidosis were independent predictors of poor outcomes.
The (interrelated) metabolic changes that are important in severe malaria are acidosis, hyperlactatemia (serum levels >5mM), and respiratory distress. The biggest culprit appears to be increased anaerobic glycolysis due to microvascular obstruction. Interestingly, serum lactate levels were found to be higher in malaria than in sepsis, indicating impaired oxygen delivery. Dichloroacetate has been shown to safely lower blood lactate concentration, but more research is needed to assess its capacity to reduce mortality in cases of severe malaria.
In addition to the hypoglycemia induced by patients who are administered quinine (due to increased insulin secretion), hypoglycemia can also be a result of the demands of anaerobic glycolysis. Every patient should be assessed for hypoglycemia on admission, and inpatient care must include regular monitoring of blood glucose levels.
Cerebral malaria is defined as “an unrousable coma with asexual P. falciparum infection at least 30 minutes after a convulsion, when hypoglycemia has been excluded and without interference by sedative drugs or other confounding variables.” However, the authors cited studies that suggest that impaired consciousness, rather than coma, may be a more accurate predictor of death. Originally, it was believed that cerebral edema resulting from increased capillary permeability, was the cause of cerebral malaria. Post-mortem studies now suggest that sequestration of the parasites in the cerebral vasculature, and the simple mechanical obstruction that ensues, is responsible for the symptoms of cerebral malaria.
Planche T, Krishna S. The relevance of malaria pathophysiology to strategies of clinical management. Current Opinion in Infectious Diseases. 2005;18(5):369-375.
Tuesday, October 27, 2009
Friday, October 16, 2009
Epidemiology of Malaria
Malaria is a potentially fatal but ultimately preventable and treatable vector-borne parasitic disease that is characterized by cycling fever and chills, and generalized flu-like symptoms. Significant findings on physical exam are frequently anemia, jaundice, and hepatosplenomegaly.
According to 2008 estimates from the World Health Organization, there are 350 to 500 million cases of malaria worldwide each year, and malaria claims an estimated one million lives annually, with the majority of deaths occurring in children under 5 years of age. Spread by Anopheles mosquitoes, malaria thrives in tropical zones with warm temperatures and humid conditions. It is endemic in 100 countries in Africa, Latin America, Asia and the Middle East, and Sub-Saharan Africa is disproportionately affected with 90% of the total deaths. Malaria is strongly linked to poverty. Inadequate housing, poor water and sanitation systems, displacement, and lack of access to adequate medical care are significant risk factors for morbidity and mortality.
There are four main species of the malaria parasite (Plasmodium falciparum, P. vivax, P. ovale, and P. malariae), each with a distinct global distribution. For the sake of simplicity, I will concentrate on P. falciparum which is responsible for the majority of deaths worldwide. P. falciparium is sometimes referred to as "the malignant malaria," although the other species are certainly not benign, despite their historical classification. Travelers to endemic areas must be provided with specific counseling and chemoprophylaxis depending on the prevalent species.
Individuals at greatest risk include:
In the US, malaria is classified as a notifiable disease, and confirmed (positive blood film, rapid diagnostic test, or PCR) cases must be reported to local and state health departments which conduct the case investigation. Findings are then submitted to the CDC through the National Malaria Surveillance System, and the National Notifiable Diseases Surveillance System. My article for this week is from the CDC's MMWR series:
Centers for Disease Control and Prevention. "Malaria Surveillance - United States, 2007." MMWR 2009;58(2).
In 2007, P. falciparum was identified in a majority of cases (43.4%), while the number of cases in which the infecting species was unreported or undetermined was surprisingly high (30.2%). Of the cases with known residential status, 73.6% occurred among U.S. residents, and 26.4% occurred among residents of other countries. The majority of patients (both US residents and non-residents) reported that their reason for travel was visiting friends and relatives (VFR), highlighting the importance of this group. The highest estimated relative case rates (using estimated number of US travelers to endemic countries) appeared among travelers from West Africa. In 80.1% of cases, clinical malaria appeared within 30 days of arrival in the US.
Strikingly, it was found that among the cases of US residents (and for whom chemoprophylaxis information was available), 62.9% had not followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. However, it was not clear in this report whether they had initially been prescribed an incorrect regimen, or had been non-adherent to an appropriately prescribed regimen. Of the total number of cases in women, 4.5% of those occurred in pregnant women, none of whom had adhered to a complete chemoprophylactic regimen. Problems with adherence make it difficult to identify areas of emerging drug resistance (by identifying cases that occurred in spite of chemoprophylaxis) as well as increasing the likelihood that resistance will develop.
This article did not discuss delays in treatment due to missed diagnosis, or the percentage of cases who were asked to report a travel history in their first contact with a healthcare provider. Nor was there an analysis of the appropriateness of clinical therapies once the diagnosis was made.
However, the article stressed the importance of prompt treatment, and the potentially life-threatening complications that can develop within a short period of time from the onset of symptoms. While malaria should always be considered in febrile patients with a travel history to malaria endemic areas, the CDC recommends that malaria should also be included in the differential diagnosis for all cases of FUO, regardless of the travel history. The article also drives home the importance of correct chemophrophylaxis (especially in at-risk individuals) and preventive measures to avoid contracting malaria in the first place!
From the CDC Website:
Health care providers needing assistance with diagnosis or management of suspected cases of malaria should call the CDC Malaria Hotline: 770-488-7788 (M-F, 9 am - 5 pm, eastern time). Emergency consultation after hours, call: 770-488-7100 and request to speak with a CDC Malaria Branch clinician.
According to 2008 estimates from the World Health Organization, there are 350 to 500 million cases of malaria worldwide each year, and malaria claims an estimated one million lives annually, with the majority of deaths occurring in children under 5 years of age. Spread by Anopheles mosquitoes, malaria thrives in tropical zones with warm temperatures and humid conditions. It is endemic in 100 countries in Africa, Latin America, Asia and the Middle East, and Sub-Saharan Africa is disproportionately affected with 90% of the total deaths. Malaria is strongly linked to poverty. Inadequate housing, poor water and sanitation systems, displacement, and lack of access to adequate medical care are significant risk factors for morbidity and mortality.
There are four main species of the malaria parasite (Plasmodium falciparum, P. vivax, P. ovale, and P. malariae), each with a distinct global distribution. For the sake of simplicity, I will concentrate on P. falciparum which is responsible for the majority of deaths worldwide. P. falciparium is sometimes referred to as "the malignant malaria," although the other species are certainly not benign, despite their historical classification. Travelers to endemic areas must be provided with specific counseling and chemoprophylaxis depending on the prevalent species.
Individuals at greatest risk include:
- Children under the age of 5 years
- Travellers to malarial zones from non-endemic areas who have little or no immunity
- Non-immune and semi-immune pregnant women
- People living with HIV/AIDS (PLWHA)
Malaria in pregnancy results in high rates of miscarriage and WHO estimates that it is responsible for 10% of maternal deaths worldwide. Even in the case of subclinical disease, severe anemia and impaired fetal growth can result. Additionally, the sequestration of malaria parasites in the placenta increases the risk of maternal to child transmission of HIV. Other groups at risk include individuals with sickle cell disease, although sickle cell trait provides some protection against malaria.
Due to targeted vector-control programs which relied largely on DDT, malaria has been eradicated from the US and Europe. (See map of previously malarious areas of the US. In 1914 there were 600,000 cases in the US!) While the cycle of transmission within the US has been broken, the CDC reported 1,505 cases of malaria in the US in 2007. This was not significantly different from the number of cases reported in 2006. Of these, the vast majority occurred among persons who had contracted malaria while travelling to endemic areas. However, in one case, transmission occurred through blood transfusion in a patient with transfusion-dependent sickle cell disease. (The implicated donor was identified, and while he confirmed that he had a history of malarial infection, he declined treatment.) In previous years, there have also been confirmed cases of congenital transmission. One death occurred after infection with P. vivax.In the US, malaria is classified as a notifiable disease, and confirmed (positive blood film, rapid diagnostic test, or PCR) cases must be reported to local and state health departments which conduct the case investigation. Findings are then submitted to the CDC through the National Malaria Surveillance System, and the National Notifiable Diseases Surveillance System. My article for this week is from the CDC's MMWR series:
Centers for Disease Control and Prevention. "Malaria Surveillance - United States, 2007." MMWR 2009;58(2).
In 2007, P. falciparum was identified in a majority of cases (43.4%), while the number of cases in which the infecting species was unreported or undetermined was surprisingly high (30.2%). Of the cases with known residential status, 73.6% occurred among U.S. residents, and 26.4% occurred among residents of other countries. The majority of patients (both US residents and non-residents) reported that their reason for travel was visiting friends and relatives (VFR), highlighting the importance of this group. The highest estimated relative case rates (using estimated number of US travelers to endemic countries) appeared among travelers from West Africa. In 80.1% of cases, clinical malaria appeared within 30 days of arrival in the US.
Strikingly, it was found that among the cases of US residents (and for whom chemoprophylaxis information was available), 62.9% had not followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. However, it was not clear in this report whether they had initially been prescribed an incorrect regimen, or had been non-adherent to an appropriately prescribed regimen. Of the total number of cases in women, 4.5% of those occurred in pregnant women, none of whom had adhered to a complete chemoprophylactic regimen. Problems with adherence make it difficult to identify areas of emerging drug resistance (by identifying cases that occurred in spite of chemoprophylaxis) as well as increasing the likelihood that resistance will develop.
This article did not discuss delays in treatment due to missed diagnosis, or the percentage of cases who were asked to report a travel history in their first contact with a healthcare provider. Nor was there an analysis of the appropriateness of clinical therapies once the diagnosis was made.
However, the article stressed the importance of prompt treatment, and the potentially life-threatening complications that can develop within a short period of time from the onset of symptoms. While malaria should always be considered in febrile patients with a travel history to malaria endemic areas, the CDC recommends that malaria should also be included in the differential diagnosis for all cases of FUO, regardless of the travel history. The article also drives home the importance of correct chemophrophylaxis (especially in at-risk individuals) and preventive measures to avoid contracting malaria in the first place!
From the CDC Website:
Health care providers needing assistance with diagnosis or management of suspected cases of malaria should call the CDC Malaria Hotline: 770-488-7788 (M-F, 9 am - 5 pm, eastern time). Emergency consultation after hours, call: 770-488-7100 and request to speak with a CDC Malaria Branch clinician.
Friday, October 9, 2009
First Post
Hi Everyone.
Just an initial disclaimer, I'm not particularly tech saavy, so please bear with me as I work out the kinks!
I was initially drawn to the topic of malaria by the statistics for missed diagnoses (59%) and subclinical treatment (64%) that were cited in one of the first week's readings: "Global infections: recognition, management, and prevention." Given our current setting, I thought it would be appropriate to focus on malaria and student health, both in terms of students planning to study abroad, and international students returning home to visit family and friends. This is likely to change as the quarter progresses, but at least these were my first musings!
Anyways, I thought for the first article, something general might be appropriate. The Up to Date article entitled "Epidemiology, pathogenesis, and clinical features of malaria," is a good introduction. In the section on Host Genetics, I was interested to read that while some traits may be protective against malaria, this tricky parasite is able to develop new techniques for invading previously "immune" red blood cells.
I've also included a link to the Doctors Without Borders (MSF) Campaign for Access to Essential Medicines website. http://www.msfaccess.org/main/other-diseases/msf-and-malaria/. It's a great resource for information regarding the fight to make artemisinin-based combination therapies for malaria affordable and accessible to those who need them the most. This year, efforts have been made to reduce the cost of antimalarials through the establishment of the Affordable Medicines Facility–malaria (AMF-m). However, the fund does not address other barriers to care in resource-poor settings such as user fees and geographically inaccessible health posts. Nor does the fund provide for Rapid Diagnostic Tests, or insist on the use of Fixed Dose Combinations that have been shown to improve patient adherence. If anyone's curious about these issues, there's an article entitled, “Focusing on Quality Patient Care in the New Global Subsidy for Malaria Medicines” at http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000106.
Have a great weekend, everyone, and see you on Tuesday!
Just an initial disclaimer, I'm not particularly tech saavy, so please bear with me as I work out the kinks!
I was initially drawn to the topic of malaria by the statistics for missed diagnoses (59%) and subclinical treatment (64%) that were cited in one of the first week's readings: "Global infections: recognition, management, and prevention." Given our current setting, I thought it would be appropriate to focus on malaria and student health, both in terms of students planning to study abroad, and international students returning home to visit family and friends. This is likely to change as the quarter progresses, but at least these were my first musings!
Anyways, I thought for the first article, something general might be appropriate. The Up to Date article entitled "Epidemiology, pathogenesis, and clinical features of malaria," is a good introduction. In the section on Host Genetics, I was interested to read that while some traits may be protective against malaria, this tricky parasite is able to develop new techniques for invading previously "immune" red blood cells.
I've also included a link to the Doctors Without Borders (MSF) Campaign for Access to Essential Medicines website. http://www.msfaccess.org/main/other-diseases/msf-and-malaria/. It's a great resource for information regarding the fight to make artemisinin-based combination therapies for malaria affordable and accessible to those who need them the most. This year, efforts have been made to reduce the cost of antimalarials through the establishment of the Affordable Medicines Facility–malaria (AMF-m). However, the fund does not address other barriers to care in resource-poor settings such as user fees and geographically inaccessible health posts. Nor does the fund provide for Rapid Diagnostic Tests, or insist on the use of Fixed Dose Combinations that have been shown to improve patient adherence. If anyone's curious about these issues, there's an article entitled, “Focusing on Quality Patient Care in the New Global Subsidy for Malaria Medicines” at http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000106.
Have a great weekend, everyone, and see you on Tuesday!
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