L3-Malaria: Epidemiology, clinical management and control. 19 January 2018 SCBM346 TROPICAL INFECTIOUS DISEASES AND CONTROLS

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1 19 January 2018 SCBM346 TROPICAL INFECTIOUS DISEASES AND CONTROLS L3-Malaria: Epidemiology, clinical management and control Lecturer: Niwat Kangwanrangsan, Ph.D. Department of Pathobiology Faculty of Science, Mahidol University

2 Objectives 1. Explain the concept of malaria biology and epidemiology 2. Explain the basic clinical management of malaria 3. Explain the general idea of prevention and control

3 Outline Introduction to malaria Biology and Epidemiology Clinical Management Malaria Prevention and Control

4 Malaria (a worldwide disease) 3.2 billion people live in areas at risk of malaria transmission in 106 countries and territories. The World Health Organization estimates that in 2016 malaria caused 216 million clinical episodes, and 445,000 deaths.

6 Malaria disease Parasite species Transmission Severity Most deadly Plasmodium spp. Female Anopheles mosquitoes 29% of global mortality. High number of malaria cases. (200 million per year) WHO Malaria Plasmodium falciparum. 1

7 Life Cycle

8 Mueller I, et al. Lancet Infect Dis (2009)

9 Pathogens and Vectors Plasmodium sp. P. falciparum P. vivax P. ovale P. malariae P. knowlesi Vector: Anopheles sp.

10 Plasmodium Infection Humans are the intermediate host and reservoir host. Mosquito is the definitive host and vector. Female Anophelinesbecome infected only if they take a blood meal from a person whose blood contains mature male and female gametocytes. infective stage to human. to mosquito..

11 Symptoms Fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), hemoglobinuria, retinal damage, and convulsions Classic symptom of malaria is cyclical occurrence of sudden coldness followed by rigor and then fever and sweating lasting four to six hours occurring every two days in P. vivaxand P. ovaleinfections every three days for P. malariae every hours for P. falciparum

12 Uncomplicated Malaria The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of a cold stage (sensation of cold, shivering) a hot stage (fever, headaches, vomiting; seizures in young children) and finally a sweating stage (sweats, return to normal temperature, tiredness). More commonly, the patient presents with a combination of the following symptoms: Fever Chills Sweats Headaches Nausea and vomiting Body aches General malaise

13 Severe Malaria a medical emergency and should be treated urgently and aggressively Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities Severe anemia due to hemolysis (destruction of the red blood cells) Hemoglobinuria(hemoglobin in the urine) due to hemolysis Acute respiratory distress syndrome (ARDS), an inflammatory reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment

14 Severe Malaria Abnormalities in blood coagulation Low blood pressure caused by cardiovascular collapse Acute kidney failure Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia Hypoglycemia (low blood glucose). Hypoglycemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.

16 Plasmodium blood stages Blood stage Ring form Trophozoite Schizont Merozoite cell Lead to hemolytic anemia Maieret al

17 Diagnosis Microscopy Rapid Diagnostic Test (RDT) Other tests PCR, radioimmunoassay, IFA

18 Microscopic Diagnosis gold standard peripheral blood; thick and thin smear high sensitivity quantify the load species differentiation requires skills to identify

19 RDT detection of parasite antigens; HRP2, Aldolase, LDH faster good sensitivity needs little training expensive antigen persistence after parasite clearance (2 weeks)

20 Other Facts Among the malaria species that infect humans, P. vivaxand P. ovalecan develop dormant liver stages that can reactivate after symptomless intervals of up to 2 (P. vivax) to 4 years (P. ovale). Pregnant women have increased susceptibility to P. falciparum malaria; in malaria-endemic countries, P. falciparum contributes to 8-14% of low birth weight, which in turn decreases the chance of a baby s survival.

21 Other Facts Five times, the Nobel Prize in Physiology or Medicine has been awarded for work associated with malaria: to Sir Ronald Ross (1902), Charles Louis Alphonse Laveran (1907), Julius Wagner- Jauregg(1927), Paul Hermann Müller (1948), and Youyou Tu (2015). Two important currently used antimalarial drugs are derived from plants whose medicinal values had been noted for centuries: 1) artemisininfrom the Qinghaosuplant (Artemisia annua, China, 4th century) 2) quinine from the cinchona tree (Cinchona spp., South America, 17th century).

22 Plate from Quinologie, Paris, 1854, showing bark of Quinquina calisaya (from Bolivia).

23 Anti-malarial drug: Chloroquine Primaquine Mefloquine Quinine Artemisinin Treatment

29 NIL near isogenic line

35 Drug Drug-resistance Introduction "First" year resistance reported Quinine Chloroquine Proguanil Sulfadoxinepyrimethamine Methoquine Atovaquone Artemisinins ? [adapted from Wongsrichanalai et al. Lancet Inf Dis :209] * Discovery of novel anti-malaria drugs is needed.

36 Epidemiology

37 Malaria geographical distribution Feachem RG, et al. Lancet (2010) 37

39 Vectors: Anopheles mosquitoes

40 Thai mosquitoes: malaria vector species 72 anopheline species: Anopheles and Cellia 36 species : man biters 5 malaria vector species - An. dirus Anthropophilic: man biting preference - An. minimus - An. maculatus - An. aconitus - An. sundaicus

41 Reported malaria cases and deaths, 2013 (World Malaria Report 2014, WHO)

Thai patients who found with Plasmodium parasite from 2009 till 2011 (2552-2554)

42 Thai patients who found with Plasmodium parasite from 2009 till 2011 ( ) Department of disease control, Ministry of Public Health,Thailand

Malaria cases in Thailand from 2013 (species differentiation) 2556-Unknow 2556-Pv+Pm+Po 2556-Pf+mix 2555 1400 1200 18 17 26 14 14 1000 800 600 400 200 0 14 234268 254 206 207208204 142 17 9 13 167

43 Malaria cases in Thailand from 2013 (species differentiation) 2556-Unknow 2556-Pv+Pm+Po 2556-Pf+mix

44 Malaria Prevention and Control Treatment program Vector control: mosquito eradication -Insecticides-treated nets (ITNs) -Indoor residual spraying (IRS) -Sterile insect technique: transgenic or genetically modified insects Prevention of mosquito bites -Mosquito nets and bedclothes: Insecticide (permethrinor deltamethrin)-treated nets Diagnosis Vaccination

45 Dichloro-diphenyl-trichloroethane(DDT) (1939) A German chemistry student, OthmerZeidler, synthesized DDT in 1874, for his thesis. The insecticidal property of DDT was not discovered until 1939 by Paul Müller in Switzerland. Various militaries in WWII utilized the new insecticide initially for control of louse-borne typhus. DDT was used for malaria control at the end of WWII after it had proven effective against malaria-carrying mosquitoes by British, Italian, and American scientists. Müller won the Nobel Prize for Medicine in 1948.

46 Eradication Efforts Worldwide: Success and Failure

47 Malaria Control

50 Vaccine Development Harvard.edu 3 stages Liver stage Blood stage Sexual stage 2

51 CDC

55 References World Health Organization (WHO) Centers for Disease Control and Prevention (other scientific journals related with malaria)

Cell and Molecular Parasitology Laboratory Malaria parasites not only live in our body,

benefit for the malaria prevention and treatment.

56 Cell and Molecular Parasitology Laboratory Malaria parasites not only live in our body, but they also need Anopheles mosquitoes to complete their life cycle and to transmit the disease. Study the biology transmission stages (mosquito-to-human and human-to-mosquito) could benefit for the malaria prevention and treatment. Research Topics Biology of human malaria in transmission stages Transmission-blocking drug and vaccine development Study of malaria gene functions by genetic manipulation Anti-malarial activities of Thai medicinal plants

57 P. vivax infection in human hepatocytes IFA H&E TEM Gametocytes, precursor of mosquito stage Giemsa in vitro culture of mosquito stages retort ookinete

58 P. vivax infection : patient blood Malaria field sites: * Thai-Myanmar border Tak Kanjanaburi 58

59 Mosquito feeding patient blood -- feed to Anopheles mosquitoes *membrane feeding assay 59

60 Dissecting of salivary gl. sporozoites infected mosquitoes bathing dissecting

61 FRGN mice Rag2 -/-, Il2rg -/- Fah -/- upa/scid mice SCID of upa Rag2 - recombination-activating gene 2, Il2rg - interleukin-2 receptor subunit gamma, Fah - fumaryl-acetoacetate hydrolase, upa - plasminogen activator, urokinase.

62 Acknowledgements Dr.Jetsumon Prajumsri Director Mahidol Vivax Research Unit Faculty of Tropical Medicine, Mahidol University Dr.Patchara Sriwichai Department of Medical Entomology Faculty of Tropical Medicine, Mahidol University

Malaria. Edwin J. Asturias, MD

Malaria. Edwin J. Asturias, MD Malaria Edwin J. Asturias, MD Associate Professor of Pediatrics and Epidemiology Director for Latin America Center for Global Health, Colorado School of Public Health Global Health and Disasters Course