Pugud Samodro Bag/SMF Ilmu Penyakit Dalam FKIK Unsoed/ RSUD Prof Margono Soekarjo Purwokerto

What is Malaria?  Parasitic infection of human red blood cells  4 species can infect humans Plasmodium falciparum Plasmodium vivax Plasmodium malariae Plasmodium ovale Pictures of P. falciparum

Etiology  Causative organism: Plasmodia  P. Vivax: tertian malaria  P. Malariae: quartan malaria  P. Falciparum: malignant malaria  P. Ovale: tertian malaria  Pathogenicity: merozoite, malarial pigment &  products of metabolism

Plasmodium falciparum  Most dangerous form of malaria Risk of cerebral malaria, renal failure, acute respiratory distress syndrome, severe anemia  Prompt treatment is essential  Untreated infection in a non-immune person would likely be fatal  Once person is treated and cured, there is no risk of relapse (but you can get infected again…) P. falciparum has no dormant liver stage (hypnozoite)

P. vivax and P. ovale  Less likely to be life threatening than P. falciparum  Symptoms (especially fever) can still be dramatic  Different drugs are used to treat blood and liver stage parasites

Etiology  Two period:  human - whole asexual reproduction  mosquito - sexual parasitic stage  Two host:  human - intermediate host  mosquito - final host  notes:  clinical symptoms: erythrocytic stage  relapse: exerythrocytic stage  infectivity: sporozoite

Epidemiology  Source of infection Patient, parasite carrier  Route of transmission  female mosquito biting person  blood transfusion  Susceptibility:  universal susceptibility  no-cross-immunity  re-infection  Epidemic features:  sporadic or endemic, tropic or subtropic

What is the Malaria Vector?  Spread by bite of infected female Anopheles mosquitoes  Night-biting mosquitoes  Indoor-biting mosquitoes

Pathogenesis  Mechanism of attack  merozoite  RBC rupture malaria pigment  products of metabolism   blood stream allergy  P. Falciparum: produce microvascular disease  magnitude of the parasitemia & age of patient  no specific Ab or cell -mediated response

Sporogonous Cycle: Mosquito Stages Gametocytes P. falciparum P. vivax P. ovale P. malariae Human Liver Stages Exo-erythrocytic (hepatic) Cycle: Human Blood Stages Erythrocytic Cycle: Malaria Lifecycle

Pathology  Anemia:  P. Vivax - retiform RBC  P. Malariae - mature RBC  P. Falciparum - every RBC  Prolifeation of mononuclear phagocyte  hepatomegaly  splenomegaly  Cerebral edema & congestion

Symptoms of Malaria  Fever is by far the most common symptom, but is by no means the only one  Often can have constellation of symptoms described as “flu-like”  Other symptoms can include: chills, fatigue, weakness, headache, nausea, vomiting, diarrhea, muscle aches, mental status changes

Clinical manifestation Incubation period: quartan malaria: day tertian malaria: 13~15 day malignant malaria: 7~12 day

Clinical manifestation  Typical attack  Chill: abrupt onset, shivering, pale face,cyanosis. Last 10 min or 1~2hr.  High fever: T rise to 40 o C with malaise, myalgia, thirsty. Last 2~6 Hr.  Sweating: profuse sweating with restlessness  regular 48 hr. or 72 hr. Cycle

Clinical manifestation  Signs  anemia  splenomegaly  hepatomegaly, ALT elevate

Clinical manifestation  Perniciouse attack: cause by P. Falciparum  cerebral malaria  high fever, headache, vomiting, convulsion delirum, respiratory failure  hyperpyrexia type  T> 42 0 C, convulsion, delirium  Relapse: early relapse - <3m,  later relapse - >6m

Clinical manifestation  Malaria caused by transfusion  incubation period: 7~10 day  no exerythrogenic phase, no relapse

Complications  Black- water- fever:  cause: 1/inadequate G-6-PD  2/The toxin release by malarial parasite  3/Allergic reaction to anti-malarial drugs  feature:1/chill & fever  2/dark red or black urine  3/severe hemolytic anemia  Acute glomerulonephritis

Malaria Mortality 2 main ways it kills:  Anemia Parasites destroy red blood cells Associated with increased mortality  Cerebral malaria Damages brain and other vital organs Fatality rate of 15% or more

Laboratory Findings  Blood picture: decrease in RBC & Hb  blood film for parasite  serological examination  ELISA for P. antigen  DNA hybridization

Plasmodium vivax Ring stage Gametocyte Trophozoite Schizont

Plasmodium malariae Ring stage Gametocyte Trophozoite Schizont

Plasmodium ovale Ring Trophozoite Schizont Gametocyte

Diagnosis  Epidemiological data  endemic zone  blood transfusion  Clinical manifestation  Laboratory findings  Diagnostic treatment:  chloroqunine for 3 days

Differential Diagnosis  Typhoid fever  Septicemia  Leptospirosis  Encephalitis B

Roll Back Malaria (RBM)  Founded by: World Health Organization (WHO), United Nations Development Program (UNDP), United Nations Children's Fund (UNICEF) and World Bank  Includes national governments, civil society and non-governmental organizations, etc.  Provides framework for coordination between Ministries of Health and various organizations

Roll Back Malaria (RBM)  The goal of Roll Back Malaria, established as a health initiative by WHO and its partners in 1998, is to halve the world's malaria burden by  At the Africa Summit on RBM, April 2000, Heads of State or senior representatives from 44 malaria- afflicted countries in Africa agreed to a series of interim goals to be attained by  Global program with clear strategies  Provides framework for Action  Touts prevention and treatment

Roll Back Malaria (RBM) Goals - At least 60%  At least 60% of those with malaria should be able to access and use correct, affordable and appropriate treatment within 24 hours. At least 60% of those at risk of malaria, particularly children under five years of age and pregnant women should use insecticide treated mosquito nets.  At least 60% of pregnant women at risk of malaria should have access to chemoprophylaxis or intermittent presumptive treatment.

Treatment  Anti-malarial drugs  Chloroquine-susceptable infection  chloroquine : 1g /d, for 3 day, p.o.  primaquine: for 8day, p.o.  Chloroquine-resistant infection  mefloguine:  artemisinine

Treatment  Pernicious attack  Chloroquine: 10mg/kg iv drop in 4 hr. Then 5mg/kg, iv drop in 2 hr.  Quinine: 500mg iv drop in 4 hr.  Radical therapy Chloroquine (3 day) + primaquine ( 8 day )

Countries with at least one study indicating pyrimethamine-sulfadoxine total failure rate > 10% No failure reported P yrimethamine-sulfadoxine total failure rate < 10% No recent data available P. falciparum resistance to sulfadoxine/pyrimethamine Source: WHO global database on drug resistance

Countries with at least one study indicating mefloquine total failure rate > 20% No failure reported Mefloquine total failure rate < 10% No recent data available Countries with at least one study indicating mefloquine total failure rate > 10% P. falciparum resistance to mefloquine Source: WHO global database on drug resistance

P.vivax malaria distribution and Reported Treatment or Prophylaxis Failures or True Resistance, 2004 Source: WHO RBM Department, 2004 Vivax resistance to CQ confirmed in Guyana, Indonesia and Peru

Rationale for antimalarial combination therapy  Advantages of combining two or more antimalarial drugs: First cure rates are usually increased. Second, in the rare event that a mutant parasite which is resistant to one of the drugs arises de-novo during the course of the infection, it will be killed by the other drug. This mutual protection prevents the emergence of resistance.  Both partner drugs in a combination must be independently effective.  Risks: Increased costs and increased side effects

The choice of artemisinin combination therapy (ACT) There are now more trials involving artemisinin and its derivatives than other antimalarial drugs, so although there are still gaps in our knowledge, there is a reasonable evidence base on safety and efficacy from which to base recommendations. Combinations which have been evaluated: piperaquine artemisinin + mefloquine artesunate + piperaquine dihydroartemisinin + mefloquine lumefantrine artemether + mefloquine naphthoquine chloroquine amodiaquine sulfadoxine-pyrimaethaminine mefloquine proguanil-dapsone chlorproguanil-dapsone atovaquone-proguanil clindamycin tetracycline doxycycline

Response to increasing resistance Combination therapies recommended by WHO Artesunate + amodiaquine Artemether/lumefantrine Artesunate + SP Artesunate + mefloquine FDC WHO Technical Consultation on “Antimalarial Combination Therapy” – April 2001 ACTs

Prevention  Drug prophylaxis  chloroquine: 0.3g once a week  doxycycline  Kill mosquito  Vaccination

TOGETHER WE CAN BEAT MALARIA THANK YOU FOR LISTENING