Maternal generalized tetanus following spontaneous abortion in a vaccinated woman: a rare but persistent threat

Introduction Tetanus has been known since Hippocrates. There have been few, if any, additions to its symptomatology though the pathophysiology has been explored to a molecular level and options for prevention and management have changed enormously. Active immunization programmes have been pursued for over 50 years and new technologically based management strategies have been developed over the past 30 years. In principle, tetanus should by now be a totally preventable disease but, even so, it is expected to have killed 10 million people in the last decade of the 20th century, the majority of them infants [1]. It continues to drain the meagre health resources of many developing countries, and to provide more occasional but nonetheless unpleasant surprises in more developed ones, appearing, as it does in several forms and guises, besides the classic picture following recognized trauma or wounding [2,3]. Reporting, incidences and mortality Tetanus is a notifiable disease in many countries, China being an exception eminently notable in view of its size and population. Overall figures may be reported, or reporting may be in terms of a number of recognized subtypes such as neonatal and maternal tetanus. Even where notification is compulsory, gross under-reporting is commonplace. Routine reporting systems for neonatal tetanus identified only about 4% of the cases estimated to have occurred worldwide in 1990 [4]. In the USA, the completeness of overall reporting to the national surveillance system between 1979 and 1984 was estimated to be 22–46% [5] and, in Switzerland, the reported cases of tetanus probably reflected no more than 13% of the actual number [6]. The available figures reflect a complex of geographical differences in reporting, lifestyle-related predisposition, application of preventative measures such as active immunization programmes, and therapeutic interventions such as the administration of antitoxin and technologically demanding treatments for the manifestations of the disease. The WHO estimates that, in 1992, there were 578 000 infant deaths from neonatal tetanus. Of these, 210 000 occurred in South East Asia, 152 000 in Africa, 114 000 in the Western Pacific region, 90 000 in the Eastern Mediterranian, 112 00 in the Americas and 1000 in Europe [6]. Table 1 summarizes recently published information on aspects of tetanus from different parts of the world. There have been many contributions to the literature from Russia but little is known of the incidence in Russia or in Eastern Europe. The incidence of maternal tetanus is not known. Probably 15 000 to 30 000 cases of maternal tetanus occur worldwide each year [17]: 27% can be attributed to post-abortal and 67% to post-partum sepsis. In Nigeria, 10% of adult tetanus cases were attributed to maternal tetanus [18].Table 1: Global prevalence of tetanus Pathophysiology Tetanus is a toxic infection caused by the obligate anaerobe Clostridium tetani. Clostridial toxins are generally regarded as the most poisonous substances known to mankind. The spores of Clostridium tetani are present in the soil and faeces and can enter the body, proliferate in devitalized tissue and produce the exotoxins, tetanospasmin and tetanolysin, which can gain access to the blood and central nervous system (CNS). Tetanolysin is a haemolysin but plays no presently recognized part in the overall clinical picture in tetanus. Tetanospasmin is primarily a very potent neurotoxin and is probably solely responsible for the manifestations of the disease. Access of the toxin to the CNS The toxin can circulate in the blood stream but does not enter the central nervous system in appreciable amounts by this route because it cannot cross the blood brain barrier except where it is deficient at the fourth ventricle. It enters motor nerves at the neuromuscular junction and travels by intra-axonal transmission at the rate of 72–250 mm day−1. It may thus take 2–14 days to reach the central nervous system. The symptoms appear only after the toxin has gained access to the presynaptic terminals of those inhibitory Renshaw cells that release gamma-aminobutyric acid (GABA) and glycine (rather than those that release acetylcholine). This blocks inhibition at brain stem and spinal cord level resulting initially in more or less localized increases in resting muscle tone (rigidity) and later in more generalized hyperreflexia and spasms [19]. The toxin enters sensory and autonomic nerves via their peripheral endings but, because of slower intra-axonal transport, it takes longer for the toxin to reach the lateral horn cells and autonomic dysfunction sets in a few days after the spasms. Autonomic dysfunction manifests as increased basal sympathetic activity and episodes of sympathetic overactivity or 'crises' involving both alpha and beta receptors. These are caused by reduced inhibition of the postsynaptic sympathetic fibres and adrenal medulla and are evidenced by outpourings of noradrenaline and adrenaline in amounts comparable with those found in patients with phaeochromocytoma (which are about ten times the basal amounts) [20,21]. Another postulated cause is the increased release of thyroid hormone and direct inhibition of the release of endogenous opioid oligopeptides. The cellular actions of tetanus toxin The principal site of action of tetanospasmin in mammals is at inhibitory synapses, though it can also affect the central excitatory synapses, the neuromuscular junction, and autonomic ganglia [22,23]. Injection of tetanus toxin into the hippocampus of the rat establishes a long lasting excitatory focus in the brain [24]. The convulsant effect either releases an inherent tendency for hippocampal nerve cells to fire repetitively or may preferentially block key inhibitory synapses, leaving excitatory influences unchecked. Whatever the cause, an excitatory effect at one group of neurones will have a secondary kindling effect on the other synapses within the brain which will reinforce and maintain the excitatory effect, and promote its extension from any primary focus. Tetanospasmin was initially thought to affect only glycinergic pathways, but effects were subsequently found on pathways mediated by GABA, which is probably the most widespread inhibitory transmitter in the mammalian nervous system. It now appears that the toxin can also interfere with other central inhibitory neurotransmitter processes such as those mediated by dopamine and noradrenaline, as well as transmission at cholinergic synapses in the peripheral somatic and autonomic nervous system [25,26]. Egea et al.[27] found that tetanus toxin blocks the release of acetyl choline from isolated nerve terminals in a dose-dependent manner, an effect prevented by antiserum to tetanus toxin. In GABA-ergic synapses that have been blocked by toxin, the responses to exogenously applied transmitter are unaffected. It follows that the effect is presynaptic, involving some aspect of events leading to release of endogenous transmitter. Tetanus toxin blocks the rearrangement of intramembrane particles at the plasma membrane of experimentally poisoned synapses. It has no effect on uptake, synthesis or storage of transmitter, but directly impairs the calcium-dependent release of GABA [28,29]. It blocks, not only the evoked release of transmitter, but also most of the spontaneous release. The blockade may be preceded by an asynchronous release of quanta of GABA. These effects are believed to result from interference with the movement of synaptic vesicles to the active zones through blockade of most of the calcium channels, because the toxin can selectively block the calcium component of the action potential in cultured neuroblastoma cells. The effects of tetanus toxin are prevented by pretreatment with ethanolamine O-sulphate or sodium valproate, drugs that enhance GABA-ergic mechanisms by inhibiting the enzyme GABA transaminase and/or succinic aldehyde dehydrogenase [30]. At a molecular level, tetanospasmin is synthesized as a single polypeptide chain with a molecular weight of 140 000–160 000, which can be enzymatically split into light and heavy chains. The carboxy terminus of the heavy chain mediates binding to the target cell membrane and the amino terminus mediates the incorporation of the toxin into the cell. Transmitter release at nerve terminals appears to be inhibited by the light chain which may interfere with exocytosis after the entry of calcium ions [2]. The light chain is a zinc endopeptidase that produces a single-site cleavage of an integral membrane protein of small synaptic vesicles, synaptobrevin. Clinical features The precipitating injury A history of some sort of injury is present in most cases, with an incubation period that can vary but is usually between 3 days and 3 weeks. However, the culprit wound may well be so trivial that the victim does not think of seeking medical attention. Tetanus may also occur following skin and middle ear infections [31]. Dental caries or a root canal procedure was considered to be the point of entry for tetanus spores in one instance [32]. Other unusual sources of injury include frostbite, gum ulceration by dentures, infected molluscum contagiosum, scratched atheroma cutis and infected granuloma pyogenicum. Thus it is unwise to exclude tetanus from a differential diagnosis just because there is no obvious portal of entry [33,34]. A series of cases of tetanus with a 96% mortality has been reported after intramuscular injections of quinine which are widely used in treatment. Quinine dihydrochloride, the usual formulation for parenteral administration has a pH of 2 and may cause local vasoconstriction and necrosis. The chemical damage and ischaemia lowers the redox potential at the injection site and provides a favourable milieu for rapid sporulation and growth of Clostridium tetani [35]. In another series reported in 1994, 89% of the cases were heroin addicts [36]. It may be relevant that heroin is often 'cut' with quinine. The cases developed severe tetanus with autonomic dysfunction. Pulmonary and gastrointestinal complications were common and the mortality rate was 25% [21]. In many countries, traditional practices continue to this day that carry a high risk for tetanus—practices such as scarification, circumcision, ear piercing and the application of oils, ghee and dung to the cut umbilical cord [37]. Clinical presentation The commonest presenting symptom is trismus. Rigidity progresses in a descending manner. Dysphagia, risus sardonicus and neck stiffness are soon followed by rigidity of the trunk and limbs. The spasms which follow may vary in severity and be localized or generalized, but tend to affect the trunk more than the limbs. Spasms may occur spontaneously or provoked by some form of stimulation. Arching of the trunk-opisthotonus is a feature of the established disease. Trismus develops to be a prominent feature, leading to considerable difficulty in feeding, maintaining oral hygiene and swallowing saliva. These difficulties often lead to aspiration bronchopneumonia—a frequent life-threatening complication. Neonatal tetanus presents most often on the seventh day of life with a short history of failure to feed. Spasms are typical but the diagnosis can be mistaken for meningitis and sepsis. Cephalic and localized tetanus are uncommon variants that may defy diagnosis for considerable periods. Cephalic tetanus [38,39] is a form that presents after wounding of the head and neck, in which trismus is often preceded by cranial nerve palsies: it accounts for 1–3% of the total number of reported cases and has a mortality of 15–30%. Localized tetanus accounts for a similarly small number of the reported cases. It has a long incubation period and manifestations, including flaccidity, restricted to muscles near the wound. The mechanism of the paralysis is not completely understood, but is likely to be related somehow to the inability of the toxin molecule to be conveyed to the central nervous system [40]. The spasms may spread from one limb to another (recruitment spasm). The signs may mimic other neurological disorders. The important clinical observation of autonomic dysfunction in tetanus was described first in the 1960s [41]. Autonomic dysfunction usually manifests itself as a hyperkinetic circulatory state with tachycardia and arrhythmias, increased stroke volume and increased cardiac index. These may be accompanied by depression of bowel motility and bladder dysfunction and episodes of sweating and pyrexia which may also indicate concurrent infection. These manifestations of sympathetic overactivity may alternate with episodes of hypotension from loss of systemic vascular resistance and bradycardia to the point of cardiac arrest from which resuscitation can be difficult. This has been attributed to sudden withdrawal of sympathetic activity rather than to an increase in parasympathetic activity because the response to atropine is variable. Other explanations for these episodes are catecholamine-induced myocardial damage, vagal stimulation and effects of the toxin on the brain stem that may impair baroreceptor function [42]. There may be complaints of abdominal pain amongst the presenting features and there is a report of a patient with Horner's syndrome and trismus from tetanus [43]. Diagnosis Early treatment is crucial to the chances of survival and recovery. The early diagnosis which enables early treatment must depend purely on clinical observation and may go by default in countries where the disease is uncommon. Tetanus may not come to mind because of the many variants from classical presentations. These can suggest a range of differential diagnoses including acute dental infections, acute tempero-mandibular disease, intracranial lesions, drug induced muscle dystonias and strychnine poisoning. These factors may delay the establishment of a definitive diagnosis [44]. Laboratory findings are virtually of no value except to rule out strychnine poisoning. Blood counts and blood chemical findings are unremarkable. Imaging studies of the head and spine reveal no abnormalities. The cerebrospinal fluid is normal and a lumbar puncture is not necessary. Recently a simple bedside test to diagnose tetanus has been described: the spatula test. A spatula is used to touch the posterior pharyngeal wall, and a positive test result is reflex spasm of the masseters. This occurred in 349 of 350 patients with tetanus (sensitivity 94%) and in no patient without tetanus (specificity 100%) [45]. Severity The severity of tetanus is usually predicted on the basis of the incubation period (time between injury and first symptom) and the onset time (time from first symptom to first spasm). Incubation periods of less than 14 days and onset periods of less than 48 h are said to herald a severe attack, though longer incubation periods and onset times do not guarantee a mild attack. A useful way of grading the severity of established symptoms for purposes of management and study is: Grade I—Trismus; Grade II—Dysphagia, neck rigidity, risus sardonicus, opisthotonus; Grade IIIa—Muscle rigidity, spasms; Grade IIIb—All of above and autonomic dysfunction. Treatment The principles of treatment once symptoms appear are: Eradication of the organism; Neutralization of toxin; Symptomatic treatment of the effects of the toxin; (3a) Control of muscle spasms and rigidity, (3b) Control of autonomic dysfunction; Supportive measures; Active immunization. Eradication of the organism Whatever the specific concerns about tetanus, ordinary clinical common sense dictates that any obvious wound must be cleaned and any devitalized tissue must be debrided, under general anaesthesia as necessary. It is, of course, also routine in all developed healthcare systems to attempt to establish or boost active immunity by giving tetanus toxoid as soon as possible after any at-risk injury. Metronidazole is the antibiotic of choice when there are specific concerns about tetanus because of its activity against anaerobes and effective penetration of devitalized tissues. Penicillin, the antibiotic of choice for decades, is a GABA antagonist and may aggravate the spasms of tetanus [46]. However, by the time symptoms present, the frequent absence of an obvious wound or tissue damage means that treatment based solely on adequate wound care is likely to be futile, and must not delay the more urgent attention that must be given to other measures, particularly neutralization of toxin. Neutralization of toxin. The importance of this measure is illustrated in experience documented by many hospitals. For instance, in a review of 2449 cases in 65 years at Charity Hospital, New Orleans, USA, the fatality rate in the pre antitoxin era (1840–1905) was 76.4%. From 1906 to 1923 the rate was 70% and, by 1966, it had dropped to 31.6%. However, in a review published in 1976, the mortality was 58% with a distinct change in the average age of patients from 25 years to 40 years and a virtual disappearance of neonatal tetanus over the period [47]. Neutralization of the toxin should be effected as early as possible after the appearance of symptoms attributable to tetanus, because the toxin becomes inaccessible to antitoxin after an indeterminate but usually relatively brief period [48]. Human tetanus immuno-globulin (HTIG) should be given intramuscularly (i.m.), preferably within 24 h of diagnosis. A dose of 500 units i.m. is now recommended in place of the larger traditional doses of 3000–5000 units. If HTIG is not available, is used after for of antitoxin the blood brain so these do no more than any toxin. In to the toxin to nerve or HTIG have been given following studies et were amongst the to report the of antitoxin which reduced the mortality from to of was with in an attempt to effects In a in HTIG was given to at an dose of to patients and an intramuscular dose of 1000 to the there were only one with the administration but 15 10 with the intramuscular administration In neonatal tetanus, a out by and to provide that with either or HTIG is of important treatment effects in some not be the for more definitive studies of the and complications of Symptomatic treatment Early treatment. sets the of spasms can be very rapid and there is a risk of In one patients are for and for or at the time as wound so that can be in a high that spasms do not occur or [31]. to the and in a is and observation is particularly to the of spasms. Control of spasms. spasms can be by spasm of either the or spasms lead to and, because is not the patient is and becomes and this often has a traditional place and are widely at in developing countries where there have been few to them with more are on the alpha of GABA and in to enhance the function of GABA by the binding of GABA to its receptors. the rate of of GABA from its receptors. The of to of cell them more to The usual dose of is 1 to a dose as high as 40 h may be necessary. At high doses of can though this is attributable to its has been used for its and mediated muscle It also produces blockade and depression of mediated by the or brain However, one of its effects is the of dopamine as a neurotransmitter in the basal ganglia and of the syndrome has tetanus with The more traditional produce effects in the in which is in short in many developing has been used for the very widely and, on its effects take h to after of et have described the of for to was for resulting in of in of 50 and a of these are no was is another for particularly as therapeutic doses have been to GABA mediated responses However, is known to produce some of and this cause difficulties in the of autonomic which may occur the of the disease. used or in are often for the of severe spasms and do in the muscle rigidity to care and muscle is very often mediated within the nervous system or more at the neuromuscular tetanus has been with of and for and with for muscle In this instance a of was also used to blood which produces muscle by an mechanism in the central nervous system has been used in few is not a prominent effect a GABA transmission of and in the spinal has been reported recently in the management of tetanus. The of injections of was on the basis of of and The first injection was effective in out of 10 patients for effects were but patients developed CNS depression with and of them in of the the difficulties were later by patients were with of of the patients had to be only one has also been used by The the of GABA is In the early of tetanus when only trismus and neck stiffness are present, GABA may produce a of the clinical of the disease. produces muscle without usually the of cardiac muscle or It has a direct action on by the of calcium from the which the of and muscle In most has been used with or as an In one study in of reduced the mortality from in a group to in the group the for neuromuscular and in patients with severe tetanus However, neuromuscular are of treatment in the more cases. The choice of on within the of is has out of in some because of the that its activity aggravate the autonomic dysfunction. In the an of has to be has been used with no effects Control of autonomic dysfunction different therapeutic have been used in the management of sympathetic nervous system depression and peripheral alpha and beta have been at the more peripheral of autonomic dysfunction. and the alpha and beta antagonist have been in the of cardiac bradycardia and cardiac in some patients with tetanus. The beta antagonist has been used on as has blockade with a lumbar of At part of the effect of heavy in autonomic dysfunction is by nervous system depression with and general a of but was by their potential has been found to be particularly to the that the of endogenous are The circulatory effects of and other are but the key feature is probably a depression of sympathetic by actions at in the Whatever the a dose of of useful in blood and rate has been used with It has been found to basal plasma and had been used in the treatment of autonomic a in which there is release of particularly of noradrenaline from nerve as in the autonomic of tetanus. was followed by in plasma noradrenaline though not to within the normal and these were accompanied by a in given has a of actions that may be useful in tetanus. It is a potent and muscle it blocks and adrenal release and has an established place in the management of and has been used to in with phaeochromocytoma There are of its to autonomic dysfunction in tetanus and it has been considered a useful to paralysis and of has used the dose against of spasms and the of the reflex clinical of the of of spasms was at which not without the for was a important Supportive treatment. in in the early the of muscle paralysis and care in the management of tetanus. This reduced the mortality from to and later to This was a not only for the treatment of tetanus, but for the overall of the of care from one restricted to the of one at all systems that were Thus in tetanus, not only are there possible of the disease and its and aspiration of oral and gastrointestinal but there is also the autonomic dysfunction that is a recognized part of the disease as well as the now recognized from fluid from of hormone and infections from There has been as to an or a should be used to of the in patients

Intensive Supportive Care and Cytokines Promote Recovery of Hematopoiesis after Total Body Irradiation (TBI) without Hematopoietic Stem Cell Support.

Defective Anti-Bacterial Carbohydrate Antibody Production after Unrelated HSC Transplantation.

The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months, at 9 months, or at 9 and 18 months of age. At 4.5 months of age, 75% had nonprotective measles virus antibody levels. Following receipt of MV at 4.5 months of age, 77% (316/408) had protective antibody levels at 9 months of age; after a second dose at 9 months of age, 97% (326/337) had protective levels at 24 months of age. In addition, the response at both 9 and 24 months of age was inversely correlated with the antibody level at receipt of the first dose of MV, and the second dose of MV, received at 9 months of age, provided a significant boost in antibody level to children who had low antibody levels. In the group of 318 children who received MV at 9 months of age, with or without a second dose at 18 months of age, 99% (314) had protective levels at 24 months of age. The geometric mean titer at 24 months of age was significantly lower in the group that received MV at 4.5 and 9 months of age than in the group that received MV at 9 months of age (P = .0001). In conclusion, an early 2-dose MV schedule was associated with protective measles virus antibody levels at 24 months of age in nearly all children. Clinical Trials Registration. NCT00168558.

Girls may have lower levels of maternal measles antibodies and higher risk of subclinical measles infection before the age of measles vaccination

Evaluation of hepatitis B vaccination status and immune response among health care workers in a tertiary care hospital in western India

Evaluation of hepatitis B vaccination status and immune response among health care workers in a tertiary care hospital in western India

SAT0600 PNEUMOCOCCAL VACCINATION IN PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES, TREATED WITH BIOLOGICAL THERAPY AND WITH A LOW LEVEL OF ANTIBODIES - A COHORT STUDY OF PATIENTS WITH VARYING VACCINATION STATUS.

Bilateral retinal detachment: a clue to diagnosis of HELLP syndrome

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<div class="WordSection1"><p><strong>Introduction</strong><strong>: </strong>Tetanus is critically ill disease with long term hospitalization period. It need to be carefully monitored, usually in intensive care unit and involves critical care physicians. Benzodiazepine is preferred by World Health Organization (WHO) for muscle spasm control in tetanus, but it will be less costly if magnesium sulphate can be used alone to control spasm and autonomic dysfunction in tetanus. We report a series of 2 tetanus cases that were treated using magnesium sulphate to provide a brief clinical description about the use of magnesium sulphate in tetanus. We also give a brief review on epidemiology, pathophysiology, clinical findings, diagnosis, and treatment of tetanus to provide implications for intensive care physicians. Methods : Case series report</p><p><strong>Results : </strong>Two patients with tetanus was given magnesium sulphate infusion to control muscle spasm and autonomic dysfunction with good results as expected. Both of them were survive and discharged home in healthy condition.</p><p><strong>Conclusions :</strong></p><p>Magnesium sulphate can also be used to control muscle spasm and autonomic dysfunction although WHO recommend benzodiazepines for controlling muscle spasm. Intensive care physicians should have enough knowledge about tetanus and how it should be managed adequately to ensure survival from tetanus.</p></div>

We conducted a serological survey to evaluate the population’s antibody level against three types of polio virus and identify high risk groups. We analyzed stored serum samples from a hepatitis immunity study conducted in 2004 on people born between 1928 and 2004. These samples were categorized into nine age cohorts and selected by random sampling. Antibody titers were tested by micro-neutralization. A protective level was defined as greater than 1:8. Protective antibody level against poliovirus and geometric mean titer (log2 reciprocal) were described by types of polio virus in the vaccine and birth cohorts. A total of 1,712 samples were tested. Protective antibody level against poliovirus type 1 was 90.9% while that of type 2 was 94.7% and type 3 was 83.9%. Means titers were 6.0 for type 1, 6.7 for type 2 and 4.9 for type 3. In the different birth cohorts, the antibody levels were the lowest against poliovirus type 2 (89.9%) in those who were born during 1955-1964. For poliovirus types 1 and 3, percentages in the 1975-1984 birth cohorts were less than 80%. Protective antibody level against the three types of poliovirus among the population in Thailand was assumed to be sufficient to generate herd immunity. People born during 1975-1984 were at risk and should be targeted for immunization if a polio outbreak occurred.

Pathogen-specific IgG antibody levels in immunodeficient patients receiving immunoglobulin replacement do not provide additional benefit to therapeutic management over total serum IgG

The standard schedule of national immunization programs for infants may not be sufficient to protect extremely and very preterm infants. To evaluate the immunogenicity of routine vaccinations administered to preterm infants. A multicenter, prospective, observational cohort study of preterm infants stratified according to gestational age recruited from 8 hospitals across the Netherlands between October 2015 and October 2017, with follow-up until 12 months of age (October 2018). In total, 296 premature infants were enrolled and compared with a control group of 66 healthy term infants from a 2011 study, immunized according to the same schedule with the same vaccines. Three primary doses of the diphtheria-tetanus toxoids-acellular pertussis-inactivated poliomyelitis-Haemophilus influenza type b-hepatitis B combination vaccine were given at 2, 3, and 4 months after birth followed by a booster at 11 months and a 10-valent pneumococcal conjugate vaccine at 2, 4, and 11 months after birth. Primary end points were (1) proportion of preterm infants who achieved IgG antibody against vaccine antigens at concentrations above the internationally defined threshold for protection after the primary series and booster dose and (2) serum IgG geometric mean concentrations after the primary series and booster vaccination. Proportions and geometric mean concentrations were compared in preterm infants and the control group of term infants. Of 296 preterm infants (56.1% male; mean gestational age, 30 weeks), complete samples before vaccination, 1 month after the primary series, and 1 month after the booster were obtained from 220 preterm infants (74.3%). After the primary series, the proportion of preterm infants across all gestational age groups who achieved protective IgG antibody levels against pertussis toxin, diphtheria, tetanus and 6 of 10 pneumococcal serotypes varied between 83.0% and 100%, Haemophilus influenzae type b between 34.7% and 46.2% (40.6% among all preterm infants overall), and pneumococcal serotypes 4, 6B, 18C, and 23F between 45.8% and 75.1%. After the booster dose, protective antibody levels were achieved in more than 95% of all preterm groups, except for Haemophilus influenzae type b (88.1%). In general, geometric mean concentrations of all vaccine-induced antibodies were significantly lower in all preterm infants vs term infants, except for pertussis toxin and pneumococcal serotypes 4 and 19F after the primary series and booster vaccination. Among preterm infants, administration of routine vaccinations during the first year of life was associated with protective antibody levels against most antigens in the majority of infants after the primary series and booster, except for Haemophilus influenzae type b. However, antibody concentrations were generally lower among preterm infants compared with historical controls.

Japanese encephalitis (JE) is a mosquito-borne viral infection of the central nervous system, while tuberculous meningitis (TBM) is another major CNS infection in endemic regions. The co-occurrence of these conditions is extremely rare and presents significant diagnostic and therapeutic challenges. We report a 13-year-old boy who presented with fever, respiratory distress, and neurological symptoms, progressing to respiratory failure that required intubation and intensive care. MRI findings of bilateral thalamic involvement suggested JE, while cerebrospinal fluid analysis confirmed CNS tuberculosis. He was managed with intensive antitubercular therapy, antibiotics, and supportive ICU care. Despite prolonged hospitalization and mechanical ventilation, he developed quadriplegia, reflecting the severity of these dual infections. Concurrent JE and CNS TB complicate both diagnosis and treatment, necessitating early recognition, multidisciplinary management, and intensive supportive care. This first documented case underscores the importance of awareness and further research to guide strategies for managing rare coexisting CNS infections.