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.

Vaccination and otitis media.

Acute otitis media (AOM) caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis may induce specific systemic and/or local immune responses, which may protect from otitis media caused by the same bacteria. However, earlier clinical trials with pneumococcal capsular polysaccharide vaccines have not been successful in preventing AOM. Recently developed pneumococcal polysaccharide-protein conjugates proved immunogenic even in infants, and a heptavalent pneumococcal CRM 197 conjugate vaccine gave a 57% reduction in the number of pneumococcal AOM episodes caused by the vaccine serotypes in infants in Finland. H. influenzae causing AOM is noncapsulated, and like M. catarrhalis, calls for another kind of vaccine development. Suitable vaccine candidates are not yet available but are under development and being tested for immunogenicity and safety. In some trials influenza vaccines have shown protection from AOM during respective viral epidemics. Passive immunoprophylaxis might be an important alternative for immunocompromised children, although this approach has not been successful so far. Mucosal immunization and the advent of DNA and gene technology will open new interesting prospects in the future.

The pure-tone hearing thresholds of otologically healthy 14-year-old children.

The mean pure-tone air conduction (AC) and bone conduction (BC) hearing thresholds (HT) of 534 randomly selected, caucasian, white, urban children with normal otoscopy, otomicroscopy and impedance audiometry, i.e. normal middle ear function, are presented here. Children with pathological middle ear findings or abnormal impedance audiometry were excluded. The average age was 13.8 years, SD 0.5, at the date of examination. The mean air conduction thresholds varied between 0.6 dB at 1 kHz and 9.9 dB at 6 kHz, and the bone conduction thresholds varied between -1.1 dB at 0.5 kHz and 1.1 dB at 4 kHz. The pure-tone average (PTA) (the average of AC hearing thresholds of 0.5, 1 and 2 kHz) of all ears was 1.5 dB. Ninety to ninety-eight per cent of pure-tone AC hearing thresholds at frequencies of 0.5-4 kHz were between -5 dB and 10 dB. The distributions are presented and compared.

Efficacy of a pneumococcal conjugate vaccine against acute otitis media.

BACKGROUND: Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae. METHODS: We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy. RESULTS: Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent. CONCLUSIONS: The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.

Clinical outcome of acute pneumococcal otitis media and serum antibody responses to pneumococcal pneumolysin and polysaccharides in children.

Serum antibody responses to pneumococcal antigens and their relationship to the clinical outcome were determined in a prospective study of 121 children with acute otitis media (AOM). Pneumococcus positive children with a pneumolysin response more often had a recurrence and middle ear effusion (MEE) after 1 month than did the non-responders (p = 0.005 and p = 0.04, respectively). All the children who responded to pneumolysin also had clinically strong symptoms and signs of AOM. Children who responded to pneumococcal polysaccharides developed otitis media with effusion within a 6-month follow-up period more often than did the non-responders (p = 0.005). The results of this study suggest that children with pneumococcal AOM and an antibody response to the intracellular pneumococcal protein pneumolysin behave clinically differently from children with an antibody response to polysaccharides.

Factors associated with the development of recurrent acute otitis media--the significance of choosing the right and accurate dependent and independent variables in the multivariate analysis.

The results of univariate and multivariate statistical analysis were compared in identifying predictive factors of the development of recurrent acuta otitis media (RAOM) after an initial episode of acute otitis media (AOM) in 121 children. Univariate correlations between the development of RAOM and potential risk factors were analysed, and variables at p < 0.10 were incorporated into the stepwise multiple logistic regression analysis. The comparisons between the univariate and multivariate analysis in identifying the predictive factors were made and the importance of changing the dependent variables in the multivariate analysis was analysed. It seems that univariate analysis is over-sensitive, but multivariate analysis is over-conservative in finding possible predictors of RAOM. Choosing the right and accurate dependent and independent variables in the multivariate analysis is extremely important, when this method is used.

Epidemiology and aetiology of middle ear cholesteatoma.

A total of 500 patients with cholesteatoma diagnosed and operated during 1982-91 in the region of Tampere University Hospital and Mikkeli Central Hospital in Finland were analysed retrospectively. The mean annual incidence was 9.2 per 100,000 inhabitants (range 3.7-13.9) and during the study period the annual incidence decreased significantly. The incidence was higher among males under the age of 50 years. There was no accumulation of cholesteatoma diseases in lower social groups. The majority (72.4%) of cholesteatoma patients had suffered from otitis media episodes. Tympanostomy was carried out in 10.2% and adenoidectomy or adenotonsillectomy in 15.9% of all cholesteatoma ears prior to cholesteatoma surgery. Cholesteatoma behind an intact tympanic membrane with no history of otitis media was verified in 0.6% of patients and in cleft palate patients in 8%. In this study, 13.2% of patients had ear trauma or ear operation in anamnes.

Intralesional electrodesiccation of syringomas.

BACKGROUND: Syringomas are common, benign adnexal tumors. In the periorbital area, they pose a cosmetic dilemma for both patients and physicians alike. Many different therapeutic modalities potentially can cause scarring, and recurrences are common. OBJECTIVE: To develop a treatment method that minimizes scarring and subsequent recurrences. METHOD: Each syringoma is treated with short bursts of high frequency low voltage electrodesiccation delivered with a fine needle electrode that is inserted into the center of the syringoma, as deeply as the reticular dermis. RESULTS: Twelve patients treated over a 4-year period showed no permanent adverse effects postoperatively and no recurrences. CONCLUSIONS: Intralesional electrodesiccation is a safe, nonscarring and, reliable method that can be used to eradicate periorbital syringomas.

Prognosis of acute otitis media: factors associated with poor outcome.

Factors associated with poor outcome of acute otitis media (AOM) were analysed in 131 children aged 1/4 to 7 1/2 (median 2 1/2) years. After AOM, altogether 37 (28%) of the children had poor outcome: 15 children (12%) clinical failure (unimprovement or worsening of pre-treatment signs and symptoms within 2 weeks of onset of therapy) and 31 (24%) persistent middle ear effusion (MEE) > or = 1 month post-treatment. Of the different variables studied in multivariate analysis, age < 2 years (p < 0.01), history of allergic skin or respiratory symptoms (p = 0.02), > or = 6 h duration of pre-treatment earache (p = 0.01) and B. catarrhalis in MEE (p = 0.05) were associated with clinical failure. Children with previous adenotomy or unilateral AOM had no failures. Persistence of MEE at 1 month was associated with age < 2 years (p = 0.05), otitis proneness (p = 0.03), bilaterality of AOM (p < 0.01) and S. pneumoniae in MEE (p = 0.01) in univariate but not in multivariate analysis.

Bacteriological findings and persistence of middle ear effusion in otitis media with effusion.

The bacteriology of middle ear effusion (MEE) of asymptomatic otitis media with effusion (OME) was studied in 165 children, aged 5 months to 12 years, from the MEE samples obtained during tympanostomy under general anaesthesia in 1993-1994. MEE had persisted for 1 to 12 (mean 3.5) months. Major otitis pathogens (S. pneumoniae, H. Influenzae, B. catarrhalis and S. pyogenes) were cultured in 41% of the children under 2 years of age and in 17% of older children (p < 0.001). Respiratory infections and attacks of acute otitis media (AOM) during the last 6 months were also more frequent in children younger than 2 years (p < 0.001). The proportion of S. pneumoniae (25%) and H. influenzae (38%), but not of other bacteria, was higher in the children with less than 2 months' persistence of MEE as compared with those with a longer duration (8% and 3%) (p < 0.01). After 2 months, the occurrence of different bacteria remained relatively unchanged until 6 months' persistence of MEE, and thereafter no pathogens were culturable. Among the children adenotomized earlier, the proportion of those with major otitis pathogens in MEE was 8% compared with 32% in non-adenotomized children (p = 0.02). S. pneumoniae, B. catarrhalis or S. pyogenes were not culturable in any of the adenotomized children, while MEE grew them in 25% of the non-adenotomized children (p < 0.001). Since the MEE bacteriology of OME with less than 2 months' persistence resembles that of AOM, it may be that these cases represent a transitory phase between AOM and an established OME.

Extended high frequency hearing and history of acute otitis media in 14-year-old children in Finland.

We studied the extended high frequency hearing of 573 white, urban, mean 13.8-year-old unselected children in Tampere, Finland. All their ear-related morbidity had been recorded since their birth and they had been examined at the ages of 7 months, 2 years, and some of them at 5 years. The extended high frequency audiometry was measured from 10 to 18 kHz, with 1 kHz steps, and the results were related to the number of attacks of acute otitis media (AOM) (0, 1-2, 3-7 and > or = 8) they had experienced. The mean pure tone hearing thresholds varied from 10.7 dB at 10 kHz to 37.0 dB at 18 kHz in the right ears and between 11.6 dB at 10 kHz and 37.4 dB at 18 kHz in the left ears. Among those with > or = 8 attacks of AOM the the thresholds were highest, the difference between them and each of the first 3 groups being statistically significant at 13 and 14 kHz. From 11 to 16 kHz the same difference was significant between the last (> or = 8 AOM) and at least 2 of the first 3 AOM groups. Numerous attacks of AOM may have a harmful effect on high frequency hearing in the long term.

Prognosis of acute otitis media. Factors associated with the development of recurrent acute otitis media.

Clinical factors associated with the development of recurrent acute otitis media (RAOM) (> or = 3 recurrences during 6 months' follow-up period) after acute otitis media (AOM) were analysed in 121 children aged 3 months to 7 years (median 2 years 6 months). After AOM, 19 (16%) children had primary recurrence (pre-treatment signs and symptoms firstly improved or cured, but worsened or recurred within 30 days' post-treatment) and 33 (27%) developed RAOM during 6 months' follow-up period. It seemed that children < 2 years of age (p = 0.04), children with bilateral disease (p = 0.007), strong infection status (p = 0.05), primary clinical failure (p = 0.04) and development of primary recurrence after AOM (p = 0.001) were significantly related to the development of RAOM in univariate analysis, but only children < 2 years of age (OR 1.5, 95% CI 1.0-5.7, p = 0.04) and the development of primary recurrence (OR 5.1, 95% CI 1.8-14.1, p = 0.002) related to the development of RAOM in multivariate analysis. None of the bacteria cultured from middle ear effusion were related to the development of RAOM.

Prognostication of Bell's palsy using transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) provides a method to noninvasive excitation of the facial nerve in its intracranial segment close to the internal acoustic meatus. Thus, the site of facial nerve activation with TMS is proximal to or within the site of the lesion in Bell's palsy. To evaluate the prognostic capability of TMS in unilateral Bell's palsy we examined 137 patients with this method, and compared the results with electroneuronography (ENoG). Within 0-4 days from the onset of palsy, the patients with elicitable TMS responses recovered better than those in whom TMS responses were not elicitable. If TMS was performed 5-9 days or 10-28 days after the onset of palsy, it did not provide any prognostic information. Based on amplitude side-to-side differences, ENoG did not contribute prognostic information during the first 9 days from the onset of palsy. Later on, 10-28 days after the onset of palsy, ENoG showed an increased capability to discriminate the patients with poor prognosis. Thus, elicitable facial motor response with TMS predicts good prognosis of Bell's palsy at an early stage whereas poor response with ENoG predicts less favorable prognosis at a later stage.

Virus-induced interferon production in leukocyte cultures from children with recurrent respiratory infections. A follow-up study.

BACKGROUND: Lowered yields of virus-induced interferon (IFN) by leukocyte cultures were previously suggested to be associated with recurrent respiratory infections in children (Pitkaranta et al. (1993) Clin. Diagn. Virol. 1, 101-108). OBJECTIVES: To investigate if the observed lowered IFN producing capacity was secondary to the underlying disease and, consequently, would be normalized after recovery of the child from the chain of infections. STUDY DESIGN: Forty-eight 3-12-year-old children suffering from recurrent upper respiratory tract infections (acute otitis media included) were followed-up for 2 years. Their clinical condition and virus-induced interferon production in cultures of peripheral blood leukocytes were examined at the beginning and end of this period. RESULTS: In 24 children the health improved strikingly during the follow-up, in 12 children a mild improvement took place, while 12 children remained constantly ill. IFN yields in cultures stimulated with corona- and respiratory syncytial viruses improved along with the clinical situation of the children. Parallel cultures induced with adeno-, influenza A or rhinoviruses did not show a similar correlation. CONCLUSION: These results suggest that the relationship between interferon production by leukocyte cultures and recurrent infections is complex and may be virus-specific.

PCR assay for detecting Streptococcus pneumoniae in the middle ear of children with otitis media with effusion.

We compared a newly developed pneumococcal polymerase chain reaction (PCR) for Streptococcus pneumoniae (Pnc) to bacterial culture in 123 middle ear effusion (MEE) samples of 123 children with otitis media with effusion (OME). For the pneumococcal PCR assay, DNA of MEE samples was purified by a QIAamp blood kit. The outer primers used amplified a 348 basepair region of the pneumolysin gene, and the inner a 208. Pnc was cultured in 14 (11%) and pneumolysin PCR was positive in 57 (46%) of the 123 MEE samples. All the culture positive samples were also PCR-positive. Both the samples with culturable Pnc and with positive pneumolysin PCR increased with shorter duration of OME and a greater number of acute otitis media during the preceding 6 months. In conclusion, pneumolysin PCR suggests pneumococcal involvement in MEE even in OMEs with no evidence of Pnc in culture, and thus offers a good diagnostic tool when a more accurate and sensitive pneumococcal diagnosis is needed.

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.