Malaria
Disease Details
Family Health Simplified
- Description
- Malaria is a life-threatening disease caused by Plasmodium parasites, transmitted to humans through the bites of infected Anopheles mosquitoes.
- Type
- Malaria is an infectious disease caused by Plasmodium parasites. It is transmitted to humans primarily through the bite of infected Anopheles mosquitoes. Malaria is not genetically inherited from person to person.
- Signs And Symptoms
- Adults with malaria tend to experience chills and fever – classically in periodic intense bouts lasting around six hours, followed by a period of sweating and fever relief – as well as headache, fatigue, abdominal discomfort, and muscle pain. Children tend to have more general symptoms: fever, cough, vomiting, and diarrhea.Initial manifestations of the disease—common to all malaria species—are similar to flu-like symptoms, and can resemble other conditions such as sepsis, gastroenteritis, and viral diseases. The presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions.The classic symptom of malaria is paroxysm—a cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae. P. falciparum infection can cause recurrent fever every 36–48 hours, or a less pronounced and almost continuous fever.Symptoms typically begin 10–15 days after the initial mosquito bite, but can occur as late as several months after infection with some P. vivax strains. Travellers taking preventative malaria medications may develop symptoms once they stop taking the drugs.Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection. Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), opisthotonus, seizures, or coma.
- Prognosis
- When properly treated, people with malaria can usually expect a complete recovery. However, severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, fatality rates can reach 20%, even with intensive care and treatment. Over the longer term, developmental impairments have been documented in children who have had episodes of severe malaria. Chronic infection without severe disease can occur in an immune-deficiency syndrome associated with a decreased responsiveness to Salmonella bacteria and the Epstein–Barr virus.During childhood, malaria causes anaemia during a period of rapid brain development, and also direct brain damage resulting from cerebral malaria. Some survivors of cerebral malaria have an increased risk of neurological and cognitive deficits, behavioural disorders, and epilepsy. Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups.
- Onset
- Malaria typically has an onset of symptoms 7 to 30 days after being bitten by an infected mosquito. Symptoms can include fever, chills, headache, nausea, vomiting, and fatigue. In some cases, the symptoms can appear within 10 to 15 days or even longer, depending on the specific Plasmodium species causing the infection.
- Prevalence
- Malaria is prevalent in tropical and subtropical regions, including parts of Africa, Asia, Central and South America, and Oceania. The highest burden of the disease is found in sub-Saharan Africa, with countries like Nigeria and the Democratic Republic of Congo contributing significantly to global case numbers. Each year, there are over 200 million cases of malaria worldwide, resulting in an estimated 400,000 deaths, most of which are in children under the age of five.
- Epidemiology
- The WHO estimates that in 2021 there were 247 million new cases of malaria resulting in 619,000 deaths. Children under five years old are the most affected, accounting for 67% of malaria deaths worldwide in 2019. About 125 million pregnant women are at risk of infection each year; in Sub-Saharan Africa, maternal malaria is associated with up to 200,000 estimated infant deaths yearly. Since 2015, the WHO European Region has been free of malaria. The last country to report an indigenous malaria case was Tajikistan in 2014. There are about 1300–1500 malaria cases per year in the United States. The United States eradicated malaria as a major public health concern in 1951, though small outbreaks persist. Locally acquired mosquito-borne malaria occurred in the United States in 2003, when eight cases of locally acquired P. vivax malaria were identified in Florida, and again in May 2023, in four cases, as well as one case in Texas, and in August in one case in Maryland. About 900 people died from the disease in Europe between 1993 and 2003. Both the global incidence of disease and resulting mortality have declined in recent years. According to the WHO and UNICEF, deaths attributable to malaria in 2015 were reduced by 60% from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin-based combination therapies. Between 2000 and 2019, malaria mortality rates among all ages halved from about 30 to 13 per 100,000 population at risk. During this period, malaria deaths among children under five also declined by nearly half (47%) from 781,000 in 2000 to 416,000 in 2019.Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; in Sub-Saharan Africa, 85–90% of malaria fatalities occur. An estimate for 2009 reported that countries with the highest death rate per 100,000 of population were Ivory Coast (86.15), Angola (56.93) and Burkina Faso (50.66). A 2010 estimate indicated the deadliest countries per population were Burkina Faso, Mozambique and Mali. The Malaria Atlas Project aims to map global levels of malaria, providing a way to determine the global spatial limits of the disease and to assess disease burden. This effort led to the publication of a map of P. falciparum endemicity in 2010 and an update in 2019. As of 2021, 84 countries have endemic malaria.The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other. Malaria is prevalent in tropical and subtropical regions because of rainfall, consistent high temperatures and high humidity, along with stagnant waters where mosquito larvae readily mature, providing them with the environment they need for continuous breeding. In drier areas, outbreaks of malaria have been predicted with reasonable accuracy by mapping rainfall. Malaria is more common in rural areas than in cities. For example, several cities in the Greater Mekong Subregion of Southeast Asia are essentially malaria-free, but the disease is prevalent in many rural regions, including along international borders and forest fringes. In contrast, malaria in Africa is present in both rural and urban areas, though the risk is lower in the larger cities.
- Intractability
- Malaria is not considered intractable. It can be treated and often cured with antimalarial medications, especially when diagnosed early. However, drug-resistant strains of malaria and challenges in accessing healthcare can complicate treatment in some regions. Prevention through mosquito control and prophylactic medications is also crucial in reducing the incidence of malaria.
- Disease Severity
- Malaria is a serious and potentially life-threatening disease caused by Plasmodium parasites, which are transmitted to humans through the bites of infected Anopheles mosquitoes. The severity of malaria can range from mild, with symptoms such as fever, chills, and flu-like illness, to severe, which can lead to complications like organ failure, cerebral malaria, and death if not promptly treated.
- Healthcare Professionals
- Disease Ontology ID - DOID:12365
- Pathophysiology
- Malaria infection develops via two phases: one that involves the liver (exoerythrocytic phase), and one that involves red blood cells, or erythrocytes (erythrocytic phase). When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days.After a potential dormant period in the liver, these organisms differentiate to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells to begin the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.Some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead, produce hypnozoites that remain dormant for periods ranging from several months (7–10 months is typical) to several years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in P. vivax infections, although their existence in P. ovale is uncertain.The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. The blockage of the microvasculature causes symptoms such as those in placental malaria. Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria.
- Carrier Status
- Malaria is caused by Plasmodium parasites, transmitted to humans through the bites of infected Anopheles mosquitoes. In malaria, there is no "carrier state" equivalent to that seen in some bacterial infections. People are either infected with the parasite or not. The term "carrier" in the context of malaria is not applicable, as the disease requires active infection with the Plasmodium parasite for someone to be considered affected. The primary concern is the presence of active, symptomatic infection or asymptomatic parasitemia, where individuals harbor the parasite without showing symptoms but can still contribute to the transmission cycle if bitten by mosquitoes.
- Mechanism
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Malaria is caused by protozoan parasites of the genus Plasmodium, with Plasmodium falciparum being the most lethal.
**Mechanism:**
1. Transmission occurs through the bite of an infected female Anopheles mosquito, which injects Plasmodium sporozoites into the bloodstream.
2. Sporozoites travel to the liver and invade hepatocytes, where they develop into merozoites.
3. Merozoites are released into the bloodstream, where they invade red blood cells (RBCs).
4. Inside RBCs, the parasite undergoes asexual reproduction, producing more merozoites which further invade RBCs (cholera cycle), and some differentiate into sexual forms called gametocytes.
5. Gametocytes are taken up by another mosquito, completing the transmission cycle.
**Molecular Mechanisms:**
1. **Invasion of hepatocytes and RBCs:** Involves interaction of parasite surface proteins, such as circumsporozoite protein (CSP) for liver invasion and merozoite surface proteins (MSPs) for RBC invasion.
2. **Immune evasion:** Plasmodium can modify the surface of infected RBCs, exposing ‘knobs’ containing erythrocyte membrane protein 1 (PfEMP1), which aids in adherence to blood vessel walls, a process called sequestration, helping the parasite avoid spleen-mediated clearance.
3. **Hemoglobin digestion:** Plasmodium degrades hemoglobin in RBCs, using proteases to release amino acids necessary for its growth. The toxic heme byproduct is converted into inert hemozoin.
4. **Antigenic variation:** The parasite frequently changes the proteins it displays on the surface of infected RBCs, particularly PfEMP1, to evade the immune system.
These molecular interactions and survival strategies make malaria a complex and resilient disease, contributing to its global health impact. - Treatment
- Malaria is treated with antimalarial medications; the ones used depends on the type and severity of the disease. While medications against fever are commonly used, their effects on outcomes are not clear. Providing free antimalarial drugs to households may reduce childhood deaths when used appropriately. Programmes which presumptively treat all causes of fever with antimalarial drugs may lead to overuse of antimalarials and undertreat other causes of fever. Nevertheless, the use of malaria rapid-diagnostic kits can help to reduce over-usage of antimalarials.
- Compassionate Use Treatment
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For malaria, "compassionate use" treatments and off-label or experimental treatments can sometimes be considered for severe or drug-resistant cases where standard therapies are ineffective or unavailable.
1. **Compassionate Use Treatment:**
- **Artemisinin-based therapies:** These are typically the first-line treatment for malaria, but in certain severe cases, intravenous (IV) formulations like artesunate might be provided under compassionate use if not otherwise accessible.
- **New antimalarial drugs:** Drugs in late-stage clinical trials might also be accessible through compassionate use programs.
2. **Off-Label or Experimental Treatments:**
- **Atovaquone-proguanil (Malarone):** Although it's approved for treatment and prophylaxis, in some cases, it might be used off-label in specific combinations or doses.
- **Doxycycline:** Used off-label as part of combination therapy for resistant malaria strains.
- **Azithromycin:** Occasionally used off-label in combination treatment where resistance to first-line drugs is suspected.
- **Experimental vaccine use:** While not directly a treatment, vaccines under development or trial phases might be offered in certain high-risk or emergency contexts.
- **Experimental drugs:** Medications like tafenoquine or other novel compounds might be used in clinical trials or experimental settings for drug-resistant malaria.
Any use of these treatments should be carefully monitored by healthcare professionals due to potential side effects and the need for appropriate dosing. - Lifestyle Recommendations
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For malaria, the following lifestyle recommendations can help prevent infection:
1. **Use Insect Repellents**: Apply insect repellents containing DEET, picaridin, or oil of lemon eucalyptus to exposed skin.
2. **Sleep Under Mosquito Nets**: Use bed nets treated with insecticides to protect against mosquito bites while sleeping, especially in areas with high malaria risk.
3. **Wear Protective Clothing**: Wear long-sleeved shirts and long pants, preferably treated with insect repellent, to reduce skin exposure.
4. **Stay Indoors During Peak Mosquito Hours**: Mosquitoes that transmit malaria are most active from dusk to dawn. Minimize outdoor activities during these times.
5. **Use Insecticide-Treated Nets and Curtains**: Ensure that windows and doors are fitted with screens treated with insecticides to prevent mosquitoes from entering.
6. **Take Antimalarial Medication**: If traveling to an area with malaria risk, take prophylactic antimalarial medication as prescribed by a healthcare provider.
7. **Eliminate Mosquito Breeding Sites**: Reduce mosquito populations by removing standing water in areas around living spaces where mosquitoes can breed.
Following these recommendations can significantly reduce the risk of contracting malaria. - Medication
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Malaria parasites contain apicoplasts, organelles related to the plastids found in plants, complete with their own genomes. These apicoplasts are thought to have originated through the endosymbiosis of algae and play a crucial role in various aspects of parasite metabolism, such as fatty acid biosynthesis. Over 400 proteins have been found to be produced by apicoplasts and these are now being investigated as possible targets for novel antimalarial drugs.With the onset of drug-resistant Plasmodium parasites, new strategies are being developed to combat the widespread disease. One such approach lies in the introduction of synthetic pyridoxal-amino acid adducts, which are taken up by the parasite and ultimately interfere with its ability to create several essential B vitamins. Antimalarial drugs using synthetic metal-based complexes are attracting research interest.
(+)-SJ733: Part of a wider class of experimental drugs called spiroindolone. It inhibits the ATP4 protein of infected red blood cells that cause the cells to shrink and become rigid like the aging cells. This triggers the immune system to eliminate the infected cells from the system as demonstrated in a mouse model. As of 2014, a Phase 1 clinical trial to assess the safety profile in human is planned by the Howard Hughes Medical Institute.
NITD246 and NITD609: Also belonged to the class of spiroindolone and target the ATP4 protein.On the basis of molecular docking outcomes, compounds 3j, 4b, 4h, 4m were exhibited selectivity towards PfLDH. The post docking analysis displayed stable dynamic behavior of all the selected compounds compared to Chloroquine. The end state thermodynamics analysis stated 3j compound as a selective and potent PfLDH inhibitor. - Repurposable Drugs
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Repurposable drugs for malaria primarily include several medications initially developed for other conditions but found to be effective against malaria. Examples include:
1. **Hydroxychloroquine and Chloroquine**: Originally developed for treating autoimmune diseases like lupus and rheumatoid arthritis, these drugs have also been used to treat malaria due to their antimalarial properties.
2. **Doxycycline**: An antibiotic that has been repurposed for malaria prophylaxis.
3. **Atovaquone**: Initially used for treating Pneumocystis pneumonia, it is combined with proguanil for malaria treatment.
4. **Azithromycin**: An antibiotic that has shown some effectiveness in treating malaria, especially when combined with other antimalarial drugs.
"Nan" appears to be an incomplete or ambiguous term in this context and doesn't provide enough information to generate a relevant response. If it refers to a specific area of inquiry related to nanotechnology or another specific topic, please provide additional details or clarify the term. - Metabolites
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In malaria, key metabolites involved in the disease include:
1. Hemozoin: A byproduct from the digestion of hemoglobin by Plasmodium parasites.
2. Lactate: Elevated levels can result from anaerobic glycolysis by Plasmodium due to the parasite's high metabolic rate.
3. Glucose-6-phosphate: Increased consumption during the glycolytic pathway of the parasite.
Nanotechnology applications (referred to as "nan") in malaria focus on:
1. Drug delivery: Using nanoparticles to enhance the delivery and efficacy of antimalarial drugs.
2. Diagnostics: Employing nanoparticle-based assays for rapid and sensitive detection of malaria antigens or DNA.
3. Vaccines: Developing nanoparticle-based platforms to improve the immunogenicity and stability of malaria vaccines. - Nutraceuticals
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Malaria is a life-threatening disease caused by Plasmodium parasites, transmitted to humans through the bites of infected Anopheles mosquitoes. Nutraceuticals, which are products derived from food sources that offer health benefits, play a role in malaria prevention and treatment. For example, certain botanicals and plant extracts, such as Artemisia annua (sweet wormwood), which contains artemisinin, have been utilized both in traditional medicine and modern treatments.
In terms of nanotechnology (nan.), research is exploring the use of nanoparticles for improved drug delivery, diagnostic tools, and mosquito control strategies in malaria management. Nanoparticles can enhance the efficacy and stability of antimalarial drugs, provide targeted delivery to infected cells, and reduce side effects. Additionally, novel diagnostic methods utilizing nanotechnology can improve the sensitivity and speed of malaria detection. - Peptides
- The use of peptides and nanotechnology in malaria research and treatment has shown promising advancements. Peptides can function as antimalarial agents by targeting specific proteins in the malaria parasite, Plasmodium spp. Nanotechnology, such as nanoparticles, enhances the delivery and efficacy of antimalarial drugs, potentially overcoming issues like drug resistance and poor solubility. Combining these approaches could lead to more effective and targeted malaria therapies.