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Three different Plasmodium species show similar patterns of clinical tolerance of malaria infection.

Müller I, Genton B, Rare L, Kiniboro B, Kastens W, Zimmerman P, Kazura J, Alpers M, Smith TA - Malar. J. (2009)

Bottom Line: The incidence of attributable disease and parasite density broadly follow similar age patterns.P. falciparum shows more age variation in disease incidence at given levels of parasitaemia than the other species.A straightforward mathematical expression might be used to project disease burden from parasite density distributions assessed in community-based parasitological surveys.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Public Health & Epidemiology, Swiss Tropical Institute, Basel, Switzerland. ivomueller@fastmail.fm

ABSTRACT

Background: In areas where malaria endemicity is high, many people harbour blood stage parasites without acute febrile illness, complicating the estimation of disease burden from infection data. For Plasmodium falciparum the density of parasitaemia that can be tolerated is low in the youngest children, but reaches a maximum in the age groups at highest risk of infection. There is little data on the age dependence of tolerance in other species of human malaria.

Methods: Parasite densities measured in 24,386 presumptive malaria cases at two local health centres in the Wosera area of Papua New Guinea were compared with the distributions of parasite densities recorded in community surveys in the same area. We then analyse the proportions of cases attributable to each of Plasmodium falciparum, P. vivax, and P. malariae as functions of parasite density and age using a latent class model. These attributable fractions are then used to compute the incidence of attributable disease.

Results: Overall 33.3%, 6.1%, and 0.1% of the presumptive cases were attributable to P. falciparum, P. vivax, and P. malariae respectively. The incidence of attributable disease and parasite density broadly follow similar age patterns. The logarithm of the incidence of acute illness is approximately proportion to the logarithm of the parasite density for all three malaria species, with little age variation in the relationship for P. vivax or P. malariae. P. falciparum shows more age variation in disease incidence at given levels of parasitaemia than the other species.

Conclusion: The similarities between Plasmodium species in the relationships between parasite density and risk of attributable disease are compatible with the hypothesis that pan-specific mechanisms may regulate tolerance to different human Plasmodia. A straightforward mathematical expression might be used to project disease burden from parasite density distributions assessed in community-based parasitological surveys.

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Estimated operating characteristics of cutoffs. Receiver Operating Characteristic (ROC) curves of density cut-offs for the definition of P. falciparum and P. vivax clinical episodes. Shaded area: Sensitivity and Specificity > 80%. Density cutoffs: filled squares: 200/μl; open diamonds: 800/μl; filled circles: 3,200/μl; open squares 12,800/μl; filled diamonds: 40,000/μl.
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Figure 4: Estimated operating characteristics of cutoffs. Receiver Operating Characteristic (ROC) curves of density cut-offs for the definition of P. falciparum and P. vivax clinical episodes. Shaded area: Sensitivity and Specificity > 80%. Density cutoffs: filled squares: 200/μl; open diamonds: 800/μl; filled circles: 3,200/μl; open squares 12,800/μl; filled diamonds: 40,000/μl.

Mentions: The estimates of the sensitivity of diagnostic cut-offs by age and parasite density show the inverse pattern to the corresponding attributable fractions (Figure 4 and Additional file 1), indicating that a low cut-off is needed to ensure high sensitivity in older individuals, while in younger children, a higher cut-off can be used. The patterns are broadly similar for all three species. A high specificity is achieved, even with very low cut-offs for all age groups, and for all species, but particularly for P. malariae in which the presence of any patent parasitaemia in a clinical case has an estimated specificity of over 90% in all age groups.


Three different Plasmodium species show similar patterns of clinical tolerance of malaria infection.

Müller I, Genton B, Rare L, Kiniboro B, Kastens W, Zimmerman P, Kazura J, Alpers M, Smith TA - Malar. J. (2009)

Estimated operating characteristics of cutoffs. Receiver Operating Characteristic (ROC) curves of density cut-offs for the definition of P. falciparum and P. vivax clinical episodes. Shaded area: Sensitivity and Specificity > 80%. Density cutoffs: filled squares: 200/μl; open diamonds: 800/μl; filled circles: 3,200/μl; open squares 12,800/μl; filled diamonds: 40,000/μl.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719654&req=5

Figure 4: Estimated operating characteristics of cutoffs. Receiver Operating Characteristic (ROC) curves of density cut-offs for the definition of P. falciparum and P. vivax clinical episodes. Shaded area: Sensitivity and Specificity > 80%. Density cutoffs: filled squares: 200/μl; open diamonds: 800/μl; filled circles: 3,200/μl; open squares 12,800/μl; filled diamonds: 40,000/μl.
Mentions: The estimates of the sensitivity of diagnostic cut-offs by age and parasite density show the inverse pattern to the corresponding attributable fractions (Figure 4 and Additional file 1), indicating that a low cut-off is needed to ensure high sensitivity in older individuals, while in younger children, a higher cut-off can be used. The patterns are broadly similar for all three species. A high specificity is achieved, even with very low cut-offs for all age groups, and for all species, but particularly for P. malariae in which the presence of any patent parasitaemia in a clinical case has an estimated specificity of over 90% in all age groups.

Bottom Line: The incidence of attributable disease and parasite density broadly follow similar age patterns.P. falciparum shows more age variation in disease incidence at given levels of parasitaemia than the other species.A straightforward mathematical expression might be used to project disease burden from parasite density distributions assessed in community-based parasitological surveys.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Public Health & Epidemiology, Swiss Tropical Institute, Basel, Switzerland. ivomueller@fastmail.fm

ABSTRACT

Background: In areas where malaria endemicity is high, many people harbour blood stage parasites without acute febrile illness, complicating the estimation of disease burden from infection data. For Plasmodium falciparum the density of parasitaemia that can be tolerated is low in the youngest children, but reaches a maximum in the age groups at highest risk of infection. There is little data on the age dependence of tolerance in other species of human malaria.

Methods: Parasite densities measured in 24,386 presumptive malaria cases at two local health centres in the Wosera area of Papua New Guinea were compared with the distributions of parasite densities recorded in community surveys in the same area. We then analyse the proportions of cases attributable to each of Plasmodium falciparum, P. vivax, and P. malariae as functions of parasite density and age using a latent class model. These attributable fractions are then used to compute the incidence of attributable disease.

Results: Overall 33.3%, 6.1%, and 0.1% of the presumptive cases were attributable to P. falciparum, P. vivax, and P. malariae respectively. The incidence of attributable disease and parasite density broadly follow similar age patterns. The logarithm of the incidence of acute illness is approximately proportion to the logarithm of the parasite density for all three malaria species, with little age variation in the relationship for P. vivax or P. malariae. P. falciparum shows more age variation in disease incidence at given levels of parasitaemia than the other species.

Conclusion: The similarities between Plasmodium species in the relationships between parasite density and risk of attributable disease are compatible with the hypothesis that pan-specific mechanisms may regulate tolerance to different human Plasmodia. A straightforward mathematical expression might be used to project disease burden from parasite density distributions assessed in community-based parasitological surveys.

Show MeSH
Related in: MedlinePlus