Clinical spectrum of uncomplicated malaria in semi-immune Amazonians: beyond the " symptomatic " vs " asymptomatic " dichotomy

Abstract

We analyzed prospectively 326 laboratory-confirmed, uncomplicated malarial infections (46.3% due to Plasmodium vivax, 35.3% due to P. falciparum, and 18.4% mixed-species infections) diagnosed in 162 rural Amazonians aged 5-73 years. Thirteen symptoms (fever, chills, sweating, headache, myalgia, arthralgia, abdominal pain, nausea, vomiting, dizziness, cough, dyspnea, and diarrhea) were scored using a structured questionnaire. Headache (59.8%), fever (57.1%), and myalgia (48.4%) were the most frequent symptoms. Ninety-six (29.4%) episodes, all of them diagnosed during cross-sectional surveys of the whole study population (96.9% by molecular technique only), were asymptomatic. Of 93 symptom-less infections left untreated, only 10 became symptomatic over the next two months following diagnosis. Fever was perceived as "intense" in 52.6% of 230 symptomatic malaria episodes, with no fever reported in 19.1% episodes although other symptoms were present. We found significant differences in the prevalence and perceived intensity of fever and other clinical symptoms in relation to parasite load at the time of diagnosis and patient's age, cumulative exposure to malaria, recent malaria morbidity, and species of malaria parasite. These factors are all likely to affect the effectiveness of malaria control strategies based on active or passive detection of febrile subjects in semi-immune populations.

No Clinical or Molecular Evidence of Plasmodium falciparum Resistance to Artesunate–Mefloquine in Northwestern Brazil

“…Uncomplicated P. falciparum malaria patients commonly reported dizziness before any treatment; for example, a recent case series found a prevalence of 75% at presentation in Brazil. 25 However, dizziness and other neurologic and psychiatric symptoms are often reported to be associated with MQ administration either for malaria chemoprophylaxis or treatment, mostly in subjects reporting previous neuropsychiatric disease. For this reason, since 2013, the Food and Drug Administration of the United States requests MQ to carry a black box warning on its potential neurological and psychiatric side effects in the drug label (http://www.fda.gov/downloads/ Drugs/DrugSafety/UCM362232.pdf).…”

The silent threat: asymptomatic parasitemia and malaria transmission

“…The few studies that have attempted to capture all new infections over a period of time, both symptomatic and asymptomatic, have found a lower proportion of asymptomatic infections using cumulative incidence than point prevalence. Employing a combination of passive and active case detection over a 14-month period to identify all new malaria infections in an area of Brazil, 326 episodes of malaria were identified, of which 96 (29.4%) were asymptomatic at the time of diagnosis [50] -a proportion much lower than has been found in any cross-sectional survey.…”

“…Few comparisons of the prevalence of symptoms among individuals infected with P. falciparum and P. vivax have been conducted in areas where the two species are sympatric, and results are contradictory. Using microscopy to diagnose infections, a larger proportion of P. f alciparum infections (37.5%) compared with P. vivax infections (18.5%) in Brazil were asymptomatic (presenting with none of the 13 malarial symptoms) [50]. In comparison, a greater proportion of P. vivax infections (97.1%) in the Solomon Islands compared with P. falciparum infections (82.2%) were asymptomatic (axillary temperature: <38°C) [51].…”

“…In Brazil, 93 asymptomatic (presenting with none of 13 malarial symptoms) infections in 33 persons aged 5 years and older were followed for 2 months after their infection was identified and ten (10.7%) became symptomatic during that period [50]. However, the background transmission rate would suggest that eight of those cases could have been the result of new infections.…”

High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

“…Yet, in malaria-endemic regions, asymptomatic malaria parasitemia, with degrees of prevalence that are geographically variable, is common. [11][12][13][14][15][16][17][18] This observation has raised two important hypotheses: 1) that asymptomatic parasitemia may contribute significantly to maintaining malaria transmission in endemic regions; and 2) different Plasmodium falciparum or P. vivax clones may differ in virulence, some more likely than others to result in symptoms. Substantial data support the former hypothesis; few data to date support the latter.…”