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Wednesday, October 28, 2020

Malaria

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Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites. The parasites are spread to people through the bites of infected Anopheles mosquitoes, called “malaria vectors”, which bite mainly between dusk and dawn. Most deaths from Malaria occur among children living in Africa where a child dies every minute from malaria.  There are four parasite species that cause malaria in humans:

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Plasmodium falciparum 

Plasmodium vivax

Plasmodium malariae

Plasmodium ovale.

Plasmodium falciparum and Plasmodium vivax are the most common. Plasmodium falciparum is the most deadly.

 

Transmission of malaria

Malaria is transmitted exclusively through the bites of Anopheles mosquitoes. The intensity of transmission depends on factors related to the parasite, the vector, the human host, and the environment.

Anopheles mosquitoes breed in water and each species has its own breeding preference. Transmission is more intense in places where the mosquito lifespan is longer (so that the parasite has time to complete its development inside the mosquito) and where it prefers to bite humans rather than other animals. For example, the long lifespan and strong human-biting habit of the African vector species is the main reason why about 90% of the world’s malaria deaths are in Africa.

Transmission also depends on climatic conditions that may affect the number and survival of mosquitoes, such as rainfall patterns, temperature and humidity. Malaria is common in tropical and subtropical regions because rainfall, warm temperatures, and stagnant waters provide an environment ideal for mosquito larvae. In many places, transmission is seasonal, with the peak during and just after the rainy season. Malaria epidemics can occur when climate and other conditions suddenly favor transmission in areas where people have little or no immunity to malaria. They can also occur when people with low immunity move into areas with intense malaria transmission, for instance to find work, or as refugees. 

Human immunity is another important factor, especially among adults in areas of moderate or intense transmission conditions. Partial immunity is developed over years of exposure, and while it never provides complete protection, it does reduce the risk that malaria infection will cause severe disease. For this reason, most malaria deaths in Africa occur in young children, whereas in areas with less transmission and low immunity, all age groups are at risk. 

 

Symptoms

Headache, fever, shivering, cough, fatigue (feeling of extreme physical and mental tiredness), malaise, rigors, joint pain, muscle pain, loss of appetite and lethargy (not much energy), nausea and vomiting, diarrhea.

Malaria is an acute febrile illness. In a non-immune individual, symptoms appear seven days or more (usually 10–15 days) after the infective mosquito bite. The first symptoms – fever, headache, chills and vomiting – may be mild and difficult to recognize as malaria. If not treated within 24 hours, P. falciparum malaria can progress to severe illness often leading to death. Children with severe malaria frequently develop one or more of the following symptoms: severe anaemia, respiratory distress in relation to metabolic acidosis, or cerebral malaria. In adults, multi-organ involvement is also frequent. In malaria endemic areas, persons may develop partial immunity, allowing asymptomatic infections to occur. The classic symptom of malaria is paroxysm—a cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every 2 to 3 depending on the species. P. falciparum infection can cause recurrent fever every 36–48 hours or a less pronounced and almost continuous fever. 

For both P. vivax and P. ovale, clinical relapses may occur weeks to months after the first infection, even if the patient has left the malaria area. These new episodes arise from dormant liver forms known as hypnozoites. 

 

Who is at risk?

Approximately half of the world’s population is at risk of malaria. Most malaria cases and deaths occur in sub-Saharan Africa. However, Asia, Latin America, and to a lesser extent the Middle East and parts of Europe are also affected.

Young children in stable transmission areas who have not yet developed protective immunity against the most severe forms of the disease; 

Non-immune pregnant women as malaria causes high rates of miscarriage and can lead to maternal death;

Semi-immune pregnant women in areas of high transmission. Malaria can result in miscarriage and low birth weight, especially during first and second pregnancies; 

Semi-immune HIV-infected pregnant women in stable transmission areas, during all pregnancies. Women with malaria infection of the placenta also have a higher risk of passing HIV infection to their newborns;

People with HIV/Aids;

International travellers from non-endemic areas because they lack immunity;

Immigrants from endemic areas and their children living in non-endemic areas and returning to their home countries to visit friends and relatives are similarly at risk because of waning or absent immunity.

 

Diagnosis and treatment

Early diagnosis and treatment of malaria reduces disease and prevents deaths. It also contributes to reducing malaria transmission. The best available treatment, particularly for P. falciparum malaria, is artemisinin-based combination (coartem) therapy (ACT). WHO recommends that all cases of suspected malaria be confirmed using parasite-based diagnostic testing (either microscopy or rapid diagnostic test) before administering treatment. Results of parasitological confirmation can be available in 15 minutes or less. Treatment solely on the basis of symptoms should only be considered when a parasitological diagnosis is not possible.

 

Antimalarial drug resistance

Resistance to antimalarial medicines is a recurring problem. Resistance of P. falciparum to previous generations of medicines, such as chloroquine and sulfadoxine-pyrimethamine (Fancidar), became widespread in the 1970s and 1980s, undermining malaria control efforts and reversing gains in child survival. This is partly due to the fact that people were abusing and misusing these drugs that led to their resistance. And as a result a new formulated drug in the form of coartem has been developed to tackle the resistant strains. However, we should not further abuse and misuse the recent antimalarial drug in order to avoid resistance.

In recent years, parasite resistance to artemisinin has been detected in four countries of the Greater Mekong sub region: Cambodia, Myanmar, Thailand and Viet Nam. When treated with an oral coartem some patients discontinue treatment prematurely following the rapid disappearance of malaria symptoms. This result in incomplete treatment and such patients still have persistent parasites in their blood and these resistant parasites survive and can be passed on to a mosquito and then another person. If resistance to coartem develops and spreads to other large geographical areas, the public health consequences could be dire, as no alternative antimalarial medicines will be available for at least five years. 

 

Elimination of malaria

Malaria elimination is defined as interrupting local mosquito-borne malaria transmission in a defined geographical area, i.e. zero incidences of locally contracted cases. Malaria eradication is defined as the permanent reduction to zero of the worldwide incidence of malaria infection caused by a specific agent; i.e. applies to a particular malaria parasite species.

On the basis of reported cases for 2012, 52 countries are on track to reduce their malaria case incidence rates by 75%, in line with World Health Assembly targets for 2015. Large-scale use of WHO-recommended strategies, currently available tools, strong national commitments, and coordinated efforts with partners, will enable more countries – particularly those where malaria transmission is low and unstable – to reduce their disease burden and progress towards elimination.

 

In recent years, 4 countries have been certified by the WHO Director-General as having eliminated malaria: United Arab Emirates (2007), Morocco (2010), Turkmenistan (2010), and Armenia (2011). We can also become one sooner or later with all hands on deck. It is not impossible!

 

The life cycle of the malaria parasite

A mosquito causes an infection by a bite. First, sporozoites enter the bloodstream, and migrate to the liver. They infect liver cells, where they multiply into merozoites, rupture the liver cells, and return to the bloodstream. Then, the merozoites infect red blood cells, where they develop into ring forms, trophozoites and schizonts that in turn produce further merozoites. Sexual forms are also produced, which, if taken up by a mosquito, will infect the insect and continue the life cycle.

In the life cycle of Plasmodium, a female Anopheles mosquito (the definitive host) transmits a motile infective form (called the sporozoite) to a vertebrate host such as a human (the secondary host), thus acting as a transmission vector. A sporozoite travels through the blood vessels to liver cells (hepatocytes), where it reproduces asexually (tissue schizogony), producing thousands of merozoites. These infect new red blood cells and initiate a series of asexual multiplication cycles (blood schizogony) that produce 8 to 24 new infective merozoites, at which point the cells burst and the infective cycle begins anew. 

Other merozoites develop into immature gametocytes, which are the precursors of male and female gametes. When a fertilized mosquito bites an infected person, gametocytes are taken up with the blood and mature in the mosquito gut. The male and female gametocytes fuse and form a ookinete—a fertilized, motile zygote. Ookinetes develop into new sporozoites that migrate to the insect’s salivary glands, ready to infect a new vertebrate host. The sporozoites are injected into the skin, in the saliva, when the mosquito takes a subsequent blood meal. 

Only female mosquitoes feed on blood; male mosquitoes feed on plant nectar, and thus do not transmit the disease. The females of the Anopheles genus of mosquito prefer to feed at night. They usually start searching for a meal at dusk, and will continue throughout the night until taking a meal. Malaria parasites can also be transmitted by blood transfusions, although this is rare. 

 

Recurrent malaria

Symptoms of malaria can recur after varying symptom-free periods. Depending upon the cause, recurrence can be classified as either recrudescence, relapse, or reinfection. Recrudescence is when symptoms return after a symptom-free period. It is caused by parasites surviving in the blood as a result of inadequate or ineffective treatment. Relapse is when symptoms reappear after the parasites have been eliminated from blood but persist as dormant hypnozoites in liver cells. Relapse commonly occurs between 8–24 weeks and is commonly seen with P. vivax and P. ovale infections. Reinfection means the parasite that caused the past infection was eliminated from the body but a new parasite was introduced. Reinfection cannot readily be distinguished from recrudescence, although recurrence of infection within two weeks of treatment for the initial infection is typically attributed to treatment failure. People may develop some immunity when exposed to frequent infections.

 

Prevention

·         Vector control is the main way to reduce malaria transmission at the community level. It is the only intervention that can reduce malaria transmission from very high levels to close to zero. 

·         For individuals, personal protection against mosquito bites represents the first line of defence for malaria prevention.

·         Two forms of vector control are effective in a wide range of circumstances. 

·         Insecticide-treated mosquito nets (ITNs)

·         Long-lasting insecticidal nets (LLINs) are the preferred form of ITNs for public health distribution programmes. WHO recommends coverage for all at-risk persons; and in most settings. The most cost effective way to achieve this is through provision of free LLINs, so that everyone sleeps under a LLIN every night.

·         Indoor spraying with residual insecticides

·         Indoor residual spraying (IRS) with insecticides is a powerful way to rapidly reduce malaria transmission. Its full potential is realised when at least 80% of houses in targeted areas are sprayed. Indoor spraying is effective for 3–6 months, depending on the insecticide used and the type of surface on which it is sprayed.

·         Antimalarial medicines can also be used to prevent malaria. For travellers, malaria can be prevented through chemoprophylaxis, which suppresses the blood stage of malaria infections, thereby preventing malaria disease. In addition, WHO recommends intermittent preventive treatment with sulfadoxine-pyrimethamine for pregnant women living in high transmission areas, at each scheduled antenatal visit after the first trimester. Similarly, for infants living in high-transmission areas of Africa, 3 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine is recommended delivered alongside routine vaccinations.

·         Community participation and health education strategies promoting awareness of malaria and the importance of control measures have been successfully used to reduce the incidence of malaria. Recognizing the disease in the early stages can stop the disease from becoming fatal. Education can also inform people to cover over areas of stagnant, still water, such as water tanks that are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is generally used in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas. 

 

Some complications

1.      Respiratory distress due to metabolic acidosis, pulmonary oedema, concomitant pneumonia, severe anaemia.

2.      Renal failure

3.      Cerebral malaria

4.      Liver and spleen enlargement

5.      Severe headache

6.      Severe reduction in blood sugar in pregnant women cause stillbirths, infant mortality and low birth weight

Key facts

Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected mosquitoes. 

Malaria is preventable and curable.

Increased malaria prevention and control measures are dramatically reducing the malaria burden in many places.

Non-immune travellers from malaria-free areas are very vulnerable to the disease when they get infected.

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