Malaria

1. Malaria Things You Need to Know

2. Historical Perspectives Half of all Civil War soldiers had yearly bouts of malaria. Devistating epidemics took place in Rome, Paris, and St. Petersberg in the 16th -18th centuries and was even seen in scandiavia. Alexander the Great died of malaria , as did Oliver Cromwell ,who refused therapy with Quinine , known as “Jesuit Powder.” In 1914 there were 500,000 cases of malaria in the U.S.Last indigenious U.S. case in 1947.

3. Malaria is a killer • Malaria kills more than 1,500,000 yearly. • Most deaths are in young children and pregant women. • Immunity is only partial and is not very durable in survivors. • Malaria is preventable in travellers.

4. Epidemiology • Approximately 300-500 million cases yearly. • 700,000-2.7 million deaths mostly children in tropical devolping countries from P. falciprum. • Greatest tranmission rates for P.falciparum are in Oceania and Sub-saharan Africa. • Transmision varies with season and altitude. • Rainy season and altitudes below 2,000m • Approximately 30,000 infx.in travellers yearly.

5. Risk to the traveler Approximate relative risk to a traveler staying one month in an endemic area not using chemoprophylaxis is: Oceania - 1:30 or higher Sub-Saharan Africa -1:50 Indian subcontinent - 1:250 S.E. Asia-1:1,000 South America - 1:2,500 Central America -1:10,000

6. Transmission Predominatley from the bite of female Anopheles sp. Mosquito between the hours of dusk and dawn. Congenitally aquired disease, transfusion related , shared needles and organ transplantation are also means of transmission. Autochthonous malaria results from a bite of a mosquito that has feed on an infected person and then bites someone else.

7. The organism • Protozoan parasite • Human malaria is caued by four sp. Of Plasmodia: P. falciparum,P. vivax, P. ovale, and P. malariae. • Majority of infection are from P. falciparum and P. vivax . • Mixed infection occurs in 5-7% of cases.

8. Life Cycle • Very complex! • Sporozites enter the blood stream from infected mosquito. They travel to the liver , invade hepatocytes and divide many thousand fold.The exoerythrocytic stage is asx. The liver schizonts rupture after 6 - 16d and are then released into the blood stream and invade RBC’s , the erythrocytic stage. • Within then RBC’s the merozites mayure from ring forms to ultimately form mature schizonts over 48 hrs(P. vivax P.falciparum P. ovale) or 72 hrs.(P. malariae.)

9. Life Cycle Continued.(Try to stay with me here) • With mosquito transmitted P. vivax and P. ovale infx. Some parasites remain dormant in the liver as hypnozites and can cause late relapse by reactivation. • P. vivax infx has been seen up to 1 yr after exposure although it is quite rare after 3-4 mos.

10. Pathogensis • Malaria parasites digest RBC protiens and derive energy from anaerobic glycolsis of glucose to lactic acid, thus the clinical problems of hypoglycemia and acidosis. • They also alter RBC membrane causing hemolysis , accelerated splenic clearance and anemia.

11. Pathogensis • Anemia is aggravated by relase of TNF-alpha which suppresses hematopoesis. • Thrombocytopenia is caused by increased splenic sequestration and decreased ppatlet survival time.

12. The pathogensis of P. falciprum. Why the f stands for fatal! • P.f parasites induce the formation of sticky knobs on the RBC surface which bind to endothelial cells in capallaries and venules. • The cytoadherence and sequestration cause obstruction to flow and also stick to uninfected RBC’sto form rosettes which obstruct the microcirculation. • Polymorphisms of TNF alpha seem to determine the severity of infx.

13. Clinical Manifesations • Incubation periods: P. falciprum 10-14 days , but can be delayed in semi-immunes or pts having taken chemopx. • About 50% of pts with P. vivax , or , P. ovale present within 2 mos. • P. malariae ususally presents within 1 mo. But can be a low grade infx for yrs.

14. Clinical Presentation • Fever, Fever, Fever ! • Flu-like symptoms : myalgias, malaise • Headache and abdominal pain. • Rigors ,chills cough and diarrhea are also be seen.Lymphadenopathy is rare. • Classical descriptions of fever patterns are often absent. • Seizures, hypoglycemia and renal failure are seen in complicated malaria.

15. Self-treatment(Controversial) • Consider for travelers who are > 24 hr from medical care if in very high risk areas such as subSaharan africa. • Self-treatment is temporizing and not definative as many other infections can have similar nonspecific sx. • Seek care ASAP ! This advice is often ignored by travelers and is well documented.

16. Malaria Work Up • Thick and thin smears from capillary blood q 6-12 X3, obtain with fever spikes if possible.Thick smears are the most sensitive and thin smears allow for speciation. Initial smears are + in 95% of cases.This is the gold standard for diagnosis. • CBC with diff, LFT’S, Chemistries, Blood Cx’s. • Antigen detection may prove to be useful in the field when microscopy is not available. Expensive and not FDA approved.

17. Malaria Prevention • Sleep in screened rooms or under a net treated with permethrin. • Use a DEET based repellant up to 38% a composite based repellant allows for a lower concentration of DEET and is good for kids. • Avoid the outdoors between dusk and dawn if possible. • Treat 1 set of clothes with permethrin for viewing game. Good for 2 wks. Even with washings. Cotton works the best.

18. Chemoprophylaxis • Chlorquine is always the drug of choice in chloroquine sensitve areas. • It is cheap and well tolerated. • Begin 1 week prior to exposure, weekly during exposure and weekly for 4 weeks post-exposure. • G.I. upset is the most common side-effect. Retinopathy not a problem with qwk. dosing.

19. STB ProblemsContinued • Advise that Malaria Presents in Various Ways • Alternative diagnosis that requires treatment may be present, particularly in travellers who have been compliant with appropriate chemoprophylaxis regimen. • Malaria is over-reported by laboratory technicians; nevertheless, if malaria is diagnosed there should be f/u ASAP.

20. Chemoprophylaxis contd. • Atovoquone/Proguanil sold as Malarone is a first line agent for areas with CRPRF. • Efficacy is equivilent to Mefloquine. • Most common side-effect is GI upset. • Availible I adult and pediatric formuations. • Begin 1-2d prior to exposure,. Daily during exposure and daily for 7d post.exposure. Malarone provides causal prophylaxis in the liver. • Cost can be a limiting factor for long term use ,approx. $1600 /yr.

21. SBT Problems • Expatriates assume that they can recognize malaria from the sx. • They do not consistently assume that faver is malaria until proven otherwise. • They do not always choose an appropriate regimen- • The drug deministered for treatment is the same as that used for prevention;

22. Chemoprophylaxis Contd. • Mefloquine is the drug of choice for longer term prophylaxis in areas with CRPF. • Many RCT’s support the long term saftey and efficacy of this drug in PCV’s and military personnel . • Contraindications are seizure d/o or major psychiatric d/o, though we try to avoid this drug in most pyschiatric d/o when possible.This is the approach of the Canadians • Most common side-effect is G.I. upset. • Begin 3 wks prior to exposure ,weekly during exposure and wekly for 4 wks. post exposure.

23. Chemoprophylaxis Contd. • Doxycycline is an alternative in areas with CRPF. Especially in Thailand’s boarders with Cambodia and Myanmar. • Efficacy is excellent and is equal to Mefloquine and Malarone. • Missed doses can be a problem with qd dosing this is also true for Malarone. • Side-effects are G.I. upset, C-Diff., monilial infx. and photosensitivity dermatitis. • Begin 1-2 d prior to exposure, daily during exposure, and daily for 4 wks., postexposure.

24. SBT Prolems Continued • Single drug therapy is chosen over comination therapy; • The dose used is often that used in the community for “semi-immunes”; • The drug used is often less offective than that used for prevention, e.g., mefloquine for prevention, chloroquine for treatment.

25. Self Treatment • Selection of therapy is crucial and these recommendation assume proper chemoprophylaxis. • Atovoquone/ Proguanil (Malarone) 4 tabs qd x 3d, or Quinine Sulfate and Doxycycline. 250mg base,2 tabs tid x 7d and 100mg. bid x 7d. • Mefloquine in tx. doses has very high rate of side-effects and should be avoided.

27. SBT Drugs to Avoid • Halofantrine (causes cardiac deaths) • Mefloquine (unacceptably high rates of severe adverse events at treatment doses) • Fansidar alone (sulfadoxine plue pyrimthamine) (resiistanace) • Fansimef (mefloquine plus Fansidar) (resistance) • Chloroquine plus Fansidar (resistance, ineffective)

28. In Summary • Pf. has the potiental to be a rapidly fatal disease. It can kill within 24-36h! • It is preventable is a proper multiprong approach is employed. • Although S.B.T. can be employed, it is not a substitute for proper prevernative methods ,and shoiuld never delay proper diagnosis.