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bioRxiv2026

A Computational Re-evaluation of Spatial Trials for Zoonotic Tuberculosis Control: Model Misspecification, Diagnostic Miss-classification, and the Illusion of Wildlife Culling Efficacy

1. Wildlife reservoir management frequently relies on the Randomised Badger Culling Trial's (RBCT) trade-off hypothesis, which posits that reductions in cattle herd infections are offset by a perturbation effect driven by disrupted host dispersal. This paper evaluates the computational and epidemiological robustness of this historical trial, which serves as the foundational empirical experiment guiding zoonotic tuberculosis (Mycobacterium bovis) control policies. 2. Using generalized linear mixed models with a generalized Poisson error distribution to explicitly address historical data overdispersion, this study contrasts traditional parametric inference against exact cluster-constrained permutation tests across distinct operational definitions of disease incidence. 3. Non-parametric diagnostics reveal that previously reported treatment and perturbation effects render as statistical artifacts under exact non-parametric permutation. Inside culling zones, parametric significance fails to withstand exact permutation verification due to extreme data leverage in localized cluster blocks. 4. Crucially, when diagnostic misclassification biases are eliminated by analysing total reactor datasets, all apparent culling effects disappear, and information criteria overwhelmingly favour nested null architectures. Unconfirmed reactors likely represent true biological infections missed by low-sensitivity post-mortem macro-necropsy, proving that host removal tracks observation noise rather than genuine zoonotic transmission pathways. 5. Finally, empirical scaling conducted in this study identifies a novel mathematical saturation effect, demonstrating that this sub-linear scaling is an operational artifact of unmodelled herd-level disease recurrence over time. 6. Policy implications. Because current zoonotic tuberculosis intervention frameworks are built upon a structurally misspecified statistical model, they have driven large-scale veterinary policies resulting in substantial, unevidenced ecological and economic interventions while failing to provide genuine public health, animal health, or disease control benefits.

ecology↗

bioRxiv2026

Low-Density Lipoprotein Modulates Plasma Fibrin Network Architecture and Impairs Fibrinolysis

Low-density lipoprotein (LDL) is a major atherogenic lipoprotein, yet its potential to directly modify the fibrin scaffold of blood clots is incompletely understood. Here, we investigated how LDL alters plasma fibrin network architecture and internal fibrinolysis across defined fibrinogen/thrombin conditions. Pooled normal human plasma was supplemented with LDL and clotted with controlled concentrations of fibrinogen and thrombin. Fibrin architecture was visualized by confocal microscopy and quantified by pore-size analysis; clot formation and lysis were monitored turbidimetrically in the presence of tissue plasminogen activator (tPA). Increasing LDL produced a pronounced reduction in fibrin-network pore size across the tested fibrinogen/thrombin conditions. The LDL dependence of pore diameter was well described by a power-law relationship, D_pore=(6.54 +/- 0.11)[LDL]^(-0.12 +/- 0.02) , (R^2 = 0.90), with a significant negative LDL exponent (p = 4 x 10^5). Increasing LDL also prolonged clot lysis time and altered turbidity kinetics. These findings extend epidemiologic and clinical associations between ApoB-containing lipoproteins and hypofibrinolytic clot phenotypes by demonstrating, in a controlled plasma system, that LDL itself can modify fibrin network architecture and fibrinolytic susceptibility. The results support a structure-function role for LDL within the fibrin biomaterial and motivate direct tests of LDL incorporation, protofibril packing, fibrinolytic-protein binding, and single-fiber mechanics.

biophysics↗

bioRxiv2018

Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries

BackgroundDrug resistance and HIV co-infection are challenges for the global control of tuberculosis.\n\nMethodsWe collected Mycobacterium tuberculosis isolates from adult patients in Cote dIvoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing (DST) was done locally and at the Swiss tuberculosis reference laboratory. We examined mortality during treatment according to DST results and treatment adequacy in logistic regression models adjusting for sex, age, sputum microscopy and HIV status.\n\nFindings634 tuberculosis patients were included; median age was 33.2 years, 239 (37.7%) were female, 272 (42.9%) HIV-positive and 69 (10.9%) patients died. Based on the reference laboratory DST, 394 (62.2%) strains were pan-susceptible, 45 (7.1%) mono-resistant, 163 (25.7%) multidrug-resistant (MDR-TB), and 30 (4.7%) had pre-extensive or extensive drug resistance (pre-XDR/XDR-TB). Results of reference and local laboratories were discordant in 121 (19.1%) cases, corresponding to a sensitivity of 84.3% and a specificity of 90.8%. In patients with drug-resistant tuberculosis, discordant results were associated with increased mortality (risk ratio 1.81; 95% CI 1.07-3.07). In logistic regression, compared to adequately treated patients with pan-susceptible strains, the adjusted odds ratio for death was 4.23 (95% CI 2.16-8.29) for adequately treated patients with drug-resistant strains and 21.54 (95% CI 3.36-138.1) for inadequately treated patients with drug-resistant strains. HIV status was not associated with mortality.\n\nInterpretationUsing a reference laboratory standard, inaccurate DST leading to inappropriate treatment of drug-resistant tuberculosis, but not HIV infection, contributed to mortality.

epidemiology↗

bioRxiv2016

Transethnic genetic correlation estimates from summary statistics

The increasing number of genetic association studies conducted in multiple populations provides unprecedented opportunity to study how the genetic architecture of complex phenotypes varies between populations, a problem important for both medical and population genetics. Here we develop a method for estimating the transethnic genetic correlation: the correlation of causal variant effect sizes at SNPs common in populations. We take advantage of the entire spectrum of SNP associations and use only summary-level GWAS data. This avoids the computational costs and privacy concerns associated with genotype-level information while remaining scalable to hundreds of thousands of individuals and millions of SNPs. We apply our method to gene expression, rheumatoid arthritis, and type-two diabetes data and overwhelmingly find that the genetic correlation is significantly less than 1. Our method is implemented in a python package called popcorn.

Genetics↗

bioRxiv2016

Discovery of a persistent Zika virus lineage in Bahia, Brazil

Metagenomic next-generation sequencing coupled with capture probe enrichment was used to recover 11 whole and partial Zika virus (ZIKV) genomes from patients in Bahia, Brazil from April 2015 to January 2016, where the majority of suspected Brazilian ZIKV cases have been reported. Phylogenetic reconstructions and molecular clock analyses using the newly generated data uncovered the existence of a Bahia-specific ZIKV lineage sharing a common ancestor in mid-2014, indicating sustained circulation of this strain in Bahia since that date.

Epidemiology↗

bioRxiv2016

Reconstructing contact network parameters from viral phylogenies

Models of the spread of disease in a population often make the simplifying assumption that the population is homogeneously mixed, or is divided into homogeneously mixed compartments. However, human populations have complex structures formed by social contacts, which can have a significant influence on the rate of epidemic spread. Contact network models capture this structure by explicitly representing each contact which could possibly lead to a transmission. We developed a method based on kernel approximate Bayesian computation (kernel-ABC) for estimating structural parameters of the contact network underlying an observed viral phylogeny. The method combines adaptive sequential Monte Carlo for ABC, Gillespie simulation for propagating epidemics though networks, and a kernel-based tree similarity score. We used the method to fit the Barabasi-Albert network model to simulated transmission trees, and also applied it to viral phylogenies estimated from five published HIV sequence datasets. On simulated data, we found that the preferential attachment power and the number of infected nodes in the network can often be accurately estimated. On the other hand, the mean degree of the network, as well as the total number of nodes, were not estimable with kernel-ABC. We observed substantial heterogeneity in the parameter estimates on real datasets, with point estimates for the preferential attachment power ranging from 0.06 to 1.05. These results underscore the importance of considering contact structures when performing phylodynamic inference. Our method offers the potential to quantitatively investigate the contact network structure underlying viral epidemics.

Epidemiology↗

bioRxiv2016

Risk estimates for microcephaly related to Zika virus infection - from French Polynesia to Bahia, Brazil

Zika virus (ZIKV) infection during pregnancy has been linked to birth defects,1 yet the magnitude of risk remains uncertain. A study of the Zika outbreak in French Polynesia estimated that the risk of microcephaly due to ZIKV infection in the first trimester of pregnancy was 0.95% (95% confidence interval: 0.34-1.91%), based on eight microcephaly cases identified retrospectively in a population of approximately 270,000 people with an estimated 66% ZIKV infection rate.2

Epidemiology↗

bioRxiv2016

Serological evidence for localized and persistent antibody response in Zika virus-positive neonates with microcephaly (Brazil, 2015)- a secondary analysis

A recent publication in The Lancet by Cordeiro and colleagues reported levels of IgM for Zika (ZIKV) and dengue (DENV) viruses in serum and cerebrospinal fluid (CSF) of 31 infants born with microcephaly in Brazil.1 Their study suggests higher titers in CSF relative to serum in individual neonates, but no quantitative comparisons were reported. In this short report, the differences in antibody titers are quantified and compared between sample sources; across sampling periods; and between sample sources within individual neonates to more comprehensively understand these data to inform serological surveillance. These are statistically significant differences in ZIKV titers between CSF and serum samples, (in contrast to DENV titers), and these ZIKV titer levels remain elevated across sampling dates, whereas the titer in serum trends downward by sampling date. In multivariate models, ZIKV titer in CSF samples is independent of titer in serum, and of DENV antibodies in both CSF and serum. These findings quantify the compartmentalization of ZIKV antigens across the blood-brain barrier, and suggest complex interplay between ZIKV and cross-reacting DENV antigens in congenital/neonatal infections.\n\nNoteDataset for analysis appears to Appendix II.

Epidemiology↗

bioRxiv2016

Potential impact of novel diagnostics and treatments on the burden of antibiotic resistant in Escherichia coli

The rising threat of antibiotic resistance in Europe and beyond is of increasing concern and is prompting renewed effort to better understand and mitigate their impact. Escherichia Coli blood stream infections are a more major concern in Europe given their incidence and severe associated outcomes. Additionally the level of 3rd generation cephalosporins and carbapenems resistance among those bacteraemia has significantly increased, limiting available treatment options. We estimated the current burden associated with E. coli blood stream infections in Europe at 17,000 (95%CI [8,000; 30,000]) excess deaths and 960,000 (95%CI [600,000; 1,450,000]) extra hospital bed days. From those, the contribution due to 3rd generation cephalosporins and carbapenems resistant strains reached 6,000 (95%CI [2,000; 12,000]) excess deaths, and 200,000 (95%CI [76,000; 420,000]) extra hospital bed stay. In the worst case scenario, we estimated the burden of E. coli blood stream infection in 2026 could increase over 4-fold, mostly resulting from an increase in the level of resistance rather than an increase in the incidence of blood stream infections. Finally, we estimated that the impact of combined novel diagnostics and treatments could substantially reduce the excess mortality by 18.5% to 55.5%, and length of stay by 13.2% to 75.6%.

Epidemiology↗

bioRxiv2016

Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

BackgroundThe ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July-August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission.\n\nMethodsWe estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July-August 2016 with different age cutoff for fractional-dose vaccines.\n\nFindingsWe estimate the effective reproductive number early in the Angola outbreak was between 5{middle dot}2 and 7{middle dot}1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%.\n\nInterpretationDose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.\n\nFundingNIH-MIDAS, HMRF-Hong Kong

Epidemiology↗

bioRxiv2016

Population effect of influenza vaccination under co-circulation of non-vaccine variants and the case for a multi-strain A/H3N2 vaccine component

Some past epidemics of different influenza (sub)types (particularly A/H3N2) in the US saw co-circulation of vaccine-type and variant strains. There is evidence that natural infection with one influenza (sub)type offers short-term protection against infection with another influenza (sub)type (henceforth, cross-immunity). This suggests that such cross-immunity for strains within a (sub)type is expected to be strong. Therefore, while vaccination effective against one strain may reduce transmission of that strain, this may also lead to a reduction of the ability of the vaccine-type strain to suppress spread of a variant strain. It remains unclear what the joint effect of vaccination and cross-immunity is for co-circulating influenza strains, and what is the potential benefit of a bivalent vaccine that protects against both strains.\n\nWe simulated co-circulation of vaccine-type and variant strains under a variety of scenarios. In each scenario, we considered the case when the vaccine efficacy against the variant strain is lower than the efficacy against the vaccine-type strain (monovalent vaccine), as well the case when vaccine is equally efficacious against both strains (bivalent vaccine).\n\nAdministration of a bivalent vaccine results in a significant reduction in the overall incidence of infection compared to administration of a monovalent vaccine, even with lower coverage by the bivalent vaccine. Additionally, we found that the stronger is the degree of cross-immunity, the less beneficial is the increase in coverage levels for the monovalent vaccine, and the more beneficial is the introduction of the bivalent vaccine.\n\nOur work exhibits the limitations of influenza vaccines that have low efficacy against non-vaccine strains, and demonstrates the benefits of vaccines that offer good protection against multiple influenza strains. The results elucidate the need for guarding against the potential co-circulation of non-vaccine strains for an influenza (sub)type, at least during select seasons, possibly through inclusion of multiple strains within a (sub)type (particularly A/H3N2) in a vaccine.

Epidemiology↗

bioRxiv2016

Sexual transmission causes a marked increase in the incidence of Zika in women in Rio de Janeiro, Brazil.

The recent emergence of Zika in Brazil and its association with increased congenital malformation rates has raised concerns over its impact on the birth rates in the country. Using data on the incidence of Zika in 2015-2016 and dengue in 2013 and 2015-16 for the city of Rio de Janeiro (pop: 6.4 million), we document a massive increase of Zika in women compared to men. Even after correcting for the bias due to the systematic testing of pregnant women for Zika, there are 90% more registered cases per 100,000 women in the sexually active age group (15-65 years) than for men but not before 15 or after 65. Assuming that infected men transmit the disease to women in their semen but that the converse is not true, some extra incidence in women is to be expected. An alternate hypothesis would be that women visit doctors more often than men. To test this, we compared the incidence of dengue fever in men and women in 2015 and in 2013 (before Zika reached Rio de Janeiro): in both years, women are 30% more likely to be reported with dengue.\n\nSumming up, women in the sexually active age bracket are far more likely to get Zika than men (+90% increase); sexual transmission is the most probable cause. Women in the 15-65 age group are also 30% more likely to be reported with dengue than men, which is probably due to women being more careful with their health.

Epidemiology↗

bioRxiv2016

Contact, travel, and transmission: The impact of winter holidays on influenza dynamics in the United States

BackgroundThe seasonality of influenza is thought to vary according to environmental factors and human behavior. During winter holidays, potential disease-causing contact and travel deviate from typical patterns, and we aim to understand these changes on age-specific and spatial flu transmission.\n\nMethodsWe characterized the changes to transmission and epidemic trajectories among children and adults in a spatial context before, during, and after the winter holidays among aggregated physician medical claims in the United States from 2001 to 2009 and among synthetic data simulated from a deterministic, age-specific spatial metapopulation model.\n\nResultsWinter holidays reduced flu transmission and delayed the trajectory of flu season epidemics. The holiday period itself observed a shift in relative risk of disease from children towards adults. Model results indicated that holidays delay epidemic peaks and synchronize incidence across locations, and contact reductions from school closures rather than age-specific mixing and travel produce these observed holiday dynamics.\n\nConclusionsWinter holidays delay seasonal influenza epidemic peaks due to changes in contact patterns. These findings may improve the future design of influenza intervention strategies, such as the proper timing and duration of school closures, and the spatial and demographic allocation of vaccines.

Epidemiology↗

bioRxiv2016

Dynamics Affecting the Risk of Silent Circulation When Oral Polio Vaccination Is Stopped

Silent circulation of polioviruses without poliomyelitis cases could threaten eradication when oral polio vaccine (OPV) use is stopped worldwide. Waning immunity promotes silent circulation by increasing poliovirus transmission from individuals not at risk of paralytic polio. There is limited data on temporal patterns of waning. Accordingly, we modeled a range of waning patterns, scaled from fast but shallow to slow but deep, while keeping constant the effect of waning on transmission dynamics before vaccination begins. Besides waning, we varied overall transmissibility, the delay from beginning vaccination to reaching specified infection levels, and type specific virus characteristics. We observed an increasing range of vaccination levels that resulted in long periods of silent circulation after eliminating paralytic polio cases as the delay in reaching final vaccination levels increased. The extent of silent circulation was higher when waning was slower and deeper, when transmissibility was higher, and when virus was type 3. In our model, modest levels of vaccination of adults reduce silent circulation risks. These modeled patterns are consistent with very long silent circulation mainly emerging as a threat to OPV cessation in the last places from which polio cases are eliminated. Our analyses indicate why previous modeling studies have not seen the threat of silent circulation. They used models with no or very short duration waning and they lacked identifiability of waning effects on silent circulation because they fit models only to paralytic polio case counts. Our analyses show that nearly identical polio case count patterns can be generated by a range of waning patterns that in turn generate diverse silent circulation risks. We conclude that the risks of prolonged silent circulation are real but unquantified, that vaccinating adults with waned immunity will reduce those risks, and that intensive environmental surveillance will be needed to detect this risk before stopping OPV.

Epidemiology↗

bioRxiv2016

Analyzing climate variations on multiple timescales can guide Zika virus response measures

BackgroundThe emergence of Zika virus (ZIKV) as a public health emergency in Latin America and the Caribbean (LAC) occurred during a period of severe drought and unusually high temperatures. Speculation in the literature exists that these climate conditions were associated with the 2015/2016 El Nino event and/or climate change but to date no quantitative assessment has been made. Analysis of related flaviviruses -such as dengue and chikungunya, which are transmitted by the same vectors- suggests that ZIKV dynamics is sensitive to climate seasonality and longer-term variability and trends. A better understanding the climate conditions conducive to the 2014-2016 epidemic may permit the development of climate-informed short- and long-term strategies for ZIKV prevention and control.\n\nResultsUsing a novel timescale-decomposition methodology, we demonstrate that extreme climate anomalies observed in most parts of South America during the current epidemic are not caused exclusively by El Nino or climate change -as speculated-, but are the result of a particular combination of climate signals acting at multiple timescales. In Brazil, the heart of the epidemic, we find that dry conditions present during 2013-2015 are explained primarily by year-to-year variability superimposed on decadal variability, but with little contribution of long-term trends. In contrast, the extreme warm temperatures of 2014-2015 resulted from the compound effect of climate change, decadal and year-to-year climate variability.\n\nConclusionsZIKV response strategies adapted for a drought context in Brazil during El Nino 2015/2016 may need to be revised to accommodate the likely return of heavy rainfall associated with the probable 2016/2017 La Nina. Temperatures are likely to remain warm given the importance of long term and decadal scale climate signals.

Epidemiology↗

bioRxiv2016

Potent Protection against H5N1 and H7N9 Influenza via Childhood Hemagglutinin Imprinting

Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit puzzling differences in age distribution of human cases. Previous explanations cannot fully account for these patterns. We analyze data from all known human cases of H5N1 and H7N9 and show that an individuals first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes of the same phylogenetic group. Statistical modeling reveals protective HA imprinting to be the crucial explanatory factor, providing 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and to demonstrate that a novel strains pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment.

Epidemiology↗

bioRxiv2016

Differences in perceived severity of Zika virus infection and dengue fever and its influence on mosquito control practices in Malaysia, a dengue-endemic country

BackgroundIt is important to study the concerns over the Zika virus (ZIKV) outbreak among the general public in dengue-endemic countries such as Malaysia, as both diseases are transmitted by the same vector species. Furthermore, investigation of public prevention measures for ZIKV is essential in order to identify the gaps in mosquito control practices. The aims of this study were to explore the differences in 1) the perception of severity towards ZIKV infection and dengue fever, and 2) mosquito control practices before and after the ZIKV outbreak was declared a Public Health Emergency of International Concern (PHEIC).\n\nMethodData were collected between February 2015 and May 2016 using a computer-assisted telephone interviewing system on a random sample of 567 people from the general Malaysian population aged above 18 years from randomly selected households.\n\nResultsThe median scale score for perceived severity of ZIKV was 3 (interquartile range [IQR] 1-5) versus 4 (IQR 3-5) for dengue (P<0.001). The majority perceived dengue as being more severe than ZIKV (41.6%). Having friends or acquaintances that had died from dengue was significantly associated with higher perceived severity of ZIKV than dengue (odds ratio [OR] 1.913 [95% confidence interval (CI) 1.032-3.547]). The scores for mosquito control practices before and after ZIKV was declared a PHEIC were similar, at 4 (IQR 3-5). Multivariate analysis revealed that participants with a higher score for perception of severity of ZIKV were more likely to report greater mosquito control practices after the declaration of the PHEIC (OR 1.822 [95% CI 1.107-2.998]).\n\nConclusionsThe emerging ZIKV pandemic requires concerted efforts to enhance mosquito control practices among the Malaysian public. Efforts to improve public mosquito control practices should focus on enhancing the perception of the severity of ZIKV.\n\nAuthor summaryInvestigation of the public perception of the severity of the re-emergence of Zika virus (ZIKV) in Malaysia, a dengue-endemic country, is of immense importance. It is also vital to know whether the public has heightened their mosquito prevention practices after the declaration of ZIKV as a Public Health Emergency of International Concern (PHEIC). The aim of this study was to explore the differences in 1) the perception of severity towards ZIKV infection and dengue fever, and 2) mosquito control practices before and after the ZIKV outbreak was declared a PHEIC. Findings showed that the public has a lower perception of severity of ZIKV than of dengue. Mosquito prevention practices were the same before and after the declaration of a PHEIC. People with a higher perception of severity of ZIKV reported higher mosquito control practices after the declaration of a PHEIC. The emerging ZIKV pandemic requires concerted efforts to enhance mosquito control practices among the Malaysian public. Efforts to improve public mosquito control practices should focus on enhancing the perception of severity of the ZIKV.

Epidemiology↗

bioRxiv2016

Ending AIDS: Progress and prospects for the control of HIV and TB in South Africa

We assess the prospects for ending AIDS in South Africa using a dynamical model to fit data on time trends in HIV prevalence and anti-retroviral treatment (ART) coverage for adults. We estimate current and project future trends in HIV incidence, prevalence and AIDS related deaths, in ART coverage and incidence, and in TB notification rates. We consider two scenarios: constant effort under which people continue to be started on treatment at the current rate and expanded treatment and prevention under which testing rates are increased, everyone is started on treatment as soon as they are found to be infected with HIV, and voluntary medical male circumcision, pre-exposure prophylaxis and condom distribution programmes are expanded.\n\nAs a result of the roll-out of ART the incidence of HIV has fallen from a peak of 2.3% per annum in 1996 to 0.65% in 2016, the AIDS related mortality from a peak of 1.4% per annum in 2006 to 0.37% p.a. in 2016 and both continue to fall at a relative rate of 17% p.a. Maintaining a policy of constant effort will lead to further declines in HIV incidence, AIDS related mortality and TB notification rates but will not end AIDS. Implementing a policy of expanded treatment and prevention in September 2016 should ensure that by 2020 new infections and deaths will be less than one per thousand adults and the UNAIDS Goal of Ending AIDS by 2030 will be reached. Scaling up voluntary medical male circumcision, pre-exposure prophylaxis and condom availability will avert some new infections but will save relatively few lives. Nevertheless, equity demands that people at very high risk of infection including commercial sex-workers, men-who-have-sex-with-men and young women should have access to the best available methods of prevention.\n\nThe current cost to the health services of managing HIV and TB among adults in South Africa is about US$2.1 Bn p.a. (0.6% of GDP p.a.) and this will rise to a peak of US$2.7 Bn p.a. in 2018 (0.8% GDP p.a.). As treatment is scaled up and prevention made available to those at high risk, the cost will fall to US$ 1.8 Bn p.a. in 2030 and US$ 1.0 Bn p.a. in 2050 as those that are living with HIV on ART, die of natural causes. The cost of testing people for HIV is never more than about 8% of the total cost and since testing is the sine qua non of treatment it will be essential to invest sufficient resources in testing. The cost of treating tuberculosis is never more than about 10% of the total and since this is the major cause of AIDS related illness and deaths, efforts should be made to optimise TB treatment.\n\nEnding AIDS in the world will depend critically on what happens in South Africa which accounts for 20% of all people living with HIV. The increasing availability of ART has had a major impact on both HIV incidence and AIDS related mortality and universal access to ART is affordable. With the commitment to make treatment available to all those infected with HIV in September 2016, the South African government is well placed to eliminate HIV as a major threat to public health by 2020 and to end AIDS by 2030. Individuals at high risk of infection deserve access to the best available methods of protecting themselves and they will become increasingly important in the final stages of ending the epidemic.

Epidemiology↗