presentation about malaria

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When to see a doctor, risk factors, complications.

Malaria is a disease caused by a parasite. The parasite is spread to humans through the bites of infected mosquitoes. People who have malaria usually feel very sick with a high fever and shaking chills.

While the disease is uncommon in temperate climates, malaria is still common in tropical and subtropical countries. Each year nearly 290 million people are infected with malaria, and more than 400,000 people die of the disease.

To reduce malaria infections, world health programs distribute preventive drugs and insecticide-treated bed nets to protect people from mosquito bites. The World Health Organization has recommended a malaria vaccine for use in children who live in countries with high numbers of malaria cases.

Protective clothing, bed nets and insecticides can protect you while traveling. You also can take preventive medicine before, during and after a trip to a high-risk area. Many malaria parasites have developed resistance to common drugs used to treat the disease.

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Signs and symptoms of malaria may include:

• General feeling of discomfort
• Nausea and vomiting
• Abdominal pain
• Muscle or joint pain
• Rapid breathing
• Rapid heart rate

Some people who have malaria experience cycles of malaria "attacks." An attack usually starts with shivering and chills, followed by a high fever, followed by sweating and a return to normal temperature.

Malaria signs and symptoms typically begin within a few weeks after being bitten by an infected mosquito. However, some types of malaria parasites can lie dormant in your body for up to a year.

Talk to your doctor if you experience a fever while living in or after traveling to a high-risk malaria region. If you have severe symptoms, seek emergency medical attention.

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Malaria is caused by a single-celled parasite of the genus plasmodium. The parasite is transmitted to humans most commonly through mosquito bites.

Mosquito transmission cycle

• Malaria transmission cycle

Malaria spreads when a mosquito becomes infected with the disease after biting 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

The greatest risk factor for developing malaria is to live in or to visit areas where the disease is common. These include the tropical and subtropical regions of:

• Sub-Saharan Africa
• South and Southeast Asia
• Pacific Islands
• Central America and northern South America

The degree of risk depends on local malaria control, seasonal changes in malaria rates and the precautions you take to prevent mosquito bites.

Risks of more-severe disease

People at increased risk of serious disease include:

• Young children and infants
• Older adults
• Travelers coming from areas with no malaria
• Pregnant women and their unborn children

In many countries with high malaria rates, the problem is worsened by lack of access to preventive measures, medical care and information.

Immunity can wane

Residents of a malaria region may be exposed to the disease enough to acquire a partial immunity, which can lessen the severity of malaria symptoms. However, this partial immunity can disappear if you move to a place where you're no longer frequently exposed to the parasite.

Malaria can be fatal, particularly when caused by the plasmodium species common in Africa. The World Health Organization estimates that about 94% of all malaria deaths occur in Africa — most commonly in children under the age of 5.

Malaria deaths are usually related to one or more serious complications, including:

• Cerebral malaria. If parasite-filled blood cells block small blood vessels to your brain (cerebral malaria), swelling of your brain or brain damage may occur. Cerebral malaria may cause seizures and coma.
• Breathing problems. Accumulated fluid in your lungs (pulmonary edema) can make it difficult to breathe.
• Organ failure. Malaria can damage the kidneys or liver or cause the spleen to rupture. Any of these conditions can be life-threatening.
• Anemia. Malaria may result in not having enough red blood cells for an adequate supply of oxygen to your body's tissues (anemia).
• Low blood sugar. Severe forms of malaria can cause low blood sugar (hypoglycemia), as can quinine — a common medication used to combat malaria. Very low blood sugar can result in coma or death.

Malaria may recur

Some varieties of the malaria parasite, which typically cause milder forms of the disease, can persist for years and cause relapses.

If you live in or are traveling to an area where malaria is common, take steps to avoid mosquito bites. Mosquitoes are most active between dusk and dawn. To protect yourself from mosquito bites, you should:

• Cover your skin. Wear pants and long-sleeved shirts. Tuck in your shirt, and tuck pant legs into socks.
• Apply insect repellent to skin. Use an insect repellent registered with the Environmental Protection Agency on any exposed skin. These include repellents that contain DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE), para-menthane-3,8-diol (PMD) or 2-undecanone. Do not use a spray directly on your face. Do not use products with oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) on children under age 3.
• Apply repellent to clothing. Sprays containing permethrin are safe to apply to clothing.
• Sleep under a net. Bed nets, particularly those treated with insecticides, such as permethrin, help prevent mosquito bites while you are sleeping.

Preventive medicine

If you'll be traveling to a location where malaria is common, talk to your doctor a few months ahead of time about whether you should take drugs before, during and after your trip to help protect you from malaria parasites.

In general, the drugs taken to prevent malaria are the same drugs used to treat the disease. What drug you take depends on where and how long you are traveling and your own health.

The World Health Organization has recommended a malaria vaccine for use in children who live in countries with high numbers of malaria cases.

Researchers are continuing to develop and study malaria vaccines to prevent infection.

Feb 09, 2023

• AskMayoExpert. Malaria. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2018.
• Jameson JL, et al., eds. Malaria. In: Harrison's Principles of Internal Medicine. 20th ed. New York, N.Y.: The McGraw-Hill Companies; 2018. https://accessmedicine.mhmedical.com. Accessed Oct. 9, 2018.
• Tintinalli JE, et al., eds. Malaria. In: Tintinalli's Emergency Medicine: A Comprehensive Study Guide. 8th ed. New York, N.Y.: McGraw-Hill Education; 2016. http://www.accessmedicine.mhmedical.com. Accessed Oct. 9, 2018.
• Malaria. Merck Manual Professional Version. http://www.merckmanuals.com/professional/infectious-diseases/extraintestinal-protozoa/malaria. Accessed Oct. 9, 2018.
• Malaria. Centers for Disease Control and Prevention. http://wwwnc.cdc.gov/travel/diseases/malaria. Accessed Nov. 6, 2015.
• Breman JG. Clinical manifestations of malaria in nonpregnant adults and children. https://www.uptodate.com/contents/search. Accessed Oct. 9, 2018.
• Daily J. Treatment of uncomplicated falciparum malaria in nonpregnant adults and children. https://www.uptodate.com/contents/search. Accessed Oct. 9, 2018.
• Key points: World malaria report 2017. World Health Organization. https://www.who.int/malaria/media/world-malaria-report-2017/en/. Accessed Oct. 9, 2018.
• Malaria. World Health Organization. https://www.who.int/malaria/en/. Accessed Oct. 9, 2018.
• Mutebi JP, et al. Protection against mosquitoes, ticks, & other arthropods. In: CDC Yellow Book 2018: Health Information for International Travelers. https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/protection-against-mosquitoes-ticks-other-arthropods. Accessed Oct. 27, 2018.
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Malaria is a mosquito-borne infectious disease caused by the bite of female Anopheles mosquitoes, which spread infectious Plasmodium parasites into a host. Traditional malaria symptoms include fever, chills, headache, muscle aches and fatigue. Nausea, vomiting and diarrhea also are common. Untreated malaria can lead to severe disease, kidney failure and death. Neurological complications can occur in severe cases, most commonly in young children.

Most malaria cases occur during rainy periods in endemic regions. The World Health Organization estimates that in 2020 , globally about 240 million people had malaria and about 627,000 of them died. A disproportionate burden of malarial disease occurs in Sub-Saharan Africa, where children under age 5 account for about 80% of all malaria deaths.

A vaccine to prevent malaria is available; however, its variable efficacy underscores the need for new interventions that offer high-level protection against disease. Malaria is a research priority at NIAID, which is the lead U.S. government agency investigating the disease. Scientists are researching improved vaccines and preventive interventions as well as mosquito control techniques, easy-to-use diagnostics, and improved therapies as parasites continue to develop resistance to currently available antimalarials.

News Releases

• Experimental NIH Malaria Monoclonal Antibody Protective in Malian Children April 26, 2024
• NIAID Marks World Malaria Day April 25, 2023
• Monoclonal Antibody Prevents Malaria Infection in African Adults October 31, 2022

See all Malaria related news releases

NIAID Now Blog

• The Hidden Link Between Malaria and Lupus July 5, 2024
• NIAID Raises Awareness to Malaria-like Diseases in W. Africa June 6, 2024
• NIAID Commemorates World Malaria Day 2024 April 25, 2024

See all Malaria related NIAID Now posts

Related Public Health and Government Information

To learn about risk factors for malaria and current prevention and treatment strategies visit the MedlinePlus malaria site .

Malaria 101 for the Healthcare Provider

COURSE NUMBER: WB4335

PROGRAM DESCRIPTION: The Malaria 101 for the Healthcare Provider course is a web-based training course designed to teach epidemiologists and healthcare professionals about the epidemiology, prevention, diagnosis, and treatment of malaria. Lesson 1 provides some background on malaria and discusses the epidemiology of malaria. Lesson 2 discusses the prevention of malaria in travelers. Lesson 3 reviews the diagnosis and treatment of malaria. After the lessons, three clinical scenarios will be presented. Content is derived from actual knowledge and practices.

At the conclusion of the session, the participant will be able to:

• Describe malaria disease epidemiology, lifecycle of Plasmodium , and risk factors for malaria.
• Describe how to manage a patient during the pre-travel consultation to prevent malaria using CDC guidelines for malaria chemoprophylaxis.
• Describe how to diagnose and treat malaria using current CDC recommendations.
• Describe how the healthcare professionals should work as a team with laboratorians to diagnose malaria.

FACULTY/CREDENTIAL

Kathrine R. Tan, MD, MPH, Centers for Disease Control and Prevention, Malaria Branch

ORIGINATION DATE: May 18, 2020

RENEWAL DATE: May 18, 2022

EXPIRATION DATE: May 18, 2024

URL   : https://www.cdc.gov/parasites/cme/malaria_101/index.html

HARDWARE/SOFTWARE: Computer hardware; Internet connection; Web browser

MATERIALS: None

TARGET AUDIENCE: Physicians, Registered Nurses, Nurse Practitioners

PREREQUISITES: Background in clinical care and knowledge

FORMAT: This activity is Web based

CONTACT INFORMATION: Kathrine Tan, MD, MPH; Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria, Malaria Branch

Phone: 404-718-4701

ACCREDITATION STATEMENTS

In support of improving patient care, this activity has been planned and implemented by Centers for Disease Control and Prevention. The Centers for Disease Control and Prevention is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the American Academy of Physicians Assistants (AAPA), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team

CME:  The Centers for Disease Control and Prevention designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

CNE:  The Centers for Disease Control and Prevention designates this activity for 1.0 nursing contact hours.

CEU:  The Centers for Disease Control and Prevention is authorized by IACET to offer 0.1 CEU’s for this program.

In compliance with continuing education requirements, all presenters must disclose any financial or other associations with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters as well as any use of unlabeled product(s) or product(s) under investigational use.

CDC, our planners, content experts, and their spouses/partners wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters. Planners have reviewed content to ensure there is no bias.

Content will not include any discussion of the unlabeled use of a product or a product under investigational use.

CDC did not accept commercial support for this continuing education activity.

INSTRUCTIONS FOR OBTAINING CONTINUING EDUCATION (CE)

In order to receive continuing education (CE) for WB4335: Malaria 101 for the Healthcare Provider please visit  TCEO and follow these  9 Simple Steps before May 18, 2024.

• Complete the activity
• Complete the course evaluation at www.cdc.gov/GetCE
• Pass the posttest at 70% at www.cdc.gov/GetCE

FEES: No fees are charged for CDC’s CE activities.

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Malaria Clinical Presentation

• Author: William N Bennett, V, MD; Chief Editor: Michael Stuart Bronze, MD  more...
• Sections Malaria
• Practice Essentials
• Epidemiology
• Pathophysiology
• Patient Education
• Physical Examination
• Approach Considerations
• Blood Smears
• Alternatives to Blood Smear Testing
• Histologic Findings
• Pharmacologic Therapy
• Inpatient Care
• Deterrence and Prevention
• Consultations
• Medication Summary
• Antimalarials
• Questions & Answers
• Media Gallery

In patients with suspected malaria, obtaining a history of recent or remote travel to an endemic area is critical. Asking explicitly if they traveled to a tropical area at any time in their life may enhance recall. Maintain a high index of suspicion for malaria in any patient exhibiting any malarial symptoms and having a history of travel to endemic areas.

Also determine the patient's immune status, age, and pregnancy status; allergies or other medical conditions that they may have; and medications that they may be using.

Patients with malaria typically become symptomatic a few weeks after infection, although the host's previous exposure or immunity to malaria affects the symptomatology and incubation period. In addition, each Plasmodium species has a typical incubation period. Importantly, virtually all patients with malaria present with headache. Clinical symptoms include the following:

Shaking chills

Patients experience a paroxysm of fever, shaking chills, and sweats (every 48 or 72 h, depending on species). The classic paroxysm begins with a period of shivering and chills, which lasts for approximately 1-2 hours and is followed by a high fever. Finally, the patient experiences excessive diaphoresis, and the body temperature of the patient drops to normal or below normal.

Many patients, particularly early in infection, do not present the classic paroxysm but may have several small fever spikes a day. Indeed, the periodicity of fever associated with each species (ie, 48 h for P falciparum, P vivax, and P ovale [or tertian fever] ; 72 h for P malariae [or quartan fever]) is not apparent during initial infection because of multiple broods emerging in the bloodstream. In addition, the periodicity often is not observed in P falciparum infections. Patients with long-standing, synchronous infections are more likely to present with classic fever patterns. In general, however, the occurrence of periodicity of fever is not a reliable clue to the diagnosis of malaria.

Less common malarial symptoms include the following:

Anorexia and lethargy

Nausea and vomiting

Notably, infection with P vivax, particularly in temperate areas of India, may cause symptoms up to 6-12 months after the host leaves the endemic area. Patients infected with P vivax or P ovale may relapse after longer periods, because of the hypnozoite stage in the liver.

P malariae does not have a hypnozoite stage, but patients infected with P malariae may have a prolonged, asymptomatic erythrocytic infection that becomes symptomatic years after leaving the endemic area.

Tertian and quartan fevers are due to the cyclic lysis of red blood cells that occurs as trophozoites complete their cycle in erythrocytes every 2 or 3 days, respectively. P malariae causes quartan fever; P vivax and P ovale cause the benign form of tertian fever; and P falciparum causes the malignant form. The cyclic pattern of fever is very rare.

Travelers to forested areas of Southeast Asia and South America have become infected by Plasmodium knowlesi , a dangerous species normally found only in long-tailed and pigtail macaque monkeys ( Macaca fascicularis and M nemestrina , respectively). This species can cause severe illness and death in humans, but, under the microscope, the parasite looks similar to the more benign P malariae and sometimes has been misdiagnosed.

Because P malariae infection typically is relatively mild, Plasmodium knowlesi infection should be suspected in persons residing or traveling in the above geographic areas who are severely ill and have microscopic evidence of P malariae infection. Diagnosis may be confirmed via polymerase chain reaction (PCR) assay test methods.

Most patients with malaria have no specific physical findings, but splenomegaly may be present. Symptoms of malarial infection are nonspecific and may manifest as a flulike illness with fever, headache, malaise, fatigue, and muscle aches. Some patients with malaria present with diarrhea and other gastrointestinal (GI) symptoms. Immune individuals may be completely asymptomatic or may present with mild anemia. Nonimmune patients may quickly become very ill.

Severe malaria primarily involves P falciparum infection, although death due to splenic rupture has been reported in patients with non– P falciparum malaria. Severe malaria manifests as cerebral malaria, severe anemia, respiratory symptoms, and renal failure.

In children, malaria has a shorter course, often rapidly progressing to severe malaria. Children are more likely to present with hypoglycemia, seizures, severe anemia, and sudden death, but they are much less likely to develop renal failure, pulmonary edema, or jaundice.

Cerebral malaria

This feature almost always is caused by P falciparum infection. Coma may occur; coma usually can be distinguished from a postictal state secondary to generalized seizure if the patient does not regain consciousness after 30 minutes. When evaluating comatose patients with malaria, hypoglycemia and CNS infections should be excluded.

Severe anemia

The anemia associated with malaria is multifactorial and usually is associated with P falciparum infection. In nonimmune patients, anemia may be secondary to erythrocyte infection and a loss of infected RBCs. In addition, uninfected RBCs are inappropriately cleared, and bone marrow suppression may be involved.

Renal failure

Renal failure is a rare complication of malarial infection. Infected erythrocytes adhere to the microvasculature in the renal cortex, often resulting in oliguric renal failure. Renal failure typically is reversible, although supportive dialysis often is needed until kidney function recovers. In rare cases, chronic P malariae infection results in nephrotic syndrome.

Respiratory symptoms

Patients with malaria may develop metabolic acidosis and associated respiratory distress, and pulmonary edema can occur. Signs of malarial hyperpneic syndrome include alar flaring, chest retraction (intercostals or subcostal), use of accessory muscles for respiration, or abnormally deep breathing.

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• Malarial merozoites in the peripheral blood. Note that several of the merozoites have penetrated the erythrocyte membrane and entered the cell.
• This micrograph illustrates the trophozoite form, or immature-ring form, of the malarial parasite within peripheral erythrocytes. Red blood cells infected with trophozoites do not produce sequestrins and, therefore, are able to pass through the spleen.
• An erythrocyte filled with merozoites, which soon will rupture the cell and attempt to infect other red blood cells. Notice the darkened central portion of the cell; this is hemozoin, or malaria pigment, which is a paracrystalline precipitate formed when heme polymerase reacts with the potentially toxic heme stored within the erythrocyte. When treated with chloroquine, the enzyme heme polymerase is inhibited, leading to the heme-induced demise of non–chloroquine-resistant merozoites.
• A mature schizont within an erythrocyte. These red blood cells (RBCs) are sequestered in the spleen when malaria proteins, called sequestrins, on the RBC surface bind to endothelial cells within that organ. Sequestrins are only on the surfaces of erythrocytes that contain the schizont form of the parasite.
• Malaria life cycle. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Proportion of 2021 Global Malaria Burden. Gray area accounts for the remaining estimated 4.4% of worldwide malaria burden. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• Confirmed P falciparum or P vivax Cases Per Country 2021. The map accounts for the total of the cases per country where either species were confirmed as the primary infection. The map does not include confirmed “mixed infections.” Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• North American Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• South American Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• African Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• Asian and Oceanic Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• South Pacific Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• Global P falciparum to P vivax Case Ratios 2021. Gray indicates that there were either no data available or there were zero endemic cases. Red indicates higher proportion of P vivax cases, whereas blue indicates higher proportion of P falciparum cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
• Thin blood smear showing the ring forms of P falciparum that look like headphones with double chromatin dots. Note how P falciparum is seen infecting erythrocytes of all ages – a trait that can be utilized by the microscopist by noting the similar size of infected erythrocytes to other surrounding uninfected erythrocytes. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Thick blood smear depicting the banana shaped gametocyte of P falciparum. Multiple ring-form trophozoite precursors are also visible in the background. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Thin blood smear of the ring forms of P vivax. Note that P vivax typically has a single chromatin dot vs the two chromatin dots in P falciparum. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• The diagnostic form of P vivax is the amoeboid trophozoite form where the cytoplasm has finger-like projections (pseudopods) without a typical round/oval structure. These pseudopods are unique to P vivax. Numerous small pink-red dots are also seen in both P vivax and P ovale; these are known as caveola-vesicle complexes (CVCs or Schüffner’s dots) and are composed of numerous flask-like indentations on infected reticulocytes membrane skeleton associated with tube-like vesicles. CVCs are thought to play a role in nutrient uptake or release of metabolites from parasite-infected erythrocytes. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Thin smear of P ovale in ring stage. Note that typically there is a single chromatin dot, larger cells are infected indicative of reticulocytes, and multiple ring forms may be present intracellularly. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Thin smear of P ovale trophozoite. Note that this species is difficult to differentiate from P vivax as it contains CVCs (Schüffner’s dots) and infects reticulocytes; a notable unique characteristic of P ovale is the presence of fimbriae on the reticulocyte membrane, which are even more likely to be seen in gametocyte infected red blood cells. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Thin blood smear of “band form” trophozoite of P malariae. Note that the infected erythrocyte is smaller than surrounding cells, indicating that P malariae infects older erythrocytes. As the trophozoite matures, the cytoplasm elongates and dark pigment granules of hemozoin are visualized toward the periphery. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Thin blood smear of P knowlesi trophozoites. An immature ring form is seen on the right next to the mature band form trophozoite on the left. Note the small size of the infected red blood cells and how the band form is similar in appearance to P malariae. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
• Table 1. Histologic Variations Among Plasmodium Species

Contributor Information and Disclosures

William N Bennett, V, MD Staff Physician, Infectious Disease Service, Chair, Antimicrobial Stewardship, Department of Medicine, Wright-Patterson Medical Center; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences School of Medicine William N Bennett, V, MD is a member of the following medical societies: American College of Physicians , American Medical Association , Infectious Diseases Society of America Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha , American College of Physicians , American Medical Association , Association of Professors of Medicine , Infectious Diseases Society of America , Oklahoma State Medical Association , Southern Society for Clinical Investigation Disclosure: Nothing to disclose.

Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha , Infectious Diseases Society of America , Infectious Diseases Society of Ohio Disclosure: Received research grant from: Regeneron.

Joseph R Masci, MD, FACP, FCCP Professor of Medicine, Professor of Preventive Medicine, Icahn School of Medicine at Mount Sinai; Director of Medicine, Elmhurst Hospital Center Joseph R Masci, MD, FACP, FCCP is a member of the following medical societies: American Academy of HIV Medicine , American Association for the Advancement of Science , American College of Chest Physicians , American College of Physicians , American Medical Association , American Society for Microbiology , American Society of Tropical Medicine and Hygiene , Association of Professors of Medicine , Association of Program Directors in Internal Medicine , Association of Specialty Professors , Federation of American Scientists , HIV Medicine Association , Infectious Diseases Society of America , International AIDS Society , International Association of Providers of AIDS Care , International Society for Infectious Diseases , New York Academy of Medicine , New York Academy of Sciences , Physicians for Human Rights , Physicians for Social Responsibility , Royal Society of Medicine Disclosure: Nothing to disclose.

Emilio V Perez-Jorge, MD, FACP Staff Physician, Division of Infectious Diseases, Lexington Medical Center Emilio V Perez-Jorge, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine , Infectious Diseases Society of America , Society for Healthcare Epidemiology of America , South Carolina Infectious Diseases Society Disclosure: Nothing to disclose.

Ryan Q Simon, MD Infectious Disease Specialist, Wright State Physicians, Wright State University School of Medicine Disclosure: Nothing to disclose.

The views expressed are those of the author and do not necessarily reflect the official policy or position of the Department of the Air Force, the Defense Health Agency, the Department of Defense, or the U.S. Government.

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Malaria. Dr R.N.Roy Associate Professor Department of Community Medicine. Malaria. A febrile illness caused by asexual plasmodium parasite transmitted by infected female anopheles mosquito Plasmodium genus of parasite infect RBC in human Occasional infections of monkey with P. knowlesi ,.

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Malaria Dr R.N.Roy Associate Professor Department of Community Medicine

Malaria • A febrile illness caused by asexual plasmodium parasite transmitted by infected female anopheles mosquito • Plasmodium genus of parasite infect RBC in human • Occasional infections of monkey with P. knowlesi,

Magnitude of problems • About half the world’s population (3.3 billion) in live in areas(109 countries & territories) endemic for malaria • Estimated 247 million malaria cases in 2006, of which 91% were due to Pf • Around 40% of the global population at risk of malaria resides in SEA Region

AFRO: African Region AMRO: Region of the Americas SEARO: South-East Asia Region WPRO: Western Pacific region EMRO: Eastern Mediterranean

Malaria Burden in India • During Pre- control era(1953) Annual Incidence was 75 mil / (22% of population) and 0.8mil death/ yr • During 2008 incidence was 1.53 million & half of these were Pf & 1055 deaths reported • About 88% of malaria cases & 97% of deaths reported from Northeastern (NE) States, Chhattisgarh, Jharkhand, MP,  Orissa,  AP  Maharashtra Gujarat  Rajasthan, W B Karnataka

Problem in India Major epidemiological types in India • Tribal malaria • Urban malaria • Malaria in project area • Border malaria Serious problem in NE states • Perennial malaria transmission • Predominance of falciparum • Drug resistance

EPIDEMIOLOGY OF MALARIA :Agent factors • Four species : (1)P. Vivax – causes BTM (2) P.Falciparum-causes MTM (3) P.Malariae-causes quartan malaria (4) P.Ovale (not in India)

Host factors • Age: Parasitemia is low during infancy due to maternal antibody • During first few weeks show resistance to Pf infection due to fetal Hb • Pregnancy: increase risk in pregnancy :anemia , LBW delivery.

Epidemiology Reservoir of infection: Human • (Exception- chimpanzee in Africa may carry P. malariae) Conditions for a successful reservoir: • Must harbor viable & mature gametocyte of both sexes in sufficient density

Route of transmission • By bite of infected female anopheles mosquito • Blood transfusion, needle stick injury, sharing needles, organ transplantation • Congenital malaria- mother to foetus

Genetic factors • HbF and Thalassaemia protect against malaria • Sickle cell trait (AS Hb) have higher immunity against P. falciparum • Person with ‘Duffy negative ‘ RBC are resistant to vivax infection

Environmental conditions • Urbanization, • Industrialization and construction projects • Consequent migration, • Deficient water and solid waste management • Indiscriminate disposal of articles (tyres, containers, junk materials, cups, etc

LIFE CYCLE OF PLASMODIUMMOSQUITO • Mosquito is definitive host (sexual multiplication takes place) • Mosquito picks up gametocytes from infected person  in gut converted into gamete, zygote, ookinets, oocist, sporozoites finally sporozoites reach the salivary gland (takes about 8- 25 days)

Other factors: • Poor socioeconomic and housing conditions, • population mobility • some human habits like • sleeping out of door • Nomadism • refusal of spray activities etc contribute to causation of malaria .

LIFE CYCLE OF PLASMODIUM IN HUMAN • Man -intermediate host (undergo asexual reprodn.) • Hepatic phase : Mosquito bite  inoculate sporozoites - reaches hepatocyte by 30mts  multiply to form hepatic schizonts  mature to daughter merozoites and released in sinusoids • Erythrocytic phase: Merozoites reach blood stream invade RBC in RBC multiply & develops schzoints  RBC ruptures 48 or 72 hourly releasing cytokinin, TNF pirogens  • Some merozoites convert & develop into gametocyte

Pathophysiology • Incubation period: infective mosquito bite to onset of sign and symptoms = 9-30 days • IP depend upon species of parasite, host immune status, infecting doses and use of antimalarial treatment • Only erythrocytic parasitic stage causes clinical disease • Relapse: after primary attack with out subsequent mosquito bite. • Recrudescence: Reappearance of clinical malaria or M.P in blood, which remain dormant in RBC.

VECTOR Only female Anopheles mosquito carry parasite and infect human

Vector factors for transmission • Vector density • Man biting rate & frequency of blood meal • Time and place of man - mosquito contact • Man - cattle ratio • Flight range • Vector’s susceptibility to infection

IMPORTANT VECTORS OF MALARIA IN INDIA

Critical density for transmission

ENTOMOLOGICAL INDICES  • Vector density (Man Hour Hand Captures ): Nos anopheles collected per man hr. catch • Mosquito infection rate • Man biting rate • Human Blood Index-indicate anthrophilism • Av. nos of larva per dip

ENTOMOLOGICAL INDICES …. PER MAN HOUR DENSITY: No. of mosquitoes collected =--- ---------------------------------------X100 No. of man hours spent in search • High vector density indicates high potential for transmission SPOROZOITE RATE (%): No. of females positive for sporozoites = --------------------------------------------------x 100 Nos. dissected

Suspected case of malaria A patient with fever but without any other obvious cause of fever • Cough and other signs of respiratory infection • Running nose and other signs of cold • Pelvic inflammation indicated by severe low backache, vaginal discharge , urinary symptoms • Skin rash suggestive of eruptive illness • Burning micturition • Skin infections e.g. boils, abscess, infected wounds • Painful swelling of joints • Diarrhoea • Ear discharge

Lab diagnosis: All suspected fever cases be investigated • Blood smear examination/Microscopy • Rapid diagnostic test (RDT)

How & when to use RDT / Smear Exam Where microscopy result is available within 24 hrs.  (Only microscopy done)  Treatment based on slide-result Where microscopy result is not available within 24hrs (Pf RDT + Slide taken) RDT +Ve  Treat Pf  Discard slide RDT –Ve  Slide microscopy  Treatment

EPIDEMIOLOGICAL SURVEILLANCE

ASSESSMENT OF PROBLEM (MALARIOMETRIC MEASUREMENT) • EPIDEMIOLOGICAL SURVEY • Proportional case rate • Spleen rate • Infant parasite rate • Children parasite rate-(% of 2-10 yr children ē MP in blood) • Annual Parasite Incidence (API) • Annual Blood Examination Rate (ABER) • Slide Positivity Rate (SPR) • Slide falciparum Rate (SFR) • Annual falciparum rate (AFR)

Child Spleen Rate(CSR) • % of 2-10 yr children ē enlarged spleen Significance : 25-40%= Endemic >40%=Hyper endemic

Infant parasite rate(IPR) Most sensitive index for recent transmission of malaria. # Positive for MP IPR= -----------------------------------------X100 # Blood slide examined from infants

Annual Blood Examination Rate (ABER) Nos of smears examined & (RDTs +Ve) in a Yr. ABER = ----------------------------------------------------------X100 Total Population under surveillance • Index of operational efficiency of surveillance • ABER should be equal to fever rate in the locality • ABER should be > 10% of population • Monthly Blood Examination Rate should be >1% of population during the transmission season

Annual Parasite Incidence (API) # of +Ve smears & +Ve RDTs in a year API=------------------------------------------------ X 1000 # Population under surveillance • Used to stratify malarious areas • Disease burden in community

Slide Positivity Rate : % of slide positive for parasite Slide Falciparum Rate : % of slide positive for Pf SFR pinpoints areas of Pf preponderance for prioritizing control measures P.falciparum percentage (Pf %)

Surveillance in malaria • Passive Case Detection- Collection of blood slides in Clinic/ institution & treatment. • Active Case Detection- system of detecting malaria cases (blood slide collection ) by HW through domiciliary visits • Mass blood survey- Examination of blood from all persons in a community (during epidemiological investigation around positive cases)

DRUG SCHEDULE FOR MALARIA

Age-specific drug schedules

Chemoprophylaxis Short term chemoprophylaxis (up to 6 wks) (e.g. travelers from non-malarious areas) • Doxycycline 100 mg daily in adults or (1.5mg / kg OD)above in children , started 2 days before reaching endemic area continued for 4 weeks after leaving • Contraindication : Pregnancy & children < 8 years. Chemoprophylaxis for longer stay (> 6 wks) (e.g Military & paramilitary troops in malarious areas duty ) • Mefloquine 250 mg weekly for adults • Mefloquine 5 mg/kg for children • Contraindication of Mefloquine : H/O convulsions, & neuropsychiatric problems

MALARIACONTROL ACTIVITIES & PROGRAMME IN INDIA

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Continued .. Continued ..

NATIONAL ANTI-MALARIA PROGRAMME1999 Under NVBDCP Objectives: • Prevention of deaths due to malaria • Prevention of morbidity due to malaria • Maintenance of ongoing socioeconomic development

Strategies • Surveillance and case management • Case detection (passive and active) • Early diagnosis and treatment • Integrated Vector Management (IVM) • Environmental Management • Stratification of the problem • Area with API<2 • Area with API ≥2 • Community Participation & BCC • Monitoring and Evaluation of the programme

Integrated Vector Management (IVM) • Use of a range of biological, chemical and physical interventions of proven efficacy, separately or in combination, in order to implement cost-effective control and reduce reliance on any single intervention

IVM Includes: • Rotation and & safe use of insecticides including management of resistance • Indoor Residual Spray (IRS) • Insecticide Treated bed Nets (Tins) / Long Lasting Insecticidal Nets (LLINs) • Antilarval measures including source reduction

Vector control methods • Methods of reducing human-vector contact: • Mosquito nets & insecticide treated nets (Synthetic pyrethroid) • House protection with screening of windows, doors etc. • Use of repellents • Anti adult measures: • Indoor residual spraying with DDT/ • Space spraying of insecticides • Anti larval measures: • Larviciding • Biological Control • Source reduction by environmental management

Anti adult measures • Indoor residual spraying with -Organo chlorine compound : DDT - OP-compounds : Malathion, Fenitrothion -Carbamate :Propoxur -Synthetic pyrethroids: Deltamethrin • Space spray: Pyrithrum • Out door space spray :Malathion, Pyrethrum

Anti larval measures • Larviciding with MLO, Temephos ( abate), Fenthion etc. • Biological Control • Use of larvivorous fish (Gambusia affinis & Poecilia reticulata) • Use of biocides: bacillus thuringiensis • Source reduction by environmental management • Drainage /Filling /flushing/change of salinity

Community Perticipation & BCC • Process of learning that empowers people to take rational and informed decisions through appropriate knowledge • Clear messages, communicated through different, credible channels are most likely to bring about change. Ignorance, prejudices must be replaced by knowledge Awareness campaign programme-observe malaria week • Legislative measures: • Model civic bye-laws:

‘High risk areas’ • Recorded deaths due to malaria • Doubling of SPR during last 3 yrs provided the SPR in 2nd / 3rd yr reaches ≥ 4% • Average SPR of the last 3 yrs ≥ 5% • P.falciparum proportion ≥ 30% provided SPR is ≥ 3% during any of the last 3 yrs • Any area with focus of CQ resistant P.f. cases • Aggregation of labour in project area & new settlements in endemic/receptive & vulnerable areas

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MALARIA. ‘MAL’ – bad ; ‘aria’- air Causative organism- Plasmodium falciparum. P. ovale, P. vivax, P. malariae Transmission- bite of female anopheles mosquito. PLASMODIUM LIFE CYCLE. An infected female anopheles mosquito bites and injects parasites ( Sporozoites ) into the blood

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Behind the malaria vaccines: A 40-year quest against one of humanity’s biggest killers

By Andrew Joseph

Aug. 1, 2024

M alaria is one of our most ancient foes — and one of the wiliest.

Caused by parasites that certain mosquitoes spread through their bites, malaria overwhelms us, establishing an infection before we can put up a fight. It can go on to destroy red blood cells, batter organs, and even damage the brain.

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There are untold millions of cases, the vast majority of them in sub-Saharan Africa. Each year, hundreds of thousands of people die from the condition — some 80% of whom are children under 5. For decades, pharmaceutical companies and academic researchers have struggled to devise vaccines that could confer protection, fueling doubts whether such a product was even possible.

And yet, scientists have now succeeded. Twice over.

Related: 4 takeaways from STAT’s story on the development of malaria vaccines

Earlier this year, routine immunization programs began rolling out a vaccine called RTS,S, reaching children in places including Cameroon, Sierra Leone, and Liberia. Last month, another shot, called R21, was introduced in South Sudan and Côte d’Ivoire, with more countries preparing campaigns for their youngest — and most vulnerable — citizens. RTS,S, also called Mosquirix, was developed by GSK and partners, while scientists at the University of Oxford built R21, which, based on the number of available doses alone, promises to be even more impactful.

Health officials have projected that the shots could save the lives of tens of thousands of kids. In some countries, malaria accounts for 25% of all childhood deaths.

The vaccines — the first to target any human parasite — represent a feat of both scientific grit and fundraising ingenuity. Researchers took on a sophisticated biological adversary that eludes our immune systems’ schemes to identify and dispatch it. They also had to find ways to nudge forward products that would never result in blockbuster sales, a reality that sapped much of the biopharma industry’s interest.

Related: Rollout of a new malaria vaccine kicks off in Africa

“We’re very fortunate, and when I say we I mean our generation, to be present for the last mile of this, and to see these vaccines be introduced,” said Eusebio Macete, a Mozambican researcher who two decades ago helped run an early trial of RTS,S. “And to see that one of the major killers in Africa could now have another tool to save lives, that’s amazing.”

The vaccines are by no means perfect, and given their limited effectiveness and durability, they are not the kinds of interventions expected to eliminate malaria in Africa. Rolling them out also poses huge challenges. The vaccines are given in four doses, starting around 5 months of age and ending over a year later with a booster, at intervals that don’t match when other childhood vaccines are administered. That means health workers must wrangle families to clinics or deliver vaccines to them in some of the globe’s most remote reaches.

The vaccines’ shortcomings have led some experts to argue against spending too much of the world’s resources on them instead of expanding existing measures, like insecticide-treated bed nets, mosquito control, and chemoprevention — that is, giving kids preventative drugs during peak transmission periods. As it is, only some 50% of kids sleep under bed nets in certain areas.

“We believe in the vaccine,” said Scott Filler, the head of malaria at the Global Fund, which helped support RTS,S. But, he said, prioritizing other strategies might offer more bang for the world’s buck. “Maybe we want to spend the world’s money first on these tried-and-true things, lay the foundation, and then start to deploy the vaccine in particular areas that have ongoing transmission, where kids continue to die,” he added.

Other experts are more sanguine, even as they agree that the other interventions need to be maintained. They also argue that now is a particularly important time to take action. Progress against malaria has stalled, and after dropping to 576,000 in 2019, deaths caused by the disease have since surpassed 600,000 a year. Mosquitoes are becoming increasingly resistant to insecticides. The parasite that causes malaria is itself becoming increasingly resistant to medications. Climate change and migrating mosquito species are reshaping transmission zones.

Related: Second-generation mosquito nets prevented 13 million malaria cases in large pilot programs

“We’re at a crossroads,” Mary Hamel, the World Health Organization’s lead for malaria vaccines, told STAT. “We’re seeing cases go up in some places, and we have donors that maybe are not wanting to continue giving as much as they used to give. We’re in a period, I think, that’s precarious.”

This history of the malaria vaccines, an odyssey that stretches across decades and continents, is necessarily an abridged one. But it captures the achievement of how two vaccines reached the finish line within months of each other after more than 40 years of work. It’s one that relied on researchers willing to take on a mission that colleagues saw as quixotic, local investigators who pioneered running trials in their communities, and ultimately, the thousands of parents and children who volunteered for the studies — those who had most closely felt the ravages of malaria and enlisted in the global effort to neutralize one of the leading threats to children.

A sk experts for a good starting point to understand the history of the malaria vaccines, and one name comes up most often: Ruth Nussenzweig. Her work not only demonstrated the theoretical foundation of such a vaccine, but also helped uncover the bullseye that the shots target.

Twice an émigré, Ruth Sonntag was born in Vienna in 1928 into a Jewish family with physician parents. They escaped the Nazi occupation in 1938, eventually settling in Brazil. Her father urged her to become a nurse, thinking she would encounter less antisemitism in that role than as a doctor, but she saw medical school as a path to her real interest: research. It was while she was training at the University of São Paulo that she met another student, Victor Nussenzweig. “I was more interested in doing leftist politics than science, but I started dating Ruth and she convinced me that research would benefit people much more than politics,” Victor once told Science .

By then married, the couple headed to New York University for what they thought would be a brief fellowship for Victor but that turned into an academic home. A 1964 coup in Brazil brought in a period of strict military rule, upending their return.

While in Brazil, the Nussenzweigs had studied a parasitic infection called Chagas disease. By the time she got to NYU, Ruth had her eye on another parasite. Her aim was “always the same thing: develop a vaccine for malaria,” she said in an oral history for the university.

Designing a vaccine is not about attacking a bug directly. It’s about priming a person’s immune system to recognize and fight off a pathogen for itself.

But at the time the Nussenzweigs got to work, it wasn’t clear that that was possible with malaria. After all, there wasn’t a strong natural immune response that a vaccine could replicate. People did accrue some protection to malaria, but only after repeated infections, and it didn’t last all that long. It explained why people could be infected multiple times every year, and while older children and adults might build up enough armor to avoid getting seriously ill, young kids remained vulnerable to severe outcomes.

Nussenzweig, however, doubted the conventional wisdom. “The dogma at the time was that malaria doesn’t induce any immune response,” she said. “This was incorrect, and I knew it.”

She also proved it. In 1967, she and her colleagues showed they could protect mice from malaria by immunizing them with parasites that they had weakened with radiation. These parasites couldn’t cause disease, but they did, Nussenzweig found, elicit an immune response that staved off a future infection. That meant that, maybe, a vaccine could do the same.

Instead of using a whole bug to build a vaccine, which would be far more complicated, scientists often rely on an antigen, or a protein from the pathogen that provokes an immune response. The idea is that those generated immune fighters, namely antibodies, can then swarm invaders when they see the antigen in the form of an actual parasite.

But scientists faced a formidable challenge in identifying a suitable antigen from the malaria parasite, which is a much more complex intruder than the bacteria and viruses other vaccines target. Take the coronavirus that causes Covid-19. It has about a dozen genes, making the virus’s spike protein, which it uses to hack into cells, an obvious antigen to design vaccines around.

The malaria parasite has some 5,000 genes. Not only that, it has infected people for so many generations — our history dates back millions of years, to before we were even Homo sapiens — that it has evolved with us, essentially learning how to throw off our immune system’s defenses.

It gets more dizzying from there. Malaria doesn’t even look the same throughout its time in our bodies. When a female Anopheles mosquito bites us (males are vegetarian), she injects a bit of saliva to ensure the blood doesn’t clot as she takes her meal, which she needs to lay eggs. If she’s infected with the parasites, a few dozen of them will slip with the saliva into our skin. At that point, the parasites are squiggly critters called sporozoites.

Within about 30 minutes, the sporozoites are whisked via the bloodstream to the liver, where they multiply into the thousands over several days before busting out and invading red blood cells, triggering the classic symptoms of fever and chills and causing anemia.

Related: Malaria parasite may trigger human odor to lure mosquitoes

With each infection phase, the parasite shapeshifts, with different genes activated and proteins expressed, becoming almost like a new creature. Any successful vaccine then would not only need the right bullseye, but be able to mount an immune response in the right place in the body, at the right stage of the infection.

Again, Nussenzweig came through. Once her earlier work showed that inducing immunity was possible, her team needed to identify which part of the parasite those elicited antibodies were recognizing — what could be a possible antigen. And together with her husband and other colleagues, she later zeroed in on a protein that surrounded the sporozoite. It became known, in the most scientifically sober way, as the circumsporozoite protein, or CSP. (Other research teams contributed key discoveries around this time.)

That finding became the blueprint for the vaccines. The question was, could you design a shot based on CSP as your antigen, building up an army of anti-CSP antibodies? And could those antibodies then block any injected parasites from making it to the liver, preventing an infection from taking hold?

Ruth Nussenzweig died in 2018 at 89, and Victor, now in his mid-90s, is so hard of hearing that an interview was not feasible, said their son Michel Nussenzweig, himself a scientist at Rockefeller University. But it seemed the couple knew their work might one day result in a breakthrough.

“It is therefore conceivable that a vaccine containing only sporozoite antigens would completely protect a portion of the exposed population,” they wrote in one review .

They authored that paper in 1984. Another 40 years of work remained.

W hen Ripley Ballou’s fever struck, he first thought that he was reacting to the home-brewed beer he had tried at a friend’s party. But as he got sicker, he realized what was actually happening: He had given himself malaria. It also meant his experimental vaccine hadn’t worked.

Ballou, who goes by Rip, was a physician at the Walter Reed Army Institute of Research helping lead a team whose task was to turn the antigen the Nussenzweigs had identified into an actual product. The Army, keen for a vaccine that could protect soldiers, selected a company called Smith, Kline & French as its development partner, striking a collaboration with the GSK precursor in 1984. Their particular target became Plasmodium falciparum — the deadliest form of the malaria parasite, and the one that dominates in sub-Saharan Africa.

When the researchers had their first candidate ready to test, Ballou rallied colleagues to join him in rolling up their sleeves for a challenge study, in which volunteers receive an experimental vaccination, then expose themselves to a pathogen to assess if it worked. (In these tests, the military used a malaria strain they knew was treatable.)

Once Ballou and his comrades got the vaccine, it was mosquito munch time. They pressed gauze-covered cups containing infected mosquitoes against their arms, offering up a blood buffet. Days later, Ballou got sick. So did four others. One person, however, did not .

It was by no means a good result, but it was an important one. “That basically showed us it could be done, that it was possible” for a vaccine to block an infection, Ballou said. But for it to be workable, they would need to show much higher rates of protection.

The team spent the next decade refining the vaccine. There are different ways to present an antigen to the immune system, so they tinkered and toiled in hopes of landing on an approach that could stimulate a response so robust as to be protective. They combined the CSP antigen with genes from other pathogens, and turned to proteins used in other vaccines, and made chains of bits of proteins, all in hopes of whipping up a phalanx of antibodies.

And it just wasn’t working.

“We probably did eight or nine challenge trials where nearly everyone had malaria,” Ballou recalled. They even ran out of friends they could rely on at Walter Reed for the studies, so had to recruit in the local community.

Part of the problem may have been that their experimental vaccines weren’t conjuring up the sky-high antibody levels needed to fend off malaria — much higher than the levels needed to protect against many bacteria and viruses, given that the parasites are so good at evading our defenses.

The antibodies also have to be quite the hunters. To stave off an infection, the immune guardians have to clear out all the injected sporozoites before they make it to the liver. While some scientists say that the more sporozoites that reach the liver, the more likely someone is to get sick, others stress that if even one infiltrates a liver cell and starts replicating, it can turn into a full-blown infection. Imagine a teenager cleaning up from the party he threw with his parents out of town — overlooking even one cup could land him in trouble.

“To say it was a discouraging period does not quite capture the feeling,” Ballou, who is now at the infectious diseases nonprofit IAVI, wrote in 2009 about the failed attempts.

But more than 3,000 miles away, a scientist had an idea.

B efore Joe Cohen became a researcher, his jobs included working in a fabric store’s stockroom and analyzing stool samples at a hospital lab.

Cohen was born in Egypt and, when he moved with his mother to France in 1962 after finishing high school, he halted his studies to support his family. He eventually made it to university, where he focused on agricultural engineering. But really, it was the nascent molecular biology field that caught his eye.

He then joined other relatives who had moved to the United States, but he didn’t know how to apply to doctorate programs. He simply showed up at nearby Brooklyn College one day and introduced himself. He was admitted.

When Cohen was wrapping up his training, he struggled to find an academic job that suited him. But he spotted an ad — he can’t remember if it was in Nature or Science — from Smith, Kline & French in Belgium looking for a molecular biologist with experience in yeast genetics. “That essentially described me,” he said.

It wasn’t academia, but he admired the group’s innovative work on a hepatitis B vaccine in development at the time. So he moved his wife, infant daughter, and aging mutt named Clebs to Belgium in 1984, joining the team right as it was wrapping up its hepatitis B work. It was his first non-trainee job in science, at age 40.

A few years later, Cohen’s bosses asked him to take the lead on the malaria project, which the company was transferring from its U.S. labs to Belgium. Other colleagues had already said no to the assignment, Cohen recalled, thinking it was a lost cause.

Cohen didn’t have much experience with parasites, but the scientific challenge appealed to him. So did the impact he might have if the team succeeded. And in taking on the project, he drew inspiration from the hepatitis B vaccine.

GSK scientists had created that shot by engineering yeast cells to express one of the virus’s proteins, which they had identified could act as an antigen. When researchers would crack open the cells, the proteins would spontaneously glom onto each other, forming what’s called a virus-like particle. The vaccine was made of schools of those particles.

What if, Cohen thought, you could just add CSP — the malaria antigen — into the mix?

Cohen grinded away in the lab, into the night, on weekends, on holidays. By linking genes from the hepatitis B virus and the malaria parasite, he was able to express what are known as fusion proteins in the yeast cells — meaning they had antigens from both pathogens — that he still got to ball together into virus-like particles. They looked like blobs encircled by a coating of hepatitis B antigens, and then, jutting out from the surface, like cloves studding an orange, were the malaria antigens.

Related: WHO recommends second malaria vaccine, hoping to address supply issues

The theory was that by presenting the body with a virus-like particle — which resembled a virus in both size and shape — the immune system was going to generate a heartier response than it would when presented with just a bit of the protein itself. After all, the immune system knows what to do when it sees something that looks like a virus.

As it happened, other GSK scientists were building up another branch of vaccine research. They were designing a line of adjuvants, which boost the power of a vaccine by deepening the immune response. Researchers started testing the malaria shot in combination with a number of the adjuvants.

Then, finally, came the challenge study of the vaccine with an adjuvant called AS02.

Ballou was in his kitchen when he got the call: Six of seven volunteers had been protected , as the scientists reported in the New England Journal of Medicine in early 1997.

The vaccine, dubbed RTS,S, had worked. It was time to test it in the field.

O ne of the team’s early calls was to a researcher named Brian Greenwood. Greenwood had already proven the power of insecticide-treated bed nets, but he believed in vaccines, even as other experts dismissed them. Greenwood once even made a bet with another senior scientist — whom he declined to name — about whether the world would ever see a malaria vaccine.

Greenwood, who is British, was running a research site in the Gambia. He had previously worked on a study in Tanzania of a vaccine candidate developed by a Colombian scientist named Manuel Patarroyo, and while that shot ultimately fizzled out, the experience left Greenwood with a lesson. “It taught us how to do a malaria vaccine trial,” he said.

Greenwood and colleagues started recruiting a cohort of men to evaluate RTS,S, with some receiving the experimental shot and some getting a rabies vaccine as the control. At the time, the researchers thought a highly effective vaccine could still be used for adults. Plus, it’s considered unethical to test a vaccine in children before its safety is established in older volunteers.

The results , published in 2001, were a bit of a bust. The shots showed some protection, but it wasn’t very strong and waned quickly. As Ballou wrote in a review , “the vaccine was still clearly not sufficiently efficacious to support its further development as a stand-alone vaccine for travelers or the military.”

But the adult trial furthered the researchers’ belief that the shot had pediatric potential. They reasoned that if the vaccine reduced the risk of malaria to an extent in adults, it was likely to be even more protective in kids, who tend to mount stronger immune responses to vaccines.

The prospect of healthy returns had evaporated, however. A company could never charge much for a product whose only takers would be children in some of the world’s poorest countries. Wealthy tourists and the Defense Department they were not.

Related: GSK CEO on pharma giant’s new direction: ‘We’re in the business of preventing and treating disease’

GSK brass allowed the team to continue with the program, but there was a catch: The company would no longer fund the project without others’ support.

It was a key inflection point, one that underscores how commercial realities shape the programs drugmakers pursue or scuttle. It’s not just the programs companies back, either. With potentially lucrative products, companies start planning future trials and scaling manufacturing at risk even before the prior step in the development gauntlet is complete, all to expedite the process. With neglected disease products, it’s likely that no one is going to put up the money for the next study until it’s clear that it’s going to happen, a factor that dragged out the timeframe of the malaria vaccines.

Public health experts credit GSK for sticking with the malaria program at all, particularly given its daunting nature, and say it’s unclear whether other companies would have done the same. Thomas Breuer, GSK’s chief global health officer, said in an interview with STAT that the company has covered the “lion’s share” of funding for RTS,S throughout its development, at more than $700 million.

While GSK has faced recent criticism for how it’s handled the development of a tuberculosis vaccine , Breuer said that the drugmaker sees a need to partner on these products, not just to share the financial risk, but because the company doesn’t have all the relevant expertise itself. He stressed that GSK continues to invest in global health.

“We have a social responsibility, and this was not just true for the malaria vaccine,” he said, citing the company’s development work in other neglected diseases. But, he added, “Even GSK, who is committed in the long run, cannot fund all the activities.”

Luckily, another funding model was emerging around that time. The Bill & Melinda Gates Foundation, established in 2000, had started backing a nonprofit called PATH and its Malaria Vaccine Initiative. And in 2001, GSK and PATH struck a partnership to push RTS,S forward. In total, said Helen Jamet, a malaria official at the Gates Foundation, the organization put $200 million into RTS,S, primarily through PATH’s work.

With that partnership in place, researchers moved to test the vaccine in kids. For the site, they selected Centro de Investigação em Saúde in Manhiça, Mozambique, which Spanish experts had helped start, but, crucially, was staffed largely by local providers. The team set out to recruit parents in the community to enroll their children in the study, setting aside time to talk with them about the vaccine and address their questions.

It helped that parents were well aware of the risks posed by malaria. Children would get sick two, five, eight times a year. Kids would miss school, and parents would miss work to care for them. At hospitals, where even now a third of consultations in some regions are tied to malaria, bags of blood being readied for transfusions would line the walls. Clinics would be so full that three children would share a bed, all pale and flopped over and breathing shallowly.

Laurinda Carlos Balate was one of the moms who said yes to the study. Some of her friends didn’t understand why, and told her the experimental shot might be dangerous. But she liked the idea of combating malaria, and she trusted the clinic’s staff.

“I’m quite happy, because the vaccine was a success,” she said recently over Zoom.

Her daughter, Loyde Carina Nhabanga, who was just a baby when her mother enrolled her in the study, now has a 7-month-old of her own, whom she said she is planning on getting vaccinated when the shots become available. “It’s going to help us fight against malaria,” she said.

Overall, the Phase 2 trial, run in 2,000 children, showed the vaccine was 30% effective at preventing malaria, and 58% effective at protecting against severe malaria, according to findings published in 2004. It was the first sign that the vaccine could generate a protective response in kids in high-transmission areas.

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Other studies of RTS,S showed similar outcomes, building evidence that was promising enough to move the shot into a pivotal Phase 3 trial. (During this series of trials, the researchers switched the adjuvant from AS02 to one called AS01 that prompted stronger immune responses. AS01 is also used in GSK’s RSV and shingles vaccines.)

It was around this time that researchers in England came up with their own vaccine candidate.

A drian Hill came to malaria vaccines through a circuitous route. Hill, now the director of the University of Oxford’s Jenner Institute, had trained as a geneticist, studying how different genetic variants that had evolved in certain communities made people less vulnerable to malaria. (If the legacy of malaria is written in our history books — it may have killed Alexander the Great, Genghis Khan, and a couple of popes — it is also imprinted in our DNA.)

It was when Hill was studying one of those variants in the Gambia in the 1980s that he got an up-close look at the parasite’s toll. Children were packed into a clinic, arriving so sick they desperately needed blood transfusions. So he pivoted.

“That kind of converted me from thinking, we’ve got to really understand susceptibility to malaria, to thinking, what’s going on with vaccines?” he said in an interview at his Oxford office.

Starting in the 1990s, Hill and his colleagues threw a number of strategies at malaria. They tried DNA-based vaccines and viral vector vaccines — like the one Oxford researchers would later develop with AstraZeneca against Covid-19 — and different combinations of those different kinds of vaccines, without much success.

But they also thought of updating RTS,S. After all, by the early 2010s, some two decades of advances in research methods — including in expressing proteins in yeast — had accrued since the early days of the GSK shot. “Making the vaccine 25 years later helped us,” Hill said.

The issue with RTS,S, at least as far as Hill and his colleagues believed, was that there wasn’t enough malaria antigen on the particle versus hepatitis B antigen. They hypothesized that if they could engineer both a greater amount and higher density of the former, the particle would elicit a more powerful anti-malaria immune response, with more antibodies produced that were even sharper at targeting sporozoites. They essentially wanted to stud more cloves onto the orange.

The task of figuring it out fell to a graduate student named Katharine Collins. The potential trip-up was that if the Oxford researchers increased the amount of malaria antigen in their recipe, the proteins wouldn’t self-assemble into a virus-like particle, which was crucial to generating an actionable immune response. Whether or not proteins arrange into that kind of particle depends on a delicate balance of chemical charges, with the right bonds needed to form for it to be a stable molecule.

It took some trial and error, but by refining the process, Collins made it happen. “I would express the protein in the yeast, bust them open, do a really simple purification, and then go and have a look under an electron microscope,” said Collins, who now works at the charity Open Philanthropy. “And we saw particles. It was like, ‘wow.’”

For their adjuvant, the Oxford team landed on one called Matrix-M from Novavax, which is now used in that company’s Covid jab. The shot became known as R21.

But like RTS,S, R21 ran into funding issues. When it came time to manufacture doses for human trials, Hill turned to Oxford’s own production site, which was cheaper than a contract manufacturer. But with limited resources and know-how, the team struggled to make the vaccine at scale. From the promising lab experiments to having doses for a challenge trial, three years would pass.

W hen data from the Phase 3 trial of RTS,S arrived , the reaction was lukewarm.

The trial, which ran from 2009 to 2014, enrolled nearly 9,000 children from 5 months to 17 months of age in seven countries, places where malaria circulated year-round as well as places with seasonal transmission. While the initial protection appeared strong, the efficacy dropped to between 30% and 50%. Adjectives like “modest” and “moderate” were thrown around.

Some experts excavated a rosier view. Given the scope of the disease, they argued, preventing even a third of malaria cases would have major repercussions for health systems, economies, and families.

“Because of the sheer number of cases of malaria — there are hundreds of millions of cases of malaria every year — what we saw was that in some of the areas where the intensity of malaria transmission was higher, where children got more malaria, we saw over 6,000 cases of malaria prevented for every thousand children vaccinated,” said Ashley Birkett, a longtime PATH official.

But another issue arose — potential safety signals with the vaccine. One was that there were more cases of meningitis, an inflammation around the brain and spinal cord, among children who received RTS,S than those who got the control shots.

It was up to regulators to weigh in. The European Medicines Agency gave the vaccine a positive review in 2015, but it was a WHO recommendation that mattered most. The global agency needs to give its stamp of approval if groups like UNICEF and Gavi, an international organization known as the Vaccine Alliance, which help purchase immunizations and deliver them to low-income countries, are going to add a shot to the portfolio of products they provide.

The WHO’s advisers weren’t overly enthusiastic. Based on the data, the vaccine didn’t seem like a game-changing intervention. With the potential safety issue, they worried not only that introducing the vaccine might lead to meningitis cases, but that moving too quickly could turn people against other immunizations.

The context of the moment also shaped experts’ thinking, those involved at the time recalled in recent interviews. The world had been making steady progress against malaria, with cases cut by 27% from 2000 to 2015. No one foresaw that tide reversing.

“There was not a sense that we desperately needed a vaccine, let alone a vaccine with modest efficacy,” said Pedro Alonso, who directed WHO’s malaria program at the time.

Related: The WHO’s chief scientist on Covid-19 vaccines, patent battles, and speeding up access in Africa

Instead of recommending the vaccine, the WHO in 2016 decided to push forward with a pilot program, which would involve deploying millions of doses to children in three countries. The move was seen as a compromise — the agency was not spurning the vaccine, but it wasn’t endorsing its wide rollout either. The program would also provide the chance for experts to assess the feasibility of using the vaccine outside a trial. Would people get their children to a clinic for four doses? Would they give up other safeguards against malaria?

But if the pilot made sense as a way of shoring up the vaccine’s evidence, it created a new challenge, one that some experts worried could jeopardize the shot. As Birkett said, “Nobody was anticipating the pilot program. Nobody had the money ready to go.”

The Gates Foundation by that point had pulled back from putting more funding into RTS,S, but the WHO scrounged $70 million for the pilot from sources including Unitaid, Gavi, and the Global Fund, with doses donated by GSK. But the time needed to fundraise and plan, including getting the three selected countries — Ghana, Malawi, and Kenya — on board, meant shots didn’t start being administered until 2019, three years after the pilot was decided on.

Once underway, it became clear that the meningitis issue was a statistical fluke from the trial — that there was no real safety issue. And in 2021, the WHO endorsed RTS,S as the world’s first malaria vaccine .

Ultimately, the pilot program demonstrated not only that RTS,S could be reliably rolled out, but that even with its modest efficacy, it could have sweeping impacts. It didn’t lead to drops in other vaccinations. Families kept up with other anti-malaria interventions. And it cut childhood mortality broadly by more than 10%, a sign, perhaps, of how malaria infections leave children vulnerable to other illnesses. Places where the shots were deployed saw malaria hospitalizations cut by a fifth.

“These numbers are huge,” said Kwaku Poku Asante, the director of Ghana’s Kintampo Health Research Centre and an investigator in the pilot program. “If you sit in a district hospital, where every child has malaria, and all of a sudden you’re seeing a reduction by one-fifth, that is huge.”

Some experts maintain the pilot program was necessary — that a wide-scale rollout would not have succeeded had WHO recommended RTS,S in 2016. But in hindsight, others are more conflicted. They find themselves wrestling with the decision, wondering if the vaccine had been put into use then, instead of years later, how many more thousands of children might have been saved?

“This has haunted me for a number of years. The question is, did we do the right thing, or did we not?” said Alonso, now at the University of Barcelona. “I do often think of the costs.”

A fter a successful challenge trial and safety tests, it was time for the Oxford team to try R21 in the field. They scraped together funding from sources including the Wellcome Trust and the European and Developing Countries Clinical Trials Partnership, and in 2019 launched a Phase 2 trial in children from 5 months to 17 months of age in Nanoro, Burkina Faso.

The results surpassed their hopes. The shot showed about 75% efficacy.

“We were expecting in the best case scenario 60% efficacy or something like that,” said Halidou Tinto, who leads the clinical research unit in Nanoro. “And then we were at almost 80%. This was a big surprise, but a very nice surprise.”

For the Phase 3 study, instead of the Oxford team having to pitch companies to fund the research, a partner came to them. One day in 2017, a man named Umesh Shaligram showed up at Hill’s office. Shaligram was a top scientist at the Serum Institute of India, the world’s largest vaccine manufacturer. The institute had heard about Oxford’s promising data, he told Hill, and was curious to learn more.

With the resulting pact between Oxford and Serum, not only did Serum start manufacturing R21, it even funded the Phase 3 trial, a study of 5,000 children in four countries run in 2021 and 2022. The vaccine showed about 70% efficacy.

Last October, the WHO recommended the vaccine .

A few months ago, a package arrived for Brian Greenwood, the old malaria hand who had helped run the early RTS,S trial in the Gambia. It contained six “very nice” bottles of red wine. The other expert with whom Greenwood had made a bet about the feasibility of a malaria vaccine was making good after losing that decades-old wager.

The bottles’ arrival coincided with the rollout of RTS,S in Cameroon in January, the first time a malaria shot was deployed in a routine immunization program. More countries will launch their own vaccination campaigns in the coming months.

Experts debate whether one vaccine is superior to the other. Many favor R21, pointing to its updated design and the higher efficacy scores it reached in trials. Others counter that the differences in the trials — including the timing of the doses relative to peak transmission periods — render comparisons impossible. The WHO has taken to saying that both shots can reduce malaria cases by about 75% when given before peak transmission periods and combined with other interventions.

“The important thing now is to get the vaccines used,” said Greenwood, who worked on studies of both shots and is now at the London School of Hygiene & Tropical Medicine.

R21 does have some inarguable advantages. While manufacturing is still being scaled up , thanks to the partnership with the Serum Institute, 100 million doses could be produced a year, at a cost of $2 to $4 per dose. GSK, meanwhile, is only producing 18 million RTS,S doses from 2023 to 2025, at an approximate cost of $10 per dose, and then committing 15 million doses a year from 2026 to 2028. The company is transferring the vaccine to Bharat Biotech, another large Indian manufacturer, which should result in more doses at a lower cost, but it’s expected that the Bharat facility won’t be supplying RTS,S until 2028.

The vaccines are important in other ways. They established how to run clinical studies, built up trial infrastructures, and gave regulators experience evaluating malaria shots. Even with the financial challenges it faced, R21, with its strong data profile, comparatively breezed through its studies and regulatory reviews, winning approval faster than many experts anticipated. Future vaccines could have an even more streamlined route.

And next-generation vaccines are coming. Some target different life stages of the parasite, so could be combined with a shot like R21. Some could protect adults — including, crucially, during pregnancy, a time when a malaria infection is dangerous to both mother and baby. They could have higher efficacy, greater durability, and even halt transmission — the type of tool that could make eradication a prospect.

In that way, then, RTS,S and R21 have another legacy. They showed that a malaria vaccine was possible.

About the Author

Andrew joseph.

Europe Correspondent

Andrew Joseph covers health, medicine, and the biopharma industry in Europe.

children's health

global health

public health

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EMBL Conference

BioMalPar XX: biology and pathology of the malaria parasite

Practical information.

This conference will take place at EMBL Heidelberg, with the option to attend virtually.

Conference overview

Malaria remains a major global public health challenge. The emergence and spread of resistance to existing antimalarial drugs further complicates the fight against this ancient foe.

As the BioMalPar Conference marks its 20th anniversary, we would like to take a moment to reflect on the critical mission of understanding the biology of the Plasmodium parasite, its interactions with hosts and vectors, and the urgent need to develop effective intervention strategies.

This year, we will focus on enhancing our research community by forging new connections. We recognize that meaningful progress in combating malaria necessitates collaboration across continents and disciplines—sharing data and employing state-of-the-art techniques to unravel Plasmodium’s secrets.

The upcoming conference is a pivotal opportunity for global scientists to convene, fostering the exchange of vital information, cutting-edge technology, and innovative ideas, all crucial to advancing our collective battle against malaria.

Session topics

• “Imaging Begins”
• “Revenge of the Mosquito”
• “Charlie & the Vaccine Factory”
• “Mr & Mrs Plasmodium”
• “V for Vivax”
• “The Parasite’s Guide to the Galaxy”

What past participants say about the conference

“ BioMalPar 2023 encompassed a spectacular range of research spanning basic to translational. The program content was topical and comprehensive, and the overall event was well-organized to achieve a dynamic environment that fuelled great discussions and networking. ” – Jacquin Niles, Massachusetts Institute of Technology, USA

“ After a decade working on malaria research, I had heard high opinions of BioMalPar. However, this was my first time attending and clearly exceeded my expectations. Excellent scientific content with a balanced blend of senior and junior scientists. Smoothly organised in a venue that favours networking organically. ” – Alejandro Marin Menendez, MIVEGEC-IRD, France

Keynote Speaker

Ifakara Health Institute

(Virtual speaker)

Takeshi Annoura

National Institute of Infectious Diseases (NIID),

Arizona State University

Alfred Cortés

Emily Derbyshire

Duke University

Tibebu Habtewold

Imperial College London

Franziska Hentzschel

Heidelberg University Hospital

Columbia University Irving Medical Center

Radboud University Medical Center

The Netherlands

Mallika Imwong

Mahidol University

Berlin Londoño-Renteria

Tulane University

Fitsum G Tadesse

Armauer Hansen Research Institute

Moritz Treeck

Gulbenkian Institute of Science

Scientific Organisers

Sabrina Absalon

Indiana University School of Medicine

Jessica Bryant

Institut Pasteur

Fredros Okumu

Emeritus steering group member

Julian Rayner

University of Cambridge

Andy Waters

University of Glasgow

Conference Organiser

Chris Stocks

EMBL Heidelberg

Are you on social media? Post using #EMBLMalaria and don’t forget to tag @EMBLEvents .

• Please note that the programme is subject to change. Some speakers may need to join virtually to give their talk.
• For registered participants, recorded talks will be accessible on demand for 2 weeks after the end of the event, unless indicated otherwise.

You can choose to attend the conference either onsite in Heidelberg or virtually. If you hope to present your research, you need to decide which mode suits you best before the abstract submission deadline, considering the below: 

If you plan to attend the conference onsite, you can register and apply for an  oral or poster presentation.  A selection process will take place with the results announced 2-3 weeks after the abstract submission deadline. Please note that once you have registered for onsite attendance and submitted an abstract for an oral presentation, you will still have the opportunity to present a poster onsite even if not selected for an onsite oral presentation. However, it is not possible to switch and apply for a  virtual oral presentation after the submission deadline. 

If you plan to attend the conference virtually, you can only  apply for a virtual oral presentation as there will be no virtual posters.  If your abstract is not selected for a virtual oral presentation, you can still participate in the conference with access to all the live streamed talks, a video library of the recorded talks and a facility to submit questions. Only participants attending the event onsite can present a poster.

On-site registration fees  include admission, conference materials, meals and coffee breaks. Participants are expected to book and pay their own accommodation and travel expenses.

Virtual registration fees include access to all of the talks (livestreamed and on demand) and facility to submit questions.

* Editors from scientific journals are allowed to attend at a reduced rate, but asked to contribute to the conference in return by taking part in ‘meet the editors’ sessions or other planned activities within the programme .

A letter to support your visa application will be issued, on request, once payment of the registration fee is confirmed. We recommend that you book your visa appointment as soon as possible, to avoid any delay with your visa application.

Accredited journalists may be eligible to register for complimentary press registration. Registrants may be required to provide accreditation or equivalent proof of press membership after registration. Please contact [email protected] for more information. Please note that we do not offer complimentary registrations for editors of scientific journals.

Confirmation and payment

Registration will be on a first come, first served basis. Your place can only be confirmed after payment of the registration fee. If you are added to our waiting list, please consider taking advantage of our offerings to participate virtually.

On-site participants: Types of payments accepted are international bank transfers and credit card payments. 

Virtual participants: We are only able to accept card payments. In exceptional cases we can accept bank transfers. Please contact  [email protected]  for details.

Abstract submission

Onsite and virtual participants registering to attend are eligible to submit an abstract.

After registration you can submit your abstract via a separate link that will be provided in the email confirmation. Alternatively, you can access the link on the confirmation page directly after registering. The same login credentials are used for both processes.

Please note:

Abstract body: The limit of 2000 characters refers to manually typed text and excludes spaces. If an error occurs try using a different web browser (preferably Google Chrome or Mozilla Firefox).

If you copy-paste the text into the form, hidden formatting might still be included which may cause the text to exceed the 2,000 character limit resulting in an error message. We recommend you clear all formatting before pasting in the text.

If you have special symbols in your text, make sure you are using Unicode characters, otherwise these will not be recognised.

Title: The title should not exceed 20 words. Only the first word of the title should start with a capital letter and the rest should be lowercase.

Authors and affiliations: Please fill in the author’s details as requested in the online form. The compulsory fields are: First Name, Last Name, Organisation Name (Affiliation or Company), Country and Email.

Kindly mark only one author in the role of First Author and please don’t forget to indicate who will be the Presenter.

Please enter your co-authors correctly via the system by adding accounts together with their organisation/institute. Do not copy-paste them into the body of the abstract text, as they will not be indexed in the abstract book.

Presentation types: When submitting your abstract, you can apply for an oral or poster presentation. A selection process will take place with the results announced 2-3 weeks after the abstract submission deadline.

For detailed instructions on how to submit a conference abstract, follow the instructions provided in this video .

Please check our   FAQs pages  for further information on how to submit an abstract.

Financial assistance

Limited financial assistance is provided by the EMBL Advanced Training Centre Corporate Partnership Programme and EMBO in the form of registration fee waivers , travel grants , and childcare grants .

Your place in the meeting is only confirmed by paying the registration fee, which is mandatory even when receiving a fee waiver.

Registration fee waiver

The  fee waiver  will cover the registration sum that you have paid to attend the course or conference.

Travel grant

The travel grant will cover the cost of travel to an on-site event (airfare, train, bus, taxi, accommodation, visa, and/or registration fees*) and is provided up to specified caps which are normally as follows:

–up to €400 for participants travelling to an EMBL Conference or EMBO|EMBL Symposium from within Europe.

–up to €1000 for participants travelling to an EMBL Conference or EMBO|EMBL Symposium from outside Europe.

–up to €500 for any participant travelling to an EMBO Workshop.

–up to €1000 for any participant working in Chile, India, Singapore or Taiwan travelling to an EMBO Workshop.

–up to €700 for any participant working in Croatia, Czech Republic, Estonia, Greece, Hungary, Italy, Lithuania, Luxembourg, Poland, Slovenia, and Turkey travelling to an EMBO Workshop.

*Registration fees are only covered for EMBO Workshops

The organisers may reduce the grant cap to accommodate more participants. Recipients will be notified of their travel cap amount when they are informed of the outcome of their application. Original receipts must be provided with your signature for all costs incurred within two months of completion of travel. Scanned copies cannot be accepted.

Childcare grant

There is the possibility to apply for a childcare grant to offset child care costs incurred by participants, speakers, and organisers when attending a conference.

Eligible costs include (but are not limited to) fees for a baby-sitter or child-care facility, and travel costs for a caregiver. Please note that priority will be given to early stage researchers. In order to apply for this grant, you must be registered by the abstract submission deadline. There is a limited amount of funding available for the childcare grants and funds will be distributed amongst eligible applicants.

Application

On-site participants

You may apply for financial assistance when submitting your abstract. The financial assistance for onsite participation  13 February 2024.   Please note that the deadline for applying for financial assistance for BioMalPar is earlier than the abstract submission deadline.  This is to allow successful applicants more time to apply for a travel visa to enter Germany, if needed. In your application you will be asked to answer questions regarding why your lab cannot fund your attendance and how your attendance will make a difference to your career. Application for financial support will not affect the outcome of your registration application. Your abstract will still be considered if you are not awarded financial help and you may still attend on a self-funding basis if you wish.

Virtual participants

If you are attending virtually, you can apply for financial assistance in the submission portal by the abstract deadline. Read the instructions on how to apply for financial assistance .

In your application you will be asked to summarise your current work,  answer questions regarding why your lab cannot fund your attendance, and how your attendance will make a difference to your career. Application for financial support will not affect the outcome of your registration application.

The scientific organisers will select the recipients of registration fee waivers and travel grants during the motivation letter or abstract selection process. Results will be announced approximately 6 – 8 weeks before the event start date, however for some events this may be delayed. Selection results do not impact your admission to the meeting. Selection for registration fee waivers and travel grants is based on scientific merit, your current work or study location, the reasons for needing financial support, and the impact this event will have on your career.

Childcare grants will be allocated in the same timeframe (6-8 weeks before the event start date). Please note that priority will be given to early-stage researchers.

Reimbursement

Costs will be reimbursed after the meeting only once a reimbursement form and original receipts (from travel costs) have been received.

Further details

View our  list of external funding opportunities  and  information on attending a conference as an event reporter .

For further information about financial assistance please refer to the  FAQ page .

Accommodation is  not included  in the conference registration fee.

The hotels below have rooms on hold for participants until 23 April 2024, in some cases at special rates. Please email the hotel directly, quoting the booking code BMP23-01  to confirm the exact price of the room.

Travel information

For travel information, please see here .

If you are travelling to the conference within Germany then you are eligible for the Deutsche Bahn ‘Event Ticket’ (called the ‘Veranstaltungsticket’ in German). This will result in a lower ticket price if your travel distance to Heidelberg is more than 100 km. You need to provide proof of your event attendance when purchasing the ticket.

For more information in English see here or in German see here .

You can book your ticket here .

Conference shuttle buses

Conference shuttle buses are free of charge for participants, and depart from designated bus stops near the hotels to EMBL and back, mornings and evenings.

The bus stops for this conference are:

• Staycity Aparthotel (Speyerer Str. 7)
• Kurfürsten-Anlage (Opposite Main Train Station)
• Premier Inn (Kurfürsten-Anlage 23)
• Leonardo Hotel Heidelberg City Center (Bergheimer Str. 63)
• Neckarmünzplatz (Heidelberg Tourist Information)
• Peterskirche (Bus stop)
• ISG Hotel (Im Eichwald 19)

Conference shuttle bus schedule

View  Conference shuttle bus stops and hotels  in a larger map . Please note that not every bus stop will be used for every event. You can find the bus schedule here .

Address: EMBL, Meyerhofstraße 1, 69117 Heidelberg, Germany.

For more information about accommodation and travel, please refer to the FAQ page .

All meals and coffee breaks are included in the registration fee. Our catering staff will prepare a wide variety of vegetarian meals, meat and fish dishes, soups, pasta, fresh fruit and vegetables, as well as a variety of desserts.

Please wear your badge at all times when serving yourself.

No food or drinks are allowed in the auditorium.

Charging lockers

There are lockers available next to the stairs leading down into the Auditorium. You will find some of those equipped with sockets to charge your smartphone/tablet etc.

Electricity and charging station

In most places the electricity is 220 volts AC (50 cycles). An adaptor and a plug that fits the German socket may be needed for your appliances/laptop (i.e. American, Japanese, etc.). A USB charging station for electronic devices is available at the registration desk.

EMBL merchandise

If you are interested in purchasing EMBL merchandise (products presented in the glass display in the registration area), please email the EMBL shop to place an order or get in contact with your Course Organiser.

Kindly note the EMBL shop is only open upon request and all purchases must be made in cash (Euros only).

Health and safety notes

Please read EMBL’s COVID-19 safety policy for on-site events. Do not smoke in any EMBL building. Eating and drinking is prohibited in the Auditorium and all laboratories. Do not enter any restricted areas or the laboratories unless instructed to do so.

If first aid is required …

• The first aid room is located next to the ATC Registration Desk (room 10- 205).
• Dial the Emergency number 222 from any EMBL internal phone only.
• Where is the accident? What happened? How many injured?
• Emergency number 06221-387 7821 from mobile phones.
• Please report all accidents to the conference officer at the registration desk.

In case of fire …

• Press the nearest fire alarm button or the Emergency number 222 from any internal phone.
• A loud fire alarm will go off if an evacuation is required. On hearing the alarm leave the building immediately following the escape route and fire wardens and head to one of the meeting points
• Do not use the lifts.

Beyond first aid…

Please remember to bring your own medication, if needed, to the conference. Note that the next pharmacy is a 4-minute drive from the EMBL, but for many medications you will be required to see a doctor to get a prescription.

Ensure in advance that your medical insurance will cover you during your visit in the event that you do need to see a doctor while in Heidelberg. In any case, the EMBL Course and Conference Office will assist you to get to the pharmacy and a doctor of your choice if necessary.

Wi-Fi is available on campus using the EMBL-Events network and the event specific password, which will be provided on site. The eduroam network (secure, worldwide roaming access service developed for the international research and education community) is also available.

Lost and found

‘’Lost and Found’’ items are kept at the registration desk until the end of the conference.

There are lockers available on-site to store your luggage, which require a 2 EURO coin to operate. There is another luggage room on level E0, which is free to use but remains unlocked during the conference.

Nursing room

There is a nursing room available in the ATC Rooftop Lounge on level A29.

Photography

During the conference, an EMBL Photographer may be taking photos. If you would not like to appear in these, please inform the photographer or a member of the Course and Conference Office.

We can help to print your boarding pass/train ticket. Please send it to [email protected] and collect your print-outs at the registration desk.

Room for prayer, yoga and meditation

There is a room for prayer, meditation and yoga located on level E0 behind the Auditorium. Please be respectful of others using the room.

Sightseeing

A variety of activities in Heidelberg can be found on the website of Heidelberg Marketing .

Travel to and from the venue

During the event, we provide conference shuttle buses to and from EMBL. In addition, there is the public bus 39A that serves the EMBL campus and taxis can be easily booked at any time. Information on the conference shuttle buses can be found on the individual event website and more detailed information on travelling to EMBL can be found on our  Travel Information  page.

Useful German expressions

What’s included?

• Access to all the livestreamed talks
• Video library of the recorded talks during the event and for two weeks afterwards. Please note: at the request of individual speakers, some talks are not recorded.
• Facility to submit questions

* Talks will only be recorded upon speaker’s consent

Please note that only on-site participants are able to submit abstracts and participate in the poster sessions.

Event platform

We are using an event platform for this conference. More information about the platform will be shared ahead of the conference.

• Do not broadcast the conference to unregistered participants.
• You are encouraged to tweet and post about the event. Tweet unless the speaker specifically says otherwise, but be mindful of unpublished data. 
• Please do not capture, transmit or redistribute data presented at the meeting.

Additional information can be found in our  Code of Conduct .

Health and well-being

It is important to stay healthy and move around, especially when you are attending an event virtually. We have put together a few coffee break stretches and yoga videos in the conference platform for you to enjoy during the event.

How to ask questions

Please use the Q&A function in the event platform.

If you have any other questions, you can go to the Help Desk in the event platform. Click on ‘more’ on the top menu and click Help Desk. 

The programme is planned based on the Europe/Berlin time zone, unless otherwise stated. Please take your time zone into consideration when planning your

Please find additional information including FAQs, terms and conditions, COVID-19 safety policy and travelling to EMBL on our Information for participants page.

COVID-19 information for on-site events at EMBL Heidelberg can be found in our COVID-19 FAQs .

Media partners

EMBO Molecular Medicine , an EMBO Press journal

International Union of Biochemistry and Molecular Biology

Medinformati c s , a Bon View Publishing journal

Open Biology , a Royal Society journal

Sponsorship opportunities

We offer a variety of event sponsoring possibilities, with the flexibility to select a set sponsorship package or combine individual sponsorship options to suit your event budget. Discounts are available for companies sponsoring multiple events at EMBL Heidelberg.  View other conferences , or contact  [email protected]  for further information on sponsoring possibilities.

If you are interested in becoming a media partner of this event, please visit our  media partnerships webpage.

Request a sponsorship brochure

EMBL wishes to warn sponsors of EMBL conferences and courses of fraudulent schemes purporting to offer sponsorship opportunities on behalf of EMBL or affiliated with EMBL officials. One current scam campaign of which we are aware is conducted using the name ‘Judy Eastman’ ([email protected]) and entails approaches to sponsors offering sponsorship opportunities on EMBL’s behalf. Please be kindly advised that all relevant communication regarding sponsorship of EMBL conferences, symposia and courses is handled by EMBL directly and is sent from an official EMBL account. EMBL does not work with any external providers on sponsorship acquisition.

Please also note that:

• EMBL never provides attendee lists for purchase. Any offers of such are fraudulent.
• EMBL will never call or email you to ask for your credit card details or to request a payment.
• All payments are on invoice.

Suspicious communications purportedly from, for or on behalf of EMBL should be reported to EMBL at the following email address [email protected].

Want to let others know you’re attending this event? Take a look at our shareable media and feel free to use them in your social media channels or presentations.

Date: 21 - 23 May 2024

Location: EMBL Heidelberg and Virtual

Venue: EMBL Advanced Training Centre

Deadline(s):

Abstract submission: Closed

Registration (On-site): Closed

Registration (Virtual): Closed

Organisers:

• Sabrina Absalon Indiana University, USA
• Jess Bryant Institut Pasteur, France
• Fredros Okumu Ifakara Health Institute, Tanzania
• Taco Kooij Radboud University Medical Center, The Netherlands

Contact: EMBL Events

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To the Editor:

Re “ Lives at Risk ” (Science Times, July 23):

The New York Times spotlights malaria, which kills nearly half a million African children annually, and the important role malaria vaccines are playing in reducing child deaths.

The malaria vaccine pilots, for which the World Health Organization provided scientific and technical leadership, demonstrate the critical role W.H.O. plays in serving countries’ needs. W.H.O. advanced the first malaria vaccine (RTS,S) at the request of member states, even as global health partners focused their attention on other agendas.

The pilots provided assurance that the vaccine is safe and highly effective — reducing child deaths by 13 percent. In some areas, combining the vaccine, insecticide-treated nets and chemoprevention can reduce malaria by more than 90 percent.

W.H.O. doesn’t stop at recommendations. We engage governments, manufacturers, social-finance companies and global funding partners to ensure that vaccines are accessible to the most vulnerable.

To continue our important role in global public health, and to ensure that interventions reach the most vulnerable, sustainable funding is critical for W.H.O., Gavi, the Vaccine Alliance and the Global Fund to Fight AIDS, Tuberculosis and Malaria. With new tuberculosis vaccines on the horizon, W.H.O. will continue providing unbiased scrutiny of evidence, with country needs at the center of our decision-making, so that health for all is achieved.

Mary J. Hamel Geneva The writer is the team lead for malaria vaccines at the World Health Organization.

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Volume 30, Number 9—September 2024

Research Letter

Powassan virus encephalitis after tick bite, manitoba, canada.

Suggested citation for this article

A case of Powassan encephalitis occurred in Manitoba, Canada, after the bite of a black-legged tick. Awareness of this emerging tickborne illness is needed because the number of vector tick species is growing. No specific treatment options exist, and cases with illness and death are high. Prevention is crucial.

Figure . Black-legged tick ( Ixodes scapularis ) after removal with tweezers from a patient in Manitoba, Canada, who was later diagnosed with Powassan virus.

On October 2, 2022, a 60-year-old male hobbyist outdoor photographer in southern Manitoba, Canada, noticed a black-legged tick ( Ixodes scapularis ) attached to his neck ( Figure ). The patient sought treatment for possible Lyme disease and was prescribed doxycycline.

On October 16, 2 weeks after the tick bite, the patient had complaints of diarrhea, nausea, and malaise. He also had a fever that reached 40°C (104°F), a 10–15-pound weight loss, difficulty concentrating, and a bilateral headache, and he became bedbound from weakness and ataxia. He was admitted to a hospital in Winnipeg, Manitoba on November 1. He had a history of hypertension for which he was taking ramipril and right arm thrombosis for which he was taking apixaban.

The patient complained of radicular pain in his arms and legs requiring opioids. He recalled no recent travel, immunizations, or mosquito bites. Physical examination revealed tachycardia, confusion, dysarthria, and difficulty following commands. He did not have fever, rash, or nuchal rigidity. A neurologic examination demonstrated a bilateral intention tremor, twitching, dysmetria, and ataxia.

Laboratory testing of the patient’s blood samples showed mild hypokalemia and leukopenia (4.1 cells/μL). Magnetic resonance imaging of the patient’s brain revealed a punctate T2 hyperintensity in the right frontal lobe white matter. Electroencephalography revealed mild bilateral fronto-temporal cerebral dysfunction. Cerebrospinal fluid (CSF) examination showed 41 nucleated cells/mm 3 (89% lymphocytes) and a protein level of 1.41 g/L (reference range 0.2–0.4 g/L); glucose level was within reference range. Results of laboratory testing of the CSF was negative for West Nile virus IgM, Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1 and 2, and varicella zoster virus; bacterial and viral cultures yielded negative results. PCR testing of the CSF was negative for human herpesvirus 6. Additional serum testing was negative for HIV, syphilis, hepatitis B and C, and Lyme disease. PCR testing on a stool sample was negative for enteroviruses.

We ordered Powassan virus (POWV) testing of convalescent serum, and results were positive for IgM. A 90% plaque reduction neutralization test (PRNT 90 ) resulted in antibody neutralization at a dilution of 1:80 on November 3 and then 1:160 on November 6. On the basis of clinical symptoms, timeline from tick attachment to symptom onset, and confirmatory PRNT 90 , we made a diagnosis of Powassan encephalitis. After 1 week, the patient improved and was discharged. Repeat serologic testing on July 14, 2023, showed that PRNT 90 had decreased to 1:20.

POWV is a flavivirus transmitted by tick species that also act as reservoirs ( 1 ). The most consequential vectors are black-legged ticks, which are known to bite humans and can spread other tickborne pathogens such as Borrelia burgdorferi (Lyme disease), Anaplasma phagocytophilum (anaplasmosis), and Babesia microti (babesiosis) ( 2 ). Those pathogens require tick attachment periods > 24 hours ( 2 ), but according to animal studies, the transmission time of POWV from vector to host can occur in 15 minutes ( 2 ), although transmission typically occurs after 3 hours in humans ( 3 ). No human-to-human transmission has been reported.

POWV is found in Canada, the United States, and Russia ( 1 ). In the northeastern United States, > 200 cases have been reported. The highest incidence is in Wisconsin and Minnesota, both bordering Manitoba ( 1 , 4 ). Cases occur predominantly in May–November, when ticks are active ( 4 ). Only 21 cases have been reported in Ontario, New Brunswick, and Quebec ( 1 ), Canada. The true prevalence in Canada is unknown because POWV is not a reportable disease. Serologic surveys from 1968–1969 in British Columbia found antibodies in 0.129% of those tested and higher rates of 12.4% in outdoor workers ( 5 ). Studies in Ontario from the 1970s found antibodies in 0.70% of persons tested ( 1 ). The range of black-legged ticks is expanding up to 46 km annually, so exposure is likely increasing ( 6 ). No data on the prevalence of POWV in black-legged ticks in Manitoba have been published.

The incubation period of POWV is 7–34 days, after which 1–3 days of influenza-like prodrome occurs ( 7 ). Central nervous system infection with encephalitis is common ( 7 ). During 2011–2020, the United States reported 194 cases; 91.75% were neuroinvasive, and 10%–15% resulted in death ( 4 , 7 ). Fevers, weakness, headaches, and altered sensorium are the most common patient complaints reported ( 7 , 8 ). Other complaints include gastrointestinal involvement, focal neurologic signs, seizures, ataxia, twitching, tremors, and radiculitis ( 7 ). Magnetic resonance imaging findings commonly include T2/flair hyperintensities in the brainstem, cortex, and deep gray structures ( 9 ). Electroencephalography slowing has been described ( 8 ). Those findings are corroborated by autopsy results showing high POWV RNA levels in brain tissue ( 10 ). Neurologic sequelae occur in > 50% of survivors. In the case we report, the patient reported persistent ataxia for months. Because no specific antiviral drug is available, disease management consists of supportive measures for airway protection and cerebral edema and analgesia for radiculitis.

A lack of reporting, limited awareness of POWV as a causative agent of encephalitis, expanding tick range, and incomplete knowledge of prevalence has led to a lack of action against this emerging virus. Prevention strategies include avoiding ticks, using insect repellant, treating clothing with 0.5% permethrin in endemic areas, and frequent tick checks.

Dr. Smith is a second-year core internal medicine resident with the Max Rady College of Medicine at the University of Manitoba. Research interests include infectious disease and general internal medicine.

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• El Khoury  MY , Camargo  JF , White  JL , Backenson  BP , Dupuis  AP II , Escuyer  KL , et al. Potential role of deer tick virus in Powassan encephalitis cases in Lyme disease-endemic areas of New York, U.S.A. Emerg Infect Dis . 2013 ; 19 : 1926 – 33 . DOI PubMed Google Scholar
• Piantadosi  A , Rubin  DB , McQuillen  DP , Hsu  L , Lederer  PA , Ashbaugh  CD , et al. Emerging cases of Powassan virus encephalitis in New England: clinical presentation, imaging, and review of the literature. Clin Infect Dis . 2016 ; 62 : 707 – 13 . DOI PubMed Google Scholar
• Normandin  E , Solomon  IH , Zamirpour  S , Lemieux  J , Freije  CA , Mukerji  SS , et al. Powassan virus neuropathology and genomic diversity in patients with fatal encephalitis. Open Forum Infect Dis . 2020 ; 7 : ofaa392 . DOI PubMed Google Scholar
• Figure . Black-legged tick (Ixodes scapularis) after removal with tweezers from a patient in Manitoba, Canada, who was later diagnosed with Powassan virus.

Suggested citation for this article : Smith N, Keynan Y, Wuerz T, Sharma A. Powassan virus encephalitis after tick bite, Manitoba, Canada. Emerg Infect Dis. 2024 September [ date cited ]. https://doi.org/10.3201/eid3009.231344

DOI: 10.3201/eid3009.231344

Original Publication Date: August 09, 2024

1 These senior authors contributed equally to this article.

Table of Contents – Volume 30, Number 9—September 2024

Please use the form below to submit correspondence to the authors or contact them at the following address:

Nathan Smith, University of Manitoba, 561 Trent Ave, Winnipeg, MB R2K1G2, Canada

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