Case report: malaria attack in southern Brazil – five-decade relapse, simian malaria or something else?

This is an account of two episodes of tertian fever separated by 51 years on two continents. The first was Plasmodium vivax malaria. The second may have been because of a long-delayed relapse, a new infection with P. simium, or not being malaria at all.

Case history

First attack, Borneo 1956

I contracted malaria during a student expedition from Cambridge to British North Borneo (now Sabah, Malaysia) in 1956. It was diagnosed at the time at the Hospital for Tropical Diseases in London as P. vivax.

I came down with it in Singapore on our way home in September, where we were stranded short of money for the rest of the return trip. This was before Malaysian independence. I remember clearly having to go to the British High Commission offices downtown in the sweltering afternoon sun wearing a jacket and scarf over a sweater, shirt, and t-shirt, and shivering with fever. A fellow-student (Brian Moser) and I were guests in the house of two physicians, and the first thing they asked me was whether I had taken my prophylaxis. I replied that I had taken Nivaquine (chloroquine sulphate) regularly every Sunday. They agreed that therefore it could not be malaria, and so probably was a case of scrub typhus, although I had no rash or eschar. I was fortunate that Brian managed to arrange a flight back to England in an ex-RAF Lancaster bomber taking freight home, for the donation to the aircrew of our duty-free allowances of cigarettes. I was able to lie on the floor of the aircraft in my sleeping bag and sweat out the tertian attacks during the 5-day flight (8 h each leg, daylight only). I recovered sufficiently in time to eat a hearty meal of frog's legs and watch with the aircrew a belly dancer perform in a nightclub during the last overnight stop, which was in Beirut – still the ‘Paris of the Middle East’ in those days.

I relapsed after a few days in England, and repeated my story to the doctors at the Hospital for Tropical Diseases in St Pancras, London, claiming it could not be malaria. But, they offered to show me my blood slide, which they said was positive for P. vivax, and admitted me for a 2-week course of Primaquine (an eight-aminoquinoline), which was well tolerated.

Second attack, Brazil 2007

Fifty-one years later, on 28 April 2007, I was retired and living in Rio de Janeiro, Brazil. My wife and I were driving in the coastal mountains to our country house (sitio), 960 metres up in the Atlantic forest in the district of Lumiar, municipality of Novo Friburgo, Rio de Janeiro state. It was night and it was pouring when we stopped at the entrance to a property for me to answer a call of nature. On reversing back into the road, one back wheel of the car fell into an invisible grass-covered ditch so deep that the four-wheel drive was unable to extract us. We got soaked through trying to lift the back wheel. There was no traffic at that time of night, and we were stranded without a towel, change of clothing, or blankets. Temperatures drop to as low as 15°C (59°F) in April in that area. We could not risk turning the car heater on for more than few minutes at a time for fear of carbon monoxide poisoning. We both got chilled. We were rescued in the morning, towed out of the ditch, and we proceeded to the sitio.

Because until then we had not heard of any malaria in the area, we never took prophylaxis before going there. The next day I fell ill with chills exactly resembling those I remembered from Singapore. The fever struck at 2 pm every second day, and would pass in a couple of hours, during which time I was delirious and instructed my wife to do crazy things such as format the hard drive of my computer, which would have erased all my files (fortunately, she did not comply). Back in Rio, a city doctor who understandably discarded a diagnosis of malaria, prescribed quinolones (broad-spectrum antibacterial drugs); the hospital told me to come in when I was febrile for a blood test, but I was too ill to move each time the tertian attacks came. Eventually, I was told a technician could be called to the apartment to take a blood slide when the next crisis occurred, but I never had another crisis. Serology done in a Rio de Janeiro laboratory was positive for both IgM and IgG for P. vivax, but in the opinion of a parasitologist colleague, malaria serology is prone to non-specific cross-reactions, especially for IgM, and there is no proof that my tertian fevers were actually malaria. Chills began on 3 May, urine went brown, next bouts 5 May (4–5:30 pm) with hallucinations, 7 May (2–3:30 pm) again with hallucinations, 9 May (pm), 11 May (pm), 13 May (2–5 pm), then no more.

Discussion

Taking into account what is now known about simian malaria in Asia, my original episode could not have been P. knowlesi, first described by Garnham 10 years after my episode (1, 2), because that simian parasite is more likely to be confused microscopically with P. malariae rather than with P. vivax. Polymerase chain reaction was not available for definitive diagnosis in 1956. Furthermore, P. knowlesi does not relapse, so could not account for my second attack. P. malariae is known to relapse after decades, but it has a quartan cycle, while P. knowlesi is quotidian, whereas my two attacks were each definitely tertian.

In 2015, a local news item reported that parasitologists at the reputed FioCruz laboratories in Rio de Janeiro had diagnosed 29 cases of autochthonous malaria since 2008 (the year after my second attack) in visitors to a waterfall near our sitio, half of those in January 2015 (3), and that in the interior of the state of Rio de Janeiro, autochthonous cases had been occurring annually since 1993 in the same region of Lumiar (4).

This led me to reconsider the source of my second attack. I learned that human infection with simian malaria in Brazil was described in the mid-1960s (5) and ‘In Brazil, two species of Plasmodium have been described infecting non-human primates, Plasmodium brasilianum and P. simium. These species are morphologically, genetically and immunologically indistinguishable from the human P. malariae and P. vivax parasites, respectively’ (6), and P. simium produces a tertian fever (4). I could not find a reference to the incubation period for P. simium in humans, but if it is similar to that of P. vivax, it would be 12–18 days. Our previous visit to the area was 18 days earlier, from 7 to 10 April 2007 with four other family members from England, two adults and two children with no previous history of malaria, none of whom subsequently came down with fever.

Conclusion

My first attack in Borneo was clearly P. vivax, with a tertian course, parasitoscopic confirmation, and cure with eight-aminoquinoline therapy. P. knowlesi can be excluded on the basis of the tertian periodicity. But what was the second?

The longest malaria relapse I have been able to find in literature was in a blood donor who had probably acquired 145 infection with P. malariae in China 50 years earlier (7). There is another report of a case of P. malariae acquired in Greece around 40 years (and possibly up to 70 years) before splenectomy and subsequent diagnosis (8). Perhaps, the chill from the night spent in the car precipitated a relapse of P. vivax or the onset of P. simium. I have not caught a chill or had another attack of a tertian fever as of September 2015, more than 8 years later.

With a course identical to the first with tertian chills and fever, plus delirium, no parasitoscopy performed, equivocal serology, and cure by quinolone therapy, if it was not malaria, what could be the differential diagnosis? A recurring Lyme disease–like syndrome has been reported from Brazil (9), but recurrence is not tertian and it presents with erythema migrans and arthritis, neither of which I had.

So was my second attack a 51-year recurrence of my Borneo vivax from 1956, or a new infection with Brazilian simium? I would welcome correspondence to [email protected].