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Dispatch
Central African Hunters Exposed
to Simian Immunodeficiency Virus
Marcia L. Kalish,*
Nathan D. Wolfe,† Clement B. Ndongmo,* Janet McNicholl,* Kenneth E. Robbins,*
Michael Aidoo,* Peter N. Fonjungo,*‡ George Alemnji,‡ Clement Zeh,* Cyrille
F. Djoko,§ Eitel Mpoudi-Ngole,‡ Donald S. Burke,† and Thomas M. Folks*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †Johns
Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; ‡Project
IRECAM (Investigation of Retroviruses in Cameroon), Yaoundé, Cameroon;
and §Johns Hopkins Cameroon Program, Yaoundé, Cameroon
Suggested
citation for this article
HIV-seronegative
Cameroonians with exposure to nonhuman primates were tested for simian
immunodeficiency virus (SIV) infection. Seroreactivity was correlated
with exposure risk (p<0.001). One person had strong humoral and weak
cellular immune reactivity to SIVcol peptides. Humans are exposed to
and possibly infected with SIV, which has major public health implications.
Two major public health priorities are ensuring the safety of the blood
supply and preventing the emergence of new infectious diseases. Phylogenetic
evidence shows that HIV-1 and HIV-2 were introduced into humans through
independent cross-species transmission of simian immunodeficiency virus
(SIV) strains from distinct, naturally infected, nonhuman primate (NHP)
hosts. HIV-1 groups M, N, and O are believed to have arisen as 3 separate
cross-species transmissions from chimpanzees, and each of the HIV-2 subtypes
A–G was the result of independent transmissions from sooty mangabeys (Cercocebus
atys) to humans. While laboratory exposure to NHPs has caused infections
with SIV (1–3), no direct evidence has been seen of ongoing
exposure to or infection with SIV in natural settings. Nevertheless, hunting
and butchering wild NHPs for food, which expose humans to NHP blood and
body fluids, are widespread in sub-Saharan Africa and may lead to ongoing
transmission from any of the 33 species of NHP that are known to harbor
their own unique SIV strains. Since ongoing lentivirus emergence would
be of substantial importance to global public health, we looked for evidence
of SIV in a unique collection of plasma from persons with known levels
of exposure to the blood and body fluids of NHPs (3).
The Study
No commercial serologic assays can detect SIV infections in humans, and
published assays for this purpose are not designed to detect a wide range
of divergent SIV strains. To determine whether humans are infected with
SIV, we developed a sensitive and specific SIV multiple antigenic peptide–based
enzyme immunoassay (SMAP-EIA) for detecting env IDR (immunodominant
region of gp41/gp36) and V3 antibodies to all of the SIV lineages for
which env sequences were available, specifically SIVsm, SIVagm,
SIVsyk, SIVcpz, SIVlhoest/SIVsun, SIVcol, SIVmnd and SIVdrl, SIVrcm, and
SIVdeb (4). The SMAP-EIA also detects other SIV strains
not represented by specific SIV lineage–based peptides.
This study was carried out under an approved protocol in accordance with
guidelines set forth by the Centers for Disease Control and Prevention
(CDC). We tested plasma samples from Cameroon that were seronegative for
HIV-1 and HIV-2 by EIA. Cameroon has extensive HIV-1 genetic diversity,
and rural bushmeat hunting is common (2). Plasma from
3 different groups in Cameroon was examined: 1) persons in remote villages
who reported a high level of exposure to SIV strains through hunting NHPs,
butchering NHPs, or keeping wild NHP pets (n = 76) (2);
2) persons from the same villages who reported a low level of NHP exposure
(n = 77) (2); and 3) persons from a general population
(n = 1,071) from urban and rural areas in Cameroon where people may handle
NHP meat but are unlikely to have repeated contact with the blood or body
fluids of freshly killed animals. We tested the seroreactivity of these
small-volume samples by using our SMAP-EIA. Of the samples that were reactive
(optical density [OD] >1.000) to >1 of a panel of 9 SIV IDR
MAPs (Figure 1), 17.1% were seroreactive in the
high exposure group, 7.8% in the low exposure group, and 2.3% in the general
group. The higher the risk for exposure to fresh NHP blood and body fluids,
the greater the frequency of reactivity (p<0.001).
Only 1 of the plasma samples, with an IDR OD >1, also reacted strongly
to the homologous V3 peptide. This sample, which was from our general
population, reacted to the SIVcol (Colobus guereza) MAPs in both
IDR (OD = 1.250) and V3 (OD = 1.798). Since frozen viable cells were available
from this person, we performed an interferon-γ enzyme-linked immunospot
(ELISPOT) assay to determine whether peripheral blood lymphocytes (PBLs)
from this person recognized SIVcol peptides from C. guereza. Since
no information is available about T-cell epitopes within the SIVcol genome,
and the SIV strains from C. guereza are highly divergent from all
known SIV isolates (5), we designed a series of overlapping
peptides (16-mers overlapping by 10) across the gag gene, on the
basis of the only available Colobus sequence (5).
Pools of 10 peptides were each tested in the ELISPOT assay. Low levels
of T-cell reactivity to pools 71–80 and 81–86 of the gag peptides
(10× and 5× background, respectively, and >25 spots/106
PBLs) and env V3 and IDR peptides (9× and 6× background,
respectively) were observed with unfractionated PBLs (Figure
2). No reactivity was observed in PBLs from an HIV-1–seronegative
African donor used as a negative control. Polymerase chain reaction (PCR)
and reverse transcription–PCR amplifications from proviral DNA lysates,
plasma from this sample, and cells from stimulated ELISPOT wells were
performed with pol primers originally used to identify the C.
guereza sequence (5) and with other primers specifically
designed from the published C. guereza sequence. Despite a strong
humoral (env IDR and V3) response and weak cellular (gag)
immune reactivity (in the range of ELISPOT results reported from sex workers
who were highly exposed to HIV but seronegative), we were unable to amplify
any SIVcol nucleic acids. Seroreactivity without PCR amplification has
been documented in those with occupational SIV exposures (1,2).
Therefore, seroreactivity to SIVcol in this person may reflect exposure
to nonviable or defective SIVcol, a nonproductive or cleared infection,
or sequestering of virus in lymphatic tissues.
Conclusions
Our data, taken together with previous reports of high prevalence of
SIV in NHP bushmeat (6) and high levels of NHP exposure
(3), offer new evidence that persons who hunt and butcher
wild NHPs are subject to ongoing exposure and potential infection with
SIV. In a study of 16 SIV isolates from 5 different primate lineages,
12 were capable of infecting human monocyte-derived macrophages, and 11
were capable of replicating in human peripheral blood mononuclear cells
(7), although cell tropism does not necessarily predict
virus pathogenicity. Productive crossover infections may occur in low
numbers in remote areas of Africa, but because of low population density
and isolation, they do not have the opportunity to become epidemic strains
and instead become dead-end infections. Ongoing transmission events may
also be missed because serologic assays for detecting a broad range of
SIVs are lacking or because monitoring is insufficient in populations
with high levels of exposure to NHP blood and body fluids. We also have
reason to believe that the frequency of SIV exposure and possible infection
has increased during recent decades because of a combination of factors
that have increased levels of NHP hunting (3); these
factors include increased access to firearms, increased access to undisturbed
NHP habitat from new logging roads, and increased demand for bushmeat
in logging camps and rural and urban markets. New roads increase travel,
increasing the probability that productive crossover SIV infections will
emerge. Further surveillance for new, potentially successful, cross-species
lentivirus transmission in Africa is needed to ensure a safe blood supply
and prevent the spread of novel, emerging HIV infections.
Acknowledgments
We thank Mark Rayfield
and John Nkengasong for helping establish and implement variant protocol
#1367 and Mbia Eloundou Agathe Feligie, Jose Esther Lyonga, and Eno
Laura Takang for sample collection, processing, and basic serologic
screening for HIV infection.
The work on remote
villagers in Cameroon was supported by an award from the US Military
HIV Research Program (to D.B.); an International Research Scientist
Development Award from the National Institutes of Health, Fogarty International
Center (5 K01 TW000003-05 to N.W.); and an award from the Johns Hopkins
University Center for AIDS Research (NIH #P30 AI42855 to N.W.).
Dr Kalish is the
associate chief for science, Laboratory Branch, Division of HIV/AIDS
Prevention, National Center for HIV, STD, TB Prevention, at CDC. Her
research interests include the evolution and molecular epidemiology
of HIV, the study of unusual HIV variants and recombinant viruses, and
investigations of atypical forms of HIV transmission of public health
importance.
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Suggested citation
for this article:
Kalish ML, Wolfe ND,
Ndongmo CB, McNicholl J, Robbins KE, Aidoo M, et al. Central African hunters
exposed to simian immunodeficiency virus. Emerg Infect Dis [serial on
the Internet]. 2005 Dec [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol11no12/05-0394.htm
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