Outcome of infants born to unbooked mothers: a short report from Goroka General Hospital, Eastern Highlands Province, Papua New Guinea.

Despite the increasing availability of antenatal care in Papua New Guinea (PNG), women continue to present for confinement without having previously attended antenatal clinic. In this brief report we present the findings of a five-year retrospective study conducted at Goroka General Hospital, Eastern Highlands Province, PNG. Mothers who had not previously accessed antenatal care ('unbooked mothers') were more likely to experience stillbirth or early neonatal death of their infant than booked mothers.

A neonatal pneumococcal conjugate vaccine trial in Papua New guinea: study population, methods and operational challenges.

Infants in Papua New Guinea (PNG) are at a high risk of invasive pneumococcal disease, and a substantial burden of this falls on children less than six months old. PNG is planning to introduce a pneumococcal conjugate vaccine for infants in the near future, but to make the maximum impact neonatal immunization will have to be considered. To provide evidence on safety and immunogenicity for neonatal and early infant immunization, we undertook an open randomized controlled trial of 7-valent pneumococcal conjugate vaccine (7vPCV). 318 children received 7vPCV at ages 0, 1 and 2 months or at 1, 2 and 3 months or not at all. All children received 23-valent pneumococcal polysaccharide vaccine at age 9 months. This was a large and complex trial: village reporters visited participants weekly during the first year and fortnightly for a further 6 months and nurses monitored self-reported morbidity and collected many thousands of biological samples. The study team was remarkably successful in achieving the study aims, with 18-month follow-up completed on 77% of enrolled children and over 80% of scheduled samples collected. While the results of the trial will be reported elsewhere, this paper discusses the design of the study and dissects out some of the main reasons for its successful completion. Strong community engagement was an essential factor in success and the principles of equitable partnership and service provision led to a strong research partnership. A two-stage consent process, comprising primary assent followed by later informed consent, led to a high drop-out before initial enrolment, but an outstanding retention of those enrolled in the study. We conclude that factors such as strong community participation, reciprocity and a good relationship between the study team and participants are just as important as the technical elements of laboratory testing and data handling in ensuring the success of a vaccine trial in PNG.

A neonatal pneumococcal conjugate vaccine trial in Papua New guinea: study population, methods and operational challenges

Infants in Papua New Guinea (PNG) are at a high risk of invasive pneumococcal disease, and a substantial burden of this falls on children less than six months old. PNG is planning to introduce a pneumococcal conjugate vaccine for infants in the near future, but to make the maximum impact neonatal immunization will have to be considered. To provide evidence on safety and immunogenicity for neonatal and early infant immunization, we undertook an open randomized controlled trial of 7-valent pneumococcal conjugate vaccine (7vPCV). 318 children received 7vPCV at ages 0, 1 and 2 months or at 1, 2 and 3 months or not at all. All children received 23-valent pneumococcal polysaccharide vaccine at age 9 months. This was a large and complex trial: village reporters visited participants weekly during the first year and fortnightly for a further 6 months and nurses monitored self-reported morbidity and collected many thousands of biological samples. The study team was remarkably successful in achieving the study aims, with 18-month follow-up completed on 77% of enrolled children and over 80% of scheduled samples collected. While the results of the trial will be reported elsewhere, this paper discusses the design of the study and dissects out some of the main reasons for its successful completion. Strong community engagement was an essential factor in success and the principles of equitable partnership and service provision led to a strong research partnership. A two-stage consent process, comprising primary assent followed by later informed consent, led to a high drop-out before initial enrolment, but an outstanding retention of those enrolled in the study. We conclude that factors such as strong community participation, reciprocity and a good relationship between the study team and participants are just as important as the technical elements of laboratory testing and data handling in ensuring the success of a vaccine trial in PNG.

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.

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.

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.

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.

Impact of active immunisation against enteritis necroticans in Papua New Guinea.

Enteritis necroticans, known locally as pigbel, has been a major cause of illness and death among children in the highlands of Papua New Guinea. After a successful trial of active immunisation against the beta toxin of the causative organism, Clostridium perfringens type C, immunisation of children was begun in 1980. The effects of the immunisation programme on pigbel admissions in 3 of the 5 major highland hospitals were assessed. In each of the centres studied the proportion of admissions due to enteritis necroticans dropped significantly after immunisation was introduced (p less than 0.001) and hospital admissions for pigbel in 1984-86, when immunisation was well established, were less than one fifth of previous figures.

Oral carriage of yeasts in two villages in Papua New Guinea.

Oral swabs were taken from 194 subjects in two villages in Papua New Guinea. Yeasts were isolated from 103 (53.1%) individuals of which 41 (21.1%) were Candida albicans. A wide variety of other yeasts were also identified.