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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