Introduction

A 2-week history of weight loss, diarrhoea, vomiting, and cough is presented by an

8-year-old boy. He has a history of diarrhea, vomiting, and coughing. There is no
proof of dangerous intake, and the family denies using traditional remedies. His
mother brought him to the emergency room because he had been having diarrhoea
for three weeks and vomiting after every meal.

As a result, he had lost a significant amount of weight and was exceedingly thin. She
also saw that he had trouble walking and sitting, and that his hands shook when he
tried to pick something up. A chronic cough was also a source of concern for the
mother. Despite the fact that he had no fever or night sweats, and his cough was
ineffective, he had been afflicted with tuberculosis a year before. She had finished
treatment, and his sputum was negative, but that kid wasn't getting TB prophylaxis at
the time, and she was concerned that he might have TB as well.

From the age of one year, the mother reported sporadic occurrences of diarrhoea,
which got better at her local clinic. There were no further illnesses or hospitalizations
reported. Since birth, the child has been properly immunized and his immunizations
are up to date. Within Sandakan, their family lives in a small wood home. There are
four adults and two older siblings, ages 11 and 12, who have all been reported. The
father works and supports the family. The house has running water and electricity.
Hepatomegaly with a coarse echogenic pattern and no focal lesions was found by
his abdominal ultrasonography.

There was also splenomegaly with scattered hypoechogenic lesions, including a

massive 2.8 x 1.6 cm hypoechogenic lesion. The boy's brain CT revealed modest
involutional alterations, but no space-occupying lesions or elevated intracranial
pressure. The X-ray of the chest revealed hilar lymphadenopathy. As a result, he
was treated empirically with a high dose of Cefoxatime.

The respiratory examination revealed a symmetrical bilateral air intake and normal
bladder sounds. Investigation of the cardiovascular system revealed normal heart
sounds without murmurs. There was no neck stiffness or other meningeal signs.
Ocular and otorhinolaryngological examinations were normal. The boy is diagnosed
with splenic tuberculosis. While splenic tuberculosis is uncommon, it is considered
an important manifestation of abdominal TB, especially in developing countries. Its
prevalence is increasing with the epidemic of HIV-TB co-infection and the
subsequent rise in extrapulmonary TB. To best understand this disease process, one
must look at the immunological processes that occur with the spread of
mycobacteria to extrapulmonary sites and HIV spread to secondary lymphoid tissue.
Spread of mycobacteria from the lungs to other organs can occur when
macrophages become infected with bacteria after phagocytosis Migration of
activated macrophages to secondary lymphoid tissue for antigen presentation to
CD4+ helper T lymphocytes can spread the bacteria to other tissues such as liver,
lymph nodes, spleen, intestine and bone marrow.

Biochemical Changes in Splenic Tuberculosis

Biochemical techniques advance our understanding of the chemical structures and

processes underlying human health and disease and reveal the underlying changes
between these two physiological states (Brunham, 2021). The implications of
uncovering the causes of pathologies at the cellular level are enormous. By being
able to draw on an in-depth knowledge of biochemistry and other related disciplines
such as molecular biology and immunology, medical professionals have the potential
to transform global healthcare. And with the rise of public health threats such as air
pollution and climate change, non-communicable diseases, antibiotic resistance and
dengue fever, research by biochemists is needed more than ever. The primary
reason biochemistry is significant in medicine is that it investigates the major
chemical substances found in the human body, such as proteins, carbohydrates,
nucleic acids, and lipids (fats, fat-soluble vitamins, and phospholipids). Because
each of these molecules has a distinct purpose, understanding how they function
and why they are vital is critical for understanding various health issues or diseases.
Professionals in the medical industry would be unable to understand even the most
basic ideas of the human body without the knowledge provided by biochemistry.
Biochemistry describes how metabolism works since it analyzes all chemical
changes in the human body.

Metabolism is a sequence of chemical events in the cells of the body that transform
the energy humans obtain from meals into the fuel the body utilizes to perform
cellular operations. Tuberculosis remains an international health issue with
significant morbidity and mortality rates, particularly in underdeveloped countries,
where approximately 10 million new infections and 1600 deaths occur each year.
The Mycobacterium tuberculosis complex causes tuberculosis. It is both treatable
and avoidable. If not treated effectively, certain factors that include human
immunodeficiency virus (HIV) infection and other co-morbidities could have an
impact on the result.

Splenic abscess is an uncommon disease and tuberculous splenic abscess is much

rarer. However, although tuberculous splenic abscess is on the rise in
immunocompromised patients due to acquired immunodeficiency syndrome (AIDS),
tuberculous abscess in immunocompetent patients is still rare. Furthermore, primary
tuberculous splenic abscess in an immunocompetent patient is extremely rare. All
these cases were diagnosed histopathologically through spleen biopsy, exploratory
laparotomy and splenectomy. In contrast, we experienced such a case diagnosed by
abdominopelvic computed tomography and biochemical markers: adenosine
deaminase and interferon-gamma release assay.

Unlike tuberculous splenic abscesses involving other organs, the five described
cases of primary tuberculous splenic abscesses were diagnosed histopathologically
by spleen biopsy, drainage of the splenic abscess, exploratory laparotomy and
splenectomy after treatment failure. However, the diagnosed primary splenic
abscess by radiological findings and biochemical markers: interferon-gamma assay
and ADA (Ferluga et al., 2020).

Non-invasive imaging modalities, such as ultrasound and CT, play an important role
in assessing the extent of organ involvement, the need for surgical intervention and
the therapeutic response. In contrast to these common imaging modalities,
abdominopelvic CT played a crucial role in the diagnosis of tuberculous abscess in
the spleen in our patient, as he had only spleen lesions and refused percutaneous
spleen biopsy.

Typical CT findings are multiple, round or egg-shaped lesions of low density and
without calcification, as in our case. Lymphoma, hydatidosis and metastases should
be considered in the differential diagnosis of CT findings. In addition to the typical
radiological findings, the interferon-gamma release assay also played an important
role. The interferon-gamma release assay is an in vitro laboratory diagnostic test
using a whole blood sample. It is an indirect test for detecting M. tuberculosis
complex infection.

Given that biochemistry explores how living organisms react to various chemicals or
chemical reactions that take place in the body, the involvement of biochemists in
pharmacology is quite essential. Thus, biochemistry enables pharmacologists to
design and develop safe and effective drugs after conducting numerous in vivo and
in vitro experiments to test the effects of drugs on biological systems. The specificity
of the test for the low-risk group was 98.1% and the sensitivity for patients with M.
tuberculosis infection was 89.0%. Another important biochemical marker was ADA in
ascites and serum. Levels above 36 IU/L in ascites fluid (sensitivity: 100%,
specificity: 97.1%) and above 54 IU/L in serum (sensitivity: 81.5%, specificity: 97.6%)
suggest tuberculosis. ADA ratio between ascites fluid and serum higher than 0.984
indicates tuberculosis (sensitivity: 57.1%, specificity: 87.7%). Our patient's ADA in
ascites fluid and serum was 76.9 IU/L and 67.5 IU/L, respectively.These biochemical
tests helped us to be sure that our patient had tuberculous splenic abscess and
tuberculous peritonitis (Grover et al., 2021).

Immunology importance in Splenic Tuberculosis

Inflammatory reactions can be triggered in the spleen, which, in addition to

eliminating old erythrocytes, plays a key role in detecting blood-borne antigens that
enter the organ via arterial blood flow. This occurs in the white pulp, a lymphoid
tissue rich in lymphocytes and antigen-presenting cells. When a foreign antigen is
recognized, inflammatory responses are triggered. The blood then continues to flow
into specialized sinuses known as the red pulp, where macrophages phagocytose
aged erythrocytes. Infected macrophages can then enter the spleen and transmit
germs to other macrophages (Grover et al., 2021). In HIV infection, the immune
system's reaction against mycobacteria is reduced, allowing the bacteria to multiply
more easily.
Extrapulmonary TB is becoming more common as a result of the HIV epidemic.
Splenic tuberculosis is an uncommon type of abdominal tuberculosis. It is most
commonly found in immunocompromised people or as part of disseminated
tuberculosis, but it can occasionally occur in immunocompetent people (Guo et al.,
2023). This patient showed immunocompetence, but there was often another TB-
infected focus. These cases also had fever of unknown origin (FUO). The patient
was immunocompetent and without FUO. In addition, no other sites were affected.
When the spleen is affected as an isolated organ, the patient may have solitary TB
or a tuberculous abscess. Rare cases of splenic abscess have been described in an
immunocompromised patient and an immunocompetent patient, respectively. In this
case, the lesion was solitary and multinodular, not a tuberculous abscess (in an
abscess, the lesion does not appear to be multinodular). Many of the reported cases
of splenic tuberculous abscess have underlying HIV infections, so it was thought that
splenic involvement was only seen in immunocompromised hosts. However, there
are sporadic cases of splenic TB in immunocompetent patients. In the present case,
however, the patient had no history of TB and showed no evidence of TB in any
other organ. Treatment with ATT is the mainstay of treatment for splenic
tuberculosis. The duration of treatment varies, but regimens typically lasting six to
nine months are considered satisfactory. In patients who do not respond to medical
treatment alone, splenectomy is a viable option. Rarely, a paradoxical phenomenon
of exaggeration of inflammatory symptoms, called immune reconstitution
inflammatory syndrome, may be observed at the start of medical treatment. It may
present as a worsening of existing lesions or the development of new lesions, or as a
worsening of clinical or radiological findings after initiation of ACT (Khan et al., 2020).

The common symptoms include fever, abdominal pain, diarrhoea and generalised
weakness. There are often significant delays in diagnosis due to inconsistent
symptomatology. Ultrasound and CT scan of the abdomen are the first-line
investigations. Tissue aspiration or biopsy is indispensable for diagnostic
confirmation in cases where splenectomy is not performed. Administration of ATT
may result in a favourable outcome and may obviate the need for splenectomy.
Doctors should be aware of isolated splenic involvement in tuberculosis, and tissue
diagnosis should be performed as early as possible in suspected cases (Kumar et
al., 2018) .
The effectiveness of Mycobacterium tuberculosis as a human pathogen depends
largely on its ability to subvert host immune responses and persist in a latent state
(Lin et al., 2016). M. bovis Bacille Calmette-Guerin (BCG) is currently the only TB
vaccine approved for human use. It has been used to vaccinate more than 4 billion
people worldwide and remains part of the childhood immunisation programme in
most countries because of its ability to confer effective protection against TB in
children. However, the protective immunity generated by BCG wanes with age and
its efficacy against the disease has been less than satisfactory in adults and the
elderly. In addition, the inability of BCG to provide sterilising immunity at the time of
primary infection results in a huge reservoir of asymptomatically infected individuals
worldwide (∼2 billion) (Metlo et al., 2019). These latently infected individuals are at
persistent risk of developing clinical disease due to endogenous reactivation if the
immune system is compromised for various reasons, such as HIV infection or
malnutrition. Latency-associated antigens are expressed by M. tuberculosis as it
adapts to long-term persistence; however, BCG, being an attenuated strain, does not
persist long enough to express these antigens (Shaker et al., 2022).

However, subsequent clinical trials and meta-analyses revealed its overall

ineffectiveness against TB in adults. Clinical trials and subsequent meta-analyses,
however, revealed its overall ineffectiveness against TB in adults. Several
laboratories around the world have therefore turned their attention to the
development of new vaccine candidates or vaccination regimens that could improve
the protection conferred by the BCG vaccine. According to one proposed
mechanism, as the individual reaches 10-15 years of age, the memory immunity
generated by BCG wanes, resulting in a gradual loss of BCG efficacy. The
introduction of a booster vaccine based on a candidate antigen specifically
recognised by BCG-induced immunity therefore emerged as one of the most
successful approaches. Among the various boosters, vaccines of a genetic nature,
such as DNA vaccines, have emerged as one of the most promising developments
in the field of vaccine discovery. DNA immunisation is known to direct the immune
system towards stronger and more persistent cellular and humoral immune
responses (Tahir et al., 2020).
Conclusion & Recommendation

Management of splenic tuberculosis is the same as that proposed for pulmonary

tuberculosis: standard combination anti-tuberculosis treatment should be given for at
least 6 months and the entire course should be completed, whether or not an
operation is performed (Ufoaroh et al., 2021). Splenectomy can be avoided in cases
where a good response is observed. Splenectomy is only indicated in patients who
do not respond to anti-tuberculosis medication. In patients presenting with FUO and
splenomegaly, tuberculosis should be considered as one of the differential
diagnoses, especially in areas where the disease is prevalent. Splenic tuberculosis
can affect even immunocompetent individuals. Extrasplenic involvement is common
in splenic tuberculosis. In patients presenting with FUO and splenomegaly, in whom
an exact diagnosis cannot be established after all possible and available
investigations, splenectomy is strongly recommended for diagnosis and subsequent
treatment. Empirical exposure to anti-tuberculosis drugs could be dangerous in these
situations, as it may mask a definitive diagnosis later on. Occasionally, these
patients may not respond to anti-tuberculosis drugs and require subsequent
splenectomy.

BCG vaccination can prevent serious diseases in children, such as miliary

tuberculosis and meningitis. Vaccination can also prevent about 40 000 cases each
year before the age of 5 years. The diagnosis in this case was made by pathology,
the gold standard diagnostic method. While splenectomy is rarely necessary in
tuberculosis of the spleen, it may be necessary when an abscess forms or there is
no response to treatment. In addition, treatment may be prolonged up to 24 months
in some cases. The differential diagnosis of splenomegaly with FUO may include
leishmaniasis, malaria, endocarditis infractasia, leukaemia, sickle cell disease,
lymphoma and myelofibrosis. Infractases can be difficult to distinguish by imaging
alone.

To summarise, patient selection for a specific modality of intervention is very

important to improve prognosis. Early detection and less invasive treatment with a
combination of anti-tuberculosis drugs can be successful in immunocompetent
patients with splenic tuberculosis. Splenectomy can be avoided in these patients and
 reserved for patients with splenic rupture and in cases of anti-tuberculosis treatment
failure. Biochemistry is, in short, the ideal diagnostic tool in medicine. Without
biochemistry, healthcare workers would not have sufficient knowledge of how the
human body works to diagnose or treat patients.

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