Flavivirus Antibodies Reactive to Zika Virus Detected in Multiple Species of Nonhuman Primates in Kenya, 2008-2017.

Background: Zika virus (ZIKV), first described in 1947, is an arthropod-borne virus associated with sporadic outbreaks and interepidemic transmission. Recent studies have implicated nonhuman primates (NHPs) as the probable reservoir hosts. We tested archived serum samples of NHPs collected in Kenya for evidence of neutralizing ZIKV antibodies. Methods: We randomly selected 212 archived serum samples from Institute of Primate Research in Kenya collected between 1992 and 2017. These specimens were tested by microneutralization test. Results: The 212 serum samples were collected in 7 counties from 87 (41.0%) Olive baboons, 69 (32.5%) Vervet monkeys, and 49 (23.1%) Sykes monkeys. Half (50.9%) were male and 56.4% were adult. We detected ZIKV antibodies in 38 (17.9%; 95% confidence interval: 13.3-23.6) samples. Conclusions: These results suggest ZIKV transmission and potential maintenance in nature by NHPs in Kenya.

The intersection of land use and human behavior as risk factors for zoonotic pathogen exposure in Laikipia County, Kenya.

A majority of emerging infectious diseases (EIDs) are zoonotic, mainly caused through spillover events linked to human-animal interactions. We conducted a survey-based human behavioral study in Laikipia County, Kenya, which is characterized by a dynamic human-wildlife-livestock interface. Questionnaires that assessed human-animal interactions, sanitation, and illnesses experienced within the past year were distributed to 327 participants among five communities in Laikipia. This study aimed to 1) describe variation in reported high-risk behaviors by community type and 2) assess the relationship between specific behaviors and self-reported illnesses. Behavioral trends were assessed in R via Fisher's exact tests. A generalized linear mixed model with Lasso penalization (GLMMLasso) was used to assess correlations between behaviors and participants' self-reported illness within the past year, with reported behaviors as independent variables and reported priority symptoms as the outcome. Reported behaviors varied significantly among the study communities. Participants from one community (Pastoralist-1) were significantly more likely to report eating a sick animal in the past year (p< 0.001), collecting an animal found dead to sell in the past year (p<0.0001), and not having a designated location for human waste (p<0.0001) when compared to participants from other communities. The GLMMLasso revealed that reports of an ill person in the household in the past year was significantly associated with self-reported illness. Sixty-eight percent of participants reported that bushmeat is available within the communities. Our study demonstrates community-level variation in behaviors that may influence zoonotic pathogen exposure. We further recommend development of targeted studies that explore behavioral variations among land use systems in animal production contexts.

Endemicity of Yaws and Seroprevalence of Treponema pallidum Antibodies in Nonhuman Primates, Kenya.

Human yaws has historically been endemic to Kenya, but current epidemiologic data are lacking. We report seroprevalence for Treponema pallidum antibodies in olive baboons (Papio anubis) and vervet monkeys (Chlorocebus pygerythrus) in Laikipia County, Kenya. Our results suggest endemicity of the yaws bacterium in monkeys, posing a possible zoonotic threat to humans.

An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses.

BACKGROUND: Schistosoma mansoni is one of the most common helminth infections affecting a large population of people in sub-Saharan Africa. This helminth infection is known to cause immunomodulation which has affected the efficacy of a number of vaccines. This study examined whether a chronic schistosoma infection has an effect on the immunogenicity of HPV vaccine which is currently administered to girls and women aged 9 to 24. Little is known about the immune responses of the HPV vaccine in individuals with chronic schistosomiasis. METHODS: This study was carried out at the Institute of Primate Research (IPR) and involved an Olive baboon model. The experimental animals were randomly placed into three groups (n = 3-4); Two groups were infected with S. mansoni cercaria, and allowed to reach chronic stage (week 12 onwards), at week 13 and 14 post-infection, one group was treated with 80mg/kg of praziquantel (PZQ). Sixty four weeks post schistosoma infection, all groups received 2 doses of the Cervarix HPV vaccine a month apart. Specific immune responses to the HPV and parasite specific antigens were evaluated. RESULTS: Animals with chronic S. mansoni infection elicited significantly reduced levels of HPV specific IgG antibodies 8 weeks after vaccination compared the PZQ treated and uninfected groups. There was no significant difference in cellular proliferation nor IL-4 and IFN-γ production in all groups. CONCLUSION: Chronic S. mansoni infection results in reduction of protective HPV specific IgG antibodies in a Nonhuman Primate model, suggesting a compromised effect of the vaccine. Treatment of schistosomiasis infection with PZQ prior to HPV vaccination, however, reversed this effect supporting anti-helminthic treatment before vaccination.

Vector competence of populations of Aedes aegypti from three distinct cities in Kenya for chikungunya virus.

BACKGROUND: In April, 2004, chikungunya virus (CHIKV) re-emerged in Kenya and eventually spread to the islands in the Indian Ocean basin, South-East Asia, and the Americas. The virus, which is often associated with high levels of viremia in humans, is mostly transmitted by the urban vector, Aedes aegypti. The expansion of CHIKV presents a public health challenge both locally and internationally. In this study, we investigated the ability of Ae. aegypti mosquitoes from three distinct cities in Kenya; Mombasa (outbreak prone), Kisumu, and Nairobi (no documented outbreak) to transmit CHIKV. METHODOLOGY/PRINCIPAL FINDINGS: Aedes aegypti mosquito populations were exposed to different doses of CHIKV (105.6-7.5 plaque-forming units[PFU]/ml) in an infectious blood meal. Transmission was ascertained by collecting and testing saliva samples from individual mosquitoes at 5, 7, 9, and 14 days post exposure. Infection and dissemination were estimated by testing body and legs, respectively, for individual mosquitoes at selected days post exposure. Tissue culture assays were used to determine the presence of infectious viral particles in the body, leg, and saliva samples. The number of days post exposure had no effect on infection, dissemination, or transmission rates, but these rates increased with an increase in exposure dose in all three populations. Although the rates were highest in Ae. aegypti from Mombasa at titers ≥106.9 PFU/ml, the differences observed were not statistically significant (χ2 ≤ 1.04, DF = 1, P ≥ 0.31). Overall, about 71% of the infected mosquitoes developed a disseminated infection, of which 21% successfully transmitted the virus into a capillary tube, giving an estimated transmission rate of about 10% for mosquitoes that ingested ≥106.9 PFU/ml of CHIKV. All three populations of Ae. aegypti were infectious as early as 5-7 days post exposure. On average, viral dissemination only occurred when body titers were ≥104 PFU/ml in all populations. CONCLUSIONS/SIGNIFICANCE: Populations of Ae. aegypti from Mombasa, Nairobi, and Kisumu were all competent laboratory vectors of CHIKV. Viremia of the infectious blood meal was an important factor in Ae. aegypti susceptibility and transmission of CHIKV. In addition to viremia levels, temperature and feeding behavior of Ae. aegypti may also contribute to the observed disease patterns.

The protein DIIIC-2, aggregated with a specific oligodeoxynucleotide and adjuvanted in alum, protects mice and monkeys against DENV-2.

Previously, we reported the ability of the chimeric protein DIIIC-2 (domain III of the dengue envelope protein fused to the capsid protein of dengue-2 virus), to induce immunity and protection in mice, when it is highly aggregated with a non-defined oligodeoxynucleotide (ODN) and adjuvanted in alum. In this work, three different defined ODNs were studied as aggregating agents. Our results suggest that the nature of the ODN influences the capacity of protein DIIIC-2 to activate cell-mediated immunity in mice. Consequently, the ODN 39M was selected to perform further experiments in mice and nonhuman primates. Mice receiving the preparation 39M-DIIIC-2 were solidly protected against dengue virus (DENV) challenge. Moreover, monkeys immunized with the same preparation developed neutralizing antibodies, as measured by four different neutralization tests varying the virus strains and the cell lines used. Two of the immunized monkeys were completely protected against challenge, whereas the third animal had a single day of low-titer viremia. This is the first work describing the induction of short-term protection in monkeys by a formulation that is suitable for human use combining a recombinant protein from DENV with alum.

Capsid protein: evidences about the partial protective role of neutralizing antibody-independent immunity against dengue in monkeys.

The role of cellular immune response in dengue virus infection is not yet fully understood. Only few studies in murine models propose that CD8(+) T-cells are associated with protection from infection and disease. At the light of recent reports about the protective role of CD8(+) T-cells in humans and the no correlation between neutralizing antibodies and protection observed in several studies, a vaccine based on cell-mediated immunity constitute an attractive approach. Our group has developed a capsid-based vaccine as nucleocpasid-like particles from dengue-2 virus, which induced a protective CD4(+) and CD8(+) cell-mediated immunity in mice, without the contribution of neutralizing antibodies. Herein we evaluated the immunogenicity and protective efficacy of this molecule in monkeys. Neither IgG antibodies against the whole virus nor neutralizing antibodies were elicited after the antigen inoculation. However, animals developed a cell-mediated immunity, measured by gamma interferon secretion and cytotoxic capacity. Although only one out of three vaccinated animals was fully protected against viral challenge, a viral load reduction was observed in this group compared with the placebo one, suggesting that capsid could be the base on an attractive vaccine against dengue.