Sustained human outbreak of a new MPXV clade I lineage in eastern Democratic Republic of the Congo.

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission.

Subclinical cardiovascular remodelling in HIV-infection: A multimodal case study of 2 serodiscordant, monozygotic twins.

Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a case study of subtle cardiovascular changes in identical twins, one without HIV-infection and the other recently diagnosed with HIV (serodiscordant). We hypothesise that cardiovascular parameters would be similar between the twins, unless non-genetic (environmental) factors are at play. These differences likely represent occult pathology secondary to the effects of early HIV-infection. A 25-year-old female incidentally diagnosed with HIV, and her HIV-uninfected identical twin, living with her since birth, underwent comprehensive cardiovascular assessments. The HIV-positive twin exhibited a globular left ventricle (LV), larger LV volumes, decreased LV strain, peak atrial longitudinal strain (PALS) and higher native T1 and T2 mapping values compared to her sister. Cardiac biomarkers high sensitivity cardiac troponin T and N-terminal proBNP, as well as the novel markers of fibrosis and remodelling, galectin-3 and soluble-ST2, were higher in the HIV-infected twin. Given the twins' shared environment and genetic makeup, these differences likely stem from HIV-infection. Our study supports previous findings and suggests potential screening markers for HIV-associated cardiovascular disease, including PALS. Further research is warranted to explore PALS' utility in this context.

Chiral nematic nanocomposites with pitch gradient elaborated by filtration and ultraviolet curing of cellulose nanocrystal suspensions.

An innovative method combining frontal filtration with ultraviolet (UV) curing has been implemented to design cellulosic nanocomposite films with controlled anisotropic textures from nanometric to micrometric length scales. Namely, an aqueous suspension containing poly (ethylene glycol) diacrylate polymer (PEGDA) as a photocurable polymer and cellulose nanocrystals (CNCs) at a 70/30 mass ratio was processed by frontal filtration, followed by in-situ UV-curing in a dedicated cell. This procedure allowed designing nanocomposite films with highly oriented and densely-packed CNCs, homogeneously distributed in a PEGDA matrix over a thickness of ca. 500 µm. The nanocomposite films were investigated with small-angle X-ray scattering (SAXS), by raster-scanning along their height with a 25 µm vertically-collimated X-ray beam. The CNCs exhibited a high degree of orientation, with their director aligned parallel to the membrane surface, combined with an increase in the degree of alignment as concentration increased towards the membrane surface. Scanning electron microscopy images of fractured films showed the presence of regularly spaced bands lying perpendicular to the applied transmembrane pressure, highlighting the presence of a chiral nematic (cholesteric) organization of the CNCs with a pitch gradient that increased from the membrane surface to the bulk.

Food Sublingual Immunotherapy: Safety and Simplicity of a Real Food Updosing Protocol.

BACKGROUND: Sublingual immunotherapy (SLIT) using food extracts is safe and effective in desensitizing patients with food allergy, yet not often used in clinical practice. OBJECTIVES: To propose a cost-effective, expedited SLIT protocol using real food. METHODS: Patients with food allergy aged 5 to 50 years (median, 11 years) initiated food SLIT in a single-clinic setting. The daily maintenance dose was 4 to 11 mg protein in 0.1 to 0.5 mL volume, depending on the food. Some foods were available in liquid form at the local grocery (milk, egg white liquid, and cashew/walnut/sunflower/hazelnut milk), whereas others were prepared in the office using flour and 50% glycerin saline (peanut/sesame/wheat). The first cohort of 20 patients began dosing at a 1:1000 dilution, the next 30 patients at 1:100 dilution. An exercise challenge was performed in a subset of patients on maintenance dosing to evaluate the need for a predose or postdose rest period. RESULTS: The 1:1000 and 1:100 cohorts both completed day 1 without adverse reactions beyond itchy mouth. There were no systemic reactions requiring epinephrine throughout the study period and 88% reached their maintenance dose. Skin testing of 6-month-old peanut flour solution was not diminished from fresh solution and similar to food extract. Exercise challenge test results in 12 patients were negative. CONCLUSIONS: Allergen extract food SLIT as used in published trials has limitations of cost and multiple office visits. Inexpensive real food, at the same or slightly higher protein dose, was well tolerated in 4 updose visits, a minimum of a week apart. Unlike food oral immunotherapy, a predose or postdose rest period may not be necessary.

Maintenance of beta-blockers and cardiac surgery-related outcomes: a prospective propensity-matched multicentre analysis.

BACKGROUND: We investigated the effects of maintaining beta-blockers on the day of surgery on the incidence of atrial fibrillation and postoperative acute kidney injury (AKI) in patients undergoing cardiac surgery. METHODS: We conducted a multicentre prospective observational study with propensity matching on patients treated with beta-blockers. We collected their baseline patient characteristics, comorbidities, and operative and postoperative outcomes. The endpoints were postoperative atrial fibrillation and AKI after cardiac surgery. RESULTS: Of the 1789 included patients, propensity matching led to 583 patients in each group. Maintenance of beta-blockers was not associated with a reduced risk of atrial fibrillation (odds ratio: 0.86 [95% confidence interval 0.66-1.14], P=0.335; 141 patients [24.2%] vs 126 patients [21.6%]). Sensitivity analysis did not demonstrate association between beta-blocker maintenance and atrial fibrillation after cardiac surgery (odds ratio: 0.93 [95% confidence interval: 0.72-1.22], P=0.625). Maintenance of beta-blockers was associated with a higher rate of norepinephrine use (415 [71.2%] vs 465 [79.8%], P=0.0001) and postoperative AKI (124 [21.3%] vs 159 [27.3%], P=0.0127). No statistically significant difference was observed in ICU length of stay. CONCLUSIONS: Maintenance of beta-blockers on the day of surgery was not associated with a reduced incidence of postoperative atrial fibrillation. However, maintenance of beta-blockers was associated with increased usage of vasopressors, potentially contributing to adverse postoperative renal events. CLINICAL TRIAL REGISTRATION: NCT04769752.

Protection enhancement strategies of potential outbreaks during Hajj.

OBJECTIVE: This study aimed to assist governments and organizers of mass gathering events in reviewing existing preventive measures for disease outbreaks to inform the adoption of enhanced strategies for risk reduction and impacts on public health. DESIGN: A cross-sectional, quantitative, descriptive study. SETTING: This study was conducted in a mass gathering of Hajj, an annual religious event in Mecca, Saudi Arabia. PARTICIPANTS: A convenience sample of 70 personnel working in government ministries of Saudi Arabia (Ministry of Health, Ministry of Hajj, and Ministry of Interior) and the Saudi Red Crescent Authority involved in health management in Hajj, including policy formulation and implementation. MAIN OUTCOME MEASURES: Perception and knowledge of health risks and outbreaks associated with Hajj. RESULTS: The majority of the respondents (60 percent) expressed concern about the potential for infection transmission during Hajj. The respondents also reported having or knowing a colleague, a friend, or a family member with a history of infection during or after Hajj. However, the respondents' knowledge of the possible modes of infection of various diseases was limited. CONCLUSIONS: Hajj is associated with various risks of outbreaks, and thus, better protection-enhancing measures are required. Training personnel involved in health management, including planners, coordinators, and healthcare providers, can help reduce the risks and prevent potential outbreaks.

Successful introgression of wMel Wolbachia into Aedes aegypti populations in Fiji, Vanuatu and Kiribati.

Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of Aedes aegypti mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium Wolbachia pipientis (wMel strain) into Ae. aegypti populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of wMel-infected Ae. aegypti in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of wMel-infected Ae. aegypti mosquitoes for between 2 to 5 months resulted in wMel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of wMel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years.

Reconstructing historic and modern potato late blight outbreaks using text analytics.

In 1843, a hitherto unknown plant pathogen entered the US and spread to potato fields in the northeast. By 1845, the pathogen had reached Ireland leading to devastating famine. Questions arose immediately about the source of the outbreaks and how the disease should be managed. The pathogen, now known as Phytophthora infestans, still continues to threaten food security globally. A wealth of untapped knowledge exists in both archival and modern documents, but is not readily available because the details are hidden in descriptive text. In this work, we (1) used text analytics of unstructured historical reports (1843-1845) to map US late blight outbreaks; (2) characterized theories on the source of the pathogen and remedies for control; and (3) created modern late blight intensity maps using Twitter feeds. The disease spread from 5 to 17 states and provinces in the US and Canada between 1843 and 1845. Crop losses, Andean sources of the pathogen, possible causes and potential treatments were discussed. Modern disease discussion on Twitter included near-global coverage and local disease observations. Topic modeling revealed general disease information, published research, and outbreak locations. The tools described will help researchers explore and map unstructured text to track and visualize pandemics.

Household air pollution and risk of pulmonary tuberculosis in HIV-Infected adults.

BACKGROUND: In low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection. METHODS: We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 - March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB. RESULTS: We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/week were more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm]. CONCLUSION: Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women.

Completion of isoniazid preventive therapy for latent tuberculosis infection among children and adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: Little is known about isoniazid preventive therapy (IPT) completion rates among children or adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: We conducted a retrospective cohort analysis including children, adolescents, and adults living with HIV who were treated at FHI360 and partners-implemented HIV care programs at six health zones in Kinshasa, DRC, from 2004 to 2020. The primary outcome was the proportion of children, adolescents versus adults who did complete 6 months of daily self-administered IPT. Log-binomial regression assessed independent predictors of IPT non-completion and Kaplan-Meier technique for survival analysis. RESULTS: Of 11,691 eligible patients on ART who initiated IPT, 429 were children (<11 years), 804 adolescents (11-19 years), and 10,458 adults (≥20 years). The median age was 7 (IQR: 3-9) years for children, 15 (IQR: 13-17) years for adolescents, and 43 (35-51) years for adults. Among those who were initiated on IPT, 5625 out of 11,691 people living with HIV (PLHIV) had IPT completion outcome results, and an overall 3457/5625 (61.5%) completion rate was documented. Compared to adults, children and adolescents were less likely to complete IPT [104/199 (52.3%) and 268/525 (51.0%), respectively, vs. 3085/4901 (62.9%)]. After adjustment, the only independent predictors for IPT non-completion were health zone of residence and type of ART regimen. Kaplan-Meier analysis showed comparable poor survival among patients who completed IPT versus those who did not (p-value for log-rank test, 0.15). CONCLUSIONS: The overall sub-optimal IPT completion rate in adults as well as children/adolescents in this setting is of great concern. Prospective studies are needed to elucidate the specific barriers to IPT completion among children, adolescents, and adults in DRC as well as the scale-up of evidence-informed interventions to improve IPT completion, such as adoption of shorter TB preventive regimens.

Advanced HIV Disease at Antiretroviral Therapy Initiation and Treatment Outcomes Among Children and Adolescents Compared to Adults Living With HIV in Kinshasa, Democratic Republic of the Congo.

Background: Little is known about advanced HIV disease (AHD) at antiretroviral therapy (ART) initiation among children and adolescents living with HIV (CALHIV) and related age disparities in the Democratic Republic of the Congo (DRC). Methods: We conducted a retrospective cohort analysis of routine program data collected among adults, adolescents, and children living with HIV in 6 health zones in Kinshasa, DRC from 2005 to 2020. Results: Thirty-two percent of those who initiated ART had AHD. Compared to adults, adolescents had a 15% higher risk of AHD (RR: 1.15; 95% CI: 1.08-1.21; P < .001). Despite their higher risk of AHD, adolescents had a lower risk of mortality (aSHR: 0.72; 95% CI: 0.52-0.99; P = .047) and lower cumulative death events versus adults (aSHR: 0.44; 95% CI: 0.34-0.59; P < .001). Conclusions: ADH at ART initiation is highly prevalent in Kinshasa, DRC, and adolescents are disproportionally impacted. There is a need to scale up high-impact HIV interventions targeting CALHIV.

A study to understand advanced HIV disease (AHD) among people living with HIV (PLHIVs) when they start antiretroviral treatment in Kinshasa, Democratic Republic of Congo, including how common it is, how it affects PLHIVs, and how AHD and its consequences differ between children, adolescent, and adult PLHIVs.Why was the study done? Some PLHIVs discover their HIV status later after being infected, and others delay starting treatment once a diagnosis is made. These situations could lead to AHD at the start of antiretroviral treatment. AHD is a severe form of HIV disease, and people who start antiretrovirals with AHD could be at risk of several complications, including death, opportunistic infections, and higher cost of treatment. There is limited evidence about AHD among PLHIV who start antiretrovirals in the DRC and related disparities between children, adolescents, and adults in the country. What did the researchers do? We analyzed data from an HIV program implemented in Kinshasa, DRC, from 2005 to 2020. The analysis examined how common AHD is among PLHIVs, how it affects them, and how AHD and its consequences differ between children, adolescents, and adult PLHIVs. What did the researchers find? The study found that a third of all PLHIVs who started antiretrovirals had AHD. Adolescents were more affected by AHD than adults, and there were no differences between adults and children. Despite their higher risk of AHD than adults, adolescents had lower chances of dying than adults. What do the findings mean? These findings have significant implications for HIV interventions in the DRC. The study highlights the need for more effective HIV interventions targeting PLHIVs, with a focus on early diagnosis and treatment initiation. The results also suggest that interventions tailored explicitly for adolescents may be necessary to address the disproportionate impact of AHD on this population. Overall, the study provides important information on the burden of HIV in the DRC and highlights the need for continued efforts to address this public health challenge.

Updating breakpoints in the United States: a summary from the ASM Clinical Microbiology Open 2022.

Accurate antimicrobial susceptibility testing (AST) and reporting are essential for guiding appropriate therapy for patients and direction for public health prevention and control actions. A critical feature of AST reporting is the interpretation of AST results using clinical breakpoints for reporting as susceptible, susceptible-dose dependent, intermediate, or resistant. Breakpoints are subject to continuous adjustment and updating to best reflect current clinical data. These breakpoint changes can benefit patients and public health only if adopted in a timely manner. A recent survey identified that up to 70% of College of American Pathologists (CAP)-accredited U.S. laboratories and 45% of CAP-accredited laboratories outside the U.S. use various obsolete clinical breakpoints to interpret AST results to guide patient care. The reason for the ongoing use of obsolete breakpoints is multifactorial, including barriers encountered by laboratories, commercial AST device manufacturers, standards development organizations, and regulatory bodies alike. To begin to address this important patient safety issue, CAP implemented checklist requirements for CAP-accredited laboratories to ensure up-to-date clinical breakpoint use. Furthermore, the topic was discussed at the June 2022 American Society for Microbiology Clinical Microbiology Open (CMO) with various stakeholders to identify potential solutions. This minireview summarizes the breakpoint setting process in the U.S. and highlights solutions to close the gap between breakpoint revisions and implementation in clinical and public health laboratories. Solutions discussed include clarification of data requirements and minimum inhibitory concentration only reporting for regulatory clearance of AST devices, clinical data generation to close breakpoints gaps, advocacy, education, and greater dialogue between stakeholders.

Household Air Pollution and Risk of Pulmonary Tuberculosis in HIV-Infected Adults.

Background: In developing countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection. Methods: We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 - March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB. Results: We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/weekwere more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm]. Conclusion: Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women.

Predictors associated with critical care need and in-hospital mortality among children with laboratory-confirmed COVID-19 infection in a high HIV infection burden region.

Introduction: Despite the extra mortality associated with COVID-19 death globally, there is scant data on COVID-19-related paediatric mortality in Sub-Saharan Africa. We assessed predictors of critical care needs and hospital mortality in South African children with laboratory-confirmed SARS-CoV-2 infection in region with high HIV infection burden. Methods: We conducted a secondary multicentre analysis of the AFREhealth cohort (a multinational, multicentre cohort of paediatric COVID-19 clinical outcomes across six African countries) of children admitted to the Inkosi Albert Luthuli, a quaternary hospital in KwaZulu-Natal, South Africa, with confirmed RT-PCR between March 2020 and December 2020. We constructed multivariable logistic regression to explore factors associated with the need for critical care (high care/ intensive care hospitalisation or oxygen requirement) and cox-proportional hazards models to further assess factors independently associated with in-hospital death. Results: Of the 82 children with PCR-confirmed SARS-CoV-2 infection (mean ± SD age: 4.2 ± 4.4 years), 35(42.7%) were younger than one year, 52(63%) were female and 59(71%) had a pre-existing medical condition. Thirty-seven (45.2%) children required critical care (median (IQR) duration: 7.5 (0.5-13.5) days) and 14(17%) died. Independent factors associated with need for critical care were being younger than 1 year (aPR: 3.02, 95%CI: 1.05-8.66; p = 0.04), having more than one comorbidity (aPR: 2.47, 95%CI: 1.32-4.61; p = 0.004), seizure (aPR: 2.39, 95%CI: 1.56-3.68; p < 0.001) and impaired renal function. Additionally, independent predictors of in-hospital mortality were exposure to HIV infection (aHR: 6.8, 95%CI:1.54-31.71; p = 0.01), requiring invasive ventilation (aHR: 3.59, 95%CI: 1.01-12.16, p = 0.048) and increase blood urea nitrogen (aHR: 1.06, 95%CI: 1.01-1.11; p = 0.017). However, children were less likely to die from COVID-19 if they were primarily admitted to quaternary unit (aHR: 0.23, 95%CI: 0.1-0.86, p = 0.029). Conclusion: We found a relatively high hospital death rate among children with confirmed COVID-19. During COVID-19 waves, a timely referral system and rapid identification of children at risk for critical care needs and death, such as those less than one year and those with comorbidities, could minimize excess mortality, particularly in high HIV-infection burden countries.

The Human Mpox Global Outbreak: Available Control Tools and the Opportunity to Break a Cycle of Neglect in Endemic Countries.

The 2022 global outbreak of human Mpox (formerly monkeypox) virus (MPXV) infection outside of the usual endemic zones in Africa challenged our understanding of the virus's natural history, transmission dynamics, and risk factors. This outbreak has highlighted the need for diagnostics, vaccines, therapeutics, and implementation research, all of which require more substantial investments in equitable collaborative partnerships. Global multidisciplinary networks need to tackle MPXV and other neglected emerging and reemerging zoonotic pathogens to address them locally and prevent or quickly control their worldwide spread. Political endorsement from individual countries and financial commitments to maintain control efforts will be essential for long-term sustainability.

Global HIV control: is the glass half empty or half full?

The massive scale-up of HIV treatment and prevention over the past two decades has resulted in important reductions in new infections and mortality globally. Reduction in HIV incidence, however, has been unequal, with worsening epidemics in regions where the reach and scale of HIV control programmes have been insufficient, especially in eastern Europe, central Asia, the Middle East, north Africa, and Latin America where HIV epidemics are concentrated among key populations, including people who inject drugs, men who have sex with men, transgender people, and some minority racial and ethnic groups. The global state of the HIV pandemic highlights disparities in HIV control efforts and provides a roadmap for what should be done, including investment to better implement the effective HIV prevention and treatment tools that are available, but whose adoption and scale-up are not yet sufficient to get us close to an AIDS-free generation. To achieve the full potential of global HIV control, we call for urgent, evidence-informed implementation at scale of our existing and novel HIV prevention and treatment strategies in ways that are better, faster, more efficient, and cost-effective, especially in key populations and regions where the HIV pandemic continues to expand.