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Biomedical subjects

L Rare

Publications and source records attributed to L Rare.

6 recordsLinked to original sources

Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea.

A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels.

Adjuvants, Immunologic↗

The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea.

Zinc is crucial for normal immune function and can reduce morbidity from multiple infectious diseases. To determine the influence of zinc on malaria morbidity we conducted a randomized placebo-controlled trial of daily zinc supplementation in children residing in a malaria endemic region of Papua New Guinea. A total of 274 preschool children aged 6 to 60 months were given 10 mg elemental zinc (n = 136) or placebo (n = 138) for 6 days a week for 46 weeks. Slide-confirmed malaria episodes were detected by surveillance of cases self-reporting to a local health center. Cross-sectional surveys were conducted at the beginning, middle, and end of the study to assess infection rates, parasite density, spleen enlargement, and hemoglobin levels. Zinc supplementation resulted in a 38% (95% CI 3-60, P = 0.037) reduction in Plasmodium falciparum health center-based episodes, defined as parasitemia > or = 9200 parasites/microl with axial temperature > or = 37.5 degreesC or reported fever. Episodes accompanied by any parasitemia were also reduced by 38% (95% CI 5-60, P = 0.028), and episodes with parasitemia > or = 100,000/microl were reduced by 69% (95% CI 25-87, P = 0.009). There was no evidence of the effects of zinc on Plasmodium vivax morbidity or on health center attendance for causes other than P. falciparum. Zinc had no consistent effect on cross-sectional malariometric indices. Although P. falciparum prevalence tended to be lower at the end of the study in children given the placebo, such changes were absent at the mid-study survey. These results suggest that improved dietary zinc intake may reduce morbidity due to P. falciparum.

Animals↗

Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial.

BACKGROUND: Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. METHODS: This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P. falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose vitamin A (n=239) or placebo (n=241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. FINDINGS: The number of P. falciparum febrile episodes (temperature > or = 37.5 degrees C with a parasite count of at least 8000/microL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p=0.0013). At the end of the study P. falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p=0.093 and p=0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p=0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p=0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124], p=0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. INTERPRETATION: Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P. falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.

Child, Preschool↗

The effect of distance from home on attendance at a small rural health centre in Papua New Guinea.

BACKGROUND: The willingness of patients in the rural tropics to seek medical care at primary health care facilities is influenced by the distance they have to travel, but few studies have tried to estimate these distance effects. METHODS: Distance decay effects in attendance rates were estimated from a database of 4348 attendances at a rural health centre in Papua New Guinea, linked to demographic and house position data for the catchment population. Small-scale spatial patterns and differences between diagnoses, age groups and gender are described. RESULTS: Attendance decreased markedly with distance both overall (50% decrease at 3.5 km) and for patients with malaria or acute respiratory infections. This decrease was non-linear (on log scale) with distance. Although constant over time, there were big differences in this distance effect among age and gender groups: Female patients showed less distance decay in adolescents and adults, but higher in the infant group. Spatial patterns accounted for 32% of the variation in age- and gender-specific attendance rates. Of the spatial effects more than 50% were due to distance effects. CONCLUSIONS: Distance effects were similar in magnitude to those reported elsewhere, suggesting that distance effects may be generalizable to many parts of the rural tropics. The non-linearity of distance decay implies that a bell-shaped demand function should be used in health planning.

Adolescent↗

The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. II. Mortality and morbidity.

Malaria mortality and morbidity were studied in a rural population of 4000 in the Wosera area, East Sepik Province, Papua New Guinea. Malaria accounted for 4.9% of the 162 deaths investigated by verbal autopsy and for 12.2% of the 49 deaths assessed through medical records. Malaria was the first cause of death in children aged 0.5-4 years. Of the 7795 subjects interviewed and bled during six cross-sectional community-based surveys, children of 1-4 years had the highest malaria-related morbidity. In this age group, point prevalences of fever, fever associated with parasitaemia, and fever plus Plasmodium falciparum (Pf) parasitaemia > or = 10,000 parasites/microliters blood were 5%, 4.1% and 1.5%, respectively. The corresponding figures for adults were 2%, 0.9% and 0.1%, respectively. The calculation of attributable fraction (AF) using a multiple logistic regression model showed that malaria accounted for 0.44 of all fevers in children of 1-4 years and 0.08 of the fevers in adults. Prevalence data derived from the AF estimate were compared with those calculated using different accepted density thresholds. The prevalences which best approximated the results from the logistic regression model were obtained using parasitaemia cut-offs of > or = 1000 Pf parasites/microliter in children aged 1-4 years and adults older than 19 years and of > or = 10,000 parasites/microliter in those aged 5-19 years. Prevalence of fever associated with parasitaemia was highly seasonal, with a peak at the beginning of the wet season. The geographical distribution of malaria morbidity was not uniform. The measurement of malaria-related morbidity, the identification of significant seasonal and local variation as well as the assessment of different methods of defining a clinical episode of Pf malaria are crucial for the design and evaluation of intervention studies, including field trials of antimalarial vaccines.

Adolescent↗

Mosquito nets for the elderly?

Nine-year follow-up (ending 1999) of survival of 3738 individuals in a malaria-endemic area of Papua New Guinea found that the use of mosquito nets was associated with a large reduction in mortality in people aged > or = 40 years as well as in children aged < 5 years. There may be substantial benefits of malaria transmission reduction for older people, that have been overlooked in public health programmes and burden of disease calculations.

Adolescent↗