Neonatal tetanus results from non-sterile instruments’ interaction with the umbilical cord. The neonatal tetanus vaccine is preferred along with neonatal tetanus treatment.

Neonatal Tetanus

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ZAKA CLINIC GULBERG LAHORE

Saad Ullah Siddiqui

Overview

Neonatal tetanus refers to tetanus that occurs in infants who are born completely normal but lose the ability to normally suck and cry between 3-28 days of being born. The condition is often characterized by the occurrence of a rigid body and spasms<a href="#accordion">[9]</a>.

The most common occurrence of tetanus is through a cut or a wound that gets infected by the spores of Clostridium tetani bacterium. Tetanus can be deadly for babies as it attacks the nerves of the body which results in muscle damage. Neonatal tetanus on the other hand does not happen due to an injury to the baby. An unvaccinated mother is the main cause of this disease. The bacterium finds its way to the baby in the womb with the help of the umbilical cord<a href="#accordion">[1]</a>. The gram-positive bacterium has become a huge cause of death in low-income countries, with around 180,000 reported deaths annually<a href="#accordion">[8]</a>.&nbsp;Neonatal tetanus has become the second leading cause of infant death worldwide. In Pakistan specifically, out of the global death record of 248,000 due to neonatal tetanus, 11% of the total number i.e., 26,400 were in Pakistan. The overall mortality rate in Pakistan is 5 in every 1000 live births<a href="#accordion">[10]</a>.

&nbsp;

Infection from Clostridium tetani is not just limited to infants. Several types of infections affect people of different age groups and different body parts. They are as follows: 
&nbsp;

<ul>
	<li>
	<h5>Localized</h5>
	</li>
</ul>

Localized tetanus is a much rarer form of tetanus. In several cases, it occurs as an initial stage of tetanus shortly followed by generalized tetanus. The biggest challenge faced in the treatment of localized tetanus is the inconsistent show of symptoms that do not allow for a quicker diagnosis of the disease<a href="#accordion">[5]</a>.&nbsp;The disease itself is characterized by the occurrence of muscle spasms that are restricted to just one or two sites of the body.&nbsp; 
&nbsp;

<ul>
	<li>
	<h5>Cephalic</h5>
	</li>
</ul>

Another rare form of tetanus is also known as trismus plus paralysis of cranial nerves. The most common victim of this type of tetanus is the 7th cranial nerve. Two-thirds of the total reported cases often transition to generalized tetanus. Common treatment of cephalic or cerebral tetanus includes the treatment of the wound through which the patient came into contact with the bacterium, initiation of active immunization, use of penicillin, and other tetanus immune-globulin intensive care<a href="#accordion">[17]</a>.

Cephalic tetanus is believed to be associated with otitis media. The incubation period in this type of tetanus ranges from 1-2 days. Cephalic tetanus causes cranial nerve palsies and does not cause spasms unlike the other forms of tetanus however there may be a prevalence of spasms of the jaw muscles involved. 
&nbsp;

<ul>
	<li>
	<h5>Generalized</h5>
	</li>
</ul>

The most prevalent form of tetanus is generalized tetanus. In several cases, other types of tetanus like cephalic and localized may transition to generalized tetanus. Around 80% of the total cases of tetanus involve the generalized type of tetanus. Lockjaw is one of the most common types of symptoms involved. The spasms however are not limited to the jaw but also travel to the neck, spinal cord, etc.&nbsp;

<div>&nbsp;</div>

Signs And Symptoms

Maternal and neonatal tetanus if identified at an early stage can aid in complete treatment or even in the avoidance of fatality. The symptoms of neonatal tetanus are similar to what adults experience. The symptoms include: 
&nbsp;

<ul>
	<li>Lockjaw or tightness of the jaw</li>
	<li>Muscular spasms</li>
	<li>Body rigidness&nbsp;</li>
	<li>Dysphagia</li>
	<li>Opisthotonos (abnormal arching of the back, neck, and spine)&nbsp;</li>
	<li>Muscle tightening in the stomach</li>
	<li>Seizures&nbsp;</li>
	<li>Headache</li>
	<li>Fever</li>
	<li>Excessive perspiring&nbsp;</li>
	<li>High blood pressure and heart rate</li>
	<li>Irritability&nbsp;</li>
	<li>Poor sucking ability</li>
	<li>Restlessness</li>
	<li><a href="https://www.merisehat.pk/disease/sleep-apnea-91" target="_blank">Apnea</a></li>
</ul>

<div>&nbsp;</div>

Causes

Clostridium tetani is a gram-positive anaerobic bacterium that commonly enters our body in the form of spores. The bacterium produces tetanus toxin which first targets the lower motor neurons and then spreads the infection to first the spinal cord and then the brain stem.&nbsp; 
&nbsp;

<h5>Mechanism Of Action Of Clostridium Tetani</h5>

Prevalent in the environment and easily spread through dirt, stool, dust, or in the case of neonatal tetanus, unsterile equipment, Clostridium tetani has the ideal environment in the bloodstream to flourish.&nbsp;

The spores when entered into the bloodstream produce tetanolysin and tetanospasmin. Not much is known about tetanolysin but tetanospasmin on the other hand is a very well-known toxin that induces harmful effects on the nervous system. The toxin works by inhibiting impulses by interfering with the release of neurotransmitters. This inhibition blocks the neural impulses leading to muscle contraction and spasms that cannot be opposed<a href="#accordion">[7]</a>. 
&nbsp;

The biggest cause of tetanus in infants is poor hygiene practices during delivery. Infants contract tetanus mainly due to infected umbilical stumps. This can be due to poor sterilization of the instruments used. However, the prevalence of neonatal tetanus in such big numbers in Pakistan is due to the fact that most births are carried out at home or in unconventional spaces<a href="#accordion">[13]</a>. 
&nbsp;

<h5>Antibody Test For Emergencies</h5>

There is no screening done for tetanus but in case of accidents and emergencies, testing can be done<a href="#accordion">[6]</a>. The antibody test is also known as a vaccine response test and is carried out during possible reactions after the administration of the diphtheria vaccine or in cases of humoral immunodeficiency in the patient.

<div>&nbsp;</div>

Diagnosis

Diagnosis of neonatal tetanus is mainly based on the physical exam, in this case, the muscle spasms of the child coupled with the crying. This examination is often linked with the vaccination history of the mother<a href="#accordion">[2]</a>.&nbsp;

The approach of taking culture does not always work in the case of tetanus. The bacterium often does not show up or indicate its presence in the test. Similar is the case with the presence of antibodies i.e., it is not an accurate indicator of neonatal tetanus or tetanus of any kind for that reason.&nbsp;

Differential diagnosis is preferred and used in most cases of tetanus now. When it comes to infants, there is a wide range of issues that can cause the same set of symptoms including seizures and severe muscle cramps, especially in metabolic diseases like hypocalcemia, birth asphyxia, hypoglycemia, etc.

Detection of tetanus toxin in plasma can also be done through PCRs and bioassay but similar to the process of taking culture from the entry sites, this facility is not available in many settings and the results are not always promising<a href="#accordion">[13]</a>.

<div>&nbsp;</div>

Treatment

Neonatal tetanus can be fatal if not treated in a timely manner. The main objectives when it comes to the treatment of neonatal tetanus include: 
&nbsp;

<ul>
	<li>Use the appropriate antibiotics and disinfectants on the site of infection</li>
	<li>Administer anti-tetanus immunoglobulin to neutralize the toxins circulating inside the body</li>
	<li>Treat and manage other symptoms involving muscle spasms, respiratory failure and any other complications that may have risen due to the infection 
	&nbsp;</li>
</ul>

Currently, there are only 4 randomized trials of treatment, which translates into limited options. The low number of trials is due to the prevalence of the disease in low-income countries especially in rural, remote areas where the conductance of a proper clinical trial is difficult due to various reasons e.g. logistics , patient participation hesitancy etc. Hence listed below are the current options for&nbsp; neonatal tetanus care: 
&nbsp;

<ul>
	<li>Antibiotics: Treatment of maternal and neonatal tetanus go hand-in-hand most of the time. Antibiotics like penicillin and metronidazole administered intravenously are used as a first-line treatment. Clostridium tetani is known to be sensitive to penicillin and metronidazole but resistant to co-trimoxazole. 
	&nbsp;</li>
	<li>Antitoxins: These are targeted toward the toxins that are in the bloodstream but have not exerted their effects yet on the nerve tissues. This phenomenon is also known as passive immunization<a href="#accordion">[2]</a>.&nbsp;The administration of antitoxins has been directly related to minimizing the risks of mortality. Human tetanus immunoglobulin or equine-derived antitetanus serum is commonly used.&nbsp; 
	&nbsp;</li>
	<li>Sedatives: Used as a form of symptom control, benzodiazepines are commonly used for this purpose. Diazepam and lorazepam are commonly used to relax the muscles and induce sedation to aid the cramps and contractions. 
	&nbsp;</li>
	<li>Magnesium: Magnesium sulfate has several therapeutic effects crucial for the symptomatic treatment of neonatal tetanus. It acts as a muscle relaxant, vasodilator and has negative chronotropic properties. This serves as a cost-effective option in the treatment of neonatal tetanus. However, it is to be noted that the use of magnesium sulfate is not as effective in cases of severe neonatal tetanus, it simply aids in reducing the usage or eliminating the need for other muscle relaxants in milder cases of tetanus.&nbsp;</li>
</ul>

<div>&nbsp;</div>

All kinds of diseases experienced by an infant can have a crucial impact on their health and development. In neonatal tetanus, following may be the complications faced by the infant: 
&nbsp;

<ul>
	<li>Trouble Breathing: The muscle spasms may lead to the tightening of the vocal cord. Since the disease has a massive impact on the neck, muscle rigidity is common and may lead to trouble breathing. This is called laryngospasm. 
	&nbsp;</li>
	<li>Broken Bones: The muscle spasms experienced by the patient are sometimes so severe that it causes fractures of the spine and some other bones especially in infants. 
	&nbsp;</li>
	<li>Pulmonary Embolism: The main artery of the lung may get blocked by a blood clot. This blood clot often travels from someplace else in the body through the involuntary contractions that affect the bloodstream<a href="#accordion">[12]</a>. 
	&nbsp;</li>
	<li><a href="https://www.merisehat.pk/disease/pneumonia" target="_blank">Pneumonia</a>: Aspiration pneumonia occurs when the patient breathes in foreign material. It is a type of lung infection. 
	&nbsp;</li>
	<li>Death: Since breathing and lung-related problems are prevalent complications in neonatal tetanus, these can cause fatality for e.g. for every 10 cases 1-2 may die due to these complications.&nbsp;</li>
</ul>

<div>&nbsp;</div>

While some risk factors may be more prevalent than others in certain environments, the most common risk factors that may lead to neonatal tetanus include<a href="#accordion">[15][16]</a>: 
&nbsp;

<ul>
	<li>At-home deliveries</li>
	<li>Unvaccinated mothers</li>
	<li>Unhygienic cutting of the umbilical cord by unsterilized equipment</li>
	<li>History of neonatal tetanus in previous pregnancies</li>
	<li>Use of alternative medicinal ointments on the umbilical stump. This may include dung, mud,&nbsp;etc.</li>
</ul>

<div>&nbsp;</div>

In many places, tetanus has been regarded as an &lsquo;inexcusable disease&rsquo;. The very first toxoid for tetanus was developed in 1924. Shortly after, the Advisory Committee on Immunization Practices (ACIP) recommended the use of tetanus vaccine in combination with pertussis and diphtheria. In 2005, a complete formulation including toxoids for tetanus, diphtheria, and acellular pertussis, was approved and made common in the form of a vaccine<a href="#accordion">[3]</a>.

The biggest cause of neonatal tetanus is an unvaccinated mother indicating that the best prevention is vaccination of the mother. This is not just limited to one-lifetime vaccination. It is preferred to get a booster after every 10 years. If you are pregnant and have not had your tetanus shot in over 10 years, now is the time.

The ideal time to get vaccinated while being pregnant is during the third trimester. WHO along with several other healthcare organizations all over the world has always recommended the use of vaccination against tetanus coupled with deliveries in a clean, sanitized environment. DTP or DTaP vaccination is done at the age of 2 months, 4 months, 6 months, 12 months, and then 4-6 years<a href="#accordion">[14]</a>.

For children over the age of 7 who have never been vaccinated, they are administered a series of 3-4 vaccines over the course of a year or more. Unvaccinated pregnant women are to receive two doses one month apart. The first dose should be administered as soon as possible<a href="#accordion">[13]</a>.

<div>&nbsp;</div>

In a paper published in Front. Public Health, the researchers suggested the use of clean birth kits as another elimination strategy for neonatal tetanus with the first strategy being immunization. Since the disease is prevalent in low-income countries where vaccination hesitancy/vaccine shortages/lack of vaccine awareness can be seen, a complete kit with all the essentials will serve best to eliminate all the threats of contracting tetanus.

The kit may include soap, a clean blade to cut the cord, clean thread to tie the cord, and other crucial yet basic disinfecting agents. However, the widespread usage of the kits is met with its own set of challenges e.g. availability, delivery, and most importantly, their use by traditional birth attendants in rural areas<a href="#accordion">[11]</a>.

On March 18, a research paper was published reporting on the stats of neonatal tetanus. The results were promising with 88% of the 59 priority countries making progress by conducting immunization activities with the help of tetanus-toxoid-containing vaccines. From 2000 to 2020 the percentage of protected infants has gone up to 86% from 74%. An 88% decrease was reported worldwide in neonatal tetanus cases<a href="#accordion">[4]</a>.

<div>&nbsp;</div>

Key Points

<ul>
	<li>Neonatal tetanus is caused by Clostridium tetani.</li>
	<li>The bacterium enters the body of the infant through the mother.</li>
	<li>The biggest cause of neonatal tetanus is an unvaccinated mother followed by unhygienic delivery practices and the use of unsterilized instruments to cut the umbilical cord.</li>
	<li>Other than neonatal tetanus, localized tetanus, cephalic tetanus, and generalized tetanus are also prevalent.</li>
	<li>There are no specific diagnostic tests to detect tetanus in blood or through culture tests. The best way to determine neonatal tetanus is through differential diagnosis.</li>
	<li>When it comes to the treatment of neonatal tetanus, the first line of therapy involves the use of penicillin and metronidazole. This is followed by the administration of vaccines of multiple kinds to target the toxins produced by the bacterium.</li>
	<li>Neonatal tetanus can be prevented through the right measures starting off with getting vaccinated for tetanus and then practicing wound cleaning and disinfection. It can also be prevented by adopting better delivery practices through the use of sterile equipment and conducting the process in a clean contamination-free space.</li>
</ul>

[1] Apollo Hospitals, n.d. Neonatal Tetanus. [Online]

[2] Mayo Clinic, 2021. Tetanus. [Online]

[3] MD, J. E. B., 2020. Clostridium tetani. Bennett's Principles and Practice of Infectious Diseases, Issue 5.

[4] Medical press, 2022. Progress identified toward maternal, neonatal tetanus elimination. [Online]

[5] Mohamed Amirali Gulamhussein, Y. L. A. G., 2016. Localized Tetanus in an Adult Patient: Case Report. J Orthop Case Rep, 6(4), pp. 100-102.

[6] Public Health Ontario, 2020. Tetanus - Serology. [Online]

[7] Tejpratap S.P. Tiwari, M., Pedro L. Moro, M. M. & and Anna M. Acosta, M., n.d. Tetanus. [Online]

[8] Victor Nizet, J. O. K., 2011. Bacterial Sepsis and Meningitis. Infectious Diseases of the Fetus and Newborn, Issue 7, p. 251–254.

[9] World Health Organization, 2018. Tetanus. [Online]

[10] Arshad Quddus, S. L. M. R. Y. P., 2002. Neonatal tetanus: mortality rate and risk factors in Loralai District, Pakistan. International Journal of Epidemiology, 31(3), p. 648–653.

[11] Avan, S. A. R. a. B. I., 2019. Eliminating Maternal and Neonatal Tetanus and Promoting Clean Delivery Practices Through Disposable Clean Birth Kits. [Online]

[12] Centers for Disease Control and Prevention, 2019. Tetanus. [Online]

[13] Dr C Louise Thwaites, M. D. N. J. B. F. a. P. C. R. N. M., 2015. Maternal and neonatal tetanus. Lancet, pp. 362-370.

[14] Hinfey, P. B., 2019. Tetanus. [Online]

[15] Hinfey, P. B., 2019. Tetanus Treatment & Management. [Online]

[16] Hinfey, P. B., 2019. Tetanus Treatment & Management. [Online]

[17] Jagoda, A. R. S. &. B. T., 1988. Cephalic tetanus: a case report and review of the literature. The American journal of emergency medicine, 6(2), p. 128–130.