Malaria

Dr. Shree Narayan Yadav

Internal Medicine Resident
NAMS
 INTRODUCTION
•Protozoan disease

•Transmitted by the bite of Female Anopheles mosquito.

•It is transmitted in 106 countries containing 3 billion people

and causes approximately 2000 deaths each day.
 ETIOLOGY
• 5 Plasmodium species known to cause malaria in humans are:
 P. falciparum
 P. vivax
 P. ovale
 P. malariae
 P. knowlesia
• P. Knowlesia is primary parasite of macque monkeys but causes human
malaria in certain areas of South-east Asia.
 Epidemiology
Malaria occurs throughout most of the tropical and Sub tropical regions of
the world.
Uncommon in areas above 2000 m.

Stable transmission:
• Where populations are continuously exposed fairly constantly to high
frequency of malarial inoculation.
• Transmission occurs consistently round the year.
• The bulk of mortality is seen in children
• Those who survive to adulthood acquire significant immunity.
 Unstable transmission:
• Where transmission is seasonal or low, erratic
• full protective immunity is not acquired and
• symptomatic disease may occur at all ages.

Malaria can also be transmitted in

• Contaminated blood transfusions
• Injection drug users who shares needles.
• Hospital acquired infection related to contaminated equipment.
• Based on the achievements the country has made over the last decade,
Nepal is preparing to move towards malaria elimination by 2026.
Life cycle of plasmodium
• Each erythrocytic schizogony takes about 48 hours in P. Falciparum ,
P. vivex and P ovale and about 72 hours in P. malariae disease.
 Pathogenesis
• The pathology of malaria is related to;
Anaemia
Cytokine release
Wide spread organ damage due to impaired micro circulation : in
case of P. falciparum malaria.
 • Causes of Anaemia in Malaria
• Hemolysis of infected RBCs
• Hemolysis of non infected RBCs (Black water fever)
• Dyserythropoesis
• Splenomegaly and sequestration
• Folate depletion
 Clinical features
• Uncomplicated malaria:
Non specific symptoms: lack of a sense of well being, headache,
fatigue, abdominal discomfort, and muscle aches followed by fever

The classic malarial paroxysms, in which fever spikes, chills, and

rigors occur at regular intervals, are relatively unusual and suggest
infection with P. vivax or P. ovale
 Severe falciparum malaria
Cerebral malaria:
The clinical case definition of cerebral malaria includes the following
criteria:
• Blantyre coma score ≤2(Gcs less than 11)
• P. falciparum parasitemia (any density)
• No other identifiable cause of coma (eg, hypoglycemia, meningitis, or a
postictal state)

Death rates of ~20% among adults and 15% among children

Failure to localize or respond appropriately to noxious stimuli; coma
persisting for >30 min after generalized convulsion
Convulsions, usually generalized and often repeated, occur in ~10%
of adults and up to 50% of children
Manifest as diffuse symmetric encephalopathy; focal neurologic signs
are unusual.
No signs of meningeal irritation
Preserved corneal reflex
Muscle tone either increased or decreased
Funduscopy shows ~15% of patients have retinal hemorrhages
The majority of these deficits improve markedly or resolve
completely within 6 months.
Hypoglycemia:
Plasma glucose level of <2.2 mmol/L (<40 mg/dL)
Associated with poor prognosis

Acidosis:
Arterial pH of <7.25 or plasma bicarbonate level of <15 mmol/L
venous lactate level of >5 mmol/L
manifests as labored deep breathing, often termed respiratory distress
Results from accumulation of organic acids
It is followed often by circulatory failure refractory to volume expansion or
inotropic drug treatment and ultimately by respiratory arrest
Associated with poor prognosis

Renal impairment:
Serum or plasma creatinine level of >265 μmol/L (>3 mg/dL); urine output
(24 h) of <400 mL in adults or <12 mL/kg in children; no improvement with
rehydration
In survivors, urine flow resumes in a median of 4 days, and serum creatinine
levels return to normal in a mean of 17 days
Hematologic abnormalities:
Normocytic normochromic anemia
Hematocrit of <15% or hemoglobin level of <50 g/L (<5 g/dL) with
parasitemia <10,000/μL
Mild thrombocytopenia is usual
Of patients with severe malaria, <5% have significant bleeding with
evidence of disseminated intravascular coagulation.
Hematemesis from stress ulceration or acute gastric erosions also may occur
rarely.
Liver dysfunction:
Mild hemolytic jaundice is common in malaria.
Severe jaundice is associated with P. falciparum infections
Serum bilirubin level of >50 mmol/L (>3 mg/dL) if combined with a
parasite density of 100,000/μL or other evidence of vital-organ dysfunction
Hypotension/shock:
Systolic blood pressure of <50 mmHg in children 1–5 years or <80 mmHg
in adults; core/skin temperature difference of >10°C; capillary refill >2 s

Non cardiogenic pulmonary edema

Hemoglobinuria
Hyperparasitemia
Extreme weakness
Complications of chronic malaria

• Tropical splenomegaly
• Quartan malarial nephropathy
• Burkitt’s lymphoma
 Diagnosis
The diagnosis of malaria rests on the demonstration of asexual forms of the
parasite in stained peripheral-blood smears
Repeat blood smears should be performed at least every 12–24 h for 2 days if
the first smears are negative and malaria is strongly suspected.
Microscopy- Thin and thick blood smears
Rapid diagnostic test (antibody based)- pfHRP2, LDH (Optimal), Microtube
concentration methods with acridine orange staining
PCR
Thick film, erythrocytes are lysed, releasing all blood stages of the parasite
- facilitates the diagnosis of low-level parasitaemia
Thin film is essential to confirm the diagnosis, to identify the species of
parasite and, in P. falciparum infections, to quantify the parasite load (% of
infected erythrocytes)
 TREATMENT
Chloroquine remains a first-line treatment for the non-falciparum malarias
except in Indonesia and Papua New Guinea, where high levels of resistance in
P. vivax are prevalent.
There is increasing resistance to chloroquine in some strains of P. vivax and
co-infection with P. falciparum.

So use of oral artemisinin combination therapy should be preferred where

available for all malaria cases.

World Health Organization (WHO) now recommends artemisinin-based

combinations (ACTs) as first-line treatment for uncomplicated falciparum
malaria.
Suitable artemisinin combinations for malaria
Drug treatment for uncomplicated malaria;
Drug treatment of severe falciparum malaria:
 In case of severe Malaria;
IV artesunate is more effective than IV quinine and should be used whenever
available. Injection in IM form is less reliable than from IV injection.
ICU facilities may be needed , including mechanical ventilation and dialysis.
Severe anemia may require transfusion.
Careful monitoring of fluid balance is essential , both pulmonary oedema and
pre renal failure is common.
Hypoglycemia can be induced both by infection itself and by quinine
treatment.
Superadded bacterial infection is common.
 Antimalarial Drugs;
Quinine and Quinidine:
 Acts mainly on trophozoite blood stage; kills gametocytes of P. vivax, P.
ovale, and P. malariae (but not P. falciparum); no action on liver stages
Adverse effect:
“Cinchonism”: tinnitus, hightone hearing loss, nausea, vomiting,
dysphoria, postural hypotension; ECG QTc interval prolongation
Hypoglycemia
Hypotension, cardiac arrhythmias
Chloroquine:
Nausea, dysphoria, pruritus in dark-skinned patients, postural hypotension,
slight ECG QTC prolongation
Hypotensive shock (parenteral), cardiac arrhythmias, neuropsychiatric
reactions

Piperaquine:
Epigastric pain, diarrhea
Amodiaquine:
Nausea

Primaquine:
Radical cure; eradicates hepatic forms of P. vivax and P. ovale; kills all stages
of gametocyte development of P. falciparum
Nausea, vomiting, diarrhea, abdominal pain, hemolysis, methemoglobinemia
Mefloquine:
Nausea, giddiness, dysphoria, fuzzy thinking, sleeplessness, nightmares,
sense of dissociation
Neuropsychiatric reactions, convulsions, encephalopathy

Lumefantrine:
Highly variable absorption related to fat intake
Artemisinin and derivatives:
Broader stage specificity and more rapid than other drugs; no action on liver
stages; kills all but fully mature gametocytes of P. falciparum
Adverse effect:
Reduction in reticulocyte count; neutropenia at high doses; in some cases,
delayed anemia after treatment of severe malaria with hyperparasitemia
Fever, urticaria
 Prevention and control
“RolI back malaria” campaign in 1998 A.D. had considerable success and
global malaria specific mortality rate decreased by 25% between 2000
and 2010 A.D.
The latest WHO malaria 2018 report shows no significant improvement
in reducing malaria incidence and mortality between 2015 and 2017 A.D.
• A 3 part strategy is now widely endorsed and supported by different
government and non governmental organization.
• The strategy are
1. Aggressive control in highly endemic countries , to reduce
mortality and decrease transmission.
2. Progressive eradication at the endemic margins, to shrink the
malaria map.
3. Research into new vaccines , new drugs, new diagnostics and better
way of delivery malaria care.
 Prevention
Insecticide treated bed nets
insecticides for spraying dwellings
recombinant protein sporozoite-targeted adjuvented vaccine (RTS,S)
New vaccine Mosquirix
 Personal protection against malaria
The avoidance of exposure to mosquitoes at their peak feeding times
(usually dusk to dawn)
The use of insect repellents containing 10–35% DEET (or, if DEET is
unacceptable, 7% picaridin)
suitable clothing
Insecticide-impregnated materials.
 Chemoprophylaxis
When there is uncertainty, drugs effective against resistant P.
falciparum should be used (atovaquone-proguanil, doxycycline, or
mefloquine)
Mefloquine is the only drug advised for pregnant women traveling to
areas with drug-resistant malaria
Children born to nonimmune mothers in endemic areas (usually
expatriates moving to malaria-endemic areas) should receive
prophylaxis from birth.
Should start 2 days to 2 weeks prior to departure and continue till 4
weeks after leaving endemic area
Atovaquine-proguanil or primaquine can be discontinued 1 week after
departure from endemic area.
Malaria prophylaxis for adult travellers
 Reference
Harrison’s principle of internal medicine 20th edition.
Davidson’s principle of medicine.
Kumar and Clarks Clinical Medicine 10th edition..
WHO guidelines for treatment of malaria.

THANK YOU.