Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021-2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy.

BACKGROUND: In 2021, a large petroleum leak contaminated a water source that supplied drinking water to military and civilians in Oahu, Hawaii. METHODS: We conducted an Assessment of Chemical Exposures (ACE) survey and supplemented that information with complementary data sources: (1) poison center caller records; (2) emergency department visit data; and (3) a key informant questionnaire. RESULTS: Among 2,289 survey participants, 86% reported ≥1 new or worsening symptom, 75% of which lasted ≥30 days, and 37% sought medical care. Most (n = 1,653, 72%) reported new mental health symptoms. Among equally observable symptoms across age groups, proportions of children ≤2 years experiencing vomiting, runny nose, skin rashes, and coughing (33, 46, 56, and 35%, respectively) were higher than other age groups. Poison center calls increased the first 2 weeks after the contamination, while emergency department visits increased in early December 2021. Key informant interviews revealed themes of lack of support, mental health symptoms, and long-term health impact concerns. DISCUSSION: This event led to widespread exposure to petroleum products and negatively affected thousands of people. Follow-up health surveys or interventions should give special consideration to longer-term physical and mental health, especially children due to their unique sensitivity to environmental exposures.

OBJECTIVE: Although vaccination reduces the risk of severe COVID-19, fatal COVID-19 cases after vaccination can occur. We examined the characteristics of decedents with COVID-19-related mortality to help inform discussions about vaccination, boosters, and mitigation strategies. METHODS: We examined COVID-19-related deaths in Kentucky resulting from infections occurring from July 1 through August 13, 2021. We used records from case investigations, medical records, the Kentucky Health Information Exchange, and the Kentucky Immunization Registry to determine demographic information, vaccination status, and underlying health conditions, including calculation of the Charlson Comorbidity Index (CCI). We calculated mortality incidence rates by vaccination status by using data for unvaccinated and fully vaccinated populations in Kentucky as of July 1, 2021. RESULTS: In total, 777 COVID-19-related deaths occurred in Kentucky during the study period; 592 (76.2%) occurred among unvaccinated people. Compared with unvaccinated decedents, fully vaccinated decedents were older (median age, 77 vs 65 years; P < .001), had higher comorbidity levels (median CCI, 3 vs 1; P < .001), and were more likely to have immunocompromised health status (26.4% vs 16.0%; P = .003). Diabetes, hypertension, heart disease, and chronic lung disease were more common among vaccinated decedents than among unvaccinated decedents. Unvaccinated adults had a significantly higher risk of death than fully vaccinated adults (incidence rate ratio for age 20-49 years: 20.5 [95% CI, 6.5-64.8]; 50-64 years: 14.6 [95% CI, 9.4-22.7]; ≥65 years: 10.2 [95% CI, 8.3-12.4]). CONCLUSIONS: Immunocompromised health status, older age, and higher comorbidity were prevalent among fully vaccinated decedents, suggesting adults with these characteristics may benefit from additional protection strategies. Further understanding of the protection of additional and booster doses is needed.

On July 26, 2022, a pediatric nephrologist alerted The Gambia's Ministry of Health (MoH) to a cluster of cases of acute kidney injury (AKI) among young children at the country's sole teaching hospital, and on August 23, 2022, MoH requested assistance from CDC. CDC epidemiologists arrived in The Gambia, a West African country, on September 16 to assist MoH in characterizing the illness, describing the epidemiology, and identifying potential causal factors and their sources. Investigators reviewed medical records and interviewed caregivers to characterize patients' symptoms and identify exposures. The preliminary investigation suggested that various contaminated syrup-based children's medications contributed to the AKI outbreak. During the investigation, MoH recalled implicated medications from a single international manufacturer. Continued efforts to strengthen pharmaceutical quality control and event-based public health surveillance are needed to help prevent future medication-related outbreaks.

SETTING: Mulago Hospital, Kampala, Uganda.OBJECTIVE: To quantify Mycobacterium tuberculosis in sputum during the first 8 weeks of pulmonary multidrug-resistant TB (MDR-TB) treatment.DESIGN: We enrolled consecutive adults with pulmonary MDR-TB treated according to national guidelines. We collected overnight sputum samples before treatment and weekly. Sputum samples were cultured on Middlebrook 7H11S agar to measure colony-forming units per mL (cfu/mL) and in MGIT™ 960™ media to measure time to detection (TTD). Linear mixed-effects regression was used to estimate the relational change in log(10) cfu/mL and TTD.RESULTS: Twelve adults (median age: 27 years) were enrolled. Half were women, and two-thirds were HIV-positive. At baseline, median log(10) cfu/mL was 5.1, decreasing by 0.29 log(10) cfu/mL/week. The median TTD was 116.5 h, increasing in TTD by 36.97 h/week. The weekly change was greater in the first 2 weeks (-1.04 log(10) cfu/mL/week and 120.02 h/week) than in the remaining 6 weeks (-0.17 log(10) cfu/mL/week and 26.11 h/week).CONCLUSION: Serial quantitative culture measures indicate a slow, uneven rate of decline in sputum M. tuberculosis over 8 weeks of standardized pulmonary MDR-TB treatment.

BACKGROUND: COVID-19 vaccines are an effective tool to prevent illness due to SARS-CoV-2 infection. However, infection after vaccination still occurs. We evaluated all infections identified among recipients of either the Pfizer-BioNTech or Moderna COVID-19 vaccine in five U.S. states during January-March 2021. METHODS: Using observational data reported to CDC, we compared the incidence of SARS-CoV-2 infection among vaccinated and unvaccinated persons, and the sex, age, and vaccine product received for individuals with vaccine breakthrough infections to those of the vaccinated population using Poisson regression models. We also compared the proportion of vaccine breakthrough cases due to a SARS-CoV-2 variant of concern to data reported to CDC's national genomic surveillance program. RESULTS: The age-adjusted incidence of reported SARS-CoV-2 infection was 97% lower among vaccinated as compared to unvaccinated persons aged ≥ 16 years (68 vs 2252 cases per 100,000 people). Vaccinated adults aged ≥ 85 years were 1.6 times (95% CI 1.3-1.9) as likely to become infected with SARS-CoV-2 than vaccinated adults aged < 65 years. Pfizer-BioNTech COVID-19 vaccine recipients were 1.4 times (95% CI 1.3-1.6) as likely to experience infection compared to Moderna COVID-19 recipients. The proportion of infections among vaccinated persons caused by SARS-CoV-2 variants of concern was similar to the proportion of circulating viruses identified as variants of concern in the five states during the same time. CONCLUSIONS: Vaccinated persons had a substantially lower incidence of SARS-CoV-2 infection compared to unvaccinated persons. Adults aged ≥ 85 years and Pfizer-BioNTech vaccine recipients had a higher risk of infection following vaccination. We provide an analytic framework for ongoing evaluation of patterns associated with SARS-CoV-2 infection among vaccinated persons using observational surveillance and immunization data. Our findings reinforce the effectiveness of COVID-19 vaccines in preventing infection in real-world settings.

In a cross-sectional study of 89,736 adolescents in Kentucky, SARS-CoV-2 vaccination provided estimated protection of 81% against infection when the highly transmissible Delta variant was predominant. Vaccination provided added benefit to those with history of prior infection. These findings support the recommendation that all adolescents receive vaccination.

In late November 2021, the Hawaii Department of Health (HDOH) received reports from Oahu residents of a fuel-like odor coming from their drinking water (1), which was later determined to be related to a November 20, 2021, petroleum (jet fuel) leak at the Red Hill Bulk Fuel Storage Facility. The petroleum leak contaminated the Joint Base Pearl Harbor-Hickam water system,* which supplies an estimated 9,694 civilian and military households (2), in addition to schools and workplaces. HDOH issued a drinking water advisory on November 30, 2021 (1), which was not lifted for all affected zones until March 18, 2022.† Persons in thousands of households were offered temporary housing, and alternative drinking water was provided to users of affected water. HDOH requested epidemiologic assistance (Epi-Aid) from CDC/Agency for Toxic Substances and Disease Registry (ATSDR) to assess the incident’s impact on civilian health in the affected area; this was later expanded to include military-affiliated persons.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m(2)), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

BACKGROUND: As vaccine supply and access remain limited in many parts of the world, understanding the duration of protection from reinfection after natural infection is important. METHODS: Distinct individuals testing positive and negative for SARS-CoV-2 between March 6, 2020, and August 31, 2020, in Kentucky, USA, were identified using the Kentucky National Electronic Disease Surveillance System. Individuals were followed for occurrence of a positive test for SARS-CoV-2 from 91 days after their initial test result through December 31, 2020. Protection from reinfection provided by a prior infection was calculated and additional analyses evaluated impact of age, sex, symptom status, long-term care facility connection, testing occurrence and frequency, and time from initial infection. RESULTS: Protective effect from prior infection was 80.3% (95% CI, 78.2% - 82.2%) for those aged 20-59 years and 67.4% (95% CI, 62.8% - 71.4%) for those 60 years and older. At 30-day time periods through 270 days (with limited exceptions), protection was estimated to be greater than 75% for those aged 20-59 years and greater than 65% for those 60 years and older. Factors associated with repeat positive testing included a connection to a long-term care facility, duration of potential exposure, and absence of symptoms during initial infection. CONCLUSIONS: Natural infection provides substantial and persistent immunologic protection for a period of several months for most individuals, although subpopulations may be at greater risk for repeat positive testing and potential poor outcomes associated with reinfection. These subgroups include individuals 60 years and older, residents and staff of long-term care facilities, and those who have mild or asymptomatic illness with initial infection. Continued emphasis on vaccination and infection prevention and control strategies remains critically important in reducing the risk for reinfection and associated severe outcomes for these groups.

Although laboratory evidence suggests that antibody responses following COVID-19 vaccination provide better neutralization of some circulating variants than does natural infection (1,2), few real-world epidemiologic studies exist to support the benefit of vaccination for previously infected persons. This report details the findings of a case-control evaluation of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May-June 2021 among persons previously infected with SARS-CoV-2 in 2020. Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58-3.47). These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection. To reduce their risk of infection, all eligible persons should be offered vaccination, even if they have been previously infected with SARS-CoV-2.

The World Health Organization (WHO) recommends providing tuberculosis preventive treatment (TPT) to all persons living with HIV and to all household contacts of persons with bacteriologically confirmed pulmonary tuberculosis disease. Regrettably, the absence of a harmonized data collection and management approach to TPT indicators has contributed to programmatic challenges at local, national, and global levels. However, in April 2020, the WHO launched the Consolidated HIV Strategic Information Guidelines, with an updated set of priority indicators. These guidelines recommend that Ministries of Health collect, report, and use data on TPT completion in addition to TPT initiation. Both indicators are reflected in the WHO's list of 15 core indicators for program management and are also required by the US President's Emergency Plan for AIDS Relief's Monitoring, Evaluation, and Reporting (MER) guidance. Although not perfectly harmonized, both frameworks now share essential indicator characteristics. Aligned indicators are necessary for robust strategic and operational planning, resource allocation, and data communication. "Collect once, use many times" is a best practice for strategic information management. Building harmonized and sustainable health systems will enable countries to successfully maintain essential HIV, tuberculosis, and other health services while combatting new health threats.

Although COVID-19 mRNA vaccines demonstrated high efficacy in clinical trials (1), they were not 100% efficacious. Thus, some infections postvaccination are expected. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants. The Kentucky Department for Public Health (KDPH) and a local health department investigated a COVID-19 outbreak in a SNF that occurred after all residents and health care personnel (HCP) had been offered vaccination. Among 83 residents and 116 HCP, 75 (90.4%) and 61 (52.6%), respectively, received 2 vaccine doses. Twenty-six residents and 20 HCP received positive test results for SARS-CoV-2, the virus that causes COVID-19, including 18 residents and four HCP who had received their second vaccine dose >14 days before the outbreak began. An R.1 lineage variant was detected with whole genome sequencing (WGS). Although the R.1 variant has multiple spike protein mutations, vaccinated residents and HCP were 87% less likely to have symptomatic COVID-19 compared with those who were unvaccinated. Vaccination of SNF populations, including HCP, is critical to reduce the risk for SARS-CoV-2 introduction, transmission, and severe outcomes in SNFs. An ongoing focus on infection prevention and control practices is also essential.

CONTEXT: Local agencies across the United States have identified public health isolation sites for individuals with coronavirus disease 2019 (COVID-19) who are not able to isolate in residence. PROGRAM: We describe logistics of establishing and operating isolation and noncongregate hotels for COVID-19 mitigation and use the isolation hotel as an opportunity to understand COVID-19 symptom evolution among people experiencing homelessness (PEH). IMPLEMENTATION: Multiple agencies in Atlanta, Georgia, established an isolation hotel for PEH with COVID-19 and noncongregate hotel for PEH without COVID-19 but at risk of severe illness. PEH were referred to the isolation hotel through proactive, community-based testing and hospital-based testing. Daily symptoms were recorded prospectively. Disposition location was recorded for all clients. EVALUATION: During April 10 to September 1, 2020, 181 isolation hotel clients (77 community referrals; 104 hospital referrals) were admitted a median 3 days after testing. Overall, 32% of community referrals and 7% of hospital referrals became symptomatic after testing positive; 83% of isolation hotel clients reported symptoms at some point; 93% completed isolation. Among 302 noncongregate hotel clients, median stay was 18 weeks; 61% were discharged to permanent housing or had a permanent housing discharge plan. DISCUSSION: Overall, a high proportion of PEH completed isolation at the hotel, suggesting a high level of acceptability. Many PEH with COVID-19 diagnosed in the community developed symptoms after testing, indicating that proactive, community-based testing can facilitate early isolation. Noncongregate hotels can be a useful COVID-19 community mitigation strategy by bridging PEH at risk of severe illness to permanent housing.

Reinfection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is believed to be rare (1). Some level of immunity after SARS-CoV-2 infection is expected; however, the evidence regarding duration and level of protection is still emerging (2). The Kentucky Department for Public Health (KDPH) and a local health department conducted an investigation at a skilled nursing facility (SNF) that experienced a second COVID-19 outbreak in October 2020, 3 months after a first outbreak in July. Five residents received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results during both outbreaks. During the first outbreak, three of the five patients were asymptomatic and two had mild symptoms that resolved before the second outbreak. Disease severity in the five residents during the second outbreak was worse than that during the first outbreak and included one death. Because test samples were not retained, phylogenetic strain comparison was not possible. However, interim period symptom resolution in the two symptomatic patients, at least four consecutive negative RT-PCR tests for all five patients before receiving a positive test result during the second outbreak, and the 3-month interval between the first and the second outbreaks, suggest the possibility that reinfection occurred. Maintaining physical distance, wearing face coverings or masks, and frequent hand hygiene are critical mitigation strategies necessary to prevent transmission of SARS-CoV-2 to SNF residents, a particularly vulnerable population at risk for poor COVID-19-associated outcomes.* Testing, containment strategies (isolation and quarantine), and vaccination of residents and health care personnel (HCP) are also essential components to protecting vulnerable residents. The findings of this study highlight the importance of maintaining public health mitigation and protection strategies that reduce transmission risk, even among persons with a history of COVID-19 infection.

Global HIV program stakeholders, including the US President's Emergency Plan for AIDS Relief (PEPFAR), are undertaking efforts to ensure that eligible people living with HIV (PLHIV) receiving antiretroviral treatment (ART) receive a course of TB preventive treatment (TPT). In PEPFAR programming, this effort may require providing TPT not only to newly diagnosed PLHIV as part of HIV care initiation, but also to treatment-experienced PLHIV stable on ART who may not have been previously offered TPT. TPT scale-up is occurring at the same time as a trend to provide more person-centered HIV care through differentiated service delivery (DSD). In DSD, PLHIV stable on ART may receive less frequent clinical follow-up or receive care outside the traditional clinic-based model. The misalignment between traditional delivery of TPT and care delivery in innovative DSD may require adaptations to TPT delivery practices for PLHIV. Adaptations include components of planning and operationalization of TPT in DSD, such as determination of TPT eligibility and TPT initiation, and clinical management of PLHIV while on TPT. A key adaptation is alignment of timing and location for TPT and ART prescribing, monitoring, and dispensing. Conceptual examples of TPT delivery in DSD may help program managers operationalize TPT in HIV care.

BACKGROUND: In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies. METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7-May 6, 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire. RESULTS: Overall, 2,875 individuals at 24 shelters and nine unsheltered outreach events underwent SARS-CoV-2 testing and 2,860 (99.5%) had conclusive test results. SARS-CoV-2 prevalence was 2.1% (36/1,684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases compared with RT-PCR. Prevalence by shelter ranged 0%-27.6%. Repeat testing 3-4 weeks later at four shelters documented decreased SARS-CoV-2 prevalence (0%-3.9%). Nine of 24 shelters completed shelter assessments and implemented IPC measures as part of the COVID-19 response. CONCLUSIONS: PEH living in shelters experienced higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission.

INTRODUCTION: The US President's Emergency Plan for AIDS Relief (PEPFAR) was launched to increase access to antiretroviral treatment (ART) among people living with HIV (PLHIV) and to prevent new HIV infections globally. As new infections have decreased in many PEPFAR-supported countries, PEPFAR is increasingly focusing on understanding and decreasing mortality among PLHIV, specifically by addressing advanced HIV disease (AHD) and its attendant opportunistic infections (OIs). Several developments in identifying AHD, in preventing, diagnosing, and treating selected OIs, and in PEPFAR's support for mortality surveillance make this an opportune moment for PEPFAR to address HIV-related mortality. DISCUSSION: AHD upon diagnosis or re-engagement in HIV care is not uncommon, and it substantially increases risk of death from OIs. The World Health Organization provides evidence-based guidelines for a package of interventions for preventing, diagnosing, and treating common OIs, including tuberculosis (TB), cryptococcal meningitis, and severe bacterial infections. PEPFAR facilitates implementation of these guidelines. To identify PLHIV with low CD4, PEPFAR plans to support expanded access to CD4 testing, including a point-of-care assay that differentiates CD4 cell count as a binary of greater than or less than 200 cells/microL. To prevent AHD-related mortality, PEPFAR supports rapid ART initiation with integrase inhibitor-based regimens and implementation and documentation of TB preventive treatment. To diagnose selected OIs, PEPFAR is implementing urine lateral flow lipoarabinomannan use to identify TB among PLHIV who have a CD4 cell count < 200 cells/microL. To treat selected OIs, PEPFAR has focused on improving patient-centered care in TB/HIV co-infection services and scaling up implementation of new drug regimens for cryptococcal meningitis. To better understand mortality, PEPFAR has introduced an indicator, TX_ML, to routinely and systematically categorize outcomes, including deaths, among PLHIV on ART. CONCLUSIONS: PEPFAR is increasing its efforts to identify AHD; to prevent, diagnose, and treat OIs; and to track mortality in its programs. These ongoing efforts, done in collaboration with other stakeholders, seek to decrease mortality among PLHIV.

BACKGROUND: Male circumcision confers partial protection against heterosexual HIV acquisition among men. The President's Emergency Plan for AIDS Relief (PEPFAR) has supported > 18,900,000 voluntary medical male circumcisions (VMMC). Glans injuries (GIs) are rare but devastating adverse events (AEs) that can occur during circumcision. To address this issue, PEPFAR has supported multiple interventions in the areas of surveillance, policy, education, training, supply chain, and AE management. METHODS: Since 2015, PEPFAR has conducted surveillance of GIs including rapid investigation by the in-country PEPFAR team. This information is collected on standardized forms, which were reviewed for this analysis. RESULTS: Thirty-six GIs were reported from 2015 to 2018; all patients were < 15 years old (~ 0.7 per 100,000 VMMCs in this age group) with a decreasing annual rate (2015: 0.7 per 100,000 VMMCs; 2018: 0.4 per 100,000 VMMC; p = 0.02). Most (64%) GIs were partial or complete amputations. All amputations among 10-14 year-olds occurred using the forceps-guided (FG) method, as opposed to the dorsal-slit (DS) method, and three GIs among infants occurred using a Mogen clamp. Of 19 attempted amputation repairs, reattached tissue was viable in four (21%) in the short term. In some cases, inadequate DS method training and being overworked, were found. CONCLUSION: Following numerous interventions by PEPFAR and other stakeholders, GIs are decreasing; however, they have not been eliminated and remain a challenge for the VMMC program. Preventing further cases of complete and partial amputation will likely require additional interventions that prevent use of the FG method in young patients and the Mogen clamp in infants. Improving management of GIs is critical to optimizing outcomes.

Tuberculosis (TB) is the leading cause of death among persons living with human immunodeficiency virus (HIV) infection. In 2018, an estimated 251,000 persons living with HIV infection died from TB, accounting for one third of all HIV-related deaths and one sixth of all TB deaths (1). TB preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV infection without active TB disease (i.e., adults with a negative clinical symptom screen for cough, fever, night sweats, or weight loss; and children with a negative clinical screen for cough, fever, contact with a person with TB, or poor weight gain) and either without* a tuberculin skin test result or with a known positive result (2). TPT decreases morbidity and mortality among persons living with HIV infection, independent of antiretroviral therapy (ART) (3); however, in 2017, fewer than 1 million of the estimated 21.3 million ART patients started TPT worldwide. Most patients receiving TPT were treated with 6 months of daily isoniazid (1,4). This report summarizes data on TB symptom screening and TPT initiation and completion among ART patients in 16 countries supported by the U.S. President's Emergency Plan for AIDS(dagger) Relief (PEPFAR) during April 1, 2017-March 31, 2019. During this period, these 16 countries accounted for approximately 90% of PEPFAR-supported ART patients. During April 1, 2017-September 30, 2018, TB symptom screening increased from 54% to 84%. Overall, nearly 2 million ART patients initiated TPT, and 60% completed treatment during October 1, 2017-March 31, 2019. Although TPT initiations increased substantially, completion among those who initiated TPT increased only from 55% to 66%. In addition to continuing gains in initiation, improving retention after initiation and identifying barriers to TPT completion are important to increase TPT scale-up and reduce global TB mortality.

BACKGROUND: Tuberculosis preventive treatment (TPT) reduces the development of tuberculosis (TB) disease and mortality in people living with human immunodeficiency virus (HIV) infection. Despite this known effectiveness, global uptake of TPT has been slow. We aimed to assess current status of TPT implementation in countries supported by the US President's Emergency Plan for AIDS Relief (PEPFAR).METHODS: We surveyed TB-HIV program staff at US Centers for Disease Control and Prevention (CDC) country offices in 42 PEPFAR-supported countries about current TPT policies, practices, and barriers to implementation. Surveys completed from July to December 2017 were analyzed.RESULTS: Of 42 eligible PEPFAR-supported countries, staff from 35 (83%) CDC country offices completed the survey. TPT was included in national guidelines in 33 (94%) countries, but only 21 (60%) reported nationwide programmatic TPT implementation. HIV programs led TPT implementation in 20/32 (63%) countries, but TB programs led drug procurement in 18/32 (56%) countries. Stock outs were frequent, as 21/28 (75%) countries reported at least one isoniazid stock out in the previous year.CONCLUSION: Despite widespread inclusion of TPT in guidelines, programmatic TPT implementation lags. Successful scale-up of TPT requires uninterrupted drug supply chains facilitated by improved leadership and coordination between HIV and TB programs.

SETTING: Diagnosing pediatric tuberculosis (TB) is difficult; to improve diagnosis, gastric aspiration (GA) was performed in 121 Botswana health facilities. OBJECTIVE: To describe treatment initiation and outcomes in children with a positive GA result and those treated empirically. METHODS: Children with smear or culture-positive GA or those clinically diagnosed were referred for anti-tuberculosis treatment. Treatment initiation and outcomes were assessed from February 2008 to December 2012 using name-based matching algorithms of the GA database; treatment initiation was captured in the electronic TB registry. Analyses included descriptive statistics and regression models. RESULTS: GA was conducted in 1268 children. Among these, 121 (9.5%) were GA-positive; and treatment was initiated in 90 (74.3%). An additional 137 (11.9%) were treated empirically. More than a third (36.4%) had known human immunodeficiency virus status (positive or negative); this was significantly associated with TB treatment initiation (adjusted odds ratio [aOR] 1.8, 95%CI 1.3-2.5); P < 0.05). Among the 90 children with a positive GA result, nearly all either completed treatment (78.9%) or were on treatment (20.0%) at the time of data collection. CONCLUSION: We could not find documentation of treatment for more than a quarter of the children with laboratory-confirmed TB, an important gap that calls for further examination. The failure to initiate prompt treatment requires investigation and urgent action.

Tuberculosis (TB) is the leading cause of death for persons living with the human immunodeficiency virus (PLHIV). TB preventive therapy (TPT) works synergistically with, and independently of, antiretroviral therapy to reduce TB morbidity, mortality and incidence among PLHIV. However, although TPT is a crucial and costeffective component of HIV care for adults and children and has been recommended as an international standard of care for over a decade, it remains highly underutilized. If we are to end the global TB epidemic, we must address the significant reservoir of tuberculous infection, especially in those, such as PLHIV, who are most likely to progress to TB disease. To do so, we must confront the pervasive perception that barriers to TPT scale-up are insurmountable in resource-limited settings. Here we review available evidence to address several commonly stated obstacles to TPT scale-up, including the need for the tuberculin skin test, limited diagnostic capacity to reliably exclude TB disease, concerns about creating drug resistance, suboptimal patient adherence to therapy, inability to monitor for and prevent adverse events, a 'one size fits all' option for TPT regimen and duration, and uncertainty about TPT use in children, adolescents, and pregnant women. We also discuss TPT delivery in the era of differentiated care for PLHIV, how best to tackle advanced planning for drug procurement and supply chain management, and how to create an enabling environment for TPT scale-up success.

BACKGROUND: While molecular methods have been recently endorsed for diagnosis of tuberculosis (TB), mycobacterial culture remains the gold standard. Lowenstein-Jensen (LJ) is often used for the cultivation of Mycobacterium tuberculosis complex (MTBC); however contamination often renders a subset of cultures useless. We compared the MTBC yield and contamination rate of processed sputum inoculated on LJ with antibiotics (LJ PACT) to LJ without antibiotics (LJ). METHODOLOGY: Sputum samples were obtained from people living with HIV enrolled in a TB screening study in western Kenya, processed using NALC/NaOH-Na citrate, then inoculated on LJ PACT and LJ media. Cultures were evaluated weekly with growth identified as acid-fast bacilli by Ziehl-Neelsen bright-field microscopy. MTBC and nontuberculous mycobacteria (NTM) were identified by immunochromatographic and line probe assays. RESULTS: A total of 700 sputum samples were cultured on both LJ PACT and LJ between March and June 2012. Of those cultured on LJ PACT, 29 (4.1%) grew MTBC, 613 (87.6%) were negative, 12 (1.7%) grew NTM, and 46 (6.6%) were contaminated; on LJ, 28 (4%) grew MTBC, 553 (79%) were negative, 9 (1.3%) grew NTM, and 110 (15.7%) were contaminated. The difference in contamination on LJ PACT and LJ was statistically significant (p<0.0001), while the difference in MTBC growth was not (p=0.566).

In 2012, Uganda introduced the use of GeneXpert MTB/RIF (Cepheid, Sunnyvale CA), a sensitive, automated, real-time polymerase chain reaction-based platform for tuberculosis (TB) diagnosis, for programmatic use among children, adults with presumptive human immunodeficiency virus (HIV)-associated TB, and symptomatic persons at risk for rifampicin (RIF)-resistant TB. The effect of using the platform's Xpert MTB/RIF assay on TB care and control was assessed using routinely collected programmatic data; in addition, a retrospective review of district quarterly summaries using abstracted TB register data from purposively selected facilities in the capital city of Kampala was conducted. Case notification rates were calculated and nonparametric statistical methods were used for analysis. No statistically significant differences were observed in case notification rates before and after the Xpert MTB/RIF assay became available, although four of 10 districts demonstrated a statistically significant difference in bacteriologically confirmed TB. Once the GeneXpert MTB/RIF platform is established and refined, a more comprehensive evaluation should be conducted.

Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.

Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006-2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum. We analyzed 297 case-patients with M. bovis TB and 30,848 case-patients with M. tuberculosis TB. After 2 months of treatment, 71% of M. bovis and 65% of M. tuberculosis TB patients showed conversion of sputum cultures to negative. Likelihood of culture conversion was higher for M. bovis than for M. tuberculosis, even after controlling for treatment administration type, sex, and a composite indicator of bacillary burden.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to successful TB control. The 2010-2011 Bangladesh Drug Resistance Survey (DRS) showed MDR-TB prevalence to be 7% overall, 1.4% in new and 28.5% in previously treated patients. We aimed to determine the rate of MDR-TB in selected sentinel sites in Bangladesh. METHODS: Fourteen hospitals from the seven divisions in Bangladesh were selected as sentinel surveillance sites. Newly registered TB patients were systematically enrolled from August 2011 to December 2014. Sputum specimens were processed for culture and drug susceptibility testing by the proportion method using Lowenstein-Jensen medium. RESULTS: Specimens from 1906 (84%) of 2270 enrolled patients were analysed. Isolates from 61 (3.2%) were identified as having MDR-TB. The proportion of MDR-TB was 2.3% among new and 13.8% among previously treated TB patients (P < 0.001). The overall proportion of MDR-TB was 3.2%:3.5% in males and 2.3% in females; by age, the MDR-TB rate was highest (5.2%) in those aged ≥65 years. CONCLUSIONS: The high proportion of MDR-TB among new patients found in this sentinel surveillance significantly differs from that reported in the DRS. While the sentinel surveillance sites were not designed to be nationally representative, it is worrying to observe a higher number of MDR-TB cases among new patients.

Despite advances in prevention, diagnosis and treatment of tuberculosis and human immunodeficiency virus (HIV), tuberculosis remains the leading cause of death and illness among people living with HIV. In 2015, an estimated 1.2 million of the people who developed tuberculosis disease worldwide were HIV positive, and tuberculosis was the direct cause of at least one third of HIV-related deaths.1 The 2015 “Treat All” strategy requires that everyone with HIV is offered antiretroviral therapy (ART) as soon as they are diagnosed. By treating HIV infections earlier, this strategy should mitigate the HIV-associated tuberculosis epidemic, but it alone is not sufficient to eliminate preventable tuberculosis suffering and deaths among people living with HIV.2 The 2016 World Health Organization (WHO) guidelines recommend differentiated HIV service delivery, which is intended to facilitate the “Treat All” strategy by tailoring services to the differing needs of individuals.3 As HIV programmes adopt these WHO guidelines, tuberculosis also needs to be addressed.3

OBJECTIVE: To assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya. DESIGN: Prospective cohort study. METHODS: PLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and "Improving Diagnosis of TB in HIV-infected persons" (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey. RESULTS: Overall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9-12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1-82.2); MOH, 77.5% (95% CI, 68.6-84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9-81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9-46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3-86.4)] and men [77.2% (95% CI, 68.3-84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4-93.9) and 96.1% (95% CI, 94.4-97.3), respectively, among asymptomatic men and non-pregnant women. CONCLUSIONS: Clinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services.