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 and viral etiology of severe infection in children less than three months old in the highlands of Papua New Guinea.

OBJECTIVE: Determine the bacterial and viral etiology of severe infection in young Papua New Guinean infants as part of a multicenter study in four developing countries aimed at improving case management guidelines. METHODS: Between March, 1991, and April, 1993, children aged <3 months were recruited at the outpatient department of Goroka Base Hospital, Papua New Guinea (PNG). Children with pre-defined inclusion criteria were enrolled, a history was taken and clinical examination was performed. Blood and urine were collected from children with signs suggestive of severe disease together with eye, umbilical and pernasal swabs as appropriate. Nasopharyngeal aspirates (NPAs) were collected from children with and without signs of severe disease for identification of viruses and Chlamydia trachomatis by direct fluorescent antibody staining. RESULTS: 3280 infants were triaged and 2168 enrolled, among whom 968 had signs suggestive of severe disease. Group A Streptococcus (Streptococcus pyogenes) and Staphylococcus aureus were the most important bacterial pathogens isolated from children < 1 month old with severe infections, and Streptococcus pneumoniae, S. pyogenes and Staphylococcus aureus were most important in older children. Of 292 eye swabs 19 (7%) grew Neisseria gonorrhoeae. Of 116 umbilical swabs 51 (44%) grew S. pyogenes and 45 (39%) grew Staphylococcus aureus. Respiratory syncytial virus was the most important viral cause of acute lower respiratory infection. CONCLUSIONS: S. pyogenes, S. pneumoniae and Staphylococcus aureus are important causes of severe infection in young children in the PNG highlands. It is necessary to improve access to clean water, promote hand-washing in the hospital and at home and investigate further the use of maternal immunization for the prevention of severe disease in young infants.

High rates of Chlamydia trachomatis infections in young Papua New Guinean infants.

OBJECTIVE: Determine the importance of Chlamydia trachomatis in the etiology of severe infection in young Papua New Guinean infants. METHODS: Between March, 1991, and April, 1993, children <3 months old were recruited as outpatients at Goroka Base Hospital, Papua New Guinea, as part of a multicenter study in four developing countries. Children with predefined inclusion criteria were enrolled. C. trachomatis was identified by direct fluorescent antibody staining in nasopharyngeal aspirates (NPAs) collected from children with and without signs of severe disease and eye swabs from children with and without conjunctivitis. Two to three radiologists read chest radiographs without knowledge of clinical and laboratory findings. RESULTS: Of 3280 outpatients seen 2168 enrolled, 955 NPAs were tested for C. trachomatis and 549 chest radiographs were read. Of 210 eye swabs from children with conjunctivitis 57% were positive for C. trachomatis compared with 8% from 167 children with no conjunctivitis. The prevalence of C. trachomatis in NPAs was 9% in asymptomatic children and 18 and 33% in children with nonsevere or severe pneumonia, respectively. C. trachomatis in NPAs was strongly associated with clinically severe pneumonia [odds ratio (OR), 2.91], reduced arterial oxygen saturation (OR 2.58) and radiographic evidence of pneumonia (OR 5.84) and was also associated with pneumococcal bacteremia (OR 3.48). CONCLUSIONS: In Papua New Guinea Chlamydia must be considered as a cause when treating pneumonia in infants, and effective treatment and prevention of sexually transmitted diseases are urgently needed for a number of reasons, including the need to curb high rates of chlamydial infection in women and infants.

Mortality rates and the utilization of health services during terminal illness in the Asaro Valley, Eastern Highlands Province, Papua New Guinea.

Between 1980 and 1989 we carried out fortnightly demographic surveillance in a random sample of people living in Goroka town, periurban areas and rural areas in the Lowa and Asaro Census Divisions, all within 1 1/2 hours' drive of the town in the Asaro Valley, Eastern Highlands Province. Cause of death was determined by verbal autopsy supplemented by any available health service information. Crude death and birth rates were 10 and 32 per 1000 person-years, respectively, in 59,906 person-years at risk. The standardized mortality ratio increased with increasing distance from town. Life expectancy at birth was 57 years for males and 55 years for females. The stillbirth rate was 19 per 1000 births, neonatal and infant mortality 21 and 60 per 1000 livebirths, respectively, and 1-4-year mortality 9 per 1000 person-years. Maternal mortality was 3 per 1000 births. Neonatal and infant mortality were respectively 7 and 3 times as high in Asaro Census Division as in Goroka town. Acute lower respiratory tract infections accounted for 22% of all deaths, chronic obstructive lung disease 10%, trauma 8% and gastroenteritis/dysentery 7%. 76% of deaths occurred at home and 44% of people who died had no treatment during their terminal illness. Health services were used most frequently by urban dwellers and by the young. To reduce mortality, a political commitment to provide functioning health services in rural areas is needed; regular supervision of health staff, ensuring the safety of staff and their families, availability of antibiotics as near people's homes as possible and regular mobile maternal and child health clinics are essential. Health education should include recognition of signs of severe disease and the importance of seeking treatment early. In view of high maternal and neonatal mortality, user fees should be waived for pregnant women.

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.

Diarrhoea morbidity in children in the Asaro Valley, Eastern Highlands Province, Papua New Guinea.

A morbidity study of diarrhoea covering 1926 children aged less than 5 years was carried out in Goroka town and the Lowa and Asaro Census Divisions, Eastern Highlands Province between 1986 and 1989. The study involved weekly demographic surveillance of the total population and morbidity surveillance of children by lay reporters who enquired about the presence or absence on any of the preceding 8 days of a range of symptoms associated with diarrhoeal and respiratory diseases. A three-day symptom-free period was used to define distinct episodes of diarrhoea. The average number of episodes/child-year for all children in the study population was 3.0. Boys suffered a significantly higher incidence of diarrhoea under 48 months of age than girls (4.4 episodes compared to 3.6/child-year). Incidence was highest among those aged 6-17 months (5.5/child-year) with a rapid decline after age 35 months. Incidence of diarrhoea was highest in the more remote Asaro Census Division and was higher in periurban areas than in Goroka town. Incidence also varied significantly between villages, some villages experiencing up to 10 times the incidence of diarrhoea found in Goroka town. The incidence of diarrhoea was significantly higher in January than at other times of year. Duration of diarrhoea varied with age, the longest duration being an average of 4.7 days in the 12-17 months age group. In order to reduce diarrhoea morbidity, it is necessary to improve access to water, encourage improved hygiene practices and breastfeeding and warn people about the risks of sleeping with pigs.

PIP: A morbidity study of diarrhea covering 1926 children aged less than 5 years was carried out in Goroka town and the Lowa and Asaro Census Divisions, Eastern Highlands Province between 1986 and 1989. The study involved weekly demographic surveillance of the total population and morbidity surveillance of children by lay reporters who enquired about the presence or absence on any of the preceding 8 days of a range of symptoms associated with diarrheal and respiratory diseases. A 3-day symptom-free period was used to define distinct episodes of diarrhea. The average number of episodes/child-year for all children in the study population was 3.0. Boys suffered a significantly higher incidence of diarrhea under 48 months of age than girls (4.4 episodes/child-year compared to 3.6 episodes/child-year). Incidence was highest among those aged 6-17 months (5.5 episodes/child-year) with a rapid decline after age 35 months. Incidence of diarrhea was highest in the more remote Asaro Census Division and was higher in periurban areas than in Goroka town. Incidence also varied significantly between villages, some villages experiencing up to 10 times the incidence of diarrhea found in Goroka town. The incidence of diarrhea was significantly higher in January than at other times of year. Duration of diarrhea varied with age, the longest duration being an average of 4.7 days in the 12-17 months age group. In order to reduce diarrhea morbidity, it is necessary to improve access to water, encourage improved hygiene practices and breastfeeding and warn people about the risks of sleeping with pigs.