Antimicrobial Consumption in the Livestock Sector in Bhutan: Volumes, Values, Rates, and Trends for the Period 2017-2021.

Data on the use of antimicrobials in humans and livestock may provide evidence to guide policy changes to mitigate the risk of antimicrobial resistance (AMR). However, there is limited information available about antimicrobial use in livestock in low- and middle-income countries, even though these nations are most vulnerable to the impact of AMR. This study aimed to assess the consumption of veterinary antimicrobials in Bhutan and identify areas for improvement to reduce the use of antimicrobials in livestock. National data on livestock numbers and annual procurement of veterinary antimicrobials over five years (2017-2021) were used to calculate rates of antimicrobial consumption and annual national expenditure on veterinary antimicrobials in Bhutan. The rate of antimicrobial consumption in Bhutan was 3.83 mg per population correction unit, which is lower than most countries in Europe, comparable with the rates of consumption in Iceland and Norway, and approximately 120-fold lower than published rates of antimicrobial consumption in South Asian countries, including Nepal and Pakistan. The low rates of antimicrobial consumption by the animal health sector in Bhutan could be attributable to stronger governance of antimicrobial use in Bhutan, higher levels of compliance with regulation, and better adherence to standard guidelines for antimicrobial treatment of livestock.

Comparison of serum antibodies to pneumolysin with those to pneumococcal capsular polysaccharides in children with acute otitis media.

BACKGROUND: Streptococcus pneumoniae is a major bacterial pathogens in acute otitis media. Pneumolysin is a species-specific protein toxin produced intracellularly by all clinically relevant pneumococcal strains, and antibodies to pneumolysin should therefore represent pneumococcal involvement in the disease, regardless of the serotype. METHODS: Antibodies to pneumococcal pneumolysin and capsular polysaccharides were measured by enzyme immunoassay in acute and convalescent sera of 121 children with acute otitis media. A pneumococcal otitis episode was defined by a positive middle ear fluid culture and/or pneumolysin PCR. RESULTS: Median age of the 10 children who developed a seroconversion response to pneumolysin was 1 year 8 months, and of the 21 children responding to polysaccharides it was 2 years 9 months. Eight of the 10 seroconversion responses to pneumolysin were of IgA class alone, whereas 17 of the 21 polysaccharide responses were of IgG class alone or IgG together with IgM and/or IgA. Of the 41 children with a pneumococcal otitis episode, 13 (39%) showed a seroconversion response, 3 (7%) to pneumolysin and 11 (27%) to capsular polysaccharides. The children with a pneumococcal otitis episode had lower titers of acute phase IgG to the capsular polysaccharide pool of S. pneumoniae (containing types 6B, 14, 19F and 23F), as compared with the titers in children with otitis caused by other pathogens and pneumococci only in the nasopharynx or not found at all (P = 0.04). CONCLUSIONS: Serum antibodies to pneumolysin can be detected at an earlier age than those to the capsular polysaccharides. However, a seroconversion is rare and therefore of no diagnostic value. The presence of serum IgG to the pneumococcal capsular polysaccharides seems beneficial in the prevention of pneumococcal otitis.

New clinical finding in vestibular neuritis: high-frequency audiometry hearing loss in the affected ear.

Twenty-one patients with established vestibular neuronitis were examined otoneurologically and audiologically. High-frequency audiometry up to 20,000 Hz was performed on all the patients. In 17 cases a high-frequency hearing loss was greater in the ear with vestibular neuritis. The mean hearing loss difference varied from 14 dB to 24 depending on the frequency. Our results reveal that in most cases of vestibular neuritis there are no isolated vestibular lesions, but most cases also involve an auditory end-organ lesion. This finding is in unison with the anatomic conditions of the cochlea and the vestibular end-organ.

High-frequency hearing of dental personnel.

234 dentists and dental nurses were examined with a normal and a high-frequency audiometer in high standard clinical conditions. Their ordinary and high-frequency hearing as compared with the controls showed no significant differences. Thus, exposure to high-frequency noise from high-speed drills and other modern dental instrumentation does not appear to be harmful to one's hearing and does not necessitate audiologic screening procedures for dental personnel.

Protein and cellular pattern of glue ear secretions.

Analysis of glue ear secretions showed that the total protein content was slightly higher than in serum and that in the effusion proteins appeared that were specific to the mucosal secretion. The cellular analysis of samples from 137 ears showed that lymphocytes and neutrophils predominated, and that monocytes and phagocytes appeared in most specimens. Eosinophils and mast cells were rare. Staining of bacteria in the smear was seen in one-third of the slides and the mucus strands were numerous. The cellular picture is in line with an infective etiology.

Prevalence of handicapping hearing loss in an aging population.

The mean hearing thresholds of 369 Finnish inhabitants, 65 years, and born in 3 consecutive years on two elected days each year, were studied in high standard measurement conditions. Eighty-nine of these subjects were reexamined 3 years later. They represented a typical partly industrialized white population with a high standard of living. With the criteria for hearing rehabilitation for presbycusis set at a mean hearing threshold of 30 dB or worse at 500 to 1,000 to 2,000 Hz, and/or 50-dB hearing loss at 2,000 Hz, the prevalence of rehabilitation need was 3.2%. Conductive hearing losses were found in 6% of the subjects.

Serum levels and urinary excretion of mequitazine after a single oral dose.

Pharmacokinetics of mequitazine, a recently introduced peripheral H1-histamine receptor antagonist of phenothiazine type, was followed up to 72 h after the single oral dose of 5 mg of the drug to eight fasted healthy volunteers. Each subject was treated thrice with a dosing interval of 15 days or more. Thus all the results were triplicated. Serum mequitazine was measured by mass fragmentography using a gas-liquid chromatograph/mass spectrometer set in the electron impact mode. Urine phenothiazines were determined fluorometrically before and after cleaving phenothiazines from their glucuronide conjugates. Peak concentration of mequitazine in serum was 3.19 +/- 1.70 (s.d.) ng.ml-1, time to peak concentration 5.67 +/- 1.68 h, elimination half-life 45 +/- 26 h, and elimination rate constant 0.018 +/- 0.007 h-1. Only 10.9 +/- 3.3% of the dose appeared in urine in unconjugated plus the glucuronidated form during the first 72 h. About 46% of the urinary phenothiazines were glucuronide conjugates. The results suggested that after the oral administration only low mequitazine concentrations appeared in serum, most of the drug seemed to be deactivated by the extrarenal route, and the kinetic properties of the drug resembled those of several phenothiazines used for psychiatric therapy.

A method to break the cognitive barrier between a deaf child and a hearing parent.

A deaf child actively uses about 1000 concepts in common with the hearing world. The rest of his up to 10,000 concepts belong to sign language and cannot be accurately translated into written language. This makes it difficult for the deaf to understand a normal written text, especially its abstractions. We have developed a new communication system in order to break the barrier between the hearing and the deaf. In this system a deaf child speaks with a writing hand-piece terminal through an FM route to a small unlimited text-to-speech synthesizer carried by the parent. The parent answers similarly to a 48-grapheme alphanumerical display carried by the child on a rack in front of him. The parent's unit with a speech synthesizer weighs about 2 kg and its size is about 7 X 20 X 25 cm; the size of the child's unit is one half of that and it weighs, with the display, 2 kg. Even a 4-year-old child carries the apparatus easily; nevertheless a still lighter unit is under construction. The system takes the learning process to everyday situations and makes it possible for a deaf child to converse in the normal written and spoken language. Thus, his concept capacity in the spoken language can be increased.

Interferon production by leukocytes in children with otitis media with effusion.

We have previously shown that leukocyte cultures of children suffering from recurrent respiratory tract infections produce less interferon (IFN) than those of healthy children. In the present study this tentative marker of recurrent infections was used to study the pathogenetic background of otitis media with effusion (OME). Altogether 57 consecutive children, aged 2-11 years, who came for tympanostomy and/or adenoidectomy were divided into three subgroups: 25 of them had OME and a history of recurrent acute otitis media (rAOM/OME+), 20 had OME without an infectious background (inf-/OME+), and 12 had a history of recurrent upper respiratory infections (inf +/OME-) without OME. All the children were free of acute illness at the time of sampling. Differences between the groups were seen in IFN yields when leukocyte cultures were stimulated with adeno-, rhino-, corona-, respiratory syncytial or influenza A viruses. Leukocytes from inf-/OME+ children produced more IFN than those of the other two groups. Though no sex differences in the IFN responses were seen among rAOM/OME+ and inf +/OME- children, leukocytes from inf-/OME+ girls produced significantly higher amounts of IFN than those of inf-/OME+ boys, or rAOM/OME+ and inf +/OME- children. These differences between clinically different groups of children support the view that the etiology of OME can be heterogeneous.

Immunological aspects of otitis media: present views on possibilities of immunoprophylaxis of acute otitis media in infants and children.

The article reviews, based on current knowledge of immunological events affecting the middle ear, the possibilities and prospects for the prevention of otitis media (OM) by immunologic measures. While pneumococcal capsular polysaccharide vaccines proved not to be effective against infant acute otitis media (AOM), pneumococcal conjugate vaccines provide good immunogenicity even in infants, and call for trials with better prospects of clinical efficacy. The other future approaches currently under development are vaccines against nontypable Haemophilus influenzae and Branhamella catarrhalis, anti-viral immunoprophylaxis, combinations of the above alternatives, or passive immunization. Also, the use of new routes or ways of immunization are under study. Furthermore, the ways to modify the present treatment practices of AOM to favour good immunologic responses in infants and children must be studied.

Pneumococcal bacteriology after pneumococcal otitis media with special reference to pneumococcal antigens.

Fifty-four ears with evidence of pneumococcus (Pn) in the first acute otitis media (AOM) in 38 infants and with prolongation or recurrence of the MEF during the follow-up were observed for 7-22 months for the presence of Pn by culture or of pneumococcal antigen (Pn-ag) by counterimmunoelectrophoresis or latex agglutination methods in their MEFs. During the first three 1-month observation periods, Pn and/or Pn-ags were detected in 24% to 9% of these ears, always of the initial type/group. Later on new Pn types/groups appeared also. In two of the 9 MEFs persisting for greater than or equal to 3 months, initial Pn-ag, with culturable Pn, was repeatedly found but not for longer than 5 months. Of the 12 ears resulting in secretory otitis media (SOM) only one showed initial Pn-ag (and Pn) in the MEF of SOM. Pneumococcal type/group pattern associated with prolongation or recurrence of infection did not differ from that of initial AOM. In another series of 151 SOM ears in 97 children, Pn-ags were detected in 7 MEFs. Four of them grew Pn, each of the corresponding group. Our studies suggest that the persistence of Pn-ags in the middle ear after AOM is limited and their occurrence in the MEFs of SOM is rare. Thus, the role of the persistence of Pn-ags in prolonged, recurrent or secretory otitis media seems questionable.

Middle ear fluid bacteriology of acute otitis media in neonates and very young infants.

The middle ear fluid (MEF) bacteriology of 107 attacks of acute otitis media (AOM) in 101 infants less than 3 months old was analyzed. A total of 108 bacteria were isolated from 85 attacks. Major AOM-pathogens, S. pneumoniae (19%), H. influenzae (9%) or B. catarrhalis (7%) were cultured in approximately one-third of all the attacks. S. aureus (17%) and coagulase-negative staphylococci (22%) without the above pathogens were commonly found, whereas gram-negative enteric bacteria were culturable from only 5 attacks. Only 8% of the MEFs were polymicrobial. More than half of all the bacterial strains produced beta-lactamase. The bacteriology of those younger than one month was not different from that of the others. The same was true with attacks of out-patients and in-patients, except for a larger proportion of beta-lactamase producing strains in in-patients. Nasal-nasopharyngeal and MEF samples showed the same bacteriology in only 20% of cases. Two-thirds of AOM attacks were present in infants with perinatal or other concomitant morbidity, but their bacteriology was not different from those without other morbidity. In addition to the examination of ears in infants presenting with any illness before the age of 3 months, the study stresses the importance of bacteriological analysis of MEF in all cases of AOM at this age.

Otoscopic diagnosis of middle ear effusion in acute and non-acute otitis media. I. The value of different otoscopic findings.

To determine the value of different pneumotoscopic findings in diagnosing the middle ear effusion (MEE) of acute (AOM) and non-acute otitis media, 11,804 ear-related visits of 2,911 unselected children at ages 0.5-2.5 years were analysed. About half of these were examined by an otolaryngologist in one, and half by a pediatrician in another, urban area. Myringotomy was always performed when MEE was suspected, and it confirmed the presence of MEE in 85% (otolaryngologist) and 82% (pediatrician) of altogether 5,462 acute and in 69% (both doctors) of 1,092 non-acute cases suspected. Redness of the tympanic membrane (TM) was found in only 18% and 27% of the visits with AOM, and it predicted MEE with only 60% and 51% probability, if seen in acute visits. Cloudiness of the TM was noticed in 81% and 67% of the visits with AOM; its specificity and the other calculated variables were good in regard to the diagnosing of MEE, especially in acute cases in both groups. Distinctly impaired mobility of the TM was of about the same diagnostic value, but its position reliably indicated MEE only when bulging. In AOM the colour or mobility of the TM was normal very rarely, but the position was normal in a third of the cases. Thus, although there were differences in the incidences of different otoscopic findings in the two study groups, the diagnostic value of certain pneumatic otoscopic findings, especially cloudiness and distinct hypomobility of the TM, seemed to be good in both groups.

Inflammatory cells in mucoid effusion of secretory otitis media.

Inflammatory cells were studied in 269 mucoid middle ear effusions of 202 patients with secretory otitis media (SOM). Although the effusions contained inflammatory cells in all cases, the number of cells, the proportion of viable cells and the proportions of different cell types showed marked heterogeneity. However, the effusions formed a sliding scale with regard to the above cellular parameters. We suggest that these differences in the cellular picture might reflect differences in immune mechanisms and responses in the different effusions, possibly representing different phases of the course of an established SOM. In the subgroups of patients with cleft palate (22) or atopy (16) the cellular picture resembled that seen in the other patients (164), with the exception that the effusions of the cleft palate patients were somewhat more lymphocytic. Thus, from the immunological point of view, the effusions in established SOM seem to behave similarly, irrespective of the differences in the etiological background of SOM.

Vertical hyoid bone displacement and fundamental frequency of phonation.

Vertical displacement of the hyoid bone as well as its effects on F0 were studied using five excised human larynges. Cranial force introduced to the hyoid bone caused a widening of the vestibule of the larynx, enlargement of the laryngeal ventricles, abduction of the ventricular folds, heightening of the epiglottis and slight abduction of the vocal folds. The displacement (X +/- SD) of the anterior part (corpus) of the bone was 8.0 +/- 5.2 mm and of the posterior part, 22.2 +/- 6.1 mm with a 10 N force. The difference was statistically significant and was found to depend mainly on the tight middle hyothyroid ligament. The cranial force displacing the hyoid bone invariably showed a positive relationship with F0. The F0 changes were statistically significant but relatively small (X +/- SD): 8 +/- 8.4 Hz (about 10%) with an intact hyothyroid ligament. When the subglottal pressure was low, a change in the vibratory pattern of the vocal folds was found in several specimens. The F0 changes found in the present study are too small to explain alone the differences in the so-called intrinsic F0 of vowels. However, they are believed to contribute to this phenomenon.

Occurrence and recurrence of acute otitis media among children.

The occurrence and recurrence of acute otitis media among 37 570 Finnish children at risk who were under 15 years of age were studied. During a one-year period, 4 337 of the children experienced a total of 6 249 attacks of acute otitis media, giving an annual incidence rate of 16.6%. The highest incidence, 75.5%, was found among infants 6--11 months old. 50% of Finnish children had experienced at least one ear infection before their third birthday and 75% before the age of 10, and among this latter group the total number of otitis attacks per child-year during a lifetime was 0.71. Among children under 10, half of the index attacks were recurrences, and among children under 16, 28% of the index attacks were followed by recurrences during the study year. The highest relative recurrence rate was found during the second year of life. Before the second birthday both incidence and recurrence rates were significantly (p less than 0.001) higher among boys. Acute otitis media was most common in the higher social class families and the lowest incidence and recurrence rates were found among children of farmers.

Incidence of acute otitis media up to the age of 1 1/2 years in urban infants.

The object of this prospective cohort investigation of 1,642 infants was to study the incidence of acute otitis media (AOM) in urban children during the first 18 months of life. The monthly incidence of AOM was greatest at the age of 10 months, and the largest proportion of children with AOM was also found in this 10-month age group. Before the age of 18 months, 56.7% of the infants had had at least one episode of AOM, while 26.9% had had one or two episodes and 29.8% three or more. The corresponding figures before the age of 12 months were: 45.3%; 26.8%; 18.5%, and before the age of 9 months: 30.5%; 22.1%; 8.4%. The AOM incidence, particularly as regards recurrent AOM, was rather higher in boys than in girls.

Immunological defects in children with chronic otitis media.

A total of 59 children with chronic otitis media were examined for possible immunological defects by determination of serum gammaglobulin and immunoglobulins IgG, IgA and IgM, and by a tuberculin test, and additionally by noting any lymphopenia. Some divergence from normal values was found in 38 patients (64%). 14 children (24%) showed pathologically low immunoglobulin levels and 7 (12%) even a subtotal absence of one of the immunoglobulin fractions. 8 of the cases (14%) also showed a reduction of gammaglobulin level. In 20 children (34%), the level of one or more of the three major Ig classes was elevated. All except one became clinically normal within a few years, showing normal gamma or immunoglobulin levels when tested. The tuberculin test was positive in all patients. The length and course of the disease in these cases was similar to that in patients with normal test values. Gammaglobulin therapy did not have any beneficail effect. Consequently, it is concluded that although humoral immunological defects may be one aetiological factor, they do not play any major role in the course of chronic otitis media in children.

Sensorineural hearing loss and acute otitis media in children.

Sensorineural hearing of 359 otoscopically and tympanometrically normal 5-year-old children with known otitis-history was studied under ideal conditions. In the subgroups of children with a different number (0, 1-2, 3-7, greater than or equal to 8) of attacks of acute otitis media (AOM) in their history, the mean bone conduction thresholds unregularly varied from 0.1 dB to 7.4 dB, depending on the frequency and the subgroup studied. The proportion of the ears with a bone conduction threshold greater than 10 dB at 0.5, 1, 2 or kHz ranged, also unregularly, from 10.8% to 0.5%, the greatest percentages being found at 0.5 and 1 kHz in the children without a history of AOM. Thus, neither AOM nor its treatment, even if frequently occurring, seem to cause permanent sensorineural hearing loss in children.

Risk factors affecting the occurrence of acute otitis media among 2-3-year-old urban children.

The factors affecting the occurrence and recurrence of acute otitis media (AOM) were studied among 471 2-3-year-old children in two cities in Finland. Of these children, 188 had experienced greater than or equal to 3 attacks of AOM, 76 had had 1-2 attacks and 207 no otitis attacks (= control group). The study showed that the risk of recurrent AOM was increased among those children attending day-care nurseries as well as among those who had several siblings. Proneness to rhinorrhea and exposure to passive smoking at home was associated with an increased risk of AOM, while prolonged breast-feeding (greater than 6 months) seemed to reduce it. No correlation was found between the risk of recurrent AOM and the place of residence or type of housing, the parental otitis history, or atopic diathesis of a child. Thus the study suggested that to protect a young child from AOM we should promote breast-feeding and home-care for babies as well as avoid smoking in the home.