Controlling Malaria

 

Controlling Malaria

PKGhatak,MD

Biologists counted over 330 species of malaria protozoa, fortunately, humans have to deal with the protozoa genus Plasmodium and that too only 5 species. But that did not prove to be that good. Malaria took 1.4 million lives every year until recently. In 2019 WHO estimated 228 million people were infected with malaria and 405,000 died, which is an improvement from the year before when 416,000 died of malaria.

Malaria was also a problem when humans first appeared in Africa. To save himself from dying from malaria, the genetic mutation had to happen. That gave rise to sickle cell disease – one disaster is replaced by a new one.

Malaria is an intracellular parasite. Mosquitoes acquire the malaria parasite when they bite and suck a bloody meal from humans suffering from malaria. In the gut of the mosquito, the sex differentiation and the sexual union of the parasites take place. And subsequently, they produce numerous daughters. The newly formed parasites travel to the mosquito's salivary gland and the Plasmodium enters the human body when a mosquito bites a human. The parasites find their way into the liver. In the liver cells, the parasites mature and multiply in huge numbers and ultimately by rupturing the liver cells they enter the bloodstream. The parasites then infect red blood cells (RBC). In the RBC malaria multiplies by the asexual process and then rupture and the released parasites. The released parasites infect more fresh red blood cells. Then this cycle repeats with the fresh bites of mosquitoes.

If the patients survive the initial infection, they suffer from chronic anemia and poor nutrition. That makes them candidates for frequent bacterial infections including tuberculosis.

Controlling malaria involves several aspects -

Controlling Mosquito.

The female anopheles must have a blood meal before they can lay eggs in a stagnant pool of water. It is reported that mosquitoes can detect people suffering from Malaria and bite them preferentially. Humans are their preferred target, if a human is not available, they go for domestic animals like cows, goats, donkeys or horses.

But humans are the only host of Plasmodium. Recently, Plasmodium knowlesi jumped from monkeys to humans. It was first reported from Thailand, then from India and now from Brazil – the species of monkey varies in different countries.

During WW II, the insecticide DDT was extensively used by the US army and nearly wiped-out malaria from the South Asian countries except in a few isolated pockets malaria remained. After DTT use was banned, malaria returned. At present, malaria is endemic in most nations of South East Asia and Sub Sahara Africa

Controlling mosquito Larvae.

The female mosquitoes lay eggs in stagnant water. After the larvae hatch, they swim just below the surface of the water and larvae breathe through tiny tubes that barely break the water surface, they take in oxygen through those tubes. Almost the same design as Scuba drivers' mouthpieces.

A thin film of oil can easily cover the opening of the tubes and the larvae will die from suffocation.

But this process requires constant surveillance by all households and local municipalities. In endemic countries, such facilities are hard to come by in remote villages on a regular basis.

Biologic control.

Fish: Sunfish, tilapia, minnow and mosquito fish are good predictors in ponds and pools.

Bacteria: Bacillus thuringiensis thrives on mosquito larvae in any collection of stagnant water.

Fungus: Laegenidium giganticum parasitize and kill larvae.

Nematodes: Mirmithid does the same

Draining pooled water:  Keep garden pots and pans, old automobile tires, birdbaths, etc. must be cleaned and kept dry when not in use. But compliance is poor. Flooded rice fields, ponds and pools in the monsoon season are good breeding grounds for mosquitoes. It is not possible to drain the rice fields.

Controlling adult mosquito.

Personal protection: Appropriately covering the body in dusk and dawn, when mosquitoes are most active, should help to limit the spread of malaria. Use of insect repellents when outdoors also limits mosquito bites.

Bed-nets: Insecticide treated bednets have proved a very effective way to greatly limit malaria in children in Africa.

Fogging insecticide: In an endemic situation, large areas can be covered with a thin layer of insecticide spray and repeated at intervals throughout the endemic period.

Properly constructed houses: Eliminating mosquito entry points inside the rooms by screens on doors and windows, repairs of cracks on walls and roof can greatly limit mosquito bites.

Release of sterile male mosquitoes: It is shown to be effective in small selected areas. When male mosquitoes have mated with females, they produce only sterile eggs which fail to hatch.

Chemoprophylaxis for Malaria:

Chloroquine, proguanil, mefloquine and doxycycline were used in the past, and some of them are currently in use.

There are two separate types of chemoprophylaxis. One for travelers, intended to stay in the malaria prevalent area for a limited time. The other is for the local inhabitants.

Protecting Locals.

All local inhabitants have some level of immunity from previous infections but the immunity levels wax and wane from time to time and due to other chronic diseases. When their natural immunity level is low, they are again susceptible to malaria.

Pregnant women are at special risk, and both mother and child are at risk of dying from malaria attacks. WHO recommends chemoprophylaxis for all pregnant women in African countries.

Selection of medication, dose and duration of prophylaxis depend on the country and the prevalence of the type of plasmodium species and drug resistance in that locale.

In general, malaria is now widely resistant to chloroquine. In Thailand malaria is resistant to mefloquine also. Recently mefloquine malaria is reported from Sub Sahara Africa.

Disruptive prophylaxis:

Plasmodium parasite uses a calcium channel signal pathway to infect RBCs. The way to disrupt this signaling has been worked out and methods are been developed to achieve that goal.

Malaria Vaccine:

Vaccine development is a frustrating aspect of malaria control. A vaccine is developed after countless hours of hard work by many researchers and generous funds provided by the WHO and NGOs - specially from the Bill and Melinda Gates Foundation, and initial trials appeared effective, but a few months later turns out not so effective due to decreased immune response and mutation of the parasite.

Recent a vaccine is been produced by combining a protein taken from the per-erythrocyte stage of the Plasmodium falciparum and a gene from the hepatitis B virus which acts as an adjuvant. This vaccine is intended to prevent infection of liver cells by the parasites due to the presence of the newly formed neutralizing antibodies and the ultimate removal of the parasites by phagocytes.

Many other vaccines are also presently in the development stages using the same principle but using different antigen/ antigens and vectors.

One novel vaccine was developed by the US armed forces and US Public Health Service by using gamma rays irradiation. Mosquitoes with malaria parasites in their stomach, subjected to gamma radiation making the parasites incapable of multiplying and infect red cells but still are capable of invading liver cells and retaining the antigen against which an immune response and antibody production takes place.

Vaccines are also being developed against P. vivax which generally resides in the liver cells of patients for a long time and continues to infect RBC at intervals. The protein used by vivax to infect red cells is identified and used in vaccine development.

Monoclonal Antibodies.

The genome of Plasmodium is known. Many suitable antigens have been identified and monoclonal antibodies are in the development stages to block or neutralize Plasmodium and prevent infecting liver cells and or RBCs.

Several approaches have been applied to control malaria at different times in the past. But none produced any lasting benefit.

Malaria protozoa have a remarkable character of developing resistance to drugs intended to kill the parasite. Protecting people from mosquito bites proved to be a daunting task because of the vast number of venerable people involved. The destruction of the environment and the warming of the climate make malaria appear in countries in the temperate zones where malaria was unknown before. The use of pesticides in mosquito control is coming under review and approved for restricted use only because of their adverse impacts on the environment and proven to be harmful to people and may even cause cancer.

Artemisinin is the most effective and widely used drug but is made ineffective due to the development of resistance in Southeast Asia. Recent reports from Africa say the artemisinin resistance is developing there also. Gene editing confirmed that this mutation can drive artemisinin resistance. This study provides evidence for the de novo emergence of artemisinin resistance in Rwanda, Africa.

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