Changing malaria epidemiology and diagnostic criteria for Plasmodium falciparum clinical malaria.

BACKGROUND: In tropical Africa, where malaria is highly endemic, low grade infections are asymptomatic and the diagnosis of clinical malaria is usually based on parasite density. Here we investigate how changes in malaria control and endemicity modify diagnostic criteria of Plasmodium falciparum attacks. METHODS AND FINDINGS: Parasitological and clinical data from the population of Dielmo, Senegal, monitored during 20 years, are analyzed in a random-effect logistic regression model to investigate the relationship between the level of parasitemia and risk of fever. Between 1990 and 2010, P. falciparum prevalence in asymptomatic persons declined from 85% to 1% in children 0-3 years and from 34% to 2% in adults ≥50 years. Thresholds levels of parasitemia for attributing fever episodes to malaria decreased by steps in relation to control policies. Using baseline threshold during following periods underestimated P. falciparum attacks by 9.8-20.2% in children and 18.9-40.2% in adults. Considering all fever episodes associated with malaria parasites as clinical attacks overestimated P. falciparum attacks by 42.2-68.5% in children and 45.9-211.7% in adults. CONCLUSIONS: Malaria control modifies in all age-groups the threshold levels of parasitemia to be used for the assessment of malaria morbidity and to guide therapeutic decisions. Even under declining levels of malaria endemicity, the parasite density method must remain the reference method for distinguishing malaria from other causes of fever and assessing trends in the burden of malaria

Age distribution of parasite rate, classes of parasite density and the mean <i>P. falciparum</i> parasitemia observed during all causes of fever episodes (geometric mean of trophozoites per µl of blood) for each study period.

<p>Age distribution of parasite rate, classes of parasite density and the mean <i>P. falciparum</i> parasitemia observed during all causes of fever episodes (geometric mean of trophozoites per µl of blood) for each study period.</p

Number of <i>P. falciparum</i> malaria attacks by treatment period and age according to three definitions of malaria attacks: A. Fever or fever-related symptoms plus parasitemia higher than the period specific threshold level.

<p>B. Fever or fever-related symptoms plus parasitemia higher than the baseline threshold. C. Fever or fever-related symptoms plus any level of parasitemia. Values in bracket with definition B indicate the proportion of underdiagnosed malaria attacks compared to definition A. Values in bracket with definition C indicate the proportion of overdiagnosed malaria attacks compared to definition A. Dielmo, October 1990–December 2010.</p

Random-effect logistic regression model derived threshold levels of parasitemia for attributing fever episodes to <i>P. falciparum</i> malaria by age and periods.

<p>Random-effect logistic regression model derived threshold levels of parasitemia for attributing fever episodes to <i>P. falciparum</i> malaria by age and periods.</p

Age distribution of parasite rate, classes of parasite density and the mean <i>P. falciparum</i> asymptomatic parasitemia (geometric mean of trophozoites per µl of blood) in control observations for each study period.

<p>Age distribution of parasite rate, classes of parasite density and the mean <i>P. falciparum</i> asymptomatic parasitemia (geometric mean of trophozoites per µl of blood) in control observations for each study period.</p

Estimates of the parameters defining the age-dependent pyrogenic threshold according to study period.

<p>Estimates of the parameters defining the age-dependent pyrogenic threshold according to study period.</p

One hundred malaria attacks since birth. A longitudinal study of African children and young adults exposed to high malaria transmissionResearch in context

Summary: Background: Despite significant progress in malaria control over the past twenty years, malaria remains a leading cause of child morbidity and mortality in Tropical Africa. As most patients do not consult any health facility much uncertainty persists about the true burden of the disease and the range of individual differences in susceptibility to malaria. Methods: Over a 25-years period, from 1990 to 2015, the inhabitants of Dielmo village, Senegal, an area of intense malaria transmission, have been monitored daily for their presence in the village and the occurrence of diseases. In case of fever thick blood films were systematically examined through microscopy for malaria parasites and patients received prompt diagnosis and treatment. Findings: We analysed data collected in 111 children and young adults monitored for at least 10 years (mean 17.3 years, maximum 25 years) enrolled either at birth (95 persons) or during the two first years of life. A total of 11,599 episodes of fever were documented, including 5268 malaria attacks. The maximum number of malaria attacks in a single person was 112. Three other persons suffered one hundred or more malaria attacks during follow-up. The minimum number of malaria attacks in a single person was 11. The mean numbers of malaria attacks in children reaching their 4th, 7th, and 10th birthdays were 23.0, 37.7, and 43.6 attacks since birth, respectively. Sixteen children (14.4%) suffered ten or more malaria attacks each year at ages 1–3 years, and six children (5.4%) each year at age 4–6 years. Interpretation: Long-term close monitoring shows that in highly endemic areas the malaria burden is higher than expected. Susceptibility to the disease may vary up to 10-fold, and for most children childhood is an endless history of malaria fever episodes. No other parasitic, bacterial or viral infection in human populations has such an impact on health. Funding: The Pasteur Institutes of Dakar and Paris, the Institut de Recherche pour le Développement, and the French Ministry of Cooperation provided funding