The 2024 Public Health Emergency of International Concern: A Global Failure to Control Mpox.

On August 14, 2024, following a regional declaration by the Africa Centres for Disease Control and Prevention, the World Health Organization declared mpox a Public Health Emergency of International Concern, marking the second such declaration in two years. A series of outbreaks involving the more virulent clade I virus (compared to clade II, which caused a global outbreak in 2022), has now spread in 13 African countries, exposing the inadequacies of the public health infrastructure in these settings. There was significant investment during the 2022 global outbreak, but these efforts failed to address vaccine access and treatment in the Global South. Regulatory delays, unequal access to vaccines, and a lack of compassionate use treatments for severe cases have resulted in preventable cases and deaths, especially among vulnerable populations such as pregnant women, children, and the immunocompromised. The current outbreak also underscores critical knowledge gaps in our understanding of mpox, including its transmission, pathogenesis, and viral evolution. We join intensified calls for global solidarity and action to control mpox, emphasizing immediate containment measures and long-term local and international investment in African public health systems, to prevent future epidemics.

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.

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.

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.

Increasing Effectiveness and Equity in Strengthening Health Research Capacity Using Data and Metrics: Recent Advances of the ESSENCE Mechanism.

Background: The ESSENCE on Health Research initiative established a Working Group on Review of Investments in 2018 to improve coordination and collaboration among funders of health research capacity strengthening. The Working Group comprises more than a dozen ESSENCE members, including diverse representation by geography, country income level, the public sector, and philanthropy. Objective: The overall goal of the Working Group is increased research on national health priorities as well as improved pandemic preparedness, and, ultimately, fewer countries with very limited research capacity. Methods: We developed a basic set of metrics for national health research capacity, assessed different models of coordination and collaboration, took a deeper dive into eight countries to characterize their national research capacity, and began to identify opportunities to better coordinate our investments. In this article, we summarize the presentations, discussions, and outcomes of our second annual (virtual) meeting, which had more than 100 participants representing funders, researchers, and other stakeholders from higher- and lower-income countries worldwide. Findings and conclusions: Presentations on the first day included the keynote speaker, Dr. Soumya Swaminathan, chief scientist of the World Health Organization (WHO), and updates on data and metrics for research capacity, which are critical to establish targets, road maps, and budgets. The second day focused on improving collaboration and coordination among funders and other stakeholders, the potential return on investment for health research, ongoing work to increase coordination at the country level, and examples of research capacity strengthening efforts in diverse health research areas from around the world. We concluded that an intentional data- and metric-driven approach to health research capacity strengthening, emphasizing coordination among funders, local leadership, and equitable partnerships and allocation of resources, will enhance the health systems of resource-poor countries as well as the world's pandemic preparedness.

Long-acting antiretrovirals and HIV treatment adherence.

Intramuscular injection of long-acting cabotegravir and rilpivirine is a novel, long-acting antiretroviral therapy (ART) combination approved for use as a fully suppressive regimen for people living with HIV. Long-acting cabotegravir with rilpivirine ART has reduced required dosing frequency from once daily to once every month or every 2 months injections. This new era of long-acting ART, which includes other antiretrovirals and formulations in various stages of clinical development, holds tremendous promise to change the standard of HIV treatment. Although long-acting ART has high potential to be revolutionary in the landscape of HIV care, prevention, and treatment cascade, more data are needed to substantiate its efficacy and cost-effectiveness among patients at risk of non-adherence and across age groups, pregnancy, and post partum. Advocacy efforts and policy changes to optimise a sustained, high-quality, equitable reach of long-acting ART, especially in low-income and middle-income countries where most people living with HIV reside, are needed to realise the full benefits of long-acting ART.

The effect of group support psychotherapy on adherence to anti-retroviral therapy and viral suppression among HIV positive young people: Study protocol for a pilot randomized controlled trial.

Background: Several studies have demonstrated an association between psychological risk factors and HIV disease progression. However, there is limited information on the use of psychological interventions to improve HIV treatment outcomes in young people living with HIV. Objective: This pilot trial aims to evaluate the feasibility, acceptability and preliminary effectiveness of group support psychotherapy in improving adherence to anti-retroviral therapy and viral suppression in young people living with HIV in Uganda. Methods: We recruited 120 young people with HIV, aged 10-18 years, who had non-viral suppression 6 months after initiating first-line anti-retroviral therapy (ART) from community based HIV clinics in Kitgum district, northern Uganda. Participants were randomly assigned to receive GSP plus IAC (N = 60) or IAC alone (N = 60). Primary outcomes will be indicators of feasibility and acceptability as well as preliminary effectiveness of GSP in improving ART adherence and viral suppression analysed by intention to treat using cluster-adjusted t tests and permutation tests. Secondary outcomes will be measures of depression, anxiety and cost-effectiveness. Results: The trial has been approved by the Makerere College of Health Sciences School of Health Sciences Research Ethics Committee, and the Uganda National Council of Science and Technology. Recruitment began in June 2021 and 120 young people living with HIV with their adult caregivers have been recruited to the trial. An analysis of baseline and 6-month data is in progress. The results of this trial will not only be presented at national and international conferences but also submitted for publication in peer-reviewed journals and as a report to the funding agencies. Conclusions: This pilot trial will provide critical evidence to support the ongoing mental health integration into routine HIV care in Uganda. Trial Registration: Pan African Clinical Trials Registry (PACTR): 202006601935462.