Avian 'Bird' Flu - undue media panic or genuine concern for pandemic potential requiring global preparedness action?

epidemics, avian influenza, H5N1, highly pathogenic avian influenza, HPAI.

Screening for latent tuberculosis in migrants-status quo and future challenges.

OBJECTIVES: To review the evidence that migrants from tuberculosis (TB) high-incidence countries migrating to TB low-incidence countries significantly contribute to active TB cases in the counties of destination, primarily through reactivation of latent TB. METHODS: This is a narrative review. The different screening programs in the countries of destination are reviewed either based on screening and preventive treatment of latent TB pre or more commonly - post arrival. RESULTS: Screening can be performed using interferon-gamma release assays (IGRA) or tuberculin skin tests (TST). Preventive treatment of latent TB is using either monotherapy with isoniazid, or in combination with rifampicin or rifapentine. We discuss the ethical issues of preventive treatment in asymptomatic individuals and how these are addressed in different screening programs. CONCLUSION: Screening migrants from TB high endemic countries to TB low endemic countries is beneficial. There is a lack of standardization and agreement on screening protocols, follow up and treatment.

Acetic Acid Enables Molecular Enumeration of Mycobacterium tuberculosis from Sputum and Eliminates the Need for a Biosafety Level 3 Laboratory.

BACKGROUND: Improved monitoring of Mycobacterium tuberculosis response to treatment is urgently required. We previously developed the molecular bacterial load assay (MBLA), but it is challenging to integrate into the clinical diagnostic laboratory due to a labor-intensive protocol required at biosafety level 3 (BSL-3). A modified assay was needed. METHODS: The rapid enumeration and diagnostic for tuberculosis (READ-TB) assay was developed. Acetic acid was tested and compared to 4 M guanidine thiocyanate to be simultaneously bactericidal and preserve mycobacterial RNA. The extraction was based on silica column technology and incorporated low-cost reagents: 3 M sodium acetate and ethanol for the RNA extraction to replace phenol-chloroform. READ-TB was fully validated and compared directly to the MBLA using sputa collected from individuals with tuberculosis. RESULTS: Acetic acid was bactericidal to M. tuberculosis with no significant loss in 16S rRNA or an unprotected mRNA fragment when sputum was stored in acetic acid at 25°C for 2 weeks or -20°C for 1 year. This novel use of acetic acid allows processing of sputum for READ-TB at biosafety level 2 (BSL-2) on sample receipt. READ-TB is semiautomated and rapid. READ-TB correlated with the MBLA when 85 human sputum samples were directly compared (R2 = 0.74). CONCLUSIONS: READ-TB is an improved version of the MBLA and is available to be adopted by clinical microbiology laboratories as a tool for tuberculosis treatment monitoring. READ-TB will have a particular impact in low- and middle-income countries (LMICs) for laboratories with no BSL-3 laboratory and for clinical trials testing new combinations of anti-tuberculosis drugs.

Variability in plasma rifampicin concentrations and role of SLCO1B1, ABCB1, AADAC2 and CES2 genotypes in Ethiopian patients with tuberculosis.

BACKGROUND: Rifampicin, a key drug against tuberculosis (TB), displays wide between-patient pharmacokinetics variability and concentration-dependent antimicrobial effect. We investigated variability in plasma rifampicin concentrations and the role of SLCO1B1, ABCB1, arylacetamide deacetylase (AADAC) and carboxylesterase 2 (CES-2) genotypes in Ethiopian patients with TB. METHODS: We enrolled adult patients with newly diagnosed TB (n = 119) who had received 2 weeks of rifampicin-based anti-TB therapy. Venous blood samples were obtained at three time points post-dose. Genotypes for SLCO1B1 (c.388A > G, c.521T > C), ABCB1 (c.3435C > T, c.4036A > G), AADACc.841G > A and CES-2 (c.269-965A > G) were determined. Rifampicin plasma concentration was quantified using LC-MS/MS. Predictors of rifampicin Cmax and AUC0-7 h were analysed. RESULTS: The median rifampicin Cmax and AUC0-7 were 6.76 µg/mL (IQR 5.37-8.48) and 17.05 µg·h/mL (IQR 13.87-22.26), respectively. Only 30.3% of patients achieved the therapeutic efficacy threshold (Cmax>8 µg/mL). The allele frequency for SLCO1B1*1B (c.388A > G), SLCO1B1*5 (c.521T > C), ABCB1 c.3435C > T, ABCB1c.4036A > G, AADAC c.841G > A and CES-2 c.269-965A > G were 2.2%, 20.2%, 24.4%, 14.6%, 86.1% and 30.6%, respectively. Sex, rifampicin dose and ABCB1c.4036A > G, genotypes were significant predictors of rifampicin Cmax and AUC0-7. AADACc.841G > A genotypes were significant predictors of rifampicin Cmax. There was no significant influence of SLCO1B1 (c.388A > G, c.521T > C), ABCB1c.3435C > T and CES-2 c.269-965A > G on rifampicin plasma exposure variability. CONCLUSIONS: Subtherapeutic rifampicin plasma concentrations occurred in two-thirds of Ethiopian TB patients. Rifampicin exposure varied with sex, dose and genotypes. AADACc.841G/G and ABCB1c.4036A/A genotypes and male patients are at higher risk of lower rifampicin plasma exposure. The impact on TB treatment outcomes and whether high-dose rifampicin is required to improve therapeutic efficacy requires further investigation.

Perspectives on development and advancement of new tuberculosis vaccines.

Tuberculosis (TB) remains a leading cause of death worldwide and is estimated to have caused 1.3 million deaths worldwide in 2022. Approximately one quarter of the world's population are infected with Mycobacterium tuberculosis, of whom up to 10% will progress to developing active TB disease. Achieving the World Health Organization End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence worldwide by 2035 remains a daunting task. The continuing spread of multidrug-resistant TB adds another obstacle to achieving global TB control. Larger funding pledges coupled with technological advances have recently enabled the enhancement of TB vaccine development efforts. These are yielding a pipeline of over 17 products currently in different stages of clinical trials. Emerging promising phase I and II trial results and advancement to phase III trials have necessitated "vaccine preparedness" in parallel so that a smooth transition from any positive clinical trial result to phase IV evaluation and implementation into policy and practice can follow. Promotion of a human rights-based approach, which recognizes and upholds the fundamental rights of all affected by the disease, is essential to ensure universal access to quality TB vaccines, regardless of their background or personal circumstances.

The Tokyo 2020 and Beijing 2022 Olympic Games held during the COVID-19 pandemic: planning, outcomes, and lessons learnt.

The COVID-19 pandemic profoundly affected all mass gatherings for sporting and religious events, causing cancellation, postponement, or downsizing. On March 24, 2020, the Japanese Government, the Tokyo Organising Committee of the Olympic and Paralympic Games, and the International Olympic Committee decided to postpone the Tokyo 2020 Olympic and Paralympic Games until the summer of 2021. With the emergence of SARS-CoV-2, the potential creation of a superspreading event that would overwhelm the Tokyo health system was perceived as a risk. Even with a delayed start date, an extensive scale of resources, planning, risk assessment, communication, and SARS-CoV-2 testing were required for the Games to be held during the COVID-19 pandemic. The effectiveness of various mitigation and control measures, including the availability of vaccines and the expansion of effective testing options, allowed event organisers and the Japanese Government to successfully host the rescheduled 2020 Tokyo Olympic Games from July 23 to Aug 8, 2021 with robust safety plans in place. In February and March, 2022, Beijing hosted the 2022 Winter Olympic Games as scheduled, built on the lessons learnt from the Tokyo Games, and developed specific COVID-19 countermeasure plans in the context of China's national framework for the plan called Zero COVID. Results from the testing programmes at both the Tokyo and Beijing Games show that the measures put in place were effective at preventing the spread of COVID-19 within the Games, and ensured that neither event became a COVID-19-spreading event. The extensive experience from the Tokyo and Beijing Olympic Games highlights that it is possible to organise mass gatherings during a pandemic, provided that appropriate risk assessment, risk mitigation, and risk communication arrangements are in place, leaving legacies for future mass gatherings, public health, epidemic preparedness, and wider pandemic response.

Two decades of endemic dengue in Bangladesh (2000-2022): trends, seasonality, and impact of temperature and rainfall patterns on transmission dynamics.

The objectives of this study were to compare dengue virus (DENV) cases, deaths, case-fatality ratio [CFR], and meteorological parameters between the first and the recent decades of this century (2000-2010 vs. 2011-2022) and to describe the trends, seasonality, and impact of change of temperature and rainfall patterns on transmission dynamics of dengue in Bangladesh. For the period 2000-2022, dengue cases and death data from Bangladesh's Ministry of Health and Family Welfare's website, and meteorological data from the Bangladesh Meteorological Department were analyzed. A Poisson regression model was performed to identify the impact of meteorological parameters on the monthly dengue cases. A forecast of dengue cases was performed using an autoregressive integrated moving average model. Over the past 23 yr, a total of 244,246 dengue cases were reported including 849 deaths (CFR = 0.35%). The mean annual number of dengue cases increased 8 times during the second decade, with 2,216 cases during 2000-2010 vs. 18,321 cases during 2011-2022. The mean annual number of deaths doubled (21 vs. 46), but the overall CFR has decreased by one-third (0.69% vs. 0.23%). Concurrently, the annual mean temperature increased by 0.49 °C, and rainfall decreased by 314 mm with altered precipitation seasonality. Monthly mean temperature (Incidence risk ratio [IRR]: 1.26), first-lagged rainfall (IRR: 1.08), and second-lagged rainfall (IRR: 1.17) were significantly associated with monthly dengue cases. The increased local temperature and changes in rainfall seasonality might have contributed to the increased dengue cases in Bangladesh.

Genetic diversity and molecular analysis of human influenza virus among pilgrims during Hajj.

The risk of transmission of respiratory tract infections is considerably enhanced at mass gathering (MG) religious events. Hajj is an annual Islamic MG event with approximately 3 million Muslim pilgrims from over 180 countries concentrated in Makkah, Saudi Arabia. This study aimed to investigate the genetic diversity of influenza viruses circulating among pilgrims during the Hajj pilgrimage. We performed a cross-sectional analytical study where nasopharyngeal swabs (NPs) from pilgrims with respiratory tract illnesses presenting to healthcare facilities during the 2019 Hajj were screened for influenza viruses. Influenza A subtypes and influenza B lineages were determined by multiplex RT-PCR for positive influenza samples. The phylogenetic analysis was carried out for the hemagglutination (HA) gene. Out of 185 nasopharyngeal samples, 54 were positive for the human influenza virus. Of these, 27 were influenza A H1N1 and 19 H3N2, 4 were untypable influenza A, and 4 were influenza B. Phylogenetic analysis revealed that the H1N1 and H3N2 strains differentiated into different and independent genetic groups and formed close clusters with selected strains of influenza viruses from various locations. To conclude, this study demonstrates a high genetic diversity of circulating influenza A subtypes among pilgrims during the Hajj Season. There is a need for further larger studies to investigate in-depth the genetic characteristics of influenza viruses and other respiratory viruses during Hajj seasons.

Current sampling and sequencing biases of Lassa mammarenavirus limit inference from phylogeography and molecular epidemiology in Lassa fever endemic regions.

Lassa fever (LF) is a potentially lethal viral haemorrhagic infection of humans caused by Lassa mammarenavirus (LASV). It is an important endemic zoonotic disease in West Africa with growing evidence for increasing frequency and sizes of outbreaks. Phylogeographic and molecular epidemiology methods have projected expansion of the Lassa fever endemic zone in the context of future global change. The Natal multimammate mouse (Mastomys natalensis) is the predominant LASV reservoir, with few studies investigating the role of other animal species. To explore host sequencing biases, all LASV nucleotide sequences and associated metadata available on GenBank (n = 2,298) were retrieved. Most data originated from Nigeria (54%), Guinea (20%) and Sierra Leone (14%). Data from non-human hosts (n = 703) were limited and only 69 sequences encompassed complete genes. We found a strong positive correlation between the number of confirmed human cases and sequences at the country level (r = 0.93 (95% Confidence Interval = 0.71-0.98), p < 0.001) but no correlation exists between confirmed cases and the number of available rodent sequences (r = -0.019 (95% C.I. -0.71-0.69), p = 0.96). Spatial modelling of sequencing effort highlighted current biases in locations of available sequences, with increased sequencing effort observed in Southern Guinea and Southern Nigeria. Phylogenetic analyses showed geographic clustering of LASV lineages, suggestive of isolated events of human-to-rodent transmission and the emergence of currently circulating strains of LASV from the year 1498 in Nigeria. Overall, the current study highlights significant geographic limitations in LASV surveillance, particularly, in non-human hosts. Further investigation of the non-human reservoir of LASV, alongside expanded surveillance, are required for precise characterisation of the emergence and dispersal of LASV. Accurate surveillance of LASV circulation in non-human hosts is vital to guide early detection and initiation of public health interventions for future Lassa fever outbreaks.

Prioritization of zoonoses for multisectoral, One Health collaboration in Somalia, 2023.

Background: The human population of Somalia is vulnerable to zoonoses due to a high reliance on animal husbandry. This disease risk is exacerbated by relatively low income (poverty) and weak state capacity for health service delivery in the country as well as climate extremes and geopolitical instability in the region. To address this threat to public health efficiently and effectively, it is essential that all sectors have a common understanding of the priority zoonotic diseases of greatest concern to the country. Methods: Representatives from human, animal (domestic and wildlife), agriculture, and environmental health sectors undertook a multisectoral prioritization exercise using the One Health Zoonotic Disease Prioritization (OHZDP) tool developed by the United States CDC. The process involved: reviewing available literature and creating a longlist of zoonotic diseases for potential inclusion; developing and weighting criteria for establishing the importance of each zoonoses; formulating categorical questions (indicators) for each criteria; scoring each disease according to the criteria; and finally ranking the diseases based on the final score. Participants then brainstormed and suggested strategic action plans to prevent, and control prioritized zoonotic diseases. Results: Thirty-three zoonoses were initially considered for prioritization. Final criteria for ranking included: 1) socioeconomic impact (including sensitivity) in Somalia; 2) burden of disease in humans in Somalia); 3) availability of intervention in Somalia; 4) environmental factors/determinants; and 5) burden of disease in animals in Somalia. Following scoring of each zoonotic disease against these criteria, and further discussion of the OHZDP tool outputs, seven priority zoonoses were identified for Somalia: Rift Valley fever, Middle East respiratory syndrome, anthrax, trypanosomiasis, brucellosis, zoonotic enteric parasites (including Giardia and Cryptosporidium), and zoonotic influenza viruses. Conclusions: The final list of seven priority zoonotic diseases will serve as a foundation for strengthening One Health approaches for disease prevention and control in Somalia. It will be used to: shape improved multisectoral linkages for integrated surveillance systems and laboratory networks for improved human, animal, and environmental health; establish multisectoral public health emergency preparedness and response plans using One Health approaches; and enhance workforce capacity to prevent, control and respond to priority zoonotic diseases.