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. Overview of topics for the day Plenary 2: Dynamics of malaria transmission Selection of strategies and methods depending on malaria epidemiology Group exercises: All groups: 2.4 & 2.5

5. Biological aspects related to parasites and human hosts

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. Human host factors 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

12. Human host factors Some haemoglobinopathies (gene polymorphisms) offer some protection: – Haemoglobin S (causing sickle cell disease) – Thalassaemias (alpha-thalassimia) – Ovalocytosis (ovale shaped blood cells) – Glycose-6-phosphate dehydrogenase (G6PD) deficiency Most of these gene polymorphisms are linked to intensity of malaria transmission

13. Human host factors Acquired malaria immunity – Clinical immunity develops by age – Offers partial protection – Determines the clinical epidemiology in an area – Strongly dependent on malaria exposure (transmissision intensity) throughout life

14. Altitude and malaria prevalence in Tanzania

15. Malaria prevalence and incidence by altitude in Tanzania

16. Acquisition of antibodies to parasites by age and transmission level in Tanzania

17. Aspects related to vectors and eco-geographical factors

18. Malaria vector’s life-cycle

19. Geographical factors Temperature – The most important factor for mosquito and parasite development – Mosquitoes less sensitive to low temperatures than parasites – Lower threshold for P vivax sporozoite development is 16 C, for P falciparum it is XX C – Average daily temperature (ADT) is main meteorological indicator

20. 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! – Rainfall should be monitored in terms of: Number of rainy days Total rainfall – In dry areas, level of water in areas my rise due to rainfall far away, facilitating new transmission and cause epidemics

21. 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 – National malaria programs should determine at which altitude cut-off regular malaria transmission do not occur. For vivax: up to 3000 m For falciparum: up to 2500 m (near the equator in Africa) – 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

22. Geographical factors Distribution of water bodies important for patterns of cases – If one man breeding site is located at some distance, 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.

23. 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.

24. Zoo-geographic regions and malaria

25. 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.

26. Prevalence and incidence of malaria

27. 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.

28. 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.

29. Relationship between prevalence and vectorial capacity Y = prevalence (proportion of positives in the human population) 1- y = proportion of negatives in the human population C = vectorial capacity (per time unit) R = recovery rate (per time unit) (t) Means “at time t” (t + 1) means “at time t + 1 time unit” Ronald Ross’s formula: Y(t+1) = y(t) + y(t) C {1-y(t)} – r y(t) The prevalence at time t (t +1) is equal to prevalence at time t, plus the new cases occuring in the interval and minus the old cases recovering in the interval.

30. Relationship between prevalence, vectorial capacity and basic reproductive rate Y = prevalence r = recovery C = vectorial capacity Ro = basic reproductive y = 1 – r/C or y = 1 – 1/Ro

31. Relationship between vectorial capacity, basic reproductive ratio, entomological inoculation rate (BR/day), and parasite prevalence

32. Relationships among measures of intensity

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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?)