Int. J. Pharm. Med. & Bio. Sc. 2014 Otoikhian C S O et al., 2014

ISSN 2278 – 5221 www.ijpmbs.com Vol. 3, No. 3, July 2014 © 2014 IJPMBS. All Rights Reserved Research Paper TETANI IN MATERNAL AND NEONATAL INFECTIONS ()

Otoikhian C S O1*, Osakwe A A1, Akporhuarho J A S1 and Ogwezi R I1

*Corresponding Author: Otoikhian C S O  [email protected]

Maternal and neonatal tetanus are the important causes of maternal and neonatal mortality claiming about 180,000 lives annually globally. Tetanus is caused by produced by , a gram positive, obligate anaerobic, rod-shaped, spore forming bacterium. Tetanus is characterized by muscle rigidity and painful muscle spasms caused by tetanus blockage in neurons. Diagnosis of tetanus is done by analysis of clinical records. Maternal and Neonatal Tetanus causes are predominant in poor, remote and disenfranchised communities where unhygienic obstetric and postnatal practices prevail, and access to maternal tetanus immunization is poor. The only reliable immunity against Maternal and Neonatal Tetanus is that induced by vaccination with tetanus toxoid. Prevention relies on avoidance of unsafe delivery, unsafe abortions, and umbilical cord care practices which can predispose to tetanus infection; and promotion of maternal tetanus immunization.

Keywords: Clostridium Neonatal Tetanus Maternal Mortality

INTRODUCTION from more than 40 countries showed that fewer Maternal and Neonatal Tetanus are important than 10% of tetanus-related cases and death causes of maternal and neonatal mortality, routinely reported in most countries: in some claiming about 180,000 lives worldwide every year, regions, the reporting fraction was as low as 2- almost exclusively in developing countries. 5%. This disease accounts for 5-7% of worldwide Tetanus in the first 28 days of life (neonatal neonatal mortality, compared with 14% in 1993. tetanus) was long recognized by clinicians in Estimates suggest that these deaths have been resource-poor setting as an important cause of reduced, but that still some 130,000 babies died neonatal death. However, since babies affected around the year 2004 from this very preventable by this disease usually are born at home and die disease (WHO, 2004). In developed countries, there without registration of either event, the true tetanus is now little more than a medical curiosity; burden was unknown. In the 1970s and 1980s maternal and neonatal tetanus are exceedingly community based surveys about neonatal tetanus rare (Rosenhlatt et at., 2005).

1 Novena University Ogume, Nigeria.

51 Int. J. Pharm. Med. & Bio. Sc. 2014 Otoikhian C S O et al., 2014

CAUSATIVE AGENT OF Figure 1: Diagram of Clostridium tetani MATERNAL AND NEONATAL (Feingold,1998) TETANUS (MNT). Tetanus is caused by a neurotoxin produced by Clostridium tetani, a grampositive, obligate anaerobic rod-shaped, spore forming bacterium as shown by Feingold (1998) in Figure 1. Tetani spores worldwide are constituent of soil and in the gastrointestinal tracts of animals (including humans), and can contaminate many surfaces and substances. The spores are extremely hardy; destruction requires autoclaving or prolonged exposure to iodine, hydrogen peroxide, formalin Toxins are poisonous substances produced by or gluteraldehyde (Feingold, 1998). Clostridium living cells or organisms although humans are tetani stains gram positive in fresh cultures; technically living organisms, man-made established cultures may stain gram negative. substances created by artificial processes During vegetative growth, the organism cannot usually are not considered toxins by this definition. survive in the presence of oxygen, is heat- Classes of Toxins sensitive and exhibits flagella mortality. Their Endotoxins: Endotoxins are toxins associated endospores, a dormant form, are indifferent to with certain bacteria. An endotoxin is a toxin that oxygen, and can survive for long periods by is a structural molecule of the bacteria that is withstanding measures of heat, desiccation, chemicals, and irradiation that would kill all recognized by the immune system. vegetative bacteria. When the appropriate : Exotoxins are toxins excreted by a conditions are renewed, these endospores microorganism including bacteria, fungi, algae, germinate, and the resulting vegetative bacteria and protozoa. They are highly potent and can may once again multiply (Feingold, 1998) cause major damage to the hosts.

Table 1: Functional Categories of Exotoxins According to the Tissue they Adversely Affect (Lalliet al., 2003)

Exotins Organisms Toxin produced

1 A-B toxins:

Neurotoxins Clostridium tetani Tetanospasmin

Enterotoxins Vibro cholera

Cytotoxins Cyrynebacterium diphtheria

2 Membrane damaging toxins Clostridium perfringes Á – toxin

3 Staphylococcus aureus Staphylococcal

4 Other toxic Microorganisms Proteases, lipases and other hydrolases.

52 Int. J. Pharm. Med. & Bio. Sc. 2014 Otoikhian C S O et al., 2014

Tetanus Toxins (Tetanospasmin) and gabinergic inhibitory (Schiavo The endotoxin responsible for tetanus is one of et al., 2000). the worst potent toxins ever identified with a Inside inhibitory ’s, the disulphide minimum lethal dose of less than 2.5 ng/kg in bond converting the heavy and light chains of the humans. This high potency is caused by the toxin is broken. The free light chain is a zinc- toxin’s absolute neuro-specificity and enzymatic endopeptidase that cleaves action. Tetanospasmin is synthesized as an in synaptic vesicle membranes. The inactive polypeptide chain during the bacterial action of inhibitory neurons is thereby impeded, growth phase. The genes for the neurotoxin and leaving motor neuron excitation unopposed, and its transitional regulator, T ox R which is needed resulting in the muscle rigidity and long-lasting for toxin production, are located in an intracellular painful spams which are characteristics of plasmid. At autolysis, after death of the bacterium, tetanus. In addition to its action on the motor the toxin molecule is released and transformed system, tetanus toxin can have profound and life by bacterial or tissue protease into its active form threatening effects on the autonomic nervous a 1000 KDa heavy chain and a 50 KDa light chain. system by interrupting spinal inhibitory The heavy chain is necessary for binding to and sympathetic reflexes, resulting in a entry into the neuron. The light chain is hyperadrenergic state. In action of tetanus toxin responsible for the toxic properties (Lalli et al., within the neurons persist for several weeks; the 2003) mechanism of functional recovery remains unclear (Feingold 1998; Schiavoet al., 2000). MECHANISM OF ACTION OF TETANUS TOXIN Figure 2: Mechanism of Action of Tetanospasmin (Schiavo et al., 2000) The complex mechanism for binding of tetanus toxin to peripheral neurons and its absorption into these cells, transport to the , and toxic activity is shown in Figure 2. After its release, tetanus toxin diffuses to adjacent muscle tissue, where it binds to specific glycoprotein in lipid-raft constituents needed for the effective binding of tetanus toxin are not fully understood. Free tetanus toxin also enters the and the bloodstream, disseminating widely before entering motor neurons at disparate sites. Inside motor neurons, tetanus toxin is transported via acetylcholine to the Central Nervous System at 3-13 mm/h by a specific retrograde system. At SYMPTOMS the spinal cord and brain stem, the toxin diffuses Tetanus is characterized by muscle rigidity and across the synaptic spaces to enter glycinergic painful muscle spasms, caused by tetanus toxins

53 Int. J. Pharm. Med. & Bio. Sc. 2014 Otoikhian C S O et al., 2014 blockade of inhibitory neuron that normally oppose DIAGNOSIS and modulate the action of excitatory motor The diagnosis of Maternal and Neonatal Tetanus neurons. Maternal and Neonatal Tetanus are both is made strictly on clinical grounds. Cultures of forms of generalized tetanus (the most common tetanus patients wounds frequently fail to detect manifestation of the disease), and have similar growth of C. tetani; moreover, the organism courses. Tetanus muscle rigidity usually begins occasionally grows in cultures from patients in the masseteur muscle, resulting in trismus without tetanus. The neonate tetanus form can (lockjaw). Dysphagia and neck, shoulders, back, be diagnosed, if the patient shows signs of or abdominal muscle stiffness and pain are other uncontrollable irritation, and the inability to take in early symptoms (Patel et al., 1999). In neonatal fluids. As this type of tetanus infection is found tetanus, trismus and up muscle rigidity interfere only in infants, they are found to have a poor with normal sucking and feeding, which is the sucking ability. Diagnosis is a step by step hallmark of disease on set, As disease severity process. The doctor has two options, either to increases, muscle rigidity extends throughout the go for the laboratory test to diagnose the patient body and muscle spasms begin, first in response or to option for analysis of clinical records. Though to sensory stimuli but later progressing to laboratory testing is done in some special cases, spontaneous long-lasting excruciating spasms of most of the diagnosis for the tetanus infection is many muscle groups (Figure 3). The onset period, done based on recent and previous clinical or time from first symptom to first spasms, is records. Here diagnosis involves four steps: typically 1-3 days, ranging from hours to 5 days • Confirmation of an infection (Patel et al., 1999). The average incubation period for Maternal Neonatal Tetanus cage (age at first • Checking symptoms of various infections symptom) is shorter than that on non neonatal • Diagnosing the infection tetanus. About 90% of neonates with tetanus develop symptoms in the first 3-14 days of life, • Stages and type of diagnosed infection mostly on day 6-8, distinguishing neonatal tetanus Once the doctor diagnoses the patient case from other causes of neonatal mortality which as a tetanus infection he has to classify the type typically occur in the first two days of life (Farrar of tetanus which has affected the patient. This is et al., 2000) important as proper treatment is possible only if

Figure 3: Photograph of Newborn Child with the correct type of infection and all symptoms Neonatal tetanus (Farrar et al., 2000) are perfectly known (Wassilak et al., 2004). Laboratory testing for the tetanus infection is used in determining the presence of the toxins in the blood sample, which will help in diagnosing the presence of tetanus bacteria (Akina et al, 2004).

EPIDEMIOLOGY Maternal and Neonatal Tetanus causes are clustered in poor, remote and disenfranchised

54 Int. J. Pharm. Med. & Bio. Sc. 2014 Otoikhian C S O et al., 2014 communities where unhygienic obstetric and tetanus toxoid. Newborn babies and young infants postnatal practices prevail, and access to born to mother with antitetanus are maternal tetanus toxoid immunization is poor. protected against tetanus by acquired maternal Home delivery assisted by untrained birth . attendants are the main reasons behind the widespread of Maternal Neonatal Tetanus in many PREVENTION AND CONTROL developing countries, especially in rural areas, Maternal and Neonatal Tetanus prevention relies and bring together many factors that confers, a on avoidance of unsafe delivery, abortion, and high risk of tetanus to both mother and child. The umbilical cord care practices, and promotion of following are the reasons behind the widespread maternal tetanus immunization. The use of topical of Maternal and Neonatal Tetanus: antimicrobials to replace traditional substances • Home delivery applied for cord care could have an important effect on neonatal tetanus in communities where • Untrained birth attendants high risk cord care practices persists, for example • Poverty in rural Pakistan (Darmstadt et al., 2005). Control involves the Maternal and Neonatal Tetanus • Lack of maternal and paternal education elimination initiative. Tetanus toxoid vaccination • Young maternal age of pregnant women to prevent neonatal tetanus • Cultural restriction in women’s access to health was included in WHO’s EPI a few year after its services inception in 1974 and only 27% of pregnant women received at least two doses of tetanus • Low antenatal care attendance toxoid in the 1980s. • Inadequate vaccination with tetanus toxoid Sustaining elimination of Maternal and • Unsafe abortion (Omoigberale and Abiodun, Neonatal Tetanus will be a challenge, especially 2005; Ogunlesi, 2007). in places where the high risk approach is needed. Routine immunization with tetanus toxoid has TREATMENT been stagnant over the past decade with only 5 The specific objectives of tetanus treatment are 0-54% of pregnant women worldwide receiving to stop the production of toxin at the site of adequate immunization, a situation largely infection with appropriate wound care and unchanged since the late 1980s. Many countries antibiotic use; to neutralize circulating toxin with still striving to achieve elimination have approved antitetanus immunoglobulin; and to provide tetanus toxoid coverage in most districts and are effective management of muscle spasm, close to meeting the objective (Figure 4) (WHO, respiratory failure, autonomic dysfunction, and 2005). Even before was available complications that arise during the cause of neonatal tetanus became increasingly rare in illness. Theurapeutic approaches depend on the most of Europe and North America through resources available in the facility to which the hygienic childbirth practices and cord care. patients present. The only reliable immunity (Rossenhlatt et al, 2005). WHO recommends that against tetanus is that induced by vaccination with at least five doses of tetanus toxoid vaccine be

55 Int. J. Pharm. Med. & Bio. Sc. 2014 Otoikhian C S O et al., 2014

given over 12-15 years, starting in infancy; a sixth Figure 5: Maternal and Neonatal tetanus dose given in early adulthood is encouraged, to Elimination Status by Country (WHO, 2005) ensure long lasting protection (WHO, 2005).

CONCLUSION Maternal and Neonatal Tetanus still contribute considerably to neonatal mortality in world, even in Nigeria. This work has been examined some of the possible causes of the persistently high incidence of the disease over the years, and has suggested that attempts to eliminate the disease be carried in a wider context of meeting millennium development goal 4. This approach is suggested on the ground that reduction is neonatal mortality, and in countries with high Maternal Neonatal Tetanus mortality, its reduction However, Nigeria as a case study is a large equally becomes an imperative. The focus here country with 774 LGA. Therefore, it would be wise is on improving health care delivery at the grass to start implementation of these suggestions in root levels to reduce or if possible eliminate the carefully selected LGA as pilot centers, and scourge of Clostridian tetani in the environment gradually expand to other communities over time.

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