Strategic investment in tuberculosis control in the Republic of Bulgaria

As Bulgaria transitions away from Global Fund grant, robust estimates of the comparative impact of the various response strategies under consideration are needed to ensure sustained effectiveness of the tuberculosis (TB) programme. We tailored an established mathematical model for TB control to the epidemic in Bulgaria to project the likely outcomes of seven intervention scenarios. Under existing programmatic conditions projected forward, the country's targets for achieving TB elimination in the coming decades will not be achieved. No interventions under consideration were predicted to accelerate the baseline projected reduction in epidemiological indicators significantly. Discontinuation of the 'Open Doors' program and activities of non-governmental organisations would result in a marked exacerbation of the epidemic (increasing incidence in 2035 by 6-8% relative to baseline conditions projected forward). Changing to a short course regimen for multidrug-resistant TB (MDR-TB) would substantially decrease MDR-TB mortality (by 21.6% in 2035 relative to baseline conditions projected forward). Changing to ambulatory care for eligible patients would not affect TB burden but would be markedly cost-saving. In conclusion, Bulgaria faces important challenges in transitioning to a primarily domestically-financed TB programme. The country should consider maintaining currently effective programs and shifting towards ambulatory care to ensure program sustainability

Transmission of non-B HIV subtypes in the UK is increasingly driven by large non-heterosexual clusters

BACKGROUND: The United Kingdom human immunodeficiency virus (HIV) epidemic was historically dominated by HIV subtype B transmission among men who have sex with men (MSM). Now 50% of diagnoses and prevalent infections are among heterosexual individuals and mainly involve non-B subtypes. Between 2002 and 2010, the prevalence of non-B diagnoses among MSM increased from 5.4% to 17%, and this study focused on the drivers of this change. METHODS: Growth between 2007 and 2009 in transmission clusters among 14 000 subtype A1, C, D, and G sequences from the United Kingdom HIV Drug Resistance Database was analysed by risk group. RESULTS: Of 1148 clusters containing at least 2 sequences in 2007, >75% were pairs and >90% were heterosexual. Most clusters (71.4%) did not grow during the study period. Growth was significantly lower for small clusters and higher for clusters of ≥7 sequences, with the highest growth observed for clusters comprising sequences from MSM and people who inject drugs (PWID). Risk group (P< .0001), cluster size (P< .0001), and subtype (P< .01) were predictive of growth in a generalized linear model. DISCUSSION: Despite the increase in non-B subtypes associated with heterosexual transmission, MSM and PWID are at risk for non-B infections. Crossover of subtype C from heterosexuals to MSM has led to the expansion of this subtype within the United Kingdom

Estimating the long-term effects of mass screening for latent and active tuberculosis in the Marshall Islands

BACKGROUND: Ambitious population-based screening programmes for latent and active tuberculosis (TB) were implemented in the Republic of the Marshall Islands in 2017 and 2018. METHODS: We used a transmission dynamic model of TB informed by local data to capture the Marshall Islands epidemic's historical dynamics. We then used the model to project the future epidemic trajectory following the active screening interventions, as well as considering a counterfactual scenario with no intervention. We also simulated future scenarios including periodic interventions similar to those previously implemented, to assess their ability to reach the End TB Strategy targets and TB pre-elimination in the Marshall Islands. RESULTS: The screening activities conducted in 2017 and 2018 were estimated to have reduced TB incidence and mortality by around one-third in 2020, and are predicted to achieve the End TB Strategy milestone of 50% incidence reduction by 2025 compared with 2015. Screening interventions had a considerably greater impact when latent TB screening and treatment were included, compared with active case finding alone. Such combined programmes implemented at the national level could achieve TB pre-elimination around 2040 if repeated every 2 years. CONCLUSIONS: Our model suggests that it would be possible to achieve TB pre-elimination by 2040 in the Marshall Islands through frequent repetition of the same interventions as those already implemented in the country. It also highlights the importance of including latent infection testing in active screening activities

Understanding COVID-19 Dynamics and the Effects of Interventions in the Philippines: A Mathematical Modelling Study

Background COVID-19 initially caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with many high-income countries; possibly because of differing demographics; socioeconomics; surveillance; and policy responses. Here; we investigate the role of multiple factors on COVID-19 dynamics in the Philippines; a LMIC that has had a relatively severe COVID-19 outbreak. Methods We applied an age-structured compartmental model that incorporated time-varying mobility; testing; and personal protective behaviors (through a “Minimum Health Standards” policy; MHS) to represent the first wave of the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon; Central Visayas; and the National Capital Region). We estimated effects of control measures; key epidemiological parameters; and interventions. Findings Population age structure; contact rates; mobility; testing; and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases; hospitalisations; and deaths. The model indicated that MHS reduced the probability of transmission per contact by 13-27%. The February 2021 case detection rate was estimated at ~8%; population recovered at ~9%; and scenario projections indicated high sensitivity to MHS adherence. Interpretation COVID-19 dynamics in the Philippines are driven by age; contact structure; mobility; and MHS adherence. Continued compliance with low-cost MHS should help the Philippines control the epidemic until vaccines are widely distributed; but disease resurgence may be occurring due to a combination of low population immunity and detection rates and new variants of concern

COVID-19 collaborative modelling for policy response in the Philippines, Malaysia and Vietnam

Mathematical models that capture COVID-19 dynamics have supported public health responses and policy development since the beginning of the pandemic, yet there is limited discourse to describe features of an optimal modelling platform to support policy decisions or how modellers and policy makers have engaged with each other. Here, we outline how we used a modelling software platform to support public health decision making for the COVID-19 response in the Western Pacific Region (WPR) countries of the Philippines, Malaysia and Viet Nam. This perspective describes an approach to support evidence-based public health decisions and policy, which may help inform other responses to similar outbreak events. The platform we describe formed the basis for one of the inaugural World Health Organization (WHO) Western Pacific (WPRO) Innovation Challenge awards, and was backed by collaboration between epidemiological modellers, those providing public health advice, and policy makers

Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number

Non-disclosed men who have sex with men in UK HIV transmission networks: phylogenetic analysis of surveillance data.

BACKGROUND: Patients who do not disclose their sexuality, including men who do not disclose same-sex behaviour, are difficult to characterise through traditional epidemiological approaches such as interviews. Using a recently developed method to detect large networks of viral sequences from time-resolved trees, we localised non-disclosed men who have sex with men (MSM) in UK transmission networks, gaining crucial insight into the behaviour of this group. METHODS: For this phylogenetic analysis, we obtained HIV pol sequences from the UK HIV Drug Resistance Database (UKRDB), a central repository for resistance tests done as part of routine clinical care throughout the UK. Sequence data are linked to demographic and clinical data held by the UK Collaborative HIV Cohort study and the national HIV/AIDS reporting system database. Initially, we reconstructed maximum likelihood phylogenies from these sequences, then sequences were selected for time-resolved analysis in BEAST if they were clustered with at least one other sequence at a genetic distance of 4·5% or less with support of at least 90%. We used time-resolved phylogenies to create networks by linking together nodes if sequences shared a common ancestor within the previous 5 years. We identified potential non-disclosed MSM (pnMSM), defined as self-reported heterosexual men who clustered only with men. We measured the network position of pnMSM, including betweenness (a measure of connectedness and importance) and assortativity (the propensity for nodes sharing attributes to link). FINDINGS: 14 405 individuals were in the network, including 8452 MSM, 1743 heterosexual women and 1341 heterosexual men. 249 pnMSM were identified (18·6% of all clustered heterosexual men) in the network. pnMSM were more likely to be black African (p<0·0001), less likely to be infected with subtype B (p=0·006), and were slightly older (p=0·002) than the MSM they clustered with. Mean betweenness centrality was lower for pnMSM than for MSM (1·31, 95% CI 0·48-2·15 in pnMSM vs 2·24, 0·98-3·51 in MSM; p=0·002), indicating that pnMSM were in peripheral positions in MSM clusters. Assortativity by risk group was higher than expected (0·037 vs -0·037, p=0·01) signifying that pnMSM were linked to each other. We found that self-reported heterosexual men were more likely to link MSM and heterosexual women than heterosexual women were to link MSM and heterosexual men (Fisher's exact test p=0·0004; OR 2·24) but the number of such transmission chains was small (only 54 in total vs 32 in women). INTERPRETATION: pnMSM are a subgroup distinct from both MSM and from heterosexual men. They are more likely to choose sexual partners who are also pnMSM and might exhibit lower-risk sexual behaviour than MSM (eg, choosing low-risk partners or consistently using condoms). Heterosexual men are the group most likely to be diagnosed with late-stage disease (ie, low CD4 counts) and non-disclosed MSM might put female partners at higher risk than heterosexual men because non-disclosed MSM have male partners. Hence, pnMSM require specific consideration to ensure they are included in public health interventions. FUNDING: National Institutes of Health

Factors limiting the transmission of HIV mutations conferring drug resistance: fitness costs and genetic bottlenecks

Transmission of HIV strains with drug-resistance mutations (DRMs) causes public health problems in resource-rich countries. We use a stochastic model, with data from viral competition experiments, to analyze the effect of fitness costs (FCs) and genetic bottlenecks on limiting transmission of 10 clinically significant DRMs. Transmission of DRMs with low FCs (∼0.2%) is similar to wild-type; transmission chains last ∼8 generations causing clusters of ∼60 infected individuals. Genetic bottlenecks substantially limit transmission of DRMs with moderately high FCs (∼0.6%); chains last ∼1–3 generations with transmission clusters of 2–7. Transmission of DRMs with extremely high FCs (>6%) only occurs from ∼5% of index cases. DRMs can revert to wild-type and remain as minority strains, within treatment-naïve individuals, undetectable by current resistance assays. We calculate, based on assay sensitivity, the length of time each DRM is detectable within individuals. Taken together, our results imply a hidden epidemic of transmitted resistance may exist

Report 26: Reduction in mobility and COVID-19 transmission

In response to the COVID-19 pandemic, countries have sought to control transmission of SARS-CoV-2 by restricting population movement through social distancing interventions, reducing the number of contacts. Mobility data represent an important proxy measure of social distancing. Here, we develop a framework to infer the relationship between mobility and the key measure of population-level disease transmission, the reproduction number (R). The framework is applied to 53 countries with sustained SARS-CoV-2 transmission based on two distinct country-specific automated measures of human mobility, Apple and Google mobility data. For both datasets, the relationship between mobility and transmission was consistent within and across countries and explained more than 85% of the variance in the observed variation in transmissibility. We quantified country-specific mobility thresholds defined as the reduction in mobility necessary to expect a decline in new infections (R<1). While social contacts were sufficiently reduced in France, Spain and the United Kingdom to control COVID-19 as of the 10th of May, we find that enhanced control measures are still warranted for the majority of countries. We found encouraging early evidence of some decoupling of transmission and mobility in 10 countries, a key indicator of successful easing of social-distancing restrictions. Easing social-distancing restrictions should be considered very carefully, as small increases in contact rates are likely to risk resurgence even where COVID-19 is apparently under control. Overall, strong population-wide social-distancing measures are effective to control COVID-19; however gradual easing of restrictions must be accompanied by alternative interventions, such as efficient contacttracing, to ensure control