SUMMARY Ebola virus subtype Zaire (Ebo‐Z) induces acute haemorrhagic fever and a 60–80% mortality rate in humans. Inflammatory responses were monitored in victims and survivors of Ebo‐Z haemorrhagic fever during two recent outbreaks in Gabon. Survivors were characterized by a transient release in plasma of interleukin‐1β (IL‐1β), IL‐6, tumour necrosis factor‐α (TNFα), macrophage inflammatory protein‐1α (MIP‐1α) and MIP‐1β early in the disease, followed by circulation of IL‐1 receptor antagonist (IL‐1RA) and soluble receptors for TNFα (sTNF‐R) and IL‐6 (sIL‐6R) towards the end of the symptomatic phase and after recovery. Fatal infection was associated with moderate levels of TNFα and IL‐6, and high levels of IL‐10, IL‐1RA and sTNF‐R, in the days before death, while IL‐1β was not detected and MIP‐1α and MIP‐1β concentrations were similar to those of endemic controls. Simultaneous massive activation of monocytes/macrophages, the main target of Ebo‐Z, was suggested in fatal infection by elevated neopterin levels. Thus, presence of IL‐1β and of elevated concentrations of IL‐6 in plasma during the symptomatic phase can be used as markers of non‐fatal infection, while release of IL‐10 and of high levels of neopterin and IL‐1RA in plasma as soon as a few days after the disease onset is indicative of a fatal outcome. In conclusion, recovery from Ebo‐Z infection is associated with early and well‐regulated inflammatory responses, which may be crucial in controlling viral replication and inducing specific immunity. In contrast, defective inflammatory responses and massive monocyte/macrophage activation were associated with fatal outcome.

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Seroepidemiological surveys were conducted to determine the frequency and distribution of haemorrhagic fever virus (HFV) activity in the Central African Republic. Human serum specimens (4295) were collected from 5 ecologically distinct zones. Serological evidence of HFV activity was found in all the zones. The filovirus antibody prevalence (24.4%, 1051/4295) was greater than the combined prevalence for Lassa virus, Rift Valley fever virus and Crimean-Congo HFV antibody (1.1%, 45/4295; P < 0.01). Evidence of filovirus activity was found in all zones: 21.3% (914/4295) of the population were seropositive for Ebola virus antibody while only 3.2% (137/4295) were seroreactive with Marburg viral antigens. Age and sex were important host-related factors influencing filovirus activity, particularly in dry grassland and moist forest communities. These communities shared many factors, but differences, such as agricultural practices and ethnic backgrounds, may also affect the risk of infection. Filovirus infections appear to occur without apparent disease. Continued investigations are needed to evaluate the true pathogenicity of the African filoviruses and the likelihood that unidentified serologically cross-reacting and non-pathogenic members of the filovirus family are active in equatorial Africa.

Seroepidemiological surveys were conducted to determine the frequency and distribution of filovirus activity among selected ethnic groups inhabiting the tropical forests of the Central African Republic. 427 serum specimens were collected from hunter-gatherers and subsistence farmers living in forest environs in the Lobaye District south of the river Lobaye and west of the river Oubangui. Striking serological evidence for filovirus activity was found in both populations. Ebola virus appears to be the most active filovirus; 17.6% (75/427) of the Lobaye survey population were seropositive for Ebola virus reactive antibody while 1.2% (5/427) were seroreactive with Marburg viral antigens. Ethnic background appeared to be an important risk factor influencing filovirus exposure in the forest communities. The filovirus antibody prevalence among 21-40 years old male Aka Pygmy hunter-gatherers was significantly (P = 0.03) 3 times higher (37.5%) than that in similarly aged male Monzombo and Mbati subsistence farmers (13.2%). Continued epidemiological investigations are needed to define ethnic-related events influencing human filovirus activity in the Congo basin of equatorial Africa.

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In order to shed light on the mechanisms of antifilarial protective immunity, we investigated the course of experimental loaiosis after vaccination in a nonhuman primate host, Mandrillus sphinx. Six vaccinated (V) mandrills received 50 irradiated L3 while six nonvaccinated (NV) received saline solution on days -60, -30 and -15. All animals were challenged with 100 intact L3 (day 0). Parasitological and immunological status were followed for 9 months. Vaccination delayed the appearance and mean peak of microfilaraemia. Five mandrills (Mf-) were never microfilaraemic (one V mandrill) or microfilaraemic on only one occasion (2 V and 2 NV), the other seven having stable microfilaraemia (Mf+). The cytokine response of peripheral blood mononuclear cells to L3 (L3 Ag) was Th2 dominated, while microfilariae (Mf Ag) elicited a Th0-like response. During vaccination, Th2 cytokine production significantly increased in V mandrills against L3 Ag, as well as Mf Ag, whereas Th1 cytokines decreased. On day 60 postinoculation, cellular proliferation was higher in V mandrills in response to L3 and Mf Ags and PHA-L mitogen. At the end of prepatency (on day 130), mandrills with delayed appearance of microfilaraemia exhibited a high, transient IL-2 and IL-4 secretion in response to L3 Ag. Finally, high anti-Mf Th2 cytokine levels characterized Mf-mandrills not only during prepatency, but also (for IL-5) before immunization. However, the presence of a balanced Th1 anti-L3 response during prepatency in the amicrofilaraemic mandrill suggests its importance in protective immunity. Taken together, our data suggest that Th2 cells and also Th1 components of the antifilarial response, especially to larval antigen, may contribute to parasite elimination.