PARASITES As Cofactors For AIDS
Excerpts from the work of
Dr. Richard Bowman Pearce
Chronic Non-Opportunistic Parasitism as a Co-Factor for AIDS © 1997 Richard Bowman
The growing body of evidence is
supporting the idea that parasitic disease may be an essential factor for AIDS. The theory
was based upon three lines of evidence :
all the risk groups for AIDS had
evidence for chronic "pan-immunosuppression" prior to HIV/AIDS
the epidemic of parasites
in homosexuals preceded AIDS by a few years. That was a common factor
with African and Haitian risk Groups.
parasites exert immunosuppressive,
antigenic and mitogenic effects on T cells.
- Between 80 and 100 percent of sexually active homosexual men worldwide are infected with
one or more species of intestinal parasite.
- The epidemic of parasites in gay men preceded AIDS by a few years.
- In separate studies, the parasites gay men carry -- E. dispar (formerly E.
histolytica), other so-called "nonpathological" amebae and Giardia
-- have been shown to be specifically associated with a suppression of cell mediated
immunity, elevation of IgM, depressed CD4:CD8 ratios, and increased risk for
seroconversion to - and seropositivity for - HIV.
- Parasites explain why AIDS develops among men and women alike in Africa and other
tropical regions (Southeast Asia, the Caribbean, India) where parasites infect men and
women indiscriminately. By contrast, in developed countries and urban settings, male
homosexuals are the principal risk group for chronic parasite infection and AIDS.
- Malaria appears to predispose to HIV in central and eastern Africa. Malaria has long
been regarded as a co-factor for EBV-induced Burkitt's lymphoma.
- E. histolytica extract activates latent HIV in T cells in culture. In
mice, parasites activate HIV transgenes, depress anti-HIV and anti-adenoviral CTL
activity, and promote a Th2 predominant state (which may favor retroviral
replication). Mice with malaria are much more susceptible to leukemia caused by Moloney
Murine Leukemia Virus than non-parasitized mice.
- Logistic regression analyses of factors predisposing to KS in gay men show that the
independent risk is exposure to feces. The intestinal parasites that colonize gay men
are transmitted exclusively through the fecal-oral route. One early survey of Kaposi's
Sarcoma in Africa showed an exact geographical confluence between KS and onchocerciasis, a
chronic parasitic disease. Thus, the development of KS in gay men without HIV may
be related to chronic immunodepression by parasites that permits the emergence of the
KS associated herpes virus, HHV8.
- Only feral cats that are parasitized naturally acquire FIV and develop feline
AIDS. Pathogen-free cats do not transmit FIV when housed together, and when inoculated
with FIV undergo an acute phase response but fail to develop feline AIDS characterized by
severe CD4 depletion, opportunistic infection, and death.
- Monkeys housed in the nation's primate centers, including those used in SIV studies,
are universally infected with intestinal parasites and the animals in which the first
reported cases of immunodeficiency appeared had been previously infected with malaria.
- Cattle with trypanosomes are significantly more likely to be infected with Bovine
Leukemia Virus (BLV) and to develop leukosis than parasite-free herds.
- Progression to fulminant AIDS is more rare in groups such as sex partners of
hemophiliacs and health care workers with occupational exposures to HIV than other
risk groups whose immune systems are chronically activated. Such persons may
seroconvert to HIV and/or develop anti-HIV cell-mediated activity, but lacking
parasites or other chronic immune stimulus, do not progress to fulminant AIDS at the high
rates observed in the major risk groups.
- In 1987, it was predicted that HIV and AIDS would most likely spread by heterosexual
transmission beyond Africa into other parasite endemic regions of the world, especially
rural South America, Southeast Asia, and India. This, in fact, has occurred. If parasites
were not an obligatory cofactor for AIDS, heterosexual transmission of HIV and AIDS would
theoretically have occurred at an equally high rate in parasite-free regions of North
America, Europe, and Australia. The comparatively low rate of HIV infection and AIDS
progression among heterosexuals in these temperate regions is consistent with the idea
that environmental cofactors are important determinants of HIV transmission and
Not widely known is the fact that 80% or more of sexually active gay men currently
carry Entamoeba dispar, E. coli, E. hartmanni, I. bütschlii, D. fragilis,
and Giardia intestinalis among other protozoa (compared to an incidence in
the general population of a 1-3%). The epidemic of parasites in gay men began in the mid
1970s and grew exponentially becoming pandemic in this group by 1979, a year or two before
AIDS began to take its toll. E histolytica lectin stimulates HIV production
in vitro while E. dispar and other "non-pathogenic" amebae in
HIV(-) gay men are independently associated with skin anergy, chronically elevated IgM,
and an increased risk for seroconversion to HIV.
In gay men, oral-anal contact is an independent risk factor for KS. KS can develop
in HIV negative homosexual men, suggesting that some other immunodepressing agent
besides HIV-1 can predispose to the putative KS virus, HHV8. This other source of
immunodepression could be parasites since, in Uganda, KS (but not other tumors) has
been found to be in exact and narrow geographical confluence with the chronic parasitic
disease onchocerciasis. In Africa and other tropical areas as well as in Belle Glade,
Florida, AIDS affects women as frequently as men.
In the U.S., between 1 and 2 million gay men are currently multiply infected with
protozoa, yet very few are even aware of the fact. No other putative cofactor
for AIDS, (e.g. mycoplasma, alcohol and drug abuse, HHV-6A) has such a uniformly high
incidence rate in the gay and tropical risk groups for AIDS.
Association between Intestinal and Other Non-opportunistic Parasites and HIV/AIDS
Largely unappreciated, but by no means unknown, is the fact that 60% to 100% of
sexually active gay men currently harbor one or more species of intestinal parasite,
including Entamoeba dispar, E. coli, E. hartmanni, Iodamoeba butschlii, Dientamoeba
fragilis, and Giardia intestinalis among others (Law et al, 1991, Esfandiari et al., 1995).
A recent surveillance for Giardia in New York City shows that the spread
of this parasite through sexual means, i.e. as a STD among mostly gay men, continues to
the present time. The highest rates are among hispanic children (mostly Dominican
immigrants) and gay men, both HIV(+) and HIV(-) (NYC Department of
Like sexually active gay men, the tropical risk groups for AIDS also have a high
prevalence of non-opportunistic parasites. In addition to enteric infections by nematodes
and protozoa, these include schistosomiasis, strongyloidiasis, onchocerciasis and malaria
(Climent, et al., 1994; Moore and Buster, 1984; Bouree, et al.,
1995; Plumelle and Edouard, 1996).
The triad of HIV, non-opportunistic parasites, and AIDS is now reported for Haiti, the
Republic of Congo (formerly Zaire), Uganda, Rwanda, Tanzania, Ethiopia, Puerto Rico,
Jamaica, Martinique, Papua New Guinea, India, Pakistan, Southeast Asia, Belle Glade,
Florida and South Los Angeles. Indeed, lymphotropic retroviruses, which require immune
activation to reproduce successfully, may have co-evolved with parasites in the tropical
regions of the world whence HIV and HTLV emerged.
Parasites Are Agents of Chronic
Even the so-called "non-pathogenic" (i.e. non-invasive) ameba can depress
cell-mediated immunity. They found that anergy significantly and independently
associated with the presence of E. histolytica [now termed E. dispar], E.
coli, and Iodamoeba bütschlii but not with other parasites (P< 0.005).
The authors concluded:
"Our main findings were that intestinal parasites and systemic deficiency of
cell-mediated immunity correlate within the group of healthy homosexual men and that this
correlation specifically involves the 3 amoebas, E. histolytica, E. coli, and I.
bütschlii. [O]ur data support the hypothesis that parasites may cause AIDS or act as
a cofactor to facilitate HIV infection and/or its progression to AIDS."
For gay men, parasitic infections are multiple, repeated (weekly exposures are not
uncommon), and encountered for the first time in the second and third decades of life.
This sudden and sustained onslaught of antigens and protozoa may have considerable impact
on immune responses and the state of immune activation not only in the gut, but
systemically as well.
Bentwich and colleagues of the Weizman Institute in Rehovot Israel have reported that
Ethiopian Jews with and without HIV-1 also carry several species of intestinal parasite
including helminths (Kalinkovich et al., 1996 XI ICA). These
patients are being followed for possible changes in the in rate of progression to AIDS but
it is these authors' opinion that progression to AIDS is slower in Ethiopians treated for
parasites. They have shown that lymphocytes from parasitized individuals are highly
susceptible to HIV infection in vitro (persona lcommunication).
Speaking at a recent conference, Dr. Bentwich reported that in Africa, Ethiopians
with HIV died two to three times more quickly than those infected in the West and who were
without parasites. In an article appearing in the Jewish Bulletin of Northern
California Bentwich was quoted as saying:
The Epidemic of Parasites in Gay Men Preceded AIDS
The incidence of gastrointestinal parasites rose exponentially in gay men during
1977-1983 (Figure 2). The transmission of parasites was associated with sexual
activity that exposed partners to feces, particularly oral-anal sex or
"rimming." By 1980, the prevalence of parasites was 60% or greater for
homosexual men attending STD clinics or private practice (Pearce,
1983; Markell and Kuritsubo, 1981; Phillips et al., 1981; William, et al., 1978; Schmerin,
et al., 1977; Mildvan et al., 1977). HIV was apparently introduced into Western
societies in the 1970s or even earlier.
One possible reason the virus didn't proliferate and produce
fulminant disease until the early 1980s might be the absence of a suitable pool of
parasitized hosts. By that time parasite epidemic in gay men had reached its height. Even
well before 1980, clinicians had warned about the emerging parasite epidemic in gays. The
first to report a homosexual case cluster of E. histolytica was Harry Most who dubbed
Manhattan a "tropical isle" (Most,
1968). This concern was echoed by another leading infectious disease
specialist who in in 1979 warned:
Evidence indicates that an epidemic of intestinal protozoan infection exists in
the homosexual male population in New York City. The difficulty in making a diagnosis,
inadequate therapy, failure to alert potential victims,and official neglect of the
epidemic have combined to create a dangerous situation. (Kean
et al., 1979)
The parasite theory led to the prediction that AIDS would spread beyond Africa and
Haiti into other regions of the world where parasites are holoendemic (Pearce, 1986, 1989). In contrast, and contrary to the warnings of
some researchers (Redfield, 1986), AIDS has not emerged as an
overwhelming epidemic among heterosexuals in the developed (and largely parasite-free)
countries of North America, Europe and Australia. This strongly suggests an environmental
component to AIDS is present in the tropical regions of the world.
Unlike Other Putative Cofactors
for HIV (e.g. HTLV-1, CMV, HHV-6A, Adenoviruses, Mycoplasma), Parasites Are Chronic,
Multiple, Recurrent, Antigenically Highly Variable, and Present in 80-100% of the Gay and
Tropical Risk Groups but Only 1-2% of the General Population
Table 2. Frequency of intestinal parasites in ARC patients with lymphadenopathy
syndrome (LAS), thrombocytopenia (ITP) compared to healthy gay controls and mostly
heterosexuals in the San Francisco Bay Area in 1982. [From Pearce and Abrams 1987].
Parasitism Has Been Etiologically
Linked to Other Lymphotropic Retroviral Diseases Including ATLL, Burkitt's Lymphoma, and
BLV-induced Bovine Leukemia, and Feline Immunodeficiency Virus (FIV) Induced AIDS in Cats
and MAIDS in Mice.
Strongyloides, filaria, malaria and other parasites are thought by several researchers
to predispose to adult T cell leukemia (ATLL) by chronically activating the HTLV-1
provirus (Nakada et al., 1983; Patey et al., 1992; Plumelle Y, et
Strongyloides has also been frequently observed in association with HTLV-1 and ATLL.
Nakada et al. reported that 60% of 166 chronic Strongyloides sterocoralis
carriers were HTLV-1 seropositive compared to only 20% of nearly 3000 controls consisting
of persons not carrying the worm at the time of the study (Nakada et
Denis Burkitt originally postulated that malaria caused Bukitt's lymphoma by
chronically activating B cells and depressing anti-EBV immune responses (Burkitt, 1969). If true, one would expect less lymphoma in Africans
with sickle cell anemia since such individuals resist malaria.
A survey of the literature reveals one study, published in 1970, showing that Nigerians
with the sickle cell trait were significantly (P<0.03) less likely to develop Burkitt's
lymphoma than persons with wild type hemoglobin (Williams A, 1966).
Primates with SAIDS are also infected with parasites. According published
reports and to James L. Blanchard, DVM Ph.D., Head Veterinarian at the Tulane Regional
Primate Research Center, all new world and old world monkeys used in research, including
those currently used in AIDS research, are infected with several species of intestinal
protozoa including E. histolytica and Giardia (van Riper, et al., 1966; JLB, personal communication).
Cattle with trypanosomes are significantly (P<0.001) more likely to be infected with
BLV, a virus related to HTLV-1, than non-parasitized herds (Hare et
al., 1970). Previously, in a USDA study, it was observed that 100% of overtly
leukemic cattle were trypanosomized (Malmquist, 1965).
In contrast to pathogen-free experimental cats, nearly all outdoor and feral cats
carry parasites including Isospora felis, I. rivolta, Dupylidium canium,
Toxocara cati, Toxascaris leonina, Ancylostoma sp and Toxoplasma gondii (Lin et al., 1990).
More recently, a group from the Colorado State University was able to induce AIDS in
cats raised and housed under pathogen-free conditions. By infusing plasma pooled
from cats with FIV infection, more than 50% of recipient kittens developed AIDS by 6-12
weeks (Diehl, et al., 1995). The model is reminiscent of
transfusion cases of AIDS in humans where allogeneic proteins may stimulate the immune
system and predispose to HIV infection and progression to AIDS.
These observations in cats, cattle, and mice merely reflect what veterinarians have
long known: animals with intestinal parasites are much more susceptible to other
infections, particularly viruses.
Confluence of Onchocerciasis and
KS in Uganda
In 1966, Williams and Williams reported a closely defined geographical confluence
between KS and onchocerciasis (a filarial parasite) in the Western Nile District of
Uganda (Williams and Williams 1966). In contrast, other
tumors such as cervical and breast cancers were present throughout the entire district
which is heavily populated. A second report on the distribution of onchocerciasis in
Africa confirms the existence of specific foci for the parasite as reported by Williams
and Williams (Oomen, 1969). It is possible that black flies (Simuliidae)
that are the insect vector for onchocerciasis also transmits the viral agent of KS.
However, HHV8, the probable agent of KS is readily transmitted by sexual contact so
clearly an insect carrier is not obligatory for transmission. A more likely scenario is
that the immunosuppression caused by chronic ochocerciasis allows for HHV8 expression just
as all herpes viruses express during periods of protracted immunosuppresion.
Based on the African Paradigm and Independent
Risk Associated with Anilingus, Parasites Explain the "Mystery" of KS in
HIV seronegative gay men with only slightly depressed or normal numbers of CD4
cells can develop KS (Chuck et al., 1996). The virus
that most likely causes KS, HHV8, is easily transmitted sexually since up to 25% of random
blood donors are seropositive for HHV8 (Lennette, et al., 1996).
The KS virus apparently disseminated through the homosexual community by sexual contact.
However, in several studies, anilingus ("rimming"), was found to be a strong
and independent risk factor for KS (Beral et al., 1992).
Anilingus is also the most important factor for the transmission of intestinal
parasites among adults in this country. It is certain, given the high prevalence of
parasites in the homosexual risk group, that these HIV-negative patients with KS and
reporting frequent oral-anal contact were heavily parasitized.
Thus, KS and lymphomas both may be present in HIV negative gay men immunosuppressed by
parasites. Those more severely immunocompromised by the CD4 depleting effects of HIV may
have more aggressive tumors. This appears to be the case as KS in HIV(-) patients runs a
more indolent course than in HIV(+) patients.
Parasites Explain the High Incidence of AIDS in
Women in the Tropical Areas Compared to Developed Countries
Parasitic infection may be a primary contributing factor to AIDS in Africa
where men and women alike are at risk (Quinn et al. 1987).
Parasites are also endemic in Belle Glade, Florida (Moore and
Buster, 1983), Ethiopia (Bentwich et al., 1995), and
among the indigenous peoples of Papua New Guinea (Dwyer et al., 1997)
and the Caribbean - all risk groups for AIDS. Activation of T cells, macrophages and other
APC is necessary for HIV replication. This fact alone, may explain why lymphotropic and
monocyte-tropic viruses originated in parasite endemic regions where suitable hosts
reside. Indeed, HTLV-1, HIV-1, HIV2, and EBV - all lymphotropic viruses - are all found in
close geographical relationship with parasite endemic regions (Tajima
et al., 1981, 1985; Merino et al.; Pearce, 1989; Burkitt, 1969).
Women, especially in the devloping countries of the world, are also prone
to harbor chronic vaginal infections such as trichomoniasis, or have other predisposing
vaginal factors for HIV.(van de Wijgert, et al., 1996).
In 1982, the CDC and Several Clinical
Researchers Recommended That Physicians Treat "Non-pathogenic" Amebae in Gay Men
In 1982, the CDC issued a recommendation that asymptomatic intestinal
parasitic infections in persons "for whom anal-oral contact is a sexual practice
should be treated in accordance with recommendations for symptomatic individuals" (CDC, 1982). With few exceptions, this recommendation has not been
Unfortunately, most physicians caring for homosexual patients are unaware
of the potential adverse consequences of chronic parasitism on the course of HIV infection
and their patients are often not being provided with the option of treating these chronic
infections. Since the infections are often aysmptomatic in terms of gastrontestinal
criteria, infections often continue undiagnosed and untreated for months and longer.
Guidelines Are Not Focused on Preventing Fecal Contamination
Although sexual behaviors in other areas have changed in response to safer sex
campaigns, the practice of rimming (anilingus) has not diminished in recent years (Elford et al., 1992) nor is it adequately addressed in safer sex
guidelines. Although some safe sex guidelines generally caution against oral-anal contact,
the need to avoid fecal contamination during foreplay and when removing condoms is not
Present-day gay erotic videos faithfully show condom use and avoidance of semen
ingestion, but rimming is frequently featured. Men viewing these socially conscious
videos may regard all activities portrayed as "safe."
Unfortunately, most gays are totally ignorant that they may be infected with
parasites or that many AIDS researchers consider them possible cofactors for AIDS.
estimated 1/2 to 1 million HIV(+) gay men in this country who are also infected with
parasites, and their physicians, ought to be informed that many leading researchers
consider parasite treatment a prudent course of action. Most importantly, from a public
health standpoint, studies of the possible exacerbating role of parasites in AIDS need to
Activating Cofactors Appear to Have a Slower Progression to AIDS
Approximately 20% of wives or sex partners of HIV(+) hemophiliacs or HIV(+) transfusion
recipients in this country have seroconverted to HIV (Kim et al.,
1988; Chorba et al., 1993; Peterman et al., 1988), but the incidence of AIDS in
these "at risk" individuals is remarkably low. This is in spite the probability
that a sizeable fraction of them may be misclassified and are actually a part of other
Low HIV infection and AIDS progression rates have been reported by others for
heterosexual partners of hemophiliacs (Kamradt, 1990). If
HIV alone were sufficient to cause disease, it is likely that a much higher percentage of
sexual partners of hemophiliacs should have gotten AIDS by now.
Their progression rate may be low because they are one of a few groups with HIV-1 but
without chronic immune activation.
Cofactor Theory has Support from Many Top AIDS Researchers and has Appeared in Mainstream
Journals Including Science, Nature, The New England Journal of Medicine, The Lancet,
Immunology Today, and JAMA
The idea that parasites are possible cofactors for AIDS has been expressed by many
researchers in reputable journals (Fauci 1988, 1993 ; Lange et al.,
1983; Bentwich et al., 1995; Quinn et al. 1987; Stanley et al., 1996 ; Rene et al., 1984;
Bergstrøm et al., 1986; Pearce, 1983, 1984, 1986; Pearce and Abrams 1984, 1987; Krogstadt
et al., 1986; Cox, 1990; Archer and Glinsman 1985, Piot et al., 1988). However,
neither the majority of gay men nor their physicians are aware of the possible
consequences of enteric infections. Most are not even aware there is an epidemic of
parasitic infections in gay men! As reviewed here, there is much circumstantial and some
direct evidence to suggest that parasites are an important if not obligatory
factor in AIDS.
The diagnosis of parasites in asymptomatic or mildly symptomatic gay men is rarely
sought and, when parasites are disclosed, treatment for non-pathological amebae is seldom
offered. Indeed, some have argued that because these parasites do not invade the bowel
wall, they do not need to be treated (Allason-Jones E et al.,
This argument has held sway among many public health officials and clinicians for
several years but it has been countered by epidemiologists, immunologists, and
retrovirologists. Parasites are likely to continue to be transmitted as an STD among
individuals at risk for HIV until and unless studies show a direct and definitive role for
non-opportunistic parasites in AIDS or KS (if any).
Chronic Non-Opportunistic Parasitism as a Co-Factor for AIDS © 1997 Richard Bowman