Lymph node and peripheral blood lymphocytes in a case of Hodgkin's disease (mixed cellularity) were studied using May-Grünwald-Giemsa (MGG), acid naphthyl acetate esterase (ANAE), immunoperoxidase staining and lymphocyte surface markers, autoradiographic, and lymphocyte stimulation techniques. According to MGG staining and autoradiographic studies of lymph, node cells, small lymphocytes, intermediate lymphoid cells, and large mononuclear cells resembling in-vitro stimulated immunoblasts, Hodgkin's cells and Reed-Sternberg (RS) cells formed a morphologically continuous DNA synthetizing series. A large majority of small lymphocytes from a lymph node were ANAE positive, thus being T-lymphocytes, and formed rosetts around large mononuclear cells and RS cells. Most RS and large mononuclear cells had ANAE positive spots in the cytoplasm, thus resembling T-lymphocytes more than diffusely staining monocytes. These cells did not contain cytoplasmic immunoglobulin and were muramidase negative. Both lymph node and peripheral blood lymphocytes responded strongly to PHA. The role of T-lymphocytes in Hodgkin's disease and the origin of RS cells are are discussed on the basis of the findings.

This study investigated the causes of invasive bacterial infections in children aged <15 years in St Petersburg, Russia, during 2001-2003, using culture and antigen detection methods (rapid antigen latex agglutination (RAL)) for normally sterile body fluids. A pathogen was detected in 90 cases (culture 50, RAL 40). Neisseria meningitidis was the most common pathogen (66%), followed by Haemophilus influenzae (19%) and Streptococcus pneumoniae (16%). Meningitis was the main clinical diagnosis (68/90, 76%), with N. meningitidis serogroup B, H. influenzae type b (Hib), and S. pneumoniae serogroup 1 being the most common isolates. Hib was less prevalent in St Petersburg than it was in industrialised countries before the introduction of Hib vaccinations.

Objective To determine predictors of death among children 2 - 59 months old admitted to hospital with severe pneumonia. methods Prospective observational study from April 1994 to May 2000 to investigate serious infections in children less than 5 years old admitted to a tertiary care government hospital in a rural province in central Philippines. The quality of clinical and laboratory work was monitored. The WHO classification for severe pneumonia was used for patient enrolment.Results There were 1249 children with severe pneumonia and no CNS infection. Thirty children died. Using univariate analysis, the following factors were significantly associated with death: age 2 - 5 months, dense infiltrates on chest radiography and presence of definite bacterial pathogens in the blood. Stepwise logistic regression analysis revealed the following independent predictors of death: age 2 - 5 months, weight for age z- score less than) 2 SD, dense infiltrates on chest radiography and definite pathogens isolated in the blood. When the results of chest radiographs and blood cultures were not included to mimic facilities available at first- level facilities, age 2 - 5 months and weight for age z- score less than) 2 SD remained independent predictors of death.Conclusion When resources are limited, children with lower chest wall indrawing ( severe pneumonia) who are 2 - 5 months old or moderately to severely malnourished should be referred for immediate higher- level care.

BACKGROUND:Respiratory viral infections are usually preceding or coinciding with acute otitis media (AOM) in children. It is not known if a given viral infection would facilitate invasion of bacterial pathogens into the middle ear in a species-specific way. We reanalysed the microbiological results of the two prospective Finnish Otitis Media (FinOM) studies for this purpose.METHODS:The children had been followed from 2 months to 2 years of age in specific study clinics and all referred AOM events were analysed. Combined results of virus detection tests from middle ear fluid and nasopharyngeal aspirate and those of bacterial culture from middle ear fluid were cross-tabulated for 529 AOM events in the FinOM Cohort Study and for 364 events in the FinOM Vaccine Trial.RESULTS:In both studies the main bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis while the main viruses detected were rhinoviruses and respiratory syncytial virus (plus enteroviruses in the Vaccine Trial). No distinct species-specific associations were observed between the viral and bacterial findings.CONCLUSION:We did not find support to the theory that respiratory infection caused by a given viral species would favour growth of a certain bacterial pathogen in the MEF more than another.

ABSTRACT We investigated the genetic relationships between serotypeable pneumococci and nonserotypeable presumptive pneumococci using multilocus sequence typing (MLST) and partial sequencing of the pneumolysin gene (ply). Among 121 nonserotypeable presumptive pneumococci from Finland, we identified isolates of three classes: those with sequence types (STs) identical to those of serotypeable pneumococci, suggesting authentic pneumococci in which capsular expression had been downregulated or lost; isolates that clustered among serotypeable pneumococci on a tree based on the concatenated sequences of the MLST loci but which had STs that differed from those of serotypeable pneumococci in the MLST database; and a more diverse collection of isolates that did not cluster with serotypeable pneumococci. The latter isolates typically had sequences at all seven MLST loci that were 5 to 10% divergent from those of authentic pneumococci and also had distinct and divergent ply alleles. These isolates are proposed to be distinct from pneumococci but cannot be resolved from them by optochin susceptibility, bile solubility, or the presence of the ply gene. Complete resolution of pneumococci from the related but distinct population is problematic, as recombination between them was evident, and a few isolates of each population possessed alleles at one or occasionally more MLST loci from the other population. However, a tree based on the concatenated sequences of the MLST loci in most cases unambiguously distinguished whether a nonserotypeable isolate was or was not a pneumococcus, and the sequence of the ply gene fragment was found to be useful to resolve difficult cases.

ABSTRACT The relative abilities of pneumococcal serotypes and strains (clones) to cause acute otitis media (AOM) were investigated by comparing the serotypes and genotypes of pneumococci recovered from cases of AOM (n = 149) in children <2 years of age with those from nasopharyngeal carriage (n = 288) in age-matched controls from the same region. The odds ratio (OR) for association of pooled vaccine serotypes with AOM was found to be slightly elevated over unity, although this was not significantly different from that of pooled nonvaccine or vaccine-related serotypes. Comparing individual serotypes, 19F and 23F had 2- to 2.5-fold higher ORs, although these were not markedly different from the ORs of nonvaccine serotypes. None of the major clones had an OR that was significantly greater than the average, and the differences in ORs among serotypes and clones were much less than those for invasive disease, suggesting little variation in their ability to cause AOM. We conclude that serotype replacement may reduce the long-term efficacy of these vaccines against AOM.

In acute otitis media (AOM), a means of prediction of the bacterial pathogen based on symptoms and signs would be valuable in selecting appropriate antimicrobial treatment. Children in the control arm (n=831) in the Finnish Otitis Media Vaccine Trial were prospectively observed in a study clinic setting from the age of 2 to 24 months. In patients with AOM, myringotomy with aspiration was performed, and middle ear fluid samples were cultured for bacterial pathogens. Symptoms and signs of respiratory infections were thoroughly recorded. Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were the most common bacterial pathogens. Pneumococcal AOM was associated with more-severe AOM characterized by fever and earache. AOM due to H. influenzae was associated with eye symptoms and findings. Accurate prediction of a bacterial cause of infection based on symptoms and signs of AOM was not possible, but a specific cause was predicted in some situations, with a high probability of applicability to clinical practice.

OBJECTIVESTo test the effect of adenoidectomy in connection with tympanostomy compared with tympanostomy only in preventing otitis media in children younger than 2 years.DESIGNProspective trial with randomized and nonrandomized arms.SETTINGPrimary care study clinics.PARTICIPANTS AND INTERVENTIONSThe study participants were selected from 2497 children who had been enrolled in the Finnish Otitis Media Vaccine Trial at the age of 2 months. A total of 306 children, aged 1 to 2 years, who had experienced recurrent episodes of otitis media were randomized into 2 treatment groups: tympanostomy with or without adenoidectomy. Of the 306 children, 137 were operated on according to random basis (randomized trial). The 169 children whose parents declined participation in the randomized trial were operated on according to the parents' preferences (nonrandomized trial). All children were followed up until 2 years of age. The mean follow-up time was 7 months.MAIN OUTCOME MEASUREThe rate of acute otitis media episodes.RESULTSThe average reduction in the rate of all acute otitis media episodes in the adenoidectomy group was 19% (95% confidence interval [CI], -14% to 43%) among children enrolled in the randomized trial and 25% (95% CI, -13% to 50%) in the nonrandomized trial. The reduction in the randomized trial was mainly due to reduction in the rate of pneumococcal otitis media (58%, 95% CI, 16%-79%).CONCLUSIONIn children younger than 2 years, concurrent adenoidectomy during the insertion of tympanostomy tubes does not seem to have a major advantage over the insertion of tympanostomy tubes alone in preventing otitis media.

To find reliable methods able to identify the “difficult” Streptococcus pneumoniae isolates, an in-house polymerase chain reaction (PCR) for pneumolysin gene (Ply-PCR) and a commercial RNA hybridisation test (AccuProbe™) were evaluated. Selected isolates of suspected pneumococci, sent for confirmation of identification and for serotyping, were classified into four groups based on their optochin sensitivity and capsule reaction. All isolates in Group 1, which consisted of 24 typical, optochin-sensitive, encapsulated pneumococcal strains, were positive in the Ply-PCR and AccuProbe™ tests. In Group 2, which consisted of 25 optochin-sensitive, but unencapsulated pneumococcal strains, all the isolates were positive in the Ply-PCR test, and 23 were positive in the AccuProbe™ test. In Group 3, which consisted of 15 atypical, optochin-resistant but encapsulated pneumococci, 12 of the isolates were positive in the Ply-PCR and 12 in the AccuProbe™ test, and 11 of these 12 strains were positive in both tests. In Group 4, which consisted of 36 equivocal optochin-resistant, unencapsulated isolates, 15 strains were positive in the Ply-PCR test and 8 strains in the AccuProbe™ test. As a conclusion, the Ply-PCR and AccuProbe™ tests identified similarly typical optochin-sensitive pneumococci, but gave partly controversial results about atypical pneumococci. Thus, they did not reliably help in the identification of suspected pneumococcal isolates lacking the conventional characteristics of pneumococcus.

BACKGROUND:Timely information on the bacteriology of primary, noncomplicated acute otitis media (AOM) may today be needed more than ever, because of the increasing antimicrobial resistance of its major bacterial causes and because of the potential of new pneumococcal and other bacterial vaccines for prevention of AOM.METHODS:The study followed 329 children from 2 to 24 months of age at scheduled healthy visits and sick visits at the study clinic. Whenever AOM was diagnosed during the follow-up, myringotomy was performed and middle ear fluid was aspirated for bacterial culture.RESULTS:At least one middle ear fluid sample was available from 772 AOM events; Streptococcus pneumoniae (Pnc) was isolated in 201 (26%), Moraxella catarrhalis (Mc) in 177 (23%) and Haemophilus influenzae (Hi) in 174 events (23%). The incidence of Pnc AOM peaked at 12 months of age, whereas the incidence of Mc AOM showed the first peak at 6 months and Hi AOM at 20 months. Pnc AOM showed less prominent seasonality in occurrence than Mc and Hi AOM. Hi was a rare cause of the first 2 AOM episodes (13%) but became increasingly common from the third episode on (32% on average).CONCLUSIONS:Pnc, Mc and Hi were almost equally common findings in AOM. Pnc seems to be the most pathogenic of these three, the role of Mc is increasing and Hi is clearly associated with recurrent AOM.

BACKGROUNDEar 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.METHODSWe 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.RESULTSOf 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.CONCLUSIONSThe 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.

Epidemiological features of blood culture confirmed typhoid fever and antibiotic sensitivity of isolated Salmonella typhi strains were investigated in Bohol Province in Central Philippines from where no earlier information of these was avialable. Typhoid fever is endemic elsewhere in the Philippines (eg Metropolitan Manila and surroundings) where also multidrug resistant S. typhi strains have been detected. A laboratory for surveillance of invasive bacterial infections was established in a tertiary care government hospital, in Bohol, Central Philippines, in 1994. Patients with suspected typhoid fever or other serious infection were managed and blood cultures from them were taken according to clinicians' judgment. Blood cultures were processed and the isolated bacteria identified using generally accepted methods. S. typhi and other Salmonella isolates were identified using commercial antisera. Patient data were collected from hospital records. Of a total of 4,699 blood cultures done during a period of 3 3/4 years, 1,530 (32%) were requested for suspected typhoid fever. S. typhi was the most common pathogen isolated from 422 patients (8.9%), followed by S. paratyphi A from 55 patients (1%). Most patients were young adults (43%) and school age children (28%). Male:female ratio was 1.5:1. Among the 422 patients, there were 9 (2%) deaths due to typhoid fever, all with complications. All S. typhi isolates were sensitive to chloramphenicol, cotrimoxazole, and ampicillin. Our observation on blood culture confirmed typhoid fever demonstrates its importance as a major infectious disease in Bohol and gives a sound basis for treatment of typhoid patients and for further clinical and epidemiologic studies of typhoid fever and for following antibiotic sensitivity of S. typhi in Bohol and elsewhere in the Philippines.

Objective: The interpretation of negative pressure tympanograms as indicators of the presence of middle ear fluid has been ambiguous. Our purpose was to assess the occurrence and implications of negative pressure tympanograms and to study their association with bacterial pathogens in otitis media. Methods: Altogether 329 infants were enrolled at a well-baby clinic for the Finnish Otitis Media Cohort Study, a longitudinal prospective cohort study. The children were closely followed in a special study clinic from 2 to 24 months of age for respiratory diseases, especially acute otitis media. Children were examined at the study clinic with tympanometry and pneumatic otoscopy whenever visiting the study clinic for respiratory disease. Myringotomy with aspiration was performed if middle ear fluid was suspected in otoscopy. Occurrence of middle ear fluid in ears with negative pressure tympanograms (less than - 100 daPa) was assessed. Nested case control design matched by visit type (acute or follow-up visit) and month of visit was used for analysis of association of bacterial pathogens and tympanometric results. Results: Middle ear fluid was encountered in 15% of cars with negative tympanometric peak pressure, a lower proportion than described previously. In otitis media with a negative tympanometric peak pressure, 71% of bacterial cultures remained negative for the main pathogens, compared to 36% in matched controls (P < 0.001). Especially Streptococcus pneumoniae but also Haemophilus influenzae were rarely found in samples from negative pressure ears. Moraxella catarrhalis was equally often found. Conclusions: Negative pressure tympanogram is a poor indicator for the presence of middle ear fluid. Furthermore, if otitis media is diagnosed with negative tympanometric peak pressure negative middle ear bacterial culture for the main pathogens is highly probable. Expectant follow-up might be more appropriate than routine antibiotic treatment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Invasive Haemophilus influenzae type b (Hib) infections remain a major problem in developing countries, where the epidemiology of the disease differs from that seen in industrialized countries. 1, 2 In developing countries the disease occurs in younger children, with most cases occurring before 12 months of age and almost one-half before 6 months of age. 1, 2 Invasive Hib infections cause substantial mortality, morbidity and health care cost even when effective antimicrobial therapy is available. Hib capsular polysaccharide protein conjugate vaccines have been effective in almost eliminating life-threatening Hib infections in industrialized countries of Europe and in the US. 3 Their effectiveness has also been demonstrated in The Gambia, Africa, 4 and in the South American countries Chile and Uruguay. 5 However, Hib vaccines are not widely used or included in the national vaccination programs in most developing countries. H. influenzae, mostly Hib, is the leading cause of bacterial meningitis in children in Asia, 2 but the limited data on the population-based incidence of invasive Hib disease in this region 2 makes the assessment of the disease burden and the need for prevention difficult. Here we present such incidence data based on 33 months of surveillance on the rural island of Bohol, Central Philippines. Materials and methods. We analyzed clinical, laboratory and demographic data from 1362 children <5 years old enrolled prospectively from April, 1994, to December, 1996, to a hospital-based surveillance study on the etiology of invasive bacterial infections at the Governor Celestino Gallares Memorial Hospital (Gallares Hospital), 6 Tagbilaran City, a government referral hospital with mostly walk-in patients. Patients were enrolled by specially trained hospital physicians who were supervised and monitored by full time study personnel. The signs and symptoms were recorded in pretested data collection forms. Children 2 to 59 months old were enrolled into the study, as described earlier, 6 if they had severe or very severe pneumonia according to the World Health Organization criteria, suspected meningitis or clinical signs of sepsis without symptoms or signs of pneumonia. Children <2 months old were enrolled if they had clinically defined severe pneumonia, suspected meningitis or suspected sepsis. For calculation of the incidence of invasive Hib infection, a continuous geographic area consisting of 10 municipalities was chosen in the immediate proximity of Gallares Hospital, accounting for a majority (63%) of the patients enrolled. Information on the annual birth rate in the 10 municipalities, collected by local midwives and reported by the Bohol Provincial and Tagbilaran City Health Offices, was collected. To estimate which proportion of all severe hospital-admitted infections from this catchment area were treated in Gallares Hospital in 1997, the discharge diagnoses of children <2 years of age from the 10 municipalities, as registered by the attending physicians, were collected by study nurses from all 7 private hospitals in Tagbilaran City and surroundings. A total of 648 children had diagnoses associated with respiratory tract infection, suspected sepsis or suspected meningitis, and 255 (39%) of them were treated in Gallares Hospital. In Gallares Hospital blood (n = 1362) and cerebrospinal fluid (CSF;n = 373) specimens from the enrolled patients were cultured for bacteria by specially trained personnel and processed in a research laboratory with systematic quality assurance. 6H. influenzae was isolated, identified and serotyped (for types a through f) by both serologic and PCR methods, and CSF specimens were tested for Hib antigen by the latex agglutination method as described earlier. 6 In the private hospitals no blood or CSF culture diagnostics were done. Results. Thirteen (72%) of a total of 18 invasive (growth from blood or CSF) H. influenzae infections from the whole catchment area of Gallares Hospital were caused by Hib. All 13 Hib infections were seen in children <1 year old, and 62% (8 of 13) were seen in children <6 months old (Table 1). All nontypable isolates lacked the genes for capsular expression and b polysaccharide.Table 1: Age distribution of invasive Haemophilus influenzae infections in Gallares Hospital, Bohol, the Philippines, April, 1994, to December, 1996Of the 13 patients with Hib infection, 8 (62%) had bacteriologically confirmed meningitis; i.e. the agent was isolated from CSF. The Hib antigen detection test was performed on 316 CSF samples, but no culture-negative, antigen-positive samples were observed. Four of the 5 children, in whom Hib was detected from blood but not from CSF, had meningitis as the clinical diagnosis based on the entry criteria. Consequently the clinical syndrome was meningitis in 12 (92%) of the 13 patients with invasive Hib disease. All 5 patients with non-b H. influenzae infection also had bacteriologically confirmed meningitis. Thus meningitis was the clinical syndrome in 17 (94%) of the total 18 patients with serious Hib or non-b H. influenzae infection. Two patients with meningitis and 1 patient with clinically defined pneumonia without meningitis had a dense lung infiltrate on chest radiography. One (7.7%) of the 13 patients with Hib disease and none of the 5 patients with non-b H. influenzae infection died. Of the 13 invasive Hib cases 8 came from the 10 municipalities in which the birth cohort in 1995 was 4098. The observed annual incidence of Hib disease in children <1 year old was 71 (95% confidence interval, 21, 120) per 100 000 live births per year. In children <5 years old, the incidence would be one-fifth of the above figure14 given that all cases occurred in children <1 year old. Assuming that somewhat less strict admission criteria were used in the private hospitals than in the Gallares Hospital where extensive training was implemented, we estimated that ∼50%, instead of the observed proportion of 39%, of the children with serious bacterial infections from the defined catchment area were treated in Gallares Hospital. With this assumption the incidence of all invasive Hib infections in children <1 year old could be as high as 142 (95% confidence interval, 72, 211) per 100 000 live births per year. In children <5 years old the figure would be 28. Discussion. We observed an incidence 71 per 100 000 in children <1 year old for invasive Hib infections based on reliable annual birth rate data in a well-defined population and prospective, carefully planned and implemented surveillance of invasive infections in children <5 years of age. To arrive at a more likely estimate of the true incidence, we also investigated the proportion of patients from the defined population with serious infections admitted to the study hospital of all those admitted to any hospital, which led to an estimated incidence twice as high as the observed incidence. Furthermore the common practice of preadmission antibiotics, 6, 7 lowering the sensitivity of bacteriologic diagnostics, would suggest that the true incidence is even higher than this. The estimated incidence figures of invasive Hib infections in Bohol (142/100 000/year in children <1 year old and 28 in those <5 years old) indicate that during the first 2 years of life these rates are roughly the same rate as they were in Scandinavian countries before Hib vaccinations. 8 These figures are much lower than those from some African countries and from the indigenous populations of North America and Australia. 9 The estimated incidence for invasive Hib disease in those <5 years old is approximately one-third of the incidence of 95/100 000/year reported recently from urban Manila, the Philippines. 10 Hib was the causative agent in most (72%) invasive H. influenzae infections in our study as it has been in most studies from Asia, 2 South America, 5 Europe and North America. By using PCR to identify the presence of H. influenzae capsular polysaccharide and capsular expression genes, we could confirm that nontypable, noncapsulated strains also cause invasive disease in young infants in the Philippines. Almost all invasive H. influenzae/Hib patients in our study had clinical meningitis, which was confirmed by CSF culture in two-thirds of cases. This finding suggests that Hib may not be an important etiologic agent of pneumonia in children in the Philippines, which would be in contrast to its inferred 21% role in The Gambia. 4 However, it is possible that we have missed cases with H. influenzae/Hib pneumonia because of deaths at home of the most fulminant cases, prehospital antibiotic uptake 7 and insensitivity of blood culture in diagnosing H. influenzae/Hib pneumonia. 11 The skewed distribution of the Hib infection incidence to the very early age is important when the timing of vaccinations is considered. We have recently shown that Hib capsular polysaccharide protein conjugate vaccines are immunogenic in Filipino infants when given in the local Expanded Program on Immunization schedule starting at 6 weeks of age. 12 Thus our report provides important regional information for decision-makers to consider the inclusion of Hib vaccination in the general vaccination programs in the Philippines and other Southeast Asian countries. Acknowledgments. We thank Grace Esparar, R.M.T., Eugenia Baluran, R.M.T., Maria Felnore Girasol, R.M.T., Leena Kuisma and Hilkka Ohukainen for laboratory work. This work was supported by grants from Academy of Finland (Contract 5569) and from the European Union INCO program (Contracts IC18CT950025 and IC18-CT97-0219).

The etiology of invasive bacterial infections was studied among 956 Filipino children less than five years old who fulfilled the World Health Organization criteria for severe or very severe pneumonia or had suspected meningitis or sepsis. The most common invasive infections were due to Streptococcus pneumoniae (12 [1.3%]) and Haemophilus influenzae (12 [1.3%]); including four cases of pneumococcal meningitis and 11 cases of H. influenzae meningitis. Type 1 was the most common (six of the 12 isolates) of the pneumococcal serotypes. Serotypes/groups 1, 6, 14, and 23 accounted for 91.7% of the invasive isolates. The majority of the H. influenzae strains from blood (10 out of 10) and cerebrospinal fluid (6 out of 7) were type b. Almost all of the invasive S. pneumoniae (9 out of 12) and H. influenzae (11 out of 12) infections were seen before one year of age, which stresses the need to investigate early immunization of children for H. influenzae type b and S. pneumoniae, as well as maternal immunization to maximize the potential of immunoprophylaxis.

BackgroundAntiadhesive compounds are promising candidates for prevention or treatment of infections. We have investigated the efficacy of such an agent, 3′-sialyllacto-Nneotetraose (NE-1530), given intranasally for prophylaxis of acute otitis media and for effect on nasopharyngeal carriage of bacteria.MethodsWe did a randomised, double-blind placebocontrolled study at one study site. 507 healthy children were randomly assigned either NE-1530 (n=254) or placebo (253) as intranasal sprays twice daily during 3 months. The children were examined by the study physicians once a month and during illness. Treatment efficacy was estimated from Cox proportional hazards model. A sample of nasopharyngeal secretion was taken at every visit for culture of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Adverse events were recorded in study diaries.FindingsAt least one event of acute otitis media was diagnosed in 108 (43%) of 254 children in the NE-1530 group and in 86 (34%) of 253 children in the placebo group. The efficacy of treatment was negative, −27% (95% CI −68 to 5; p=0·10). The nasopharyngeal carriage of S pneumoniae, H influenzae, and M catarrhalis was not affected by treatment, and the adverse event profiles were almost identical for NE-1530 and placebo.InterpretationNE-1530 did not have a beneficial effect on the occurrence of acute otitis media or on the nasopharyngeal carriage of bacteria in children.

A clinical bacteriologic laboratory was established in a tertiary care government hospital in The Philippines, where expert bacteriologic laboratories do not usually exist at this level of health care. The laboratory was jointly established by the Research Institute for Tropical Medicine (RITM) (Manila, The Philippines) and the National Public Health Institute (KTL) (Helsinki, Finland). The laboratory was planned, its personnel were trained, and its functioning was continuously supported by the RITM and KTL. The following aspects were of utmost importance in establishing the laboratory and launching its work: 1) the support of the RITM bacteriologic laboratory, with back-up and consultations from KTL; 2) creation and maintenance of personal contacts between clinicians and laboratory staff with an emphasis on clinical relevance and rapid reporting of laboratory results; 3) the consideration of the quality aspects of the work from the start; and 4) keen follow-up of the bacteriologic results and their clinical significance and use, of practical laboratory work, and of quality assurance aspects. In the first two years of its operation, the laboratory identified Streptococcus pneumoniae and Haemophilus influenzae as the most important causes of severe pneumonia, sepsis or meningitis in children less than two years of age, and Salmonella typhi as the most frequent significant isolate from the blood cultures, being found most often in school age children and young adults.

The effectiveness of simultaneously administered influenza and pneumococcal vaccines vs. influenza vaccine alone in preventing pneumonia, pneumococcal pneumonia and pneumococcal bacteraemia among the elderly was studied. The vaccines were offered to all persons aged 65 years or older (N=43500) living in 35 administrative districts in Northern Finland. A total of 26925 persons (62%) decided to participate. Allocation to the vaccination groups took place by year of birth (odd/even). The total follow-up of those vaccinated consisted of 38037 person years. The incremental effectiveness of the pneumococcal vaccine was −20 (95% CI −50–+10%) for pneumonia, −20 (95% CI −90–+20%) for pneumococcal pneumonia and +60% (95% CI −40–+90%) for pneumococcal bacteraemia. Thus the pneumococcal polysaccharide vaccine did not offer any additional protection from pneumonia among elderly people in Finland although it reduced the incidence of bacteraemia.