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

Prevalence and genetic variants of G6PD deficiency among two Malagasy populations living in Plasmodium vivax-endemic areas

Abstract Background The prevalence and variants of G6PD deficiency in the Plasmodium vivax-endemic zones of Madagascar remain unknown. The admixed African-Austronesian origins of the Malagasy population make it probable that a heterogeneous mix of genetic variants with a spectrum of clinical severity will be circulating. This would have implications for the widespread use of P. vivax radical cure therapy. Two study populations in the P. vivax-endemic western foothills region of Madagascar were selected for G6PD screening. Both the qualitative fluorescent spot test and G6PD genotyping were used to screen all participants. Results A total of 365 unrelated male volunteers from the Tsiroanomandidy, Mandoto, and Miandrivazo districts of Madagascar were screened and 12.9% were found to be phenotypically G6PD deficient. Full gene sequencing of 95 samples identified 16 single nucleotide polymorphisms, which were integrated into a genotyping assay. Genotyping (n = 291) found one individual diagnosed with the severe G6PD Mediterranean C563T mutation, while the remaining G6PD deficient samples had mutations of African origin, G6PD A- and G6PD A. Conclusions Deployment of P. vivax radical cure in Madagascar must be considerate of the risks presented by the observed prevalence of G6PDd prevalence. The potential morbidity associated with cumulative episodes of P. vivax clinical relapses requires a strategy for increasing access to safe radical cure. The observed dominance of African G6PDd haplotypes is surprising given the known mixed African-Austronesian origins of the Malagasy population; more widespread surveying of G6PDd epidemiology across the island would be required to characterize the distribution of G6PD haplotypes across Madagascar

Multivariate predictors of malarial infection at double bleed time points diagnosed by light microscopy.

<p>GEE-model based estimates with semi-robust confidence intervals.</p><p>OR: Odds ratio. CI₉₅: 95% confidence intervals</p>1<p>Comparison level: Iliata 1. ² Comparison level: January. ³ Average bed net usage as continuous variable. ⁴Per g/dl increase.</p

Age dependence of risk of malarial illness: Effect of age at start of 8/9 weeks follow-up period on incidence of malarial illness with different parasite cut-offs.

<p>GEE model based estimates and semi-robust standard errors for age categories. Fitted lines: best fitting 1^st, 2^nd or 3^rd degree polynomials of age as continuous variable.</p

Multivariate predictors of incidence of infections in 8 × 8/9 weeks intervals: <i>P. vivax</i> and <i>P. malariae</i> episodes of different parasite density.

<p>GEE-model based estimates with semi-robust confidence intervals.</p><p>IRR: Incidence rate ratio. CI₉₅: 95% confidence intervals</p>1<p>Comparison level: Iliata 1. ² Comparison level: January. ³ Average bed net usage as continuous variable. ⁴Per g/dl increase.</p

Age dependence of risk of malarial infections: age-prevalence at 7 cross-sectional survey time points with 2 consecutive bleeds 24 hrs apart.

<p>GEE model based estimates and semi-robust standard errors for age categories. Fitted lines: best fitting 1^st, 2^nd or 3^rd degree polynomials of age as continuous variable.</p

Association of personal bed net use on risk of malarial infections and disease.

<p>Closes circles: univariate estimates, open triangle: adjusted for age and time trends, closed diamonds: age, time and village adjusted, open squares: estimates from best fitting model (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009047#pone-0009047-t001" target="_blank">Table 1</a> & <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009047#pone-0009047-t002" target="_blank">2</a>). All estimates from GEE model with semi-robust standard errors.</p

Prevalence of malaria at regular cross-sectional surveys: A) first samples only, B) double bleed samples 24 hrs apart, C) study retention profile.

<p>Prevalence of malaria at regular cross-sectional surveys: A) first samples only, B) double bleed samples 24 hrs apart, C) study retention profile.</p

Incidence of <i>P. falciparum</i> and <i>P. vivax</i> clinical episodes with different parasitaemia threshold for individual 8/9 weekly intervals.

<p>Incidence of <i>P. falciparum</i> and <i>P. vivax</i> clinical episodes with different parasitaemia threshold for individual 8/9 weekly intervals.</p