The risk of malarial infections and disease in Papua New Guinean children

Abstract

In a treatment re-infection study of 206 Papua New Guinean school children, we examined risk of reinfection and symptomatic malaria caused by different Plasmodium species. Although children acquired a similar number of polymerase chain reaction-detectable Plasmodium falciparum and P. vivax infections in six months of active follow-up (P. falciparum = 5.00, P. vivax = 5.28), they were 21 times more likely to develop symptomatic P. falciparum malaria (1.17/year) than P. vivax malaria (0.06/year). Children greater than nine years of age had a reduced risk of acquiring P. vivax infections of low-to-moderate (>150/microL) density (adjusted hazard rate [AHR] = 0.65 and 0.42), whereas similar reductions in risk with age of P. falciparum infection was only seen for parasitemias > 5,000/microL (AHR = 0.49) and symptomatic episodes (AHR = 0.51). Infection and symptomatic episodes with P. malariae and P. ovale were rare. By nine years of age, children have thus acquired almost complete clinical immunity to P. vivax characterized by a very tight control of parasite density, whereas the acquisition of immunity to symptomatic P. falciparum malaria remained incomplete. These observations suggest that different mechanisms of immunity may be important for protection from these malaria species.

Figure 1

Location of study site, schools, and participants’ houses in Papua New Guinea.

Figure 2

Prevalence of malarial infections at baseline and at active bi-weekly follow-up obtaining of blood samples. Top, Diagnosis by light microscopy (LM). Bottom, Diagnosis using post–polymerase chain reaction and ligation detection reaction–fluorescent microsphere assay (LDR-FMA). The number of children at risk, treated, and withdrawn during each two-week period and number of children seen during each follow-up are shown below the bottom panel.

Figure 3

Risk of acquiring new infections after treatment of blood-stage infections. Kaplan-Meier curves for A, Asymptomatic infections diagnosed by post–polymerase chain reaction and ligation detection reaction–fluorescent microsphere assay (LDR-FMA), B, Asymptomatic infections diagnosed by light microscopy (LM), and C, Episodes of febrile illness with concurrent malarial infection of any density (by LM).

Figure 4

Kaplan-Meier curves of time to first Plasmodium falciparum (Pf) and P. vivax (Pv) infections exceeding increasing density thresholds. LM = positive by light microscopy; LDR-FMA = positive by post–ligation polymerase chain reaction ligation detection reaction–fluorescent microsphere assay. Shown are species-specific density cut-offs: higher cut-offs are set at species-specific pyrogenic thresholds and lower cut-offs are set at approximately 1.5 times the geometric mean density observed at baseline.

Figure 5

Risk of acquiring new infections in relations to age and increasing density cut-offs. Values are adjusted hazard ratios and 95% confidence intervals. ● = Plasmodium falciparum (Pf); ○ = P. vivax (Pv). Because of low number of infections, no age effect for Pv parasitemias > 1,000/mL was estimated. LDR-FMA = positive by post–polymerase chain reaction ligation detection reaction–fluorescent microsphere assay; LM = positive by light microscopy. Shown are species-specific density cut-offs: higher cut-offs for Pf are set at species-specific pyrogenic thresholds and lower cut-offs set at approximately 1.5 times the geometric mean density observed at baseline.

Figure 6

Kaplan-Meier curves of risk of experiencing an episode of symptomatic Plasmodium falciparum (Pf) malaria with a parasite density greater than 5,000 parasites/μL in relation to age.