ANAEROBIC BACTERIAL INFECTIONS IN CHILDREN

Infection in youngsters is frequently caused by anaerobic bacteria. Since anaerobes make up the majority of the bacterial flora that normally inhabits human skin and mucous membranes, they are frequently the source of endogenous bacterial illnesses. They are frequently disregarded and challenging to isolate from infectious locations due to their meticulous nature. Any part of the body, including the central nervous system, mouth, head, neck, chest, belly, pelvis, skin, and soft tissues, is susceptible to anaerobic infections. After birth, anaerobic bacteria invade the infant and have been found to be responsible for a number of neonatal illnesses.  

There are three types of infections in children, which are as follows:

• Botulism
• Tetanus
• Clostridium Difficile Infection (CDI)

Botulism

This particular form of symmetric flaccid paralysis is brought on by neurotoxins made by Clostridium family members. This is most frequently caused by Clostridium botulism, while it can also occasionally be caused by Cl. Butyricum and Cl. baratii.

Cl. Botulism is an obligatory anaerobe, gram-positive bacterium that forms spores. It naturally exists in dust and soil. Most spores can withstand boiling. Botulism toxin is the name of its toxin.

One kind of neurotoxic created by actively proliferating cells is botulinum toxin. The highest effective and fatal dosage is 10–6 mg/kg. A variety of forms of this toxin have been identified. Both type A and type B bacteria can cause botulism in humans.

1. A. Cl. Botulinum produces Type A and Type B.
2. B. Cl. Butyricum produces Type E, and Type F is produced by Cl. Baratii.

Mechanism Of Botulism

Synaptic vesicles in the neuromuscular junction store acetylcholine during normal transmitter release. Synaptobrevin, a protein found on the outside of synaptic vesicles, and syntaxin and SNAP 25, two complementary proteins, are found inside them. Membranes, not vesicles, contain complementary proteins.

The three proteins are members of the Snare Protein family.When the signal for contracting muscles arises, synaptobrevin, syntaxin, and SNAP 25 work together to form a trimer. Acetylcholine is released when the vesicle fuses into the membrane to create the trimer. Muscle will contract when acetylcholine binds to the receptors.

The pre-synaptic area is where the botulinum toxin binds when there is botulism. The poison is made up of light and heavy chains. Disulfide bonds bind these chains together; the heavy chain is necessary for penetration into the neural structure, while the light chain is the source of issues.

Following SNAP25's destruction, syntaxin is likewise disturbed. Thus, the trimer is not developing. Additionally, the muscle will become paralyzed and acetylcholine will not be released into the lumen. We refer to that as a neuromuscular blockade. which is powerful and irreversible. Motor nerves are involved in this blockage.

The toxin enters the vesicle after entering the presynaptic area, whereupon the heavy chain attaches to the receptor and releases the light chain. The snare protein, specifically Snap 25, is destroyed by the light chain when it emerges.

Types Of Botulism

• Consumption of infected honey is linked to infant botulism (MC)
• Anytime a pre-formed toxin is present, food-borne botulism can develop. frequently found in canned goods.
• Wound botulism: In the event of trauma, an infection with Cl. botulinum will occur. 

Two uncommon types of botulism

• Inhalational botulism: This happens in lab settings whenever botox is administered.
• Idiopathic botulism: When a significant quantity of botox injections enter the bloodstream, poisoning may result.

Interesting Facts

• Meckel's diverticulum intestinal colonization has been linked to infant botulism caused by Cl butyricum;
• Botulism toxin is not a cytotoxin and no obvious pathological alterations are observed.
• Paraesthesia, seizures, and poor sensorium are never observed in botulism. 
• The healing process in botulism consists of the sprouting of new terminal unmyelinated motor neurons; this healing process begins approximately 4 weeks after the exposure. Since there is no involvement of the sensory nerves, paresthesias are not observed. The poison does not pass across the blood-brain barrier, hence seizures and poor sensorium are likewise absent.

Clinical Features Of Infant Botulism

There is the three to thirty day incubation period.  The paralysis will progress in a symmetric, descending, and flaccid manner.
The most common symptom of the earliest affects the cranial nerve and is known as bulbar palsy.
• Constipation is the initial symptom, though it's frequently overlooked.
• Poor sucking, drooling, and eating.
• Ptosis might exist.
• There may be a loss of head control.
• There's a weak whimper.
• It may be obstructive apnea.
• Advances to hypotonia and widespread weakness.

Other Types Of Botulism

Botulism Arising From Food

Time of incubation: 12–36 hours. Along with 7D (diplopsia, dry mouth, dysphagia, drooling, dysphonia, dysarthria, diminished gag reflex, and corneal reflexes), there will also be ptosis. In 30% of instances, GIT symptoms such diarrhea, vomiting, nausea, and constipation occur. They eventually reach generalized hypotonia. 

Damaged Botulism

Time of incubation: 4–14 days. There might be a fever. Although there are no GIT symptoms, the features resemble food-borne botulism.

Cause Of Death in Botulism

Botulism is caused by the respiratory system; the primary cause may be airway obstruction by pooled secretions or paralysis of the respiratory muscles.

Diagnosis

NCV: Typical. EMG readings may be vague or contain hints: When high-frequency (50 Hz) stimulation is applied, the evoked muscle AP is observed to be facilitated (potentiated). 

Clinically weak muscles in newborn botulism exhibit a specific pattern called BSAP (short, small, abundant motor unit action potential).  Toxin detection, which can be performed on blood or stool samples, is a diagnostic procedure for patients.For newborn botulism, the presence of Clostridium botulinum in feces is a reliable sign of the disease.

1. Treatment

The primary focus of treatment is support.  Laying down faceup on a firm bed with the head end elevated by thirty degrees.In order to tilt the head back and allow secretions to flow to the posterior pharynx and away from the airway, a tiny cloth roll is positioned beneath the cervical vertebrae.

2. Early intubation

Particularly if drooling or the gag reflex are absent.  Feeding: Initially through a nasogastric or nasojejunal tube until the patient gains the strength to take oral feeds. It is best to utilize expressed blood milk for young newborns.

It's important to make sure you get enough hydration and stool softeners (such lactulose).  Use nosocomial care to primarily manage problems
Antibiotics in botulism

Since the toxin, not the bacteria, causes botulism, antibiotics should be avoided in cases of the disease. Additionally, as bacteria die, an intracellular poison is secreted. The use of antibiotics can exacerbate the situation by killing off a lot of bacteria and releasing more toxins.
Use antibiotics sparingly (aminoglycosides aggravate NM blockage); only use them in cases of wound botulism or secondary bacterial infections in patients (local debridement is crucial in these cases).

Preventions and Prognosis

Keep honey away from newborns. Steer clear of outdated or cold canned food; always reheat for 5 to 7 minutes before consuming.  All wounds should be treated, debrided, and managed aseptically to prevent wound botulism.  The average youngster stays in the hospital for four to eight weeks.  If young infants' mortality is properly managed, it should be less than or equal to 1%..  Better results are attained.  The risk of strabismus is higher in later age.

Tetanus

Etiological agent: Cl tetani is the cause.Gram-positive, spore-forming, obligately anaerobic, and motile bacillus is Clostridium tetani. Cl tetani has spores of the terminal kind. It looks like a tennis racket.Spores can be found in soil, water, and the stomachs of many humans and animals.There are two forms of tetanus toxin: tetanolysin and tetanospasmin.

The neurotoxin known as tetanospasmin, which is generated by Clostridium tetani, causes the spastic sickness known as tetanus. A light A unit and a heavy B unit make up tetanospasmin. The heavy B unit is in charge of both entry into and localization within neurons, while the light A unit is in charge of inhibiting activity in neurons. Tetanospasm is not found in spores; it can only be made by dividing the bacteria.

Pathogenesis Of Tetanus

Vegetative cells will emerge from contaminated or infected spores upon germination. These vegetative cells will also generate additives. Tetanospasmin attaches itself to the neuromuscular junction (NMJ) and, once there, initiates RETROGRADE AXONAL TRANSPORT. When there is relative hypoxia in the tissues, pus development, or muck contamination of the tissues, the process of germination and synthesis of toxins is promoted. This suggests that the poison will travel through the axon and cytoplasm to reach the spinal cord cell from the NMJ. Dynein is the mediator of RETROGRADE AXONAL TRANSPORT.

The toxin then travels to the alpha motor neurons in the spinal cord. It then moves on to interneurons, which are resident interneurons in the spinal cord that are frequently inhibitory. GABA and glycine are normally found in synapses resides in interneurons; when it enters the interneuron, it inhibits these neurotransmitters, resulting in spasms in the individuals who experience them.They require the release of synaptobrevin activity. Synaptobrevin is broken down by tetanospasmin's light chain, preventing the release of neurotransmitters. There is no turning back now.  The dangerous dosage of 10–5 mg/kg.

Clinical Types Of Tetanus

On average, the incubation phase lasts two to fourteen days.  The first symptom is spasms of the masseter muscle, which cause trismus, or lock jaw.  Patients with a condition called Risus Saronicus frequently experience dysphagia, dysarthria, and a high-grade fever, which is a fever brought on by muscle spasm. The patient starts to have a severe spasm. This could cause sudden spasms of the larynx and throat that resemble the symptoms of choking or a seizure-like state. 

Eating or touching can occasionally trigger excruciating muscle spasms, in addition to loud noises.  In developed countries, the death rate from generalized tetanus is 5–30%, but in developing countries, it is 30–50%. There are painful spasms and an obstructive posture.

Neonatal Tetanus

Since 2015, India has declared the eradication of newborn tetanus.
Usually in young toddlers, this happens.  It appears between three and twelve days of life.  Neither the first 48 hours of life nor the first two weeks of life witness any manifestation. 

Risk factors include an immunized mother and infected umbilical cord.
The symptoms of neonatal tetanus include cyanosis, insufficient feeding, prolonged wailing, and apnea episodes. Posisthotonus may or may not be in place. Its prognosis is poor and its death rate can reach 90%.

Localized Tetanus

• Cephalic tetanus is a type of local tetanus that arises from minor contaminated wounds in the head and neck region; it is a precursor to generalized tetanus. Mild cases are rare. In most cases, toxins involve the bulging muscle.
• It is widely acknowledged that protection against tetanus is provided by serum antitoxin levels larger than or equivalent to 0.01 IU/mL. As a result, their prognosis is frequently very poor.

Diagnosis Of Tetanus

It is probable that the presence of Cl tetani is not constant.

• Blood and CSF testing are frequently normal.
• Muscle CPK and aldolase levels may be elevated and non-specific.
• Spatula test: incredibly sensitive and specific. The negative spatula test causes the participant to gag and remove the spatula when it comes into contact with the posterior wall of the oropharynx in a healthy person. Conversely, a robust contraction of the masseter muscles and the patient biting the spatula with his teeth while holding it in his mouth are signs of a positive spatula test..

Treatment Of Tetanus

• Inject 500–1000 IU of human tetanus immunoglobulin intramuscularly, and eliminate the source of Cl tetani. 
• Antibiotics: The suggested drug is metronidazole. The dosage is 7.5 mg/kg/dose every 6 hours for a duration of 7 to 10 days. An alternative is penicillin G.

Management Of Spasms in Tetanus

Supportive

• The patient should ideally be cared for in a quiet, dark, and isolated space. There shouldn't be any social interaction either.
• Hydration levels and vital indicators were tracked. (because many people have a high probability of developing growing ANS dysfunction)

Specific

• Benzodiazepines, including diazepam (bolus or low dose infusion), are the recommended therapy. Pancuronium, a muscle relaxant, may be used in cases of severe spasms (patient should be intubated; if not, tracheostomy should be performed). 
• When treating pain, NSAIDs—which include opioids and morphine—should be used. • Autonomous functions should be managed by ? and ? blockers.

Prognosis

There is not a good prognosis for cephalic tetanus. high fever with a short incubation period. Trismus appears <7 days after the injury.
Tetanic spasm starts less than three days after trismus first appears.
Neonatal tetanus is more likely to result in mortality.  Death tolls from generalized tetanus: 5–30% in wealthy countries, 30–50% in undeveloped countries. 

Clostridium Difficile Infection (CDI)

It is also referred to as enterocolitis, pseudomembranous colitis, and diarrhea associated with Cl difficile.The causal agent is Clostridium difficile, now known as Clostridiodes difficile. Babies and newborns are carriers, but they don't show any symptoms.Toxins fall into two categories: toxins A and B. Because they impede intracellular signaling, both of these cause early cell death.

Risk Factors

• Using cephalosporins and clindamycin, two broad-spectrum antibiotics.
• Prolonged hospital stays.
• GIT protocols.
• Drugs
• Syndrome of irritable bowel.
• Abuse of PPIs and H2 blockers.
• The feeding tube method.
• Prolonged ailments like cystic fibrosis.

Clinical Features Of CDI 

Varies from mild, self-limiting diarrhea to episodes lasting one to two days.  Severe inflammation of the gastrointestinal tract, exhibiting symptoms like nausea, bloody diarrhea, toxic megacolon perforations, abdominal discomfort, and pseudo membrane formations.

Diagnosis

Toxin detection in excrement is the basis of diagnostics.

• Enzyme immunoassay: sensitivity up to 88–93%, specificity 94–100%.
• PCR/NAAT: Highly sensitive and specific. A PCR test may overdiagnose some carriers as infected.
• Culture: labor-intensive, sporadic, delicate, but general.
• Pseudomembranous lesions and nodules/plaques may be seen during a colonoscopy or sigmoidoscopy.

Treatment Of CDI

• For a mild to moderate condition, the suggested therapy is metronidazole (7.5 mg/kg/dose, six hours a day for 10 days). 
• Severe case: the recommended course of treatment is oral Vancomycin, administered for 7–10 days. 
• Refractory cases: A very broad spectrum drug called nitazoxanide is used. 

Advanced Therapies

• Fidaxomicin: A macrolide antibiotic with a narrow spectrum that works better in preventing recurrences than vancomycin but not any less effectively. It is a second-line drug that is not yet authorized for usage in pediatric patients.
• Faecal microbiota transplantation (FMT): from an unaffected donor.

Prognosis Of CDI

Recurrences are frequent, typically happening in 4 weeks, and they happen 5–20% of the time. Over 95% of patients respond well to therapy in the beginning. Recurrence prevention measures include tapering or pulsed Vancomycin. 

• Ritoxanide (Rifaximin) 
• Tolevamer: Toxin-binding polymer
• Probiotics Saccharomyces boulardii and Lactobacillus GG in an intravenous immunoglobulin (IVIG) experiment.

Miscellaneous Anaerobic Infections

• Lemierre Syndrome: Fusobacterium-induced lateral pharyngeal suppurative infection leads to unilateral septic thrombophlebitis of the jugular venous system. 
• Bacteremia: Children can develop bacteremia from Clostridium, Fusobacterium spp., Peptostreptococcus, and the Bacteroides fragilis group. 
• Brain Abscess: Polymicrobial, comprising a mix of anaerobes such as Peptostreptococcus and Staph aureus. 
• Ludwing Angina: Sublingual and submandibular cellulitis caused by Fusobacterium.Vincent Angelini developed an oro-gingival infection caused by Prevotella and Fusobacterium. 
• Typhilitis: This intraabdominal infection is brought on by a variety of anaerobic bacteria. This is typically seen in neutropenic individuals. 

The most common cause of Clostridial myonecrosis/gas gangrene is Clostridium perfringens, while it can also sometimes result from Cl novyi, Cl septicum, and Cl histolycticum. Alpha toxin is the main toxin responsible for gas gangrene.

New Advances in The Diagnosis Of Anaerobic Infections

• Matrix-assisted laser desorption/ionization-time of flight mass spectrometry. (MALDI-TOF MS). 
• 16 rRNA gene sequencing (higher sensitivity than MALDI-TOFMS). Among the technologies are multiplex PCR, oligonucleotide arrays, and DNA hybridization.

Also Read: Mumps : Virus Characteristics, Pathology and Pathogenesis, Investigations, Complications and Treatment

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