Modeling the impact of universal tuberculosis molecular testing and timing of tuberculosis preventive treatment during antiretroviral therapy initiation in South Africa.

OBJECTIVES: Targeted universal tuberculosis (TB) testing can improve TB detection among people with HIV. This approach is being scaled up in South Africa through Xpert MTB/RIF Ultra testing for individuals starting antiretroviral therapy and annually thereafter. Clarity is needed on how Universal Xpert testing may affect TB preventive treatment (TPT) provision, and on whether TPT should be delayed until TB is ruled out. DESIGN: State-transition microsimulation. METHODS: We simulated a cohort of South African patients being screened for TB while entering HIV care. We compared clinical and cost outcomes between four TB screening algorithms: symptom-based, C-reactive protein-based, and Universal Xpert testing with either simultaneous or delayed TPT initiation. RESULTS: Prompt TB treatment initiation among simulated patients with TB increased from 26% (24-28%) under symptom screening to 53% (50-56%) with Universal Xpert testing. Universal Xpert testing led to increased TPT uptake when TPT initiation was simultaneous, but to approximately 50% lower TPT uptake if TPT was delayed. Universal Xpert with simultaneous TPT prevented incident TB compared to either symptom screening (median 17 cases averted per 5000 patients) or Universal Xpert with delayed TPT (median 23 averted). Universal Xpert with Simultaneous TPT cost approximately $39 per incremental TPT course compared to Universal Xpert with delayed TPT. CONCLUSIONS: Universal Xpert testing can promote timely treatment for newly diagnosed people with HIV who have active TB. Pairing universal testing with immediate TPT will improve the promptness, uptake, and preventive effects of TPT. Simultaneous improvements to TB care cascades are needed to maximize impact.

Global incidence in hospital-associated infections resistant to antibiotics: An analysis of point prevalence surveys from 99 countries.

BACKGROUND: Hospital-associated infections (HAIs) are an important cause of morbidity and mortality around the world. Many HAIs are caused by drug-resistant bacterial pathogens, but there are major gaps in our understanding of the number of hospital-associated drug-resistant infections (HARIs) worldwide. As such, we estimated trends in prevalence of HARIs caused by high priority pathogens (Escherichia coli, Acinetobacter spp., Klebsiella spp., Staphylococcus aureus, Enterobacter spp., and Pseudomonas spp.) in 195 countries. METHODS AND FINDINGS: Resistance prevalence estimates were extracted from 474-point prevalence surveys (PPS) from 99 countries published between 2010 and 2020 coupled with country-level estimates of hospitalization rates and length of stay. Prevalence estimates were transformed in yearly incidence of HARIs per year by country and income group. We estimate the global number of HARIs per year to be 136 million (95% credible interval (CI) 26 to 246 million) per year, with the highest burden in China (52 million, 95% CI 10 to 95 million), Pakistan (10 million, 95% CI 2 to 18 million), and India (9 million, 95% CI 3 to 15 million). Among income groups, middle-income countries bore the highest burden of HARIs per year (119 million, 95% CI 23 to 215 million). Our analysis was constrained by the limited number of PPS for HARIs, lack of community-associated data on antibiotic-resistant infections, and our population level analysis. CONCLUSIONS: In this study, we observe, in the absence of systematic surveillance systems for HARIs, a baseline overview of their rates. Our yearly estimates highlight the global threat of HARIs and may help define strategies to tackle resistance in hospital settings.

SARS-CoV-2 testing strategies for outbreak mitigation in vaccinated populations.

Although COVID-19 vaccines are globally available, waning immunity and emerging vaccine-evasive variants of concern have hindered the international response and transition to a post-pandemic era. Testing to identify and isolate infectious individuals remains the most proactive strategy for containing an ongoing COVID-19 outbreak. We developed a stochastic, compartmentalized model to simulate the impact of using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) assays, rapid antigen tests, and vaccinations on SARS-CoV-2 spread. We compare testing strategies across an example high-income country (the United States) and low- and middle-income country (India). We detail the optimal testing frequency and coverage in the US and India to mitigate an emerging outbreak even in a vaccinated population: overall, maximizing testing frequency is most important, but having high testing coverage remains necessary when there is sustained transmission. A resource-limited vaccination strategy still requires high-frequency testing to minimize subsequent outbreaks and is 16.50% more effective in reducing cases in India than the United States. Tailoring testing strategies to transmission settings can help effectively reduce disease burden more than if a uniform approach were employed without regard to epidemiological variability across locations.

Projected Impact of Expanded Long-Acting Injectable PrEP Use Among Men Who Have Sex With Men on Local HIV Epidemics.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a key component in helping to reduce HIV incidence in the United States. Long-acting injectable (LAI) PrEP is a new alternative to oral PrEP; its potential to affect local HIV epidemics remains unclear. METHODS: The Johns Hopkins HIV Economic Epidemiological model (JHEEM) is a dynamic model of HIV transmission in 32 US urban areas. We used JHEEM to project the HIV incidence among men who have sex with men (MSM) from 2020 to 2030 under a range of interventions aimed at increasing PrEP use. RESULTS: In the absence of any intervention (ie, current levels of oral PrEP and HIV care engagement), we projected a 19% reduction (95% credible interval, CrI 1% to 36%) in HIV incidence among MSM from 2020 to 2030 across all 32 cities. Adding 10% LAI PrEP uptake (above a base case of all oral PrEP) reduced the incidence by 36% (95% CrI 23% to 50%) by year 2030. This effect varied between cities, ranging from 22% in Atlanta to 51% in San Francisco. At 25% additional LAI PrEP uptake, this incidence reduction increased to 54% (95% CrI 45% to 64%). Reductions in incidence after introducing LAI PrEP were driven primarily by increased uptake and sustained usage rather than increased efficacy. CONCLUSIONS: LAI PrEP has the potential to substantially reduce HIV incidence among MSM, particularly if it increases PrEP uptake and continued use beyond existing levels. Because potential effects vary by city, the effectiveness of expanding PrEP use is dependent on local dynamics.

The epidemiology of dengue outbreaks in 2016 and 2017 in Ouagadougou, Burkina Faso.

BACKGROUND: Dengue is prevalent in as many as 128 countries with more than 100 million clinical episodes reported annually and four billion people estimated to be at risk. While dengue fever is systematically diagnosed in large parts of Asia and South America, the disease burden in Africa is less well investigated. This report describes two consecutive dengue outbreaks in Ouagadougou, Burkina Faso in 2016 and 2017. METHODS: Blood samples of febrile patients received at Schiphra laboratory in Ouagadougou, Burkina Faso, were screened for dengue infection using SD Bioline Dengue Duo rapid diagnostic test kits (Standard Diagnostics, Suwon, Republic of Korea). RESULTS: A total of 1,397 and 1,882 cases were reported by a single laboratory in 2016 and 2017, respectively. Most cases were at least 15 years of age and the results corroborated reports from WHO indicating the circulation of three dengue virus serotypes in Burkina Faso. CONCLUSION: This study complements data from other, simultaneously conducted surveillance efforts, and indicates that the dengue disease burden might be underestimated in sub-Saharan African nations. Dengue surveillance should be enhanced in African settings to determine the burden more accurately, and accelerated efforts towards a dengue vaccine should be put in place.

The global burden and epidemiology of invasive non-typhoidal Salmonella infections.

Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas.