1. Learning Unit 2 Basic malaria epidemiology and transmission dynamics

2. Learning Unit 2: Learning objectives Specify biological and epidemiological features of P. vivax and P. falciparum that are favouring or hindering elimination Specify factors that influence malaria elimination, related to: Vectors Human hosts Eco-geographical factors Define the major parameters of transmission intensity which are used in malaria epidemiology Identify the relationships between vectorial capacity, basic reproductive rate, entomological inoculation rate, and incidence and prevalence of malaria infection Describe how the relationship between vectorial capacity and other concepts of malaria transmission intensity influence the selection of strategies and methods in different epidemiological situations

3. Overview of topics for the day Plenary 1: Biological aspects related to parasites and human hosts Aspects related to vectors and eco-geographical factors Group exercises: Group 1 and 2: 2.1 & 2.2 Group 3 and 4: 2.1 & 2.3

4. Biological aspects related to parasites, vectors and human hosts

5. Biological aspects related to parasites Plasmodium falciparum Plasmodium vivax Plasmodium malariae Plasmodium ovale

6. Life-cycle of human malaria parasites

7. The four processes in the life-cycles of plasmodia in humans Name of the process Host organ Host cellStages involvedDuration Dormancy (for certain species of plasmodia) liverhepatocytehypnozoiteusually 5-18 months Exo-erythrocytic schizogony liverhepatocyte exo-erythrocytic schizont -> merozoite 6-15 days, depending on the species Erythrocytic schizogony blood red blood cell merozoite -> trophozoite -> schizont -> merozoite-> etc. a number of cycles, each of 2 or 3 days duration Gametocytogonyblood red blood cell merozoite -> gametocytes (male and female) Days/weeks

8. Life-cycle of P. falciparum

9. Life-cycle of P. vivax

10. Duration of critical intervals for P. falciparum and P. vivax CharacteristicsP. falciparumP. vivax Prepatency (from inoculation to the appearance of microscopy detectable parasitaemia) 7-10 days11-13 days Incubation: short (from inoculation to the appearance of symptoms) 8-14 days10-18 days Incubation: long (from inoculation to the appearance of symptoms) Not applicable5-18-months Minimum time to appearance of mature gametocytes after the appearance of parasitaemia 12 days0 days Maximum time of disappearance of circulating gametocytes (after treatment with blood schizontocides) 8 weeks< 1 day Asexual cycle in the blood48 hours Typical duration of untreated infectionOne year or less in about 80% of cases 1 - 2 years (exceptionally, up to 5 years)

11. Biological aspects related to vectors Life-cycle of anopheline mosquito

12. Biological aspects related to vectors A batch of eggs develops in a female only after a blood-meal; Gonotrophic period is 2-4 days, shorter than sporogony duration (12 days at comparable temperatures) - female must make 3-4 journeys between the feeding and breeding places before it becomes infective

13. Biological aspects related to vectors Vector efficiency – susceptibility to malaria parasites: Poor susceptibility  NOT good vector – longevity - probability of a mosquito’s survival through one day: Mosquitoes with short life span die before the maturation of sporozoites (11-13 days) – Anthropophily - man-biting rate and man-biting habit – Risk of transmission (vectorial capacity)

14. Biological aspects related to vectors Some vectors have combined characteristics: An. gambiae in sub-Saharan Africa: high susceptibility to parasites+ high survival rate + anthropophily + ability to exploit many different kinds of breeding places. North European An. Messeae: short life span + easily attracted by cattle + selective regarding breeding sites.

15. Biological aspects related to vectors Mosquito properties important for vector control endophagy or exophagy: tendency to feed inside or outside houses; endophily or exophily: tendency to rest within or outside houses during the blood digestion; biting time Preference to rest at a particular height of a wall surface

16. Biological aspects related to human host Susceptibility to malaria is universal in humans. Only exception: People with no Duffy antigen on red cell surfaces are refractory to P. vivax. – This genotype is widespread among Africans (especially West Africa) – Therefore, a sufficient pool of susceptible individuals to vivax do not exist – That’s why vivax transmission is limited in Africa

17. Some haemoglobinopathies (gene polymorphisms) offer some protection: – Haemoglobin S (causing sickle cell disease) – Thalassaemias (alpha-thalassimia): missing genes that affect how the body makes hemoglobin. RBC weak and destroyed – Ovalocytosis (ovale shaped blood cells) – Glycose-6-phosphate dehydrogenase (G6PD) deficiency: the enzyme is important red blood cell metabolismred blood cell Most of these gene polymorphisms are linked to intensity of malaria transmission Biological aspects related to human host

18. Acquired malaria immunity – Clinical immunity develops by age – Offers partial protection – Determines the clinical epidemiology in an area – Strongly dependent on malaria exposure (transmission intensity) throughout life Biological aspects related to human host

19. A. Low endemicity B. Moderate endemicity C. High endemicity D. Hyperendemicity E. Epidemic

20. Altitude and malaria prevalence in Tanzania

21. eco-geographical factors

22. Geographical factors Temperature – The most important factor for mosquito and parasite (in mosquito) development – Mosquitoes less sensitive to low temperatures than parasites – anophelines can breed at temperature above 10  C where the lower threshold of sporogony is 16  C – Lower threshold for P. vivax sporozoite development is 16  C, for P. falciparum it is 18°C – Optimum temperature for mosquito development is 25- 27°C and maximum is 40°C – Optimum temperature for parasite development is 27°C – Extremely high temperature is deleterious to vectors and parasites – Average daily temperature (ADT) is main meteorological indicator

23. Geographical factors Rainfall – Important for availability of breeding sites – In dry areas, rainfall may be followed by epidemics starting 3-4 weeks later – Too heavy rainfall may flush out breeding sites! – In dry areas, level of water in areas my rise due to rainfall far away, facilitating new transmission and cause epidemics – Rainfall should be monitored in terms of: Number of rainy days Total rainfall

24. Geographical factors Altitude – One of the most important indicators of malaria transmission – Altitude above sea level indirectly affects malaria through temperature – Mountainous areas may also have different rainfall and breeding place possibility – Altitude is an easy indicator to record (maps, GPS) and should be registered for any foci

25. Geographical factors Altitude – National malaria programs should determine at which altitude cut-off regular malaria transmission do not occur. For vivax: up to 3000 m (South Asia) For falciparum: up to 2500 m (near the equator in Africa) – This altitude decreases towards the poles E.g. 2000 m in Ethiopia or Yemen or 900/1200 m in Zimbabwe

26. Geographical factors Altitude, continue – Increasing temperature means that transmission may occur above the usual cut-off altitude line, causing epidemics among non-immune populations. – Moving from home to lower altitude areas for work means often increased malaria exposure – In some countries, hilly areas around 200-600 m have more malaria than adjoining lowlands because more suitable rainfall and temperatures and vectors may prefer streams (foothill malaria)

27. Geographical factors Relative humidity Amount of moisture in the air, expressed as a percentage; Relative humidity affects malaria transmission through its effect on the activity and survival of mosquitoes. Mosquitoes survive better under conditions of high humidity. They also become more active when humidity rises. Mosquitoes are more active and prefer feeding during the night – the relative humidity If the average monthly relative humidity is  60%, the life of the mosquito is so short that very little or no malaria transmission is possible.

28. Geographical factors Hydrology and water supply systems – Presence of water bodies are important indicators for malaria, depending on vector species – Important to consider for mapping of transmission foci Rice fields are important for transmission in parts of Central Asia, but not in the plains along eastern coast of India Swamps are associated with malaria transmission in southern Europe, but is not in sub-Saharan Africa.

29. Geographical factors Distribution of water bodies important for patterns of cases – If one big breeding site is located at some distance from the locality, then cases tend to be scattered in the area (since the infected mosquito is unlikely to return to the spot where it got infected – If there are many small breeding sites, mosquitoes more likely to return to the site of infection, causing more secondary cases close to the source of infection – Providing proper water supplies by pipes and improving wells is important to prevent malaria – Breeding may also be caused by human construction works, irrigation and other activities, depending on vectors.

30. Technical feasibility of malaria elimination by zoo-geographic region Zoogeographic Region Malaria species present and technical feasibility of elimination of malaria Palaearctic/ NearcticOnly P. vivax at present: elimination is feasible everywhere Neotropical/ Indo- malay P. vivax and P. f alciparum roughly at par: elimination is feasible in some areas,but very difficult in forested areas in much of Southeast Asia and South America and urban areas in the Indian sub-continent Australasian Elimination was achieved in Australia, but is very difficult in other areas with favourable ecological conditions and multiple, efficient vectors as in New Guinea. AfrotropicalP. falciparum overwhelmingly predominant: Elimination is not feasible with existing tools, except some islands, mountain and desert fringe areas, at the southern fringe and in some urban areas.

31. END

32. Exercise 2.1: Comparing natural history and epidemiology of Pf and Pv a)Analyze biological traits of falciparum and vivax that are responsible for major distinctions in their natural history and epidemiology. b)Which species is easier to eliminate in your area? Organize the information in tabular form.

33. Exercise 2.2: Factors determining transmission of malaria Identify the factors in the area you work that are most important in shaping the local epidemiology of malaria.

34. Exercise 2.3: Geography of malaria Examine the map (Fig 2.5). Compare the red line representing the limits of the area distribution of malaria during the time of its maximum extent with its present distribution. Questions for discussion Which species of malaria is responsible for the historic limit in the North? Enumerate geographical/ecological factors limiting the area of distribution of malaria. Why there are lacunae in the historic area of distribution (e.g. in Central Asia, East Africa and elsewhere). Why did the area of distribution of malaria contract to different degree in different continents? Compare the patterns of malaria in six zoogeographic regions. Or: describe the patterns of malaria encountered in the zoogeographic region, you know best.

35. Exercise 2.4: Examination of a simple transmission model Excel file “Exercise 2_4.xls” Play with the figures – identify the parameters that influence the vectorial capacity the strongest way.

36. Exercise 2.5: Prevalence, incidence and duration Describe the mathematical relationships between these 3 parameters. Give examples of how these relationships can be used in practical malaria control or elimination work.

37. Answers to exercise 2.1 Following traits are important: – Temperature dependence, geographical distribution – Total duration of infection – Incubation periods, duration of sporogony – Appearance of gametocytes – Susceptibility of different stages to different antimalarials, emergence of resistance – Clinical manifestations (severity of Pf versus Pv?)