The epidemiology of malaria in the Papua New Guinea highlands: 7. Southern Highlands Province.

As the last part of a program to survey the extent of malaria transmission in the Papua New Guinea highlands, a series of rapid malaria surveys were conducted in 2003-2004 and 2005 in different parts of Southern Highlands Province. Malaria was found to be highly endemic in Lake Kutubu (prevalence rate (PR): 17-33%), moderate to highly endemic in Erave (PR: 10-31%) and moderately endemic in low-lying parts (< 1500 m) of Poroma and Kagua (PR: 12-17%), but was rare or absent elsewhere. A reported malaria epidemic prior to the 2004 surveys could be confirmed for the Poroma (PR: 26%) but not for the lower Kagua area. In Kutubu/Erave Plasmodium falciparum was the most common cause of infection (42%), followed by P. vivax (39%) and P. malariae (16%). In other areas most infections were due to P. vivax (63%). Most infections were of low density (72% < 500/ microl) and not associated with febrile illness. Overall, malaria was only a significant source of febrile illness when prevalence rates rose above 10%, or in epidemics. However, concurrent parasitaemia led to a significant reduction in haemoglobin (Hb) level (1.2 g/dl, CI95: [1.1-1.4.], p < 0.001) and population mean Hb levels were strongly correlated with overall prevalence of malarial infections (r = -0.79, p < 0.001). Based on the survey results, areas of different malaria epidemiology are delineated and options for control in each area are discussed.

Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children.

BACKGROUND: Where P. vivax and P. falciparum occur in the same population, the peak burden of P. vivax infection and illness is often concentrated in younger age groups. Experiences from malaria therapy patients indicate that immunity is acquired faster to P. vivax than to P. falciparum challenge. There is however little prospective data on the comparative risk of infection and disease from both species in young children living in co-endemic areas. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 264 Papua New Guinean children aged 1-3 years (at enrolment) were actively followed-up for Plasmodium infection and febrile illness for 16 months. Infection status was determined by light microscopy and PCR every 8 weeks and at each febrile episode. A generalised estimating equation (GEE) approach was used to analyse both prevalence of infection and incidence of clinical episodes. A more pronounced rise in prevalence of P. falciparum compared to P. vivax infection was evident with increasing age. Although the overall incidence of clinical episodes was comparable (P. falciparum: 2.56, P. vivax 2.46 episodes / child / yr), P. falciparum and P. vivax infectious episodes showed strong but opposing age trends: P. falciparum incidence increased until the age of 30 months with little change thereafter, but incidence of P. vivax decreased significantly with age throughout the entire age range. For P. falciparum, both prevalence and incidence of P. falciparum showed marked seasonality, whereas only P. vivax incidence but not prevalence decreased in the dry season. CONCLUSIONS/SIGNIFICANCE: Under high, perennial exposure, children in PNG begin acquiring significant clinical immunity, characterized by an increasing ability to control parasite densities below the pyrogenic threshold to P. vivax, but not to P. falciparum, in the 2(nd) and 3(rd) year of life. The ability to relapse from long-lasting liver-stages restricts the seasonal variation in prevalence of P. vivax infections.

Effect of the malaria vaccine Combination B on merozoite surface antigen 2 diversity.

Extensive genetic polymorphism is generally found in Plasmodium falciparum surface antigens. This poses a considerable obstacle to the development of a malaria vaccine. In order to assess possible effects of a polymorphic vaccine, we have analyzed the genetic diversity of parasites collected in the course of a phase 2b field trial of the blood stage vaccine Combination B in Papua New Guinea. The full-length 3D7 allele of the merozoite surface protein 2 (MSP2) was included in Combination B as one of three subunits. Vaccinees had a lower prevalence of parasites carrying a 3D7-type allele (corresponding to that in the vaccine) and selection appeared to favour the alternative FC27-type alleles resulting in a higher incidence of morbid episodes associated with FC27-type parasites. We sequenced MSP2 alleles detected in study participants after vaccination to identify breakthrough genotypes. Extensive genetic diversity of MSP2 was observed in both the repetitive and family-specific domains, but alleles occurring in vaccine recipients were no different from those found in placebo recipients. A phylogenetic analysis showed no clustering of 3D7-type breakthrough infections from vaccine recipients. The repeat unit present in the vaccine molecule occurred in a number of alleles from the trial area and was also observed in vaccinated individuals. Thus the anti-repeat immune response did not lead to elimination of parasites carrying the same repeat unit. We conclude that the conserved epitopes in the family-specific domain were the most important determinants of the vaccine effect against new 3D7-type infections and that the hypervariable domains were not subject to selective effects of the vaccine.