Malaria (มาลาเรีย) Local names: ไข้จับสั่น ไข้ ป่า ไข้ป้าง ไข้ร้อนเย็น ไข้ ดอกสัก Pathophysiology, diagnosis, epidemiology and control 1

Human malarial parasites Plasmodium malariae (Quartan malaria) P. vivax (Benign tertian malaria) P. falciparum (Malignant tertian malaria) P. ovale (Ovale tertian malaria) Primate malaria parasites infecting man e.g. Plasmodium knowlesi 2

Life Cycle Anopheles ยุงก้นปล่อง Human Sporogony Schizogony (Asexual phase) (Sexual phase) 3

Life cycle of malaria parasites 4

Tissue schizont and hypnozoite vivax, ovale hypnozoite 5

Malarial infections 1. Bitten by an infected anopheline 2. Blood transfusion 3. Congenital 6

Course of infection Prepatent period (days) Incubation period (days) av.(range) Patent period (yr) av./max Pv ( ) 2/8 Po ( ) 1/5 Pf (9-14) 1/4 Pm (18-90) 4/53 7

Infection DEATH Infection RECRUDESCENCE Infection Treatment RECRUDESCENCE (R1 RESISTANCE) Re-infection RELAPSE (hypnozoite) Possible outcome of malaria infections PF All PF All PV, PO Parasite density Time (Blood stages) 8

Vivax and ovale malaria (Benign tertian malaria) Non-specific symptoms 2-3 days followed by febrile paroxysm (malaria paroxysm) every other day Cold stage 5-60 min Hot stage 2-6 hr Sweating stage 2-4 hr Clinical aspects malaria paroxysm 9

Days C o 37 Febrile paroxysm P. vivax, P. ovale 10

Malariae malaria (Quartan malaria) Febrile paroxysm every 72 hr. Nephrotic syndrome - the presence of nephrotic-range proteinuria, edema, hyperlipidemia, and hypoalbuminemia 11

Days C o 37 Febrile paroxysm P. malariae 12

non-specific symptoms fever (every day or every other day) chill, headache, influenza-like, pains of limbs and back, nausea etc. Falciparum malaria (Malignant tertian malaria) 13

Complications of severe falciparum malaria Cerebral malaria Anaemia Renal failure Hypoglycaemia etc. 14

Malaria relapse Recrudescence (Pf, Pv, Po, Pm) caused by low parasitaemia Recurrent (Pv, Po) caused by hypnozoites in the liver 15

Malaria Pathology - rupture of infected and uninfected rbc - release of toxins, malarial pigment - packing capillaries (cytoadherence) in brain, kidney, etc.(only Pf) - enlarged spleen - black water fever 16

Liver 17

Kidney 18

Malaria immunity Natural immunity Animal malarias Human P. vivax Duffy bl. gr. Neg. P. falciparum HbS P. falciparum G-6-PD def. Acquired immunity Active: experience infections Passive: congenital Imm. 19

Malaria epidemiology and Control Endemic area Area with cases occurring at a constant but relatively high rate in the population Epidemic area Area with new cases in a given human population, during a given period, at a rate that substantially exceeds what is "expected," based on recent experience 20

Climate & Environment Human Vector Agent Malaria epidemiology 21

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Key terms used in malaria epidemiology Indigenous malaria - Malaria is natural to an area or country (Autochthonous malaria) or Locally contracted malaria Imported malaria - Malaria acquired outside the specified area in which it was found Introduced malaria - Secondary case contracted locally, but derived from an imported case Induced malaria- Accidental infection by blood transfusion, needles, organ transplant etc. Anophelism without malaria - A situation when anopheles mosquito is present in the area but there is no case of human malaria (e.g. malaria-free Soviet Armenia in ) 24

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Endemicity TransmissionSpleen rate (<5yr old) Parasitaemia (<5 yr old) HoloendemicityVery high, all yr>70%60-70% HyperendemicityHigh, seasonal50-70% Mesoendemicitymoderate20-50%<20% Hypoendemicitylow0-10% 26

Population areas of high malaria transmission 1 or more/1000 pop./year areas of low malaria transmission <1/1000 pop./year malaria-free areas no cases for several years Population at risk The population at risk is the total population living in areas where malaria is endemic (low and high transmissions), excluding the population living in malaria-free areas. 27

Annual blood examination rate (ABER): the number of parasitological tests done (by microscopy and/or RDTs) divided by the total population at risk. Malaria test positivity rate: the number of parasitologically positive cases per 100 cases examined by RDT or microscopy Malaria morbidity – number of cases with illnesses Malaria mortality – number of death due to malaria 28

Malaria prevalence - positive cases at one time Malaria incidence - new cases at a period of time Annual parasite incidence (API) - number of cases per 1000 populations in one year Entomological inoculation rate - No. infective bites/man/night Sporozoite rate - No. infective mosq./No. examined X 100 Passive case detection – malaria clinic, hospital Active case detection – mobile team, mass blood survey 29

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Malaria Vectors in Thailand Primary vectors Anopheles minimus complex An. dirus complex (An. dirus, An. baimaii) An. maculatus Secondary vectors An. epiroticus (formerly An. sundaicus A) An. aconitus An. pseudowillmori An. sawadwongporni An. barbirostris complex 33

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2 P. knowlesi distribution 36

Crab-eating macaque (ลิงแสม) Pig-tailed macaque (ลิงกัง) 38

Malaria control 1. Blocking man-vector contact bednets, repellant 2. Vector control residual spray, insecticide-treated bednets, environmental control 3. Treatment of malaria cases active and passive case detections 4. Drug prophylaxis 40

Residual spray 41

Bednet 42

Impregnating bednets 43

Chemotherapy 1. Prophylactic use 2. Therapeutic use -blood schizontocides Pf - mefloquine, quinine, artesunate, artemether Pv, Po, Pm - chloroquine - tissue schizontocides primaquine (Pv, Po) 3. Prevent transmission primaquine (Pf gametocyte) 44

Laboratory today 1.Stain the prepared thick film with Giemsa 2.Parasite count 45

Parasite count Objectives: To demonstrate the parasite concentration in the blood at a particular point in time 1. Semi-quantitative estimation 2. Parasite count using thick films 3. Parasite count using thin films 46

Semi-quantitative estimation Average number/thick film field +: 1-10 per 100 fields ++: per 100 fields +++: 1-10 per field ++++: > 10 per field 47

Parasite count using thick film Number of parasites counted Number of leucocytes counted X 8,000 /ul blood e.g X 8000= 6000 Count parasites against 200 leucocytes 48

Giemsa stained thick blood film PvPm Pf 49

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In case of heavy infection > 40,000/ul (> 20/field) Count no. leucocytes against 500 parasites e.g X 8,000 = 400,000 51

Parasite count using thin films Count parasites against red blood cells (~ 10,000 – 20,000 rbc) Should know 1. Average no. of rbc (~ ) per oil imm. field. 2. 5,000,000 rbc/ul in male. 3. 4,500,000 rbd/ul in female. 52

e.g. No. rbc/field = 250 No. parasites in 50 fields = 30 No. rbc with 30 parasites = 250 x 50 = 12,500 No. parasite per ul = 30 x 5,000,000 = 12,000 12,500 53