malaria, oetiology, epidemiology, clinical features, diagnosis, treatment, complicated or sever malaria, management of complication, profilaxis, prevention.

1. MALARIA
CLINICAL FEATURES, DIAGNOSIS AND
MANAGEMENT.
DR. RAJKOTI REDDY
DNB INTERNAL MEDICINE RESIDENT

2. 37 male, school attender, shift duties, from Shankar palli.
p/w Tertian fever with chills, rigors and muscle aches since one
week. Black colour urine since six days. Jaundice since four
days. All symptoms progressively increasing in severity.
no h/o travel, no fever in family members.
Know DM2, HTN.
no addictions
evaluted out side and treated for typhoid.
o/e concious, oriented, Icterus
Afebrile, Tachy Cardia 100/min, Tachypnea 34/min, BP
120/80mmhg.
Chest B/L air entry there, CNS no focal deficits
p/a non tender no organomegaly

3. Evaluated for fever with jaundice
RPG 45
HB 10, Plt 1.28 lakhs, WBC 6210
LFT TB 37, DB 25, ALP 169, ALT 40, AST 54, ALB 2.3
CUE Dark Amber colour, Turbid, no RBC no Cast
ABG met acidosis
USG mild spleenomegaly
PT INR normal
RFT normal
HBSAg HCV negetive.
Leptospira and scrub antibody negetive
Malaria V and F RDT negative
Smear Falciparum Gametocytes occasionally seen.

4. Smear positive falciparum
Hypoglycemia, LacticAcidosis, Hyper bilirubin, severe anemia,
hemoglobinuria.
Diagnosed as Sever Malaria
Treated with
IV Artisunate 2.4mg/kg 0, 12hr then daily once for three
days.
Ceftriaxone 1gm IV bd empirical
Patient euglycemic and afebrile for two days, CBP LFTs
improved.
Discharged on Artemether plus Lumefantrine 80/480mg for
5days
G6PD not done primaquine not given.

5. 55 yrs male, two weeks back traveld to Maharastra
p/w Intermittent fever, jaundice and abdominal discomfort
since three days.
no h/o headache, body aches. Cough, burning mucturation,
and diarrhoea.
no fever in family members and co travelers.
Know HTN, DM2
Ethanolic last bout seven days back
o/e Icterus, concious oriented, afebrile,
Pr 120/min, Spo2 97% on room air, BP 120/80mmhg.
Chest B/L air entry there, CNS no focal deficits,
P/A non tender no organomegaly megaly

6. Evaluated for Fever with jaundice
CBP HB 14, PLT 88k, TLC 10140
LFT TB 10 DB 6.8 ENZYMES normal, ALB 2.3.
RFT normal
HBSAg, HCV negetive
Leptospira antibody negetive.
SMEAR POSITIVE for both vivax and falciparum
Parasite index 0.7%.(0.1 vivax, 0.6 falciparum)
USG abdomen normal
ECG new LBBB, Trop I negetive, 2D rwama + , ef 52%.

7. Falciparum and Vivax co infection
Treated with
IV Artisunate 2.4mg/kg 0hr, 12hr then daily once for three
days.
At discharge Converted to Artemether plus Lumefantrine
80/480mg PO/BD.
Asked for review with G6PD levels report.
Planned CAG.

8. 1. OETIOLOGY
2. EPIDEMOLOGY
3. PAHTHOPHYSIOLOGY AND CLINICAL FEATURES
4. UNCOMPLICATED AND SEVER MALARIA
5. DIAGNOSIS
6. MANAGEMENT
7. PREVENTION
8. CASE DISCUSSION

9. 1. OETIOLOGY
Malaria is a protozoan disease transmitted by the bite of infected
Anopheles mosquitoes.
Six species of the genus Plasmodium
1. P. falciparum
2. P. vivax
3. Two species P. Ovale
4. P. malariae
5. P. knowlesi

10. P. falciparum, P. knowlesi and occasionally P. vivax also can
cause severe illness.
There are many vectors of malaria Anopheles culicifacies is
the main vector of malaria.
Extensive breeding is generally encountered following
monsoon rains
Most of the vectors, including Anopheles culicifacies, start
biting soon after dusk.

12. 2. EPIDEMOLOGY
P. falciparum, P. vivax prevalence is approximately equal in the
Indian subcontinent.
P. ovale is relatively unusual comprises <1% of isolates.
Stable transmission: In areas where transmission Is Constant,
frequent, year round infection.
 People infected repeatedly throughout their lives,
 Nonspecific host defense mechanisms stop the infection’s
expansion.
 subsequent strain-specific immune response then controls the
infection

13.  Eventually, exposure to sufficient strains confers protection from
high-level parasitemia and disease but not from infection.
 As a result of this state of infection without illness, “asymptomatic
parasitemia “is common among adults and older children
 But rates of morbidity and mortality due to malaria are
considerable during early childhood.

14.  But often an increased incidence of symptomatic malaria
coinciding with increased mosquito breeding and transmission
during the rainy season
Unstable transmission: areas where transmission is low, erratic, or
focal,
 full protective immunity is not acquired, and symptomatic disease
may occur at all ages.

16. TREND OF MALARIA PARAMETERS (2001-2014)

17. 3. PAHTHOPHYSIOLOGY AND CLINICAL FEATRES
Mosquito Sexula cycle. Man asexual cycle
Definitive Host. Intermediate Host.

20. • merozoites in the red blood cells (RBCs) and multiply six- to twenty fold
every 48 h (P. knowlesi, 24 h; P. malariae, 72 h).
• By the end of the intraerythrocytic life cycle, the parasite consume two-
thirds of the RBC’s hemoglobin and grow to occupy most of the cell.
called a schizont.
• Initially, the host responds to plasmodial infection by activating
nonspecific defense mechanisms.
• Splenic immunologic and filtrative clearance functions are augmented in
malaria
• The spleen remove damaged ring-form parasites and return the once
infected erythrocytes to the circulation, where their survival period is
shortened.

21. material released induces the activation
of macrophages and the release of pro-inflammatory
cytokines
Paroxysms Fever synchronize
the parasitic cycle and other
clinical feature.

22. CLINICALFEATURES – UNCOMPLICATED MALARIA
 The first symptoms of malaria are nonspecific; the lack of a sense
of wellbeing, headache, fatigue, abdominal discomfort, and muscle
aches followed by fever are all similar to the symptoms of a minor
viral illness.
 The classic malarial paroxysms, in which fever spikes, chills, and
rigors occur at regular intervals
 The fever is usually irregular at first (that of falciparum malaria may
never become regular) in P. vivax or P. ovale.
 Mild anemia, mild jaundice
 In some cases a palpable spleen and slight enlargement of the
liver

23. CLINICALFEATURES- SEVERE MALARIA

24. • Sequestration of RBC
• Increased endothelial
permeability
• Inflammatory mediators
• Activated coagulation
cascade
Cerebral Malaria:
• Coma is a characteristic and ominous feature
• Convulsions generalized
• Symmetric encephalopathy
• focal neurologic signs are unusual
• deep coma—have residual neurologic deficits
when they regain consciousness
• hemiplegia, cerebral palsy, cortical blindness,
deafness, and impaired cognition, most recover
in 6months.
Pulmonary Manifestations:
• vary from tachypnea and asymptomatic respiratory alkalosis to acute respiratory
failure.
• Self-limiting cough is the most common symptom.
• Acute lung injury (ALI) and ARDS occur in 3% to 30% of patients with severe malaria
and has been described with P falciparum as well as with P vivax and P ovale.
• Pulmonary manifestations are common in children, pregnant women, and travelers
with malaria

25. Malarial acute renal failure (MARF):
• complicates 1% to 4.5% of native population of endemic areas such as India.
• Clinically significant renal dysfunction mainly occurs with P falciparum and P
malariae
• Malarial acute renal failure in falciparum malaria is mostly due to acute tubular
necrosis (ATN).
• Factors such as hypovolemia hyperparasitemia, hyperbilirubinemia, intravascular
coagulation, hemolysis, rhabdomyolysis, severe pyrexia, and sepsis contribute to
MARF
• Malarial acute renal failure lasts from few days to several weeks and is occasionally
nonoliguric type
Hematological Abnormalities:
• Hemolysis
• increased reticuloendothelial activity in organs
such as spleen.
• massive intravascular hemolysis,
hemoglobinuria “Black water fever”
• Thrombocytopenia
• DIC

26. Gastrointestinal and Hepatic Complications:
• Hemolysis and hepatic parenchymal involvement –
Hyperbilirubinemia.
• predominantly conjugated hyperbilirubinaemia,
followed by mixed patterns, and unconjugated
hyperbilirubinemia.
• Spontaneous rupture of the spleen is an uncommon
but often fatal complication, more often reported with
P vivax.
Nosocomial Infections and/or ‘‘Algid Malaria’’:
• The term ‘‘algid malaria’’ is used for severe malaria complicated with hypovolemic
shock and septicemia.
• Most common aspiration pneumonia and primary gram-negative bacteremia
• In endemic area, Salmonella bacteremia has been associated specifically with P
falciparum infections
• Aspiration pneumonia following seizures is an important cause of death in cerebral
malaria
• In comatose patient, catheter associated urinary tract infection and nosocomial
respiratory infection, may aggravate the clinical condition

27. • Acute Renal Failure
• Impaired hepatic gluconeogenesis
• Metabolic demands of parasite -
increased glucose consumption
• anaerobic glycolysis
Metabolic Complications:
• Hypoglycemia
• Acidosis - The plasma concentrations of bicarbonate or lactate are the best
biochemical prognosticators in severe malaria.
• Quinine, a potent stimulant of pancreatic insulin secretion, also contribute to the
occurrence of hypoglycemia

28. 4. UNCOMPLICATEDAND SEVER MALARIA
Definition of uncomplicated malaria:
A patient presented with symptoms of malaria and positive parasitological test
(Microscopy or RDT) but no features of severe malaria is defined as having
uncomplicated malaria.
Criteria of complicated malaria:

29. 5. DIAGNOSIS
Suspected malaria:
In endemic area any patient presenting with fever > 37.5 C and no
other obvious cause.
In low incidence area in patients who may have been exposed to
malaria.
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. Alternatively, a rapid antigen detection card or stick test
should be performed.

30. Patient may be suffering from more than one illness:
consider co infection such as:
URTI, Pneumonia
measles, dengue, influenza
typhoid
meningitis
leptospira

32. Parasite Density:
Hyperparasitemia: Increased mortality at >100,000/μL
High mortality at >500,000/μL

33. Rapid malaria diagnostic tests (MRDT):
• use lateral flow immunochromatographic technology, using
monoclonal antibodies, for the detection of malaria antigens
either specific to a Plasmodium species or common across all
human malarias.
• P falciparum-specific tests use either histidine-rich protein 2
(HRP-2) or P falciparum lactate dehydrogenase
• pan-plasmodium antigens used include Plasmodium lactate
dehydrogenase (PLDH) and aldolase enzymes
• P vivax-specific tests have undergone only limited evaluation

34. Limitations of MRDTs:
• Performance of a particular test may vary depending on the type of
monoclonal antibody used, the source of antigen used to induce the
MRDT antibodies, and polymorphism of a particular antigen that
can escape monoclonal recognition.
• Unreliable in the presence of low-level parasitemia (less than 100
parasites per microliter of blood).
• Give false-positive reactions in individuals with positive rheumatoid
factor (especially HRP-detecting assays).
• All current antigen assays may revert to positive if gametocytes
subsequently appear in bloodstream.
• Not quantitative.

35. Polymerase chain reaction (PCR)-based techniques, based on the
detection of nucleic acid sequences (DNA or mRNA) specific to
Plasmodium species, have the ability to detect parasitemia levels as
low as 1 to 5 parasites/mL(0.00001% infected red blood cells).
The cost and required technical expertise rule out their routine use.

36. 6. MANAGEMENT

43. Severe malaria management:
1. Malarial treatment

44. 2. Supportive Management:
• Patients with severe malaria should preferably be managed in a critical
care unit
• Hyperpyrexia should be adequately managed as it may lead to coma and
convulsions
• Control of seizures should be achieved using intravenous
benzodiazepines, phenytoin sodium, or phenobarbital with careful
monitoring for respiratory depression
• Blood sugar should be routinely monitored as hypoglycemia is very
common
• Hypokalemia is also a common complication of severe malaria and often
becomes apparent on correction of acidosis. Careful, serial monitoring of
serum potassium with adequate supplementation is suggested

45. • Bacterial co infection should always be suspected and treated
empirically with broad-spectrum antibiotics, until the results of cultures
are available.
• In patients with hypotension or signs of dehydration, volume expansion
corrects the hemodynamic abnormalities and is associated with
improved organ function
• Deteriorating respiratory status requires mechanical ventilation and
adequate management of the airway
• Early-positive pressure ventilation helps prevent the high mortality
associated with ARDS in severe malaria
• Patients with renal failure should initially be treated conservatively. Early
dialysis should be instituted if the urine output does not increase and
there is further deterioration of renal parameters.

46. 7. PREVENTION

48. Vaccine:
The complexity of the immune response in malaria, the sophistication of
the parasites’ evasion mechanisms, and the lack of a good in vitro
correlate with clinical immunity have all slowed progress toward an
effective vaccine.
one vaccine candidate (the RTS,S vaccine) will soon be considered for
registration
Despite the enormous investment in efforts to develop a malaria vaccine
and the 30–60% efficacy in African children of a recombinant protein
sporozoite-targeted adjuvanted vaccine (RTS,S) in field trials, no safe,
highly effective, long-lasting vaccine is likely to be available for general
use in the near future.

49. MALARIA CONTROL STRATEGIES (NVBDCP)
1. Early case Detection and Prompt Treatment (EDPT)
2. Vector Control
Chemical Control
• Use of Indoor Residual Spray (IRS) with insecticides
• Use of chemical larvicides like Abate in potable water
• Aerosol space spray during day time
• Malathion fogging during outbreaks
Biological Control
• Use of larvivorous fish in ornamental tanks, fountains etc
Personal Prophylatic Measures that individuals
• Use of mosquito repellent creams, liquids, coils, mats etc.
• Screening of the houses with wire mesh
• Use of bednets treated with insecticide
• Wearing clothes that cover maximum surface area of the body

50. Thank you