* Ispat General Hospital, Rourkela-769 005.

E D I T O R I A L
Jaundice in Falciparum Malaria
SK Mishra*, S Mohapatra*, S Mohanty*
JIACM 2003; 4(1): 12-3
Malaria remains an overwhelming problem in the
tropical developing countries, with 300 to 500 million
new cases, and about a million deaths per year. Malaria
is a potentially life-threatening disease in the tropics.
According to the World Health Organisations criteria, the
recognition of one or more of the following clinical
features should raise the suspicion of severe malaria:
cerebral malaria (unrousable coma), severe anaemia
(haemoglobin <5 g/dl), renal failure (serum creatinine
>3 mg/dl), pulmonary oedema or adult respiratory
distress syndrome (ARDS), hypoglycaemia (glucose <40
mg/dl), circulatory collapse or shock, disseminated
intravascular coagulation (DIC), repeated generalised
convul si ons, aci dosi s (pH <7.25), macroscopi c
haemoglobinuria, hyperparasitaemia (>5 percent of the
erythrocytes infested by parasites), or jaundice (bilirubin
>3 mg/dl). A number of patients with malaria develop
severe manifestations, and these patients require the
most urgent and intensive care. Mortality among
patients with cerebral malaria, even when treated in a
modern intensive care unit, exceeds 30%; and when
complicated by the adult respiratory distress syndrome,
it may approach 80%. Mortality remains a serious issue
because of fai l ure to obtai n and use preventi ve
measures, delay in seeking medical attention, and
misdiagnosis
1,2,3
.
Jaundice is one of the common severe manifestations
of falciparum malaria. Its incidence varies between 10 to
45% in different reports, and is seen more in adults than
in children. It may be present alone or with other
complications. A study from Vietnam reported that 63%
of the adults who had acute renal failure were jaundiced
vs 20% of those without renal failure
4
. Similarly, half of
the patients with cerebral malaria were associated with
jaundice. Presence of jaundice in falciparum malaria
indicates a more severe illness with higher incidence of
complications. Mortality also was higher in the group of
patients with jaundice (40% vs. 17%;
2
= 4.85, p < 0.05)
5
.
Jaundice may vary from mild to very severe. However,
clinical signs of hepatic encephalopathy (such as liver
flaps) are never seen unless there is presence of
concomitant viral hepatitis
1
. Tender hepatomegaly and
splenomegaly are common findings in all human malaria,
and most commonly in young children. Recovery from
jaundice is usually faster than the hepatitis, which usually
takes a longer time to return to normal. A high bilirubin
level should alert the clinician to look for black water
fever and/or acute renal failure in some patients
6
.
Malarial hepatitis, jaundice, and hepatic dysfunction have
been loosely interchanged. This has caused confusion and
misconception. Liver is the first organ to be affected in a
case of P. falciparum malaria. After the initial stage (pre-
erythrocyte schizogony), merozoites are released into the
blood stream. They do not have exo-erythrocytic
schizogony. But in the patients of severe malaria, liver may
be involved to different extents.
Liver biopsy/necropsy usually shows Kupffer cell
hyperplasia, mononuclear cell infiltration, and pigment
deposits; while other studies have demonstrated either
no structural change or slight hepatocyte swelling.
Centrizonal necrosis has also been reported. But
unfortunately, studies are scant from our country
7,8
. In this
issue of JIACM, an article pertaining to the histopatho-
logical study in severe malaria (p. 34) should interest you.
Impairment of hepatic function is common in severe
malaria. It leads to improper handling of drugs and
antimalarials (as evidenced by hepatic blood flow
measurement indocyanine green (ICG) clearance). In
severe malaria, ICG clearance is significantly lower than in
patients with uncomplicated malaria. It returns to normal
during convalescence. Acute malaria also adversely affects
the function of cytochrome P450 microsomal enzymes
9
.
Unfortunately, assessment of liver function by
measurement of blood concentrations of bilrubin and liver
enzymes is imprecise, particularly in presence of
haemolysis. So, it becomes difficult to state whether the
index patient is having hepatic dysfunction or not. As we
have seen, there may be some element of hepatic
dysfunction, but to state that hepatitis is present in this
situation is erroneous.
Jaundice in severe P. falciparum malaria is
multifactorial
Intravascular haemolysis of pRBCs.
Haemolysis of non-pRBCs (innocent bystanders).
Possibly micro-angiopathic haemolysis associated
with DIC.
Hepatic dysfunction.
Associated haemoglobinopathies (not uncommon in
malaria-prone areas).
Drug-induced haemolysis (including quinine, etc.).
G6PD deficiency, etc.
The laboratory findings
Hyperbilirubinaemia is mostly of unconjugated type.
Often jaundice is mild, and total serum bilirubin is below
5 mg/dl, but at times bilirubin rises beyond 50 mg/dl.
Enzymes are usually raised (within 3 to 8 times), alanine
transaminase (ALT) never reaches to the level of viral
hepatitis. 5 nucleotidases and GGT concentrations may
be moderately elevated. Hypoalbuminaemia is also
seen in these patients. Prothrombin time may be
moderatel y prol onged. Other abnormal i ti es may
include low serum cholesterol and triglycerides
1,10
.
There i s hardl y any study avai l abl e showi ng
pathological and biochemical correlation (of SGPT and
liver biopsy reports) in malaria.
Routine liver biopsy in patients of malaria with jaundice
is unethical as it never helps in the diagnosis or
management of the patients. It takes longer time than
examination of blood film, rapid diagnosis tests, or even
bone marrow examination. Hence, it cannot be advocated
as a diagnostic tool for acute malaria. Liver function tests
are of value to a limited extent (as mentioned before).
When SGPT is excessively elevated, one should search and
exclude concomitant presence of viral hepatitis,
leptospirosis, infectious mononucleosis, or dengue. Falling
short of this, we suggest that instead of labelling a patient
as malarial hepatitis, one should classify it as malaria with
jaundice.
We hope more high quality work on malaria be pursued
and published in times to come.
References
1. WHO. Severe falciparum malaria. Transaction of Roy Soc Trop
Med Hyg 2000; 94 (suppl 1): 1-90.
2. Mishra SK, Satpathy SK, Mohanty S. Survey of malaria
treatment and deaths. Bulletin of WHO 1999; 77: 1020.
3. Mohapatra S, Mishra SK. Difficulty in diagnosis and
treatment of malaria. Medicine Update, Vol-11, (Editor : Panja
M), Association of Physicians of India, New Delhi 2001; p 265-
73.
4. Trang TT, Phu NH, Vinh H et al. Acute renal failure in patients
with severe falciparum malaria. Clin Inf Dis 1992; 15: 874-80.
5. Murthy GL, Sahay RK, Sreenivas DV et al. Heptitits in
falciparum malaria. Trop Gastroenterol 1998; 19: 152-4.
6. Tran TH, Day NP, Ly VC et al. Blackwater fever in southern
Vietnam: a prospective descriptive study of 50 cases. Clin
Infect Dis 1996; 23: 1274-81.
7. Mishra SK, Mohanty S, Das BS et al. Hepatic changes in P.
falciparum malaria. Ind J Malariol 1992; 29: 167-71.
8. Dash SC, Bhuyan UN, Gupta A et al. Falciparum malaria
complicating cholestatic jaundice and actue renal failure. J
Assoc Physicians India 1994; 42: 101-2.
9. Pukrittayakamee S, Looareesuwan S, Keerataikul D et al. A
study of factors affecting the metabolic clearance of
quinine in malaria. Euro J Clin Pharmacol 1997; 52: 487-93.
10. Wilairatana P, Looareesuwan S, Charoenlarp P. Liver profile
changes and complications in jaundiced patients with
falciparum malaria.. Trop Med Parasitol 1994; 45: 298-300.
Journal, Indian Academy of Clinical Medicine

Vol. 4, No. 1

January-March 2003 13
ACKNOWLEDGEMENT
The Editorial Board of the Journal
is extremely thankful to
Dr. Dhiman Ganguly
Chairman
and
Dr. Madhuchanda Kar
Honorary Secretary of Indian Academy of Clinical
Medicine, W.B. Chapter
for contributing Rs. 15,000/-
towards JIACM account, out of the savings of
IACMCON-2001
held at Kolkata