1. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Greater Mekong Subregion Malaria Elimination Training. The Imerial Mae Ping Hotel, Chiang Mai, Thailand 10 – 21 st August 2015. Transmission of malaria and measures of transmission intensity Dr Rabindra Abeyasinghe (MVP) Regional Office for the Western Pacific Transmission of malaria and measures of transmission intensity Dr Rabindra Abeyasinghe (MVP) Regional Office for the Western Pacific

2. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Outline Malaria vector life cycle Malaria vector characteristics - GMS Main Malaria Vectors in Greater Mekong Subregion Species complexes and relevance to elimination Understanding concepts on transmission dynamics

3. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Malaria parasite life cycle

4. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Understanding the life cycle of malaria vectors – Key points for control

5. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Biological aspects related to vectors Only female mosquitoes have blood meals on humans Development of a batch of eggs only takes place after a female mosquito has had a blood-meal; Gonotrophic period (time required for the laying of a batch of eggs is approximately 2 days. Sporogony is the time taken for completion of the parasite development in the mosquito and could take 10 – 12 days in GMS conditions. This means a female mosquito must make 3-5 journeys between the feeding and breeding places before it becomes infective

6. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Characteristics of malaria vectors Anthropophilic – preference for feeding on humans Endophilic/exophilic – preference for resting in/out doors Endophagic/exophagic – preference for feeding in/out doors Breeding in close proximity to humans Longevity Susceptibility status to insecticides

7. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Main malaria vectors of the Greater Mekong Subregion Cambodia –An. dirus complex, An. Minimus complex, Maculatus Group China –An. Sinensis (Hyrcanus Group), An. Anthropophagus (An. lesteri) Lao PDR –An. dirus complex, An. Minimus complex, Maculatus Group Myanmar –An. culicifacies complex, An. dirus complex, Maculatus Group, An. minimus complex, An. sinensis complex, An. subpictus complex,

8. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Main malaria vectors of the Greater Mekong Subregion Vietnam –An. dirus, An. varuna (minimus) – non-vector, An. epiroticus (sundaicus) Thailand –An. leucosphyrus Complex (A. latens), An. Maculatus Group (An. sawadwongporni, An. pseudowillmori), An. epiroticus (sundaicus) Secondary vectors –An. aconitus, An. annularis, An. barbirostris complex, An. subpictus, An. sundaicus complex in some coastal sites.

9. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand.

10. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Vector bionomics Factors defining the bionomics: Larval breeding sites, feeding and resting behaviours including peak biting times, insecticide susceptibility and behavioural resistance Larval site characteristics: light intensity, salinity, turbidity, flow or movement, vegetation, size, natural or man made Feeding and resting behaviours: feeding habit, biting habit, biting time, pre-feeding and post-feeding resting sites

11. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Use of bionomics for vector control Most control interventions are based on exploiting the bionomics of vectors. Hence it is imperative to know and understand the bionomics of major vector species. Monitoring and evaluation of VC interventions should be closely linked to epidemiological information and review of vector bionomics.

12. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Anopheles species complexes

13. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Main malaria vectors in Asia

14. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Bionomics of dirus complex …………… An. dirus complex, due to its longevity and the highly anthropophilic behaviour of its members, is considered to be the dominant vector group in any area where it is present Members of the An. dirus complex have clear differences, but ecologically, they tend to occupy the same ecological niche and are generally considered as forest-dwelling species, specifically in mountainous areas and foothills, with an affinity for humid, shaded environments.

15. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Distribution of Anopheles dirus complex

16. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Dirus Complex The primary disease vectors are An. dirus and An. baimaii, which transmit P. falciparum and P. vivax, as well as Wuchereria bancrofti. Both species are highly anthropophilic, exophagic as well as endophagic and exophilic. Biting activity is species-specific, in Thailand, An. dirus has a tendency to bite between 20:00 and 23:00 h and An. baimaii from 22:00 h to 02:00 h. Anopheles scanloni is also anthropophilic and plays a more focal role in malaria transmission of both P. falciparum and P. vivax in Thailand. It is an early evening biter with peak activity starting at dusk, between 18:00-19:00 h.

17. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Breeding habitats dirus complex Typically breed in small, shallow, usually temporary, mostly shaded bodies of fresh, stagnant (or very slowly flowing) water, such as pools, puddles, small pits (e.g. gem pits), animal footprints (e.g. elephant footprints), wheel ruts, hollow logs, streams and even wells located in forests, bamboo forests and fruit or rubber plantations. Water can be clear or turbid, and habitats with nitrogenous wastes, due to elephant and buffalo excreta or rotten leaves, appear more productive. They are most abundant during the rainy (monsoon) season due to the larval requirement and oviposition preference for small temporary pools.

18. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Distribution of the Maculatus group

19. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Bionomics of the An. Maculatus group Members of the Maculatus Group are typically found in or near hilly and mountainous areas. Larvae have been collected in a diverse number of permanent or semi-permanent bodies of clean water that are often exposed to direct sunlight, or partially shaded habitats. Usually 100 – 400 m from human settlements. Anopheles maculatus prefers to use pools of water formed on the banks of rivers and waterfalls. The common larval habitats are shallow pools 5-15 cm deep with clear water, mud substrate and emergent plants.

20. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Challenge of A. maculatus control The combination of the early evening biting activity of these malaria vectors (particularly An. maculatus and An. sawadwongporni) and their zoophilic and exophilic tendencies indicates that they will be less affected by vector control methods

21. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Distribution of the Minimus Complex

22. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Anopheles minimus Complex The Minimus Complex belongs to the Minimus Subgroup within the Funestus Group. Anopheles minimus s.l. is considered a primary malaria vector in the hilly forested regions of mainland Southeast Asia. Anopheles minimus s.l. comprises three sibling species, namely An. minimus, An. harrisoni and An. yaeyamaensis (Japan only)

23. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Bionomics of minimus Anopheles minimus was also involved in the transmission of W. bancrofti in southern China and Thailand. Larvae are generally found in small to moderate-sized streams or canals with slow-running, clear and cool water, partially shaded and with grassy margins where females prefer to lay their eggs. They develop in various pools (rock, ground, stream and seepage), rice agro-irrigation systems and also unusually in rain water tanks in Hanoi. Anopheles minimus s.l. is commonly found at elevations ranging from 200 to 900 m and is rare at altitudes above 1500 m.

24. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Bionomics of minimus Females of An. minimus mainly bite humans, but the degree of anthropophily/zoophily depends on the availability of alternative hosts (e.g. cattle). Mainly endophagic in Thailand and central Vietnam, and more exophagic in Cambodia and northern Vietnam. Studies showed that housing in central Vietnam, made with incomplete walls of split bamboo and very large eaves, allows easy entry of the mosquito which would otherwise show exophagic behaviour. Its resting behaviour is reported as exophilic in southern China, Thailand and Vietnam. An. minimus tends to feed with peak activity occurring around 22:00 h in Cambodia and Thailand, after 22:00 h in Vietnam.

25. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Distribution of An. leucosphyrus complex

26. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Environmental factors Ambient temperature Rainfall Altitude Relative humidity Physical environment (type of human habitat, its location in relation to potential breeding sites Biological environment, e.g. alternative blood sources, predators, competitors including human ecology,

27. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Incidence rate The incidence rate is number of new infections occurring in a given population unit in a given time period. Not all inoculations lead to new infections due to a variety of factors: –The inoculum's intrinsic factors –The human host's intrinsic factors –Interaction between parasite diversity and host diversity –Prophylactic interventions. The traditional API (annual parasite index) is an incidence rate.

28. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Prevalence of malaria Prevalence is the number of existing cases, new and old, in a defined population during a specified period (period prevalence) or at a given point in time (point prevalence). SPR (slide positivity rate) is the prevalence of malaria among fever cases examined. TPR (total positivity rate) is used more and more instead of SPR. Parasite rate is used for the prevalence of malaria found in a survey of a given population. Prevalence is expressed as a proportion (it is not a rate).

29. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Prevalence Prevalence is the number of existing cases, new and old, in a defined population during a specified period (period prevalence) or at a given point in time (point prevalence). The traditional SPR (slide prevalence ratio) is the prevalence of malaria among fever cases. Prevalence is expressed as a proportion.

30. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Measuring intensity of transmission Empirically estimating transmission intensity –Entomological Inoculation Rate (EIR) –Incidence Rate –Prevalence Basic concepts –Vectorial Capacity (C) –Basic Reproduction Ratio (R 0 )

31. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Entomological Inoculation Rate The entomological inoculation rate is the number of mosquito bites (inoculations) containing sporozoites received by the population unit in a given period of time (day, month or year).

32. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Vectorial Capacity Vectorial capacity (C) is the potential number of secondary cases originating from one primary case in one day, assuming that the human population is, and remains, fully susceptible. Vectorial capacity measures the potential of the mosquito population to transmit malaria in a region. This can be affected by human factors (such as living in screened houses or using insecticide treated nets). Vectorial capacity does not measure the amount of malaria in a population.

33. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Vectorial capacity The expression for the definition of vectorial capacity can be divided into 5 stages: –The primary, infective, case is bitten by a certain number of mosquitoes per day (ma) or the man-biting rate (bites per man per night by vector population) –Man biting habit (a) –Some of these mosquitoes get infected (c). –Some of these mosquitoes survive the extrinsic incubation period so they are alive and infectious (e -ng ). –They bite a certain number of humans before they die (a/g). –Some of these humans get infected (b). C = ma 2 bce -ng g

34. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. VC is also defined as Vectorial capacity is also defined as C = ma 2 bcp n - log e p where p = e -g is the probability that the mosquito survives one day.

35. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Basic Reproductive Ratio (R 0 ) The basic reproduction ratio, R 0, is the expected number of secondary cases that would originate from one primary case during the whole period of the patient's infectivity, assuming that the community is, and remains, fully susceptible to malaria infection. R 0 does not give the actual number of new infections at any time (which depends on the susceptibility of the population) but the potential for new infections.

36. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Basic Reproductive Ratio (R 0 ) R 0 forms a threshold condition: when R 0 1, the steady state with disease is unstable and malaria can sustain itself in the population.

37. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Basic Reproductive ratio and vectorial capacity The basic reproductive ratio is the product of the vectorial capacity and the duration of infectivity of humans: R 0 = C X 1/r =C/r Where D = Duration of infection = 1/r = C D

38. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Basic reproductive ratio and vivax infections Each infection of P. vivax can be considered as multiple (k) episodes, each with recovery rate, r v. For P. vivax, the basic reproductive ratio is: R 0 = C x k x 1/r v = Ck/r v

39. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Equilibrium Relationship Between prevalence and vectorial capacity

40. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Effects of control interventions Long lasting insecticidal nets reduce m, a, and 1/g (increase g) Indoor Residual Spraying reduces m and 1/g (increases g), it may also reduce a if the insecticide has a repellent effect; Space spraying, source reduction and larviciding reduce m; Reduction of man-vector contact reduces a; Treatment of cases increases r (decreases 1/r).

41. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Effects of Parameters on C and R 0 Reduction of m reduces C (and R 0 ) linearly. Reduction of 1/r reduces R 0 linearly. Reduction of a result in a squared reduction in C (and R 0 ). Increase of g is amplified much more by the exponential form of the survival of the mosquito through the extrinsic incubation period, e -gn, in addition to the reduction of the longevity 1/g. C = ma 2 bc e -ng R 0 = ma 2 bc e -ng g rg

42. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Important Not all interventions have equivalent effects on the parameters. The effectiveness of interventions programmes also depends on: – Coverage of the interventions attainable due their cost – Quality of operations, and their maintenance – Acceptability of the interventions and their sustainability. Vector control interventions will also lose effectiveness due to the development of physiological and behavioural resistance in mosquitoes.

43. Transmission of malaria and measures of transmission intensity, 10 th – 21 st August 2015, The Imperial Mae Ping Hotel, Chiang Mai, Thailand. Thank you