Serotype Composition Research Articles

Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations.

BackgroundEnteroviruses are common human pathogens occasionally associated with severe disease, notoriously paralytic poliomyelitis caused by poliovirus. Other enterovirus serotypes such as enterovirus A71 and D68 have been linked to severe neurological syndromes. New enterovirus serotypes continue to emerge, some believed to be derived from nonhuman primates. However, little is known about the circulation patterns of many enterovirus serotypes and, in particular, the detailed enterovirus composition of sewage samples.MethodsWe used a next-generation sequencing approach analyzing reverse transcriptase polymerase chain reaction products synthesized directly from sewage concentrates.ResultsWe determined whole-capsid genome sequences of multiple enterovirus strains from all 4 A to D species present in environmental samples from the United Kingdom, Senegal, and Pakistan.ConclusionsOur results indicate complex enterovirus circulation patterns in human populations with differences in serotype composition between samples and evidence of sustained and widespread circulation of many enterovirus serotypes. Our analyses revealed known and divergent enterovirus strains, some of public health relevance and genetically linked to clinical isolates. Enteroviruses identified in sewage included vaccine-derived poliovirus and enterovirus D-68 stains, new enterovirus A71 and coxsackievirus A16 genogroups indigenous to Pakistan, and many strains from rarely reported serotypes. We show how this approach can be used for the early detection of emerging pathogens and to improve our understanding of enterovirus circulation in humans.

Molecular Investigation of Dengue Virus Serotype 2 Circulation in Kassala State, Sudan.

The tropical environment of Sudan promotes the spread of mosquito-transmitted diseases such as dengue virus (DENV) infection. The current understanding of the geographical distribution of DENV serotypes and genotypes in Sudan is limited. In this study, molecular techniques (reverse transcriptase [RT]-PCR and sequencing) followed by phylogenetic analysis were used to characterize DENV isolated from the blood samples of suspected dengue patients admitted to Kassala Hospital, Kassala state, Sudan, in 2016 and 2017. We identified DENV infection in 4 patients by RT-PCR. Phylogenetic analysis revealed that the isolated virus sequences belong to the Cosmopolitan genotype of DENV serotype 2. This is the first study to confirm the presence of DENV serotype 2 in Kassala state, Sudan. Our results indicate the need for wider investigations of the DENV serotype composition and studies to evaluate their contribution to ongoing transmission.

Streptococcus suis serotype 3 and serotype 18 capsular polysaccharides contain di-N-acetyl-bacillosamine

Streptococcus suis serotype 3 is counted among the S. suis serotypes causing clinical disease in pigs. Yet, limited information is available on this serotype. Here we determined for the first time the chemical composition and structure of serotype 3 capsular polysaccharide (CPS), a major bacterial virulence factor and the antigen at the origin of S. suis classification into serotypes. Chemical and spectroscopic data gave the repeating unit sequence for serotype 3: [4)D-GlcA (β1-3)d-QuiNAc4NAc(β1-]n. To the best of our knowledge, this is the first report of di-N-acetyl-d-bacillosamine (QuiNAc4NAc) containing polysaccharides in Streptococci and the second time this rare diamino sugar has been observed in a Gram-positive bacterial species since its initial report. This led to the identification of homologues of UDP-QuiNAc4NAc synthesis genes in S. suis serotype 18. Thus, the repeating unit sequence for serotype 18 is: [3)d-GalNAc(α1-3)[d-Glc (β1-2)]d-GalA4OAc(β1-3)d-GalNAc(α1-3)d-QuiNAc4NAc(α1-]n. A correlation between S. suis serotypes 3 and 18 CPS sequences and genes of these serotypes' cps loci encoding putative glycosyltransferases and polymerase responsible for the biosynthesis of the repeating unit was tentatively established. Knowledge of CPS structure and composition will contribute to better dissect the role of this bacterial component in the pathogenesis of S. suis serotypes 3 and 18.

Triptych of the Hermit Saints: pneumococcal polysaccharide vaccines for the elderly.

Pneumococcal pneumonia is a serious disease with considerable morbidity and mortality in the elderly. Despite adequate antibiotic treatment, the long-term mortality of pneumococcal pneumonia remains high. Preventive measures in the form of vaccination, therefore, are warranted. Twenty-three-valent polysaccharide vaccines have a broad coverage but limited efficacy. Pneumococcal conjugate vaccines have been shown in children to be able to prevent invasive and mucosal pneumococcal diseases. It should be realized that the serotype composition of current pneumococcal conjugate vaccines is not tailored for the elderly, and that replacement disease can occur. Yet, the current 13-valent conjugate vaccine has been shown to protect against infections with vaccine serotypes. Long-term mortality of pneumococcal pneumonia should be included in policy making about the introduction of these vaccines for the elderly.

Geographic variation in pneumococcal vaccine efficacy estimated from dynamic modeling of epidemiological data post-PCV7

Although mean efficacy of multivalent pneumococcus vaccines has been intensively studied, variance in vaccine efficacy (VE) has been overlooked. Different net individual protection across settings can be driven by environmental conditions, local serotype and clonal composition, as well as by socio-demographic and genetic host factors. Understanding efficacy variation has implications for population-level effectiveness and other eco-evolutionary feedbacks. Here I show that realized VE can vary across epidemiological settings, by applying a multi-site-one-model approach to data post-vaccination. I analyse serotype prevalence dynamics following PCV7, in asymptomatic carriage in children attending day care in Portugal, Norway, France, Greece, Hungary and Hong-Kong. Model fitting to each dataset provides site-specific estimates for vaccine efficacy against acquisition, and pneumococcal transmission parameters. According to this model, variable serotype replacement across sites can be explained through variable PCV7 efficacy, ranging from 40% in Norway to 10% in Hong-Kong. While the details of how this effect is achieved remain to be determined, here I report three factors negatively associated with the VE readout, including initial prevalence of serotype 19F, daily mean temperature, and the Gini index. The study warrants more attention on local modulators of vaccine performance and calls for predictive frameworks within and across populations.

Pre-vaccine serotype composition within a lineage signposts its serotype replacement - a carriage study over 7 years following pneumococcal conjugate vaccine use in the UK.

Serotype replacement has been reported in carriage and disease after pneumococcal conjugate vaccine (PCV) introductions in the UK and globally. We previously described concurrent expansion and decline of sequence types associated with serotype replacement over 5 years following PCV introductions in the UK. Here we use whole-genome sequencing to fully characterise the population structure of pneumococcal isolates collected over seven winters encompassing PCV7 and PCV13 introductions in the UK, investigating the importance of lineages in serotype replacement. We analysed 672 pneumococcal genomes from colonised children of 4 years old or less. The temporal prevalence of 20 lineages, defined by hierarchical Bayesian analysis of population structure (BAPS), was assessed in the context of serotype replacement. Multiple serotypes were detected in the primary winter of sampling within three vaccine-type (VT) lineages BAPS4, BAPS10 and BAPS11, in which serotype replacement were observed. In contrast, serotype replacement was not seen in the remaining three VT lineages (BAPS1, BAPS13 and BAPS14), that expressed a single serotype (6B, 6A and 3, respectively) in the primary winter. One lineage, BAPS1 serotype 6B was undetectable in the population towards the end of the study period. The dynamics of serotype replacement, in this UK population, was preceded by the presence or absence of multiple serotypes within VT lineages, in the pre-PCV population. This observation could help predict which non-vaccine types (NVTs) may be involved in replacement in future PCV introductions here and elsewhere. It could further indicate whether any antibiotic resistance associated with the lineages is likely to be affected by replacement.

Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae in the Philippines, 2004-2011

Objective. Scarcity of data on the serotype composition and antibiotic resistance of invasive pneumococci from developing countries has been noted. We describe in this study the serogroup distribution and antimicrobial resistance patterns of Streptococcus pneumoniae in the Philippines from 2004-2011. Methodology. S. pneumoniae isolated from patients with invasive pneumococcal disease were referred to the Antimicrobial Resistance Surveillance Reference Laboratory from 2004 to 2011. Typing of isolates was done through slide agglutination and antimicrobial susceptibility was determined following CLSI methods. Results. The penicillin-resistant meningitis isolates were of serotypes 1, 5 and 14 which are covered by PCV10 and 13. The erythromycin resistant isolates were serotype 9 while cotrimoxazole resistant isolates were serotypes 1, 5, 6, 12 and 14. Forty-one percent of the cotrimoxazole resistant isolates are covered by PCV7, and 88% are covered by both PCV10 and PCV13. Levofloxacin resistant isolates were of serotypes 5 and 23 with PCV7 coverage of 50% and PCV10 and PCV13 coverages of 100%. Conclusion. S. pneumoniae serotypes causing IPD in the country is largely similar to the dominant IPD serotypes worldwide. The serotype distribution in the Philippines remained stable from 2004 to 2011 and antimicrobial resistance among the isolates remained low. The serotypes of antibiotic resistant S. pneumoniae in this study were not similar with known serotype resistance profiles in other Asian countries. With the inclusion of PCV in the national free national immunization program of the country beginning 2013, continued surveillance of prevailing pneumococcal serotypes should be done to monitor any shift in the prevalence of PCV associated serotypes to guide disease control measures including control of emergence of resistant pneumococcal isolates.

Structure determination of Streptococcus suis serotype 9 capsular polysaccharide and assignment of functions of the cps locus genes involved in its biosynthesis

Streptococcus suis serotype 9 is the most prevalent S. suis serotype in several European countries. In spite of its pathogenicity for pigs and increasing zoonotic potential, limited information is available on this serotype. Here we determined for the first time the chemical composition and structure of serotype 9 capsular polysaccharide (CPS), a major bacterial virulence factor and the antigen at the origin of S. suis classification into serotypes. Chemical and spectroscopic data gave the repeating unit sequence: [3)Glcol-6-P-3-[D-Gal(α1-2)]D-Gal(β1-3)D-Sug(β1-3)L-Rha(α1-)]n. Compared to previously characterized S. suis CPSs (serotypes 1, 1/2, 2 and 14), serotype 9 CPS does not contain sialic acid but contains a labile 4-keto sugar (2-acetamido-2,6-dideoxy-β-D-xylo-hexopyranos-4-ulose), one particular feature of this serotype. A correlation between S. suis serotype 9 CPS sequence and genes of this serotype cps locus encoding putative glycosyltransferases and polymerase responsible for the biosynthesis of the repeating unit was tentatively established. Knowledge of CPS structure and composition will contribute to better dissect the role of this bacterial component in the pathogenesis of S. suis serotype 9.

Next generation protein based Streptococcus pneumoniae vaccines

All currently available Streptococcus pneumoniae (Spn) vaccines have limitations due to their capsular serotype composition. Both the 23-valent Spn polysaccharide vaccine (PPV) and 7, 10, or 13-valent Spn conjugate vaccines (PCV-7, 10, -13) are serotype-based vaccines and therefore they elicit only serotype-specific immunity. Emergence of replacement Spn strains expressing other serotypes has consistently occurred following introduction of capsular serotype based Spn vaccines. Furthermore, capsular polysaccharide vaccines are less effective in protection against non-bacteremic pneumonia and acute otitis media (AOM) than against invasive pneumococcal disease (IPD). These shortcomings of capsular polysaccharide-based Spn vaccines have created high interest in development of non-serotype specific protein-based vaccines that could be effective in preventing both IPD and non-IPD infections. This review discusses the progress to date on development of Spn protein vaccine candidates that are highly conserved by all Spn strains, are highly conserved, exhibit maximal antigenicity and minimal reactogenicity to replace or complement the current capsule-based vaccines. Key to development of a protein based Spn vaccine is an understanding of Spn pathogenesis. Based on pathogenesis, a protein-based Spn vaccine should include one or more ingredients that reduce NP colonization below a pathogenic inoculum. Elimination of all Spn colonization may not be achievable or even advisable. The level of expression of a target protein antigen during pathogenesis is another key to the success of protein based vaccines.. As with virtually all currently licensed vaccines, production of a serum antibody response in response to protein based vaccines is anticipated to provide protection from Spn infections. A significant advantage that protein vaccine formulations can offer over capsule based vaccination is their potential benefits associated with natural priming and boosting to all strains of Spn. One of the most universal and comprehensive approaches of identifying novel vaccine candidates is the investigation of human sera from different disease stages of natural infections. Antigens that are robustly reactive in preliminary human serum screening constitute a pathogen-specific antigenome. This strategy has identified a number of Spn protein vaccine candidates that are moving forward in human clinical trials.

Serotypes and genotypes of invasive Streptococcus pneumoniae before and after PCV10 implementation in southern Brazil.

To reduce the burden of pneumococcal diseases, different formulations of pneumococcal conjugate vaccines (PCV) have been introduced in many countries. In Brazil, PCV10 has been available since 2010. We aimed to analyze the serotype and genetic composition of invasive pneumococci from Brazil in pre- and post- vaccination periods (2007–2012). Antibiotic susceptibility was determined and genotypes of macrolide and fluoroquinolone resistance were characterized. The genotypes of isolates of the most frequent serotypes were determined by multilocus sequence typing. The study included 325 isolates, which were primarily recovered from blood. The most common serotypes recovered were 14, 3, 4, 23F, 7F, 9V, 12F, 20, 19F, 8, 19A, and 5. Thirty-eight pneumococci (11.7%) were from children ≤5 years old. Considering the overall population, PCV10 and PCV13 serotype coverage was 50.1% and 64.9%, respectively. During the pre-vaccine period, isolates with serotypes belonging to the PVC10 represented 51.5% (100/194), whereas in the post vaccine they represented 48.0% (63/131). PCV13 serotypes represented 67.5% (131/194) and 59.2% (77/131) of total for pre- and post-vaccination periods, respectively. Seventy different sequence types [STs] were found, accounting for 9 clonal complexes [CCs] and 45 singletons. Eight STs (156, 180, 218, 8889, 53, 191, 770, and 4967) represented the majority (51.5%) of isolates. Fifty STs were associated with the pre-vaccination period (27 exclusive) and 43 (20 exclusive) with the post-vaccination period; 23 STs were identified in both periods. Some serotypes were particularly clonal (7F, 8, 12F, 20). Non-susceptibility to penicillin was associated with serotype 19A, CC320. Erythromycin resistance was heterogeneous when considering serotype and ST. A single serotype 23F (ST4967) isolate was resistant to levofloxacin. Continued surveillance is required to determine vaccine impact and to monitor changes in pneumococcal population biology post-PCV10 introduction in Brazil.

Pneumococcal vaccines in adults: an update

The burden of pneumococcal disease is high worldwide, mainly among elderly and immunosuppressed patients. Vaccines are important tools as preventive strategy for this population. There are two types of pneumococcal vaccines approved for adults, these are polysaccharide and conjugate, which are inactivated, have different serotype composition and immunogenicity. As new studies are available for pneumococcal conjugate vaccine, new recommendations have been made for its use in adults.

Streptococcus pneumoniae in saliva of Dutch primary school children.

While nasopharyngeal sampling is the gold standard for the detection of Streptococcus pneumoniae carriage, historically seen, saliva sampling also seems highly sensitive for pneumococcal detection. We investigated S. pneumoniae carriage in saliva from fifty schoolchildren by conventional and molecular methods. Saliva was first culture-enriched for pneumococci, after which, DNA was extracted from all bacterial growth and tested by quantitative-PCR (qPCR) for pneumococcus-specific genes lytA and piaA. Next, serotype composition of the samples was determined by serotype-specific qPCRs, conventional-PCRs (cPCR) and sequencing of cPCR amplicons. Although only 2 (4%) of 50 samples were positive by conventional diagnostic culture, 44 (88%) were positive for pneumococci by qPCR. In total, we detected the presence of at least 81 pneumococcal strains representing 20 serotypes in samples from 44 carriers with 23 carriers (52%) positive for multiple (up to 6) serotypes. The number of serotypes detected per sample correlated with pneumococcal abundance. This study shows that saliva could be used as a tool for future pneumococcal surveillance studies. Furthermore, high rates of pneumococcal carriage and co-carriage of multiple pneumococcal strains together with a large number of serotypes in circulation suggests a ubiquitous presence of S. pneumoniae in saliva of school-aged children. Our results also suggest that factors promoting pneumococcal carriage within individual hosts may weaken competitive interactions between S. pneumoniae strains.

Optimal Serotype Compositions for Pneumococcal Conjugate Vaccination under Serotype Replacement

Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children <5 years of age by 75%. However, due to replacement through herd effects, the decrease among the older population is predicted to be much less (20–40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including new serotypes in the vaccine (e.g. 22 and 9N).

Pseudomonas aeruginosa population structure revisited under environmental focus: impact of water quality and phage pressure

Pseudomonas aeruginosa attracts research attention as a common opportunistic nosocomial pathogen causing severe health problems in humans. Nevertheless, its primary habitat is the natural environment. Here, we relate the genetic diversity of 381 environmental isolates from rivers in northern Germany to ecological factors such as river system, season of sampling and different levels of water quality. From representatives of 99 environmental clones, also in comparison with 91 clinical isolates, we determined motility phenotypes, virulence factors, biofilm formation, serotype and the resistance to seven environmental P.aeruginosa phages. The integration of genetic, ecological and phenotypic data showed (i) the presence of several extended clonal complexes (ecc) which are non-uniformly distributed across different water qualities, and (ii) a correlation of the hosts' serotype composition with susceptibility towards distinct groups of environmental phages. For at least one ecc (eccB), we assumed the ecophysiological differences on environmental water adaptation and phage resistance to be so distinct as to reinforce an environmentally driven cladogenic split from the remainder of P.aeruginosa. In summary, we conclude that the majority of the microevolutionary population dynamics of P.aeruginosa were shaped by the natural environment and not by the clinical habitat.

Invasive Pneumococcal Disease among Children in Rural Bangladesh: Results from a Population‐Based Surveillance

Streptococcus pneumoniae infection is recognized as a global priority public health problem, and conjugate vaccines have been shown to prevent vaccine-type invasive pneumococcal disease (IPD) in children. However, better estimates of the disease burden and reliable population-based data on serotype composition are needed for vaccine development and implementation in developing countries. We initiated a population-based surveillance in the rural Bangladesh community of Mirzapur, covering a population of approximately 144,000. Village health care workers made weekly visits to approximately 12,000 children 1-59 months of age in the study area. Children with reported fever, cough, or difficulty breathing were assessed by the village health care workers using a clinical algorithm and were referred to the hospital if required. Children from the study area who were seen in the hospital underwent clinical examination and laboratory testing if they met standardized case definitions. IPD was confirmed by blood and/or cerebrospinal fluid culture results. Isolates were identified, tested for susceptibility to antibiotics, and serotyped in accordance with standard laboratory methods. We present here the results from the first 3 years of the surveillance (July 2004-June 2007). Village health care workers identified 5020 cases of possible severe pneumonia and/or very severe disease (165 cases per 1000 child-years)and 9411 cases of possible pneumonia (310 cases per 1000 child-years) as well as 2029 cases of suspected meningitis and/or very severe disease (67 cases per 1000 child-years) and 8967 cases of high fever and/or possible bacteremia (295 cases per 1000 child-years). Pneumonia was the single most common form of illness observed among 2596 hospitalizations (found in 977 [38%] of cases). We recovered 26 S. pneumoniae isolates (25 isolates from 6925 blood cultures and 1 isolate from 41 cerebrospinal fluid cultures), which gave an overall IPD incidence of 86 cases per 100,000 child-years. Invasive pneumococcal infection was common during infancy (with infants accounting for 23 of the 26 cases), and 50% of the total isolates were obtained from nonhospitalized patients who received a diagnosis of upper respiratory tract infection and fever. The most prevalent pneumococcal serotypes were serotypes 1, 5, 14, 18C, 19A, and 38. Ten of the 26 isolates were completely resistant to trimethoprim-sulfamethoxazole, and another 10 isolates had intermediate resistance. IPD contributes substantially to childhood morbidity in rural Bangladesh. S. pneumoniae can cause invasive but nonsevere disease in children, and IPD incidence can be seriously under reported if such cases are overlooked. The emerging high resistance to trimethoprim-sulfamethoxazole should be addressed. Data on serotype distribution would help to guide appropriate pneumococcal conjugate vaccine formulation.

Epidemiologic impact of blood culture practices and antibiotic consumption on pneumococcal bacteraemia in children

This study examined the roles of two different diagnostic approaches to children with fever of unknown origin in determining the patterns of pneumococcal bacteraemia in two Spanish regions by comparing their main epidemiologic characteristics. Whereas a blood culture is routinely obtained in this setting in Navarre, this is not generally the case in Majorca. Additionally, the potential role of antibiotic consumption in each region was also analysed. Cumulative incidences in children under the age of 14 years were 26.6 per 100,000 child-years in Navarre (121.1 in children <2 years of age) and 7.3 per 100,000 child-years in Majorca (33.3 in children <2 years of age). In contrast, the incidences per 1,000 blood cultures were similar in both regions. The relative risks of occult bacteraemia, bacteraemic pneumonia and meningitis among the children of Navarre compared to Majorcan children were 11.8, 2.6 and 0.8, respectively. The risk for less virulent (vaccine serotypes plus 6A, 19A and 23A) and for more virulent serotypes (1 and 7) was 4.9 and 3.1 times higher in Navarre, respectively. The number of 7-valent pneumococcal conjugate vaccine (PCV7) doses administered between 2003 and 2004 were also higher in Navarre. Conversely, antibiotic resistance and paediatric prescriptions for broad-spectrum antibiotics were greater in Majorca. Although the most salient differences between both regions, including the effectiveness of pneumococcal conjugate vaccine in Navarre, appeared to be confounded by the higher frequency of blood cultures taken there, certain differences in serotype composition may be explained by the higher antibiotic consumption in Majorca.

WHO expert consultation on serotype composition of pneumococcal conjugate vaccines for use in resource-poor developing countries, 26–27 October 2006, Geneva

Pneumococcal conjugate vaccines induce serotype specific protection, with cross-protection seen between serotypes within certain serogroups. Though most serious pneumococcal infections are caused by relatively small number of serotypes, choices need to be made on the serotypes to be included in the vaccine because of the complexity and cost related to developing and producing vaccines with increasing number of serotypes. The choice is rendered difficult because of differences in the distribution of serotypes causing serious disease between different geographic regions and age groups as well as changes over time. The World Health Organization convened an expert consultation to formulate a data-driven approach to determine the minimum or optimal formulation of pneumococcal conjugate vaccines, particularly keeping in mind the needs of developing countries as well as the epidemiologic, regulatory, formulation and manufacturing issues involved. The deliberations and conclusions of this meeting are summarized in this report.

Comparison of antibiotic resistance and serotype composition of carriage and invasive pneumococci among Bangladeshi children: implications for treatment policy and vaccine formulation.

The nasopharyngeal carriage of Streptococcus pneumoniae is thought to pose a risk for invasive pneumococcal diseases, and the evaluation of carriage strains is thus often used to inform antibiotic treatment and vaccination strategies for these diseases. In this study, the age-specific prevalences, resistance to antibiotics, and serotype distributions of 1,340 carriage strains were analyzed and compared to 71 pneumococcal strains isolated from the cerebrospinal fluid of children under 5 years old with meningitis. Overall, the nasal carriage rate was 47%. One-fourth (26%) of the infants under 1 month of age and one-half (48%) of the infants under 12 months of age were colonized with S. pneumoniae. Rural children were colonized earlier than those from urban areas. Approximately one-fourth and one-half of the cases of pneumococcal meningitis occurred in the first 3 and 6 months of life, respectively. The respective rates of resistance for carriage and meningitis strains to penicillin (7 and 3%), cotrimoxazole (77 and 69%), and erythromycin (2 and 1%) were similar, whereas chloramphenicol resistance was lower among carriage strains (3%) than among meningitis strains (15.5%). The predominant serogroups of carriage and invasive isolates were variable and widely divergent. Thus, hypothetical 7-, 9-, and 11-valent vaccines, based on the predominant carriage strains of the present study, would cover only 23, 26, and 30%, respectively, of the serotypes causing meningitis. Further, currently available 7-, 9-, and 11-valent vaccines would protect against only 26, 43, and 48%, respectively, of these meningitis cases. In conclusion, while the surveillance of carriage strains for resistance to antibiotics appears useful in the design of empirical treatment guidelines for invasive pneumococcal disease, data on the serotypes of carriage strains have limited value in vaccine formulation strategies, particularly for meningitis cases.

Bacterial vaccines and serotype replacement: lessons from Haemophilus influenzae and prospects for Streptococcus pneumoniae.

Conjugate vaccines have reduced the incidence of invasive disease caused by Haemophilus influenzae, type b (Hib), in industrialized countries and may be highly effective against Streptococcus pneumoniae. However, the serotype specificity of these vaccines has led to concern that their use may increase carriage of and disease from serotypes not included in the vaccine. Replacement has not occurred with the use of Hib vaccines but has occurred in trials of pneumococcal vaccines. Mathematical models can be used to elucidate these contrasting outcomes, predict the conditions under which serotype replacement is likely, interpret the results of conjugate vaccine trials, design trials that will better detect serotype replacement (if it occurs), and suggest factors to consider in choosing the serotype composition of vaccines.

Epidemiological study of the G serotype distribution of group A rotaviruses in Kenya from 1991 to 1994.

An epidemiological study on the G serotype distribution of group A rotaviruses (GARV) isolated in Kenya was carried out in one urban hospital in Nairobi and in two rural hospitals in Nanyuki and Kitui to clarify the prevalent G serotypes before future introduction of the ready licensed rotavirus vaccine in Kenya. A total of 1,431 stool specimens were collected from children, who were mainly outpatients, aged from 0 to 6 years old with acute gastroenteritis from August 1991 to July 1994. Samples positive for GARV by conventional ELISA were then analyzed by subgrouping and serotyping ELISA and by PAGE. To ascertain the G serotypes of viruses in samples that were unable to be typed by serotyping ELISA, polymerase chain reaction was also attempted. The prevalence of GARV was 28.4% in the urban hospital, 22.5% in Nanyuki, and 13.7% in Kitui. Among rotavirus-positive samples, subgroup II rotaviruses were detected in 63.1%, and subgroup I rotaviruses were 25.9%. Serotype G4 was most prevalent, accounting for 41.6% followed by 23.3% of serotype G1, 17.0% of serotype G2, and serotype G3 was rarely isolated. Seven strains of serotype G8/P1B rotavirus was detected for the first time in Kenya by RT-PCR. Eleven specimens with an unusual composition of subgroup, serotype, and electropherotype were atypical GARV in which the P-serotype was P1A, P1B, or P2. Although uncommon GARV serotype G8/P1B and atypical GARV were detected, the four major GARV serotypes, G1 through G4, should be targeted at this moment for vaccination to control this diarrheal disease in Kenya. Continuous monitoring of the G- and P-serotype distribution of GARV should provide important information about the impact of rotavirus vaccination in Kenya.