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CDC Travel Notice: Malaria in Brazil

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A malaria outbreak has been reported in the town of Wenceslau Guimarães in Bahia State, Brazil. Antimalarial medication is now recommended for travelers to this area.

CDC has received reports of an outbreak of P. vivax malaria in Wenceslau Guimarães. Bahia State is not a malaria-endemic area. However, in the town of Wenceslau Guimarães there were 21 locally transmitted cases reported January 16–22. The Brazilian Ministry of Health and the public health authorities in Bahia State are continuing to monitor and respond to this outbreak.

As Bahia State is not a malaria-endemic area, CDC has previously not recommended malaria prophylaxis. However, with this focal outbreak, CDC now recommends that travelers to the town of Wenceslau Guimarães in Bahia State take antimalarials to prevent malaria. Effective antimalarial options for P. vivax include atovaquone-proguanil, chloroquine, doxycycline, mefloquine, and in those without glucose-6-phosphate dehydrogenase deficiency, primaquine. CDC will continue to monitor the malaria situation in Bahia State and will update these recommendations as needed.

Check our updated travel notice.

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\ \ The number of US students studying abroad has tripled over the past 20 years. Kristina Angelo, one of CDC Travelers’ Health experts, recommends that health care practitioners emphasize location-specific disease risks during pre-travel consultations, particularly for diseases with a high prevalence in the destination or diseases with high morbidity or mortality, such as malaria. Check out Kristina’s recently published article in the Journal of Travel Medicine, Illness among US resident student travelers after return to the USA: a GeoSentinel Analysis](https://app.figure1.com/case-detail/018d764f-4f71-49d6-b3ad-d9d712255251)

\ \ Rapid tests for diagnosing malaria caused by Plasmodium vivax in people living in areas where malaria is very common\ What is the aim of the review?\ Malaria infection is caused mainly by two species of malaria parasite: Plasmodium falciparum and Plasmodium vivax. The aim of this review was to evaluate rapid diagnostic tests (RDTs) to diagnose P vivax infection.\ Why are rapid tests for P vivax malaria important?\ For clinical management, knowing which parasite species is causing the malaria is important as the drug treatments differ. For P vivax infection, an additional drug is required to eliminate the infection from the liver. For public health control of malaria, we know that P falciparum is declining over the previous 15 years, and infections from P vivax have therefore increased in importance.\ What was studied in this review?\ RDTs provide results quickly and are often as a dipstick. We studied RDTs that specifically test for P vivax malaria. RDTs are simple to use, point‐of‐care tests. They are suitable for use in rural settings by primary healthcare workers, using drop of blood on the dipstick that causes colour change and a distinct line that indicates a positive test result. Healthcare workers in rural areas can perform RDTs for P vivax without needing a laboratory or special equipment. We wanted to find out which brands of RDTs were the most accurate for diagnosing P vivax malaria. We compared the new tests against the standard form of diagnosis with microscopy, and also more recent methods polymerase chain reaction (PCR): a molecular method to identify P vivax DNA in blood samples.\ What are the main results of the review?\ We included 10 studies that looked at the accuracy of six diagnostic test brands for detecting P vivax malaria in people with suspected malaria symptoms. The studies were conducted in Ethiopia (four studies), India (two studies) and Bangladesh, Brazil, Colombia, and Sudan (one study each).\ Compared with microscopy, the Care Start Malaria Pf/Pv Combo test performed well with 99% sensitivity and specificity (four studies). This means that:\ • for every 100 people tested who have P vivax malaria, one person will have a negative test result, and might not receive the right treatment soon enough;\ • for every 100 people tested who do not have P vivax malaria, one will have a positive result, and might receive unnecessary treatment.\ Compared with microscopy, the Falcivax Device Rapid test had a sensitivity of 77% and a specificity of 99% (two studies). This means that:\ • For every 100 people tested who have P vivax malaria, 23 people will have a negative test result; and,\ • for every 100 people tested who do not have P vivax malaria, one person will have a positive result.\ We are moderately confident (certain) in the accuracy results for the Care Start Malaria Pf/Pv Combo test. The results are from a small number of studies (four), so our findings may change when results from further studies become available.\ We are less confident in the accuracy results for the Falcivax Device Rapid test, because these came from only two studies. Our findings for this test will probably change when results from further studies become available.\ Our results are based on a small number of studies, so we could not reliably assess all six brands of antibody test or compare their accuracy. Most studies included in this review had limitations: it was not clear how people were selected for testing, or how the study results were assessed and checked, which could have affected the results. Some rapid antibody tests were investigated by only one study. Some studies did not report clearly how common P malaria was in the area where the study was done.\ How up‐to‐date is this review?\ The review authors searched for studies published up to 30 July 2019.](https://app.figure1.com/case-detail/04cd14a2-cd8d-4352-935a-48b1862bfe72)

\ \ What are the benefits and risks of atovaquone‐proguanil for treating uncomplicated malaria caused by the Plasmodium falciparum parasite?\ What is the aim of this review?\ The most common, and most serious, type of malaria is caused by Plasmodium falciparum. In its mild (uncomplicated) form, the symptoms are fever, headaches, muscle pain, and vomiting. The disease can become severe and life‐threatening if it is not treated soon enough or with the right medicines.\ This review aimed to find out whether atovaquone‐proguanil is effective and safe for treating uncomplicated cases of P falciparum malaria. We aimed to achieve this by comparing the results of studies that had compared atovaquone‐proguanil to other malaria treatments.\ Key messages\ Atovaquone‐proguanil is as effective for treating uncomplicated Plasmodium falciparum malaria as artesunate‐mefloquine. It may be less effective than artemether‐lumefantrine, artesunate‐amodiaquine, and artesunate‐atovaquone‐proguanil, though more robust evidence is needed to confirm this. Side effects seem similar with atovaquone‐proguanil.\ What was studied in this review?\ The World Health Organization (WHO) recommends treating uncomplicated malaria with oral (by mouth) artemisinin‐based combination medicines (called ACTs).\ ACTs are not always available worldwide and, in some places, Plasmodium falciparum is becoming resistant to recommended treatments (the medicines stop working). We looked at the evidence about the benefits and harms of combinations of medicines that are not artemisinin‐based, but contain atovaquone‐proguanil. This is an oral treatment commonly used by people from non‐malaria areas to prevent them catching malaria when they travel to malaria areas. We wanted to find out whether it works as well for treating uncomplicated Plasmodium falciparum malaria as ACTs and other malaria treatments.\ We searched for randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) that compared atovaquone‐proguanil against other malaria treatments. These studies provide the most robust evidence about the effects of a treatment. We compared results, summarized the evidence, and rated our confidence in the evidence.\ What are the main results of the review?\ We found 17 studies involving 4763 adults and children in Africa, South America, and South East Asia. People were followed for 28 days to one year.\ Fifteen studies compared atovaquone‐proguanil against 12 different antimalarial treatments (ACTs in five studies; other therapies that combined several medicines in two studies; single medicines in nine studies).\ Five studies compared atovaquone‐proguanil plus another medicine (artesunate or chloroquine) against atovaquone‐proguanil alone (three studies); atovaquone‐proguanil plus a different medicine (one study); a combination of therapies that did not include atovaquone‐proguanil (one study); or single medicines (two studies).\ In 15 studies, the researchers and people who were treated knew which medicines participants received. Pharmaceutical companies funded 10 studies.\ Atovaquone‐proguanil against ACTs recommended by the WHO\ Atovaquone‐proguanil may work less well to clear Plasmodiumfalciparum parasites from the blood or prevent them from returning (treatment success) than artemether‐lumefantrine (rates of success compared 28 and 42 days after treatment; one study). However this evidence was based on one small study.\ Atovaquone‐proguanil may work as well as, or less well than, artesunate‐amodiaquine depending on whether new infections appearing after the start of treatment were counted or not (rates of success compared three and 28 days after treatment; one study). However this evidence was based on one small study of children aged under five years.\ When new infections after the start of treatment were excluded, there is strong evidence of little to no difference in treatment success between atovaquone‐proguanil and artesunate‐mefloquine after 42 days (two studies). When new infections were counted, atovaquone‐proguanil may be better than artesunate‐mefloquine, but this evidence was based on the imprecise results of one study.\ Atovaquone‐proguanil against atovaquone‐proguanil plus artesunate\ Compared to atovaquone‐proguanil plus artesunate, atovaquone‐proguanil may be less successful at treating uncomplicated malaria after three and 28 days, however this evidence is based on the results of two small studies. It is probably less successful at treating uncomplicated malaria after 42 days (two studies).\ Side effects\ Studies reported several side effects, such as nausea and vomiting, or headaches. Overall, they were similar between groups.\ How‐up‐to date is this review?\ The evidence is current to 30 January 2020.](https://app.figure1.com/case-detail/05987ad0-052b-474d-88e2-d78038854e3d)

\ \ What was the aim of this review?\ The aim of this review was to see if tafenoquine could prevent relapses of vivax infections and if this effect is equivalent to that of standard‐dose primaquine. Standard‐dose primaquine is defined as 15 mg/day for 14 days for adults.\ Key messages\ Tafenoquine prevents vivax malaria relapses (measured as recurrences of infection in all studies as it is not possible to differentiate a true relapse from a reinfection) in adults compared to no relapse prevention treatment (placebo). There is also probably little or no difference between tafenoquine and primaquine in preventing relapses. The evidence was of moderate certainty due to the low number of studies and few data. There is probably little or no difference in the overall adverse events with tafenoquine compared to placebo or primaquine. However, we are uncertain if tafenoquine causes more serious adverse events such as a drop in blood haemoglobin.\ What was studied in this review?\ Vivax malaria is caused by the parasite Plasmodium vivax. The disease includes a dormant (inactive) stage of liver infection and this can cause relapse (worsening) unless it is treated.\ The most frequently used medicine for relapse prevention until recently was primaquine, but now there is a new alternative named tafenoquine. The US agency responsible for protecting public health, the Food and Drug Administration (FDA), recommends tafenoquine for relapse prevention at a single 300 mg dose. Compared to primaquine, which is usually given daily for 14 days, single‐day dosing provides a significant advantage. However, both primaquine and tafenoquine can cause rupture or destruction of red blood cells (called haemolysis) in people with a hereditary condition called glucose‐6‐phosphate dehydrogenase (G6PD) enzyme deficiency.\ We conducted a Cochrane Review on the effect of tafenoquine on clearing the dormant P vivax parasites in infected people to prevent a relapse. However, it is difficult to differentiate between a true relapse and a new infection in the same individual unless the person was removed from a malaria‐endemic area after initial treatment. All trials included in this review did not do that and have actually measured recurrences as a proxy measure to infer on relapses. While acknowledging this limitation, in giving recommendations and results in this review we used the word 'relapse' as preventing relapses is the intention for using tafenoquine as a single dose in these trials.\ What are the main results of the review?\ We examined the research published up to 3 June 2020. We identified three trials conducted in nine countries in 747 adults with confirmed P vivax malaria. All adults received chloroquine (to clear the parasites from the blood) and some groups received either tafenoquine in a single dose of 300 mg, primaquine or placebo (an inactive tablet matched for the duration of primaquine). All were observed for recurrences of P vivax malaria (up to six months) and all trials tested people for G6PD activity and excluded people who were deficient. Pregnant women and children were also excluded.\ Adults receiving tafenoquine 300 mg had fewer relapses (inferred from the lower number of recurrences of infection) than adults who had placebo (moderate‐certainty evidence). There was probably little or no difference between Tafenoquine 300 mg and primaquine for relapse prevention (moderate‐certainty evidence). There is probably little or no difference in overall side effects between tafenoquine and primaquine (moderate‐certainty evidence). We are uncertain though if tafenoquine causes more serious adverse events compared to placebo or premaquine (for example, haemolysis; very low‐certainty evidence).](https://app.figure1.com/case-detail/162452bb-bc65-4e8a-9c71-79bdd7949586)

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