Amitabh Bipin Suthar

Antimicrobial resistance (AMR) is among the top ten global public health threats, demanding immediate attention and action [1]. To effectively tackle AMR, it is crucial to have a comprehensive understanding of the extent of the problem. Specifically, reliable, accurate, and representative information on the incidence of resistant infections is vital for monitoring the national and global scale of AMR, identifying emerging threats, and evaluating the impact of interventions. As part of PLoS Medicine's Special Issue dedicated to AMR, Balasubramanian and colleagues shed light on the global magnitude of hospital-associated infections due to hospital acquired resistant infections (HARI) [2]. One of the strengths of the study is the combination of data from hospital-based point prevalence surveys (PPS) with estimates of hospitalization rates, resistance prevalence, and country population size to predict the number of HARIs globally, across country income categories, and within nations. Using this approach, the authors estimated approximately 136 million HARI annually worldwide between 2010-2020. To our knowledge, these are among the first global incidence estimates of HARI. However, as acknowledged by the authors, results heavily rely on the availability of PPS data, which is limited in some regions and countries. According to the authors, only 11 low-and middle-income countries report this information, often based on small sample sizes, which may introduce bias and limit the generalizability of their findings. Additionally, the study relies on extrapolating country-level infection rates and resistance prevalence from available but scarce data at the hospital level, thus introducing uncertainties and assumptions that could impact the accuracy of the results. The heterogeneity of data from various sources and countries, with differences in data collection methods, diagnostic criteria, and reporting practices, could also affect the reliability of the estimates. Furthermore, due to the lack of available data, the study reports infections in an aggregated manner, without distinguishing specific infectious syndromes, which hampers the identification of more targeted syndrome-based interventions. Recent AMR burden estimates indicate that in 2019, 1.27 million deaths were attributed to drug resistant bacterial infections [3]. Comparing estimates from different sources is limited by a lack of standardized reporting. Balasubramanian et al. included six bacteria and 13 antibiotic classes, across all infectious syndromes. [2]. WHO's Global Antimicrobial Resistance and Use Surveillance System (GLASS) currently recommends 11 antibiotic classes, eight bacteria (Acinetobacter spp., E. coli, K. pneumoniae, Salmonella spp., S. aureus, Streptococcus pneumoniae, Shigella spp., and N. gonorrhoeae) and blood, urine, feces, and urethral and cervical swabs as priority specimen types for routine AMR surveillance and reporting to WHO [4]. These criteria will be expanded and updated in the forthcoming WHO GLASS 2.0 manual.

We compared characteristics of HIV diagnosis and recent HIV infection (ie, likely acquired within the last year) in Cambodia. We included individuals ≥ 15 years old accessing HIV testing. From August 2020 to August 2022, 53 031 people were tested for HIV, 6868 were newly diagnosed, and 192 were recently infected. We found differences in geographical burden and risk behaviors with diagnosis and recency (eg, men who have sex with men, transgender women, and entertainment workers had a nearly 2-fold increased odds of testing positive for recent infection compared to being diagnosed with HIV). Recent infection surveillance may provide unique insights into ongoing HIV acquisition to inform programs.

Dr Amitabh Suthar and Dr Christopher Dye give their perspective on infection, immunity and surveillance of COVID-19.

Background: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. Methods: This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. Results: Median time on ART was 86.4 months (interquartile range [IQR], 44.8–130.2 months), and median CD4 count at ART initiation was 311 cells/mm ³ (IQR, 197–484 cells/mm ³ ). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022–10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028–0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016–0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084–0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198–5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435–7.278], p = 0.005). Conclusion: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

Objective To evaluate the impact of vaccine scale-up on population level covid-19 mortality and incidence in the United States. Design Observational study. Setting US county level case surveillance and vaccine administration data reported from 14 December 2020 to 18 December 2021. Participants Residents of 2558 counties from 48 US states. Main outcome measures The primary outcome was county covid-19 mortality rates (deaths/100 000 population/county week). The secondary outcome was incidence of covid-19 (cases/100 000 population/county week). Incidence rate ratios were used to compare rates across vaccination coverage levels. The impact of a 10% improvement in county vaccination coverage (defined as at least one dose of a covid-19 vaccine among adults ≥18 years of age) was estimated During the eras of alpha and delta variant predominance, the impact of very low (0-9%), low (10-39%), medium (40-69%), and high (≥70%) vaccination coverage levels was compared. Results In total, 30 643 878 cases of covid-19 and 439 682 deaths associated with covid-19 occurred over 132 791 county weeks. A 10% improvement in vaccination coverage was associated with an 8% (95% confidence interval 8% to 9%) reduction in mortality rates and a 7% (6% to 8%) reduction in incidence. Higher vaccination coverage levels were associated with reduced mortality and incidence rates during the eras of alpha and delta variant predominance. Conclusions Higher vaccination coverage was associated with lower rates of population level covid-19 mortality and incidence in the US.

COVID-19 Definitions, Testing, and Surveillance

Objective We compared suspect, probable, and confirmed case definitions, as well as diagnostic testing criteria, used in the COVID-19 pandemic’s 25 highest burden countries to aid interpretation of global and national surveillance data. Methods We identified the COVID-19 pandemic’s 25 countries with the highest disease burden based on the number of cumulative reported cases to the World Health Organization (WHO) as of 1 October 2020. We searched official websites of these countries for suspect, probable, and confirmed case definitions. Given that confirmation of COVID-19 usually requires diagnostic testing, we also searched for diagnostic testing eligibility criteria in these countries. Extracted case definitions and testing criteria were managed in a database and analyzed in Microsoft Excel. Findings We identified suspect, probable, and confirmed case definitions in 96%, 64%, and 100% of countries, respectively. Testing criteria were identified in 100% of countries. 56% of identified countries followed WHO recommendations for using a combination of clinical and epidemiological criteria as part of the suspect case definition. 75% of identified countries followed WHO recommendations on using clinical, epidemiological, and diagnostic criteria for probable cases. 72% of countries followed WHO recommendations on using PCR testing for confirming a case of COVID-19. Finally, 64% of countries used testing eligibility criteria at least as permissive as WHO. Conclusion There is marked heterogeneity in who is eligible for testing in countries and how countries define a case of COVID-19. This affects the ability to compare burden, transmission, and response impact estimates derived from case surveillance data across countries.

Civil registration and vital statistics (CRVS) systems play a key role in upholding human rights and generating data for health and good governance. They also can help monitor progress in achieving the United Nations Sustainable Development Goals. Although many countries have made substantial progress in strengthening their CRVS systems, most low- and middle-income countries still have underdeveloped systems. The objective of this systematic review is to identify national policies that can help countries strengthen their systems. The ABI/INFORM, Embase, JSTOR, PubMed, and WHO Index Medicus databases were systematically searched for policies to improve birth and/or death registration on 24 January 2017. Global stakeholders were also contacted for relevant grey literature. For the purposes of this review, policies were categorised as supply, demand, incentive, penalty, or combination (i.e., at least two of the preceding policy approaches). Quantitative results on changes in vital event registration rates were presented for individual comparative articles. Qualitative systematic review methodology, including meta-ethnography, was used for qualitative syntheses on operational considerations encompassing acceptability to recipients and staff, human resource requirements, information technology or infrastructure requirements, costs to the health system, unintended effects, facilitators, and barriers. This study is registered with PROSPERO, number CRD42018085768. Thirty-five articles documenting experience in implementing policies to improve birth and/or death registration were identified. Although 25 countries representing all global regions (Africa, the Americas, Southeast Asia, the Western Pacific, Europe, and the Eastern Mediterranean) were reflected, there were limited countries from the Eastern Mediterranean and Europe regions. Twenty-four articles reported policy effects on birth and/or death registration. Twenty-one of the 24 articles found that the change in registration rate after the policy was positive, with two supply and one penalty articles being the exceptions. The qualitative syntheses identified 15 operational considerations across all policy categories. Human and financial resource requirements were not quantified. The primary limitation of this systematic review was the threat of publication bias wherein many countries may not have documented their experience; this threat is most concerning for policies that had neutral or negative effects. Our systematic review suggests that combination policy approaches, consisting of at least a supply and demand component, were consistently associated with improved registration rates in different geographical contexts. Operational considerations should be interpreted based on health system, governance, and sociocultural context. More evaluations and research are needed from the Eastern Mediterranean and Europe regions. Further research and evaluation are also needed to estimate the human and financial resource requirements required for different policies.

Objectives Achieving the Sustainable Development Goals will require data-driven public health action. There are limited publications on national health information systems that continuously generate health data. Given the need to develop these systems, we summarised their current status in low-income and middle-income countries. Setting The survey team jointly developed a questionnaire covering policy, planning, legislation and organisation of case reporting, patient monitoring and civil registration and vital statistics (CRVS) systems. From January until May 2017, we administered the questionnaire to key informants in 51 Centers for Disease Control country offices. Countries were aggregated for descriptive analyses in Microsoft Excel. Results Key informants in 15 countries responded to the questionnaire. Several key informants did not answer all questions, leading to different denominators across questions. The Ministry of Health coordinated case reporting, patient monitoring and CRVS systems in 93% (14/15), 93% (13/14) and 53% (8/15) of responding countries, respectively. Domestic financing supported case reporting, patient monitoring and CRVS systems in 86% (12/14), 75% (9/12) and 92% (11/12) of responding countries, respectively. The most common uses for system-generated data were to guide programme response in 100% (15/15) of countries for case reporting, to calculate service coverage in 92% (12/13) of countries for patient monitoring and to estimate the national burden of disease in 83% (10/12) of countries for CRVS. Systems with an electronic component were being used for case reporting, patient monitoring, birth registration and death registration in 87% (13/15), 92% (11/12), 77% (10/13) and 64% (7/11) of responding countries, respectively. Conclusions Most responding countries have a solid foundation for policy, planning, legislation and organisation of health information systems. Further evaluation is needed to assess the quality of data generated from systems. Periodic evaluations may be useful in monitoring progress in strengthening and harmonising these systems over time.