Seronegative Children Research Articles

Helicobacter pylori is not a determinant factor of persistent diarrhoea or malnutrition in Peruvian children

To investigate the role of Helicobacter pylori in childhood diarrhoea, specific IgG antibodies to H. pylori (determined by an ELISA) were sought in 119 infants aged 3–36 months in Peru. Thirty one of the infants had acute diarrhoea (defined as lasting <72 h and not present in the previous 3 weeks), 67 had persistent diarrhoea (lasting ⩾ 14 days with no more than 1 intervening diarrhoea-free day) and the remaining 21 had not had diarrhoea in the previous 3 weeks. The children with diarrhoea had been admitted to hospital in Lima for diarrhoea treatment, and the diarrhoea-free children for investigation of possible tuberculosis. Aspirates of duodenal contents and duplicate stool samples were investigated for the presence of bacterial overgrowth and of pathogenic bacteria, viruses and parasites. Anthropometric measurements were also made. There were no statistically significant differences between the prevalence rates of IgG against H. pylori in the children with acute diarrhoea, persistent diarrhoea and without diarrhoea (32%, 43% and 29%, respectively). In addition, H. pylori infection (as evidenced by specific antibodies) had no apparent influence on the presence of small-bowel overgrowth (in 20% of seropositive children compared with 18% of seronegative children) or of pathogens in the stool (in 53% of seropositive children compared with 49% of seronegative children) or on the occurrence of malnutrition in the groups of children considered as a whole. We conclude that H. pylori infection is not associated with acute or persistent diarrhoeal disease, small-bowel overgrowth, stool pathogens or malnutrition in Peruvian children.

Previous exposure to measles, mumps, and rubella--but not vaccination during adolescence--correlates to the prevalence of pancreatic and thyroid autoantibodies.

This study was designed to determine whether a relationship exists between previous exposure to measles, mumps, and rubella (MMR) by natural infection or vaccination or by new immunization with MMR vaccine, and either the presence or levels of autoantibodies against thyroid cell and pancreatic beta-cell antigens. Antibodies against MMR and autoantibodies against thyroglobulin, thyroid peroxidase, pancreas islet cells (ICA), islet cell surface, glutamic acid decarboxylase 65k autoantibodies, and insulin were studied before, and 3 months after, vaccination with combined MMR vaccine in 386 school children between 11 and 13 years of age. The vaccination changed neither the prevalence nor the level of autoantibodies. Children with rubella antibodies before vaccination had higher levels of ICA than did the rubella seronegative children. In contrast, thyroid autoantibody levels and prevalence were lower in children with antibodies against measles, mumps, or both before vaccination than in children without those antibodies. Previous natural infection or vaccination against measles, mumps, or both seemed to have an inhibitory effect on the development of thyroid autoantibodies. In contrast, children with previous exposure to rubella had higher levels of ICA. No evidence was found that MMR vaccination during adolescence may trigger autoimmunity.

HIV-related gender biases among malnourished children in Abidjan, Côte D'Ivoire.

This study, conducted in a health centre in Abidjan for malnourished children, shows that there were more girls than boys among children admitted who were HIV seropositive whereas there were more boys than girls among seronegative children. Reasons for this gender bias are investigated.

Clinical symptoms and social factors in a cohort of children spontaneously clearing Helicobacter pylori infection

Tindberg Y, Blennow M, Granström M. Clinical symptoms and social factors in a cohort of children spontaneously clearing Helicobacter pylori infection. Acta Pædiatr 1999; 88: 631‐5. Stockholm. ISSN 0803‐5253In a cohort study of 305 Swedish children, repeated blood samples and structured questionnaires were obtained from 6 mo to 11 y of age. Of the 40 children seropositive for Helicobacter pylori in one or more samples, 32 (80%) had cleared the infection by 11 y of age. No association was found between H. pylori seropositivity at any time and reported antibiotic consumption, size of home and family, type of day‐care, history of atopic disease, length of breastfeeding or peptic ulcer disease in the family. Girls reported more (p = 0.002) unspecified abdominal pain during childhood than boys, but the difference in H. pylori infection rate (15/150, 10% for boys and 25/144, 17% for girls) was not significantly different (p = 0.09). Unspecified abdominal pain during childhood was reported more often (OR adjusted for gender = 2.2, 95% CI = 1.0‐4.4, p = 0.04) for the children seropositive at some point (17/39, 44%) than for the seronegative children (54/217, 25%). RAP at 11 y of age was more often reported by the 9/36 (25%) children seropositive at some time in life than by the 23/172 (13%) seronegatives, but the difference was not statistically significant (OR adjusted for gender = 2.0, 95% CI = 0.8‐4.6, p = 0.1). The study shows that H. pylori seropositivity was associated with a parental report of unspecified abdominal pain during childhood. Also, a history of unspecified abdominal pain was more common (OR = 51.6, 95% CI = 15.6‐220, p&lt; 0.001) in children reporting RAP at 11 y of age. □Childhood infection, H. pylori, socioeconomic conditions

Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa.

While in the United States and northern Europe, human herpesvirus 8 (HHV-8) appears to be mainly sexually transmitted with primary infection occurring in adulthood, the modes of transmission remain unknown in East and Central Africa, where Kaposi's sarcoma (KS) is a long-standing endemic disease, occurring not only in adults but also in children. The aim of our present study was to determine the prevalence of HHV-8 infection in children from Yaounde, Cameroon, Central Africa. Specific antibodies directed against both latent and lytic HHV-8 antigens were detected and titrated, with an immunofluorescence assay using the KS-1 cell line, in the plasma of 258 children and adolescents, of 32 mother and child pairs and of 189 pregnant women. Two different HHV-8 DNA-specific sequences were searched in the buffy coat by PCR assays. The overall HHV-8 seroprevalence was 27.5% among these children and adolescents. In newborns, seroprevalence reached 46%, reflecting passive transmission of maternal IgG. This was followed by a marked drop. Then, beginning around 4 years of age, a regular increase of HHV-8 antibodies took place, reaching 39% in the 12- to 14-year age group and 48% above 15 years, a rate similar (54.5%) to that observed in pregnant women. PCR detection of HHV-8 sequences was negative in seronegative children and positive in the buffy coat in 17% of HHV-8-seropositive children, reflecting a low viral load in the peripheral blood. Our results establish that in Central Africa HHV-8 infection takes place during childhood by casual routes, in contrast to the sexual transmission observed in adults in northern Europe and the United States. We hypothesize that the lymphadenopathic form of KS seen in African children is related to an early and massive infection by HHV-8 in susceptible individuals.

Nasopharyngeal carriage of multidrug-resistant Streptococcus pneumoniae in institutionalized HIV infected and HIV-negative children in Northeastern Romania

Objectives: The study compared nasopharyngeal carriage of resistant pneumoniae in human immunodeficiency virus (HIV)-seropositive and -seronegative children. Methods: Nasopharyngeal colonization with Streptococcus pneumoniae was investigated during May 1996 in 162 HIV-negative infants and children (age range, 1–38 mo) and 40 HIV-infected children (age range, 39–106 mo) living in an orphanage in Iasi, northeastern Romania. The HIV-infected children lived separated from the other children and were cared for by a different staff. Streptococcus pneumoniae was isolated from 12 of 40 (30%) HIV-infected and from 81 of 160 (50%) HIV-negative children. Antimicrobial susceptibility to penicillin and ceftriaxone was determined by E-test, and to another five antibiotics by disk diffusion. Serotyping was performed by the Quellung method on 81 of 93 (87%) isolates. Results: Serotypes 6A, 613, 19A, and 23F together represented 98% of all isolates. Ninety-nine percent of S. pneumoniae isolates were resistant to penicillin, and 74% were highly resistant to penicillin (minimum inhibitory concentration [MIC] > 1 μg/mL); MIC 50 and MIC 90 to penicillin of the isolates were 2 μg/mL and 8 μg/mL, respectively. Eighty-nine of ninety-one isolates were susceptible to ceftriaxone; 99%, 87%, 87%, 48%, and 21 % of the isolates were resistant to trimethoprim-sulphamethoxazole, erythromycin, clindamycin, tetracycline, and chloramphenicol, respectively. Eighty-two (89%) isolates were multidrug resistant (resistant to ≥3 antibiotic classes); 37 of 92 (40%) isolates were resistant to 5 or more antibiotic classes, and 16 of these 37 (43%) belonged to serotype 19A. All serotype 19 isolates were highly resistant to penicillin. Conclusions: No significant differences were observed in the resistance rates of S. pneumoniae in HIV-infected children compared to HIV-negative children. Multidrug-resistant pneumococci were highly prevalent in this Romanian orphanage in both HIV-negative and older HIV-infected children. The observed high prevalence of multidrug-resistant pneumococci (coupled with high penicillin resistance) with a limited number of circulating serotypes emphasizes the need to further evaluate the conjugate vaccines in children at risk for invasive pneumococcal infection.

Helicobacter pylori infection in Ethiopian children: a cohort study.

Risk factors for infection with Helicobacter pylori (HP) were investigated in a cohort study of 121 seronegative children in Ethiopia aged 2-4 y, who had previously participated in a case-control study. Blood samples were drawn at inclusion in the cohort study and again after 12 and 30 months. At 12 months the parents were also interviewed about putative risk factors for infection, using a structured questionnaire. Analyses were made by comparing risk factors in seropositive and seronegative children. The seroconversion rate during the first year was 31% (27/87) and during the following 18 months 34% (17/50; corresponding to an annual incidence of 24%). After a period of 30 months, 58% (14/24) of the children who were 24-29 months old at inclusion in the study had seroconverted, compared with 40% (4/10) of those who were 30-35 months old, 73% (22/30) of those who were 36-41 months old and 31% (4/13) of those who were 42 months old or more. These results indicate that peak age for HP infection is below 6 y in this cohort in Ethiopia, and might also reflect a pattern of repeated seroconversion and sero-reversion in early childhood. Independent predictors of HP-seroconversion were the variables 'drinking-water', comparing water from a well with water from rivers or pipes (RR = 1.46, 95% CI 1.0-2.15) and 'antibiotic treatment' (RR = 1.84, 95% CI 1.16-2.92).

Prospective study of the incidence of diarrheal disease and Helicobacter pylori infection among children in an orphanage in Thailand.

To evaluate the hypothesis that gastric infection with Helicobacter pylori increases risk for diarrheal disease in children, we conducted a yearlong prospective study among 160 orphanage children < 5 years of age in Nonthaburi, Thailand. Serum samples collected at six-month intervals were examined by ELISA for antibodies to H. pylori, and children were followed daily for the development of diarrhea. Seven percent of children were seropositive on enrollment, 59% were seronegative, and 34% were indeterminate. Among the seronegative children, seroconversion occurred at a rate of 7% per six months. Forty-six percent of children developed 214 total episodes of diarrhea. By age group, children < 18 months, 18-24 months and > 24 months of age experienced 2.6, 1.1, and 0.2 mean diarrhea episodes per six months. The incidence of diarrhea was not significantly different between children by H. pylori serostatus. We conclude that H. pylori infection was not associated with an increased risk of diarrheal disease.

Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children.

As part of a major epidemiologic study on Chagas' disease, we compared the prevalence of electrocardiographic (ECG) abnormalities among 141 school children 7-12 years of age and seropositive for Trypanosoma cruzi, and 282 age-, sex-, and school-matched seronegative children in an endemic area in Brazil. The prevalence of ECG abnormalities was 11.3% among seropositive children and 3.5% among seronegative children (odds ratio = 3.5, 95% confidence interval [CI] = 1.5-8.4). The prevalence rate of ECG alterations was 10.7% for seropositive males versus 8.9% for seropositive females. Complete right bundle branch block (CRBBB), which is highly suggestive of Chagas' disease cardiopathy, was diagnosed in nine (6.4%) seropositive children and in only one (0.3%) seronegative child (odds ratio = 18.5, 95% CI = 2.3-146.5, attributable fraction = 58.3%). Five incident new cases of CRBBB were diagnosed after a 36-month follow-up of seropositive children who were enrolled in an independent clinical field trial. No case of frequent and/or multifocal ventricular premature beats was found in the cohort of children. The surprisingly high frequency of early ECG abnormalities, which indicates a rapid evolution from infection to disease, suggests the existence of endemic areas with a particular accelerated disease progression that was not described before. Under such conditions, a public health chemotherapy program focusing on the treatment of young seropositive children would be recommended.

Relationship between unsupplemented vitamin A serum concentrations and measles vaccine response in Jamaican children.

Relationship between unsupplemented vitamin A serum concentrations and measles vaccine response in Jamaican children.

Immunity to mumps before and after MMR vaccination at 12 years of age in the first generation offered the two-dose immunization programme

Sweden was the first country in the world to introduce a two-dose programme of vaccination against measles, mumps and rubella with a combined vaccine (MMR). It was commenced in 1982 and the vaccination was carried out at the ages of 18 months and 12 years. In 1992–1993 the first age-group vaccinated at 18 months reached the age of 12 and accordingly received a second dose of MMR. A total of 382 children participated in the present study. Sero-immunity against mumps was studied by testing neutralizing antibodies using serial dilutions inoculated into cell cultures before and after the 12-year vaccination. Of the 229 children earlier vaccinated (group A), 27% lacked demonstrable antibodies before the booster. Of those without documented vaccination records (group B), 56% were seronegative before vaccination. After vaccination, 93% of group A and 86% of group B were seropositive (titre ⩾2). In the seronegative children, whether vaccinated earlier or not, the seroconversion was ca 75%. Previously unvaccinated children positive before vaccination and thus likely to be naturally immune had a higher mean-titre both before and after vaccination than the seropositive chlidren earlier vaccinated. So far, the two-dose programme has proceeded as expected.

Activation of lymphocytes by HHV-6 antigen in normal children and adults.

We investigated the immune reaction of lymphocytes in response to human herpes virus-6 (HHV-6) in normal children and adults. Cell proliferation was assayed by measurement of the incorporation of 5-bromo-2'-deoxyuridine (BrdU) by enzyme-linked immunosorbent assay (ELISA), and changes in expression of interleukin-2 receptors (IL-2Rs) (alpha-, beta3-, and gamma-chain) were assayed by flow cytometry. Incorporation of BrdU and expression of IL-2Rs (alpha-, beta-, and gamma-chain) in CD4+, CD8+, and CD45RO+ lymphocytes were increased when peripheral blood mononuclear cells (PBMC) from HHV-6 seropositive children aged 3 to 12 years and adults were cultured with HHV-6 antigen compared with control antigen. In contrast, cord blood mononuclear cells (CBMC) and PBMC from seronegative children did not show cell proliferation and changes in expression of IL-2Rs. In seropositive children less than 2 years of age, the magnitude of cell proliferation was low and IL-2Rs (alpha-, beta-, and gamma-chain) in CD8+ cells and IL-2Rs (alpha-chain) in CD45RO+ cells were increased. These data suggest that children below the age of 2 had immature lymphocytic response to HHV-6 antigen. Deletion of monocytes from PBMC and the addition of a mixture of anti-IL-2Rs (alpha-, beta-, and gamma-chain) antibodies reduced cell proliferation in response to HHV-6, suggesting the requirement of the presence of monocytes and expression of IL-2Rs.

Serum levels of Fas/Apo-1 and Bcl-2 in children with HIV-1 infection.

Apoptosis of CD4-positive T cells is considered to be involved in depletion of CD4-positive T cells in adult patients with HIV-1 infection. In this report we evaluated serum levels of soluble Fas/Apo-1 and circulating bcl-2 protein (an antiapoptotic molecule) in HIV-1-infected children, and 30 HIV-1 seronegative children. Significantly higher levels of Fas/Apo-1 were observed in 13 HIV-1-infected children than in non-infected control children (p < 0.001), whereas serum levels of bcl-2 were significantly decreased (p=0.002). Seronegative children born to HIV-infected mothers displayed significantly decreased (p < 0.05) serum levels of bcl-2. By contrast, children born to HIV-seronegative mothers and suffering from acute lower respiratory infection had normal levels of bcl-2 and Fas/Apo-1. These data suggest that upregulation of Fas/Apo-1 along with downregulation of bcl-2 protein may contribute to apoptosis in children with HIV-1 infection.

A long-term prospective study of varicella vaccine in healthy children.

Studies in Japan and the United States have shown that varicella vaccine is both safe and efficacious. In 1984, we undertook a 10-year prospective study using a research lot of Oka/Merck varicella vaccine to assess antibody persistence and breakthrough chickenpox rates. In 1987, we began a similar prospective study with lots made in production facilities that ended after 6 years because many children were given a second dose. The purpose of this study is to report humoral antibody persistence and breakthrough chickenpox rates after 6 to 10 years of prospective follow-up. One hundred forty-three seronegative children received a research lot (950 plaque-forming units/dose) with 97.9% seroconversion by an assay for fluorescent antibody to membrane antigen (FAMA). One hundred thirty-eight children received production lots (1145 to 3265 plaque-forming units/dose) with 93.5% seroconversion. Yearly chickenpox exposure surveys were completed by phone, and children were seen by a study nurse whenever chickenpox was suspected. A subset in each group had serum collected every 2 years and tested for FAMA antibody. In the research group there have been 25 cases of chickenpox in 137 seroconverters in a period of more than 10 years (yearly rate of 1.7%). In the production lot group there have been 22 cases of chickenpox in 129 seroconverters in a 6-year period (yearly rate of 2.8%). In the research group the median titer rose from 1:16 to 1:64 between 1 and 10 years. In the production group, the median titer did not change between 1, 2, and 4 years. Median antibody titers were compared between the research and production groups at 1, 2, and 4 years and did not differ. The rate of development of modified chickenpox has not increased with time since vaccination, and neither has the case severity. Children with FAMA titers </=8 at 6-weeks' postvaccination were four times more likely to develop chickenpox than those with titers >/=64. 1) Modified chickenpox has occurred in approximately 2% to 3% of vaccinees per year, regardless of the vaccine lot given. 2) FAMA titers have risen between 1 and 10 years in research lot recipients and remained the same in production lot recipients. 3) The likelihood of modified chickenpox developing is inversely related to the 6-week postvaccination FAMA titer.

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children

Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.

Altenative Routes of Measles Immunization: a Review

Measles is one of the major causes of childhood mortality in developing countries, despite current prevention of over 2 million child deaths each year by measles vaccination programmes. New strategies, such as mass campaigns, and possibly new preparations of measles vaccines, may facilitate further progress in controlling the disease and improving the prospects for its ultimate eradication. To evaluate the potential for non-percutaneous routes of vaccine administration to improve control, we reviewed studies of serological responses to measles vaccine after intradermal, conjunctival, oral, aerosol and intranasal administration.The response to intradermal vaccination exceeded percutaneous results in only one of eight instances in five studies where such comparisons could be made, often producing substantially lower seroresponses. Further, intradermal administration using a needle and syringe is more difficult than subcutaneous vaccination. After oral administration of vaccine, less than 50% of children seroconverted in three small studies. Intranasal administration has not yet been studied extensively, but it may be susceptible to interference by upper respiratory infections. Seroconversion after conjunctival administration was very variable, and this route was difficult practically in young children.In infants below 9 months of age, aerosol administration of vaccine resulted in 80% or better seroresponse in seven of nine trials, with the Edmonston–Zagreb strain in standard titre doses consistently producing better results than the Schwarz strain. However, seroresponses after subcutaneous administration clearly exceeded those from aerosols of the same vaccine in four of six comparisons. Several trials noted practical difficulties in aerosol administration in young infants. In contrast, older seronegative children generally responded well to aerosol administration of vaccine (above 90% and often 100% seroresponse), regardless of vaccine strain and often with surprisingly low estimated retained doses. In each of three studies where it was possible to compare the same vaccines given percutaneously and by aerosol to seropositive children, better seroresponses followed aerosols. In older children, aerosols of the Edmonston–Zagreb strain also rather consistently provided better seroresponses than aerosols of the Schwarz strain, with the most notable differences in seropositive children. Thus, with the possible exception of very young infants, the aerosol route is promising and offers several theoretical and practical advantages as well.Further randomized trials should be conducted to evaluate comparative responses to aerosolized, intranasal, and subcutaneous vaccine, especially in those age ranges targeted for mass campaigns (most commonly 9 months to 15 years). The development of improved technology for aerosol delivery of measles vaccine would greatly advance the potential for wide scale use of this route, especially in mass campaigns in low income countries.

Evaluation of bivalent live attenuated influenza A vaccines in children 2 months to 3 years of age: safety, immunogenicity and dose-response

1126 children, 2 months to 3 years old, received a single intranasal dose of 10 4, 10 6, or 10 7 TICD 50 of cold adapted (ca) A/Kawasaki/9/86 (H1N1) and A/Beijing/352/89 (H3N2) or placebo, in a double blind, placebo-controlled, safety and immunogenicity trial. No reactogenicity attributable to vaccine was demonstrated. A single bivalent 10 6 or 10 7 dose produced high rates of seroconversion to H1N1 (77%) and H3N2 (92%) in seronegative children > 6 months old; serologic responses were lower to H1N1 ( P < 0.001) and H3N2 ( P = 0.01) in younger infants. A single 10 6 dose of bivalent ca influenza A vaccine can be immunogenic in children, but response is age dependent.

Impact of HIV infection on the development, clinical presentation, and outcome of tuberculosis among children in Abidjan, Côte d'Ivoire.

To assess the impact of HIV infection upon the development, clinical presentation, and outcome of tuberculosis (TB) among children. Case-control study and prospective cohort study. From March 1994 to November 1995, children aged 0-9 years with newly diagnosed TB were enrolled at the two outpatient TB centers and the two principal university hospitals in Abidjan, Côte d'Ivoire. Children were examined, blood samples were collected for HIV serology and lymphocyte phenotyping, chest radiography was performed, and gastric aspirates and sputum samples were collected for acid-fast bacilli smear and culture. Children were then followed every 2 months during a standard 6-month course of anti-TB therapy. To examine risk factors for TB, age- and sex-matched healthy control children were enrolled from among the siblings of children referred for TB skin testing. Overall, 161 children with TB were enrolled, including 39 (24%) with culture-confirmed pulmonary TB, 80 (50%) with clinically diagnosed pulmonary TB, and 42 (26%) with extrapulmonary TB. Children with TB were significantly more likely than 161 control children to be HIV-seropositive (19 versus 0%), to have a past TB contact (55 versus 16%) and to live in very low socioeconomic status housing (24 versus 6%). No significant differences between HIV-seropositive and seronegative children were found in the distribution of radiologic abnormalities for pulmonary TB or in the site of extrapulmonary TB. The mortality rate in HIV-seropositive children was significantly higher than in seronegative children (23 versus 4%; relative risk, 3.6; 95% confidence interval, 2.0-6.6), and all deaths in HIV-seropositive children with available lymphocyte subtyping results occurred in those with a CD4 percentage of < 10%. This study documents the importance of HIV infection as an independent risk factor for the development of TB in children, and demonstrates that HIV-related immunosuppression is a critical risk factor for mortality in this population.

Nasopharyngeal pneumococcal colonization among Kenyan children: antibiotic resistance, strain types and associations with human immunodeficiency virus type 1 infection.

To compare pneumococcal nasopharyngeal colonization rates among HIV-1-infected children with those of uninfected children born to seropositive mothers and those of seronegative controls. To determine the predominant serotypes and antimicrobial susceptibility among pneumococcal isolates in Kenya. Nasopharyngeal pneumococcal colonization was examined in 207 children recruited from the Perinatal HIV-1 Transmission Study conducted in Nairobi, Kenya. Colonization was compared among HIV-1-infected children, uninfected children born to seropositive mothers and control seronegative children. Isolates were serotyped and tested for antibiotic susceptibility to penicillin, tetracycline, erythromycin, chloramphenicol, clindamycin and rifampin. Colonization was higher among HIV-1-infected and uninfected children than among controls only when associated with respiratory illnesses (86% of 7 and 60% of 20 vs. 29% of 31, P = 0.004). No differences were observed when children were asymptomatic (20% of 35, 35% of 94 and 22% of 101). Intermediate penicillin resistance was found in 60% of 94 isolates, 28% were resistant to tetracycline and all isolates were susceptible to the other antibiotics tested. Sixteen serotypes were identified, with 13, 15, 14, 6B and 19F comprising 73% of isolates. Serotype 13 was found in 31% of colonized children. This serotype and 2 others isolated are not found in the current 23-valent polysaccharide vaccine. Overall 41% of colonized children harbored nonvaccine strains. Although nasopharyngeal pneumococcal colonization was high among children with respiratory illness born to HIV-1-seropositive mothers, increased asymptomatic colonization did not explain the increased risk of invasive pneumococcal disease associated with HIV-1 infection. Intermediate penicillin resistance was common but high level penicillin and multiple antibiotic resistance were not seen. The prevalence of the unique strains circulating in this region will need to be considered in the design of effective pneumococcal vaccines for use in East Africa.

Further evaluation of the safety and protective efficacy of live attenuated hepatitis A vaccine (H2-strain) in humans

A study on the possibility of transmission of live hepatitis A vaccine (H2-strain) from vaccinees to nonvaccinees was conducted. As a result, no seroconversion was found among 87 seronegative nonvaccinees, who had a close contact with their 141 subcutaneously vaccinated classmates nor was it found among 101 seronegative children administered the vaccine orally. The above findings suggest that by losing the ability to be transmitted orally the vaccine virus may result in a decreasing possibility of dissemination among contacts. A 4-year study on the protective efficacy of the H2-strain vaccine was done at 11 primary schools starting at 1991 in Shaoxing County. Since then, there has been no hepatitis A reported among 18102 cumulative person-years in the vaccination group, while 495 cases occurred among 242168 cumulative person-years in the control groups. A large scale vaccination with a cumulative vaccination coverage of 89.45% was carried out in Jiaojiang City among children 1–15 years old. Hepatitis A in this age group in the city, which had 12–87 cases per annum with an average of 32 for 8 years before vaccination, decreased drastically to 0–1 cases after vaccination. The protective efficacy of H2-strain vaccine proved to be satisfactory.