Imperial College London

Dr. Nimalan Arinaminpathy (Nim Pathy)

Faculty of MedicineSchool of Public Health

Reader in Mathematical Epidemiology
 
 
 
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nim.pathy Website

 
 
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Praed StreetSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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54 results found

Arinaminpathy N, Batra D, Maheshwari N, Swaroop K, Sharma L, Sachdeva K, Khaparde S, Rao R, Gupta D, Vadera B, Nair S, Rade K, Kumta S, Dewan Pet al., Tuberculosis treatment in the private healthcare sector in India: an analysis of recent trends and volumes using drug sales data, BMC Infectious Diseases, ISSN: 1471-2334

JOURNAL ARTICLE

Reid MJA, Arinaminpathy N, Bloom A, Bloom BR, Boehme C, Chaisson R, Chin DP, Churchyard G, Cox H, Ditiu L, Dybul M, Farrar J, Fauci AS, Fekadu E, Fujiwara PI, Hallett TB, Hanson CL, Harrington M, Herbert N, Hopewell PC, Ikeda C, Jamison DT, Khan AJ, Koek I, Krishnan N, Motsoaledi A, Pai M, Raviglione MC, Sharman A, Small PM, Swaminathan S, Temesgen Z, Vassall A, Venkatesan N, van Weezenbeek K, Yamey G, Agins BD, Alexandru S, Andrews JR, Beyeler N, Bivol S, Brigden G, Cattamanchi A, Cazabon D, Crudu V, Daftary A, Dewan P, Doepel LK, Eisinger RW, Fan V, Fewer S, Furin J, Goldhaber-Fiebert JD, Gomez GB, Graham SM, Gupta D, Kamene M, Khaparde S, Mailu EW, Masini EO, McHugh L, Mitchell E, Moon S, Osberg M, Pande T, Prince L, Rade K, Rao R, Remme M, Seddon JA, Selwyn C, Shete P, Sachdeva KS, Stallworthy G, Vesga JF, Vilc V, Goosby EPet al., 2019, Building a tuberculosis-free world: The Lancet Commission on tuberculosis, The Lancet, Vol: 393, Pages: 1331-1384, ISSN: 0140-6736

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Vesga JF, Hallett TB, Reid MJA, Sachdeva KS, Rao R, Khaparde S, Dave P, Rade K, Kamene M, Omesa E, Masini E, Omale N, Onyango E, Owiti P, Karanja M, Kiplimo R, Alexandru S, Vilc V, Crudu V, Bivol S, Celan C, Arinaminpathy Net al., 2019, Assessing tuberculosis control priorities in high-burden settings: a modelling approach, The Lancet Global Health, ISSN: 2214-109X

BackgroundIn the context of WHO's End TB strategy, there is a need to focus future control efforts on those interventions and innovations that would be most effective in accelerating declines in tuberculosis burden. Using a modelling approach to link the tuberculosis care cascade to transmission, we aimed to identify which improvements in the cascade would yield the greatest effect on incidence and mortality.MethodsWe engaged with national tuberculosis programmes in three country settings (India, Kenya, and Moldova) as illustrative examples of settings with a large private sector (India), a high HIV burden (Kenya), and a high burden of multidrug resistance (Moldova). We collated WHO country burden estimates, routine surveillance data, and tuberculosis prevalence surveys from 2011 (for India) and 2016 (for Kenya). Linking the tuberculosis care cascade to tuberculosis transmission using a mathematical model with Bayesian melding in each setting, we examined which cascade shortfalls would have the greatest effect on incidence and mortality, and how the cascade could be used to monitor future control efforts.FindingsModelling suggests that combined measures to strengthen the care cascade could reduce cumulative tuberculosis incidence by 38% (95% Bayesian credible intervals 27–43) in India, 31% (25–41) in Kenya, and 27% (17–41) in Moldova between 2018 and 2035. For both incidence and mortality, modelling suggests that the most important cascade losses are the proportion of patients visiting the private health-care sector in India, missed diagnosis in health-care settings in Kenya, and drug sensitivity testing in Moldova. In all settings, the most influential delay is the interval before a patient's first presentation for care. In future interventions, the proportion of individuals with tuberculosis who are on high-quality treatment could offer a more robust monitoring tool than routine notifications of tuberculosis.InterpretationLinked to transmission

JOURNAL ARTICLE

Arinaminpathy N, Deo S, Singh S, Khaparde S, Rao R, Vadera B, Kulshrestha N, Gupta D, Rade K, Nair SA, Dewan Pet al., 2019, Modelling the impact of effective private provider engagement on tuberculosis control in urban India, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322

JOURNAL ARTICLE

Subbaraman R, Nathavitharana RR, Mayer KH, Satyanarayana S, Chadha VK, Arinaminpathy N, Pai Met al., 2019, Constructing care cascades for active tuberculosis: A strategy for program monitoring and identifying gaps in quality of care, PLoS Medicine, Vol: 16, ISSN: 1549-1277

The cascade of care is a model for evaluating patient retention across sequential stages of care required to achieve a successful treatment outcome. This approach was first used to evaluate HIV care and has since been applied to other diseases. The tuberculosis (TB) community has only recently started using care cascade analyses to quantify gaps in quality of care. In this article, we describe methods for estimating gaps (patient losses) and steps (patients retained) in the care cascade for active TB disease. We highlight approaches for overcoming challenges in constructing the TB care cascade, which include difficulties in estimating the population-level burden of disease and the diagnostic gap due to the limited sensitivity of TB diagnostic tests. We also describe potential uses of this model for evaluating the impact of interventions to improve case finding, diagnosis, linkage to care, retention in care, and post-treatment monitoring of TB patients.

JOURNAL ARTICLE

Arinaminpathy N, Deo S, Singh S, Khaparde S, Rao R, Vadera B, Kulshrestha N, Gupta D, Rade K, Nair SA, Dewan Pet al., 2018, Delays, behaviour and transmission: modelling the impact of effective private provider engagement on tuberculosis control in urban India, Publisher: Cold Spring Harbor Laboratory

<jats:p>In India, the country with the world's largest burden of tuberculosis (TB), most patients first seek care in the private healthcare sector, which is fragmented and unregulated. Ongoing initiatives are demonstrating effective approaches for engaging with this sector, and form a central part of India's recent National Strategic Plan: here we aimed to address their potential impact on TB transmission in urban settings, when taken to scale. We developed a mathematical model of TB transmission dynamics, calibrated to urban populations in Mumbai and Patna, two major cities in India where pilot interventions are currently ongoing. We found that, when taken to sufficient scale to capture 75% of patient-provider interactions, the intervention could reduce incidence by upto 21.3% (95% Bayesian credible interval (CrI) 13.0 - 32.5%) and 15.8% (95% CrI 7.8 - 28.2%) in Mumbai and Patna respectively, between 2018 and 2025. There is a stronger impact on TB mortality, with a reduction of up to 38.1% (95% CrI 20.0 - 55.1%) in the example of Mumbai. The incidence impact of this intervention alone may be limited by the amount of transmission that has already occurred by the time a patient first presents for care: model estimates suggest an initial patient delay of 4-5 months before first seeking care, followed by a diagnostic delay of 1-2 months before ultimately initiating TB treatment. Our results suggest that the transmission impact of such interventions could be maximised by additional measures to encourage early uptake of TB services.</jats:p>

WORKING PAPER

Trauer JM, Dodd PJ, Gomes MGM, Gomez GB, Houben RM, McBryde ES, Melsew YA, Menzies NA, Arinaminpathy N, Shrestha S, Dowdy DWet al., 2018, The Importance of Heterogeneity to the Epidemiology of Tuberculosis., Clin Infect Dis

Although less well-recognised than for other infectious diseases, heterogeneity is a defining feature of TB epidemiology. To advance toward TB elimination, this heterogeneity must be better understood and addressed. Drivers of heterogeneity in TB epidemiology act at the level of the infectious host, organism, susceptible host, environment and distal determinants. These effects may be amplified by social mixing patterns, while the variable latent period between infection and disease may mask heterogeneity in transmission. Reliance on notified cases may lead to misidentification of the most affected groups, as case detection is often poorest where prevalence is highest. Assuming average rates apply across diverse groups and ignoring the effects of cohort selection may result in misunderstanding of the epidemic and the anticipated effects of control measures. Given this substantial heterogeneity, interventions targeting high-risk groups based on location, social determinants or comorbidities could improve efficiency, but raise ethical and equity considerations.

JOURNAL ARTICLE

Tlhajoane M, Masoka T, Mpandaguta E, Rhead R, Church K, Wringe A, Kadzura N, Arinaminpathy N, Nyamukapa C, Schur N, Mugurungi O, Skovdal M, Eaton J, Gregson Set al., 2018, A longitudinal review of national HIV policy and progress made in health facility implementation in eastern Zimbabwe, Health Research Policy and Systems, Vol: 16, ISSN: 1478-4505

BackgroundIn recent years, WHO has made major changes to its guidance on the provision of HIV care and treatment services. We conducted a longitudinal study from 2013 to 2015 to establish how these changes have been translated into national policy in Zimbabwe and to measure progress in implementation within local health facilities.MethodsNational HIV programme policy guidelines published between 2003 and 2013 (n = 9) and 2014 and 2015 (n = 5) were reviewed to assess adoption of WHO recommendations on HIV testing services, prevention of mother-to-child transmission (PMTCT) of HIV, and provision of antiretroviral therapy (ART). Changes in local implementation of these policies over time were measured in two rounds of a survey conducted at 36 health facilities in Eastern Zimbabwe in 2013 and 2015.ResultsHigh levels of adoption of WHO guidance into national policy were recorded, including adoption of new recommendations made in 2013–2015 to introduce PMTCT Option B+ and to increase the threshold for ART initiation from CD4 ≤ 350 cells/mm3 to ≤ 500 cells/mm3. New strategies to implement national HIV policies were introduced such as the decentralisation of ART services from hospitals to clinics and task-shifting of care from doctors to nurses. The proportions of health facilities offering free HIV testing and counselling, PMTCT (including Option B+) and ART services increased substantially from 2013 to 2015, despite reductions in numbers of health workers. Provision of provider-initiated HIV testing remained consistently high. At least one test-kit stock-out in the prior year was reported in most facilities (2013: 69%; 2015: 61%; p = 0.44). Stock-outs of first-line ART and prophylactic drugs for opportunistic infections remained low. Repeat testing for HIV-negative individuals within 3 months decreased (2013: 97%; 2015: 72%; p = 0.01). Laboratory testing remained low across both surve

JOURNAL ARTICLE

Fu H, Lin H-H, Hallett TB, Arinaminpathy Net al., 2018, Modelling the effect of discontinuing universal Bacillus Calmette-Guérin vaccination in an intermediate tuberculosis burden setting, Vaccine, Vol: 36, Pages: 5902-5909, ISSN: 0264-410X

BackgroundBacillus Calmette-Guérin (BCG) vaccination is a widely-used public health intervention for tuberculosis (TB) control. In Taiwan, like other intermediate TB burden settings, steadily declining TB incidence raises important questions on whether universal BCG vaccination should be discontinued. Recent surveys on adverse events following immunisation, such as BCG-induced osteomyelitis/osteitis, also suggest a need to re-evaluate the vaccination programme.MethodsWe developed an age-structured transmission dynamic model, calibrated to population demography and age-specific TB notification rates in Taiwan. We adopted ‘weak-protection’ and ‘strong-protection’ scenarios, representing a range of characteristics including the duration of BCG protection and vaccine efficacies against TB infection and progression. We estimated averted disability-adjusted life years (DALYs) and incremental costs over 10 years after discontinuing universal BCG vaccination in 2018, 2035, and 2050. We also examined the potential impact of ‘surveillance-guided’ discontinuation, triggered once notification rates fall to a given threshold.ResultsIn the weak-protection scenario, discontinuing BCG would result in 2.8 (95% uncertainty range: 2.3, 3.1) additional notified TB cases and −4.1 (−7.7, 0.8) net averted DALYs over 2018–2027. In the strong-protection scenario, 82.9 (72.6, 91.6) additional cases and −402.7 (−506.6, −301.2) averted DALYs would be reported, suggesting a robustly negative health impact. However, in this vaccine scenario, there could be an overall health benefit if BCG is discontinued once TB notification falls below 5 per 100,000 population. The most influential vaccine characteristic for the net health impact is the vaccine efficacy against progression to pulmonary TB. In financial terms, the eliminated cost of the vaccination programme substantially outweighed the incremental cost for TB treatme

JOURNAL ARTICLE

Braham C, White P, Arinaminpathy N, 2018, Management of tuberculosis by healthcare practitioners in Pakistan: A systematic review, PLoS ONE, Vol: 13, ISSN: 1932-6203

Objective:To assess the quality of tuberculosis (TB) care in Pakistan, through determining comparison of healthcare practitioners’ knowledge and practices to national and international TB care guidelines.Methods:Studies reporting on knowledge, attitudes and practices of public and private practitioners with TB patients were selected through searching electronic databases and grey literature.Findings:Of 1458 reports, 20 full-texts were assessed, of which 11 met the eligibility and quality criteria; all studies focused on private sector care. Heterogeneity precluded meta-analysis. In 3 of 4 studies, over 50% of practitioners correctly identified a cough as the main TB symptom. However, 4 out of 6 studies showed practitioners’ compliance to be low (under 50%) for the use of sputum microscopy in diagnosis. The poorest quality care occurred in the later stages of treatment, with low compliance in prescribing practices for continuation-phase care and in monitoring and recording treatment progress, the latter of which is particularly critical for treatment success.Conclusion:TB care was variable and generally inadequate, with both a lack of knowledge and a small ‘know-do’ gap evident—practitioners did not use methods that they know they should use. A lack of recent evidence found suggests that the quality of current practices may not be fully captured and further research is needed, especially on non-allopathic, rural and public-sector contexts. Improved training of practitioners, greater availability of recommended diagnostic tools and expansion of public-private partnerships are suggestions for improving the quality of TB care in Pakistan.

JOURNAL ARTICLE

Pandey S, Chadha VK, Laxminarayan R, Arinaminpathy Net al., 2017, Estimating tuberculosis incidence from primary survey data: a mathematical modeling approach, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 21, Pages: 366-374, ISSN: 1027-3719

BACKGROUND: There is an urgent need for improved estimations of the burden of tuberculosis (TB).OBJECTIVE: To develop a new quantitative method based on mathematical modelling, and to demonstrate its application to TB in India.DESIGN: We developed a simple model of TB transmission dynamics to estimate the annual incidence of TB disease from the annual risk of tuberculous infection and prevalence of smear-positive TB. We first compared model estimates for annual infections per smear-positive TB case using previous empirical estimates from China, Korea and the Philippines. We then applied the model to estimate TB incidence in India, stratified by urban and rural settings.RESULTS: Study model estimates show agreement with previous empirical estimates. Applied to India, the model suggests an annual incidence of smear-positive TB of 89.8 per 100 000 population (95%CI 56.8–156.3). Results show differences in urban and rural TB: while an urban TB case infects more individuals per year, a rural TB case remains infectious for appreciably longer, suggesting the need for interventions tailored to these different settings.CONCLUSIONS: Simple models of TB transmission, in conjunction with necessary data, can offer approaches to burden estimation that complement those currently being used.

JOURNAL ARTICLE

Pandey S, Chadha VK, Laxminarayan R, Arinaminpathy Net al., 2017, Estimating tuberculosis incidence from primary survey data: a mathematical modeling approach., Int J Tuberc Lung Dis, Vol: 21, Pages: 366-374

BACKGROUND: There is an urgent need for improved estimations of the burden of tuberculosis (TB). OBJECTIVE: To develop a new quantitative method based on mathematical modelling, and to demonstrate its application to TB in India. DESIGN: We developed a simple model of TB transmission dynamics to estimate the annual incidence of TB disease from the annual risk of tuberculous infection and prevalence of smear-positive TB. We first compared model estimates for annual infections per smear-positive TB case using previous empirical estimates from China, Korea and the Philippines. We then applied the model to estimate TB incidence in India, stratified by urban and rural settings. RESULTS: Study model estimates show agreement with previous empirical estimates. Applied to India, the model suggests an annual incidence of smear-positive TB of 89.8 per 100 000 population (95%CI 56.8-156.3). Results show differences in urban and rural TB: while an urban TB case infects more individuals per year, a rural TB case remains infectious for appreciably longer, suggesting the need for interventions tailored to these different settings. CONCLUSIONS: Simple models of TB transmission, in conjunction with necessary data, can offer approaches to burden estimation that complement those currently being used.

JOURNAL ARTICLE

Arinaminpathy N, Kim IK, Gargiullo P, Haber M, Foppa IM, Gambhir M, Bresee Jet al., 2017, Estimating Direct and Indirect Protective Effect of Influenza Vaccination in the United States., American Journal of Epidemiology, Vol: 186, Pages: 92-100, ISSN: 1476-6256

With influenza vaccination rates in the United States recently exceeding 45% of the population, it is important to understand the impact that vaccination is having on influenza transmission. In this study, we used a Bayesian modeling approach, combined with a simple dynamical model of influenza transmission, to estimate this impact. The combined framework synthesized evidence from a range of data sources relating to influenza transmission and vaccination in the United States. We found that, for seasonal epidemics, the number of infections averted ranged from 9.6 million in the 2006-2007 season (95% credible interval (CI): 8.7, 10.9) to 37.2 million (95% CI: 34.1, 39.6) in the 2012-2013 season. Expressed in relative terms, the proportion averted ranged from 20.8% (95% CI: 16.8, 24.3) of potential infections in the 2011-2012 season to 47.5% (95% CI: 43.7, 50.8) in the 2008-2009 season. The percentage averted was only 1.04% (95% CI: 0.15, 3.2) for the 2009 H1N1 pandemic, owing to the late timing of the vaccination program in relation to the pandemic in the Northern hemisphere. In the future, further vaccination coverage, as well as improved influenza vaccines (especially those offering better protection in the elderly), could have an even stronger effect on annual influenza epidemics.

JOURNAL ARTICLE

Yuan H-Y, Baguelin M, Kwok KO, Arinaminpathy N, van Leeuwen E, Riley Set al., 2017, The impact of stratified immunity on the transmission dynamics of influenza, Epidemics, Vol: 20, Pages: 84-93, ISSN: 1755-4365

Although empirical studies show that protection against influenza infection in humans is closely related to antibody titres, influenza epidemics are often described under the assumption that individuals are either susceptible or not. Here we develop a model in which antibody titre classes are enumerated explicitly and mapped onto a variable scale of susceptibility in different age groups. Fitting only with pre- and post-wave serological data during 2009 pandemic in Hong Kong, we demonstrate that with stratified immunity, the timing and the magnitude of the epidemic dynamics can be reconstructed more accurately than is possible with binary seropositivity data. We also show that increased infectiousness of children relative to adults and age-specific mixing are required to reproduce age-specific seroprevalence observed in Hong Kong, while pre-existing immunity in the elderly is not. Overall, our results suggest that stratified immunity in an aged-structured heterogeneous population plays a significant role in determining the shape of influenza epidemics.

JOURNAL ARTICLE

Mandal S, Chadha VK, Laxminarayan R, Arinaminpathy Net al., 2017, Counting the lives saved by DOTS in India: a model-based approach, BMC MEDICINE, Vol: 15, ISSN: 1741-7015

Background:Against the backdrop of renewed efforts to control tuberculosis (TB) worldwide, there is a need for improved methods to estimate the public health impact of TB programmes. Such methods should not only address the improved outcomes amongst those receiving care but should also account for the impact of TB services on reducing transmission.Methods:Vital registration data in India are not sufficiently reliable for estimates of TB mortality. As an alternative approach, we developed a mathematical model of TB transmission dynamics and mortality, capturing the scale-up of DOTS in India, through the rollout of the Revised National TB Control Programme (RNTCP). We used available data from the literature to calculate TB mortality hazards amongst untreated TB; amongst cases treated under RNTCP; and amongst cases treated under non-RNTCP conditions. Using a Bayesian evidence synthesis framework, we combined these data with current estimates for the TB burden in India to calibrate the transmission model. We simulated the national TB epidemic in the presence and absence of the DOTS programme, measuring lives saved as the difference in TB deaths between these scenarios.Results:From 1997 to 2016, India’s RNTCP has saved 7.75 million lives (95% Bayesian credible interval 6.29–8.82 million). We estimate that 42% of this impact was due to the ‘indirect’ effects of the RNTCP in averting transmission as well as improving treatment outcomes.Conclusions:When expanding high-quality TB services, a substantial proportion of overall impact derives from preventive, as well as curative, benefits. Mathematical models, together with sufficient data, can be a helpful tool in estimating the true population impact of major disease control programmes.

JOURNAL ARTICLE

Subramaniam R, Graham A, Grenfell B, Arinaminpathy Net al., 2016, Universal or specific? A modeling-based comparison of broad-spectrum influenza vaccines against conventional, strain-matched vaccines, Plos Computational Biology, Vol: 12, ISSN: 1553-7358

Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to beupdated continually to keep up to date with this antigenic change, but emerging ‘universal’ vaccines –targeting more conserved components of the influenza virus –offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compareagainst similar mass programmes utilizing conventional vaccines?Specifically, how might novel and conventional vaccines compare,in terms of cumulative incidence andrates of antigenic evolution of seasonal influenza?What are theirpotential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenicevolution of influenzain a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy,universal vaccinescould dampen population-level transmissionover several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunityin the population,conventional vaccines could allow the increasedspread of a novel pandemic strain. Conversely, universal vaccines couldmitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage,the duration and breadth of immunity raised by universal vaccines arecritical determinants of their performance relative toconventional vaccines. In future,conventionaland novelvaccines are likely to play complementary roles in vaccination strategies

JOURNAL ARTICLE

Arinaminpathy N, Dewan P, 2016, Tuberculosis burden in India's private sector Reply, LANCET INFECTIOUS DISEASES, Vol: 16, Pages: 1329-1329, ISSN: 1473-3099

JOURNAL ARTICLE

Houben RM, Menzies NA, Sumner T, Huynh GH, Arinaminpathy N, Goldhaber-Fiebert JD, Lin HH, Wu CY, Mandal S, Pandey S, Suen SC, Bendavid E, Azman AS, Dowdy DW, Bacaër N, Rhines AS, Feldman MW, Handel A, Whalen CC, Chang ST, Wagner BG, Eckhoff PA, Trauer JM, Denholm JT, McBryde ES, Cohen T, Salomon JA, Pretorius C, Lalli M, Eaton JW, Boccia D, Hosseini M, Gomez GB, Sahu S, Daniels C, Ditiu L, Chin DP, Wang L, Chadha VK, Rade K, Dewan P, Hippner P, Charalambous S, Grant AD, Churchyard G, Pillay Y, Mametja LD, Kimerling ME, Vassall A, White RGet al., 2016, Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models, Lancet Global Health, Vol: 4, Pages: e806-e815, ISSN: 2214-109X

BACKGROUND: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. METHODS: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. FINDINGS: Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. INTERPRETATION: Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB S

JOURNAL ARTICLE

Menzies NA, Gomez GB, Bozzani F, Chatterjee S, Foster N, Baena IG, Laurence YV, Qiang S, Siroka A, Sweeney S, Verguet S, Arinaminpathy N, Azman AS, Bendavid E, Chang ST, Cohen T, Denholm JT, Dowdy DW, Eckhoff PA, Goldhaber-Fiebert JD, Handel A, Huynh GH, Lalli M, Lin HH, Mandal S, McBryde ES, Pandey S, Salomon JA, Suen SC, Sumner T, Trauer JM, Wagner BG, Whalen CC, Wu CY, Boccia D, Chadha VK, Charalambous S, Chin DP, Churchyard G, Daniels C, Dewan P, Ditiu L, Eaton JW, Grant AD, Hippner P, Hosseini M, Mametja D, Pretorius C, Pillay Y, Rade K, Sahu S, Wang L, Houben RM, Kimerling ME, White RG, Vassall Aet al., 2016, Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models, Lancet Global Health, Vol: 4, Pages: e816-e826, ISSN: 2214-109X

BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation.

JOURNAL ARTICLE

Arinaminpathy N, Batra D, Khaparde S, Vualnam T, Maheshwari N, Sharma L, Nair SA, Dewan Pet al., 2016, The number of privately treated tuberculosis cases in India: an estimation from drug sales data, Lancet Infectious Diseases, Vol: 16, Pages: 1255-1260, ISSN: 1473-3099

BackgroundUnderstanding the amount of tuberculosis managed by the private sector in India is crucial to understanding the true burden of the disease in the country, and thus globally. In the absence of quality surveillance data on privately treated patients, commercial drug sales data offer an empirical foundation for disease burden estimation.MethodsWe used a large, nationally representative commercial dataset on sales of 189 anti-tuberculosis products available in India to calculate the amount of anti-tuberculosis treatment in the private sector in 2013–14. We corrected estimates using validation studies that audited prescriptions against tuberculosis diagnosis, and estimated uncertainty using Monte Carlo simulation. To address implications for numbers of patients with tuberculosis, we explored varying assumptions for average duration of tuberculosis treatment and accuracy of private diagnosis.FindingsThere were 17·793 million patient-months (95% credible interval 16·709 million to 19·841 million) of anti-tuberculosis treatment in the private sector in 2014, twice as many as the public sector. If 40–60% of private-sector tuberculosis diagnoses are correct, and if private-sector tuberculosis treatment lasts on average 2–6 months, this implies that 1·19–5·34 million tuberculosis cases were treated in the private sector in 2014 alone. The midpoint of these ranges yields an estimate of 2·2 million cases, two to three times higher than currently assumed.InterpretationIndia's private sector is treating an enormous number of patients for tuberculosis, appreciably higher than has been previously recognised. Accordingly, there is a re-doubled need to address this burden and to strengthen surveillance. Tuberculosis burden estimates in India and worldwide require revision.

JOURNAL ARTICLE

Hastings DL, Tokars JI, Aziz IZAMA, Alkhaldi KZ, Bensadek AT, Alraddadi BM, Jokhdar H, Jernigan JA, Garout MA, Tomczyk SM, Oboho LK, Geller AI, Arinaminpathy N, Swerdlow DL, Madani TAet al., 2016, Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014, Emerging Infectious Diseases, Vol: 22, Pages: 794-801, ISSN: 1080-6059

During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks.

JOURNAL ARTICLE

Nair SA, Raizada N, Sachdeva KS, Denkinger C, Schumacher S, Dewan P, Kulsange S, Boehme C, Paramsivan CN, Arinaminpathy Net al., 2016, Factors Associated with Tuberculosis and Rifampicin-Resistant Tuberculosis amongst Symptomatic Patients in India: A Retrospective Analysis, PLOS One, Vol: 11, ISSN: 1932-6203

BackgroundTuberculosis remains a major public health challenge for India. Various studies have documented different levels of TB and multi-drug resistant (MDR) TB among diverse groups of the population. In view of renewed targets set under the End TB strategy by 2035, there is an urgent need for TB diagnosis to be strengthened. Drawing on data from a recent, multisite study, we address key questions for TB diagnosis amongst symptomatics presenting for care: are there subgroups of patients that are more likely than others, to be positive for TB? In turn, amongst these positive cases, are there factors—apart from treatment history—that may be predictive for multi-drug resistance?MethodsWe used data from a multi-centric prospective demonstration study, conducted from March 2012 to December 2013 in 18 sub-district level TB programme units (TUs) in India and covering a population of 8.8 million. In place of standard diagnostic tests, upfront Xpert MTB/RIF testing was offered to all presumptive TB symptomatics. Here, using data from this study, we used logistic regression to identify association between risk factors and TB and Rifampicin-Resistant TB among symptomatics enrolled in the study.ResultsWe find that male gender; history of TB treatment; and adult age compared with either children or the elderly are risk factors associated with high TB detection amongst symptomatics, across the TUs. While treatment history is found be a significant risk factor for rifampicin-resistant TB, elderly (65+ yrs) people have significantly lower risk than other age groups. However, pediatric TB cases have no less risk of rifampicin resistance as compared with adults (OR 1.23 (95% C.I. 0.85–1.76)). Similarly, risk of rifampicin resistance among both the genders was the same. These patterns applied across the study sites involved. Notably in Mumbai, amongst those patients with microbiological confirmation of TB, female patients showed a higher risk of having MDR-TB than

JOURNAL ARTICLE

Arinaminpathy N, Dowdy D, 2015, Understanding the incremental value of novel diagnostic tests for tuberculosis, Nature, Vol: 528, Pages: S60-S67, ISSN: 0028-0836

Tuberculosis is a major source of global mortality caused by infection, partly because of a tremendous ongoing burden of undiagnosed disease. Improved diagnostic technology may play an increasingly crucial part in global efforts to end tuberculosis, but the ability of diagnostic tests to curb tuberculosis transmission is dependent on multiple factors, including the time taken by a patient to seek health care, the patient's symptoms, and the patterns of transmission before diagnosis. Novel diagnostic assays for tuberculosis have conventionally been evaluated on the basis of characteristics such as sensitivity and specificity, using assumptions that probably overestimate the impact of diagnostic tests on transmission. We argue for a shift in focus to the evaluation of such tests' incremental value, defining outcomes that reflect each test's purpose (for example, transmissions averted) and comparing systems with the test against those without, in terms of those outcomes. Incremental value can also be measured in units of outcome per incremental unit of resource (for example, money or human capacity). Using a novel, simplified model of tuberculosis transmission that addresses some of the limitations of earlier tuberculosis diagnostic models, we demonstrate that the incremental value of any novel test depends not just on its accuracy, but also on elements such as patient behaviour, tuberculosis natural history and health systems. By integrating these factors into a single unified framework, we advance an approach to the evaluation of new diagnostic tests for tuberculosis that considers the incremental value at the population level and demonstrates how additional data could inform more-effective implementation of tuberculosis diagnostic tests under various conditions.

JOURNAL ARTICLE

Sachdeva KS, Raizada N, Gupta RS, Nair SA, Denkinger C, Paramasivan CN, Kulsange S, Thakur R, Dewan P, Boehme C, Arinaminpathy Net al., 2015, The potential impact of up-front drug sensitivity testing on India's epidemic of multi-drug resistant tuberculosis, PLOS One, Vol: 10, ISSN: 1932-6203

BackgroundIn India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects.ResultsWe find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 – 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

JOURNAL ARTICLE

Sachdeva KS, Raizada N, Sreenivas A, van't Hoog AH, van den Hof S, Dewan PK, Thakur R, Gupta RS, Kulsange S, Vadera B, Babre A, Gray C, Parmar M, Ghedia M, Ramachandran R, Alavadi U, Arinaminpathy N, Denkinger C, Boehme C, Paramasivan CNet al., 2015, Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India, PLOS One, Vol: 10, ISSN: 1932-6203

BackgroundXpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India.MethodsThis demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates.ResultsIn the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST.ConclusionIntroduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-noti

JOURNAL ARTICLE

Heesterbeek H, Anderson RM, Andreasen V, Bansal S, De Angelis D, Dye C, Eames KTD, Edmunds WJ, Frost SDW, Funk S, Hollingsworth TD, House T, Isham V, Klepac P, Lessler J, Lloyd-Smith JO, Metcalf CJE, Mollison D, Pellis L, Pulliam JRC, Roberts MG, Viboud Cet al., 2015, Modeling infectious disease dynamics in the complex landscape of global health, SCIENCE, Vol: 347, Pages: 1216-U29, ISSN: 0036-8075

JOURNAL ARTICLE

Arinaminpathy N, Cordier-Lassalle T, Lunte K, Dye Cet al., 2015, The Global Drug Facility as an intervention in the market for tuberculosis drugs, Bulletin of the World Health Organization, Vol: 93, Pages: 237-248, ISSN: 1564-0604

Objective To investigate funding for the Global Drug Facility since 2001 and to analyse the facility’s influence on the price of high-qualitytuberculosis drugs.Methods Data on the price of tuberculosis drugs were obtained from the Global Drug Facility for 2001 to 2012 and, for the private sectorin 15 countries, from IMS Health for 2002 to 2012. Data on funding of the facility were also collected.Findings Quality-assured tuberculosis drugs supplied by the Global Drug Facility were generally priced lower than drugs purchased inthe private sector. In 2012, just three manufacturers accounted for 29.9 million United Stated dollars (US$) of US$ 44.5 million by valueof first-line drugs supplied. The Global Fund to Fight AIDS, Tuberculosis and Malaria provided 73% (US$ 32.5 million of US$ 44.5 million)and 89% (US$ 57.8 million of US $65.2 million) of funds for first- and second-line drugs, respectively. Between 2010 and 2012, the facility’smarket share of second-line tuberculosis drugs increased from 26.1% to 42.9%, while prices decreased by as much as 24% (from US$ 1231to US$ 939). Conversely, the facility’s market share of first-line drugs fell from 37.2% to 19.2% during this time, while prices increased fromUS$ 9.53 to US$ 10.2.Conclusion The price of tuberculosis drugs supplied through the facility was generally less than that on the private market. However, torealize its full potential and meet the needs of more tuberculosis patients, the facility requires more diverse and stable public funding andgreater flexibility to participate in the private market.

JOURNAL ARTICLE

Mandal S, Arinaminpathy N, 2015, Transmission modeling and health systems: the case of TB in India, INTERNATIONAL HEALTH, Vol: 7, Pages: 114-120, ISSN: 1876-3413

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Kouyos RD, Metcalf CJE, Birger R, Klein EY, zur Wiesch PA, Ankomah P, Arinaminpathy N, Bogich TL, Bonhoeffer S, Brower C, Chi-Johnston G, Cohen T, Day T, Greenhouse B, Huijben S, Metlay J, Mideo N, Pollitt LC, Read AF, Smith DL, Standley C, Wale N, Grenfell Bet al., 2014, The path of least resistance: aggressive or moderate treatment?, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 281, ISSN: 0962-8452

JOURNAL ARTICLE

Faria NR, Rambaut A, Suchard MA, Baele G, Bedford T, Ward MJ, Tatem AJ, Sousa JD, Arinaminpathy N, Pepin J, Posada D, Peeters M, Pybus OG, Lemey Pet al., 2014, The early spread and epidemic ignition of HIV-1 in human populations, SCIENCE, Vol: 346, Pages: 56-61, ISSN: 0036-8075

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