1. Chapter 22 Malaria: The Challenge of Scaling-Up Multiple Effective Tools

2. Learning Objectives Outline the life cycle of malaria and its effect on clinical disease Describe the global burden of malaria and factors that affect who bears that burden Detail the range of available effective malaria control measures Discuss some of the challenges that impede the scaling up of effective malaria control interventions and propose some possible solutions to these problems

3. History Considered one of the most oldest human diseases Causative agent was not discovered until the late 19 th century by researchers in India Transmission was common in Italy, Europe and Southeast U.S., but effective control efforts helped interrupt transmission in the middle of the 20 th century

4. Basic Science Malaria is caused by an infection from a single-celled, nucleated protozoan of the genus Plasmodium Four species of Plasmodium that cause human diseases exist: –P. vivax –P. falciparum (causes almost all diseases and death due to malaria) –P. ovale –P. malariae

5. Basic Science: Malaria Malaria goes through both asexual and sexual reproduction during its lifecycle Asexual reproduction occurs in the human while sexual reproduction in the gut of Anopheles spp. (only genus of mosquitoes to transmit human malaria) mosquito Only female mosquitoes of this genus bite to transmit the disease

6. Life Cycle of Malaria Female anopheline obtains “blood meal” to get heme, an iron-containing compound in hemoglobin (heme is needed for mosquito eggs to completely mature) Upon taking “blood meal,” parasitic sporozoites from the mosquito’s mouth enter the human bloodstream and travel to liver “Extra-erythrocytic cycle”: Sporozoites infect hepatocytes, mature, multiply, and get released back to the blood stream After leaving hepatocyte, parasites infect red blood cells and go through a 2 nd round of asexual reproduction known as the “erythrocytic cycle” Parasites mature, multiply, and eventually rupture red blood cells and go on to infect other red blood cells

7. Life Cycle of Malaria (Cont’d) Some of the parasites will not go through asexual reproduction, but instead differentiate into male or female gametocytes A bite from another Anopheles spp. Mosquito will take both male and female gametocytes from the human bloodstream Gametocytes transferred to the mosquito will mature into gametes and fuse into a zygote Zygote produces sporozoites, which travel to anophelines mouth and repeat the infective cycle

8. P. Vivax and P. Ovale Infection from both species of Plasmodium can cause some of the parasites that infect hepatocytes to become dormant after maturing Reactivation of these hypnozoites will complete their lifecycle and cause another parasitemia, a process known as relapse

9. Malaria Symptoms Symptoms of malaria include: fever, irritability, decreased appetite, and sometimes diarrhea Left untreated, a patient may become comatose, have seizures, develop severe anemia or respiratory distress Most typical patients affected with malaria are children in sub-Saharan Africa during their second year of life

10. Diagnosis Symptoms of malaria are indistinguishable from a number of common infections The nonspecific nature of these symptoms poses a significant challenge for clinicians who often confuse other causes of febrile illness with malaria The “gold standard” of diagnosis remains the examination under a microscope a drop of giemsa- stained, capillary blood, obtained from a finger prick A series of rapid diagnostic tests (RDTs) that use antibodies to specific parasite proteins have been developed and are increasingly being used to diagnose malaria in locations where malaria microscopy is not available

11. Severe Malaria Severe malaria may result in persons infected with P. falciparum Cerebral malaria and severe anemia are the most common manifestations Uncomplicated malaria often progresses to severe disease when care and treatment are delayed The clinical manifestations of malaria vary significantly depending on the intensity of transmission

12. Malaria Treatment Rapid detection and treatment is key to survival Once malaria has been diagnosed, the clinician must prescribe the correct treatment at an appropriate dose, based on the child’s age or weight Weak health systems, an uneducated population, cultural beliefs and norms, and the financial and opportunity costs of care and treatment pose significant barriers to the rapid diagnosis and treatment of children with malaria in sub-Saharan Africa

13. Public Health Perspective Sub-Saharan Africa bears more than 80% of the global burden of malaria transmission Malaria results in more than one million deaths each year, of which about 90% are among children less than five years in sub- Saharan Africa Malaria= leading cause of school and work absenteeism Household expenditures on malaria treatment and prevention can consume upwards of 30% of disposable income

14. Interventions 2 strategies involved in controlling malaria: –treating people infected with malaria –preventing people from getting infected Artemisinin-based combination therapies (ACTs) are the gold standard for treatment of uncomplicated malaria –rapidly clear infection even when the parasite is resistant to other drugs, such as chloroquine –Intravenous or intramuscular treatment needed for patients with severe malaria

15. Protective Factors Insecticide-treated bed nets (ITNs): –have been proven to reduce child mortality by an average of 20% Indoor residual spraying (IRS): –used very successfully to reduce and in some cases eliminate malaria burden, particularly outside of Africa and in the subtropical zones of southern Africa and the Horn of Africa Intermittent preventive treatment of pregnant women (IPTp) –Single dose of sulfadoxine-pyrimethamine given to pregnant women after quickening –Mainly effects developing fetus by reducing low birth weight

16. Burden and Barriers of Malaria Experiences in malaria control in sub- Saharan Africa over the last decade should serve to dispel the notion that simply developing effective control tools is sufficient to achieve public health impact Investments in malaria control have now shifted to taking existing tools and interventions to scale, rather than focusing on developing better tools

17. Further Challenges Supplies of ACTs have been limited by the available amount of harvestable Artemesia –price is 10 to 20-fold higher than previously used first- line treatments –weak public health infrastructures in most malaria- affected countries limit the ability of governments to deliver ACTs to rural areas Access to health services is limited by distance, staff shortages, the cost of services, and opportunity costs of time lost from work Barriers to the use of both ITNs and IRS are often related to the cost and logistics and infrastructure requirements ###