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PubMed1994

[Onchocerciasis control program in West Africa: socioeconomic development and risk of recrudescence of transmission. 2. Experimental study of the transmission of Onchocerca volvulus strains from Southwestern Sierra Leone by Simulium yahense and Simulium squamosum].

The movements of human populations towards the mining wealth of the northern parts of Sierra Leone are favorable to a high contact rate between onchocerciasis patients coming from the south-western area of this country and the vector species Simulium yahense and Simulium squamosum which assume the essential of onchocerciasis transmission in the above-mentioned mining area. In fact, the Onchocerca volvulus strains concerned by this contact seem to be more pathogenic than those locally transmitted. In order to assess the danger it could represent for the Onchocerciasis Control Programme in West Africa, we carried out the experimental study of transmission which may result from this contact when more or less infected onchocerciasis patients are involved. The results indicated that this transmission by S. yahense may reach high proportions only when heavily infected onchocerciasis patients are implicated. We took also notice of the low capacity of S. squamosum to transmit the O. volvulus strains from the south-western Sierra Leone, irrespective of the microfilarial load of patients. Thus, in the most favorable conditions of a high parasite-vector contact of the study, involvement of S. yahense and onchocerciasis patients with high skin microfilarial loads is the only occurrence to which a high risk of intensive transmission may be related. The authors consider that the probability of such a risk occurring will be drastically reduced, due to the considerable decrease of skin microfilarial loads in human communities which regularly have the advantage of ivermectin (Mectizan) mass treatments.

Animals↗
PubMed1994

Risk factors for woman-to-man sexual transmission of the human immunodeficiency virus. Italian Study Group on HIV Heterosexual Transmission.

A cross-sectional study of stable monogamous couples, recruited from 16 clinical and surveillance centers in Italy between 1987 and 1992, was carried out to investigate the risk factors of woman-to-man sexual transmission of human immunodeficiency virus (HIV). The male partners of all HIV-infected women attending the centers were invited to participate in the study. Of the 275 male partners who were tested for HIV and interviewed with use of a structured questionnaire, 51 were excluded because they had other possible risk factor for HIV infection, no established risk factor was found in the index case, or they had stopped engaging in sexual intercourse. Fourteen of the 224 men (6.3%) were seropositive for HIV. At logistic regression, the highest risks of transmission were for men practicing peno-anal intercourse [odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0-22.2] and for men whose partner had acquired immune deficiency syndrome (AIDS) or a CD4+ lymphocyte count of < or = 400/mm3. No seropositive men were observed among those who were aware of the woman's HIV seropositivity since the beginning of the relationship or were partners of a zidovudine-treated woman. The results suggest that the risk factors described in man-to-woman and man-to-man HIV sexual transmission also operate in woman-to-man transmission.

Adult↗
PubMed1996

Transmissible spongiform encephalopathies (TSE): minimizing the risk of transmission by biological/biopharmaceutical products: an industry perspective.

Several guidelines and recommendations have been published on assessing the potential risk of a biological product being contaminated with an agent causing a Transmissible Spongiform Encephalopathy (TSE). Basic principles which can be used during the manufacturing of biological products to minimize the risk of transmission of TSE agents include the following: (i) obtaining animals, tissues or animal-derived raw materials from countries in which the relevant TSE agent is reported to be absent; (ii) screening animal-derived material for appropriate animal husbandry, feeding practices, health certification, tissue procurement and processing practices, and human-derived material for appropriate medical history information and, if relevant, plasma donor exclusion criteria; (iii) selection of tissue source of raw material with reference to potential risk for harbouring or amplifying TSE agents; (IV) human tropism of TSE agent of concern; (v) quantity of raw material used to manufacture a dose of product; (vi) number of daily doses required for indication; (vii) route of administration; (viii) indication and age of patient; and (ix) clearance capabilities by the product purification scheme. A risk evaluation will be represented for Trasylol (Aprotinin) which is manufactured from bovine lung tissue. Trasylol is a protease inhibitor used in the control of blood loss during open heart surgery. Bovine Spongiform Encephalopathy (BSE) is a concern when a product is derived from a bovine source. Even though only bovine lung tissue from BSE-free countries is used to manufacture Trasylol, it was decided, based on the primary tissue source selection, to evaluate the potential of the purification process to clear a TSE agent. Duplicate "spiking experiments" were performed using a mouse-adapted strain of scrapie as the model for BSE. Four steps in the purification process were evaluated. Titration of "spiked" loading material and output samples was performed at dilutions of 10(-4) to 10(-7) and undiluted to 10(-7), respectively. The sum of the purification steps evaluated provided a clearance factor in excess of 18 log10 for a TSE agent. An overall safety factor of 30 is obtained using the notification document issued by the Federal Health Office (Germany), dated February 16, 1994, on "Safety Requirements for Medical Products Derived from Body Constituents of Cattle, Sheep, or Goats to Avoid Risk of Transmission of BSE or Scrapie". Based on a six-parameter risk assessment, this document considered a product of low-risk for transmitting TSE agents if obtaining or exceeding a score of 20. Principles for minimizing the risk of transmission of TSE agents in products derived from primary tissues are contrasted to strategies for biotechnology products.

Animals↗
PubMed1997

Transmission of a highly drug-resistant strain (strain W1) of Mycobacterium tuberculosis. Community outbreak and nosocomial transmission via a contaminated bronchoscope.

CONTEXT: Nosocomial transmission of multidrug-resistant tuberculosis (MDR TB) has been reported primarily in New York State and has generally been presumed to occur via respiratory aerosols. OBJECTIVE: To assess nosocomial transmission of MDR TB. In 1995, 8 patients with MDR TB were identified in South Carolina; all were resistant to 7 drugs and had matching DNA fingerprints (strain W1). Community linkswere identified for 5 patients (Patients 1-5). However, no links were identified forthe other 3 patients (Patients 6-8) except being hospitalized at the same hospital as 1 community patient. DESIGN: Outbreak investigation. SETTING: Community and hospital. PATIENTS: Eight patients whose MDR TB isolates had DNA fingerprint patterns matching strain W1. MAIN OUTCOME MEASURES: Clinical characteristics of patients with strain W1 Mycobacterium tuberculosis isolates. RESULTS: Patient 5 (community patient) and Patient 8, diagnosed April 1995 and November 1995, respectively, had clinical courses consistent with MDR TB, with smear-positive and culture-positive specimens and cavitary lesions on chest radiograph; both died of MDR TB less than 1 month after diagnosis. Patients 6 and 7 (diagnosed May 1995) each had 1 positive culture for MDR TB; specimens were collected during bronchoscopy. Patient 6 had a skin test conversion after bronchoscopy. Neither Patient 6 nor Patient 7 had a clinical course consistent with MDR TB, neither was treated for MDR TB, and both are alive and well. No evidence of laboratory contamination of specimens, transmission on inpatient wards, or contact among patients was found. All 4 received bronchoscopies in May 1995; Patients 6, 7, and 8 had bronchoscopies 1, 12, and 17 days, respectively, after Patient 5. Observations revealed that bronchoscope cleaning was inadequate, and the bronchoscope was never immersed in disinfectant. CONCLUSIONS: Inadequate cleaning and disinfection of the bronchoscope after the procedure performed on Patient 5 led to subsequent false-positive cultures in Patients 6 and 7 and transmission of infection to Patient 6 and active MDR TB to Patient 8.

Aged↗
PubMed2003

Transmission profile of hepatitis B virus infection in the Batam region, Indonesia. Evidence for a predominantly horizontal transmission profile.

The aim of this study was to describe the distribution of hepatitis B virus markers among the autochthonous and immigrant multicultural populations of Riau province, Indonesia, in order to define the groups at risk and their infrastructure. This investigation was part of a large hepatitis B vaccination study. A total of 9701 healthy individuals, aged 5 years or older and living in the urbanised area of Batam, near Singapore, and on the surrounding islands were included. Socio-epidemiological data were collected, blood was drawn, and sera were tested for antibodies to hepatitis B core (anti-HBc) and surface antigen (anti-HBs). Anti-HBc-positive sera were tested against hepatitis B surface antigen (HBsAg). All tests comprised immunoassays from Roche (Germany) using Elecsys 2010. Complete data were available from 9314 subjects. The results showed relatively low prevalences of anti-HBc (a marker of a previous hepatitis B infection) and HBsAg in the 5-year-old chiLdren (5.8 and 1.9%, respectively) that increased continuously with increasing age. High anti-HBs levels (>1000 IU/L) were found in all age cohorts, indicating a lifelong threat of active hepatitis B infection. In conclusion, the transmission profile of hepatitis B appeared to be mainly horizontal (person-to-person) in the highly endemic region studied. Vertical transmission was less than 5%. The horizontal transmission routes included non-sexual activities of life since children <10 years of age also showed considerable infection rates. The results underline the need for catch-up hepatitis B vaccination programs for children and adults.

Adolescent↗
PubMed1982

Periodic fluctations in synaptic transmission and enhancement of transmission in hippocampal slices.

The properties of the synchronously activated radiatum fiber-CA1 synaptic population were examined with the in vitro hippocampal slice preparation. Periodic fluctuations in synaptic transmission and in the enhancement of synaptic transmission were observed with periods ranging from 8 to 20 s. Such periodic fluctuations did not arise from fluctuations in afferent radiatum fiber activity. The period and amplitude of the cyclic variations in the enhancement of synaptic transmission were found to be altered with repeated electrical stimulation of the radiatum fibers. These results reflect cooperative synaptic actions which must be taken into consideration in the delineation of the mechanisms of potentiation.

Afferent Pathways↗
PubMed2004

The risk of accidental transmission of transmissible spongiform encephalopathy: identification of emerging issues.

The transmissible spongiform encephalopathies (TSEs), thought to be caused by prions, are fatal neurodegenerative disorders of humans and animals. Despite their rarity, human prion diseases have received prominence because the consumption of prion-contaminated meat from cattle with bovine spongiform encephalopathy (BSE) is thought to be responsible for the emergence of variant Creutzfeldt-Jakob disease (vCJD) in humans. Clinical criteria for the diagnosis of vCJD is now available. Recent, more startling evidence suggests that the clinical presentation of vCJD may vary and that patients may present as classical (sporadic) CJD or may have subclinical infection and be apparently healthy. These patients may still pose a risk of iatrogenic transmission through surgical or medical (blood transfusion) procedures. The aim of future work is to develop preclinical screening tests for the identification of infected but still healthy individuals. The future course of vCJD is still uncertain. Modelling studies to predict the cases of vCJD depend on the date of origin of BSE and time of infection, which is, at best, only approximated. As the number of cases of BSE in the UK declines, the risk of BSE in other countries from imported cattle or meat and bone meal from the UK has been increasing. It is also recognized that other animal species (farmed, domestic and wild animals) other than cows are susceptible to TSEs. The possibility of interspecies transmission of TSEs and the global presence of the disease suggests a need for a co-ordinated worldwide risk management approach to eradicate TSEs.

Animals↗
PubMed1999

Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group.

BACKGROUND: Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour. METHODS: In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR. FINDINGS: Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery. INTERPRETATION: A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.

Administration, Oral↗
PubMed1997

Absence of hepatitis C virus transmission but frequent transmission of HIV-1 from sexual contact with doubly-infected individuals.

Hepatitis C virus (HCV) is transmitted through infected blood and blood products, but evidence of other routes of transmission is less clearly understood. In a study designed to examine human immunodeficiency virus (HIV) transmission, the prevalence of HCV has also been measured. Sixty-one couples were analysed, 30 in which partners were at risk through sexual contact alone, of whom 12 (40%) became infected with HIV and none with HCV. Thirty-one partners were exposed sexually and additionally through intravenous drug use. Of these, 16 (52%) became infected with HIV and 25 (80%) contracted HCV infection. These findings support the evidence of others that HCV is only rarely transmitted by sexual intercourse in heterosexual relationships and that HIV is not a co-factor for HCV transmission.

Adolescent↗
PubMed2003

Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking.

Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.

Adolescent↗
PubMed1997

Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers: rate of infection and assessment of risk factors for transmission.

The risk of perinatal transmission of hepatitis C virus (HCV) from a cohort of 95 human immunodeficiency virus (HIV)-negative intravenous drug users (IVDU) is described, 89 of whom were positive for antibodies to HCV (anti-HCV). Infection, defined as the presence of HCV RNA in a serum sample collected from an infant at any time during follow-up, was detected in six of 63 (9.5%) infants born to HCV antibody-positive viraemic mothers. No mother who was HCV RNA negative at delivery transmitted HCV to her infant. Hepatitis C virus antibodies became undetectable in uninfected infants by 15 months, but persisted in all HCV-infected infants throughout follow-up. An abnormal alanine aminotransferase (ALT) level was observed on at least one occasion in all HCV-infected infants and in six occasions in uninfected infants. Two of the six HCV-infected infants became HCV RNA negative during follow-up by 27 and 29 months. Both of these infants had a large ALT elevation (mean peak ALT 398U l-1) at around 12 months of age. Analysis of a range of potential risk factors revealed that maternal HCV RNA load was important in predicting transmission, but suggested that other factors play a role in perinatal transmission from mother to child. No difference was found between mothers who transmitted HCV to their infants and those who did not for HCV genotype, duration of drug use, duration of methadone use, methadone dose, history of alcohol abuse, past hepatitis B virus (HBV) infection, mode of delivery, maternal and gestational age, birth weight and incidence of breast-feeding. Mothers who transmitted HCV to their infants had a longer duration between membrane rupture and delivery than the mothers who did not transmit (P = 0.03). HCV RNA was not detected in breast milk and colostrum samples from 38 viraemic mothers, including two who transmitted HCV to their infant.

Alanine Transaminase↗
PubMed1998

Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV.

Although individuals infected with human immunodeficiency virus (HIV) seem to be more infectious in the late stages of HIV infection and possibly also during the seroconversion period, most estimates of per-sexual-contact infectivity have been obtained without allowing for variability over the course of infection. In this analysis, a probabilistic model was fitted to data from a European study carried out between 1987 and 1992 that involved 499 (359 males and 140 females) HIV-infected subjects (index cases) and their regular heterosexual partners. The model used allowed infectivity (the per-sexual-contact HIV transmission probability, mu) to vary through three stages: the first 3 months following infection, the subsequent asymptomatic period, and the advanced stage (HIV-related clinical symptoms or a CD4-positive T lymphocyte count less than 200/mm3). Male-to-female infectivity through penile-anal sex was found to be higher in both the early and advanced stages of infection (mu=0.183) than in the longer intermediate period (mu=0.014) (p < 0.03). Failure to demonstrate significant differences between stages for other types of contact (male-to-female penile-vaginal contacts: mu=0.0007; female-to-male transmission: mu=0.0005) may reflect insufficient power rather than a true lack of variability. Indeed, the results for penile-anal sex suggest that persons who are in the process of seroconverting may be much more infectious than asymptomatic infected persons, whatever the type of contact. Prevention education should stress the risk of HIV transmission from subjects who may be unaware of their infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Comparison of methods of estimating the mother-to-child transmission rate of human immunodeficiency virus type 1 (HIV-1). New York City Perinatal HIV Transmission Collaborative Study Group.

Four methods of estimating mother-to-child transmission rates of human immunodeficiency virus type 1 (HIV-1), based on the 1992 Ghent workshop, were compared in a multicenter New York City prospective cohort study in 1986-1992. Of 833 infants born to women at risk of HIV-1 infection, 388 were born HIV-1 seropositive and 445 were HIV-1 seronegative. The four methods, the Antibody Only, Indirect, Direct, and Virologic Methods, yielded transmission rate estimates of 19-25%, classifying 59-89% of the cohort. Estimation based on persistence of HIV-1 antibody and clinical assessment yielded transmission rates similar to those methods that incorporated virologic testing.

Adult↗
PubMed2000

Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother-child transmission of HIV.

OBJECTIVES: To determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia. DESIGN: A blinded, prospective, community-based cohort study of 29.549 pregnant women attending the eight largest antenatal clinics in The Gambia. METHODS: Women were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age. RESULTS: The study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28-33], 41% (95% CI 39-42) and 47% (95% CI 45-49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15,100 copies x 10(3) ml (95% CI 10,400-19,000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies x 10(3) ml (95% CI 150-910) (P < 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6-33.9) and that of HIV-2 was 4.0% (95% CI 1.9-7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2-7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1-5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1-7.8) were risk factors for transmission that applied equally to both viruses. CONCLUSION: Low maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.

CD4 Lymphocyte Count↗
PubMed2000

Oral zidovudine during labor to prevent perinatal HIV transmission, Bangkok: tolerance and zidovudine concentration in cord blood. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To evaluate tolerance for the oral administration of zidovudine (ZDV) during labor and measure the resulting ZDV concentrations in umbilical cord blood. DESIGN: A cross-sectional study of women in a placebo-controlled trial of short-course ZDV (twice a day from 36 weeks' gestation until labor and every 3 h during labor) to prevent perinatal HIV transmission in Bangkok. METHODS: Umbilical cord blood was collected. Sixty control specimens and specimens from 372 women (182 in the ZDV group, 190 in the placebo group) were tested for ZDV by radioimmunoassay (lower detection limit < 1 ng/ml). RESULTS: All women in the ZDV group took one or more labor dose, 170 (93%) took their last dose within 3 h of delivery, and only five (3%) experienced nausea or vomiting, a proportion similar to the placebo group. The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml (range, < 1-1133 ng/ml); 31 (17%) specimens were less than 130 ng/ml (0.5 microM), the concentration thought to be active against HIV in vitro. Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses, 290 ng/ml in those taking three or four doses, and 293 ng/ml in those taking more than four doses (P < 0.01). The ZDV concentration was not associated with time since the last dose, body weight, or perinatal transmission. CONCLUSION: Oral intrapartum ZDV was feasible and well tolerated. Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration. Although concentrations were not associated with perinatal transmission, these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective.

Administration, Oral↗
PubMed2000

Mother-to-infant transmission of TT virus: prevalence, extent and mechanism of vertical transmission.

OBJECTIVE: It is currently unknown which mechanisms are responsible for TT virus (TTV) infection in early childhood and whether it may be transmitted in utero from mother to infant. METHODS: The prevalence, mode and extent of maternal TTV transmission was investigated by testing blood, cord blood and breast milk samples from mother-infant pairs for the existence of the novel DNA virus. RESULTS: By means of polymerase chain reaction, TTV DNA was detected in 57 (41.3%) of 138 mothers and in 19 (13.8%) of 138 cord blood samples; therefore 33.3% of infants are likely to be infected by their mothers during the fetal period. Direct sequencing of TTV DNA from 2 mother-child pairs showed identical isolates. Follow-up sera from 3 TTV infected babies showed persistence of viremia. In blood samples from newborns older than 1 week 9 (27.3%) of 33 sera were TTV-positive. Viral sequences were also detected in 2 of 2 breast milk samples. In none of the infected subjects were biochemical or clinical signs of hepatitis observed. CONCLUSIONS: Our data prove that TT virus is efficiently transmitted transplacentally. The increase of its prevalence in the group of newborns older than 1 week suggests that it may be furthermore transmitted postnatally. Therefore in our Caucasian population, vertical transmission, particularly in utero transmission, of TTV is likely to account for a major part of TTV infection in early childhood. However, no disease activity could be established for the novel virus by this infection route.

Adult↗
PubMed1996

Probability of heterosexual transmission of HIV: relationship to the number of unprotected sexual contacts. European Study Group in Heterosexual Transmission of HIV.

The objective of this study was to investigate the relationship between the number of unprotected heterosexual contacts with an HIV-infected person and the probability of HIV transmission. Data from a European study involving 563 heterosexual partners of HIV-infected subjects were analyzed. The number of unprotected contacts could be estimated for 525 couples (377 with male index case, 148 with female index case) from the reported frequency of unprotected contacts and an estimate of the length of the period during which transmission could have occurred. Nonparametric (isotonic regression) and parametric (Bernoulli model) analyses were performed on data at study entry and on follow-up data (121 couples). The nonparametric analysis resulted in several exposure groups, with the proportion of infected partners increasing with the number of contacts. For example, the percentage of female partners infected ranged from 10%, among those with < 10 unprotected contacts with an infected male, to 23% after 2,000 unprotected contacts. The parametric estimates of (assumed constant) per-contact infectivity were higher for male-to-female than for female-to-male transmission, but not significantly so. However, in comparison with nonparametric estimates, the model assuming constant infectivity appears to seriously underestimate the risk after very few contacts and to seriously overestimate the risk associated with a large number of contacts. Our results suggest that the association between the number of unprotected sexual contacts and the probability of infection is weak and highly inconsistent with constant per-contact infectivity. Probable explanations for these findings include large variability in infectivity between couples and within individuals over time. Estimates based on partner study data under the hypothesis of constant infectivity can, therefore, be highly misleading at a public health level, particularly when extrapolated to multiple casual contacts.

Disease Transmission, Infectious↗