Safety and immunogenicity of two Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given with diphtheria-tetanus-pertussis vaccine to young Papua New Guinean children.

BACKGROUND: In view of high mortality and morbidity from Haemophilus influenzae type b (Hib) in young Papua New Guinean children, the incorporation of a Hib conjugate vaccine into a nationwide immunization program would be of major public health benefit. METHODS: We evaluated the safety and immunogenicity of a lyophilized and a liquid form of Hib polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given in the same syringe as diphtheria-tetanus-pertussis (DTP) vaccine to children in Goroka, Eastern Highlands Province. In Part 1 of the study 209 children were randomized to receive at ages 1, 2 and 3 months either DTP alone or a liquid formulation of DTP/PRP-T or lyophilized PRP-T dissolved in DTP suspension. A further 75 children were given the liquid DTP/PRP-T formulation at ages 2, 3 and 4 months (Part 2). 54 children aged 15-18 months were given a booster of the same preparation of PRP-T/DTP as they had received during Part 1. Blood for antibody assays was collected at enrolment, before (Part 1 only) and one month after the third dose, then just before and 3 weeks after the booster dose. RESULTS: Follow-up to age of 12 months showed that PRP-T was safe with no evidence of impaired response to individual vaccine components when combined with DTP. Geometric mean titres (GMTs) of anti-PRP antibody before vaccination (n = 64, mean age 41 days), after 2 doses (mean age 99 days) and after 3 doses (mean age 132 days) of the lyophilized formulation were 0.21, 1.48 and 5.04 microg/ml, respectively, with 58% and 89% having anti-PRP antibody titres > or = 1.0 microg/ml after 2 and 3 doses, respectively. Anti-PRP antibody responses to the liquid Hib vaccine formulation were lower (GMT post-dose 3 = 0.48 microg/ml) than to the lyophilized formulation, but better responses were elicited from older children (Part 2; GMT post-dose 3 = 0.78 microg/ml, with 79% > or = 0.15 microg/ml). Both PRP-T preparations elicited excellent booster responses suggesting that children are likely to be protected if exposed to Hib infection. CONCLUSIONS: Lyophilized PRP-T given together with DTP is safe and immunogenic when given to young infants. The liquid DTP/PRP-T formulation showed a lower immunogenicity than in earlier studies with this vaccine, which might have been due to exposure to low temperature during shipment or the younger age at immunization.

Bacterial, viral and parasitic aetiology of paediatric diarrhoea in the highlands of Papua New Guinea.

Enteropathogens and clinical features associated with diarrhoea were investigated in 1526 children admitted over a 5-year period to the paediatric ward of a hospital in the highlands of Papua New Guinea. Overall, a recognized pathogen was isolated from 39 per cent of the children admitted with diarrhoea. The most commonly isolated agents were rotavirus (23 per cent), Shigella spp. (13 per cent), Campylobacter spp. (12 per cent), Cryptosporidium parvum (10 per cent) and enteropathogenic Escherichia coli (8 per cent). The clearest clinical associations were rotavirus with vomiting, and Shigella with blood and pus in the stool. A control series of children admitted with other complaints was also included, and the odds ratios for diarrhoea for the above five pathogens were 18.2, 9.6, 3.7, 2.2, and 1.6, respectively.

Aetiology and clinical signs of bacterial meningitis in children admitted to Goroka Base Hospital, Papua New Guinea, 1989-1992.

Children aged 1-59 months admitted to Goroka Base Hospital with signs suggestive of meningitis were recruited to determine what proportion of such children have clinical or bacterial meningitis and to investigate the bacterial aetiology. A laboratory classification of definite, probable, possible, indeterminate and no meningitis was established. Thirty per cent of 697 children had a final clinical diagnosis of meningitis, 12% had culture-proven bacterial meningitis (case fatality rate 34%) and 10% had probable or possible meningitis. Inability to feed, vomiting, drowsiness, "staring eyes" and haemoglobin < 9 g/dl in addition to the classical signs of meningitis were associated with increased mortality. Isolates from cerebrospinal fluid were 62 pneumococci, 22 Haemophilus influenzae type b (Hib) and one Neisseria meningitidis. Including blood culture-proven and antigen-proven Hib disease, Hib and pneumococci accounted for 44% and 46% of bacterial meningitis, respectively, and 23% of pneumococci were intermediately resistant to penicillin. Inability to feed, bulging fontanelle, convulsions in young children, neck stiffness, fever and "staring eyes" were all independently associated with bacterial meningitis. Conjugate Hib vaccine must be given to infants as early as possible. Conjugate pneumococcal vaccines, maternal immunization with 23-valent vaccine and pneumococcal protein vaccines are under investigation for prevention of pneumococcal disease.

Arterial oxygen saturation in healthy young infants in the highlands of Papua New Guinea.

To determine the effect of moderate altitude on arterial oxygen saturation (SaO2), pulse oximetry was performed on 302 children aged <3 months attending a clinic in Goroka, Eastern Highlands Province (1584 metres above sea level) for minor ailments or immunization. Respiratory and heart rates were also measured. The overall mean SaO2 was 96%. Comparison between log-transformed means showed that SaO2 was significantly lower in the first month of life than later (p=0.04). 6% of SaO2 values were <92%, which is a practical cut-off for normal SaO2 in this population of highland children aged <3 months. Mean respiratory and heart rates were 50/minute and 145/minute, respectively. After adjusting for age, respiratory rate increased significantly as SaO2 declined (p=0.002). We have thus defined reference values for SaO2, respiratory rate and heart rate in healthy young infants residing in the highlands of Papua New Guinea. Further investigation is needed to determine whether SaO2 is lower in babies when they are asleep and to define reference values for older children in the highlands.

Safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine (PedvaxHIB) in Papua New Guinean children.

BACKGROUND: In view of high mortality and morbidity from Haemophilus influenzae type b (Hib) in young Papua New Guinean children, the incorporation of a Hib conjugate vaccine into a nationwide immunization program would be of major public health benefit. The choice of the Hib conjugate vaccine will be based on the evaluation of several Hib conjugate vaccines, after consideration of such factors as the ease of incorporation into the current vaccination schedule, cost, kinetics of antibody responses and safety. METHODS: This study evaluated the safety and immunogenicity of Hib polysaccharide-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMPC) in Papua New Guinea. 95 children were recruited at Goroka Base Hospital, Eastern Highlands Province, and enrolled in the study. PRP-OMPC was administered at ages 2, 4 and 12 to 15 months. Blood was collected before each dose, one month after the second and booster doses, and at ages 18 and 24 months. Antibody to PRP (anti-PRP) was measured by radioimmunoassay. RESULTS: PRP-OMPC was generally well tolerated. At successive sampling times from the prevaccination bleed through the 1-month post-booster bleed, geometric mean titres were 0.18, 1.45, 2.54, 1.03 and 8.05 micrograms/ml, respectively (n = 60). The proportions of subjects with anti-PRP titres > or = 1.0 microgram/ml were 2%, 62%, 73%, 47% and 93%, respectively (n = 60). Persistence of anti-PRP was ascertained in 41 subjects. The GMTs at 18 and 24 months were 3.42 and 2.0 micrograms/ml, respectively. CONCLUSIONS: PRP-OMPC was found to be immunogenic after the first dose and to elicit a robust booster response. Antibody titres persisted until age 24 months, at which time 100% of subjects had anti-PRP > or = 0.15 microgram/ml. These results are consistent with previous studies in US Native American infants and in Gambian infants.

A review of measles admissions and deaths in the paediatric ward of Goroka Base Hospital during 1989.

We reviewed all measles cases admitted to the paediatric ward of Goroka Base Hospital in 1989, and also interviewed a sample of measles patients attending the paediatric outpatient department. Measles accounted for 11% of all paediatric admissions and 32% of deaths. The case fatality rate for measles was 17%. Children with nosocomial infections and children with low birthweight were more likely to die. The most common complications of measles were pneumonia and diarrhoea, pneumonia being the most common cause of death. Twelve cases of subacute sclerosing panencephalitis were admitted during the year (0.5% of paediatric admissions). Measles was underreported because it was frequently omitted from the discharge diagnosis, the emphasis being placed on the complications. The majority of children with measles admitted to the ward and seen in outpatients had not been vaccinated. Nosocomial infections could have been reduced if all paediatric admissions aged 6-35 months had been vaccinated on admission. We strongly endorse the policy of vaccinating children in Papua New Guinea against measles from the age of 6 months.

PIP: The authors reviewed all measles cases admitted to the pediatric ward of Goroka Base Hospital in 1989, and also interviewed a sample of measles patients attending the pediatric outpatient department. Measles accounted for 11% of all pediatric admissions and 32% of deaths. The case fatality rate for measles was 17%. Children with nosocomial infections and those of low birthweight were more likely to die. The most common complications of measles were pneumonia and diarrhea, pneumonia being the most common cause of death. 12 cases of subacute sclerosing panencephalitis were admitted during the year (0.5% of pediatric admissions). Measles was underreported because it was frequently omitted from the discharge diagnosis, the emphasis being placed on complications. The majority of children with measles admitted to the ward and seen as outpatients had not been vaccinated. Nosocomial infections could have been reduced if all pediatric admissions ages 6-35 months had been vaccinated on admission. The authors strongly endorse the policy of vaccinating children in Papua New Guinea against measles from the age of 6 months.