Biomedical subjects
P Piot
Publications and source records attributed to P Piot.
Complete nucleotide sequence of an African human T-lymphotropic virus type II subtype b isolate (HTLV-II-Gab): molecular and phylogenetic analysis.
We report the first complete nucleotide sequence of an African human T-cell lymphotropic virus type II. This new strain, called HTLV-II-Gab (Gab), was obtained from the uncultured peripheral blood mononuclear cells of a 44-year-old healthy Gabonese male who lived in a remote rural area, with neither history of blood transfusion nor sexual intercourse with non-Africans. Using nested PCR, 25 overlapping fragments, representing the entire proviral genome, were obtained, cloned and sequenced. The overall nucleotide sequence comparison with the four other available complete HTLV-II genomes indicated that Gab was more closely related to the HTLV-II subtype b prototypes (98.9, 99.3 and 98.2% nucleotide similarity with G12, NRA and GU respectively) than to the subtype a prototype (95.1% nucleotide similarity with Mo). Restriction profiles studies and phylogenetic analyses confirmed that Gab was a subtype b strain. However, this strain represents a newly described restriction fragment length polymorphism subtype, closely related to one of the rare partially sequenced African isolates originating from a pygmy living in Cameroon (PYGCAM). Nevertheless, the very low genetic divergence observed between this new African strain and the American strains raises several questions on the origins and level of genetic variability over time of this human retrovirus.
Global prevalence and incidence estimates of selected curable STDs.
OBJECTIVES: To update the WHO global and regional estimates of the prevalence and incidence of syphilis, gonorrhoea, chlamydia, and trichomoniasis. METHODS: Prevalence estimates for syphilis, gonorrhoea, chlamydia, and trichomoniasis were generated for each of the nine UN regions for males and females between the ages of 15 and 49 in 1995 based on an extensive review of the published and unpublished medical literature since 1985. Incidence estimates were based on the prevalence figures and adjusted to take into account the estimated average duration of infection for each disease in a particular region. The latter was assumed to depend upon a number of factors including the duration of infection in the absence of treatment, the proportion of individuals who develop symptoms, the proportion of individuals treated, and the appropriateness of treatment. RESULTS: In 1995 there were over 333 million cases of the four major curable STDs in adults between the ages of 15 and 49--12 million cases of syphilis, 62 million cases of gonorrhoea, 89 million cases of chlamydia, and 170 million cases of trichomoniasis. Geographically, the vast majority of these cases were in the developing world reflecting the global population distribution. CONCLUSIONS: STDs are among the most common causes of illness in the world. Estimates of the global prevalence and incidence of these infections are limited by quantity and quality of data available from the different regions of the world. Improving global STD estimates will require more well designed epidemiological studies on the prevalence and duration of infection.
A new urgency.
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The neutralization relationship of HIV type 1, HIV type 2, and SIVcpz is reflected in the genetic diversity that distinguishes them.
Neutralizing antibody (NA) patterns in the sera of individuals naturally infected with human immunodeficiency virus (HIV) type 1, HIV-2, and the simian immunodeficiency virus (SIVcpz) to their homologous and heterologous isolates were determined in a peripheral blood mononuclear cell-based neutralization assay. We examined the role of the V3 loop of HIV-1 and SIVcpz in neutralization and the cross-reactivities among them. Cross-neutralization by sera of humans and chimpanzees naturally infected, respectively, with HIV-1 and SIVcpz isolates was more extensive than the infrequent and low-titer cross-neutralizations observed between HIV-1 and HIV-2. Neutralization of 9 of the 16 HIV-1 isolates by 9 of 10 HIV-2 and all 3 SIVcpz antibody-positive sera were weak and sporadic (titer, 1:10-1:160). Twelve of 15 HIV-1 sera neutralized the 2 SIVcpz isolates with titers of 1:10-1:320 but only sporadically neutralized the 6 HIV-2 isolates (titers: 1:10-1:20). The majority of HIV-1 and SIVcpz sera bound to the V3 peptides although their binding capacity did not readily reflect their neutralizing capacity. The HIV-2 sera did not or only weakly bound to the V3 peptides. These results suggest that HIV-1 and SIVcpz share some structural and functional similarities that set them apart from HIV-2.
STDS in women attending family planning clinics: a case study in Addis Ababa.
For cultural reasons modern contraception has been slow to gain acceptance in Ethiopia. Knowledge about contraception and abortion is still limited in many family and community settings in which it is socially disapproved. By 1990 only 4% of Ethiopian females aged 15-49 used contraception. Little is known of sexually transmitted disease (STD) prevalence in family planning (FP) attenders in Africa in general and Ethiopia in particular, even though attenders of family planning clinics (FPCs) are appropriate target groups for epidemiological studies and control programmes. A study of 2111 women of whom 542 (25.7%) attended FPCs in Addis Ababa showed utilisation rates to be highest in women who were: Tigre (33%) or Amhara (31%), aged 20-34 years (30%), age 16 or older at first marriage/coitus (28%:38% in those first married after 25 years); who had a monthly family income of 10 Ethiopian Birr (EB) or more (33%:36% for those with income 100-500 EB), three or more children (37%), more than five lifetime husbands/sexual partners (39%); or were bargirls (73%) or prostitutes (43%). The seroprevalence rates for all STDs, higher in FPC attenders compared with other women, were syphilis (TPHA) 39%, Neisseria gonorrhoeae 66%, genital chlamydia 64%, HSV-2 41%, HBV 40% and Haemophilus ducreyi 20%. Only 4% of FPC attenders had no serological evidence of STD: 64% were seropositive for 3 or more different STD. Clinical evidence of pelvic inflammatory disease (PID) was also more common in the FPC attenders (54%), 37% having evidence of salpingitis. The FPC provides a favourable setting for screening women likely to have high seroprevalence of STD, who for lack of symptoms will not attend either an STD clinic nor a hospital for routine check up. We recommend that measures be taken to adequately screen, treat and educate FPC attenders, their partners, and as appropriate and when possible their clients, in an attempt to control STDs and ultimately HIV in the community. Social, economic and cultural factors in the occurrence of STDs, prostitution, family planning and modern contraception coverage in Ethiopia are identified and deficiencies of current programmes briefly discussed with the objective of targeting services more effectively.
Macrophage-tropism of HIV-1 isolates of different genetic subtypes.
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Study of the dynamics of neutralization escape mutants in a chimpanzee naturally infected with the simian immunodeficiency virus SIVcpz-ant.
Here we report on the use of spectral map analysis of time-paired sequential neutralization data of 11 serum samples of a chimpanzee naturally infected with a simian immunodeficiency virus (SIVcpz-ant) and 8 primary consecutive SIVcpz-ant isolates, taken at about 4-month intervals. The analysis reveals the existence of three SIVcpz-ant isolate and serum neutralization clusters. Each cluster groups virus isolates and/or sera based on similarities of their neutralization spectra. On average, neutralization escape mutants emerged after 15 months and mounted a neutralization response approximately 8 months later. The entire gp160 regions of eight consecutive isolates were sequenced and analyzed by a new statistical method called polygram, which allowed the deduction of amino acid sequence motifs of gp160 which were specific for SIVcpz-ant isolates belonging to the same isolate neutralization clusters. Changes in specific amino acid quadruplets in V1, V2, C3, V4, V5, and CD4 domains of gp120 and gp40 were seen to correlate with the neutralization clusters with most of the specific changes occurring in the V4 region. This method of analysis may facilitate an understanding of the study of the dynamic interplay between human immunodeficiency virus (HIV) and host neutralization responses as well as providing possible insights into mechanisms of persistence of HIV-1-related lentiviruses in their natural hosts.
Virologic, immunologic, and clinical follow-up of a couple infected by the human immunodeficiency virus type one, group O.
The pathogenic course (virologic, immunologic, and clinical changes) of infection due to human immunodeficiency virus type one (HIV-1) group O viruses is unknown at present. To address this issue, serial HIV-1 isolates from a married couple (patients A and B) infected with a group O virus were analyzed to determine the temporal association between disease status and alterations in several parameters including plasma viral burden as measured by semiquantitative polymerase chain reaction, changes in CD4+ T cells, presence of neutralizing antibodies, and the ability to induce syncytia on the MT2 cells. For patient A who has been asymptomatic for at least 8 years, both the absence of syncytium-inducing (SI) variants and the presence of autologous and heterologous neutralizing antibodies correlated with a clinically healthier status. In contrast, a switch from NSI to SI variants was observed in patient B in 1990, followed by an expanded in vitro host range, increased viral burden, and a sharp decrease in CD4+ T cells 4 years later. Moreover, plasma obtained from this patient uniformly failed to neutralize both autologous and heterologous viruses. These observations in patient B correlated with a slightly unfavorable clinical status. Based on our preliminary results, it appears that the pathogenic course of infections due to group O viruses is similar to that reported previously for infections due to group M viruses.
International treatment access and research, how you can help--interview with Dr. Peter Piot of UNAIDS. Joint United Nations Programme on HIV/AIDS. Interview by John S. James.
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AIDS: a global response.
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Signs and symptoms of prevalent and incident cases of gonorrhea and genital chlamydial infection among female prostitutes in Kinshasa, Zaire.
Most studies that have examined the clinical features of gonorrhea and chlamydial infection have been based on prevalent cases (cases of undetermined onset). In our investigation, we compared signs and symptoms of incident (new) cases of these infections with those observed in prevalent cases (involving the same women) that were diagnosed at enrollment in a prospective study of female prostitutes in Kinshasa, Zaire. Neisseria gonorrhoeae or Chlamydia trachomatis was present at enrollment in 29.2% (225 of 771) of the women in the study. As they were followed during the study, 509 (66.0%) had at least one episode of gonorrhea or chlamydial infection. No symptom was significantly associated with these infections at enrollment or during follow-up. Clinical signs, such as endocervical mucopus (P < .001) and vaginal discharge (P = .001), were associated with both the prevalent and incident cases. However, none of these signs was simultaneously sensitive and specific for detection of these infections. The frequency of clinical signs was significantly reduced after successful treatment (all P values, < .05). This study shows that a syndromic approach to screening for gonococcal and chlamydial infections in female prostitutes is as problematic for acute incident cases as for prevalent cases. Therefore, there is still an urgent need for simple, cheap, reliable tests that could be used in sexually transmitted disease intervention programs in developing countries.
International perspectives on individual and community approaches to the prevention of sexually transmitted disease and human immunodeficiency virus infection.
Risks for sexually transmitted disease (STD) and human immunodeficiency virus (HIV) infection have been addressed in two categories: the individual and the population. Emphasis in STD and HIV prevention has largely been placed on the first, with interventions that address individuals and attempt to bring about changes in individuals being the norm. The relative ease of evaluating these interventions and the ability to know that they have been delivered as intended make these interventions attractive. Community interventions are more difficult to manage and to evaluate but are nonetheless commonly used. Structural interventions that address the environment in which risk behavior takes place are also possible but used much less frequently. In a comprehensive intervention program for STD and HIV prevention, it is necessary to consider opportunities for all three types of intervention approaches.
Multivariate analysis of human immunodeficiency virus type 1 neutralization data.
We report on the use of spectral map analysis of the inter- and intraclade neutralization data of 14 sera of human immunodeficiency virus type 1 (HIV-1)-infected individuals and 16 primary isolates, representing genetic clades A to H in group M and group O. This multivariate analysis has been used previously to study the interaction between drugs and receptors and between viruses and antiviral compounds. The analysis reveals the existence of neutralization clusters, not correlated with the known genetic clades. The structural factors that have been identified may correlate with the most important neutralization epitopes. Three key primary HIV-1 isolates, which allow discrimination of sera that are likely or unlikely to neutralize primary isolates from most of the genetic clades, were identified. Our method of analysis will facilitate the evaluation as well as the design of suitable HIV-1 vaccines, which induce high-titer interclade cross-neutralizing antibodies.
Virologic and serologic characteristics of a natural chimpanzee lentivirus infection.
This study set out to characterize the unique features of natural lentivirus infection in chimpanzees over time. The virologic and serologic characteristics of this infection were followed longitudinally in a naturally infected chimpanzee together with a small cohort of experimentally HIV-1-infected chimpanzees. The subsequent isolates from the naturally infected chimpanzee were all non-syncytium forming (NSI) versus syncytium forming in the experimentally infected animals. In contrast to HIV-1-infected chimpanzees virus load was higher and plasma viremia occurred but in a cyclic pattern. Serologic follow-up suggested the development of neutralizing antibodies with subsequent escape of new isolates. Interestingly, the sequence of the principal neutralizing (V3 loop) domain (of HIV-1) remained constant over time. Antibodies to peptides from the V3 loop were type specific. The occurrence of persistent, fluctuating plasma viremia and NSI-type virus variants of this natural lentivirus infection are unique characteristics not previously reported in experimentally infected chimpanzees.
The right not to know HIV-test results.
Large numbers of pregnant women in Africa have been invited to participate in studies on HIV infection. Study protocols adhere to guidelines on voluntary participation after pre-test and post-test counselling and informed consent; nevertheless, women may consent because they have been asked to do so without fully understanding the implications of being tested for HIV. Our studies in Nairobi, Kenya, show that most women tested after giving informed consent did not actively request their results, less than one third informed their partner, and violence against women because of a positive HIV-antibody test was common. It is important to have carefully designed protocols weighing the benefits against the potential harms for women participating in a study. Even after having consented to HIV testing, women should have the right not to be told their result.
HTLV-I infection among prostitutes and pregnant women in Kinshasa, Zaïre: how important is high-risk sexual behavior?
High-risk sexual behavior as risk factor for human T-cell lymphotropic virus type I (HTLV-I) infection was assessed in cross-sectional studies with 1,183 prostitutes and 1,166 pregnant women in Kinshasa, Zaire. Eighty six (7.3%) prostitutes were positive for HTLV-I. The seroprevalence among prostitutes from the regions along the equator was 12.7%, whereas among prostitutes from the other regions it ranged between 0 and 4.3%. In the prostitutes from the high-prevalence regions, but not in the prostitutes from the low-prevalence regions, HTLV-I infection was associated with increasing age [odds ratio (OR) = 1.1 per year increment], active syphilis (OR = 2.3), and human immunodeficiency virus (HIV) infection (OR = 2.0). Forty three (3.7%) pregnant women were HTLV-I seropositive. Among the women from low-prevalence regions, there was no significant difference in HTLV-I seroprevalence between prostitutes (4.3%) and pregnant women (3.5%). In a group of 409 prostitutes who were observed for a mean duration of 23 months, the incidence of HTLV-I infection was 0.7 per 100 women-years, whereas the incidence of HIV infection was 9.8 per 100 women-years. We conclude that in Kinshasa prostitution per se was not associated with an increased risk of HTLV-I infection.
Infectious virus titer, replicative and syncytium-inducing capacity of human immunodeficiency virus type 1.
The relationship was investigated between a viral infectious titer in peripheral blood mononuclear cells (PBMC) and plasma on the replicative and syncytium-inducing capacity of human immunodeficiency virus type 1 (HIV-1) isolates. The replicative capacity was defined as the minimum time required for p24 antigen to become positive in PBMCs or plasma of HIV-1 infected individuals, cocultured with PBMCs of healthy donors. Syncytium induction was determined by the MT-2 cell assay and defined as the presence of giant multinucleated cells. The replicative capacity of HIV-1 in PBMCs of healthy donors correlated with the infectious viral titer in PBMCs, but not in the plasma of HIV-1 positive patients. Syncytia formation in MT-2 cells was not related to the infectious viral titer in PBMCs or plasma of HIV-1 positive patients. These findings suggest that syncytium formation, not replicative capacity, is an intrinsic HIV-1 phenotype.