week 4 Flashcards
# of cases of DHF/DSS between 1990-1999 # of cases DHF/DSS between 2000-2004
1990-1999 < 500,000 cases
2000-2004 > 900,000 cases of DHF/DSS
DHF and DSS are more prevalent in SE Asia. How much more dz is seen in SE Asia compared to the Americas?
Rate of severe dengue in SE Asia is 18x that of the Americas
why is there a worldwide increase in DF?
due to the spread of dengue into new areas
Worldwide increase in DHF/DSS due to presence of multiple serotypes in one area
Origins of Dengue?
each serotype evolved from an ancestral virus of monkeys
500-1000 years ago
describe evolution of dengue prior to 1800
Dengue was present in tropical/subtropical ports
movement was slow
transport of A. aegypti and people around the world
epidemics every 10-40 years
WWII affected spread of dengue how?
At the end of WWII what changes were noted?
WWII spread dengue by modern transportation, troops dispersed inland rather than remaining on the coast
by the end of the war dengue was hyperendemic in most SE asian countries and severe dz had emerged.
Dengue virus genotypes are classified by epidemiological impact (likelihood of human transmission and severity of dz). List the 3 genotypes and briefly explain each.
1) Sylvatic genotypes (circulate in primates, rarely infect humans, maybe source for add’l emerging viruses)
2) Low- virulence genotypes (circulate in humans, associated w/ milder dz)
3) High virulence genotypes (circulate in humans, associated w/ more severe dz, outcompeting low-virulence phenotypes)
Key factors in the expansion of dengue
Rapid urbanization
- ** particularly important in low-middle income countries (ones that lack infrastructure for collection, storage and disposal of water)
- -it can be important even in higher income situations because construction can create habitat for mosquitos to breed.
A study was done that showed higher infection rates of dengue in Mexico vs US (border town study)…Why was Mexico’s rate of infection higher?
**identical climate, vector density, geography
- 32% seroprevalence on Mexican side of border
- 4% seroprevalence on US side
- Air conditioning, window screens, water and water disposal infrastructure (lowered rates on US side)
what are the current strategies for controlling the spread of dengue?
( no vaccine, no effective tx) Vector control (chemical, nonchemical methods tageted to areas of high human to vector contact)
The scientific name for Malaria and the 5 subtypes?
Plasmodium species
- P. falciparum
- P. vivax
- P. malariae
- P. ovale
- P. knowlesi
how long is malaria’s incubation period?
7-30 days
What are the symptoms of Malaria and what is the main cause of the symptoms?
ha fatigue vomiting myalgia malaise fever chills -caused by the rupture of Erythrocytes which release hemoglobin and bilirubin into the system
Which subtype causes Cerebral malaria and what are the symptoms/complications?
P. falciparum
progresssive ha very high fever (may exceed 108º) psychosis convulsions coma death can occur w/i hours (25%-50%)
Which subtype causes Blackwater fever and what are the symptoms?
P. falciparum
kidney damage (from RBC's) black urine renal failure autoimmune component (antibodies aid in the lysis of Erythrocytes) mortality 20%-50%
What are the complications of Blackwater fever?
Metabolic acidosis (lactic acid in blood)
Hypoglycemia (this is because the parasite uses a lot of glucose)
Acute pumonary edema (cause is unknown)
do individuals have immunity after contracting malaria? Explain?
Once parasite is cleared, partial immunity develops
Subsequent infections are less severe (generally)
In regions were Malaria transmission rates are high/stable who is most likely to contract a more severe subtype?
What about in areas where the transmission rate is low/unstable who is most susceptible to severe malaria?
High/Stable areas- severe dz in young
low/unstable areas- severe dz at any age
travelers/immigrants from malaria-free areas are at high risk of contracting severe dz in endemic areas*
how is Malaria transmitted?
Direct Penetration (mosquito bite, anopheles)
describe stages/life cycles of malaria
1) Mosquito stages (what is happening inside mosquito)
2) In Human both the liver stages and the blood stage
FYI …long one!!
Mosquito
- takes a blood meal (from infected human) ingests gametocytes
- Macrogametocyte combines with exflagellated microgametocye
- prooducing ookinete
- producing oocyte
- oocyte ruptures releasing sporozoites
Mosquito takes a blood meal injecting human with sporozoites
- (liver stages aka exoerythrocyctic cycle) liver cell becomes infected liver cell
- which produces schizont
- schizont ruptures
(Blood stage aka Erythrocytic cycle)
- produces immature trophozoites
- EITHER becomes a mature schizont, schizont, and then ruptures
OR
becomes a gametocyte (infected with one of the malaria subtypes)
The gametocyte is then ingested by mosquito during blood meal.
explain P. falciparum in detail
- most sever form of malaria (malignant tertian malaria)
- 48 hr erythrocytic cycle
(infects any erythrocyte)
- most common cause of cerebral malaria and blackwater fever
describe P. vivax in detail
- less severe (benign tertian malaria)
- 48 hr erythrocytic cycle
- can remain in liver for decades
- infects ONLY reticulocytes (leading to fewer people infected and milder symptoms)
describe in detail P. malariae
- causes quartan malaria
- 72 hr erythrocytic cycle
- can cause chronic infections
- less common than P. falciparum and P. vivax
- tends to infect older erythrocytes
describe P. ovale in detail
Mild tertian malaria
48 hr erythrocytic cycle
can remain in liver (like P. vivax)
tends to infect young erythrocytes
describe P. knowlesi
Parasite of non-human primates in SE Asia
people living in area commonly infected
24 hr erythrocytic cycle
OFTEN misdx as P. malariae
is there immunity to malaria after infection? describe
Repeated exposure leads to an immune response (humoral immunity is stimulated)
NOT completely protective (subsequent infections are generally less severe)
CD8+ T-cells and NK cells are IMPORTANT for protective immunity
are there Malaria vaccines? explain
none currently available
Sporozoite- based vaccines are impractical and they canNOT be grown in culture, success in mice but not in humans
Gametocyte- based vaccines are intended to prevent infection of mosquito and block transmission
What are the current issues with Malaria infection control?
Vector control
drug resistance
what actions have been taken for vector control and what issues have arisen from vector control?
Indoor residual spraying (DDT)
- remains on walls for months
- mosquito rests on walls after blood meal
- low cost
ISSUES:
- vectors developed resistance
- DDT was banned (alternatives were expensive and more toxic to humans)
in 2006 WHO endorsed DDT for control
name the antimalarial drugs
Quinine chloroquine primaquina mefloquine amodiaquine
The antimalarial drug that prevents processing of heme, it was discovered in S America and still used to tx severe malaria
Quinine
The antimalarial drug that is effective against gametocytes and eliminates the exoerythrocytic stage of P. vivax and P. ovale
Primaquine
The antimalarial drug that is more effective against chloroquine resistant parasites?
Amodiaquine
give details about Choloquine
Antimalarial drug developed in 1930's (until recently) most used drug low cost binds DNA
Sulfadoxine/pyrimethamine and
Sufamethoxazole/trimethoprim
are used how (in tx of malaria)
Antimalarial Drugs
They are used in combinations
Dihydrofolate reductase inhibitors/sulfa drug
this is done to inhibit the folate metabolism pathway
How are antibiotics (Doxycyxline, Tetracycline, and Clindamycin) used in malaria tx?
Antibiotics are generlly used in combonation with quinine or a derivative to inhibit protein synthesis
What are Artemisinin based drugs and why are they important?
oldest antimalarial compound
china 4th century
Currently very effective- reduces parasite burden and fever w/i days
*WHO guidlines tight control to maintain effectiveness– and it is used only in combination
Describe in detail Chloroquine resistance
1960’s
developed in SE Asia and S America
spread to Africa
virtually all areas with P. falciparum have some resistance
Mechanism- efflux pump
Details of Anti-folate resistance
Replaced Chloroquine as the drug of choice
Mechanism- mutation in genes that code for DHFR and DHPS
Resistance to chloroquine is common in S. America, SE Asia and increasing in Africa
Give details about resistance to Artemisnin
VERY recent
develpoed in SE Asia
Mechanism is unknown
What are some of the factors that contribute to drug resistance
Not all parasites are killed by drug therapy ( the immune system must step up and clean up the remaining parasites)
Failure of the immune system to kill the remaining parasites may result in selection of drug resistant organisms.
Poor drug compliance
The more commonly a drug is used in an area the more likely resistance is to develop
improper dosing of drugs
Presumptive dx of malaria w/o confirmation
poor drug quality
What are the factors that may limit the immune system’s ability to clear parasite? (leading to drug resistance)
Non-Immune status (important in SE Asia resistance)
malnutrition
HIV infection
Why does resistance to one drug possibly facilitate the development of resistance to another antimalarial drug?
Chemical structure of drugs is similar
Resistance may lead to “genetic plasticity”
Control of malaria also requires the pairing of effective vector control. What are examples of effective vector control programs?
habitat removal
indoor residual spraying
insecticide treated bed nets
lavorious fish and crustaceans
release of genetically altered mosquitos
