Noah J. Robinson

The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

Objectives: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. Design and methods: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. Results: HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. Conclusions: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection

Objective: To identify factors that could explain differences in rate of spread of HIV between different regions in sub-Saharan Africa. Design: Cross-sectional study. Methods: The study took place in two cities with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon), and two cities with a high HIV prevalence (Kisumu, Kenya and Ndola, Zambia). In each of these cities, a representative sample was taken of about 1000 men and 1000 women aged 15-49 years. Consenting men and women were interviewed about their socio-demographic background and sexual behaviour; and were tested for HIV, herpes simplex virus type 2 (HSV-2), syphilis, Chlamydia trachomatis and Neisseria gonorrhoea infection, and (women only) Trichomonas vaginalis. Analysis of risk factors for HIV infection was carried out for each city and each sex separately. Adjusted odds ratios (aOR) were obtained by multivariate logistic regression. Results: The prevalence of HIV infection in sexually active men was 3.9% in Cotonou, 4.4% in Yaoundé, 21.1% in Kisumu, and 25.4% in Ndola. For women, the corresponding figures were 4.0, 8.4, 31.6 and 35.1%. High-risk sexual behaviour was not more common in the high HIV prevalence cities than in the low HIV prevalence cities, but HSV-2 infection and lack of circumcision were consistently more prevalent in the high HIV prevalence cities than in the low HIV prevalence cities. In multivariate analysis, the association between HIV infection and sexual behavioural factors was variable across the four cities. Syphilis was associated with HIV infection in Ndola in men [aOR = 2.7, 95% confidence interval (CI) = 1.5-4.9] and in women (aOR = 1.7, 95% CI = 1.1-2.6). HSV-2 infection was strongly associated with HIV infection in all four cities and in both sexes (aOR ranging between 4.4 and 8.0). Circumcision had a strong protective effect against the acquisition of HIV by men in Kisumu (aOR = 0.25, 95% CI = 0.12-0.52). In Ndola, no association was found between circumcision and HIV infection but sample sizes were too small to fully adjust for confounding. Conclusion: The strong association between HIV and HSV-2 and male circumcision, and the distribution of the risk factors, led us to conclude that differences in efficiency of HIV transmission as mediated by biological factors outweigh differences in sexual behaviour in explaining the variation in rate of spread of HIV between the four cities.

Multicentre study on factors determining differences in rate of spread of HIV in sub-Saharan Africa: methods and prevalence of HIV infection

Objective: The objective of this study was to explore whether the differences in rate of spread of HIV in different regions in sub-Saharan Africa could be explained by differences in sexual behaviour and/or factors influencing the probability of HIV transmission during sexual intercourse. Methods: A cross-sectional, population-based study was conducted in two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia) and two cities with a relatively low HIV prevalence (Cotonou in Benin and Yaoundé in Cameroon). In each of these cities, approximately 1000 men and 1000 women, aged 15-49 years, were randomly selected from the general population. Consenting men and women were interviewed and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection and trichomoniasis (the latter for women only). In addition, a survey was conducted on a random sample of 300 sex workers in each city. The research instruments, including the questionnaires and the laboratory procedures, were standardized to permit comparison of results. Results: The numbers of men interviewed were 1021 in Cotonou, 973 in Yaoundé, 829 in Kisumu, and 720 in Ndola. The corresponding figures for women were 1095, 1116, 1060 and 1130. In Yaoundé, Kisumu and Ndola, the response rates for men were lower than for women due to failure to make contact with eligible men. The proportion of eligible women who were interviewed was 86% in Yaoundé, and 89% in Kisumu and Ndola. In Yaoundé, 76% of eligible men were interviewed, along with 82% in Kisumu and 75% in Ndola. The prevalence of HIV infection in men was 3.3% in Cotonou, 4.1% in Yaoundé, 19.8% in Kisumu and 23.2% in Ndola. For women, the respective figures were 3.4, 7.8, 30.1 and 31.9%. The prevalence of HIV infection among women aged 15-19 years was 23.0% in Kisumu and 15.4% in Ndola. Among women in Kisumu who had their sexual debut 5 years before the interview, the prevalence of HIV infection was 46%; in Ndola, it was 59%. Among sex workers, the prevalence of HIV infection was 57.5% in Cotonou, 34.4% in Yaoundé, 74.7% in Kisumu and 68.7% in Ndola. Conclusions: The HIV prevalence rates in the general population confirmed our preliminary assessment of the level of HIV infection in the four cities, which was based on estimates of HIV prevalence from sentinel surveillance among pregnant women. The very high prevalence of HIV infection among young women in Kisumu and Ndola calls for urgent intervention.

The multicentre study on factors determining the differential spread of HIV in four African cities: summary and conclusions

In all regions of sub-Saharan Africa the predominant mode of transmission of HIV is through heterosexual intercourse however there are large variations in the rate and extent of the spread of HIV in different populations. This study was conducted to identify the factors that influence the rapid spread of HIV in four African cities namely Cotonou (Benin) Yaounde (Cameroon) Kisumu (Kenya) and Ndola (Zambia). Results demonstrated that high rates of partner change and being married are risk factors for HIV infection in men in at least one city but are risk factors for women in all four cities. In addition condom use among sex workers did not show a difference between the low and high prevalence cities. Furthermore no evidence of changes towards safer sexual behavior was identified in the high HIV prevalence cities. The only factors that were more common in the two high HIV prevalence cities than in the two low HIV prevalence cities were young age at first intercourse for women young age at first marriage and large age difference between the spouses. It was also noted that the high levels of HIV infection among young people especially among female adolescents in Kisumu and Ndola highlight the importance of interventions targeted at young people and their partners.

Seroepidemiological study of herpes simplex virus types 1 and 2 in Brazil, Estonia, India, Morocco, and Sri Lanka

Background: The association between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) and the development of HSV vaccines have increased interest in the study of HSV epidemiology. Objectives: To estimate the age and sex specific seroprevalence of HSV-1 and HSV-2 infections in selected populations in Brazil, Estonia, India, Morocco, and Sri Lanka. Methods: Serum samples were collected from various populations including children, antenatal clinic attenders, blood donors, hospital inpatients, and HIV sentinel surveillance groups. STD clinic attenders were enrolled in Sri Lanka, male military personnel in Morocco. Sera were tested using a common algorithm by type specific HSV-1 and HSV-2 antibody assay. Results: 13 986 samples were tested, 45.0% from adult females, 32.7% from adult males, and 22.3% from children. The prevalence of HSV-1 varied by site ranging from 78.5%–93.6% in adult males and from 75.5%–97.8% in adult females. In all countries HSV-1 seroprevalence increased significantly with age (p<0.001) in both men and women. The prevalence of HSV-2 infection varied between sites. Brazil had the highest age specific rates of infection for both men and women, followed by Sri Lanka for men and Estonia for women, the lowest rates being found in Estonia for men and India for women. In all countries, HSV-2 seroprevalence increased significantly with age (p<0.01) and adult females had higher rates of infection than adult males by age of infection. Conclusions: HSV-1 and HSV-2 seroprevalence was consistently higher in women than men, particularly for HSV-2. Population based data on HSV-1 and HSV-2 will be useful for designing potential HSV-2 vaccination strategies and for focusing prevention efforts for HSV-1 and HSV-2 infection.

Potential effect of HIV type 1 antiretroviral and herpes simplex virus type 2 antiviral therapy on transmission and acquisition of HIV type 1 infection.

Biological strategies for interrupting transmission of human immunodeficiency virus (HIV) type 1 should be directed at reducing infectiousness of and susceptibility to HIV-1. Potential antiretroviral interventions include reducing the likelihood of transmission of HIV-1 by reducing HIV-1 load in the blood and genital tract of HIV-1--infected person, prophylaxis after high-risk exposure, and pre-exposure prophylaxis for very high risk populations. Antiviral treatment of herpes simplex virus (HSV) type 2, the most common cause of genital ulcers, should be evaluated as a strategy for HIV-1 infection prevention by reducing infectiousness of and susceptibility to HIV-1, on the basis of biological and epidemiological data indicating that HSV-2 facilitates transmission and acquisition of HIV-1. The rationale for antiretroviral and HSV-2-specific interventions and studies to test these strategies are described.

The epidemiology of gonorrhoea, chlamydial infection and syphilis in four African cities.

Objectives: To compare the epidemiology of gonorrhoea, chlamydial infection and syphilis in four cities in sub-Saharan Africa; two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon). Design: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa. Methods: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) Trichomonas vaginalis infection. Risk factor analyses were carried out for chlamydial infection and syphilis seroreactivity. Results: The prevalence of gonorrhoea ranged between 0% in men in Kisumu and 2.7% in women in Yaoundé. Men and women in Yaoundé had the highest prevalence of chlamydial infection (5.9 and 9.4%, respectively). In the other cities, the prevalence of chlamydial infection ranged between 1.3% in women in Cotonou and 4.5% in women in Kisumu. In Ndola, the prevalence of syphilis seroreactivity was over 10% in both men and women; it was around 6% in Yaoundé, 3-4% in Kisumu, and 1-2% in Cotonou. Chlamydial infection was associated with rate of partner change for both men and women, and with young age for women. At the population level, the prevalence of chlamydial infection correlated well with reported rates of partner change. Positive syphilis serology was associated with rate of partner change and with HSV-2 infection. The latter association could be due to biological interaction between syphilis and HSV-2 or to residual confounding by sexual behaviour. At the population level, there was no correlation between prevalence of syphilis seroreactivity and reported rates of partner change Conclusion: Differences in prevalence of chlamydial infection could be explained by differences in reported sexual behaviour, but the variations in prevalence of syphilis seroreactivity remained unexplained. More research is needed to better understand the epidemiology of sexually transmitted infections in Africa.

The epidemiology of trichomoniasis in women in four African cities.

Objectives: To describe the epidemiology of Trichomonas vaginalis infection and its association with HIV infection, in women in four African cities with different levels of HIV infection. Design: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa: two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low prevalence of HIV (Cotonou, Benin and Yaoundé, Cameroon). Methods: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) T. vaginalis infection. Risk factor analyses were carried out for trichomoniasis for each city separately. Multivariate analysis, however, was only possible for Yaoundé, Kisumu and Ndola. Results: The prevalence of trichomoniasis was significantly higher in the high HIV prevalence cities (29.3% in Kisumu and 34.3% in Ndola) than in Cotonou (3.2%) and Yaoundé (17.6%). Risk of trichomoniasis was increased in women who reported more lifetime sex partners. HIV infection was an independent risk factor for trichomonas infection in Yaoundé [adjusted odds ratio (OR) = 1.8, 95% confidence interval (CI) = 0.9-3.7] and Kisumu (adjusted OR = 1.7, 95% CI = 1.1-2.7), but not in Ndola. A striking finding was the high prevalence (40%) of trichomonas infection in women in Ndola who denied that they had ever had sex. Conclusion: Trichomoniasis may have played a role in the spread of HIV in sub-Saharan Africa and may be one of the factors explaining the differences in levels of HIV infection between different regions in Africa. The differences in prevalence of trichomoniasis between the four cities remain unexplained, but we lack data on the epidemiology of trichomoniasis in men. More research is required on the interaction between trichomoniasis and HIV infection, the epidemiology of trichomoniasis in men, and trichomonas infections in women who deny sexual activity.

Prevalence of diagnosed chronic immune thrombocytopenic purpura in the US: analysis of a large US claim database: a rebuttal

We read with interest the paper by Segal and Powe [1] on the prevalence of immune thrombocytopenic purpura (ITP). ITP is a disease caused by inadequate platelet production, as well as increased platelet destruction, and is traditionally categorized into acute and chronic forms. For the latter, thrombocytopenia needs to be present for at least 6 months [2]. In this paper, Segal and Powe refer to ITP as immune (rather than idiopathic) thrombocytopenia purpura. There is relatively little epidemiological evidence on chronic ITP, and its prevalence in the US is poorly documented. The paper by Segal and Powe is one of the first population-based studies of prevalence of ITP in the US that provides an estimate of chronic ITP (albeit informal). However, as the authors noted, there were some limitations in their study. Most of these were related to the limitations in the data source. In the analysis presented here, we aimed to estimate the diagnosed prevalence of chronic ITP in the US in 2005, using a large US claims data base. In particular, our analysis overcomes some of the main limitations in Segal and Powes paper. (i) Segal and Powe used only one calendar year (2002) of data and identified potentially chronic ITP patients as those with at least two ITP ICD-9 codes (287.3), which were separated by at least 6 months. Therefore, a patient whose first ITP ICD-9 code occurred in the second half of 2002 had no chance of presenting a second code within the 2002 calendar year. Hence, as the authors pointed out, their estimation of the prevalence of chronic ITP in all people under 65 years (4.5 per 100 000) may be a considerable underestimate. (ii) Segal and Powe se stimation only includes patients under 65 years old. The increased risk of ITP with age is well documented [3–5] and excluding patients over 64 years of age would lead to an underestimate. We analyzed the Integrated Healthcare Information System (IHCIS) database, one of the largest US health care managed databases, fully de-identified, with over 70 million patients from more than 45 health plans. It covers 7 out of 10 census regions and contains patient demographics, age, gender and morbidity. Our patient population consisted of patients enrolled to one of the health plans before or any time between 2002 and 2006 with a continuous enrollment throughout the year 2004. Chronic ITP cases were defined as patients with at least two diagnoses (ICD-9 code 287.3) for primary thrombocytopenia separated by at least 6 months between 2002 and 2006. A patient sfi rst identified 287.3 ICD-9 code over the period 2002–2006 had to be in 2004 or earlier and the last one in 2004 or later. Prevalence rates of chronic ITP were calculated as the total number of identified chronic ITP cases divided by the total population with continuous enrollment in the data base in 2004 stratified by age group and gender. The total age- and gender-adjusted rate was estimated as the total number of expected ITP cases divided by the total 2005 US population (given the observed age- and gender-specific rates, and the structure of the 2005 US population). To assess chronic idiopathic thrombocytopenia rather than chronic immune thrombocytopenia, and following the Segal and Powe approach, we repeated the above estimates, excluding patients with a diagnosis of human immunodeficiency virus (HIV) infection, hematological malignancies or aplastic anemia, any time between 2002 and 2004.

Chronic hepatitis B virus infection in the Asia–Pacific region and Africa: Review of disease progression

Abstract  Countries in the the Asia–Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia–Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975–2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia–Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84–2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0–2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0–6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5‐year mortality rates (<4%); rates (>50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co‐infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.