Zika: History of an Emerging Virus

Marc Gozlan, MD

Disclosures

February 25, 2016

The Zika Forest, 1947

In Lugandan (the major language of Uganda), the word "Zika" means "overgrown." The Zika Forest is a narrow, dense belt of high but broken canopy growth with clumps of large trees, situated along the edge of Lake Victoria near Entebbe, about 15.5 mi east of the Uganda capital, Kampala[1] (Figures 1 and 2).

Figure 1. The Zika Forest, near Entebbe, Uganda. Image courtesy of AP Photo/Stephen Wandera

For 10 years, a team from the East African Virus Research Institute in the Bwanba County in western Uganda, led by Alexander J. Haddow, had been doing studies on yellow fever epidemiology in the Zika Forest.[2] Five years earlier, Dr A.F. Mahhafy isolated the yellow fever virus from a sick African patient and from Aedes simpsoni, a sylvan mosquito found in banana plantations.[3] Repeated isolation of the yellow fever virus showed that this virus circulated in an enzootic state in forest monkeys, its primary sylvan host population.[2] Mahhafy and colleagues set out to study the nonhuman cycle of sylvan yellow fever, hoping to discover the vector for the transmission of the yellow fever virus to the monkeys of western Uganda.

Figure 2. Gerald Mikusa, caretaker and tour guide, poses in the Zika Forest. Image courtesy of AP Photo/Stephen Wandera

To study the sylvanic cycle of transmission of the yellow fever virus between monkeys and mosquitos (in which a mosquito becomes infected by biting one monkey and then reinjects the virus into another monkey), virologists and entomologists began a sentinel rhesus monkey program in the Zika Forest in 1946.[1] They chose an area where there were large numbers of monkeys and larvae of the Aedes africanus mosquito. Mosquitos remain above the forest canopy when night is falling, but monkeys stay at ground level during the daytime and climb up into the trees to sleep at night. At first, the monkeys were kept in cages on wooden platforms that were 40-60 feet high in the tree canopy. However, when the researchers found that the mosquitos did not readily enter the monkeys' cages, the monkeys were left uncaged, secured by wires on the tree platforms.[4] Their temperatures were monitored daily.

As many as 41,168 mosquitos were collected in 1947, including 1140 A africanus mosquitos.[5] On April 19, 1947, the temperature of one of the monkeys (rhesus 766) was recorded as 40° C (increased from 39° C the previous day). Rhesus 766 was taken to the laboratory for observation, although it showed no abnormalities other than mild pyrexia.

A blood sample was taken on the third day of fever. Serum from rhesus 766 was injected intracerebrally and intraperitoneally into two groups of Swiss albino mice. The intraperitoneally injected mice showed no abnormalities during a 30-day observation period. In contrast, all mice infected by intracerebral inoculation became ill on the 10th day after inoculation. Another monkey (rhesus 771) was inoculated with serum of rhesus 766, but rhesus 771 did not become febrile or ill during 23 days of observation.[1] Researchers George W. Dick, Stuart F. Kitchen, and Alexander J. Haddow succeeded in isolating a filterable transmissible agent from the brains of the sick mice.[1]

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