Study Report on “Malaria – An Overview” Submitted by: V N Samiksha Grade 11 AA1 NBNS MALARIA - AN OVERVIEW Malaria is a life-threatening disease spread to humans by some types of mosquitoes. It is mostly found in tropical countries. It is preventable and curable. The infec on is caused by a parasite and does not spread from person to person. Symptoms can be mild or life-threatening. Mild symptoms are fever, chills and headache. Severe symptoms include fa gue, confusion, seizures, and difficulty breathing. Infants, children under 5 years, pregnant women, travellers and people with HIV or AIDS are at higher risk of severe infec on. Malaria can be prevented by avoiding mosquito bites and with medicines. Treatments can stop mild cases from ge ng worse. Malaria mostly spreads to people through the bites of some infected female Anopheles mosquitoes. Blood transfusion and contaminated needles may also transmit malaria. The first symptoms may be mild, similar to many febrile illnesses, and difficulty to recognize as malaria. Le untreated, P. falciparum malaria can progress to severe illness and death within 24 hours. There are 5 Plasmodium parasite species that cause malaria in humans and 2 of these species – P. falciparum and P. vivax – pose the greatest threat. P. falciparum is the deadliest malaria parasite and the most prevalent on the African con nent. P. vivax is the dominant malaria parasite in most countries outside of subSaharan Africa. The other malaria species which can infect humans are P. malariae, P. ovale and P. knowlesi I. SYMPTOMS: In the early stages, malaria symptoms are sometimes similar to those of many other infections caused by bacteria, viruses, or parasites. It can start with flu-like symptoms. Symptoms may include: • Fever. (This is the most common symptom) • Chills. • Headache. • Sweats. • Fa gue. • Nausea and vomi ng. • Body aches. • Generally feeling sick. People who get infected many mes may have the disease but have few or no symptoms. How bad malaria symptoms are can vary depending on your age, general health, and the kind of malaria parasite that you have. In rare cases, malaria can lead to impaired func on of the brain or spinal cord, seizures, or loss of consciousness. The most serious types of malaria infec on can be deadly. The me from the ini al malaria infec on un l symptoms appear (incuba on period) is usually 7 to 30 days. But with infec ons from some parasite species, signs of illness may not appear for many months a er exposure. For example, you may get a fever up to a year a er traveling to a country where malaria is found. The incuba on period may also be longer if you are taking medicine to prevent infec on. If you have some immunity due to previous infec ons, your symptoms may be less severe, or you may not have any symptoms. Symptoms may appear in cycles. The me between episodes of fever and other symptoms varies with the specific parasite infec on that you have. II. CAUSES: Malaria is caused by a single-celled parasite of the genus plasmodium. The parasite is transmi ed to humans most commonly through mosquito bites. Mosquito transmission cycle: Malaria transmission cycle: Malaria spreads when a mosquito becomes infected with the disease a er bi ng an infected person, and the infected mosquito then bites a noninfected person. The malaria parasites enter that person's bloodstream and travel to the liver. When the parasites mature, they leave the liver and infect red blood cells. • Uninfected mosquito. A mosquito becomes infected by feeding on a person who has malaria. • Transmission of parasite. If this mosquito bites you in the future, it can transmit malaria parasites to you. • In the liver. Once the parasites enter your body, they travel to your liver — where some types can lie dormant for as long as a year. • Into the bloodstream. When the parasites mature, they leave the liver and infect your red blood cells. This is when people typically develop malaria symptoms. • On to the next person. If an uninfected mosquito bites you at this point in the cycle, it will become infected with your malaria parasites and can spread them to the other people it bites. Other Modes of Transmission: Because the parasites that cause malaria affect red blood cells, people can also catch malaria from exposure to infected blood, including: • From mother to unborn child • Through blood transfusions • By sharing needles used to inject drugs III. DIAGNOSIS AND TEST: Malaria must be recognized promptly in order to treat the pa ent in me and to prevent further spread of infec on in the community via local mosquitoes. Malaria should be considered a poten al medical emergency and should be treated accordingly. Delay in diagnosis and treatment is a leading cause of death in malaria pa ents in the United States. Malaria can be suspected based on the pa ent’s travel history, symptoms, and the physical findings at examina on. However, for a defini ve diagnosis to be made, laboratory tests must demonstrate the malaria parasites or their components. Where malaria is not endemic any more (such as in the United States), healthcare providers may not be familiar with the disease. Clinicians seeing a malaria pa ent may forget to consider malaria among the poten al diagnoses and not order the needed diagnos c tests. Laboratorians may lack experience with malaria and fail to detect parasites when examining blood smears under the microscope. In some malaria-endemic areas, malaria transmission is so intense that a large propor on of the popula on is infected but not made ill by the parasites. Such carriers have developed just enough immunity to protect them from malarial illness but not from malarial infec on. In that situa on, finding malaria parasites in an ill person does not necessarily mean that the illness is caused by the parasites. CLINICAL DIAGNOSIS: Clinical diagnosis is based on the pa ent’s symptoms and on physical findings at examina on. The first symptoms of malaria (most o en fever, chills, sweats, headaches, muscle pains, nausea and vomi ng) are o en not specific and are also found in other diseases (such as the “flu” and common viral infec ons). Likewise, the physical findings are o en not specific (elevated temperature, perspira on, redness). In severe malaria (primarily caused by Plasmodium falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficul es) are more striking and may increase the index of suspicion for malaria. Clinical findings should always be confirmed by a laboratory test for malaria. In addi on to ordering the malaria specific diagnos c tests described below, the health-care provider should conduct an ini al workup and request a complete blood count and a rou ne chemistry panel. In the event that the person does have a posi ve malaria test, these addi onal tests will be useful in determining whether the pa ent has uncomplicated or severe manifesta ons of the malaria infec on. Specifically, these tests can detect severe anemia, hypoglycemia, renal failure, hyperbilirubinemia, and acid-base disturbances. MICROSCOPIC DIAGNOSIS: Malaria parasites can be iden fied by examining under the microscope a drop of the pa ent’s blood, spread out as a “blood smear” on a microscope slide. Prior to examina on, the specimen is stained (most o en with the Giemsa stain) to give the parasites a dis nc ve appearance. This technique remains the gold standard for laboratory confirma on of malaria. However, it depends on the quality of the reagents, of the microscope, and on the experience of the laboratorian. IV. TREATMENT: Ideally malaria treatment should not be ini ated un l the diagnosis has been established by laboratory tes ng. “Presump ve treatment”, i.e., without prior laboratory confirma on, should be reserved for extreme circumstances, such as strong clinical suspicion of severe disease in a se ng where prompt laboratory diagnosis is not available. Once the diagnosis of malaria has been made, appropriate an malarial treatment must be ini ated immediately. The Malaria Treatment TablesPdf can be used as a guide for treatment of malaria in the United States. The drug or drug combina on recommended for each specific situa on is listed, as well as the adult and pediatric doses. It is important to note that the base/salt conversions for an malarials are a recurrent source of confusion and can contribute to treatment errors. In the treatment table, where appropriate, the an malarial dose is expressed in base with the salt equivalency noted in parentheses. Treatment should be guided by the following four main factors: • Infec ng Plasmodium species; • Clinical status of the pa ent; • Expected drug suscep bility of the infec ng parasite as determined by the geographic area where the infec on was acquired; and • Previous use of an malarials, including those taken for malaria chemoprophylaxis. Infec ng Plasmodium species: Determina on of the infec ng Plasmodium species for treatment purposes is important for four main reasons. Firstly, Plasmodium falciparum and P. knowlesi infec ons can cause rapidly progressive severe illness or death, while the other species, P. vivax, P. ovale, and P. malariae, are less likely to cause severe disease. Secondly, P. vivax and P. ovale infec ons also require treatment for the hypnozoites, which remain dormant in the liver and can cause relapsing episodes. Thirdly, P. falciparum and P. vivax species have different drug resistance pa erns in different geographic regions of the world. Finally, for P. falciparum and P. knowlesi infec ons, the urgent ini a on of appropriate therapy is especially cri cal. Clinical status of the pa ent: Pa ents diagnosed with malaria are generally categorized as having either uncomplicated or severe malaria. Pa ents diagnosed with uncomplicated malaria can be effec vely treated with oral an malarials. However, pa ents who have one or more of the following clinical criteria—impaired consciousness/coma, severe anemia (hemoglobin <7 g/dL), acute kidney injury, acute respiratory distress syndrome, circulatory collapse/shock, disseminated intravascular coagula on, acidosis, jaundice (along with at least one other sign of severe malaria)—and/or percent parasitemia of ≥5% are considered to have manifesta ons of severe disease and should be treated aggressively with intravenous an malarial therapy. Drug suscep bility of the infec ng parasites: Knowledge of the geographic area where the infec on was acquired provides informa on on the likelihood of drug resistance of the infec ng parasite and enables the trea ng clinician to choose an appropriate drug or drug combina on. Informa on on malaria risk and parasite resistance can be found on the CDC malaria website. If the diagnosis of malaria is suspected and cannot be confirmed or if the diagnosis of malaria is confirmed but species determina on is not possible, an malarial treatment effec ve against chloroquine-resistant P. falciparum must be ini ated immediately and revisited once confirmatory results become available. Previous use of an malarials: It is important to consider if malaria occurred while an individual was taking a drug for malaria chemoprophylaxis. In this case, the treatment regimen should not include the drug or drug combina on used for prophylaxis unless no other op ons are available. A er ini a on of treatment, the pa ent’s clinical and parasitological status should be monitored. In infec ons with P. falciparum, P. knowlesi, or suspected chloroquine-resistant P. vivax, blood smears should be repeated every 12–24 hours to monitor parasitological response to treatment, i.e., decrease in parasite density. It is recommended to document a nega ve malaria smear a er treatment, but this could be done as an outpa ent depending on clinical and parasitological response and the judgement of the trea ng clinician. Note that gametocytes, the sexual stage of the parasite, are not targeted by most an malarials and should not be counted in assessing parasite density. TREATMENT FOR SEVERE MALARIA: Pa ents with any manifesta ons of severe malaria, e.g., impaired consciousness/coma, hemoglobin <7 g/dL, acute kidney injury, acute respiratory distress syndrome, circulatory collapse/shock, acidosis, jaundice (with other signs of severe malaria), disseminated intravascular coagula on, and/or parasite density of ≥5% should be treated promptly and aggressively with parenteral an malarial therapy regardless of the species of malaria seen on the blood smear. If severe malaria is strongly suspected but a laboratory diagnosis cannot be made at that me, blood should be collected for diagnos c tes ng to be done as soon as it becomes available and parenteral an malarial drugs should be started. Severe malaria can progress to a fatal outcome rapidly, so its treatment should be ini ated as soon as possible. Pa ents with severe malaria, regardless of infec ng species, should be treated with intravenous (IV) artesunate. Clinicians at hospitals where IV artesunate is not in stock should consider interim treatment with an effec ve oral an malarial while obtaining IV artesunate emergently from a commercial source. If the pa ent is unable to tolerate oral medica ons, clinicians will need to consider alterna ve ways to administer oral medica ons while awai ng IV artesunate. For example, for pa ents with nausea and vomi ng, an an -eme c preceding the an malarial may help, and, for comatose pa ents, a nasogastric tube can be considered. The preferred an malarial for interim oral treatment is artemetherlumefantrine (Coartem®) because of its fast onset of ac on. Other oral op ons include atovaquone-proguanil (Malarone™), quinine, and mefloquine. IV or oral clindamycin and tetracyclines, such as doxycycline, are not adequate for interim treatment. These drugs are slow-ac ng an malarials that would not take effect un l well a er 24 hours, and they are not effec ve an malarials for treatment of severe malaria when used alone. As for any malaria treatment, the interim regimen should not include the medica on used for chemoprophylaxis if possible. When IV artesunate arrives, immediately discon nue the oral medica on and start parenteral treatment. Each dose of IV artesunate is 2.4 mg/kg. A dose of IV artesunate should be given at 0, 12, and 24 hours. Note that the weight-based dosing applies to both adults and children. Previously, weight-based dosing was differen ated between children <20kg and those ≥20kg. Current dosing in small children <20kg is based on an unpublished FDA analysis modeling pharmacokine cs in this popula on using available data. Pa ents on treatment for severe malaria should have one set of blood smears (thick and thin smear) performed on admission and every 12–24 hours un l a nega ve result (no Plasmodium parasites are detected) is reported. A er the ini al course of IV artesunate is completed, if parasite density is ≤1% (assessed on a thin blood smear collected 4 hours a er the last dose of IV artesunate) and pa ent can tolerate oral treatment, a full treatment course with a follow-on regimen must be administered. Artemether-lumefantrine (Coartem®) is the preferred follow-on treatment but adequate alterna ves are atovaquoneproguanil (Malarone™), quinine plus doxycycline or clindamycin, or mefloquine. Because of a risk of severe neuropsychiatric adverse events at treatment doses, mefloquine should only be used if other op ons are not available. If the pa ent received oral treatment prior to receiving IV artesunate, the same medica on can be used as follow-on treatment, but a full regimen is required. As for any malaria treatment, the regimen selec on should not include the medica on used for chemoprophylaxis. If, a er the third IV artesunate dose, the pa ent’s parasite density is >1%, IV artesunate treatment should be con nued with the recommended dose once a day for a maximum of seven days un l parasite density is ≤1%. Doses given at 0, 12, and 24 hours count as one day, which means up to six addi onal days. Clinicians should proceed with full course of oral follow-on treatment as above as soon as parasite density ≤1% and the pa ent is able to tolerate oral medica ons. Clinicians can consider placement of nasogastric tube or use of an eme cs to facilitate administra on of oral treatment. For those pa ents with parasite density ≤1% but who s ll cannot tolerate oral medica ons a er comple ng IV artesunate treatment, clinicians can con nue IV artesunate, one dose daily not to exceed a total course of seven days. IV artesunate can be used in infants, children, and pregnant women. Given that severe malaria is especially life threatening for pregnant women and their fetuses, and the lack of other treatment op ons for severe malaria in the United States, the benefits of treatment with IV artesunate outweigh the risks and IV artesunate should not be withheld. The only formal contraindica on to IV artesunate treatment is known allergy to IV artemisinins. IV artesunate is well tolerated. While rare, delayed post-artemisinin hemoly c anemia has been noted in published case reports following treatment of severe malaria with IV artesunate. Persons with higher parasite density seem to have a higher likelihood of delayed hemoly c anemia a er treatment. All persons treated for severe malaria with IV artesunate should be monitored weekly for up to four weeks a er treatment ini a on for evidence of hemoly c anemia. Weekly laboratory evalua on should include hemoglobin concentra on, re culocyte count, haptoglobin, lactate dehydrogenase (LDH), and total bilirubin. Depending on the intensity of hemolysis and presence of anemia signs and symptoms, blood transfusion may be needed. Cases of delayed post-artemisnin hemoly c anemia in pa ents who received Artesunate for Injec onTM should be reported to MedWatchExternal, FDA’s Safety Informa on and Adverse Event Repor ng Program. Previously, CDC recommended exchange transfusion be considered for certain severely ill persons. However, exchange transfusion has not been proven beneficial in an adequately powered randomized controlled trial. In 2013, CDC conducted an analysis of cases of severe malaria treated with exchange transfusion and was unable to demonstrate a survival benefit of the procedure. Considering this evidence, CDC no longer recommends the use of exchange transfusion as an adjunct procedure for the treatment of severe malaria. V. PREVENTION AND CONTROL Malaria can o en be prevented by the use of an malarial drugs and use of protec on measures against mosquito bites. Medica ons When planning to travel to an area where malaria occurs, talk with your doctor well in advance of your departure. Drugs to prevent malaria can be prescribed for travelers to malarious areas, but travelers from different countries may receive different recommenda ons, reflec ng differences in treatment protocols as well as availability of medicines in different countries. Travelers visi ng only ci es or rural areas where there is no risk of malaria may not require preven ve drugs, but an exact i nerary is necessary to determine what degree of protec on may be needed. According to the Centers for Disease Control and Preven on (CDC), there are several medica ons recommended for preven on of malaria in travelers. Determining which medica on is best depends on several factors, such as your medical history and the amount of me before your scheduled departure. Strict adherence to the recommended doses and schedules of the an malarial drug selected is necessary for effec ve protec on. Protec on from mosquitoes: Be aware that you are s ll at risk for malaria even with the use of protec on. To avoid mosquito bites, the CDC recommends the following: • Apply insect repellent to exposed skin. The recommended repellent contains 20-35% percent N,N-Diethyl-meta-toluamide (DEET). • Wear long-sleeved clothing and long pants if you are outdoors at night. • Use a mosquito net over the bed if your bedroom is not air-condi oned or screened. For addi onal protec on, treat the mosquito net with the insec cide permethrin. • Spray an insec cide or repellent on clothing, as mosquitoes may bite through thin clothing. • Spray pyrethrin or a similar insec cide in your bedroom before going to bed.
