BACKGROUND: To help distinguish vaccine-related adverse events following immunization (AEFI) from coincidental occurrences, active vaccine pharmacovigilance (VP) prospective surveillance programs are needed. From February to May 2021, we assessed the system and facility readiness for implementing active AEFI VP surveillance in Addis Ababa, Ethiopia. METHODS: Selected hospitals were assessed using a readiness assessment tool with scoring measures. The site assessment was conducted via in-person interviews within the specific departments in each hospital. We evaluated the system readiness with a desk review of AEFI guidelines, Expanded Program for Immunization Guidelines and Ethiopian Food and Drug Administration and Ethiopian Public Health Institute websites. RESULTS: Of the hospitals in Addis Ababa, 23.1% met the criteria for our site assessment. During the system readiness assessment, we found that essential components were in place. However, rules, regulations and proclamations pertaining to AEFI surveillance were absent. Based on the tool, the three hospitals (A, B and C) scored 60.6% (94/155), 48.3% (75/155) and 40% (62/155), respectively. CONCLUSIONS: Only one of three hospitals assessed in our evaluation scored >50% for readiness to implement active AEFI surveillance. We also identified the following areas for improvement to ensure successful implementation: training, making guidelines and reporting forms available and ensuring a system that accommodates paper-based and electronic-based recording systems.

Since at least the 1970s, immunization programs have been challenged by periodic vaccine safety scares “going viral” (Kullenkamp 1974, Hall 1999, IOM 2004). The causes of such scares are complex, but likely due in part to the increasing relative prominence of adverse events following immunizations (AEFI) as vaccine coverage increases and the targeted vaccine-preventable diseases decrease (Gangarosa 1998). Being able to answer in a timely manner whether or not a particular vaccine actually causes a specific adverse event became increasingly important. Because the sample size of pre-licensure clinical trials of new vaccines usually number <100,000, detection of rare AEFIs is practical only post-licensure when millions may be immunized. In the United States, the development of a new passive surveillance Vaccine Adverse Event Reporting System (VAERS) in 1990 (Shimabukuro 2015) led to a recognition that while useful for signal generation, more rigorous databases are needed to test hypotheses and answer the causality question. In addition, although pre-licensure trials are usually adequately powered to evaluate vaccine efficacy under highly standardized conditions, evaluation of vaccine effectiveness is often necessary post-licensure to assess the benefits of vaccination in real world settings that may include population groups that were not enrolled in pre-licensure trials (e.g., pregnant women) and that may be subject to other forces, such as waning immunity and herd immunity (Lopalco 2015).

Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: (1) adapting from the current relevant regulatory guidelines; (2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely potential or known AEFI and establish the optimal risk window(s); and (3) conducting "near real-time" prospective monitoring for unknown clustering's of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with (4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators.

As each national immunization program matures with increasing uptake of vaccines in the population and control of their targeted vaccine-preventable diseases (VPD), vaccine safety concerns become more prominent. Such concerns are frequently a mix of coincidental adverse events falsely attributed to the memorable immunization event and real vaccine-induced reactions.(1) (2) Sorting the two types of concerns out requires implementation of appropriate surveillance systems for adverse events following immunizations (AEFI)s, and timely and rigorous scientific assessment (and occasionally good media skills) to maintain public confidence in immunization programs.(3) Failures to do so have tragically resulted in resurgence of VPD’s in multiple countries. (4) (5). | Traditionally, in high income countries, large populations with computerized databases that link vaccination history exposures and medical visits have been used for rigorous testing of hypothesized vaccine safety concerns raised by passive surveillance systems for AEFI’s.(6, 7) Pilot projects for similar large linked databases (LLDB) in low and middle-income countries (LMIC)’s have begun, but are not without problems.(8) Given the major challenges in obtaining the substantial resources needed to develop and sustain such LLDB’s,(9) affordable, timely and reliable alternative solutions for LMICs (even if imperfect) are needed. This need is highlighted by the accelerated introduction of new vaccines for diseases endemic in LMICs (e.g., Meningitis A, Rotavirus, Cholera and Dengue) without prior use in countries with strong pharmacovigilance systems. (10)

BACKGROUND: HIV disease staging with referral laboratory-based CD4 cell count testing is a key barrier to the initiation of antiretroviral treatment (ART). Point-of-care CD4 cell counts can improve linkage to HIV care among people living with HIV, but its effect has not been assessed with a randomised controlled trial in the context of home-based HIV counselling and testing (HBCT). METHODS: We did a two-arm, cluster-randomised, controlled efficacy trial in two districts of western Kenya with ongoing HBCT. Housing compounds were randomly assigned (1:1) to point-of-care CD4 cell counts (366 compounds with 417 participants) or standard-of-care (318 compounds with 353 participants) CD4 cell counts done at one of three referral laboratories serving the study catchment area. In each compound, we enrolled people with HIV not engaged in care in the previous 6 months. All participants received post-test counselling and referral for HIV care. Point-of-care test participants received additional counselling on the result, including ART eligibility if CD4 was less than 350 cells per muL, the cutoff in Kenyan guidelines. Participants were interviewed 6 months after enrolment to ascertain whether they sought HIV care, verified through chart reviews at 23 local clinics. The prevalence of loss to follow-up at 6 months (LTFU) was listed as the main outcome in the study protocol. We analysed linkage to care at 6 months (defined as 1-LTFU) as the primary outcome. All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02515149. FINDINGS: We enrolled 770 participants between July 1, 2013, and Feb 28, 2014. 692 (90%) had verified linkage to care status and 78 (10%) were lost to follow-up. Of 371 participants in the point-of-care group, 215 (58%) had linked to care within 6 months versus 108 (34%) of 321 in the standard-of-care group (Cox proportional multivariable hazard ratio [HR] 2.14, 95% CI 1.67-2.74; log rank p<0.0001). INTERPRETATION: Point-of-care CD4 cell counts in a resource-limited HBCT setting doubled linkage to care and thereby improved ART initiation. Given the substantial economic and logistic hindrances to providing ART for all people with HIV in resource-limited settings in the near term, point of care CD4 cell counts might have a role in prioritising care and improving linkage to care. FUNDING: US Centers for Disease Control and Prevention.

BACKGROUND: CD4+ T-lymphocyte count testing at the point-of-care (POC) may improve linkage to care of persons diagnosed with HIV-1 infection, but the accuracy of POC devices when operated by lay-counselors in the era of task-shifting is unknown. We examined the accuracy of Alere's Pima POC device on both capillary and venous blood when performed by lay-counselors and laboratory technicians. METHODS: In Phase I, we compared the perfomance of POC against FACSCalibur for 280 venous specimens by laboratory technicians. In Phase II we compared POC performance by lay-counselors versus laboratory technicians using 147 paired capillary and venous specimens, and compared these to FACSCalibur. Statistical analyses included Bland-Altman analyses, concordance correlation coefficient, sensitivity, and specificity at treatment eligibility thresholds of 200, 350, and 500cells/mul. RESULTS: Phase I: POC sensitivity and specificity were 93.0% and 84.1% at 500cells/mul, respectively. Phase II: Good agreement was observed for venous POC results from both lay-counselors (concordance correlation coefficient (CCC)=0.873, bias -86.4cells/mul) and laboratory technicians (CCC=0.920, bias -65.7cells/mul). Capillary POC had good correlation: lay-counselors (CCC=0.902, bias -71.2cells/mul), laboratory technicians (CCC=0.918, bias -63.0cells/mul). Misclassification at the 500 cells/mul threshold for venous blood was 13.6% and 10.2% for lay-counselors and laboratory technicians and 12.2% for capillary blood in both groups. POC tended to under-classify the CD4 values with increasingly negative bias at higher CD4 values. CONCLUSIONS: Pima results were comparable to FACSCalibur for both venous and capillary specimens when operated by lay-counselors. POC CD4 testing has the potential to improve linkage to HIV care without burdening laboratory technicians in resource-limited settings.

PURPOSE: In March 1992, eight infants who had died within 36 hours of receiving whole-cell pertussis vaccine (diphtheria, tetanus, and whole-cell pertussis [DTwP]) prompted the Taiwan health authorities to suspend its use. We conducted an investigation of vaccination and sudden unexplained infant death (SUID) and repeated it more recently after Taiwan switched to acellular pertussis vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]) in 2010. METHODS: All SUIDs aged 31-364 days during 1990-1992 and 1996-2013 were selected from the death registration databases. The case-control investigation matched each case to two controls on clinic, sex, and birth date, whereas the follow-up self-controlled case series study compared risk of death during the 30-day post-vaccination risk periods with those in the control periods within the same case. RESULTS: Sudden unexplained infant death was associated with never receiving DTwP (odds ratio 2.28, 95% confidence interval 1.25-4.15) in the case-control investigation. The odds ratios within 0-1, 2-7, 8-14, and 15-30 days of DTwP administration were 1.18, 0.26, 0.50, and 0.77. In the 1996-2013 self-controlled case series studies, this temporal shift between DTwP and SUID was consistently observed for female (incidence rate ratio 1.70, 0.75, 1.01, and 0.84) but not male or DTaP recipients. A pooled analysis showed significant risk within 2 days of receiving DTwP in female infants (incidence rate ratio 1.66, 95% confidence interval 1.05-2.60). CONCLUSIONS: Being unvaccinated and recent receipt of DTwP in female infants was significantly associated with SUID; the latter was consistent with a temporal shift pattern without overall increase in risk. The currently used pertussis vaccine, DTaP, did not increase risk of SUID.

Administering vaccines specifically to pregnant women as part of a disease prevention strategy has not been routinely practiced, with the major exception of protecting against neonatal tetanus. Pregnancy continues to be a contraindication for receipt of most live viral (e.g., measles, mumps, rubella, varicella) vaccines. In the wake of the thalidomide tragedy [1], real or perceived risks of teratogenicity have served as a deterrent to administration of many medicines during pregnancy. Little is known about the effects of new medications or vaccines on pregnant women since they are often excluded from clinical research designed to determine safety. In recent years, however, a groundswell of public and provider opinion has developed urging reconsideration of the practice of excluding pregnant women from drug safety studies for some vaccines. The morbidity and mortality following some infections (e.g., influenza and pertussis) can be disproportionally greater among infants and pregnant women [2], [3]. Consequently, the Advisory Committee on Immunization Practices (ACIP) has recommended routine immunization of pregnant women with influenza vaccine since 1997 [2] and a dose of Tdap during every pregnancy since 2012 [4]. Future vaccines for use in pregnancy may include group B streptococcal, Zika, and respiratory syncytial virus vaccines. The challenges and opportunities for maternal immunization have begun to be addressed in various vaccine stakeholder meetings. For example, the US National Vaccine Advisory Committee (NVAC formed a Maternal Immunization Working Group in 2012 and issued a report in 2014 on “Reducing Patient and Provider Barriers to Maternal Immunizations” [6].

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viral and other microbial pathogens in their genome (so-called "chimeric virus vaccines"). Many such viral vector vaccines are now at various stages of clinical evaluation. Here, we introduce an attenuated form of recombinant vesicular stomatitis virus (rVSV) as a potential chimeric virus vaccine for HIV-1, with implications for use as a vaccine vector for other pathogens. The rVSV/HIV-1 vaccine vector was attenuated by combining two major genome modifications. These modifications acted synergistically to greatly enhance vector attenuation and the resulting rVSV vector demonstrated safety in sensitive mouse and non-human primate neurovirulence models. This vector expressing HIV-1 gag protein has completed evaluation in two Phase I clinical trials. In one trial the rVSV/HIV-1 vector was administered in a homologous two-dose regimen, and in a second trial with pDNA in a heterologous prime boost regimen. No serious adverse events were reported nor was vector detected in blood, urine or saliva post vaccination in either trial. Gag specific immune responses were induced in both trials with highest frequency T cell responses detected in the prime boost regimen. The rVSV/HIV-1 vector also demonstrated safety in an ongoing Phase I trial in HIV-1 positive participants. Additionally, clinical trial material has been produced with the rVSV vector expressing HIV-1 env, and Phase I clinical evaluation will initiate in the beginning of 2016. In this paper, we use a standardized template describing key characteristics of the novel rVSV vaccine vectors, in comparison to wild type VSV. The template facilitates scientific discourse among key stakeholders by increasing transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus-vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.

In 1999, the Global Advisory Committee on Vaccine Safety (GACVS) was established by the World Health Organization (WHO) to provide independent scientific advice on issues relating to the safety of vaccines and immunization. Fifteen years onward, we conducted a multi-faceted review to evaluate the impact, reach and challenges facing GACVS, including the role GACVS plays in informing global, regional and WHO member state vaccine policy. The methods included measures of organizational structure, citation impact, themes approached, and a discussion by previous and current members to evaluate past, present and future challenges. Given the increasing range of data sources and the deployment of many new vaccines, the Committee is facing the complex task of identifying the best available evidence for recommendations on vaccine safety. To help meet the increased demand for public transparency in decision making, GACVS-structured methodology for evidence-based decisions is evolving. GACVS also promotes best practices and capacity building for timely and accurate risk assessment; risk communications; outreach to help countries maintain and, if needed, rebuild public trust in vaccines; and advocacy for bridging the major gaps in vaccine safety capacity globally.

Major vaccine safety controversies have arisen in several countries beginning in the last decades of 20th century. Such periodic vaccine safety controversies are unlikely to go away in the near future as more national immunization programs mature with near elimination of target vaccine-preventable diseases that result in relative greater prominence of adverse events following immunizations, both true reactions and temporally coincidental events. There are several ways in which vaccine safety capacity can be improved to potentially mitigate the impact of future vaccine safety controversies. This paper aims to take a "lifecycle" approach, examining some potential pre- and post-licensure opportunities to improve vaccine safety, in both developed (specifically U.S. and Europe) and low- and middle-income countries.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.

We estimated HIV prevalence and identified correlates of HIV infection among 1106 men and women aged 16-34 years residing in Kisumu, Kenya. Demographic, sexual, and other behavioural data were collected using audio computer-assisted self-interview in conjunction with a medical examination, real-time parallel rapid HIV testing, and laboratory testing for pregnancy, gonorrhoea, chlamydia, syphilis, and herpes simplex virus type 2. Multivariate logistic regression was used to identify variables associated with prevalent HIV infection by gender. Overall HIV prevalence was 12.1%. HIV prevalence among women (17.1%) was approximately two and one half times the prevalence among men (6.6%). Odds of HIV infection in men increased with age (aOR associated with one year increase in age = 1.21, CI = 1.07-1.35) and were greater among those who were uncircumcised (aOR = 4.42, CI = 1.41-13.89) and those who had an herpes simplex virus type 2 positive (aOR = 3.13, CI = 1.12-8.73) test result. Odds of prevalent HIV infection among women also increased with age (aOR associated with one year increase in age = 1.16, CI = 1.04-1.29). Women who tested herpes simplex virus type 2 positive had more than three times the odds (aOR = 3.85, CI = 1.38-10.46) of prevalent HIV infection compared with those who tested herpes simplex virus type 2 negative. Tailored sexual health interventions and programs may help mitigate HIV age and gender disparities.

Men who have sex with men (MSM) are a crucial and marginalized at risk population for HIV in Africa but are poorly studied. Like other areas of Africa, homosexuality is illegal in Kenya. We assessed MSM comfort in accessing health services and willingness to participate in HIV prevention research in Kisumu, Kenya-an area of high HIV prevalence. We conducted a two-phase formative study with individual interviews (n = 15) and a structured survey (n = 51). Peer contact or snowball method (n = 43, 84.3%) was the primary recruitment strategy used to locate MSM. Exact logistic regression models were used for survey data analysis. Over 60% (32/51) of survey participants were not very comfortable seeking health services from a public hospital. Almost all MSM (49/51; 96.1%) reported willingness to be contacted to participate in future HIV research studies. Efforts to provide facilities that offer safe and confidential health services and health education for MSM is required. Continued community engagement with the MSM population in Kenya is needed to guide best practices for involving them in HIV prevention research.

Recombinant viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate viral vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed.

INTRODUCTION: In 2012, the American Academy of Pediatrics (AAP) and the American Congress of Obstetricians and Gynecologists (ACOG) published recommendations that physicians should discuss with parents the benefits and risks of newborn male circumcision. Our objective was to assess physicians' perspectives of newborn male circumcision. METHODS: A self-administered, cross-sectional electronic survey of US physicians was conducted in 2008 (N = 1500). RESULTS: Approximately one-third (33.2%) of the respondents reported that their current perspective was that the medical benefits outweigh the risks associated with newborn male circumcision and less than one-third (31.1%) reported they would recommend the procedure when counseling parents. CONCLUSIONS: In 2008, only about one-third of the physicians surveyed thought that the benefits of male circumcision outweighed the risks and recommended it to parents of newborn sons. These attitudes may be relevant to the declining circumcision rates in the United States. Repeat surveys may be useful, given the new AAP and ACOG recommendations.

IMPORTANCE: Approximately 1.4 million male circumcisions (MCs) are performed annually in US medical settings. However, population-based estimates of MC-associated adverse events (AEs) are lacking. OBJECTIVES: To estimate the incidence rate of MC-associated AEs and to assess whether AE rates differed by age at circumcision. DESIGN: We selected 41 possible MC AEs based on a literature review and on medical billing codes. We estimated a likely risk window for the incidence calculation for each MC AE based on pathogenesis. We used 2001 to 2010 data from SDI Health, a large administrative claims data set, to conduct a retrospective cohort study. SETTING AND PARTICIPANTS: SDI Health provided administrative claims data from inpatient and outpatient US medical settings. MAIN OUTCOMES AND MEASURES: For each AE, we calculated the incidence per million MCs. We compared the incidence risk ratio and the incidence rate difference for circumcised vs uncircumcised newborn males and for males circumcised at younger than 1 year, age 1 to 9 years, or 10 years or older. An AE was considered probably related to MC if the incidence risk ratio significantly exceeded 1 at P &lt; .05 or occurred only in circumcised males. RESULTS: Records were available for 1 400 920 circumcised males, 93.3% as newborns. Of 41 possible MC AEs, 16 (39.0%) were probable. The incidence of total MC AEs was slightly less than 0.5%. Rates of potentially serious MC AEs ranged from 0.76 (95% CI, 0.10-5.43) per million MCs for stricture of male genital organs to 703.23 (95% CI, 659.22-750.18) per million MCs for repair of incomplete circumcision. Compared with boys circumcised at younger than 1 year, the incidences of probable AEs were approximately 20-fold and 10-fold greater for males circumcised at age 1 to 9 years and at 10 years or older, respectively. CONCLUSIONS AND RELEVANCE: Male circumcision had a low incidence of AEs overall, especially if the procedure was performed during the first year of life, but rose 10-fold to 20-fold when performed after infancy.

BACKGROUND: While laboratory aetiological diagnosis is considered the gold standard for diagnosis and management of sexually transmitted infections, syndromic management has been presented as a simplified and affordable approach for sexually transmitted infection management in limited resource settings. METHODS: Sexually transmitted infection signs and symptoms were collected using staff-administered computer-assisted personal interview and audio computer-assisted self-interview. Participants underwent a medical examination and laboratory testing for common sexually transmitted infections. The performance of syndromic management was assessed on the agreement between interviewing methods as well as accurate diagnosis. RESULTS: We screened 846 participants, of whom 88 (10.4%) received syndromic sexually transmitted infection diagnosis while 272 (32.2%) received an aetiological diagnosis. Agreement between syndromic and aetiological diagnoses was very poor (overall kappa = 0.09). The most prevalent sexually transmitted infection was herpes simplex virus type 2 and the percentage of persons with any sexually transmitted infection was higher among women (48.6%) than men (15.6%, p < 0.0001). Agreement between audio computer-assisted self-interview and computer-assisted personal interview interviewing methods for syndromic diagnosis of sexually transmitted infections ranged from poor to good. CONCLUSION: Our findings suggest that syndromic management of sexually transmitted infections is not a sufficient tool for sexually transmitted infection diagnosis in this setting; development and improvement of sexually transmitted infection diagnostic capabilities through laboratory confirmation is needed in resource-limited settings.

Cost-effective HIV prevention programs should target persons at high risk of HIV acquisition. We conducted an observational HIV incidence cohort study in Kisumu, Kenya, where HIV prevalence is triple that of the national rate. We used referral and venue-sampling approaches to enroll HIV-negative persons for a 12-month observational cohort, August 2010 to September 2011, collected data using computer-assisted interviews, and performed HIV testing quarterly. Among 1292 eligible persons, 648 (50%) were excluded for HIV positivity and other reasons. Of the 644 enrollees, 52% were women who were significantly older than men (P < .01). In all, 7 persons seroconverted (incidence rate [IR] per 100 person-years = 1.11; 95% confidence interval [CI] 0.45-2.30), 6 were women; 5 (IR = 3.14; 95% CI 1.02-7.34) of whom were ≤25 years. Most new infections occurred in young women, an observation consistent with other findings in sub-Saharan Africa that women aged ≤25 years are an important population for HIV intervention trials in Africa.

With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC's are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety.

There is increased emphasis on physician attention to the overall health and wellness of homosexual and bisexual men, though little is known about the health-related attitudes of these groups. This study determined factors associated with the health attitudes of homosexual and bisexual men and identified preferred sources of health information. For this study, the 2008 ConsumerStyles panel survey was used to create three health attitude scales and to determine factors associated with each scale. The three scales were labeled: (1) health motivation; (2) relationship with health care provider; and (3) self-perception of health literacy. In addition to other factors, higher scores for health motivation and relationship with health care provider were associated with black compared with white men. In contrast, lower scores for self-perception of health literacy were associated with black compared with white men. For information on an unfamiliar health condition, most homosexual and bisexual men chose the Internet. Black homosexual and bisexual men reported being motivated to be healthy and working well with their health care provider to manage their health. However, their perception of their own health motivation was low compared with the white men. Attempts to improve health literacy through Internet sites may be helpful in improving health attitudes and reducing negative health outcomes. (2013 Ministry of Health, Saudi Arabia.)

INTRODUCTION: During Brazil's national measles, mumps, and rubella (MMR) vaccination campaign in August 2004, an unexpectedly high rate of hypersensitivity-type adverse events (HAEs) was reported. MATERIALS AND METHODS: We reviewed information about children with suspected HAEs reported by clinicians to Brazil's national passive surveillance system for adverse events following immunization (AEFI), compared attack rate of HAE by manufacturer of MMR vaccine used in the campaign, and conducted a case-control study to determine possible risk factors for HAEs. RESULTS: During the 2004 national campaign, the rate of HAEs following MMR vaccination was one log higher for manufacturer A (15.2/100,000 doses administered) compared to the other two manufacturers (1.2 and 0.6/100,000 doses; p<0.0001); a similar pattern was observed retrospectively in analysis of the 2000-2003 AEFI surveillance (0.95 vs. 0.07 per 100,000 doses administered; p<0.0001). In the case-control study, among the 49 case-patients with HAEs identified, reported symptoms included conjunctival injection (60%), urticaria (55%), fever (54%), and facial edema (53%); no deaths occurred. The median time interval between vaccination and symptom onset was 42min (range: 5min-24h). We did not identify any differences in the proportion of case-patients and control children with a history of known allergy to food (including egg, egg-containing products or gelatin), drugs, or environmental antigens. DISCUSSION: Our study highlights the importance of a well-functioning routine AEFI surveillance system linked with mass vaccination campaigns. Such a system in Brazil permitted timely detection of HAEs and validation of a safety signal associated with one vaccine manufacturer. Unlike earlier publications, this outbreak linked to a single manufacturer of MMR showed no association with a prior allergic history to eggs or other foods, including gelatin; subsequent studies implicate the dextran stabilizer in MMR from manufacturer A as the likely cause of HAEs.

INTRODUCTION: In an analysis of baseline findings of an HIV incidence cohort study, an assessment was made of HIV prevalence among persons presenting for enrollment and any differences in demographic characteristics between persons not enrolled compared to those enrolled. We also described and compared HIV risk behaviors in males and females enrolled in the study. METHODOLOGY: A computer-assisted survey was administered to collect baseline demographic and HIV risk data from 1,277 men and women aged 18-34 years. Testing for HIV and other sexually transmitted infections (STI) was conducted. Out of 1,277 persons prescreened for eligibility, 625 were enrolled. RESULTS: HIV prevalence of all persons who completed screening was 14.8% (females: 21.1%; males: 8.1%). The odds of being enrolled in the study were higher for persons 18-24 years compared to those 30-34 years of age [adjusted odds ratio (AOR)=2.18, CI=1.13, 4.21] and males compared to females [AOR=2.07, CI=1.43, 2.99]. Among those enrolled in the study, the most prevalent HIV risk behaviors were unprotected sex (49%), alcohol use (45%), and transactional sex (30%) in the last three months. Compared to females, a significantly greater proportion of males reported using any alcohol or recreational drug in the last three months, a history of oral sex, sex with partner other than a spouse or main partner, ever having a blood transfusion, ever being treated for an STI, and having knowledge of their last HIV test result. CONCLUSION: The Kisumu Field Station successfully recruited individuals with HIV risk characteristics for the HIV incidence cohort study.

Physicians may be called upon to counsel male patients or parents of newborn males regarding their decision to circumcise their newborn sons. The purpose of the present study was to describe physicians who do not understand the benefits and risks associated with male circumcision well enough to counsel parents of newborn male infants and adult men. A self-administered, cross-sectional electronic survey of physicians was conducted in 2008. We analyzed responses from 1,500 physicians (510 family practitioners, 490 internists, 250 pediatricians, and 250 obstetricians/gynecologists). Nearly 22% (n = 327/1500) reported they did not understand the risks and benefits of newborn male circumcision well enough to counsel parents and 40.3% (n = 504/1250) reported not understanding the risks and benefits well enough to counsel adult men. A substantial minority of physicians may need additional training and/or information about current male circumcision research to feel comfortable counseling parents of newborn male infants or adult men.

BACKGROUND: Associations between vaccinations, particularly hepatitis B, and onset of rheumatoid arthritis (RA) have been reported, but examined in few large-scale studies. METHOD: Onset of RA cases and dates of vaccination against hepatitis B, tetanus, and influenza were identified in a retrospective chart review of approximately 1 million Kaiser Permanente Northern California members ages 15-59 years from 1997 through 1999. In a cohort analysis, rates of new-onset RA were compared between vaccinated and unvaccinated within 90, 180, and 365 days. In a case-control analysis, rates of vaccination during exposure intervals (90, 180, 365, and 730 days) were compared between cases and controls using conditional logistic regression. RESULTS: 378 RA cases were included in the cohort analysis; 37 additional cases were included in the case-control analysis. In the cohort analysis the relative risks of RA onset within 90, 180, or 365 days of hepatitis B vaccination were not significant (R.R.=1.44, p=0.53; R.R.=1.67, p=0.22; R.R.=1.23, p=0.59 respectively). We found a possible association between RA and influenza vaccine in the previous 180 and 365 days in the cohort analysis (R.R=1.36, p=0.03; R.R.=1.34, p=0.01 respectively), but in the case-control analysis, cases were no more likely than controls to have received any of the three vaccines. CONCLUSIONS: In this large retrospective study we found no statistically significant association between exposure to hepatitis B vaccine and onset of RA. A possible association between RA and influenza vaccination in the cohort study was not borne out in the larger case-control analysis.

Some 30 years after the public first became aware of AIDS, the need for a safe, effective, and affordable HIV vaccine remains compelling [1]. To date, the road to an HIV vaccine has been rocky, marked by the well-publicized failures of the first two candidates to reach large population trials. The first, a recombinant gp120 AIDSVAX® B/E vaccine, proved ineffective [2, 3]. The second, a Merck recombinant adenovirus 5 gag/pol/nef HIV-1 vaccine targeting cell-mediated immunity in the STEP trial, actually increased the risk of HIV acquisition among vaccinees relative to placebo recipients [4]. Then, just as vaccine developers were returning to their drawing boards [5], the roller-coaster swung up again. On 20 October 2009, results of RV144 – a large, long duration, expensive (~120 million US$), community Phase III trial in Thailand evaluating a combination of two vaccines, ALVAC® HIV vaccine (a 4-dose prime) and the aforementioned AIDSVAX® B/E vaccine (a 2-dose boost) – were announced at the AIDS Vaccine 2009 Conference in Paris, France. There were 51 infections in 26,507 vaccinated person-years versus 74 in 26,478 unvaccinated person-years (p=0.04). Excluding 7 trial participants who were infected before vaccination, this prime-boost combination reduced the risk of HIV infection by 31.2% (95% CI, 1.1 to 51.2) overall compared to placebo [6]. | In March of 2010, at the request of the Ministry of Public Health in Thailand, a consultation was co-sponsored by the WHO, UNAIDS, Global HIV Vaccine Enterprise, Thai Ministry of Public Health, and US Military HIV Research Program to address the utility of RV144 trial results, particularly public health and future access; ethical, regulatory, and community issues; science and vaccine development; and clinical trial design and statistics. Among the recommendations was to encourage modeling teams to estimate the cost and impact on the HIV epidemic of vaccine regimens with varying efficacy and durability, including a 31% efficacious general population vaccine with a 1-year duration of protection [7]. Accordingly, the editors invited modelers capable of evaluating the potential impact of RV144-like vaccines to investigate a common scenario with variations for a number of countries. This special issue of Vaccine contains several articles from this joint modeling exercise, along with several other HIV vaccine papers, most of which were presented at a satellite symposium, entitled ‘Preparing for the Availability of a Partially Effective HIV Vaccine’, held at the AIDS Vaccine 2010 Conference in Atlanta, USA.

The 2009 RV144 trial in Thailand shows that a partially effective vaccine against human immunodeficiency virus (HIV) acquisition is possible (1). Past mathematical models have shown HIV vaccines with partial effectiveness (assuming availability and no compensatory risk behavior) may have important public health impact (2). While we are still many years away from a licensed HIV vaccine, what might be some of the “downstream” considerations for the implementation of a partially effective HIV vaccine in the developed and developing world in the current era? Are there any changes since the HIV domain last considered this issue in anticipation of the results of the first Phase III trials of HIV vaccine (Vaxgen gp120) a decade earlier? (3, 4). | During the Acquired Immunodeficiency Disease Syndrome (AIDS) Vaccine 2010 Conference, a satellite symposium cosponsored by AIDS Vaccine Advocacy Coalition (AVAC), the U. S. Centers for Disease Control and Prevention (CDC), Gates Foundation, the Joint United Nations Programme on HIV/AIDS (UNAIDS), US Agency for International Development (USAID), US Military HIV Research Program (USMHRP), World Health Organization (WHO) took advantage of the conference location in Atlanta to draw upon some of the experience of CDC and its associated partners in preparing for the availability and implementation of newly licensed vaccines to further this dialogue. This paper summarizes the presentations on some lessons for future HIV vaccine implementation from the introduction of hepatitis B vaccine, human papillomavirus (HPV) vaccine, the annual influenza virus vaccine strain selection, a potential annual HIV vaccine strain selection, as well as planning for next steps in Thailand in response to the RV144 trial, and highlights from the moderated discussions with the audience on issues relevant to low/middle income countries and developed countries (Table 1). Hopefully these ideas will facilitate preparations for the introduction of a future licensed HIV vaccine.

Guillain-Barré syndrome has been a focus of safety monitoring since the report in 1976 of an increased risk of almost one extra case per 100 000 influenza vaccinations of swine origin.1 Subsequent studies have shown either no increased risk or a slightly increased risk (1-2 per million vaccinees) after vaccination for seasonal flu.2 The spread of the 2009 pandemic influenza A (H1N1) virus, which contained genes of swine origin, resulted in the development and widespread use of influenza A (H1N1) monovalent vaccines (2009 H1N1 vaccines).3 These included formulations containing oil in water adjuvants that had not previously been widely used in flu vaccines in Europe. Although available evidence suggested that the adjuvanted vaccines had acceptable safety profiles,3 data on the risk of rare adverse events, such as Guillain-Barré syndrome, were limited. | In the linked study (doi:10.1136/bmj.d3908), Dieleman and colleagues report the first data on adjuvanted 2009 H1N1 vaccines and the risk of Guillain-Barré syndrome from a case-control study conducted in five European countries.4 Overall, the results suggest that if there was an increased risk associated with the adjuvanted 2009 H1N1 vaccines studied, it was considerably smaller than that seen with the 1976 swine flu vaccines. Whether there was an increased risk, however, is not clear.

BACKGROUND/PURPOSE: To understand whether information from the African clinical trials about the partially protective effect of male circumcision against human immunodeficiency virus (HIV) infection could influence adults to circumcise a newborn son. METHODS: Using the 2008 ConsumerStyles panel survey data, multiple regression analysis was performed to identify correlates of (1) inclination toward circumcising a newborn son and (2) being influenced to have a newborn son circumcised if it would reduce the chance of becoming HIV infected later in life. RESULTS: Response rate was 50.6% (10,108/19,996). Approximately 12% reported not being inclined to circumcise a newborn son. Higher odds of not being inclined to circumcise a newborn son were associated with Hispanic and "other" race/ethnicity, being an uncircumcised man and a man not reporting circumcision status, postgraduate education, region, and negative health-related attitudes. Lower odds were associated with black race and less number of household members. Fifty-three percent of respondents reported that information about the protective effect of circumcision would make them more likely to have a newborn son circumcised. Higher odds of being influenced to have a newborn son circumcised were associated with being ≥45 years of age, black race, living in a household with fewer than 5 members, having high school or some college education, region, and positive health-related attitudes; lower odds were associated with being an uncircumcised man and lower income. CONCLUSIONS: Our findings suggest that providing educational information about the HIV prevention and benefit of circumcision may increase the inclination to circumcise a newborn son for some people.