Syphilis Prevalence Among People Living With and Without HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Syphilis is a curable sexually transmitted infection that, untreated, is associated with significant morbidity and mortality. In people living with HIV (PLWH), syphilis carries greater risks of disease progression. We estimated syphilis prevalence among PLWH in the general population in sub-Saharan Africa and compared the prevalence among PLWH and without HIV. METHODS: We searched for studies published January 1, 2011, to March 28, 2022, reporting syphilis prevalence among PLWH in sub-Saharan Africa (PROSPERO No. CRD42020167328). We excluded studies in high-risk subpopulations. We estimated pooled syphilis prevalence among PLWH using random-effects modeling and compared the prevalence with people without HIV when included in the same study. We examined influences of region, study setting, and test type in subgroup analyses. RESULTS: We identified 926 studies; 53 were included in the meta-analysis. Pooled syphilis prevalence among PLWH was 7.3% (95% confidence interval [CI], 6.3%-8.5%). Prevalence differed by region: 3.1% (95% CI, 2.2%-4.0%) in Southern, 5.5% (95% CI, 2.3%-9.3%) in West/Central, and 10.5% (95% CI, 8.0%-13.1%) in Eastern Africa. Prevalence also differed by study setting: 13.8% (95% CI, 5.7%-23.0%) in sexual and reproductive health/sexually transmitted infection care, 8.7% (95% CI, 5.0%-12.8%) in HIV care, 7.1% (95% CI, 5.8%-8.5%) in antenatal care, and 3.8% (95% CI, 2.0%-5.8%) in household/community-based settings. Syphilis prevalence was higher among PLWH than without HIV (relative risk, 3.5; 95% CI, 2.8-4.5). CONCLUSIONS: Syphilis is highly prevalent among PLWH in sub-Saharan Africa and is more common among PLWH than without HIV. Integration of syphilis screening and management into HIV care may reduce complications of HIV-syphilis coinfection among PLWH in sub-Saharan Africa.

Distinguishing Severe Acute Respiratory Syndrome Coronavirus 2 Persistence and Reinfection: A Retrospective Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. METHODS: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. RESULTS: Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections. CONCLUSIONS: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.

Ocular Monkeypox - United States, July-September 2022.

As of October 11, 2022, a total of 26,577 monkeypox cases had been reported in the United States.* Although most cases of monkeypox are self-limited, lesions that involve anatomically vulnerable sites can cause complications. Ocular monkeypox can occur when Monkeypox virus (MPXV) is introduced into the eye (e.g., from autoinoculation), potentially causing conjunctivitis, blepharitis, keratitis, and loss of vision (1). This report describes five patients who acquired ocular monkeypox during July-September 2022. All patients received treatment with tecovirimat (Tpoxx)†; four also received topical trifluridine (Viroptic).§ Two patients had HIV-associated immunocompromise and experienced delays between clinical presentation with monkeypox and initiation of monkeypox-directed treatment. Four patients were hospitalized, and one experienced marked vision impairment. To decrease the risk for autoinoculation, persons with monkeypox should be advised to practice hand hygiene and to avoid touching their eyes, which includes refraining from using contact lenses (2). Health care providers and public health practitioners should be aware that ocular monkeypox, although rare, is a sight-threatening condition. Patients with signs and symptoms compatible with ocular monkeypox should be considered for urgent ophthalmologic evaluation and initiation of monkeypox-directed treatment. Public health officials should be promptly notified of cases of ocular monkeypox. Increased clinician awareness of ocular monkeypox and of approaches to prevention, diagnosis, and treatment might reduce associated morbidity.

Infectious Diseases/Human Immunodeficiency Virus Physician Ambassadors: Advancing Policy to Improve Health.

Infectious diseases/human immunodeficiency virus (ID/HIV) physicians and other healthcare professionals advocate within the healthcare system to ensure adults and children receive effective treatment. These advocacy skills can be used to inform domestic and global infectious diseases policies to improve healthcare systems and public health. ID/HIV physicians have a unique frontline perspective to share with federal policymakers regarding how programs and policies benefit patients and public health. Providing this input is critical to the enactment of legislation that will maximize the response to infectious diseases. This article discusses the advocacy of ID/HIV physicians and other healthcare professionals in federal health policy. Key issues include funding for ID/HIV programs; the protection of public health and access to healthcare; improving research opportunities; and advancing the field of ID/HIV, including supporting the next generation of ID/HIV clinicians. The article also describes best practices for advocacy and provides case studies illustrating the impact of ID/HIV physician advocacy.

Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Modeling Adherence Interventions Among Youth with HIV in the United States: Clinical and Economic Projections.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.

RESUMEN: La Red de Ensayos Médicos sobre Adolescentes para Realizar Intervenciones sobre el VIH/SIDA está evaluando intervenciones de adherencia (IAs) al tratamiento para mejorar la supresión virológica (SV) entre los jóvenes con VIH (JCV). Usando un modelo de microsimulación, comparamos dos estrategias: cuidado convencional (CC) y una intervención de adherencia hipotética durando 12 meses que aumentaría la SV a nivel de cohorte entre JCV en tratamiento por 10 puntos de porcentuales y que costaría US$ 100/mes/persona. Resultados proyectados incluyeron transmisiones de VIH primarias, muertes y esperanza de vida, costos de por vida asociados con el VIH, y razones incrementales de costo-efectividad (RICEs, $/año de vida ajustado por la calidad [AVAC]). Comparado al CC, la IA reduciría transmisiones de VIH por 15% y muertes por 12% a los 12 meses. La IA mejoraría esperanza de vida descontada/persona por 8 meses a un costo de por vida adicional/persona de US$ 5.300, resultando en una RICE de US$ 7.900/AVAC. La IA sería costo-efectiva a un costo de US$ 2.000/mes/persona o si mejorara SV por al menos un punto porcentual. Intervenciones de adherencia dirigidas a jóvenes con una eficacia incluso modesta podrían mejorar esperanza de vida, prevenir transmisiones de VIH, y ser costo-efectivas.

Clinical Impact and Cost-effectiveness of Genotype Testing at Human Immunodeficiency Virus Diagnosis in the United States.

BACKGROUND: US guidelines recommend genotype testing at human immunodeficiency virus (HIV) diagnosis ("baseline genotype") to detect transmitted drug resistance (TDR) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors. With integrase strand inhibitor (INSTI)-based regimens now recommended as first-line antiretroviral therapy (ART), the of baseline genotypes is uncertain. METHODS: We used the Cost-effectiveness of Preventing AIDS Complications model to examine the clinical impact and cost-effectiveness of baseline genotype compared to no baseline genotype for people starting ART with dolutegravir (DTG) and an NRTI pair. For people with no TDR (83.8%), baseline genotype does not alter regimen selection. Among people with transmitted NRTI resistance (5.8%), baseline genotype guides NRTI selection and informs subsequent ART after adverse events (DTG AEs, 14%). Among people with transmitted NNRTI resistance (7.2%), baseline genotype influences care only for people with DTG AEs switching to NNRTI-based regimens. The 48-week virologic suppression varied (40%-92%) depending on TDR. Costs included $320/genotype and $2500-$3000/month for ART. RESULTS: Compared to no baseline genotype, baseline genotype resulted in <1 additional undiscounted quality-adjusted life-day (QALD), cost an additional $500/person, and was not cost-effective (incremental cost-effectiveness ratio: $420 000/quality-adjusted life-year). In univariate sensitivity analysis, clinical benefits of baseline genotype never exceeded 5 QALDs for all newly diagnosed people with HIV. Baseline genotype was cost-effective at current TDR prevalence only under unlikely conditions, eg, DTG-based regimens achieving ≤50% suppression of transmitted NRTI resistance. CONCLUSIONS: With INSTI-based first-line regimens in the United States, baseline genotype offers minimal clinical benefit and is not cost-effective.

Racial and Ethnic Disparities in Disease Severity on Admission Chest Radiographs among Patients Admitted with Confirmed Coronavirus Disease 2019: A Retrospective Cohort Study.

Background Disease severity on chest radiographs has been associated with higher risk of disease progression and adverse outcomes from coronavirus disease 2019 (COVID-19). Few studies have evaluated COVID-19-related racial and/or ethnic disparities in radiology. Purpose To evaluate whether non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission chest radiographs compared with White or non-Hispanic patients. Materials and Methods This single-institution retrospective cohort study was approved by the institutional review board. Patients hospitalized with confirmed COVID-19 infection between March 17, 2020, and April 10, 2020, were identified by using the electronic medical record (n = 326; mean age, 59 years ±17 [standard deviation]; male-to-female ratio: 188:138). The primary outcome was the severity of lung disease on admission chest radiographs, measured by using the modified Radiographic Assessment of Lung Edema (mRALE) score. The secondary outcome was a composite adverse clinical outcome of intubation, intensive care unit admission, or death. The primary exposure was the racial and/or ethnic category: White or non-Hispanic versus non-White (ie, Hispanic, Black, Asian, or other). Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race and/or ethnicity. Results Non-White patients had significantly higher mRALE scores (median score, 6.1; 95% confidence interval [CI]: 5.4, 6.7) compared with White or non-Hispanic patients (median score, 4.2; 95% CI: 3.6, 4.9) (unadjusted average difference, 1.8; 95% CI: 0.9, 2.8; P < .01). For both White (adjusted hazard ratio, 1.3; 95% CI: 1.2, 1.4; P < .001) and non-White (adjusted hazard ratio, 1.2; 95% CI: 1.1, 1.3; P < .001) patients, increasing mRALE scores were associated with a higher likelihood of experiencing composite adverse outcome with no evidence of interaction (P = .16). Multivariable linear regression analyses demonstrated that non-White patients presented with higher mRALE scores at admission chest radiography compared with White or non-Hispanic patients (adjusted average difference, 1.6; 95% CI: 0.5, 2.7; P < .01). Adjustment for hypothesized mediators revealed that the association between race and/or ethnicity and mRALE scores was mediated by limited English proficiency (P < .01). Conclusion Non-White patients hospitalized with coronavirus disease 2019 infection were more likely to have a higher severity of disease on admission chest radiographs than White or non-Hispanic patients, and increased severity was associated with worse outcomes for all patients. © RSNA, 2020 Online supplemental material is available for this article.

Provider- and patient-level costs associated with providing antiretroviral therapy during the postpartum phase to women living with HIV in South Africa: A cost comparison of three postpartum models of care.

OBJECTIVE: To compare the unit and total costs of three models of ART care for mother-infant pairs during the postpartum phase from provider and patient's perspectives: (i) local standard of care with women in general ART services and infants at well-baby clinics; (ii) women and infants continue to receive care through an integrated maternal and child care approach during the postpartum breastfeeding period; and (iii) referral of women directly to community adherence clubs with their infants receiving care at well-baby clinics. METHODS: Capital and recurrent cost data (relating to buildings, furniture, equipment, personnel, overheads, maintenance, medication, diagnostic tests and immunisations) were collected from a provider's perspective at six sites in Cape Town, South Africa. Patient time, collected via time-and-motion observation and questionnaires, was used to estimate patient perspective costs and is comprised of lost productivity time, time spent travelling and the direct cost of travelling. RESULTS: The cost of postpartum ART visits under models I, II and III was US $13, US $10 and US $7 per visit for a mother-infant pair, respectively, in 2018 US$. The annual costs for the mother-infant pair utilising the average visit frequencies (a mean of 4.5, 6.9 and 6.7 visits postpartum for models I, II and III, respectively) including costs for infant immunisations, visits, medication and diagnostic tests for both mothers and infants were: I - US $222, II - US $335 and III - US $249. Sensitivity analysis to assess the impact of visit frequency on visit cost showed that Model I annual costs would be most costly if visit frequency was equalised. CONCLUSION: This comparative analysis of three models of care provides novel data on unit costs and insight into the costs to provide ART and care to mother-infant pairs during the delicate postpartum phase. These costs may be used to help make decisions around integrated services models and differentiated service delivery for postpartum WLH and their children.

OBJECTIF: Comparer le coût et unitaire et total de trois modèles de soins ART pour les paires mère-enfant pendant la phase post-partum selon les perspectives du fournisseur et du patient: (I) - normes locales des soins avec les femmes dans les services généraux de l'ART et les nourrissons dans les cliniques de bien-être pour bébés; (II) - les femmes et les nourrissons continuent de recevoir des soins via une approche intégrée de soins maternels et infantiles pendant la période d'allaitement post-partum; et (III) - orientation des femmes directement vers les clubs d'adhésion communautaires, leurs nourrissons recevant des soins dans les cliniques de bien-être pour bébés pour bébés. MÉTHODES: Les données sur les coûts d'investissement et les coûts récurrents (relatifs aux bâtiments, au mobilier, à l'équipement, au personnel, aux frais généraux, à l'entretien, aux médicaments, aux tests de diagnostic et aux vaccinations) ont été recueillies selon le point de vue du prestataire sur six sites à Cape Town, en Afrique du Sud. Le temps du patient, recueilli via l'observation du temps et des mouvements et des questionnaires, a été utilisé pour estimer les coûts selon le point de vue du patient, et comprend le temps de productivité perdu, le temps passé en déplacement et le coût direct du déplacement. RÉSULTATS: Le coût des visites ART post-partum dans les modèles I, II et III était respectivement de 13 USD, 10 USD et 7 USD par visite pour une paire mère-enfant en USD de 2018. Les coûts annuels pour la paire mère-enfant en utilisant la fréquence moyenne des visites (une moyenne de 4,5 ; 6,9 et 6,7 visites post-partum pour les modèles I, II et III respectivement), y compris les coûts des vaccinations infantiles, des visites, des médicaments et des tests diagnostiques pour les mères et les nourrissons étaient: I - 222 USD, II - 335 USD et III - 249 USD. L'analyse de sensibilité pour évaluer l'impact de la fréquence des visites sur le coût des visites a montré que les coûts annuels du modèle I seraient les plus élevés si la fréquence des visites était égalisée. CONCLUSIONS: Cette analyse comparative de trois modèles de soins fournit de nouvelles données sur les coûts unitaires et un aperçu des coûts de fourniture de l'ART et de soins aux paires mère-enfant pendant la phase délicate du post-partum. Ces coûts peuvent être utilisés pour aider à la prise des décisions concernant les modèles de services intégrés et la prestation de services différenciés pour les femmes en période de post-partum et leurs enfants.

Risks and Benefits of Dolutegravir- and Efavirenz-Based Strategies for South African Women With HIV of Child-Bearing Potential: A Modeling Study.

Background: Dolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception. Objective: To project clinical outcomes of ART policies for women of child-bearing potential in South Africa. Design: Model of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach). Data Sources: Published data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women). Target Population: 3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children. Time Horizon: 5 years. Perspective: Societal. Intervention: EFV, DTG, and WHO approach. Outcome Measures: Deaths among women and children, sexual and pediatric HIV transmissions, and NTDs. Results of Base-Case Analysis: Compared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths). Results of Sensitivity Analysis: Women's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater. Limitation: Uncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses. Conclusion: Although NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential. Primary Funding Source: National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Massachusetts General Hospital; and Harvard University Center for AIDS Research.

Rapid-Growing Mycobacteria Infections in Medical Tourists: Our Experience and Literature Review.

BACKGROUND: "Medical tourism" has gained popularity over the past few decades. This is particularly common with patients seeking elective cosmetic surgery in the developing world. However, the risk of severe and unusual infectious complications appears to be higher than for patients undergoing similar procedures in the United States. OBJECTIVES: The authors describe their experience with atypical mycobacterial infections in cosmetic surgical patients returning to the United States postoperatively. METHODS: A review of patient medical records presenting with infectious complications after cosmetic surgery between January 2010 and July 2015 was performed. Patients presenting with mycobacterial infections following cosmetic surgery were reviewed in detail. An extensive literature review was performed for rapid-growing mycobacteria (RGM) related to cosmetic procedures. RESULTS: Between January 2010 and July 2015, three patients presented to our institution with culture-proven Mycobacterium abscessus at the sites of recent cosmetic surgery. All had surgery performed in the developing world. The mean age of these patients was 36 years (range, 29-44 years). There was a delay of up to 16 weeks between the initial presentation and correct diagnosis. All patients were treated with surgical drainage and combination antibiotics with complete resolution. CONCLUSIONS: We present series of patients with mycobacterial infections after cosmetic surgery in the developing world. This may be related to the endemic nature of these bacteria and/or inadequate sterilization or sterile technique. Due to low domestic incidence of these infections, diagnosis may be difficult and/or delayed. Consulting physicians should have a low threshold to consider atypical etiologies in such scenarios. LEVEL OF EVIDENCE: 5 Therapeutic.

Separating the rash from the chaff: novel clinical decision support deployed during the mpox outbreak.

A clinical decision support system, EvalMpox, was developed to apply person under investigation (PUI) criteria for patients presenting with rash and to recommend testing for PUIs. Of 668 patients evaluated, an EvalMpox recommendation for testing had a positive predictive value of 35% and a negative predictive value of 99% for a positive mpox test.

Second Time's the Charm? Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting.

Background: For persons with suspected pulmonary tuberculosis, the guidelines of the Centers for Disease Control and Prevention recommend collecting 3 respiratory specimens 8 to 24 hours apart for acid-fast bacilli (AFB) smear and culture, in addition to 1 nucleic acid amplification test (NAAT). However, data supporting this approach are limited. Our objective was to estimate the performance of 1, 2, or 3 AFB smears with or without NAATs to detect pulmonary tuberculosis in a low-prevalence setting. Methods: We conducted a retrospective study of hospitalized persons at 8 Massachusetts acute care facilities who underwent mycobacterial culture on 1 or more respiratory specimens between July 2016 and December 2022. We evaluated percentage positivity and yield on serial AFB smears and NAATs among people with growth of Mycobacterium tuberculosis on mycobacterial cultures. Results: Among 104 participants with culture-confirmed pulmonary tuberculosis, the first AFB smear was positive in 41 cases (39%). A second AFB smear was positive in 11 (22%) of the 49 cases in which it was performed. No third AFB smears were positive following 2 initial negative smears. Of 52 smear-negative cases, 36 had a NAAT performed, leading to 23 additional diagnoses. Overall sensitivity to detect tuberculosis prior to culture positivity was higher in any strategy involving 1 or 2 NAATs (74%-79%), even without AFB smears, as compared with 3 smears alone (60%). Conclusions: Tuberculosis diagnostic testing with 2 AFB smears offered the same yield as 3 AFB smears while potentially reducing laboratory burden and duration of airborne infection isolation. Use of 1 or 2 NAATs increased sensitivity to detect culture-positive pulmonary tuberculosis when added to AFB smear-based diagnostic testing alone.

Prevalence and Risk Factors for School-Associated Transmission of SARS-CoV-2.

Importance: School-associated SARS-CoV-2 transmission is described as uncommon, although the true transmission rate is unknown. Objective: To identify the SARS-CoV-2 secondary attack rate (SAR) in schools and factors associated with transmission. Design, Setting, and Participants: This cohort study examined the risk of school-based transmission of SARS-CoV-2 among kindergarten through grade 12 students and staff in 10 Massachusetts school districts during 2 periods: fall 2020/spring 2021 (F20/S21) and fall 2021 (F21). School staff collected data on SARS-CoV-2 index cases and school-based contacts, and SAR was defined as the proportion of contacts acquiring SARS-CoV-2 infection. Exposure: SARS-CoV-2. Main Outcomes and Measures: Potential factors associated with transmission, including grade level, masking, exposure location, vaccination history, and Social Vulnerability Index (SVI), were analyzed using univariable and multivariable logistic regression models. Results: For F20/S21, 8 school districts (70 schools, >33 000 students) were included and reported 435 index cases (151 staff, 216 students, and 68 missing role) with 1771 school-based contacts (278 staff, 1492 students, and 1 missing role). For F21, 5 districts (34 schools, >18 000 students) participated and reported 309 index cases (37 staff, 207 students, and 65 missing role) with 1673 school-based contacts (107 staff and 1566 students). The F20/S21 SAR was 2.2% (lower bound, 1.6%; upper bound, 26.7%), and the F21 SAR was 2.8% (lower bound, 2.6%; upper bound, 7.4%). In multivariable analysis, during F20/S21, masking was associated with a lower odds of transmission compared with not masking (odds radio [OR], 0.12; 95% CI, 0.04-0.40; P < .001). In F21, classroom exposure vs out-of-classroom exposure was associated with increased odds of transmission (OR, 2.47; 95% CI, 1.07-5.66; P = .02); a fully vaccinated vs unvaccinated contact was associated with a lower odds of transmission (OR, 0.04; 95% CI, 0.00-0.62; P < .001). In both periods, a higher SVI was associated with a greater odds of transmission. Conclusions and Relevance: In this study of Massachusetts schools, the SAR for SARS-CoV-2 among school-based contacts was low during 2 periods, and factors associated with transmission risk varied over time. These findings suggest that ongoing surveillance efforts may be essential to ensure that both targeted resources and mitigation practices remain optimal and relevant for disease prevention.

Cost-effectiveness of broadly neutralizing antibody prophylaxis for HIV-exposed infants in sub-Saharan African settings.

INTRODUCTION: Infant HIV prophylaxis with broadly neutralizing anti-HIV antibodies (bNAbs) could provide long-acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost-effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub-Saharan African settings. METHODS: We conducted a cost-effectiveness analysis using the CEPAC-Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO-designated "high-risk" HIV-exposed infants (HR-HIVE) or to all HIV-exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1-dose), at birth and 3 months (2-doses), or every 3 months throughout breastfeeding (Extended). Base-case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost-effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV-related costs. RESULTS: The model projects that bNAbs would reduce absolute infant HIV incidence by 0.3-2.2% (9.6-34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR-HIVE-1-dose would be cost-saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE-Extended would be cost-effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost-effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost-effective strategy would become HR-HIVE-1-dose in Côte d'Ivoire and Zimbabwe and HR-HIVE-2-doses in South Africa. Findings regarding the cost-effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs. CONCLUSIONS: At current efficacy and cost estimates, bNAb prophylaxis for HIV-exposed children in sub-Saharan African settings would be a cost-effective intervention to reduce vertical HIV transmission.

Cost-effectiveness of broadly neutralizing antibodies for infant HIV prophylaxis in settings with high HIV burdens: a simulation modeling study.

Introduction: Approximately 130 000 infants acquire HIV annually despite global maternal antiretroviral therapy scale-up. We evaluated the potential clinical impact and cost-effectiveness of offering long-acting, anti-HIV broadly neutralizing antibody (bNAb) prophylaxis to infants in three distinct settings. Methods: We simulated infants in Côte d'Ivoire, South Africa, and Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Pediatric (CEPAC-P) model. We modeled strategies offering a three-bNAb combination in addition to WHO-recommended standard-of-care oral prophylaxis to infants: a) with known, WHO-defined high-risk HIV exposure at birth (HR-HIVE); b) with known HIV exposure at birth (HIVE); or c) with or without known HIV exposure (ALL). Modeled infants received 1-dose, 2-doses, or Extended (every 3 months through 18 months) bNAb dosing. Base case model inputs included 70% bNAb efficacy (sensitivity analysis range: 10-100%), 3-month efficacy duration/dosing interval (1-6 months), and $20/dose cost ($5-$100/dose). Outcomes included pediatric HIV infections, life expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, in US$/year-of-life-saved [YLS], assuming a ≤50% GDP per capita cost-effectiveness threshold). Results: The base case model projects that bNAb strategies targeting HIVE and ALL infants would prevent 7-26% and 10-42% additional pediatric HIV infections, respectively, compared to standard-of-care alone, ranging by dosing approach. HIVE-Extended would be cost-effective (cost-saving compared to standard-of-care) in Côte d'Ivoire and Zimbabwe; ALL-Extended would be cost-effective in South Africa (ICER: $882/YLS). BNAb strategies targeting HR-HIVE infants would result in greater lifetime costs and smaller life expectancy gains than HIVE-Extended. Throughout most bNAb efficacies and costs evaluated in sensitivity analyses, targeting HIVE infants would be cost-effective in Côte d'Ivoire and Zimbabwe, and targeting ALL infants would be cost-effective in South Africa. Discussion: Adding long-acting bNAbs to current standard-of-care prophylaxis would be cost-effective, assuming plausible efficacies and costs. The cost-effective target population would vary by setting, largely driven by maternal antenatal HIV prevalence and postpartum incidence.

Curable sexually transmitted infections among women with HIV in sub-Saharan Africa.

OBJECTIVES: Sexually transmitted infections (STIs) cause significant morbidity among women with HIV and increase HIV transmission. We estimated the prevalence of four STIs among women with HIV in sub-Saharan Africa (SSA) and compared prevalence among women with and without HIV. DESIGN: Systematic review and meta-analysis. METHODS: We searched for studies published 1 January 1999 to 19 December 2019 reporting prevalence of gonorrhea, chlamydia, trichomoniasis, or Mycoplasma genitalium among women with HIV in SSA. We excluded studies conducted in high-risk groups (e.g. female sex workers). We extracted data on laboratory-confirmed STIs among women with HIV, and when included, among women without HIV. We estimated pooled prevalence for each STI among women with HIV using inverse variance heterogeneity meta-analysis, compared prevalence to women without HIV, and examined the influences of region, clinical setting, and pregnancy status in subgroup analyses. RESULTS: We identified 3756 unique records; 67 studies were included in the meta-analysis. Prevalence of gonorrhea, chlamydia, trichomoniasis, and M. genitalium was 3.5, 4, 15.6, and 10.2%, respectively. Chlamydia prevalence was lower in Eastern (2.8%) than in Southern (12.5%) and West/Central (19.1%) Africa combined. Prevalence of chlamydia and trichomoniasis was higher among pregnant (8.1%, 17.6%) than nonpregnant (1.7%, 12.3%) women. All STIs were more prevalent among women with than without HIV (relative risks ranging 1.54-1.89). CONCLUSION: STIs are common among women with HIV in SSA, and more common among women with than without HIV. Integrated STI and HIV care could substantially impact STI burden among women with HIV, with potential downstream impacts on HIV transmission.

Development and implementation of a clinical decision support system tool for the evaluation of suspected monkeypox infection.

Monkeypox virus was historically rare outside of West and Central Africa until the current 2022 global outbreak, which has required clinicians to be alert to identify individuals with possible monkeypox, institute isolation, and take appropriate next steps in evaluation and management. Clinical decision support systems (CDSS), which have been shown to improve adherence to clinical guidelines, can support frontline clinicians in applying the most current evaluation and management guidance in the setting of an emerging infectious disease outbreak when those guidelines are evolving over time. Here, we describe the rapid development and implementation of a CDSS tool embedded in the electronic health record to guide frontline clinicians in the diagnostic evaluation of monkeypox infection and triage patients with potential monkeypox infection to individualized infectious disease physician review. We also present data on the initial performance of this tool in a large integrated healthcare system.

Prevalence of undiagnosed HIV among children in South Africa, Côte d'Ivoire and Zimbabwe: a model-based analysis to inform paediatric HIV screening programmes.

INTRODUCTION: To improve the diagnosis and survival of children living with HIV (CLWH), the World Health Organization recommends testing approaches beyond traditional infant HIV testing programmes. Information about undiagnosed HIV prevalence among children of varying ages in the general population is needed to guide innovative national/subnational case-finding and testing approaches. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to estimate the prevalence of undiagnosed HIV in 2-, 5- and 10-year-old children in South Africa, Côte d'Ivoire and Zimbabwe in 2018. We simulated cohorts of children born in 2008 (10-year-olds), 2013 (5-year-olds) and 2016 (2-year-olds). Country-/year-specific inputs for pregnant/breastfeeding women included: HIV prevalence (4.2-32.3%), HIV incidence (0.03-0.24%/month), knowledge of HIV status (27-89%) and antiretroviral drug coverage (36-95%). Paediatric inputs included early infant testing coverage (6-95%) and breastfeeding duration (0-20 months). We projected the proportion of surviving CLWH in whom HIV remained undiagnosed and the undiagnosed HIV prevalence among surviving children of each age in the general population. For children born in 2016, we projected survival and diagnosis of all CLWH through 2026. We conducted sensitivity analyses on model parameters. RESULTS: In 2018, the projected proportion of surviving CLWH whose HIV remained undiagnosed in South Africa/Côte d'Ivoire/Zimbabwe was 44.2%/55.8%/52.9% among 2-year-old CLWH; 29.0%/37.8%/33.2% among 5-year-old CLWH; and 18.3%/25.4%/23.1% among 10-year-old CLWH. Projected general population undiagnosed HIV prevalence in South Africa/Côte d'Ivoire/Zimbabwe was 0.44%/0.32%/0.68% among 2-year-olds; 0.25%/0.17%/0.41% among 5-year-olds; and 0.24%/0.14%/0.38% among 10-year-olds. Among all CLWH born in 2016, 50-54% were projected to die without HIV diagnosis (and subsequently without treatment) within 10 years after birth; 80-85% of these deaths occurred in the first 2 years. CONCLUSIONS: Projected population-level undiagnosed HIV prevalence is low and sharply decreases after age 2, with more CLWH dying than being diagnosed. Despite low undiagnosed prevalence in the general population of older children, we project that a large proportion of CLWH remain undiagnosed, suggesting that innovative strategies targeting untested children of all ages outside of health facility settings should be prioritized. Programmes could consider routine testing of the general population of children below 2 in all settings and children of all ages in high-prevalence settings.