Please enable JavaScript.
Coggle requires JavaScript to display documents.
PBL for Antimicrobial (Group 3), CONCLUSION: Patient infected with Malaria…
PBL for Antimicrobial (Group 3)
Learning Outcome 4
Chloroquine therapy
Introduction
A drug that is used to prevent and cure malaria, which is spread by mosquito bites.
Belong to a group of medications called as antimalarials.
First developed for the treatment of malaria in the 1940s.
Chloroquine and its derivative hydroxychloroquine have now been repurposed for the treatment of a variety of other illnesses, including HIV, rheumatoid arthritis, and systemic lupus erythematosus.
Mechanism of action
Malarial parasite will tend to consume the hemoglobin of the host cell to gain necessary amino acids
A substantial amount of heme will be released as a result of the process
Malarial parasite is very hazardous to free heme because it can lyse membranes. In order to protect themselves, they will use the heme polymerase that is stored in the food vacuole to polymerizes heme to non-toxic hemozoin.
Chloroquine will inhibit the function of heme polymerase
Chloroquine binds to released heme to produce a heme quinoline complex, which inhibits the heme polymerase enzyme and prevents heme polymerization.
Inhibited heme polymerase will lead to failure in converting heme to non-toxic hemozoin
The free heme in the body will cause lysis of both malarial parasite and the infected RBC.
Pharmacokinetics
Distribution
Distributed at a rate of 200 - 800 L/kg.
Bind to alpha-1-acid glycoprotein and serum albumin for their distribution in the body.
Metabolism
Chloroquine is rapidly dealkylated by cytochrome P450 enzymes (CYP) into pharmacologically active desethylchloroquine and bisdesethylchloroquine after ingestion.
Absorption
Bioavailability of chloroquine oral solution is 52–102%
Bioavailability of chloroquine oral tablet is 67–114 %.
Bioavailability of intravenous chloroquine has a 100%
Oral chloroquine has a Cmax of 65–128 g/L
Intravenous chloroquine has a Cmax of 650–1300 g/L.
Elimination
Chloroquine is mostly removed through the urine
Half-life of 20 to 60 days
Dosage & strength
Prevention
Take 500 mg (300 mg base) every week on the same day. Consume the medication for 1–2 weeks before going to an endemic area and for 4 weeks after leaving the endemic region.
Treatment
Take 1 g (600 mg base) orally, then 500 mg (300 mg base) orally 6–8 hours later, then 500 mg (300 mg base) orally 24 hours and 48 hours later. In a chloroquine-resistant area, add 100 mg of proguanil.
Side effects and contraindication
Common
Headache, nausea, loss appetite, diarrhea,
upset stomach, stomach pain, rash, itching, hair loss
Severe
Seeing light flashes and streaks, blurred vision, difficulty hearing,
muscle weakness, drowsiness, vomiting, irregular heartbeats, convulsions, difficulty breathing, mental changes,
decrease consciousness
Contraindication
Hypersensitivity
Acute extrapyramidal disorder
Hemolytic anemia
Gene mutation
Cardiomyopathy
Conduction disorder
Hypoglycemia
Retinopathy
Psoriasis & Porphyria
QT prolongation
Chloroquine resistance
Drug resistant P. vivax
P. vivax malaria resistant to chloroquine was first discovered in Australia and Papua New Guinea in 1989. Chloroquine resistance in P. vivax has now been discovered in Southeast Asia, Ethiopia, and Africa.
Drug resistant P. falciparum
In the late 1950s and early 1960s, chloroquine-resistant P. falciparum formed independently in Southeast Asia, Oceania, Gabon, Gambia, Ghana, and South America.
Post choloroquine therapy condition
Mr Smith received chloroquine as part of his malaria treatment. But he become obtunded, pale, dehydrated, and more icteric with profuse sweating, fever, tachypnea and hemodynamic instability. Hemoglobin fall to 4.8 g/dL accompanied by hyperbilirubinemia. The patient was admitted to ICU and therapy was started. During the oral therapy he was experiencing vomiting and dizziness after drug administration.
Mr. Smith's symptoms may indicate that the medication provided, chloroquine, is ineffective and inappropriate for him. The main explanation could be because Mr Smith is originated from Gabon, a chloroquine-resistant country. As a result, the malarial parasite becomes resistant toward the chloroquine treatment, and the drug has no impact on the malarial parasite.
.
Drug regimen
Intravenous (IV) Artesunate
Artemisinin derivatives
Highly effective and rapid schizonticidal drug
Water-soluble (it can be given via parenteral route)
Antimalarial treatment
It is considered as the first-line of treatment for severe malaria
It has a rapid parasite clearance
Devoid of major side effects and its use does not warrant intensive monitoring
Can be used in remote-peripheral centers
rapid drug delivery is said to be greatest here
Dose (adult): 2.4 mg/kg BW per dose
should be used for at least 24 hours
3 doses of IV artesunate should be given:
First dose is given immediately
Second dose is given at 12 hours
Third dose is given at 24 hours
Dispensed as a powder of artesunic acid
Dissolved in sodium bicarbonate (5%)
Diluted in 5 ml of 5% dextrose
It should be prepared freshly for each administration and should not be stored. This is because artesunate is rapidly hydrolysed in-vivo to dihydroartemisinin (main antimalarial effect)
Injectable antibacterial agents with antimalarial activity should be used alone
Its spectrum and speed of action are found to be inadequate.
As soon as the patient is able to tolerate oral medications, a regimen of a follow-up drug should be insituted
Artemether and lumefantrine
It is an artemisinin-based combination therapy (ACT)
A combination of a rapidly acting artemisinin derivative with a longer-acting partner drug
The artemisinin component can rapidly clear parasites from the blood
Active against the sexual stages of the gametocytes
Longer-acting partner drug clears the remaining parasites
Provides protection against development of resistance to the artemisinin derivative
Oral artemether drugs should never be administered without a second agent
Risk of developing transmissible artemether-resistant parasites
A full 3-day regimen of ACT is recommended
It covers 2 asexual cycles to ensure a small fraction of parasites remain for clearance by the partner drug
To reduce possibility of resistance to the partner drug
Artemether: 5-24 mg/kg
Lumefantrine: 29-144 mg/kg
This combination is given twice a day for 3 days (total of 6 doses). The first two doses should be given 8 hours apart.
80 mg/kg and 480 mg/kg for 3 days (more than 35 kg)
Paracetamol (acetaminophen)
To treat his fever accompanied with tepid sponging and fanning
Dose: Two 500 mg tablets
Paracetamol is given four times a day for 3 days (a total of 24 doses)
Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided
Can cause gastrointestinal bleeding
Lorazepam
To control seizures in the patient
Administer intravenously
Dose: 10 mg
Slow administration of IV lorazepam within that dose can control his seizures
It has to be given slowly to prevent respiratory depression
It can be repeated every 15 minutes if seizure persists
Total dose should not exceed 100 mg in 24 hours
Phenobarbitone is no longer recommended due to high mortality rate although it reduces seizures
Learning Outcome 1
Definition of Malaria
caused by protozoan parasites under the Plasmodium family
transmitted through the infected female anopheles mosquito bite, blood transfusion or contaminated needle
most dangerous and caused the most death case is Falciparum malaria
Plasmodium falciparum malaria has good prognosis as if it is treated early and appropriately
Types of Malarial Parasites
Plasmodium malariae
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
P. vivax and P. ovale can be reactivated after 2 to 4 years
P. falciparum is the most common while P. ovale is rare
Sign and Symptoms
shaking chills, high fever, sweating, headache as well as muscle ache
nausea, vomiting, diarrhoea, fatigue, spleen enlargement, rapid breathing and rapid heart rate and also coughing
malaria “attacks” which it normally starts with shivering and also chill, then followed by a very high fever, sweats and then return back to normal body temperature
begin in a few weeks after the person got the bite or stay inside the body for years without giving any symptoms
Severe Complicated Malaria
confusion, alteration of consciousness such as drowsiness developed to coma, respiratory distress which the patient will have acidotic breathing, seizures, shock, bleeding problem, jaundice on eyes as well as skin, liver and kidney failure which the patient might have oliguria or anuria, anaemia as well as hypoglycaemia
begin within 10 days to 4 weeks after getting infected
infected person might feel sick in 7 days or 1 year later
P. vivax and P. ovale infections, they both can cause relapsing malaria as some of the parasite will remain dormant in the patient liver
Risk Factors
who live or visited the area which malaria cases are high
tropical and subtropical regions such as Sub-Saharan Africa, South and Southeast Asia, Central America and Northern South America as well as Pacific Islands
young children, infants, elderly, pregnant women with the unborn child and also travelers who came from the place that does not have malaria case
pregnant women will have higher chances and there is lower chance of the baby to be survive
non-immune pregnant women > miscarriage and maternal death
semi-immune pregnant women > low birth weight infants in first and second pregnancy
young children
people who has HIV or AIDS
Epidemiology
Malaria is endemic in most of the tropics and sub-tropics which are including in areas of the Sub-Saharan Africa, Asia, Caribbean, Oceania, and South America.
In 2019, World Health Organization (WHO) had already estimated that two hundred and twenty-nine million new cases of malaria which resulting in four hundred and nine thousand deaths.
The global incidence of the disease and mortality was declined in recent years. According to the statistics from WHO and UNICEF, the deaths due to malaria in 2015 was reduced by 60% from a 2000 estimate of nine hundred and eighty-five thousand.
In 2020, World Health Organization estimates 241 million clinical cases of malaria occurred, and six hundred and twenty-seven thousand people died of malaria in Africa, and most of them children.
Etiology
Malaria is caused by the single-celled parasite of the genus plasmodium. So, it is commonly transmitted from biting of the female Anopheles mosquito which has infected with parasites, then the infected mosquito will transfer the parasites into the person’s bloodstream, where the parasites will multiply and cause the malaria infection in the human body.
Parasites enter the body, then travel to the liver and wait for the parasites mature. Then, they leave the liver and infect the red blood cells and cause the development of malaria symptoms.
So, there are many different types of plasmodium parasite, but commonly there are 4 types of protozoa that cause malaria in humans which include Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae.
Learning Issue 5
Patient counselling
Oral Artemether-Lumefantrine (AL)
Adverse effects & Toxicity
Severity increases as dosage of artemether in combination therapy increases
Artemether more prone to maternal toxicity, embryotoxicity & malfunction in animals (in vivo)
Lumefantrine (>1000 mg/kg/day) showed no evidence
Adverse rxn
Embryotoxicity
Teratogenicity
Foetal loss
QT prolongation
Hypersensitivity
Common side effects
Anorexia
Asthenia
Headache
Precautions
Aware of symptoms of heart problems
e.g. pounding, irregular heartbeats
QT prolongation
NOT suggested to pt. w/ medical history of heart problem
Diet
NO grapefruit / grape juice
increases risk of side effects
Breastfeeding is not suggested
Restricted until at least 1 - 4 weeks after last administration
Longer half-life Lumefantrine (2 - 6 days)
If pt. vomit after taking meds (within 1 - 2 hours)
Take another full dose of the meds again
If vomit again, immediately seek the doctor / emergency
MOA
Artemether
Short-acting drug
Half-life (1 - 3 hours)
Metabolism
CYP450 (2B6, 3A4, 2A6) into DHA
Convert into inactive metabolites via glucuronidation @ bile elimination
More rapid onset of action
Rapid symptomatic relief
1 more item...
Active agents against sexual & asexual stages of parasite cycle
Lumefantrine
Long-acting drug
Half-life: Healthy (6 days) & P. falciparum malaria pt. (3 - 4 days)
Metabolism
N-debutylation by converting CYP450 3A4 to desbutyl-lumefantrine w/ 5-8-fold antiparasitic effect than lumefantrine
Inhibits CYP450 2D6
involved in inhibition of β-hematin by:
2 more items...
Slower absorption & clear from body
Longer elimination of remaining parasite after effects of artemether is cleared
Minimizing risk of recrudescence
Recrudescence: Repeated malaria attack due to survival in RBC
Relapse: Recurrence of malaria after cure
Relapse ≠ Recrudescence
IV Artesunate
Adverse Effects & Toxicity
1st & 2nd Trial
Hemoglobinuria (6.7%)
Jaundice (2.3%)
Dialysis (8.9%)
3rd Trial
Increase of transaminase (27%)
Anemia (65%)
Thrombocytopenia (18%)
In-hospital mortality of patient with severe malaria (13%)
Precautions
Post-treatment hemolysis
Monitor patient for 4 weeks after given IV Artesunate
Hypersensitivity
found to be likely in IV Artesunate treatment
Discontinue IV Artesunate & Replace with another antimalarial drug
Renal impairement
Hepatic impairment
In pregnancies
Estimated risk
Major birth defects (2% - 4%)
Miscarriage (15% - 20%)
Insufficient clinical records on risks
MOA
Has endoperoxide bridge
Causing
Inhibition of protein & nucleic acid synthesis
Ultrastructural changes
Oxidative stress
Decreased growth & survival of parasite
Activated by heme Iron
Derivatives of artemisinin
acts for conversion of DHA
Active against gametocytes of Plasmodium species (including chloroquine-resistant strains)
Acetaminophen (Paracetamol)
MOA
The conversion of arachidonic acid to prostanoids is a two-step process that begins with COX activity, which produces the unstable intermediate hydroperoxide prostaglandin G2 (PGG2), which is then transformed to prostaglandin H2 (PGH2) by POX
The oxidised form of COX is required for its enzymatic activity, but paracetamol interferes with this indirectly by serving as a reducing co-substrate at the POX site.
When arachidonic acid levels are low in intact cells, paracetamol inhibits prostaglandin production by preventing the natural regeneration of POX.
It also been suggested that acetaminophen inhibit the COX-1 splice variant known as COX-3, however this has yet to be proven in humans.
Acetaminophen’s suppression of COX pathway activity is suggested to inhibit the prostaglandins synthesis in the central nervous system, resulting in analgesic and antipyretic effects.
The analgesic actions could be related to a stimulating influence on the descending serotonergic pathways in central nervous system.
In the presence of fatty acid amide hydrolase (FAAH), a central nervous system enzyme, paracetamol is conjugated with arachidonic acid via an intermediary, p-aminophenol, generated in the liver, to form the active metabolite, N-arachidonoylphenolamine (AM404).
AM404 reduces the absorption of the endocannabinoid anandamide from synaptic clefts, enhancing cannabinoid receptor activity on the post-synaptic membrane, similar to serotonin or norepinephrine reuptake inhibitors
Drug disease interaction
Liver disease
Acetaminophen is mostly converted to inactive forms in the liver
Metabolites that can cause hepatotoxicity or methemoglobinemia via minor routes
Due to increased minor metabolic pathway activity, patients with hepatic impairment may be at an elevated risk of toxicity
Similarly, persistent or excessive acetaminophen use might overburden major hepatic enzymes, resulting in increased metabolism via secondary routes.
Adverse effect and toxicity
The most common side effects of paracetamol consumption are drowsiness, fatigue, rashes and itching
Serious side effects of paracetamol are low fever with nausea, stomach pain, loss of appetite, dark urine, clay-colored stools, or jaundice
Acute overdose of paracetamol can cause potentially catastrophic kidney, brain, and liver damage, and in rare cases, even after a therapeutic dose, due to the existence of subclinical risk factors such as 'fast-metabolizer' status, glutathione deficiency, or both.
Precaution
In the worst-case situation, unintentional overdosage can generate enough toxicity to cause death, usually owing to severe liver failure.
Even at the recommended dosage levels, people who are at a higher risk of side effects should be cautious when using paracetamol.
IV Lorazepam
MOA
Lorazepam binds to benzodiazepine receptors on postsynaptic GABA-A ligand-gated chloride channel neuron at various places throughout the central nervous system (CNS) allosterically
It increases the conductance of chloride ions into the cell by enhancing the inhibitory effects of GABA. The cellular plasma membrane is hyperpolarized and stabilised as a result of the shift in chloride ions.
Drug disease interaction
Seizure
increase the incidence or hasten the beginning of generalised tonic-clonic seizures (grand mal).
Seizures and other withdrawal symptoms may occur if benzodiazepine therapy is abruptly stopped, especially if it has been used for a long time or at high doses
Patients with a history of seizures who are abruptly removed from benzodiazepine medication may develop status epilepticus.
Drug dependence
After extended use or excessive dosages, tolerance as well as physical and psychological dependence might develop
Sudden termination after as little as 6 weeks of continuous use at therapeutic doses has occasionally resulted in withdrawal symptoms
The usage of benzodiazepines has the potential to lead to addiction and misuse
Adverse effect and toxicity
In status epilepticus, in which if not treated properly, this could be a life-threatening illness with a high chance of permanent neurological disability, hypotension, somnolence and respiratory failure are the most adverse clinical event observed
Result in central nervous system and respiratory depression. It can cause hypotension, ataxia, disorientation, and coma, as well as death
Lorazepam, like other benzodiazepines, is seldom linked to increased serum alanine aminotransferase (ALT) levels, and clinically obvious liver impairment caused by lorazepam is extremely rare
Precaution
The possibility of extreme tiredness or drowsiness when lorazepam injection is given intravenous as a premedicant prior to regional or local anaesthesia may interfere with patient cooperation in selecting anaesthesia dosage
Due to risk of hypoventilation and hypoxic cardiac arrest, injection should be given with extreme caution to elderly patients, severely unwell patients, or patients with poor pulmonary reserve
Precaution of Malaria
Awareness of risk
It helps to check if we need to take malaria prevention treatment due to the country that will be visited.
To take advice as for malaria prevention when already confirmed the place that going to be travelling
Although malaria is common in our own country, precautions steps still required to prevent any infection at the risk area.
Bite prevention
Mosquito bitten can be avoided by stay at place that provide effective air conditioning and screening on doors and windows or either ensure that the doors and windows are close properly.
Insect repellent using also recommended to apply frequently for skin and in sleeping environments. Repellents that contain of diethyltoluamide (DEET) are the most effective
Check if need to take malaria prevention medication
No vaccine was available to protect against malaria, thus antimalarial medication was given to decrease the risk of getting malaria
Choosing of antimalarial medication is depending on strain of malaria that carried by the mosquitoes and if it is resistant towards certain types of antimalarial medication
Diagnosis
Blood smear test
Polymerase chain reaction (PCR)
Complete blood count (CBC)
Blood glucose test
Learning Outcome 3
BLOOD SMEAR INTERPRETATION (Identifying patients plasmodium)
Types of Malaria Plasmodium
P. ovale
Sub-Saharan Africa and tropical western Africa
P. malariae
South America, Asia, and Africa
P. falciparum
Sub-Saharan Africa
P. vivax
southeast asia and western pacific regions
Geography of Plasmodiums
P. knowlesi
Southeast asia
Pathophysiology with transmission of Plasmodium
Vector: Female Anopheles Mosquito
Life cycle of Plasmodium species
Gametocyte
Start of cycle: Gametocyte carried by female mosquito
Sporozoite
Gametocyte mature into sporozoite
Mosquito released sporozoites then enter the blood stream
Taken up by Hepatocytes
asexual pre-erythrocytic liver stage (liver schizonts)
1 more item...
Merozoite
Formed by multiplying within hepatocytes
Transport to circulation and infect RBCs'
Cycle of asexual merozoite replication stages
4 more items...
Patient's plasmodium diagnosis
WHO says
Major plasmodium species in Angola: P. falcipuram by 100%
total estimated case: 4.6 million. total estimated deaths: 13.3K
Minor plasmodium species in Angola: P. vivex by 0%
Major Anopheles species in Angola: An. gambiae, An. funestus and An. Nili
Morphology of P. falciparum
Ring
consists of a central vacuole, cytoplasm as well as a nucleus, ring forms, which are about a sixth the diameter of red blood cells and it has also been demonstrated to be incredibly thin and delicate
patient blood sample showspresence of ring structures can be seen in the red blood cells which shows that plasmodium is in the ring stage
Trophozoite
contains a vacuole and only a one nucleus,They're tiny, measuring between 1.25 and 1.5 microns in diameter. They may also have a signet ring shape and a thin cytoplasm
Schizont
about two-thirds of the size of a red cell, measuring between 4.5 and 5 um in diameter. They have two or four merozoites (which are created by dividing Schizonts) and can grow to have up to 30 merozoites as well as pigments that appear dark when stained. P. falciparum schizonts are also tiny and stationary, and they represent the parasite's dividing form
Gametocyte
reproductive forms of the parasite, have a crescent shape. Both male and female versions of the parasite, which are about one and a half the size of a normal red cell, are sexual forms
LAB RESULT
Haemoglobin
Low value of haemoglobin with 11.9 g/dL
normocytic and normochromic anaemia
due to life cycle of the malarial parasite at blood stage infection
Merozoites are released into the bloodstream.
Invasion towards RBCs.
In RBC, merozoite changes to trophozoite.
Parasite feeds on the haemoglobin in trophozoite form.
Plasmodium falciparum
infection have high possibility to induce severe anaemia from moderate anaemia
because of a rapid rate of multiplication while producing antigens (Pf-EMP-1) that are clonally variant on the surface of infected RBCs.
Platelet
Low platelet count: 27, 000/μL
thrombocytopenia
due to
innate host defence against malaria
by direct lytic
kill directly through platelet factor 4 (PF4), an abundant antimicrobial after entry into the infected RBCs
entry via the Duffy antigen, chemokine receptor found on RBCs
selectively lysing the parasite digestive vacuole to kill parasite
Platelets have variety of antimicrobial molecules, possess broad-spectrum pathogen-killing activity and required for host-mediated pathogen control
5% of circulating blood-stage parasite are destroyed by platelets
platelet-RBC complexes
Haematological analysers unable to detect the complex
Platelets have a high capacity to bind to Plasmodium infected-RBCs (iRBCs)
PfEMP1 of P. falciparum causes platelets-RBC binding by CD36
half of the total platelet pool made up of the complexes because the complexes are higher than free plateles
enlargement of spleen causes the complexes unable to be eliminated
contribution to malaria infection
platelets required for iRBCs' cytoadhesion to endothelial cells with presence of Willebrand factor (WWF) multimers
platelets enhance iRBC clumping and cause malaria microvasculature blockage
it promotes the development of inflammation and endothelial cells activation
Mild liver cytolysis without hyperbilirubinemia
In a study: 732 adult with
falciparum
malaria and 18 of them (2.45%) only had malaria hepatopathy
Liver is a main target of parasite for its life cycle
sporozoite pass through the endothelium of the capillaries to enter blood
migrate to the liver
cross the Kupffer cells (KC), hepatocytes and infecting them
gain access by
binding to CD68 receptor on KC
interaction between sporozoites and KC cause apoptosis
generation of OH radical triggers oxidative-stress-induced mitochondrial pathway of hepatocyte's apoptosis
a synthetic protein (P39) by phage in gateway model was discovered through inhibition of binding between sporozoite at the CD68 receptor
merozoites formation for blood-stage infection
manifested by an increase in transaminase
slightly elevations of plasma alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
consequences of malaria-related liver after haemolysis that can increase ALT or AST ratio
inflammatory response of immune system
Pre-erythrocytic stage
Target free sporozoites and infected hepatocytes
Production of antibodies against free sporozoites and circumsporozoite protein (CSP)
Neutralise the proteins of cell transversal and invasion
Activate phagocytosis and lysis
Kill parasite neoantigens on the surface of infected hepatocytes
natural killer, natural killer T cells and T cells can kill intrahepatic parasite by releasing of type I interferons and IFN- γ
Learning Objective 2
Risk of his job
-it was shown that the patient is used to working in building construction.
The construction sites are used for the breeding places for many types species of those mosquitoes which one of it is malaria.
This is because of the clear and stagnant water that will be the breeding ground for those mosquitoes
The Anopheles stephensi which is one of the malaria vector usually prefer to breed in either wells, overhead and ground level after tanks, fountains and curing water in the construction sites.
Medical history
He do not drink any type of alcohol and also do not have the smoking habits nor have any sexual risk contact.
But he was having eye problem which makes him to wear spectacles.
There is no any relation between the malaria with the eye problem that was faced by the patient.
Drug abuse
Sharing the same usage of needles or syringes that has been contaminated with the blood of the person infected. Anopheles mosquito could able to transmit the malaria disease and they had to be infected through the blood meal that was taken before from the person that is infected. So when the mosquito bites the infected person, there is small amount of blood has been taken in that may contain the microscopic malaria parasite. After approximately by one week later, when this mosquito make it the next blood level, the parasite will be mixed with the mosquito’s saliva and it is injected into the person that is being bitten by the mosquito
Lifestyle
Our risk of getting infected are increased by some lifestyle factors.
It is usually spread by certain geographic location where there is tropical climate and the abundance of water
The patient is born in Angola and resident in Gabon which are more prone of getting infected easily with the malaria.
A) Temperature
The minimum or the maximum of temperature could affect the development of those malaria disease which are the malaria parasite and mosquito vector.
The time that is required for the parasite to have a complete development for the mosquito lasts for 10 days however it could be longer or shorter that depends on the temperature.
When the temperature decrease, the number for the development of the mosquito increase for Plasmodium species
B) Rainfall
-Mosquitos breed in water which causes the places which has rainy season could be the breeding places of most of the mosquitos such as the anopheline mosquitoes.
When there is too much of rainfall it tend to flush away all the breeding habitats temporary however there are mosquitoes which could start breeding when the rain has stopped.
Anopheline mosquitoes are used to breed in many fresh water collection that was created after the rainy season
C) Relative humidity
refer to the amount of moisture that contain in the air as it is expressed in percentage.
This relative humidity bring an affect to the malaria transmission that is through the effect for the activity and the survival for most of the mosquitoes.
Mosquitoes usually survive better when there is high humidity. - They tend to get more active too when the humidity increases which cause them to prefer the feeding during night since the relative humidity is higher at night.
D) Water development projects.
It could either be big or small water-related developments projects could increase the chances of getting malaria such as the dams and ponds and irrigation channels.
The villagers are most likely to get infected if they are staying near those places.
The development on the agricultural where there is usage of the irrigation that will create the breeding sites for those malaria mosquitoes that lead to the increases of the transmission
Patient History (case-based)
Age
Patient aged >40 risk in getting severe malaria
Environment
Hometown : Angola
one of the top country with the highest number of malaria cases
3% of the global cases
2016-2019 (14.4% increase in malaria cases from 205 to 235 cases per 1000 of the at-risk population)
8% of yearly malaria report are severe cases
Household : Gabon
It kills at least 1 million people every year in Africa alone. Of the 300 million to 500 million annual cases of malaria, 90% occur in sub-Saharan Africa. .
Reported cases of Malaria from P.falciparum is recorded based on the 2018 Malaria report
Initial Symptoms
Patient
intermittent fever
General Malaise
Watery Stool
Irritated
Decreased apetite
Discomfort upon lying down
Profuse sweating
no vomitting
Seizure
Lethargic
dehydrated
Malaria
fever
flu-like symptoms
Nausea and vomitting
muscle pains
generally feeling unwell
Pathophysiology
Mosquito
Human
Dormant cases
Liver cells are infected with the parasite
Sporrozoites enter and replicate in the hepatic cells and burst relaseas more parasites in the body
The parasites that burst from the liver cells are called merozoites
Blood Stage
Immature trophozoite
mature Trophozoite
Schizont
Rupture schizont
Gametocyte
Male
Female
Life cycle
the microgametes penetrate the macrogametes generating zygotes .
The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop
The oocysts grow, rupture, and release sporozoites, which make their way to the mosquito’s salivary glands.
Inoculation of the sporozoites
Female Anopheles
Plasmodium falciparum,
P. vivax
P. ovale
P. malariae.
CONCLUSION: Patient infected with Malaria plasmodium falciparum
(Clinical trial: 730 patients)
Inhibition of prostaglandin synthesis
Serotonergic pathway
Cannabinoid receptor activity