Amsterdam Institute for Global Health and Development

Amsterdam, Netherlands

Amsterdam Institute for Global Health and Development

Amsterdam, Netherlands

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Schouten J.,Amsterdam Institute for Global Health and Development | Cinque P.,San Raffaele Scientific Institute | Gisslen M.,Gothenburg University | Reiss P.,Amsterdam Institute for Global Health and Development | Portegies P.,OLVG Hospital
AIDS | Year: 2011

With the introduction of combination antiretroviral therapy AIDS dementia complex or HIV-associated dementia, as it was termed later, largely disappeared in clinical practice. However, in the past few years, patients, long-term infected and treated, including those with systemically well controlled infection, started to complain about milder memory problems and slowness, difficulties in concentration, planning, and multitasking. Neuropsychological studies have confirmed that cognitive impairment occurs in a substantial (15-50%) proportion of patients. Among HIV-1-infected patients cognitive impairment was and is one of the most feared complications of HIV-1 infection. In addition, neurocognitive impairment may affect adherence to treatment and ultimately result in increased morbidity for systemic disease. So what may be going on in the CNS after so many years of apparently controlled HIV-1 infection is an urgent and important challenge in the field of HIV medicine. In this review we summarize the key currently available data. We describe the clinical neurological and neuropsychological findings, the preferred diagnostic approach with new imaging techniques and cerebrospinal fluid analysis. We try to integrate data on pathogenesis and finally discuss possible therapeutic interventions. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Newman L.,World Health Organization | Kamb M.,Centers for Disease Control and Prevention | Hawkes S.,University College London | Gomez G.,Amsterdam Institute for Global Health and Development | And 4 more authors.
PLoS Medicine | Year: 2013

Background: The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of pregnant women to be tested for syphilis and ≥90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Methods and Findings: Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage. Conclusions: Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary.


Gomez G.B.,Amsterdam Institute for Global Health and Development | Kamb M.L.,Centers for Disease Control and Prevention | Newman L.M.,World Health Organization | Mark J.,Centers for Disease Control and Prevention | And 2 more authors.
Bulletin of the World Health Organization | Year: 2013

Objective To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. Methods PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Findings Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I2 = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I2 = 95.9%; P < 0.001). Conclusion Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.


Hayes R.,MRC Tropical Epidemiology Group | Watson-Jones D.,London School of Hygiene and Tropical Medicine | Celum C.,University of Washington | Van De Wijgert J.,University of Amsterdam | And 3 more authors.
AIDS | Year: 2010

Observational and biological data provide compelling evidence of the importance of sexually transmitted infections (STIs) in HIV transmission, but only one of nine intervention trials has shown an effect. This article reviews the observational studies, critically examines the nine randomized controlled trials evaluating the impact of STI treatment interventions on HIV incidence, and discusses implications for HIV prevention policy, programs and future research. The role of other vaginal infections is also briefly considered. In aggregate, the evidence strongly supports the concept that STI treatment prevents HIV infection. However, issues in trial design and conduct, including HIV epidemic phase, STI prevalence, intervention in comparison groups, and power have affected five of the six trials of treatment of curable STIs. In the three herpes intervention trials, antivirals for HSV suppression were insufficiently potent to alleviate persistent genital inflammation in HIV-negative HSV2-positive persons, and the reduction in HIV levels in HIV-positive persons was insufficient to reduce HIV transmission. It is time for a new phase of exploration of how, when, and in whom to include STI control as a key component of HIV prevention, driven by basic research to elucidate the mechanisms by which STIs and vaginal infections facilitate HIV transmission. From a policy perspective, treatment of curable STIs is an essential part of primary healthcare and is a cheap, simple, and effective intervention when appropriately targeted and delivered. It should be promoted as an essential component of HIV control programs in communities in which the burden of STIs is substantial. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Eisingerich A.B.,Imperial College London | Wheelock A.,Imperial College London | Gomez G.B.,Amsterdam Institute for Global Health and Development | Garnett G.P.,Imperial College London | And 2 more authors.
PLoS ONE | Year: 2012

Background: The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. Methods and findings: Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. Conclusions: Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development. © 2012 Eisingerich et al.


Hawkes S.J.,University College London | Gomez G.B.,Amsterdam Institute for Global Health and Development | Gomez G.B.,Imperial College London | Broutet N.,World Health Organization
PLoS ONE | Year: 2013

Objective: Despite an increase in the proportion of women who access antenatal care, mother-to-child transmission of syphilis continues to be a consequence of undiagnosed, untreated, or inadequately treated maternal syphilis. We reviewed evidence on the optimal timing of antenatal interventions to prevent mother-to-child transmission of syphilis and its associated adverse outcomes. Design: Systematic review and meta-analysis of published literature. English-language articles were included if they (1) reported the gestational age at which the mother was screened or tested for syphilis; (2) reported on pregnancy outcome. No publication date limits were set. Results: We identified a total of 1,199 publications, of which 84 were selected for further review and five were included. All showed a lower prevalence of any adverse outcome among women who received an intervention (to include screening and treatment) in the first and second trimesters of pregnancy compared to the third trimester. The overall odds ratio for any adverse outcome was 2.24 (95% CI 1.28, 3.93). All sub-analyses by type of outcome presented important heterogeneity between studies, except for those studies reporting an infected infant (odds ratio 2.92, 95% CI 0.66, 12.87; I2 = 48.2%, p = 0.165). Conclusions: Our review has shown that the timing of antenatal care interventions makes a significant difference in the risk of having an adverse outcome due to syphilis. Women who sought care in the first two trimesters of their pregnancy, and received the appropriate intervention, were more likely to have a healthy infant, compared to women screened and treated in the third trimester. Encouraging ALL pregnant women to seek care in the first two trimesters of their pregnancy should be a priority for health programmes. For interventions to be effective within these health programmes, health systems and community engagement programmes need to be strengthened to enable pregnant women to seek antenatal care early. © 2013 Hawkes et al.


Cobelens F.G.J.,Amsterdam Institute for Global Health and Development
Science Translational Medicine | Year: 2013

The expected increase in drug-resistant tuberculosis due to large-scale preventive treatment in people living with HIV calls for reconsidering the "double use" of isoniazid for prophylaxis and curative treatment (Mills et al., this issue).


Oti S.O.,African Population and Health Research Center | Oti S.O.,Amsterdam Institute for Global Health and Development
Current Opinion in HIV and AIDS | Year: 2013

PURPOSE OF REVIEW: Many low-and middle-income countries face a double burden of disease from infectious diseases such as HIV/AIDS and noncommunicable diseases (NCDs) such as diabetes, stroke and cancers. The health systems in such countries are weak and are severely challenged by the weight of a double burden of disease. The aim of this review is to examine current calls for a coordinated global response to HIV and NCDs and make a case for health system building in resource-constrained settings. RECENT FINDINGS: The main argument in favour of a coordinated approach is that HIV and NCDs share many similarities that make them ideal candidates for a coordinated approach. Therefore, there is no need to reinvent the wheel, as experiences with HIV programmes can be leveraged to NCD programmes, and vice versa. Critics, however, worry that coordinated approaches could among other things adversely affect the gains of HIV programmes. SUMMARY: Going forward, the overall benefit of a coordinated approach will be that health systems could be strengthened in a sustainable manner. However, such approaches must carefully weigh the benefits against risks to existing structures and must consider all the relevant stakeholders in their implementation. © Lippincott Williams & Wilkins.


Zanni M.V.,Harvard University | Schouten J.,Amsterdam Institute for Global Health and Development | Grinspoon S.K.,Harvard University | Reiss P.,Amsterdam Institute for Global Health and Development
Nature Reviews Cardiology | Year: 2014

The lives of individuals infected with HIV who have access to combination antiretroviral therapy (cART) are substantially prolonged, which increases the risk of developing non-AIDS comorbidities, including coronary heart disease (CHD). In Europe and the USA, individuals with HIV infection have a â 1/41.5-fold increased risk of myocardial infarction relative to uninfected individuals. In Africa, the relative risk of myocardial infarction is unknown, but broadened access to life-extending cART suggests that rates of CHD will rise in this and other resource-constrained regions. Atherogenesis in HIV is affected by complex interactions between traditional and immune risk factors. cART has varied, regimen-specific effects on metabolic risk factors. Overall, cART seems to lessen proatherogenic immune activation, but does not eliminate it even in patients in whom viraemia is suppressed. Current strategies to decrease the risk of CHD in individuals infected with HIV include early initiation of cART regimens with the fewest metabolic adverse effects, and careful management of traditional CHD risk factors throughout treatment. Future strategies to prevent CHD in patients with HIV infection might involve the use of HIV-tailored CHD risk-prediction paradigms and the administration of therapies alongside cART that will further decrease proatherogenic HIV-specific immune activation. © 2015 Macmillan Publishers Limited.


Zwerling A.,McGill University | Van Den Hof S.,KNCV Tuberculosis Foundation | Van Den Hof S.,Amsterdam Institute for Global Health and Development | Scholten J.,KNCV Tuberculosis Foundation | And 4 more authors.
Thorax | Year: 2012

Healthcare workers (HCWs) are at increased risk of exposure to tuberculosis (TB). Traditionally, screening for latent TB infection (LTBI) is done using the tuberculin skin test (TST). Interferon-gamma release assays (IGRAs) are now increasingly being used for diagnosis of LTBI, but their role in HCW screening is unclear. A systematic review was conducted of all IGRA studies in HCWs to summarise their performance in cross-sectional and serial testing settings. By searching four electronic databases and other sources, all available studies using any one of the commercial IGRA assays in HCWs were retrieved and screened. 50 unique studies were identified which met the inclusion criteria including five from high TB incidence settings. Among 24 cross-sectional studies in low TB incidence settings, the pooled prevalence of positive IGRA using either test was significantly lower than for a positive TST. However, in high-incidence settings (n=2) there were no consistent differences in the prevalence of positive tests. IGRAs showed good correlation with occupational risk factors for TB exposure in low-incidence settings. Only 10 studies assessed use of IGRA for serial testing and all showed large variation in the rates of conversions and reversions, with no data suggesting that IGRAs are better at identifying the incidence of new TB infection than the TST. The use of IGRAs instead of TST for one-time screening may result in a lower prevalence of positive tests and fewer HCWs who require LTBI treatment, particularly in low TB incidence settings. However, the use of IGRAs for serial testing is complicated by lack of data on optimum cut-offs for serial testing and unclear interpretation and prognosis of conversions and reversions. Further longitudinal research will be required to inform guidelines on serial testing using IGRAs.

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