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\begin{document}

\title{Cerebral toxoplasmosis in a human immunodeficiency virus (HIV)
seronegative patient with liver cirrhosis}



\author[1]{Elroy Weledji}%
\author[1]{Frank Zouna}%
\affil[1]{University of Buea}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\textbf{Cerebral toxoplasmosis in a human immunodeficiency virus (HIV)
seronegative patient with liver cirrhosis.}

\textsuperscript{1}Elroy Patrick Weledji, \textsuperscript{2}Frank Zouna

\textsuperscript{1}Department of Surgery, Faculty of Health sciences,
University of Buea, Cameroon, W/Africa; Regional hospital Limbe, S.W.
Region, Cameroon. E-mail: elroypat@yahoo.co.uk

\textsuperscript{2}Department of Medicine, Faculty of Health Sciences,
University of Buea, Cameroon , W/Africa, Regional Hospital Limbe, S.W.
Region, Cameroon. Email: zounafrank@yahoo.fr

\textbf{Corresponding author} : EP Weledji, Holy family foundation,
Livanda Kongo Hill, lumpsum quarters, PO Box 126, Limbe, Cameroon. Tel
237699922144. Email: elroypat@yahoo.co.uk

\textbf{Abstract:}

Cerebral toxoplasmosis can affect a patient who is immunocompromised
with chronic liver disease. Liver cirrhotic patients with central
nervous system (CNS) infection could easily be misdiagnosed for hepatic
encephalopathy. A case of cerebral toxoplasmosis in an HIV-seronegative
patient with liver cirrhosis in a low-resource setting is reported.
Although the cerebral toxoplasmosis improved with medical treatment, the
patient died from progressive hepatic failure. Despite the usually poor
prognosis, early diagnosis and prompt treatment of CNS infection
complicating immunosuppression would prevent early death.

\textbf{Keywords} : Liver, cirrhosis, brain, toxoplasmosis, sepsis,
encephalopathy

Key Clinical message

Liver cirrhotic patients with central nervous system (CNS) infection
could easily be misdiagnosed for hepatic encephalopathy. A clinical
suspicion of a cranial infection would necessitate a brain CT or an MRI
to exclude the presence of CNS lesions.

\textbf{INTRODUCTION}

CNS infection often develops as an opportunistic infection in patients
with impaired host defence mechanisms due to malignancy, diabetes
mellitus, alcoholism, liver cirrhosis and, the prognosis is usually
poor\textsuperscript{1, 2}. It develops either by spread from a
contiguous focus or by haematogenous spread from a distant focus, such
as intra-abdominal infection, endocarditis, urinary tract infection, or
pulmonary infection. It is rare and life-threatening in decompensated
liver cirrhosis. Liver cirrhosis is an immune-compromised state because
of reticuloendothelial dysfunction and porto-systemic
shunting\textsuperscript{3}. Bacterial infections in cirrhosis are
common, particularly in decompensated patients and account for
significant mortality \textsuperscript{4, 5}. A case of a cerebral
parasitic toxoplasmosis in an HIV-seronegative patient with liver
cirrhosis is reported.

\textbf{CASE HISTORY/ EXAMINATION}

A 40-year-old African man was admitted as an emergency with a sudden
left arm and leg weakness. He had no history of hypertension, diabetes
mellitus, cardiovascular disease, atrial fibrillation or human
immunodeficiency virus (HIV) infection. He was single and a severe
alcohol consumer. On admission, he was conscious with a Glasgow Coma
Scale score of 15. His blood pressure was 120/80 mmHg, pulse rate
80/minute and regular, respiratory rate 20/min, and normal body
temperature, 37\selectlanguage{ngerman}°C. The conjunctivae were pink and oral mucosa moist.
Chest and cardiovascular examinations were unremarkable. Abdominal
examination revealed dilated supraumbilical veins consistent
with\emph{caput medusa} a sign of chronic liver disease and portal
hypertension. Apart from a nodular liver, there was no other stigmata of
chronic liver disease. He had a left hemiparesis, but there was no neck
stiffness nor flapping tremor indicating meningism or encephalopathy
respectively. The laboratory test results revealed anaemia (Haemoglobin
7.6 g/dl) , a normal white cell count (WBC 9.5 x
10\textsuperscript{9}/mm3, thrombocytopenia (119 x 109/ mm3), negative
HIV serology and malaria parasite, normal urea, creatinine, clotting
screen and serum albumin. Urinary urobilinogen, glucose, bilirubin and
ketone were negative. Liver function tests and a toxoplasma IgG serology
were not done due to financial constraints. Abdominal ultrasound showed
a nodular liver with irregular borders. A cerebral computed tomography
(CT) scan revealed multiple cerebral contrast ring-enhancing lesions
with massive perifocal oedema and mass effect with effacement of the
right frontal horn (figure 1).The findings were suggestive of cerebral
toxoplasmosis and CNS tuberculosis was a possible differential. The
patient was treated empirically for cerebral toxoplasmosis with a
combination of double strength pyrimethanine (\emph{dihydrofolate
reductase inhibitor} ) and sulphadiazine (\emph{sulphonamide antibiotic}
) (960mg) thrice daily for 6 weeks, vitamin B1, proton pump inhibitor
(omeprazole) and physiotherapy. There were both clinical (regaining of
motor strength in both left upper and lower limbs) and radiological (CT
scan) response (figure 2) after a week of treatment. The patient was
discharged a week later with continuation of medical treatment. He
returned after 12 months with decompensated liver disease and died from
hepatic encephalopathy a few months later.

\textbf{DISCUSSION}

The case demonstrated the presentation of cerebral toxoplasmosis in an
HIV-negative patient immunocompromised from probable alcoholic liver
cirrhosis. The presumptive diagnosis was made from the clinical
findings, ultrasound of the liver, and a brain CT scan. The neurological
symptoms were relieved following the empirical treatment of cerebral
toxoplasmosis. The patient, however, died of hepatic encephalopathy from
the progressive liver disease about a year later. Cirrhotic patients are
susceptible to several infectious diseases, such as septicaemia,
meningitis, pneumonia, urinary tract infection, and spontaneous
bacterial peritonitis (SBP) \textsuperscript{5}. Six (11\%) of 53 cases
of brain abscess had liver cirrhosis, presenting with non-specific
symptoms and all died soon after \textsuperscript{6{]}} The high
mortality in cirrhotic patients is firstly due to the difficulty in
differentiating brain abscess from hepatic encephalopathy. Only 34\% of
the patients have the complete triad of headache, fever, and focal
neurological deficits \textsuperscript{1{]}} In the advanced stage of
liver cirrhosis, hepatic encephalopathy is common and usually presents
with disorientation, confusion, drowsiness and coma. Furthermore,
cirrhotic patients can often have episodes of fever caused by
endotoxaemia or SBP. Neck stiffness occurs in only 8\% of patients with
brain abscess and it is not always easy in clinical settings to detect
mild neurological findings in patients with impaired consciousness.
Secondly, bacteria infections worsen hepatic failure. The systemic
inflammatory response syndrome (SIRS) from increased endotoxins, bile
acids, nitric oxide, and cytokines such as \selectlanguage{greek}\emph{tumour necrosis factor-
α} \selectlanguage{english}and \emph{interleukin 6} , may occur resulting in sepsis, renal
failure, encephalopathy and death. It is important to start treatment as
quickly as possible to prevent SIRS as the cytokine cascade is usually
irreversible. Thirdly, most cirrhotic patients are not surgical
candidates because of their bleeding tendency and low hepatic reserve.
Only 33\% of cirrhotic patients received surgical treatment, compared
with 66\% of non-cirrhotic patients \textsuperscript{1}. Liver
dysfunction leads to several abnormalities of defence mechanisms because
of the depressed humoral and cell-mediated immunity. Bacterial
translocation from the intestine induces bacteraemia, and impaired
hepatic bacterial clearance results in failure to control
bacteraemia\textsuperscript{3{]}} Severe bacteraemia may cause
infections of several organs, but pathogenic bacteria may not be
identified in 30\% of brain abscesses \textsuperscript{1, 4}. In the
present case, the causative pathogen was the parasite, \emph{Toxoplasma
gondii.} \emph{T. gondii} infection of humans occurs either congenitally
or by ingestion of foodstuffs contaminated by infected cat faeces or
lamb or pork contaminated with \emph{T. gondii} cysts
\textsuperscript{7}. Primary infection in immune competent host is
asymptomatic or may produce a mild flu-like illness, malaise, headache,
cervical lymphadenopathy. Infection acquired during pregnancy may lead
to serious fetal malformations\textsuperscript{8}. After primary
infection cysts are formed in the tissue and remained inactive until
reactivation. Cellular immunity mediated by T cells, macrophages and
cytokines plays a crucial role in controlling the tissue cysts
\textsuperscript{9}. The infection is self-limiting in immunocompetent
individuals because an efficient immune control limits the dissemination
of the rapidly multiplying tachyzoite stage \textsuperscript{7}.
However, the parasite still remains viable in the tissue cysts.
Chronically infected individuals who possess defects in cell-mediated
immunity as in chronic liver disease (CLD), HIV/AIDS etc, are at risk
for reactivation of the infection and its dissemination, causing serious
complications and death\textsuperscript{10- 12}. \emph{T. gondii} is the
most frequent obligate intracellular protozoan causing opportunistic
infections in immunocompromised patients mostly in the developing
world\textsuperscript{10}. An association between \emph{T. gondii}
infection and chronic liver disease (CLD) has been observed.
Co-infection in both\emph{T. gondii} / hepatitis B virus (HBV) and
\emph{T. gondii} / hepatitis C virus (HCV) was 33.3\% and 31.4\% ,
respectively with a highly significant association between \emph{T.
gondii} parasitaemia and HCV viral load. There was also a significant
increase of liver enzymes in the serum of patients positive for \emph{T.
gondii} compared with negative patients \textsuperscript{11}.Toxoplasma
seropositivity was higher in patients with Child-Pugh class C CLD than
Child- Pugh class A and, may signify disease evolution
\textsuperscript{12}. Several studies have reported the parasite found
in 20\%- 90\% of patients with cirrhosis through IgG and polymerase
chain reactions PCR tests\textsuperscript{13}. The three forms of
cerebral toxoplasmosis are focal toxoplasma meningoencephalitis,
multifocal encephalitis and diffuse toxoplasma meningoencephalitis. The
common presentations include decreased consciousness, headache,
hemiparesis, cranial nerve palsy, seizure, meningeal signs, dementia and
psychosis \textsuperscript{13, 14}. Diagnosis is considered from
clinical findings, CT scan, or magnetic resonance imaging (MRI) of the
brain with serological findings\textsuperscript{1.}

\textbf{CONCLUSIONS}

Cerebral toxoplasmosis can affect an HIV-negative patient who is
immunocompromised with liver cirrhosis. Cirrhotic patients with CNS
infection could easily be misdiagnosed for hepatic encephalopathy. A
clinical suspicion of a cranial infection is important when encountering
cirrhotic patients with disturbance of consciousness and fever. Brain CT
or MRI must be considered to exclude the presence of CNS lesions. Early
treatment is important for this complication of immunosuppression which
has a poor prognosis.

\textbf{ACKNOWLEDGEMENTS}

None

\textbf{CONFLICT OF INTEREST}

The authors declares no competing interests

\textbf{AUTHOR CONTRIBUTIONS}

EPW was the main author, FZ was the main physician and contributed to
literature search and writing of the paper

\textbf{CONSENT}

Written informed consent from the next of kin to the patient was granted
to write and publish the paper.

\textbf{DATA AVAILABILITY STATEMENT}

The data that support the findings of this study are available on
request from the corresponding author. The data are not publicly
available due to privacy or ethical restriction.

\textbf{ORCID}

Elroy Patrick Weledji https://orcid.org/0000-0002-0473-4883

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  2015;8(10):784-791\textbf{Legends}Figure 1: Brain CT scan showing
  contrast enhanced rings of T. gondii with surrounding oedema and
  effacement of Right lateral ventricular horn. Figure 2. CT Scan
  showing response to 1 week of medical treatment of\emph{toxoplasmosis
  gondii}
\end{enumerate}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

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\end{figure}

Figure 1: Brain CT scan showing contrast enhanced rings of \emph{T.
gondii}

with surrounding oedema and effacement of right lateral ventricular
horn.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2. CT Scan showing response to 1 week of medical treatment
of\emph{toxoplasmosis gondii}

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