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j Infect Dis.-1999-Georges-s65-75 (Article Ebola Virus)

j Infect Dis.-1999-Georges-s65-75 (Article Ebola Virus)

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j Infect Dis.-1999-Georges-s65-75 (Article Ebola Virus)
j Infect Dis.-1999-Georges-s65-75 (Article Ebola Virus)

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S65
Ebola Hemorrhagic Fever Outbreaks in Gabon, 1994–1997: Epidemiologic andHealth Control Issues
Alain-Jean Georges, Eric M. Leroy, Andre´A. Renaut,
Centre International de Recherches Me´ dicales de Franceville, Franceville, Ministe`re de la Sante´ Publique, Faculte´ de Me´decine,
Carol Tevi Benissan, Rene´J. Nabias, Minh Trinh Ngoc,
Universite´ Omar Bongo, Mission Franc ¸aise de Cooperation et d’Action
Paul I. Obiang, J. P. M. Lepage,* Eric J. Bertherat,*
Culturelle, and Ministe`re de la Sante´ Publique, Libreville, Gabon
David D. Be´noni, E. Jean Wickings, Jacques P. Amblard,*Joseph M. Lansoud-Soukate, J. M. Milleliri, Sylvain Baize,and Marie-Claude Georges-Courbot*
From the end of 1994 to the beginning of 1995, 49 patients with hemorrhagic symptoms werehospitalized in the Makokou General Hospital in northeastern Gabon. Yellow fever (YF) virus wasfirst diagnosed in serum by use of polymerase chain reaction followed by blotting, and a vaccinationcampaign was immediately instituted. The epidemic, known as the fall 1994 epidemic, ended 6weeks later. However, some aspects of this epidemic were atypical of YF infection, so a retrospectivecheck for other etiologic agents was undertaken. Ebola (EBO) virus was found to be present concomi-tantly with YF virus in the epidemic. Two other epidemics (spring and fall 1996) occurred in thesame province. GP and L genes of EBO virus isolates from all three epidemics were partiallysequenced, which showed a difference of 
õ
0.1% in the base pairs. Sequencing also showed that allisolates were very similar to subtype Zaire EBO virus isolates from the Democratic Republic of theCongo.
Johnson et al. [1] isolated and identified Ebola (EBO) virus associated with a mortality rate similar to that seen during theDRC and Sudan epidemics [7].from human cases during a 1976 epidemic of hemorrhagicfever (HF) in the Democratic Republic of the Congo (DRC). During 1994 and 1995, an outbreak of HF occurred in north-eastern Gabon. It was first considered to be caused only byDuring the same year, EBO virus was isolated from patientsduring an HF epidemic in Sudan [2]. The viruses, which were yellow fever (YF) virus on the basis of the clinical symptom-atology, routine biochemical tests, and specific laboratory re-closely related to Marburg virus (all members of the Filoviri-dae), had an 88% and a 53% case fatality rate in DRC [3] and sults provided by the Centre National de Re´fe´rence des Fie`vresHemorragiques Virales (InstitutPasteur, Paris) [8, 9]. However,Sudan [2], respectively. A third outbreak, with a case fatalityof 60%, occurred in Sudan in 1979 [4]. In addition, a death retrospective serologic tests detected concomitant EBO virusantibodies among some of the patients and the general popula-was registered in Tandala, DRC, in 1979 [5]. In 1994, a newstrain of EBO virus was isolated from a Swiss researcher with tion [10, 11]. Later efforts to isolate the EBO virus from someof the specimens from the first epidemic (1994) were success-a dengue-like syndrome, who had likely been infected duringthe necropsy of a chimpanzee (see Formenty et al., this supple- ful. One year later, in February and in July 1996, two moreHF outbreaks occurred in northeastern Gabon [10–13].ment). The animal had been found dead in the Taı
 F
NationalForest (Coˆte d’Ivoire) during a 2-year epidemic that killed half Herein, we report on three EBO epidemics that occurred  between late 1994 and early 1997 in northeastern Gabon [10].of the population of chimpanzees [6]. A third serious humanepidemic of EBO occurred in 1995 in Kikwit, DRC; it was
The Epidemics
It is important to note that during this investigation, we
Informed consent was obtained from the patients or their parents or guard-
continually faced many difficulties (e.g., logistics problems and 
ians.Financial support:CIRMF is supported bythe Republic of Gabon,the French
cultural and political constraints) in the collection of data and 
Ministry of Foreign Affairs (Coope´ration et Action Culturelle), and ELF GA-
managementof our research on this disease. Despiteour efforts,
BON Co. Ltd. (Libreville).
the difficulties sometimes led to the loss of important informa-
Reprints or correspondence (current affiliation): Dr. Alain-Jean Georges,Chefferie, Hopital d’Instruction des Arme´es Desgenettes, 108 Bd Pinel, 69
tion, and at times, forced us to report the scientific data in a
275 Lyon, Cedex 03, France (ajgeorges@wanadoo.fr).
rather unorthodox manner.
* Current affiliations:CHA, Lamaloules Bains,France (J.P.M.L.);IMTSSA,
 First epidemic (fall 1994).
The first epidemic in Gabon
Le Pharo, Marseille Arme´es, France (E.J.B.); Ministe`re Affaires Etrange`res,Service de l’Action Humanitaire, Paris (J.P.A.); and CBMS, Institut Pasteur,
had two waves of patients, with the first beginning in early
Paris (M-C.G.C.).
December 1994 and the second beginning at the end of January
The Journal of Infectious Diseases 1999;179(Suppl 1):S65–75
to February 1995. All patients in the first wave came from 3
1999 by the Infectious Diseases Society of America. All rights reserved.0022–1899/99/79S1–0013$02.00
gold-panning encampments (Me´kouka, Andock, and Minke´ be´)
 / 9d49$$se13 01-12-99 11:06:39 jinfa UC: J Infect
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S66 Georges et al. JID 1999;179 (Suppl 1)
situated in small clearings of 2000–3000 m
2
at the edge of the the physicians in charge of the Makokou hospital (a very poorlyequipped facility), was rather broad, and at least 4 of the 49rain forest. Figure 1 and table 1 show the geographic locationof these and other villages with case-patients. Table 1 also patients appeared unlikely to have HF. On 18 December 1994,during the middle of the first wave, the Gabonese health author-shows the chronology of illness for the cases. Three hundred fifty people, mainly of the Bakota ethnic group but also some ities requested that we examine 9 patients in Makokou GeneralHospital. Biologic samples from those patients led to the identi-Bakwe´le´, inhabit this area (30 in Me´kouka, 20 in Andock, and 300 in Minke´ be´). cation of the etiologic agents.Between December 1994 and March 1995, CIRMF collected A total of 32 sick persons from the three forest encampments(23 from Me´kouka, 4 from Andock, and 5 from Minke´ be´) 22 samples in Mayela from contacts (all
§
15 years old) of sick persons and 88 samples from the local population of traveled 100 km south by river to the nearest hospital at Mako-kou, the main town of the region, for treatment. In addition to Ogooue´-Ivindo Province, Gabon, where the epidemic occurred.At that time, many people had fled the area in terror; therefore,the primary cases in Andock, we were also informed that deathshad occurred in the local population of great apes (chimpan- itwas difficult to conductan investigation. A year later (January1996), we sampled 236 people from the three initially infected zees,
Pan p. troglodytes
, and gorillas,
Gorilla g. gorilla).
How-ever, despite intensive searches of the forest by teams from villages and from villages in the Makokou area in order tofurther assess exposure to EBO virus in the local population.Centre International de Recherches Me´dicales de Franceville(CIRMF), no cadavers or skeletons were ever found, even when
Second epidemic (spring 1996).
A second epidemic beganduring early February 1996 in the village of Mayibout 2, Ga-a patient told us that he had killed a chimpanzee with abnormal behavior inside his encampment. This report could be anec- bon, which is located on the Ivindo River. Mayibout 2 is 40km south (6 h by boat) of Me´kouka and Andock, where thedotal, but it cannot be totally ignored.The second wave of patients did not originate from the en- first epidemic broke out, and north of Makokou (7 h by boat).Eighteen people who had skinned and chopped a chimpanzeecampments: They were what we should have called (in a surveyfollowing accepted procedures) secondary (or tertiary ?) cases. cadaver that they found became ill (fever, headache, bloodydiarrhea). They were evacuated from Mayibout 2 to MakokouUnfortunately, the information that was available from the au-thorities regarding thesepatients did not providea precise gene- on the decision of the village chief, despite governmental in-structions to the contrary. All patients were admitted to Mako-alogy of all cases. The first patient in the second wave wasfrom Mayela, a small village close to Makokou, far from the kou Ge´ne´ral Hospital, where 4 moribund patients died within48 h.forest encampments. This person, who was probably the firstsecondary or tertiary case, lived near a traditional healer (a The bodies of the 4 patients were returned by river to Mayi- bout 2; a fifth patient, who was moribund when he escaped ‘‘nganga’’) and was probably infected as a result of contactwith a hospitalized patient who, against medical advice, left from the hospital, died after returning to Mayibout 2. Tradi-tional burial ceremonies were performed without any specialthe hospital to seek care from the nganga. Sixteen more cases(table 1) occurred in mid January: 1 case at Makokou Ge´ne´ral precautions to avoid disease transmission. Two other ‘‘primarycases’’ occurred, which appeared not to be connected to theHospital, 12 cases from Mayela, and 3 cases from two villages(Ekataniabe´, 1 patient; Ekobakoba, 2 patients) on the road chimpanzee episode; 1 died. Fifteen serum samples from theseinitial 18 primary cases and 6 from secondary and tertiary casesrunning south toward Franceville. None of these patients had  been in the area affected by the first wave of the epidemic were obtained. An additional 205 serum samples were obtained from the population of Mayibout 2 and neighboring villagesduring the previous 3 months; however, all had been either indirect contact with sick relatives (people hospitalized at Mako- (Mayibout 1 and Mvadi, which are 2 km south and 20 kmnorth, respectively, of Mayibout 2).kou Ge´ne´ral Hospital or sleeping in the nganga traditional heal-er’s home) or with people caring for patients.
Third epidemic (fall 1996).
On 5 October 1996, we in-formed the Gabonese health authorities (who 1 week earlier The last reported case (infected while caring for a relativeat Makokou’s hospital) occurred at Ekobakoba on 9 February had requested our assistance in the investigation) that we had isolated EBO viruses from 2 of 6 samples from patients hospi-1995, and the epidemic was declared over by Gabonese healthauthorities on 17 February 1995. talized at Booue´. Personnel from CIRMF carried out a retro-spective investigation of this third epidemic, which probablyOverall, 49 persons were admitted to Makokou’s hospitalwith suspected HF. Patients were suspected of having HF if started as early as 13 July with the death (undeclared) of a 39-year-old hunter in a logging camp near Booue´(0
06
S, 11
57
they had a well-identified contact with an ill person or at leasttwo of the following clinical signs: fever, diarrhea, vomiting, E) between Ovan and Koumameyong, 200 km from Me´koukaand 120 km from Makokou to the southwest (figure 1). Themelena, conjunctivitis, arthralgia or myalgia, diarrhea, or vom-iting. Of the first 9 patients, 2 who we examined during the symptoms of this first case were suggestive of viral HF (VHF;fever, bleeding, vomiting, diarrhea, and headache). At the be-first wave also had jaundice, which has never been described as a symptom of EBO infection but is consistent with YF ginning of August 1996, information was obtained that severalchimpanzees may have died in the same area, and a field collab-infection. This case definition of HF, which was proposed by
 / 9d49$$se13 01-12-99 11:06:39 jinfa UC: J Infect
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Figure 1.
Geographic location of sites of primary and secondary cases of hemorrhagic fever.
A
, Gabon,
B
, Africa,
C
, sites.
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