The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000 -100,000 ring forms/mL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil. . Written informed consent was obtained from all subjects, and the ethical ferent regimens raises the cost and the chance of side effects guidelines for Universidade de São Paulo and Walter Reed Army Institute of and leads to poor compliance. The development of new Research were followed. drugs is costly and slow (relative to the development of para-

BACKGROUND: COVID-19 is affecting almost the entire world, causing more than four hundred thousand deaths and undermining the health care systems, as much as the economy, of the afflicted countries. The strategies for prevention depend on largely lacking information, as infection prevalence and virus pathogenicity. This study aimed to determine the prevalence, the pathogenicity, and the speed of infection spreading in a large population in Brazil. MATERIALS AND METHODS: This is a serial cross-sectional study designed on a population basis and structured over houses as the sampling units. The sampling consisted of four visits at 15 days intervals in randomly selected census-designated sectors of the State major municipalities (reference municipalities) and two visits at 30 days intervals in smaller municipalities of the same regions of those of reference. At each visit, the investigators sampled houses and sampled one individual in each house for data collection. After the informed consent, the investigators performed a rapid antibody detection test (Celer Technology, Inc) and applied a questionnaire containing clinical and demographic questions. RESULTS: From May 13th to 15th, the investigators performed 6,393 rapid tests in 4,612 individuals of the reference municipalities, 1,163 individuals of the smaller municipalities, and 166 contacts of the positive individuals. Ninety-seven dwellers were positive in the reference municipalities, giving a prevalence of 2.1% (CI 95%: 1.67-2.52%). In the smaller municipalities, the figure was 0.26% (CI 95%: 0.05%-0.75%) (three positives). There was an association of the positive result with female sex (p = 0.013) and houses with five dwellers or more (p = 0.003). Seventy-eight positive individuals reported symptoms in the previous 15 days (80.4%), being anosmia (45.4%), cough (40.2%), and myalgia (38.1%) the more frequent. About one-third of them reported fever (28.9%). CONCLUSIONS: The results reveal a still small prevalence of infection in the study area, despite the significant number of sick people overloading the health system. The figures indicate an important underreporting in the area and a frequency that still can grow, making necessary public health actions for the containment of the transmission.

BackgroundThe hypotheses put forward to explain the malaria transmission cycle in extra-Amazonian Brazil, an area of very low malaria incidence, are based on either a zoonotic scenario involving simian malaria, or a scenario in which asymptomatic carriers play an important role.ObjectivesTo determine the incidence of asymptomatic infection by detecting Plasmodium spp. DNA and its role in residual malaria transmission in a non-Amazonian region of Brazil.MethodsUpon the report of the first malaria case in 2010 in the Atlantic Forest region of the state of Espírito Santo, inhabitants within a 2 km radius were invited to participate in a follow-up study. After providing signed informed consent forms, inhabitants filled out a questionnaire and gave blood samples for PCR, and thick and thin smears. Follow-up visits were performed every 3 months over a 21 month period, when new samples were collected and information was updated.ResultsNinety-two individuals were initially included for follow-up. At the first collection, all of them were clearly asymptomatic. One individual was positive for Plasmodium vivax, one for Plasmodium malariae and one for both P. vivax and P. malariae, corresponding to a prevalence of 3.4% (2.3% for each species). During follow-up, four new PCR-positive cases (two for each species) were recorded, corresponding to an incidence of 2.5 infections per 100 person-years or 1.25 infections per 100 person-years for each species. A mathematical transmission model was applied, using a low frequency of human carriers and the vector density in the region, and calculated based on previous studies in the same locality whose results were subjected to a linear regression. This analysis suggests that the transmission chain is unlikely to be based solely on human carriers, regardless of whether they are symptomatic or not.ConclusionThe low incidence of cases and the low frequency of asymptomatic malaria carriers investigated make it unlikely that the transmission chain in the region is based solely on human hosts, as cases are isolated one from another by hundreds of kilometers and frequently by long periods of time, reinforcing instead the hypothesis of zoonotic transmission.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2263-z) contains supplementary material, which is available to authorized users.

Ninety-four patients with falciparum malaria were treated with mefloquine (1000-mg single dose) and remained hospitalized in a malaria-free area for a minimum of 28 days. There was 1 parasitologic failure (grade I resistance [RI]) for a 99% cure rate (95% confidence interval, 94.2%-99.7%). Mean parasite clearance time by thick smear was 45.7 h (SD, 11.4 h). The subject in whom therapy failed had a parasite clearance time (71 h) >2 SD above the population mean. His plasma mefloquine level 48 h after administration was lower (578 ng/mL) than the range of levels from 8 randomly selected cured subjects (834-2360 ng/mL). The IC50 to mefloquine for the recrudescent strain of the RI failure was in the upper 90th percentile of IC50 values from 30 cured subjects. These results show a high mefloquine cure rate but document the onset and mechanism of the emergence of resistance.