Comparison of Overall Sensitivity and Specificity across Different Newborn Screening Algorithms for Congenital Cytomegalovirus.

Screening newborns for congenital cytomegalovirus (cCMV) infection is critical for early detection and prompt diagnosis of related long-term consequences of infection, such as sensorineural hearing loss and neurodevelopmental delays. The objective of this study was to describe the validity of different newborn cCMV infection screening approaches and compare the expected number of cCMV cases detected across targeted and universal screening algorithms. The overall sensitivity (OSn) of targeted screening algorithms that required failure of auditory brain stem response and transient evoked otoacoustic emissions (TOAE; two-fail serial testing) or TOAE only (one-fail serial testing) before diagnostic CMV testing using saliva and urine PCR tests was 79% and 88%, respectively. The OSn for two-fail serial testing with diagnostic CMV testing using dried blood spot (DBS) was 75%. In contrast, OSn was 90% for universal screening (saliva and urine PCR tests) and 86% for universal screening with DBS testing alone. Overall, specificities were 100% across all algorithms. Universal screening using DBS testing and universal screening using saliva and urine testing can potentially detect 312 and 373 more cCMV cases per 100,000 live births, respectively, than two-fail serial testing. Overall, implementing universal cCMV newborn screening would improve cCMV detection, ultimately leading to better health outcomes.

Implementation of a standardised and quality-assured enhanced gonococcal antimicrobial surveillance programme in accordance with WHO protocols in Kampala, Uganda.

OBJECTIVES: The emergence of multidrug-resistant Neisseria gonorrhoeae (NG) is a major global health threat necessitating response and control measures. NG antimicrobial resistance (AMR) surveillance data from sub-Saharan countries is exceedingly limited. This paper aims to describe the establishment, design and implementation of a standardised and quality-assured gonococcal surveillance programme and to describe the susceptibility patterns of the cultured gonococcal isolates in Kampala, Uganda. METHODS: From March 2018 to September 2019, using the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) protocol, consecutive males with urethral discharge syndrome were recruited from 10 surveillance sites in Kampala City, Uganda, in collaboration with the Ministry of Health. Males completed a questionnaire and provided a urethral swab specimen. Culture, identification and antimicrobial susceptibility testing (Etest) were performed. RESULTS: Of the 1013 males recruited, 73.1% (740/1013) had a positive Gram stain and 51.1% (n=518) were culture-positive for NG. Using Etest (458 isolates), the resistance to ciprofloxacin was 99.6%. Most isolates were susceptible to azithromycin, cefoxitin and gentamicin, that is, 99.8%, 98.5% and 92.4%, respectively, and all isolates were susceptible to ceftriaxone and cefixime. CONCLUSIONS: We established a standardised, quality-assured WHO EGASP. Using Etest, 458 isolates were characterised, with associated epidemiological surveillance data, in 1.5 years, which by far exceed the minimum 100 isolates per year and country requested in the WHO Global GASP, to detect AMR levels with confidence. These isolates with the epidemiological data can be used to develop population level interventions.

Antimicrobial Resistance of Neisseria Gonorrhoeae in a Newly Implemented Surveillance Program in Uganda: Surveillance Report.

BACKGROUND: Neisseria gonorrhoeae (commonly known as gonorrhea) has developed resistance to all first-line therapy in Southeast Asia. East Africa has historically had absent or rudimentary gonorrhea surveillance programs and, while the existence of antimicrobial-resistant gonorrhea is recognized, the extent of its resistance is largely unknown. In 2016, the World Health Organization's Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) was initiated in Uganda to monitor resistance trends. OBJECTIVE: This study characterizes gonorrhea and antibiotic resistance in a large surveillance program of men with urethral discharge syndrome from Kampala, Uganda. METHODS: Men attending sentinel clinics with urethritis provided demographic information, behavior data, and a urethral swab in line with the World Health Organization's EGASP protocols for culture, identification, and antibiotic-sensitivity testing using 2 methods-disk diffusion (Kirby-Bauer test) and Etest (BioMérieux Inc). A subset of samples underwent detailed antimicrobial resistance testing. RESULTS: Of 639 samples collected from September 2016 to February 2018, 400 (62.6%) were culture-positive though 414 (64.8%) had microscopic evidence of gonorrhea. The mean age of the men from whom the samples were collected was 26.9 (SD 9.6) years and 7.2% (46/639) reported having HIV. There was high-level resistance to ciprofloxacin, tetracycline, and penicillin (greater than 90%) by Kirby-Bauer disk diffusion and 2.1% (4/188) had reduced azithromycin sensitivity by Etest. Of the early isolates that underwent detailed characterization, 60.3% (70/116) were culture-positive, 94% (66/69) isolates were either ciprofloxacin-resistant or ciprofloxacin-intermediate by Etest, 96% (65/68) were azithromycin-sensitive, and 96% (66/69) were gentamicin-sensitive. Resistance profiles were comparable between methods except for ceftriaxone (disk diffusion: 68/69, 99%; Etest: 67/69, 97%) and for gentamicin (disk diffusion: 2/8, 25%; Etest: 66/69, 96%) sensitivity. CONCLUSIONS: This is the first report from a systematic gonorrhea surveillance program in Uganda. Findings demonstrated resistance or increased minimum inhibitory concentration to all key antigonococcal antibiotics. There was evidence of poor antibiotic stewardship, near-universal resistance to several antibiotics, and emerging resistance to others. Individuals in the population sampled were at exceptionally high risk of STI and HIV infection requiring intervention. Ongoing surveillance efforts to develop interventions to curtail antimicrobial-resistant gonorrhea are needed.

Evaluation of the Direct MacConkey Method for Identification of Carbapenem-Resistant Gram-Negative Organisms from Rectal Swabs: Reevaluating Zone Diameter Cutoffs.

The optimal method to screen for gastrointestinal colonization with carbapenem-resistant organisms (CRO) has yet to be established. The direct MacConkey (direct MAC) plate method demonstrates high sensitivity for CRO detection, but established zone diameter (ZD) criteria for ertapenem (≤27 mm) and meropenem (≤32 mm) result in high rates of false positives upon confirmatory testing. To increase specificity, we screened for CRO in two high-risk wards using the direct MAC plate method, recorded ZDs for each sample, and generated receiver operating characteristic (ROC) curves to evaluate the optimal ZD cutoff criteria. Of 6,868 swabs obtained over an 18-month period, 4,766 (69%) had growth on MAC plates, and 2,500 (36%) met criteria for further evaluation based on previously established ZDs around the carbapenem disks. A total of 812 (12%) swabs were confirmed positive for at least one CRO and included 213 (3%) carbapenemase-producing organisms (CPO), resulting in a specificity of 78% for the direct MAC plate method. Reducing the ertapenem and meropenem ZDs to ≤25 mm improved specificity to 83%, decreasing the confirmatory testing workload by 32%. The sensitivities with the lower ZD criteria were 89% for CRO and 94% for CPO, respectively. The direct MAC plate method criteria for CRO testing can be modified to balance the sensitivity and specificity of CRO while reducing the burden on clinical microbiology laboratories. These modifications can be particularly helpful in regions with a low CRO prevalence.

A Cross-Cutting Approach to Surveillance and Laboratory Capacity as a Platform to Improve Health Security in Uganda.

Global health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda.

Antimicrobial Resistance of Sterile Site Infections in Sub-Saharan Africa: A Systematic Review.

Sparse data exist from sub-Saharan Africa (SSA) on the prevalence of antimicrobial resistance (AMR). A prior review of antimicrobial resistance in SSA from 1990 to 2013 showed a high prevalence of AMR to commonly used antibiotics in this setting. We reviewed the literature published since 2013. Four databases (PubMed, EMBASE, Cochrane, and African Journals Online) were searched for articles between February 2013 and March 2016 with a focus on sterile site infections (bacteremia, urinary tract infections [UTIs], and meningitis). We focused on the original World Health Organization-identified priority pathogens and antibiotics, prior to the release of the most recently updated and expanded list in 2017. There were 19 eligible studies: bacteremia (12), UTI (6), and meningitis (1). Eight studies were from Western and Central Africa, 8 from Eastern Africa, and 4 from Southern Africa. Prevalence of Escherichia coli resistance to third-generation cephalosporins ranged from 0% to 75%. No studies reported resistance to carbapenems among Klebsiella spp. Prevalence of fluoroquinolone resistance ranged from 8.3% to 100% among E. coli and 0% to 15% among Salmonella spp. Prevalence of resistance to penicillin among Streptococcus pneumoniae isolates ranged from 25% to 100%. Testing for extended-spectrum beta-lactamase was reported in 7 studies (range, 1.3-60% among tested isolates). Methods for evaluating AMR varied across studies; standardized approaches are needed in the region. Testing for mechanisms of resistance is low even in research settings, but important mechanisms of resistance such as ESBL production are present.

Bypass graft infection and bacteremia caused by Anaerostipes caccae: First report of human infection caused by a recently described gut anaerobe.

We report a case of bypass graft infection and bacteremia caused by Anaerostipes caccae. A review of the literature shows no reported human infection caused by this microorganism to date. The patient was initially treated with vancomycin and piperacillin-tazobactam on admission and with amoxicillin-clavulanate upon discharge. The slow-growing organism was subsequently found to be susceptible to metronidazole and ertapenem.

Achieving pregnancy safely: perspectives on timed vaginal insemination among HIV-serodiscordant couples and health-care providers in Kisumu, Kenya.

In female-positive HIV-serodiscordant couples desiring children, home timed vaginal insemination (TVI) of semen during the fertile period along with consistent condom use may reduce the risk of HIV transmission when the man is HIV-uninfected. In sub-Saharan Africa, up to 45% of HIV-infected women desire to have more children. HIV viral load assessment is not routinely available in low-resource countries for monitoring adherence and response to antiretroviral therapy. Therefore, in these settings, timed unprotected intercourse without assurance of HIV viral suppression may pose unnecessary risks. TVI, a simple and affordable intervention, can be considered an adjunct method and option of safer conception for HIV prevention with treatment of the HIV-infected partner and/or pre-exposure prophylaxis. We conducted five mixed and single-sex focus group discussions comprised of 33 HIV-serodiscordant couples and health-care providers in the Nyanza region of Kenya to assess the acceptability and feasibility of TVI as a safer method of conception. The transcribed data were analyzed using a grounded theory approach. We found that educating and counseling HIV-serodiscordant couples on TVI could make it an acceptable and feasible safer conception method when associated with frequent communication and home visits by health-care providers. The findings of this study indicate that implementation studies that integrate training and counseling of HIV-serodiscordant couples and health-care providers on TVI combined with consistent condom use are needed. Acknowledging and supporting the reproductive choice and needs of female positive, male negative HIV-serodiscordant couples who desire children should also include the use of assisted reproductive services at the same time as pharmaceutical options that prevent sexual HIV transmission.

Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-Cancer Registry Match Study.

Although more than 25 million people in sub-Saharan Africa have human immunodeficiency virus (HIV) infection, little is known regarding their cancer risk. We investigated cancer risk among persons with HIV/AIDS in Uganda using record-linkage. We linked records of 12,607 HIV-infected persons attending The AIDS Support Organization (TASO) in Kyadondo County from October 1988 through December 2002 to the Kampala Cancer Registry. We calculated standardized incidence ratios (SIRs) to identify increased cancer risks in the early (4-27 months after TASO registration), late (28-60 months), or combined (4-60 months) incidence periods. We identified 378 cancers (181 prevalent, 197 incident) among TASO participants. Of incident cancers, 137 (70%) were AIDS-defining cancers. Risk was increased in the early-incident period, compared to the general population, for the AIDS-defining cancers: Kaposi sarcoma (SIR 6.4, 95%CI 4.8-8.4), non-Hodgkin lymphoma (6.7, 1.8-17), and cervical carcinoma (2.4, 1.1-4.4). These three cancers were also increased in the combined periods. Risks of five non-AIDS-defining cancers were increased in the combined periods: Hodgkin lymphoma (5.7, 1.2-17) and cancers of the conjunctiva (SIR 4.0; 1.5-8.7), kidney (16, 1.8-58), thyroid (5.7, 1.1-16), and uterus (5.5, 1.5-14). Cancers of the breast, nasopharynx, and lung were increased either in the early or late incident periods only. Among 407 children, seven cancers were observed, of which five were Kaposi sarcoma. The application of a record-linkage design in Africa broadens the repertoire of epidemiological tools for studying HIV-infected populations. We confirm the increased risks of AIDS-defining cancers and report increased risks of a few non-AIDS-defining cancers.