Streptococcus pneumoniae and Haemophilus influenzae type b Carriage, Central Asia.A study of children was conducted in 3 Central Asian Republics Central Asian Republics, the countries of Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. Constituent republics of the former Union of Soviet Socialist Republics, they all achieved independence in late 1991. . Approximately half of the Streptococcus pneumoniae Streptococcus pneu·mo·ni·ae n. Pneumococcus. Streptococcus pneumoniae Microbiology A pathogenic streptococcus with 90 serotypes associated with pneumonia, bacteremia, meningitis Transmission Person to person Incidence isolates were serotypes included in available vaccine formulations. Approximately 6% of children carried Haemophilus influenzae type b Haemophilus influenzae type b n. Abbr. Hib A gram-negative, rod-shaped bacterium of the genus Haemophilus that is found in the human respiratory tract and causes acute respiratory infections, such as pneumonia, and other diseases, (Hib). Using pneumococcal pneumococcal /pneu·mo·coc·cal/ (-kok´al) pertaining to or caused by pneumococci. and Hib conjugate vaccines may decrease illness in the Central Asian Republics. ********** Streptococcus pneumoniae and Haemophilus influenzae Haemophilus in·flu·en·zae n. A gram-negative, rod-shaped bacterium of the genus Haemophilus, especially Haemophilus influenzae type b, that occurs in the human respiratory tract and causes acute respiratory infections, acute conjunctivitis, and cause a large percentage of acute respiratory and invasive bacterial infections throughout the world (1). Acute respiratory infection is the leading cause of childhood death in the Central Asian Republics of the former Soviet Union (2,3), a region that includes Kazakhstan, Uzbekistan, Turkmenistan, Tajikistan, and the Kyrgyz Republic. These deaths occur despite the availability and use of antimicrobial drugs throughout the former Soviet Union (4,5). To prevent illness from S. pneumoniae in the United States, the 7-valent pneumococcal conjugate vaccine Pneumococcal conjugate vaccine is a vaccine used to protect infants and young children against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). (Prevnar, Wyeth Pharmaceuticals, Philadelphia, PA, USA) was added to the routine infant immunization immunization: see immunity; vaccination. schedule in 2000. Prevnar contains S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Higher valency valency - degree formulations (9-, 11-, and 13-valent) are under evaluation. The 9-valent formulation (including types 1 and 5) was successful in South Africa (6) and The Gambia (7), and an 11-valent formulation (including types 1, 3, 5, and 7F) is being studied in the Philippines. An accelerated development and introduction plan for pneumococcal conjugate vaccines for use in developing countries is supported by the Global Alliance for Vaccines and Immunization The GAVI Alliance (GAVI) (formerly The Global Alliance for Vaccines and Immunization) is an alliance between different stakeholders, in both the private and public sectors, committed to the mission of saving children's lives and protecting people's health through the (www.preventpneumonia.com). H. influenzae type b (Hib) conjugate vaccines have been recommended for infants in the United States since 1990. Widespread use of these vaccines has dramatically reduced Hib invasive disease in both industrialized in·dus·tri·al·ize v. in·dus·tri·al·ized, in·dus·tri·al·iz·ing, in·dus·tri·al·iz·es v.tr. 1. To develop industry in (a country or society, for example). 2. and developing countries (8,9). The World Health Organization (WHO) has recommended use of the Hib conjugate vaccine in regions of the world where the extent of Hib disease Hib disease An infection caused by Haemophilus influenza type b (Hib). This disease mainly affects children under the age of five. In that age group, it is the leading cause of bacterial meningitis, pneumonia, joint and bone infections, and throat has been established. Prevalence of Hib invasive disease must be assessed in countries in the Central Asian Republics before introducing the Hib conjugate vaccine. Laboratory data to determine prevalence of S. pneumoniae and Hib are not collected in the Central Asian Republics. To determine the benefits of using the pneumococcal and Hib conjugate vaccines in these countries, we conducted a nasopharyngeal nasopharyngeal pertaining to the nasal and pharyngeal cavities. nasopharyngeal meatus see nasopharyngeal meatus. nasopharyngeal spasm see reverse sneeze. swab survey of pediatric patients to identify the most prevalent serotypes and penicillin-resistance patterns of S. pneumoniae and to assess the presence of Hib. The Study In January 1997, we obtained nasopharyngeal swabs from a convenience sample of both ill and well children, ages 2-59 months, who were visiting outpatient clinics in Taraz City (formerly Djambul), Kazakhstan; Fergana, Uzbekistan; and Osh, Kyrgyz Republic. Before swabs were obtained, written parental consent was obtained in Russian, Kazak, Kyrgyz, or Uzbek under a protocol approved by a local institutional review board and the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (CDC See Control Data, century date change and Back Orifice. CDC - Control Data Corporation ). Nasopharyngeal swab collection and pathogen isolation have been described previously (1). Briefly, a flexible calcium alginate alginate /al·gi·nate/ (al´ji-nat) a salt of alginic acid; water-soluble alginates are useful as materials for dental impressions. swab was inserted through the nares to the nasopharynx nasopharynx /na·so·phar·ynx/ (-far´inks) the part of the pharynx above the soft palate.nasopharyn´geal na·so·phar·ynx n. , rotated =180[degrees], and withdrawn. While in the field, the swabs were first streaked on chocolate agar (CA) plates containing bacitracin bacitracin (băs'ĭtrā`sĭn), antibiotic produced by a strain of the bacterial species Bacillus subtilis. It is widely used for topical therapy such as for skin and eye infections; it is effective against gram-positive bacteria, to isolate H. influenzae, and then onto Trypticase soy 5% sheep blood agar blood agar n. A nutrient culture medium that is enriched with whole blood and used for the growth of certain strains of bacteria. plates containing gentamicin gentamicin /gen·ta·mi·cin/ (jen?tah-mi´sin) an aminoglycoside antibiotic complex isolated from bacteria of the genus Micromonospora, to isolate S. pneumoniae. All plates were brought back to the laboratory and incubated appropriately. Pure H. influenzae cultures were isolated and spread onto quad plates. Those colonies that grew on only the XV and blood quadrants were considered to be H. influenzae and were saved on CA slants. Suspected S. pneumoniae colonies were streaked onto conventional 5% sheep blood agar plates with an optochin disk added. After appropriate incubation, [alpha]-hemolytic isolates with an optochin inhibition zone >14 mm were considered to be S. pneumoniae and saved on CA slants. CA slants of both H. influenzae and S. pneumoniae were transported to CDC in Atlanta. Isolates of H. influenzae were serotyped with Difco H. influenzae serotype-specific rabbit antisera (BD, Sparks, MD, USA), and S. pneumoniae isolates were serotyped with CDC-prepared antiserum antiserum /an·ti·se·rum/ (an´ti-se?rum) a serum containing antibody(ies), obtained from an animal immunized either by injection of antigen or by infection with microorganisms containing antigen. . S. pneumoniae cultures were tested for antimicrobial susceptibility to penicillin with broth dilution MIC testing by using the guidelines of the Clinical and Laboratory Standards Institute (formerly NCCLS NCCLS National Committee for Clinical Laboratory Standards ) and customized MIC panels. Results were similar in all 3 sites, so data were combined. The method of isolate storage and transport resulted in different survival rates among isolates (Tables 1 and 2). Low rates of S. pneumoniae isolates among children receiving antimicrobial drugs prevent any conclusions about that group. Among S. pneumoniae and H. influenzae isolates, survival was negatively associated with duration of storage. Among S. pneumoniae isolates, survival was positively associated with increasing age. However, the lack of any trends in Hib colonization and S. pneumoniae nonsusceptibility by age and duration of storage suggests that differential survival did not produce bias. Of 630 children swabbed, 375 (59%) were colonized Colonized This occurs when a microorganism is found on or in a person without causing a disease. Mentioned in: Isolation with S. pneumoniae. Of the 375 isolates, 224 S. pneumoniae isolates were available for susceptibility testing and serotyping. Of the 224 isolates, 54 (24%) were nonsusceptible to penicillin. The 9 most common serotypes in decreasing order were 19F (17% of isolates), 6B (15%), 6A (9%), 14 (6%), 23B (4%), 19A (3%), 23F (3%), 18C (2%), and 4 (2%). These accounted for 61% of all isolates. In our sample, the 7-valent pneumococcal conjugate vaccine would cover 47% ofpneumococcal isolates, the 9-valent would cover 48%, and the 11-valent would cover 51%. Of all the serotypes covered in these vaccines, serotypes 6B, 14, 19F, and 23F account for all nonsusceptible strains. Because all 3 vaccines contain these 4 serotypes, each vaccine would cover 33 (61%) of 54 nonsusceptible isolates of S. pneumoniae. An additional 13% of nonsusceptible strains are vaccine-related (strains 6A [4 of 54, 7%] and 23B [3 of 54, 6%]). Of the 630 children from whom nasopharyngeal swabs were obtained, 357 (57%) were carrying H. influenzae. Of the 300 isolates available for serotyping, 34 (11%) were Hib. When Hib carriage is determined by multiplying the percentage of children colonized with H. influenzae times the percentage of Hib among all H. influenzae isolates tested, the carriage rate is 6% (Table 2). Conclusions Our survey showed that most children in these Central Asian Republics were colonized with at least 1 potential respiratory pathogen. Approximately half of the S. pneumoniae isolates and more than half of the penicillin-nonsusceptible S. pneumoniae isolates are included in the available pneumococcal conjugate vaccine formulations. Approximately 6% of the children in this convenience sample were carrying Hib. The colonization rate of Hib found in our study is similar to rates observed in industrialized populations before Hib conjugate vaccines were widely used. Carriage rates for Hib before widespread vaccination in Finland, the United Kingdom, and the United States were 2%-6% (10-13). In these countries, introduction of the Hib vaccine Hib vaccine n. A conjugate vaccine that provides immunization against infections caused by Haemophilus influenzae type b, especially bacterial meningitis and pneumonia in children. virtually eliminated Hib invasive disease (13). Assessing the prevalence of disease due to specific respiratory pathogens is difficult; blood cultures are insensitive, and other diagnostic tests are not specific. Nasopharyngeal colonization surveys of groups of children identify the predominant organisms circulating in the community and the presence or absence of antimicrobial-drug resistance. The presence of S. pneumoniae serotypes found in the pneumococcal conjugate vaccine suggests this vaccine may decrease some illness from acute respiratory infection. The experience in other countries with similar prevaccination Hib nasopharyngeal carriage rates suggests that the Hib conjugate vaccine may also decrease illness. These findings may be helpful in the decision-making process regarding the value of introducing conjugate vaccines for Hib and pneumococcal disease prevention. Funding for this work was provided by the US Agency for International Development under a participating agency service agreement with CDC. Dr Factor was an Epidemic Intelligence Service The Epidemic Intelligence Service is a program of the United States' Centers for Disease Control and Prevention. Established in 1951 due to biological warfare concerns arising from the Korean War, it has become a hands-on two-year postgraduate training program in epidemiology, with officer in the Respiratory Diseases Branch of CDC when she led the field investigations in the Central Asian Republics. She is currently a medical epidemiologist in the CDC Bioterrorism Preparedness Response Program assigned to the New York City New York City: see New York, city. New York City City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S. Department of Health and Mental Hygiene mental hygiene, the science of promoting mental health and preventing mental illness through the application of psychiatry and psychology. A more commonly used term today is mental health. to develop emergency response plans for New York City. References (1.) Centers for Disease Control and Prevention, World Health Organization. Manual for the laboratory identification and antimicrobial susceptibility testing of bacterial pathogens of public health importance in the developing world [monograph on the Internet]. 2003 [cited 2005 Jul 5]. Available from www.who.int/csr/ resources/publications/drugresist/en/IAMRmanual.pdf (2.) Kyrgyz Republic demographic and health survey, 1997. Calverton (MD): Ministry of Health of the Kyrgyz Republic and Macro International Inc; 1998. p. 109. (3.) Uzbekistan demographic and health survey, 1996. Calverton (MD): Ministry of Health of Uzbekistan and Macro International Inc; 1997. p. 115. (4.) Pavin M, Nurgozhin T, Hafner G, Yusufy F, Laing R. Prescribing practices of rural primary health care physicians in Uzbekistan. Trop Med Int Health. 2003;8:182-90. (5.) Stratchounski LS, Andreeva IV, Ratchina SA, Galkin DV, Petrotchenkova NA, Demin AA, et al. The inventory of antibiotics in Russian home medicine cabinets. Clin Infect Dis. 2003;37:498-505. (6.) Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N, et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. infection. N Engl J Med. 2003;349:1341-8. (7.) Cutts FT, Zaman SMA (1) See SMA connector. (2) (Shared Memory Architecture) See shared video memory. (3) (Software Maintenance Association) A membership organization that began in 1985 and ended in 1996. , Enwere G, Jaffar S, Levine OS, Okoko JB, et al. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised Adj. 1. randomised - set up or distributed in a deliberately random way randomized irregular - contrary to rule or accepted order or general practice; "irregular hiring practices" , double-blind, placebo-controlled trial. Lancet. 2005 ;365:1139-46. (8.) Wenger JD, DiFabio JL, Landaverde JM, Levine OS, Gaafar T. Introduction of Hib conjugate vaccines in the non-industrialized world: experience in four 'newly adopting' countries. Vaccine. 1999;18:736-42. (9.) Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide polysaccharide: see carbohydrate. polysaccharide Any of a large class of long-chain sugars composed of monosaccharides. Because the chains may be unbranched or branched and the monosaccharides may be of one, two, or occasionally more kinds, vaccine and a decade after the advent of conjugates. Clin Microbiol Rev. 2000;13:302-17. (10.) Takala AK, Eskola J, Leinonen M, Kayhty H, Nissinen A, Pekkanen E, et al. Reduction of oropharyngeal oropharyngeal /oro·pha·ryn·ge·al/ (-fah-rin´je-al) 1. pertaining to the mouth and pharynx. 2. pertaining to the oropharynx. carriage of Haemophilus influenzae type b (Hib) in children immunized with an Hib conjugate vaccine. J Infect Dis. 1991;164:982-6. (11.) Michaels RH, Poziviak CS, Stonebraker FE, Norden CW. Factors affecting pharyngeal pharyngeal /pha·ryn·ge·al/ (fah-rin´je-al) pertaining to the pharynx. pha·ryn·geal or pha·ryn·gal adj. Of, relating to, located in, or coming from the pharynx. Haemophilus influenzae type b colonization rates in children. J Clin Microbiol. 1976;4:413-7. (12.) Howard AJ, Dunkin KT, Musser JM, Palmer SR. Epidemiology of Haemophilus influenzae type b invasive disease in Wales Wales, Welsh Cymru, western peninsula and political division (principality) of Great Britain (1991 pop. 2,798,200), 8,016 sq mi (20,761 sq km), west of England; politically united with England since 1536. The capital is Cardiff. . BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift . 1991;303:441-5. (13.) Wenger JD. Epidemiology of Haemophilus influenzae type b disease and impact of Haemophilus influenzae type b conjugate vaccines Haemophilus influenzae type b conjugate vaccine n. See Hib vaccine. in the United States and Canada. Pediatr infect Dis J. 1998;17(9 Suppl):S132-6. Stephanie H. Factor, * ([dagger]) Leslye LaClaire, * Melinda Bronsdon, * Fleura Suleymanova, ([double dagger]) Gulbanu Altynbaeva, * Bakhtiyar A. Kadirov, ([section]) Uulkan Shamieva, ([paragraph]) Scott F. Dowell, * # Anne Schuchat, * Richard Facklam, * Benjamin Schwartz, * and Terence Chorba * * Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) New York City Department of Health and Mental Hygiene, New York New York, state, United States New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of , New York, USA; ([double dagger]) Zhambyl Oblast oblast (ō`bläst, ŏ`–, Rus. ô`bləstyə) [Rus.,=region], administrative and territorial division in Russia, Ukraine, Belarus, and the former USSR. Children's Infectious Disease Infectious disease A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. Hospital, Taraz City, Kazakhstan; Uzbekistan Ministry of Health, Tashkent, Uzbekistan; ([paragraph]) Osh Oblast Children's Infectious Diseases Hospital, Osh, Kyrgyz Republic; and # Thai Ministry of Public Health, Bangkok, Thailand Address for correspondence: Stephanie H. Factor, Department of Disease Intervention, New York City Department of Health and Mental Hygiene, 125 Worth St, CN #22E, New York, NY 10013, USA; fax: 212-788-4734; sfactor@health.nyc.gov
Table 1. Streptococcus pneumoniae in convenience sample, Central Asian
Republics, January 1997 *
% SP SP PCN
% SP colonization isolate survival nonsusceptible
Variable (n/N) (n/N) isolates (n/N)
Age (mo)
2-5 49(47/95) 49(23/47) 17(4/23)
6-11 64(74/115) 54 38(15/40)
12-23 66(94/142) 60(56/94) 27(15/56)
24-35 62(65/105) 62(40/65) 23(9/40)
36-47 58(61/106) 64(39/61) 18(7/39)
48-59 51 (34/67) 79(27/34) 19(5/27)
Sex
Male 60 (197/331) 60 (119/197) 27(32/119)
Female 60 (178/299) 60 (106/178) 22(22/106)
Reported use of antimicrobial drugs in past 7 days
Yes 49(34/70) 29(10/34) 10(1/10)
No 61 (335/552) 64 (213/335) 24(52/213)
Weeks storagbefore transport
3 65(72/110) 25(18/72) 11 (2/18)
2 56 (175/315) 62 (108/175) 24(27/108)
1 62 (128/205) 77(99/128) 26(26/99)
Total 59 (375/630) 60 (225/375) 24(55/225)
Calculated % colonization with
Variable PCN-nonsusceptible SP ([dagger])
Age (mo)
2-5 8
6-11 24
12-23 18
24-35 14
36-47 10
48-59 10
Sex
Male 16
Female 13
Reported use of antimicrobial drugs in past 7 days
Yes 5
No 15
Weeks storage
3 7
2 13
1 16
Total 14
* SP, S. pneumoniae; PCN, penicillin.
([dagger]) Result obtained by multiplying the percentage of children
colonized with SP times the percentage of SP isolates that are
nonsusceptible to penicillin (percentages in column 1 multiplied by the
percentages in column 3).
Table 2. Haemophilus influenzae in convenience sample, Central Asian
Republics, January 1997 *
% HI colonization % HI isolate survival
Variable (n/N) (n/N)
Age (mo)
2-5 45 (43/95) 77 (33/43)
6-11 59 (68/115) 76 (52/68)
12-23 60 (85/142) 89 (76/85)
24-35 60 (63/105) 87 (55/63)
36-47 58 (62/106) 85 (53/62)
48-59 54 (36/67) 86 (31/36)
Sex
Male 57 (187/331) 82 (154/187)
Female 57 (170/299) 86 (146/170)
Reported use of
antimicrobial drugs in
past 7 days
Yes 57 (40/70) 82 (33/40)
No 56 (310/552) 84 (260/310)
Weeks storage before
transport
3 59 (65/110) 71 (46/65)
2 57 (178/315) 83 (147/178)
1 56 (114/205) 94 (107/114)
Total 57 (357/630) 84 (300/357)
Calculated %
% Hib among all HI colonization
Variable isolates (n/N) with Hib ([dagger])
Age (mo)
2-5 6(2/33) 3
6-11 17(9/52) 10
12-23 8 5
24-35 13(7/55) 8
36-47 13(7/53) 4
48-59 10(3/31) 5
Sex
Male 13(20/154) 7
Female 10(14/146) 8
Reported use of
antimicrobial drugs in
past 7 days
Yes 9(3/33) 5
No 12(31/260) 7
Weeks storage before
transport
3 20(9/46) 12
2 10(14/147) 6
1 10(11/107) 6
Total 11 (34/300)
* HI, Haemophilus influenzae; Hib, H. influenzae type b.
([double dagger]) Result obtained by multiplying percentage of children
colonized with HI times the proportion of Hib isolates (percentages in
column 1 multiplied by percentages in column 3).
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