~) INSTITUTPASTEUR/ELSEVIER Paris 1992

Res. Viroi.

1992, 143, 205-209

Association between HIV1 infection and sexually transmitted disease among men in Central Africa P.M.V. Martin t~), G. Gresenguet (2) M. Massanga (2), A. Georges (2) and J. Testa (3) (I) lnstitut Territorial de Recherches M~dicales Louis Malard~, BP 30, Papeete (Polyn~sie Francaise), ¢2) lnstitut Pasteur, BP 923, Bangui, and (3) Facultd des Sciences de la Sant~, Bangui

SUMMARY

In Africa, heterosexual contact is the major route of transmission of the human immunodeficiency virus (HIV). Previous studies have strongly suggested that other sexually transmitted diseases (STD) may facilitate HIV transmission. However, the association of HIV infection with other STD may simply be a marker of sexual promiscuity. Thus, we compared the association of different STD, HIV status, and sexual behaviour of 160 STD patients and 95 STD-free control individuals. Results showed that STD patients differed from controls in most of the sociological and behavioural parameters, as well as in HIV serological status. Within the STD group, people with genital ulcer disease (GUD) (n = 62l were more likely to be HIV-seropositive ( 2 1 % } than people with urethritis (n = 98, 11.2 %). Meanwhile, there was almost no difference in the sociological and behavioural parameters between the GUD and the urethritis group. Thus, our results reinforce the specific role of mucosal breakage (i.e. genital ulcers) in the transmission of HIV.

K e y - w o r d s : STD, HIV; Sexual behaviour, Central Africa, Genital ulcers, Urethritis, Transmission.

INTRODUCTION In Africa, infection with the human immunodeficiency virus (HIV) within the adult population occurs mainly through heterosexual intercourse. Moreover, such a route of transmission is becoming increasingly important in European and North American countries as the epidemic develops. These observations recently strengthened the interest for mucosal immunity during HIV infection as well as prospects for

vaccines which will be active at the mucosal surface (Forrest, 1991). When the numerous viral particles contained in the sperm of an infected man enter in contact with the vaginal surface of the non-infected female partner, they are accompanied by immunoglobulins of the IgG and IgA classes; the same applies in the inverse situation. These antibodies are d i r e c t e d against s u r f a c e glycoproteins, as well as against internal core

Submitted September 10, 1991, accepted February 28, 1992.

P.M.V. M A R T I N E T A L .

206

proteins (Belec et aL, 1989) and may play a role in limiting the infection. Conversely, IgG antibodies coated on the surface of the virus could enhance its entry into target cells, possibly by means of FclgG receptors present on Langerhans' cells (LC) (Stingl et al., 1977). Whatever the role of local antibodies in sperm or vaginal fluid, there are two possible ways for the virus to enter the hosh depending on the integrity of the receptive mucosal surface. First, if the surface of the mucosa is not damaged, it has been postulated that the virus could cross the mucosal barrier by infecting LC (Braathen et al., 1987). However, the role of epidermal LC in HIV disease is still a controversial issue. Several groups have described morphological changes and a decrease in the number of LC in the epidermis of HIV-infected individuals (Belsito and Thorbecke, 1984; Tschaschler et al., 1987). Furthermore, electron microscopic studies and culture of skin biopsies, as well as in vitro experiments with purified LC suggest that skin LC serve as a primary target and vehicule for HIV (Rappersberger et al., 1988). Inversely, recent experiments with cutaneous biopsies, using more sophisticated methods, do not support the theory that LC serve as a major viral reservoir in the patients (Kalter et al., 1990). Moreover, when nasal or oral mucosae were studied, results obtained with skin biopsies were not confirmed (Becker et al., 1988).

the 3 major risk factors for HIV seroconversion in men were a high frequency of intercourse with prostitutes, a current genital ulcer disease (GUD), and uncircumcision (a fact which putatively increases the risk of bleeding during sexual intercourse). Finally, Latif et al. (1989) showed that male to female transmission of HIV is facilitated by the presence of genital ulcers in infected men. Although the last two studies strongly suggest that ulcers are an independent risk factor for infection with HIV, the association of HIV infection with another STD may simply be a marker of sexual promiscuity (Kreiss et ai., 1988). The comparison of associations of different STD, including HIV, with the sexual behaviour of the subjects investigated should permit a more accurate delineation of the role of classic STD in the transmission of HIV. The present study of sexual behaviour of male STD patients and controis in Central Africa reinforces the role of GUD in HIV transmission.

MATERIALS AND METHODS

Second, if the surface of the mucosa is already damaged by some other cause, such as a preexisting sexually transmitted disease (STD), this could facilitate the entry of HIV into the host. Several studies have shown an association between the presence of HIV antibodies and several STD: gonorrhoea in Kenya, hepatitis B in Copenhagen, Herpes simplex virus type 2 (HSV2) and Treponema pallidum, but not Chlamydia trachomatis or HSV1, in the United States (Kreiss et aL, 1986, Hofman et al., 1988). Cameron et al. (1989) showed that in Nairobi,

The study was limited to male patients and controis, recruited as described previously (Gresenguet et ai., 1990) from the STD (consecutive patients) and surgical wards of the Centre National HospitaloUniversitaire of Bangui. Informed consent was given by patients and controls. Indications for surgery were unrelated to HIV infection, and the majority were for accidental bone fracture. We compared HIV serological status, using an enzyme-linked immunosorbent assay (ELAVIA 1 +2, Diagnostics Pasteur, Marnes-la-Coquette, France), of 98 male patients with acute urethritis (gonococcal in 70 cases, as confirmed by culture), 62 male patients with GUD (syphilis in 28 cases) and 95 STD-free male controls ; positive sera were confirmed by Western blotting (LAVBLOT1, Diagnostics Pasteur). Patients were interviewed in their own language. The questionnaire contained 36 sections concerning the age, profession, education, religion, marital status, the age and

GUD HIV

LC STD

= =

genital ulcer disease. h u m a n immunodeficiency

virus.

= =

Langerhans' cell. sexually transmitted disease.

STD IN HIV TRANSMISSION IN AFRICA

207

Table I. Comparison of sociological and behavioural parameters and HIV seropositivity in individuals with G U D and urethritis and in controls. Controls n = 95 HIV (% positive) Mean age (years)

6.3 28.1

p ~.) 0.01 0.01

GUD n = 62 21 27

p

ioo)

0.01 0.01

Urethritis n = 98 11.2 24.3

Socioprofessional category (070) Unemployed Farmer Worker Middle class Upper class/military Student/school pupil

15.8 9.5 14.7 21. l 9.5 29.4

0.001

19.4 3.2 12.9 17.7 8.1 31.7

NS

23.5 I 17.3 12.2 3.1 42.8

Education (07o) None Primary school Middle level " A " level University

7.5 36.6 24.7 24.7 6.5

0.001

0 18.6 33 39.2 9.3

NS

3.2 27.4 30.6 30.6 8.1

NS

43.9 23.5 6.1 26.3 19.4

Religion (%) Catholic Protestant Muslim Other/none Scarifications (07o)

55.3 28.7 6.4 9.6 64.9

< 0.05 0.01

48.4 22.6 3.2 25.8 46.8

0.001

Marital status (07o) Monogamous Polygamous Unmarried Age at first sexual intercourse (years) No. of regular partners (mean) No. o f occasional partners (mean)

33.9 14.7 46.3 15 1.46 0.77

0.01 0.01 0.001 0.001

23.5 9.1 73.5 16 1.2 1.5

NS NS NS NS

29 11.3 59.7 15.7 0.9 1.7

Category of occasional partner (%) Married woman Friend "Free woman" Prostitute

6.3 31.3 62.5 0

0.01

2.5 70 27.5 0

NS

6.3 46.9 46.9 0

Frequentation of prostitutes (070) Never Rarely Often

47.3 50.5 2.2

0.001

61.2 24.5 14.3

NS

21.1 60.5 18.4

NS

59.7 35.5 4.8

Price of prostitutes (in CFA) (070) < 500 500-1,000 > 1,000

49 44.9 6.1

< 0.05

(*) Comparison between controls and individuals with STD (both GUD and urethritis). (**) Comparison between GUD and urethritis patients. NS = not significant.

32 68 0

208

P.M.V. M A R T I N E T A L .

category of partner (girlfriend, prostitute, or "free woman") of first sexual intercourse, the number of regular partner(s), the number and category of occasional partner(s), frequency of intercourse per week, travel in or outside the country, the frequency of intercourse while on travel, the frequency of visits to prostitutes, the price of prostitutes and the use of condoms. In Central Africa, women with multiple partners but who do not receive payment for their sexual activities are called "femmes libres" or "free women". A detailed history was obtained on the number of injections and blood transfusions received in the past year, and previous medical problems, hospital visits, and scarifications in the past two years. All were circumcised. Answers were coded and computerized for statistical analysis. A chi-squared test was used for comparison of percentages and Student's t test for comparison of means. Details of the questionnaire are described in Gresenguet et al. (1990).

RESULTS Among the 160 patients with STD, 24 (15 o70) had HIV antibodies while only 6/95 (6.3 °70) of the controls were HIV-seropositive ; this difference was highly significant (p < 0.01). Table I shows a clear difference in the percentage of HIV-positive individuals between controls (6.3 o70), patients with urethritis (11.2 °/0) and patients with GUD (21 o70). It is clear from the results in the table that the urethritis group did not differ in sociological and behavioural parameters from the group with GUD, while both STD groups differed from controls in all parameters. There was no significant difference between STD and control groups concerning circumcision, the mean frequency of intercourse per week with a regular partner (3.83 versus 3.97), the total frequency of intercourse per week (7.12 versus 7.58), the category of first partner (friend, 89.2 070 versus 87.1 070; prostitute, 10.8 °70 versus 12.9 o70), the use o f c o n d o m s (3.8 070 versus 3.2 o70), travel in or outside the country and the frequency of intercourse while on travel (81.4 °7o versus 77.6 °70). However, there was a significant difference in age and scarifications between the urethritis and the GUD groups. Whether the difference in the proportion of scarified patients was a reflection of HIV seropositivity, or was related to age is not clear, and further investigation is necessary.

DISCUSSION We have previously shown that men with acute STD make up a core group of younger, educated, unemployed individuals, with a high diversity in their sexual life (Gresenguet et aL, 1990). We now show that men with acute STD are significantly more often HIV-seropositive than controls. Within the STD group, men with GUD are far more often infected with HIV than men with urethritis, while they do not differ markedly in their sexual behaviour. Our study confirms those of others on the association between STD and HIV infection, and highlights the role of GUD among individuals who belong to the same behavioural group. One reason for a higher prevalence o f HIV a m o n g men with GUD is the high recurrence rate of genital herpes among HIV-positive individuals. Further study in Africa should focus on this point. Whether the high proportion of HIV-positive men in the urethritis group is due to risky sexual behaviour or to a direct causal effect o f urethritis remains to be investigated. Conditions for transmission of HIV to heterosexual men in Africa are now better understood. First, a series of social and behavioural factors, including high sexual diversity, increase the risk of acquiring classic STD, either urethritis or GUD. Second, when the mucosal barrier is damaged, there appears to be an increased risk of becoming infected by HIV on encountering the virus, independently of sexual behaviour. The prevention of genital ulcers, many of which are of bacterial origin and curable with antibiotics, may prove to be very effective in the limitation of the spread of the epidemic in Africa. Moreover, if disruption of the mucosal barrier facilitates viral entry into the blood stream, vaccines which are active solely at the mucosal surfaces are unlikely to be efficient in preventing the epidemic. Future research should focus on target cells on mucosal surfaces, the neutralizing capacity of natural and induced local antibodies and the lack of enhancing power of vaccine-induced antibodies at the mucosal surface.

STD IN HIV TRANSMISSION

Association entre I'infection par le VIHI et ies maladies sexuellement transmissibles dans la population masculine d'Afrique Centrale En Afrique, la transmission h6t~rosexuelle est le mode majeur de transmission du virus de l ' i m m u n o d6ficience humaine (VIH). Des 6tudes r6alis6es au Kenya et en Zimbabwe ont tr~s fortement sugg6r6 que les autres maladies sexuellement transmissibles (MST) facilitaient la transmission du VIH. Cependant, l'association entre une quelconque MST et une infection ~t V I H peut simplement 8tre le t~moin, pour les sujets 6tudi6s, d'une promiscuit6 sexuelle plus importante. Nous avons donc compar6 I'association entre diff6rentes MST, la pr6sence d'anticorps anti-VIH et le c o m p o r t e m e n t sexuei de 160 malades atteints de MST et 95 t6moins sans MST. Les r6sultats ont montr6 que presque tous les param~tres sociologiques et c o m p o r t e m e n t a u x 6tudi6s ainsi que le statut s6rologique vis-h-vis du V I H , 6taient diff6rents pour ies malades atteints de MST et pour les t6moins. A l'int6rieur du groupe des patients MST, les porteurs d ' u n uic~re g6nital (n = 62) 6taient plus souvent s6ropositifs pour le V I H ( 2 1 % ) que les malades ayant une ur6thrite (n = 98, 11,2 %). Cependant, il n'existait pas de diff6rence entre presque t o u s l e s param~tres sociologiques et c o m p o r t e m e n t a u x 6tudi6s pour les deux groupes de malades. Nos r6sultats renforcent donc l'id6e du r61e jou~ en soi par ies ulc~res g~nitaux dans la transmission du V I H . Mots-cl~s: VIH, M S T ; Ulc~res g~nitaux, Ur6thrites, Transmission, Afrique Centrale, C o m p o r t e ments sexuels.

References Becker, J., Ulrich, P., Kunze, R. et aL (1988), Immunohistochemical detection of HIV structural proteins and distribution of T lymphocytes and Langerhans' cells in the oral mucosa of HIV-infected patients. Virchows Arch. A Path. Anat. Histopathol., 412, 413-419.

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Belec, L., Georges, A.J., Steenman, G. & Martin, P.M.V. 0989), Antibodies to human immunodeficiency virus in vaginal secretions of heterosexual women. J. infect. Dis., 160, 385-391. Belsito, D.V. & Thorbecke, G.J. (1984), Reduced lapositive Langerhans' cells in AIDS. New Engl. J. Med., 311, 857-858. Braathen, L.R., Ramirez, G., Kunze, R.O. & Gelderblom, H. 0987), Langerhans' cells as primary target cells for HlV infection. Lancet, II, 1094. Cameron, D.W., Simonsen, J.N., D'costa, L.J. et al. (1989), Female to male transmission of human immunodeficiency virus type i : risk factors for seroconversion in men. Lancet, I1, 403-407. Forrest, B.D. (1991), Women, HIV and mucosal immunity. Lancet, l, 835-836. Gresenguet, G., Testa, J., Georges, A.J., Massanga, M. & Martin, P.M.V. (1990), Sexual behaviour in Central African men with sexually transmitted disease and in controls. AIDS, 4, 1158-1160. Hofman, B., Kryger, P., Pedersen, N.S. et al. (1988), Sexually transmitted diseases, antibodies to human immunodeficiency virus, and subsequent development of acquired immunodeficiency syndrome in visitors of homosexual sauna clubs in Copenhagen: 1982-83. Sex. Transmit. Dis., 15, 1-4. Kalter, D.C., Gendelman, H.E. & Meltzer, M.S. (1990), Infection of human epidermal Langerhans' cells by HIV [reply]. AIDS, 4, 266-268. Kreiss, J.M., Koech, D., Plummer, F.A. et al. (1986), AIDS virus infection in Nairobi prostitutes: spread of the epidemic to East Africa. New Engl. J. Med., 314, 414-418. Kreiss, J.M., Carael, M.A. & Meheus, A. (1988), Role of sexually transmitted diseases in transmitting human immunodeficiency virus. Genitourinary Med., 64, 1-2. Latif, A.S., Katzenstein, D.A., Basset, M.T., Houston, S., Emmanuel, J.C. & Marow, E. (1989), Genital ulcers and transmission of HIV among couples in Zimbabwe. AIDS, 3, 519-523. Rappersberger, K., Gartner, S., Schenk, P. et al. (1988), Langerhans' cells are an actual site of HIV-I replication. Intervirology, 29, 185-194. Stingl, G., Wolff-Schreiner, E.C., Pichler, W.J., Gschnait, F., Knapp, W. & Wolff, K. (1977), Epidermal Langerhans' cells bear Fc and C3 receptors. Nature (Lond.), 268, 245-246. Tschaschler, E., Groh, V., Popovic, M. et al. (1987), Epidermal Langerhans' cells - - a target for HTLVIlI/LAV infection. J. invest. Dermatol., 88, 233-237.

Association between HIV1 infection and sexually transmitted disease among men in Central Africa.

In Africa, heterosexual contact is the major route of transmission of the human immunodeficiency virus (HIV). Previous studies have strongly suggested...
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