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OBJECTIVES Describe the causes of death among infants and children

Purpose of Review Through December 2020, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) supported more than 25 million voluntary medical male circumcisions (VMMC) as part of the combined HIV prevention strategy in 15 African countries. PEPFAR monitors defined adverse events (AEs) occurring within 30 days of VMMC through its notifiable adverse event reporting system (NAERS). All NAERS reports through December 2020 were reviewed to quantify AE type, severity, and relation to the VMMC procedure. Interventions to improve client safety based on NAERS findings are described. Recent Findings Fourteen countries reported 446 clients with notifiable adverse events (NAEs); 394/446 (88%) were determined VMMC-related, representing approximately 18 NAE reports per million circumcisions. Fatalities comprised 56/446 (13%) with 24/56 (43%) of fatalities determined VMMC-related, representing 0.96 VMMC-related fatalities per million circumcisions. The remaining 390 NAEs were non-fatal with 370/390 (95%) VMMC-related. Multiple programmatic changes have been made based on NAERS data to improve client safety. Summary Client safety is paramount in this surgical program designed for individual and population-level benefit. Surveillance of rare but severe complications following circumcision has identified pre-existing or new safety concerns and guided continuous programmatic improvement.

In a phase-IIa trial, we investigated the influence of 90 days continuous-delivery tenofovir (TFV) intravaginal rings (IVRs) with/without levonorgestrel (LNG) on the genital microbiota of Kenyan women. Eligible women (n = 27; 18-34 years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use of IVRs containing TFV, TFV/LNG, or placebo. Using vaginal wall and IVR swabs at IVR insertion and removal, the genital microbial composition was determined using 16S rRNA gene sequencing. The presence of Candida spp. was determined using qPCR. The vaginal total bacterial burden appeared to decrease with TFV and TFV/LNG IVR use (log

Background Approximately 80% of the population residing in sub-Saharan Africa relies on Traditional Medicine (TM). However, literature on factors motivating the use of TM for children under the age of five in these settings is limited. Such information can guide policy formulation for integration of TM into mainstream health care services. This study aimed to describe the motivation on use of TM among caregivers of children residing in rural and urban communities in western Kenya. Methods The socio-behavioral sciences (SBS) arm of the Child Health and Mortality Prevention Surveillance (CHAMPS) program in western Kenya, conducted a cross-sectional qualitative study in Manyatta—an urban informal settlement located in Kisumu town and Karemo—a rural setting in Siaya County. We performed 29 in-depth interviews, 5 focus group discussions and 11 semi-structured interviews with community representatives (n = 53), health workers (n = 17), and community leaders (n = 18). All the participants were purposively sampled. We performed thematic analysis using both inductive and deductive approaches. Data management was completed on Nvivo 11.0 software (QSR International, Melbourne, Australia). Results Our findings reveal that some caregivers prefer TM to treat some childhood diseases. Use of TM was informed by illness beliefs about etiology of disease. We observed an appreciation from the study participants that malaria can effectively be treated by Conventional Medicine (CM) while TM was preferred to treat measles and diseases believed to be associated with supernatural etiology such as witchcraft, evil spirit or breaching cultural taboos. TM was also used in instances where CM failed to provide a diagnosis or when CM was ‘slow’. TM in such cases was used as a last resort. Conclusion We observed varied beliefs that motivate caregivers’ choice of TM use among children in western Kenya. It is therefore crucial to consider perceptions and socio-cultural beliefs about illnesses when formulating interventions that are geared towards child health.

We report on two outbreaks of Salmonella enteritidis which occurred in 1992; both were associated with Monte Cristo sandwiches. The first outbreak, which occurred in Woods Hole, Massachusetts, was investigated as a case-control study, and involved 74 persons. The second outbreak, investigated as a cohort study, occurred in Brewster, Massachusetts, and involved 32 persons. Monte Cristo sandwiches were strongly implicated in both outbreaks; the odds ratio in the case-control study was 43, and the relative risk in the cohort study was 13. Food-preparation procedures were reviewed and food handlers were educated about safe food-preparation practices. Because of the short grilling time for Monte Cristo sandwiches, (usually several minutes) the eggs used in the preparation may only be partially cooked. As a result, this food should be viewed as high risk for S. enteritidis . Pasteurized eggs should be used to prepare Monte Cristo sandwiches, especially in a commercial setting.

Introduction: Devices for male circumcision (MC) are becoming available in 14 priority countries where MC is being implemented for HIV prevention. Understanding potential impact on demand for services is one important programmatic consideration because countries determine whether to scale up devices within MC programs. Methods: A population-based survey measuring willingness to undergo MC, assuming availability of surgical MC and 3 devices, was conducted among 1250 uncircumcised men, ages 10–49 years in Zambia and 1000 uncircumcised men, ages 13–49 years in Zimbabwe. Simulated Test Market methodology was used to estimate incremental MC demand and the extent to which devices might be preferred over surgery, assuming availability of: surgical MC in both countries; the devices PrePex, ShangRing, and Unicirc in Zambia; and PrePex in Zimbabwe. Results: Modeled estimates indicate PrePex has the potential to provide an overall increase in MC demand ranging from an estimated 13%–50%, depending on country and WHO prequalification ages, replacing 11%–41% of surgical procedures. In Zambia, ShangRing could provide 8% overall increase, replacing 45% of surgical procedures, and Unicirc could provide 30% overall increase, replacing 85% of surgical procedures. Conclusions: In both countries, devices have potential to increase overall demand for MC, assuming wide scale awareness and availability of circumcision by the devices. With consideration for age and country, PrePex may provide the greatest potential increase in demand, followed by Unicirc (measured in Zambia only) and ShangRing (also Zambia only). These results inform one program dimension for decision making on potential device introduction strategies; however, they must be considered within the broader programmatic context.

ObjectiveThis article provides an overview and interpretation of the performance of the US President’s Emergency Plan for AIDS Relief’s (PEPFAR’s) male circumcision programme which has supported the majority of voluntary medical male circumcisions (VMMCs) performed for HIV prevention, from its 2007 inception to 2017, and client characteristics in 2017.DesignLongitudinal collection of routine programme data and disaggregations.Setting14 countries in sub-Saharan Africa with low baseline male circumcision coverage, high HIV prevalence and PEPFAR-supported VMMC programmes.ParticipantsClients of PEPFAR-supported VMMC programmes directed at males aged 10 years and above.Main outcome measuresNumbers of circumcisions performed and disaggregations by age band, result of HIV test offer, procedure technique and follow-up visit attendance.ResultsPEPFAR supported a total of 15 269 720 circumcisions in 14 countries in Southern and Eastern Africa. In 2017, 45% of clients were under 15 years of age, 8% had unknown HIV status, 1% of those tested were HIV+ and 84% returned for a follow-up visit within 14 days of circumcision.ConclusionsOver 15 million VMMCs have been supported by PEPFAR since 2007. VMMC continues to attract primarily young clients. The non-trivial proportion of clients not testing for HIV is expected, and may be reassuring that testing is not being presented as mandatory for access to circumcision, or in some cases reflect test kit stockouts or recent testing elsewhere. While VMMC is extremely safe, achieving the highest possible follow-up rates for early diagnosis and intervention on complications is crucial, and programmes continue to work to raise follow-up rates. The VMMC programme has achieved rapid scale-up but continues to face challenges, and new approaches may be needed to achieve the new Joint United Nations Programme on HIV/AIDS goal of 27 million additional circumcisions through 2020.

Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President's Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged ≥10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for ≥3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5).

World Health Organization recommends that countries with hyperendemic and generalized HIV epidemics implement voluntary medical male circumcision programs for HIV prevention. Innovative methods of male circumcision including devices have the potential to simplify the procedure, reduce time and cost, increase client acceptability, enhance safety, and expand the numbers of providers who may perform circumcision. We describe work led by World Health Organization and supported by global partners to define a pathway for the evaluation of efficacy and safety of male circumcision devices, to set priority criteria, and to establish a process to guide the use of devices in publicly funded voluntary medical male circumcision programs for HIV prevention. A device classification scheme, an expert Technical Advisory Group on Innovations in Male Circumcision, and a formal prequalification program have also guided considerations on safe use of devices. A rigorous approach was deemed appropriate given the intervention is for use among healthy men for public health purposes. The pathway and processes led to coordinated research, better standardization in research outcomes, and guidance that informed the research, introduction and implementation phases. The lessons learnt from this case study can inform evaluation and use of future public health innovations.

Innovation, whether related to drugs, vaccines, or even program design, can allow services to be provided in a timely and efficient manner and to be appealing to beneficiaries. Examples such as point-of-care CD4 cell counts, rapid malaria diagnostic tests, tuberculosis diagnosis by cartridge-based nucleic acid amplification test, rapid HIV test kits (and more recently HIV self-testing), and fixed-dose combination antiretroviral therapy innovations in HIV treatment and prevention improve the efficiency and reach of services. Choice is also an important factor in acceptability and uptake of health services, as seen in contraceptive programs where an increased number of options are associated with increased contraceptive uptake.1 A recent example of an innovation with potential impact is medical devices developed for adolescent and adult voluntary medical male circumcision (VMMC) HIV prevention programs. VMMC progress in the 14 priority countries of southern and East Africa is an impressive public health HIV prevention effort. By the end of 2015, 10 million males had been provided with medical circumcision by HIV prevention programs, the vast majority also receiving HIV testing, many for the first time.2 Additionally, VMMC was one of 19 global health priorities referred to by the Copenhagen Consensus Centre as a ‘best-buy’ to reach the sustainable development goals.3 Beyond the prevention of HIV infection, added benefits of VMMC include prevention of other sexually transmitted infections such as herpes simplex virus and human papillomavirus infections.4,5 Not to be forgotten is the fact that an uninfected partner is the best protection against the sexual transmission of HIV, and therefore, the HIV prevention beneficiaries of male circumcision include women and also men. A model for Zambia predicts that reaching a goal of 80% circumcision among males of 15–49 years would reduce HIV incidence among females as much as 26% in the long term.6 Models predict that in some countries, almost half of HIV infections averted within a generation's time of VMMC scale-up will be among women.7 Achieving VMMC coverage of priority populations is not without challenges and complexities, including cultural barriers, establishment of new supply chains, need for high-quality services, creation of demand for services, funding, and need for efficiencies for service delivery.8 Given the goal of VMMC scale-up at a time of decreasing resources for primary prevention modalities, strategies and innovations are needed to improve accessibility, increase uptake of services, ensure sustainability, and improve cost efficiencies, all while maintaining public trust and safety of the program. In contrast to conventional surgical methods, medical devices for circumcision of adults and adolescent males are an innovation that may alleviate some scale-up challenges through the elimination of complexities inherent to surgery, including the need for sutures and injected anesthesia. Device-based techniques are typically shorter, easier to learn, simpler to perform, and have been safely conducted by nurses. Devices have thus been promoted as a means to extend the reach of programs, reduce costs, and potentially increase demand and program efficiency, while maintaining or even improving on safety.9 Advantages need to be weighed against the requirement that clients return 7 days after device placement for removal, whereas follow-up after surgical VMMC is voluntary. Two medical devices for adolescent and adult VMMC, PrePex and ShangRing, have been prequalified by World Health Organization (WHO) and can be used in VMMC programs supported by the President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund for AIDS, Tuberculosis and Malaria.10 Initial research on devices demonstrated safety and acceptability in the setting of clinical trials.11,12 Despite this, additional questions that cannot be answered in the clinical trial setting remain, including requirements and timelines for in-country regulatory processes, safety with use in routine service delivery settings (including at fixed, outreach, and mobile service delivery sites), strategies for integration of devices into ongoing programs, client demand, impact on program reach, and the cost of services. To further explore these issues, the Bill & Melinda Gates Foundation and PEPFAR developed a systematic research agenda, independent from device manufacturers, to understand the potential of devices to accelerate VMMC scale-up. As part of the evaluation agenda, it was also important that questions be addressed in contexts as close as possible to “real-life” scaled programs. This collection of 16 articles examines research on the introduction of the 2 devices prequalified by WHO, PrePex, and ShangRing. These studies provide a firm body of evidence to inform development of recommendations regarding device introduction into VMMC programs already operating at scale. We offer a brief description of the findings on introduction, including on safety, supply, demand, and cost of VMMC using devices, as summarized in Figure ​Figure11. FIGURE 1. Framework for systematically assessing the role of devices in accelerating the scale-up and improving the efficiency of the VMMC program. COGS, cost of goods sold; HR, human resources; OR, operational research.

OBJECTIVE: To assess how to best manage co-administration of rifabutin (RFB) and human immunodeficiency virus 1 (HIV-1) protease inhibitor (PI) containing antiretroviral treatment (ART). Recommended for initial anti-tuberculosis treatment, rifampicin (RMP) lowers PI concentrations below therapeutic levels, posing significant challenges for ART. As RFB has little effect on PI concentrations, it could be an alternative to RMP. METHODS: A review of the scientific literature on the safety and efficacy of RFB for adult tuberculosis (TB) treatment was conducted, focusing on ART-TB co-therapy. A cost comparison was performed between treatment regimens, and estimates of the burden of TB disease in patients on ART were used to model RFB demand in low- and middle-income countries (LMICs). RESULTS: Eleven clinical studies were identified, comprising 1543 TB patients treated with RFB; 980 (64%) were living with HIV. RFB was as safe and effective as RMP, including in 313 patients receiving co-administered ART (unboosted PIs included indinavir, nelfinavir or saquinavir; a minority received ritonavir [RTV] boosted amprenavir or saquinavir). The total cost for 6 months of all HIV and TB treatment containing RTV-boosted lopinavir (LPV) and RFB is US$410, compared to US$455 if RMP is used with LPV super-boosted with RTV. Our model suggests that demand for RFB in LMICs could be between 10 000 and 18 000 courses by 2012. CONCLUSION: RFB is effective and safe in combination with the PIs studied, cost-saving for co-therapy with currently recommended boosted PIs, and may have a pivotal role in the roll-out of ART. Further research into a daily dose of RFB to simplify dosing regimens and developing fixed-dose combinations can enhance the public sector roll-out of ART.

Despite significant advances in the development of therapeutic strategies for HIV over the past 25 years, the AIDS pandemic continues to grow worldwide. Access to life-saving medicines is not universal and there is a critical need for better prevention strategies. This review will highlight current research in the area of HIV prevention strategies, including preventive HIV vaccines, effective microbicides, treatment of sexually transmitted infections and the impact on HIV transmission, in addition to the role of male circumcision and pre-exposure prophylaxis with antiretroviral medications in HIV prevention.

Objective:To investigate a possible nosocomial outbreak of tuberculosis (TB).Design:Retrospective cohort study.Setting:Community hospital.Methods:We reviewed medical records, hospital infection control measures, and potential locations of nosocomial exposure. We examined the results of acid-fast bacilli (AFB) smears, cultures, and drug susceptibility testing, and performed a DNA fingerprint analysis. We observed laboratory specimen processing procedures and bronchoscope disinfection procedures. We also reviewed bronchoscopy records.Results:In October 2000, three patients had bronchoscopy specimen cultures that were positive forMycobacterium tuberculosis.Of the three, only one had clinical signs and symptoms consistent with TB and positive AFB sputum smears. The other two did not have signs and symptoms consistent with TB and had no known exposure to individuals with infectious TB. The threeM. tuberculosisisolates had matching DNA fingerprints. No evidence of laboratory cross-contamination was identified. The three culture-positive specimens ofM. tuberculosiswere collected with the same bronchoscope within 9 days. This bronchoscope was inadequately cleaned and disinfected between patients, and the automated reprocessor used was not approved for use with the hospital bronchoscope.Conclusions:One of the bronchoscopes at this hospital was contaminated withM. tuberculosisduring bronchoscopy of an AFB-smear-positive patient. Subsequent specimen contamination likely occurred because the bronchoscope had been inadequately cleaned and disinfected. Patients who subsequently underwent bronchoscopy were also potentially exposed toM. tuberculosisfrom this bronchoscope.

On November 19, 2001, a suspected case of inhalational anthrax in a 94-year-old woman was reported to the Connecticut Department of Public Health (CTDPH) (1–3). This was the first case of Bacilus anthracis infection reported to the CTDPH since 1968 and the eleventh inhalational anthrax case in the United States since October 4, 2001 (1–6). The patient’s symptoms of fever, fatigue, malaise, dry cough, and shortness of breath began 20 days after the last confirmed inhalational anthrax patient became ill and 36 days after the last known intentionally contaminated letters, addressed to U.S. Senators Thomas Daschle and Patrick Leahy, were postmarked in Trenton, New Jersey (1–4) (Figure 1).The patient in Connecticut was not in the known categories of intentionally contaminated letter recipients and was not a postal worker or a mailhandler (1,5). This report describes the epidemiologic and environmental investigation conducted to determine whether her case was related to the other bioterrorism-related cases; whether she was the only case in Connecticut or a sentinel of a larger outbreak; and the source, place, and time of her exposure. The clinical aspects of the case have been described (2,3). Figure 1 Bioterrorism-related inhalational anthrax cases by week of symptom onset—United States, 2001.The first two cases of inhalational anthrax occurred in Florida. Though no direct exposure source was found, environmental samples of the media company ...

In 1998–1999, the Baltimore TB control program detected a cluster of 21 tuberculosis (TB) cases. Patients reported frequent travel to various East Coast cities. An investigation was conducted to determine whether transmission of the same Mycobacterium tuberculosis strain was occurring in these other localities. A collaborative investigation among federal, state, and local TB controllers included TB record reviews, interviews of patients, and restriction fragment length polymorphism (RFLP) analysis of selected M. tuberculosis isolates from diagnosed TB patients in several cities in 1996–2001. A national TB genotyping database was searched for RFLP patterns that matched the outbreak pattern. Eighteen additional outbreak-related cases were detected outside of Baltimore—the earliest diagnosed in New Jersey in 1996, and the most recent in New York City in late 2001. The outbreak demonstrates the need for strategies to detect links among patients diagnosed with TB across multiple TB control jurisdictions.

The use of rifamycins is limited by drug interactions in human immunodeficiency virus (HIV)-infected persons who are receiving highly active antiretroviral therapy (HAART). During a tuberculosis (TB) outbreak at a prison housing HIV-infected inmates, rifabutin was used to treat 238 men (13 case patients and 225 contacts). Steady-state peak plasma rifabutin concentrations were obtained after rifabutin dosages were adjusted for men receiving single-interacting HAART (with either 1 protease inhibitor [PI] or efavirenz), multi-interacting HAART (with either 2 PIs or > or =1 PI with efavirenz), and for noninteracting HAART (>1 nucleoside reverse-transcriptase inhibitor or no HAART) without rifabutin dose adjustments. Low rifabutin concentrations occurred in 9% of those receiving noninteracting HAART, compared with 19% of those receiving single-interacting and 29% of those receiving multi-interacting HAART (chi2, 3.76; P=.05). Of 225 contacts treated with rifabutin-pyrazinamide, 158 (70%) completed treatment while incarcerated. Rifabutin-pyrazinamide therapy was difficult to implement, because of the need for dosage adjustments and expert clinical management.

On November 19, 2001, a case of inhalational anthrax was identified in a 94-year-old Connecticut woman, who later died. We conducted intensive surveillance for additional anthrax cases, which included collecting data from hospitals, emergency departments, private practitioners, death certificates, postal facilities, veterinarians, and the state medical examiner. No additional cases of anthrax were identified. The absence of additional anthrax cases argued against an intentional environmental release of Bacillus anthracis in Connecticut and suggested that, if the source of anthrax had been cross-contaminated mail, the risk for anthrax in this setting was very low. This surveillance system provides a model that can be adapted for use in similar emergency settings.

We collected data during postexposure antimicrobial prophylaxis campaigns and from a prophylaxis program evaluation 60 days after start of antimicrobial prophylaxis involving persons from six U.S. sites where Bacillus anthracis exposures occurred. Adverse events associated with antimicrobial prophylaxis to prevent anthrax were commonly reported, but hospitalizations and serious adverse events as defined by Food and Drug Administration criteria were rare. Overall adherence during 60 days of antimicrobial prophylaxis was poor (44%), ranging from 21% of persons exposed in the Morgan postal facility in New York City to 64% of persons exposed at the Brentwood postal facility in Washington, D.C. Adherence was highest among participants in an investigational new drug protocol to receive additional antibiotics with or without anthrax vaccine--a likely surrogate for anthrax risk perception. Adherence of

In 1998, a city in Indiana reported 4-fold increase in the number of cases of tuberculosis (TB). An investigation to assess the increase in cases and to identify possible epidemiologic links among persons with TB identified 41 cases of active TB. Epidemiologic links and/or matching DNA fingerprints were identified for 31 patients (76%). The majority of these patients were members of a single social network within the community. Links for most of these patients were identified after multiple interviews with patients and their contacts. TB control activities in the county were limited prior to the identification of the outbreak. At least 24 cases may have been preventable. This outbreak may have been prevented with prompt case identification and effective contact tracing and screening during the years before the outbreak. The use of social networks should be considered in the investigation of outbreaks that involve difficult-to-reach populations. TB control measures should be maintained in areas with historically low TB incidence.

Use of rifampin is required for short-course treatment regimens for tuberculosis. Tuberculosis caused by isolates of M. tuberculosis with resistance to rifampin and susceptibility to isoniazid is unusual, but it has been recognized through surveillance. Patients with tuberculosis (cases) with rifampin monoresistance were compared with HIV-matched controls with tuberculosis caused by a drug-susceptible isolate. A total of 77 cases of rifampin mono-resistant tuberculosis were identified in this multicenter study. Three were determined to be laboratory contaminants, and 10 cases had an epidemiologic link to a case with rifampin mono-resistant tuberculosis, suggesting primary acquisition of rifampin-resistant isolates. Of the remaining 64 cases and 126 controls, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, or history of incarceration. Cases were more likely to have a history of prior tuberculosis than were controls. Of the 38 cases and 74 controls with HIV infection, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, history of incarceration, or prior tuberculosis. Cases were more likely to have histories of diarrhea, rifabutin use, or antifungal therapy. Laboratory analysis of available isolates showed that there was no evidence of spread of a single clone of M. tuberculosis. Further studies are needed to identify the causes of the development of rifampin resistance in HIV-infected persons with tuberculosis and to develop strategies to prevent its emergence. Ridzon R, Whitney CG, McKenna MT, Taylor JP, Ashkar SH, Nitta AT, Harvey SM, Valway S, Woodley C, Cooksey R, Onorato IM. Risk factors for rifampin mono-resistant tuberculosis. AM J RESPIR CRIT CARE MED 1998;157:1881‐1884.

Background: In spring 1993, four students in a high school were diagnosed with tuberculosis resistant to isoniazid, streptomycin, and ethionamide. Methods: To investigate potential transmission of drug-resistant tuberculosis, a retrospective cohort study with case investigation and screening by tuberculin skin tests and symptom checks was conducted in a high school of approximately 1400 students. Current and graduated high-school students were included in the investigation. DNA fingerprinting of available isolates was performed. Results: Eighteen students with active tuberculosis were identified, Through epidemiologic and laboratory investigation, 13 cases were linked; 8 entered 12th grade in fall 1993; 9 of 13 had positive cultures for Mycobacterium tuberculosis with isoniazid, streptomycin, and ethionamide resistance, and all 8 available isolates had identical DNA fingerprints. No staff member had tuberculosis. One student remained infectious for 29 months, from January 1991 to June 1993, and was the source case for the outbreak. Another student was infectious for 5 months before diagnosis in May 1993 and was a treatment failure in February 1994 with development of rifampin and ethambutol resistance in addition to isoniazid, streptomycin, and ethionamide. In the fall 1993 screening, 292 of 1263 (23%) students tested had a positive tuberculin skin test. Risk of infection was highest among 12th graders and classroom contacts of the two students with prolonged infectiousness. An additional 94 of 928 (10%) students tested in spring 1994 had a positive tuberculin skin test; 22 were classroom contacts of the student with treatment failure and 21 of these had documented tuberculin skin test conversions. Conclusion: Extensive transmission of drug-resistant tuberculosis was documented in this high school, along with missed opportunities for prevention and control of this outbreak. Prompt identification of tuberculosis cases and timely interventions should help reduce this public health problem. (J Pediatr 1997;131:863-8)

For persons infected with Mycobacterium tuberculosis resistant to isoniazid (INH), rifampin is recommended for the prevention of active disease. However, the adverse effects and acceptability of this preventive therapy are largely uncharacterized. We prospectively followed 157 high-school students exposed to, and probably infected with, M. tuberculosis strains resistant to INH. All 157 students were prescribed preventive therapy with rifampin (10 mg/kg up to 600 mg daily) for 24 wk. While receiving therapy, 41 (26%) reported one or more adverse effects; of these, 18 had therapy interrupted temporarily, two permanently. Four (2.5%) had alanine aminotransferase elevations greater than two times the upper limit of normal (range, 91 to 161 U/L); of these, one had therapy permanently stopped. Six (3.8%) self-discontinued therapy. No student was found to have active disease during the 2 yr of the study (exact 95% upper confidence limit, 2.2). We assumed that without preventive therapy, seven cases of tuberculosis would have occurred during these 2 yr. Therefore, we estimated that rifampin had a minimum protective effect of 56%. In conclusion, preventive therapy with rifampin was well tolerated and well accepted, and it appears effective in preventing active tuberculosis.

Foreign-born persons from countries where tuberculosis (TB) is endemic make up a significant percentage of poultry industry workers in Delaware, a leading poultry-producing state. Many of these workers enter the United States without documentation and assume multiple identities, making it difficult for public health staff to investigate TB contacts who work in the poultry plants. The Sussex County Health Unit of the Delaware Division of Public Health developed a no-name TB tracking system to facilitate identification and treatment of poultry plant workers with TB infection and disease in a high-risk population whose members assume one or more aliases. Completion rates for treatment of latent TB infection in this group increased from 48% to 64% 2 years after the program’s implementation.

As the science demonstrating strong evidence for voluntary medical male circumcision (VMMC) for HIV prevention has evolved, the President's Emergency Plan for AIDS Relief (PEPFAR) has collaborated with international agencies, donors, and partner country governments supporting VMMC programming. Mathematical models forecast that quickly reaching a large number of uncircumcised men with VMMC in strategically chosen populations may dramatically reduce community-level HIV incidence and save billions of dollars in HIV care and treatment costs. Because VMMC is a 1-time procedure that confers life-long partial protection against HIV, programs for adult men are vital short-term investments with long-term benefits. VMMC also provides a unique opportunity to reach boys and men with HIV testing and counseling services and referrals for other HIV services, including treatment. After formal recommendations by WHO in 2007, priority countries have pursued expansion of VMMC. More than 1 million males have received VMMC thus far, with the most notable successes coming from Kenya's Nyanza Province. However, a myriad of necessary cultural, political, and ethical considerations have moderated the pace of overall success. Because many millions more uncircumcised men would benefit from VMMC services now, US President Barack Obama committed PEPFAR to provide 4.7 million males with VMMC by 2014. Innovative circumcision methods-such as medical devices that remove the foreskin without injected anesthesia and/or sutures-are being rigorously evaluated. Incorporation of safe innovations into surgical VMMC programs may provide the opportunity to reach more men more quickly with services and dramatically reduce HIV incidence for all.

La reinfection exogene par Mycobacterium tuberculosis est un phenomene important qui se produit a une frequence inconnue a la fois chez des sujets immunodeprimes et immunocompetents. Puisque des investigations anterieures suggerent que la reinfection exogene peut survenir dans ces deux populations, nous avons revu les donnees de 40 cas de suspicion de rechute de tuberculose afin d'essayer de determiner la frequence de ce phenomene chez les patients traites a l'Unite de Recherche de Tuberculose de Kampala en Ouganda. Nos observations suggerent que, alors que la reinfection exogene par M. tuberculosis peut survenir chez des patients immunocompetents, son risque est probablement plus eleve chez les sujets en etat d'immunodepression.

Infectious respiratory pathogens were the suspected cause of 480 outbreaks investigated by the Centers for Disease Control and Prevention's Epidemic Intelligence Service officers during 1946-2005. All epidemic-assistance investigation reports and associated articles from scientific journals were reviewed. Investigations identified 25 different infectious respiratory pathogens including, most frequently, tuberculosis, influenza, and legionellosis. Other bacterial-, viral-, and fungal-related pathogens also were identified. Epidemic-assistance investigations were notable for first identifying Legionnaires disease and Pontiac fever, hantavirus pulmonary syndrome, and new strains of human and avian influenza, as well as emerging challenges (e.g., multidrug-resistant tuberculosis and pneumococcus). The investigations provided clinical insights into such diseases as pulmonary anthrax and identified high risks of serious respiratory illnesses for persons infected with human immunodeficiency virus, other immunocompromised persons, and persons with diabetes. They identified settings placing persons at high risk of acquiring disease, including nursing homes, prisons, homeless shelters, and hospitals. Travel also placed persons at risk. Key environmental factors related to spread of diseases and occupational risks for brucellosis and psittacosis were identified. The outbreak investigations constitute a wealth of prevention experience and provide the basis for recommendations to mitigate outbreaks and reduce future risks.

There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P

Summary Background Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners. Methods 922 uncircumcised, HIV-infected, asymptomatic men aged 15–49 years with CD4-cell counts 350 cells per μL or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878. Findings The trial was stopped early because of futility. 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0·36). Cumulative probabilities of female HIV infection at 24 months were 21·7% (95% CI 12·7–33·4) in the intervention group and 13·4% (6·7–25·8) in the control group (adjusted hazard ratio 1·49, 95% CI 0·62–3·57; p=0·368). Interpretation Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention. Funding Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.

OBJECTIVE To investigate the effect of adult medical male circumcision on female sexual satisfaction. SUBJECTS AND METHODS We investigated self-reported sexual satisfaction among 455 women partners of men circumcised in a randomized trial of male circumcision for the prevention of human immunodeficiency virus in Rakai, Uganda. Women aged 15-49 years were interviewed about their sexual satisfaction before and after their partners were circumcised. We analysed female-reported changes in sexual satisfaction using chi-square or Fisher's exact tests. RESULTS Only 2.9% (13/455) of women reported less sexual satisfaction after their partners were circumcised; 57.3% (255/455) reported no change in sexual satisfaction and 39.8% (177/455) reported an improvement in sexual satisfaction after their partner's circumcision. There were no statistically significant differences in sexual satisfaction before and after partner's circumcision by age, religion and education status. CONCLUSION The overwhelming majority of women (97.1%) report either no change or improved sexual satisfaction after their male partner was circumcised. These findings suggest that male circumcision has no deleterious effect on female sexual satisfaction.

Background The objective of the study was to compare rates of adverse events (AEs) related to male circumcision (MC) in HIV-positive and HIV-negative men in order to provide guidance for MC programs that may provide services to HIV-infected and uninfected men. Methods and Findings A total of 2,326 HIV-negative and 420 HIV-positive men (World Health Organization [WHO] stage I or II and CD4 counts > 350 cells/mm3) were circumcised in two separate but procedurally identical trials of MC for HIV and/or sexually transmitted infection prevention in rural Rakai, Uganda. Participants were followed at 1–2 d and 5–9 d, and at 4–6 wk, to assess surgery-related AEs, wound healing, and resumption of intercourse. AE risks and wound healing were compared in HIV-positive and HIV-negative men. Adjusted odds ratios (AdjORs) were estimated by multiple logistic regression, adjusting for baseline characteristics and postoperative resumption of sex. At enrollment, HIV-positive men were older, more likely to be married, reported more sexual partners, less condom use, and higher rates of sexually transmitted disease symptoms than HIV-negative men. Risks of moderate or severe AEs were 3.1/100 and 3.5/100 in HIV-positive and HIV-negative participants, respectively (AdjOR 0.91, 95% confidence interval [CI] 0.47–1.74). Infections were the most common AEs (2.6/100 in HIV-positive versus 3.0/100 in HIV-negative men). Risks of other complications were similar in the two groups. The proportion with completed healing by 6 wk postsurgery was 92.7% in HIV-positive men and 95.8% in HIV-negative men (p = 0.007). AEs were more common in men who resumed intercourse before wound healing compared to those who waited (AdjOR 1.56, 95% CI 1.05–2.33). Conclusions Overall, the safety of MC was comparable in asymptomatic HIV-positive and HIV-negative men, although healing was somewhat slower among the HIV infected. All men should be strongly counseled to refrain from intercourse until full wound healing is achieved. Trial registration: http://www.ClinicalTrials.gov; for HIV-negative men, #NCT00047073 and for HIV-positive men, #NCT00047073., Ron Gray and colleagues report on complications of circumcision in HIV-infected and HIV-uninfected men from two related trials in Uganda, finding increased risk with intercourse before wound healing., Editors' Summary Background Worldwide over 33 million people are thought to be living with HIV, and in the absence of a vaccine, preventing its spread is a major health issue. The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimate that 68% of 2.5 million new infections worldwide in 2007 took place in sub-Saharan Africa, where 76% of 2.1 million AIDS-related deaths also took place. One of the principal means of person-to-person transmission of HIV is through sex without the protection of a condom. In parts of Africa, male circumcision is performed in infancy or childhood for religious or cultural reasons or is a traditional rite of passage that marks the transition from child to man. Three trials, in South Africa, Kenya, and Uganda, each found that circumcised men were around half as likely as uncircumcised men to contract HIV from HIV-positive female partners. After reviewing the results, WHO and UNAIDS issued joint advice that male circumcision should be promoted for preventing HIV infection in heterosexual men. As male circumcision does not provide complete protection against HIV infection, they advised that it should be promoted in addition to existing strategies of promoting condom use, abstinence, and a reduction in the number of sexual partners. Why Was This Study Done? Although earlier studies had shown that adult male circumcision, when performed in Africa under optimal conditions, is a safe procedure for HIV-negative men, it was not known whether it would also be a safe procedure for HIV-positive men. WHO guidelines recommend that HIV-positive men who request the procedure or have a medical need and no contraindications for it should be circumcised. Also, exclusion of HIV-positive men from circumcision programs may result in stigmatization of these men, and discourage participation by men who do not wish to be tested for HIV. Therefore, it is important to know whether the procedure is safe for HIV-positive men. What Did the Researchers Do and Find? The authors compared results from two separate clinical trials carried out with identical procedures in rural Rakai, Uganda. The first, which compared the effect of circumcision with no circumcision in HIV-negative men, was one of the three trials that persuaded the WHO and UNAIDS to promote male circumcision as an HIV prevention strategy. The second Rakai trial did the same comparison but in men who were HIV positive and without symptoms. In this present study, the authors used data from both trials to compare the likelihood of surgery-related complications following circumcision for HIV-negative and HIV-positive men. The trials recruited men aged 15–49, who were randomly assigned to be circumcised either on enrollment or two years later and were followed up to monitor complications related to the procedure, such as infections, as well as wound healing and when the participant first had sex after the operation. Condom use was recorded at enrollment and six months after enrollment. The researchers found that most complications were infrequent, mild, and comparable in both groups, with moderate-to-severe complications occurring in only 3%–4% of men in each group. However, delayed wound healing was more frequent in HIV-positive men. Complications were more likely among men who had sex before healing was complete; such men were more likely to be HIV-positive and/or married. Similarly, moderate or severe complications were more likely where men had symptoms of sexually transmitted disease at enrollment, although these were treated before surgery, and these men were more likely to be HIV-positive. Six months after enrollment, similar proportions of HIV-positive and HIV-negative men used condoms consistently, but HIV-positive men were more likely to report using condoms inconsistently than HIV-negative men. However, consistent use of a condom increased among the HIV-positive men compared to when they enrolled. What Do these Findings Mean? Circumcision in HIV-positive men without symptoms of AIDS has a low rate of complications, although healing is slower than in HIV-negative men. Because of the greater risk of complications if sex is resumed before full healing, both men and their women partners should be advised to have no sex for at least six weeks after the operation. A separately reported analysis from one of these studies found that women partners are more likely to become HIV infected by HIV-positive men who resume sex prior to complete wound healing. Therefore, for protection of both men and their female partners, it is essential to refrain from intercourse after circumcision until the wound has completely healed. Because the study found no increased risk of surgical complications in HIV-positive men who undergo circumcision, it should not be necessary to screen men with no symptoms of HIV in future circumcision programs. This should reduce the complexity of implementing such programs and reduce any stigma resulting from exclusion, making it likely that more men will be willing to be circumcised. The rise in consistent condom use among HIV-positive men suggests that messages of safe sex are reaching an important target group and changing their behavior, and that circumcision does not make men less likely to use a condom. The authors also noted that the rates of complications they observed were low compared with those following traditional circumcision procedures. Others have found that circumcision carried out under unsafe conditions has a high rate of complications. The authors of this study comment that the resources and standards of surgery during the trial represented best practice and that to attain similarly low rates of complications—and the confidence of men in the safety of the procedure—there is a need to ensure sufficient resources and high standards of training. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050116. WHO and the UNAIDS issued a joint report recommending male circumcision for HIV prevention and another on the HIV epidemic worldwide in December 2007 An information pack here on male circumcision and HIV prevention has also been developed jointly by WHO/UNAIDS, the United Nations International Children's Emergency Fund (UNICEF), the United Nations Population Fund (UNFPA), and the World Bank The University of California San Francisco's HIV InSite provides information on HIV prevention, treatment, and policy AEGIS is the world's largest searchable database on HIV and AIDS The National AIDS Trust provides information on HIV prevention