A 44-year-old male engineer from Rio de Janeiro, Brazil, presented at Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz (IPEC, Fiocruz), with a history of persistent fever (39°C) for 16 days: initially continuous during the first week followed by intermittent high febrile peaks every 48 hours over the most recent nine days. The fever was accompanied by severe headache and chills, and followed by sweating. The man also complained of abdominal pain, nausea, myalgia, and arthralgia. Eleven days prior to his first consultation at IPEC, the patient had visited the emergency department of another hospital for these symptoms and for a single episode of gum haemorrhage, attributed to dengue fever that was not confirmed by laboratory tests. Because his symptoms did not resolve, he visited IPEC for two walk-in consultations (on days 16 and 18 of the disease).
During the first consultation, the patient reported a stay at a small farm in Sana, in the Atlantic Forest during a three-week holiday, 23 days before the onset of fever. The Atlantic Forest is a commonly visited touristic region in the Serra do Mar mountain range. The reserve of Sana is situated at an altitude of 735 m and is 165 km northeast of Rio de Janeiro. The median temperature in the area ranges from 10°C to 18°C, in the summer and winter, respectively.
The patient had no co-morbid diseases or any history of blood transfusion, tissue/organ transplantation, intravenous drug use, or travel to a malaria-endemic area. He had not been injured by needle sticks, nor lived or recreated near ports or airports. Furthermore, he had not experienced high fevers in the years prior to this event, and he had not taken drugs with anti-malarial activity either prior to or after the onset of the disease. During physical examination, his body temperature was 39°C, his blood pressure was 110/60 mmHg, and his pulse rate was 93 beats per minute. He appeared pale and had hepatomegaly and abdominal pain, but neither his spleen nor any of his lymph nodes were enlarged, and he did not have a cutaneous rash or any obvious clinical manifestations of bleeding.
A routine laboratory tests diagnosis for fever of undeterminated origin was performed: complete blood count, routine blood chemistry determinations, chest radiograph, erythrocyte sedimentation rate, antinuclear antibodies, rheumatoid factor, blood and urine cultures, Cytomegalovirus IgM antibodies, heterophile antibody, Human immunodeficiency virus antibodies, tuberculin skin test, and, considering the presented fever pattern, blood films, RTC and PCR were requested to exclude the possibility of malaria in the individual.
Laboratory test results on admission on the 16th day of disease were as follows: C-reactive protein, 5 mg/dL; haemoglobin, 11.9 g/dL; haematocrit, 35%; white blood cell count, 4,440/L (2,175 neutrophils and 1,864 lymphocytes); platelet count, 258,000/mm3; total serum bilirubin, 0.36 mg/dL (direct fraction, 0.11 mg/dL); creatinine, 0.94 mg/dL; alanine aminotransferase (ALT), 45 IU/L; aspartate aminotransferase (AST), 129 IU/L; serum albumin, 3.8 g/dL; urea, 37 mg/dL; creatinine, 0.94 mg/dL; LDH, 115 UI/L; sodium, 144 mmol/L; potassium, 4.4 mmol/L and glucose, 91 md/dL.
Routine blood cultures, microscopic urinalysis, and urine cultures were all negative. Serologic tests for toxoplasmosis and cytomegalovirus were positive for both IgG and IgM antibodies. The test results for ANF and RF were also positive, showing antibody titres of 320 (speckled pattern) and 64, respectively, whereas the test result for anti-HIV was negative. Abdominal ultrasound, echocardiography, and chest radiography results were normal. A microscopic direct blood examination (thick and thin blood films) was performed every 48 hours and assessed by two independent experts (on days 11, 13, and 15 of the disease), and rapid malaria tests (OptiMal®, on days 16 and 18) repeatedly reported negative results. On day 18 of the disease, single PCR tests for Plasmodium and Plasmodium vivax were positive, confirming the clinical suspicion of malaria.
Treatment with chloroquine and primaquine was initiated, and the patient’s fever resolved 24 hours after the start of treatment. He made a full clinical recovery and the laboratory abnormalities had normalised by the end of the treatment. The PCR tested negative for the first time on the second day and further negative results were reported on days 7, 21, 28, 40, 60, and 100 after treatment initiation, confirming that the treatment was curative. Serologic test results for toxoplasmosis and cytomegalovirus were negative on day 100 after the onset of symptoms, whereas the titres for both RF and ANF were reduced on the eighth day after treatment.