41 results on '"Thindwa, D."'
Search Results
2. Effect of patient-delivered household contact tracing and prevention for tuberculosis: A household cluster-randomised trial in Malawi
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Kaswaswa, K, MacPherson, P, Kumwenda, M, Mpunga, J, Thindwa, D, Nliwasa, M, Mwapasa, M, Odland, J, Tomoka, T, Chipungu, G, Mukaka, M, and Corbett, EL
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Adult ,Family Characteristics ,Malawi ,Multidisciplinary ,Adolescent ,Child, Preschool ,Isoniazid ,Humans ,Tuberculosis ,Contact Tracing ,Child - Abstract
Background Household contact tracing provides TB screening and TB preventive therapy (TPT) to contacts at high risk of TB disease. However, it is resource intensive, inconvenient, and often poorly implemented. We investigated a novel model aiming to improve uptake. Methods Between May and December 2014, we randomised patient with TB who consented to participate in the trial to either standard of care (SOC) or intervention (PACTS) arms. Participants randomised to PACTS received one screening/triage tool (adapted from WHO integrated management of adolescent and adult illnesses [IMAI] guidelines) and sputum pots for each reported household contact. The tool guided participants through symptom screening; TPT (6-months of isoniazid) eligibility; and sputum collection for contacts. Patients randomised to SOC were managed in accordance with national guidelines, that is, they received verbal instruction on who to bring to clinics for investigation using national guidelines. Main outcome and measures The primary outcome was the proportion of adult contacts receiving treatment for TB within 3 months of randomisation. Secondary outcomes were the proportions of child contacts under age 5 years (U5Y) who were commenced on, and completed, TPT. Data were analyzed by logistic regression with random effects to adjust for household clustering. Results Two hundred and fourteen index TB participants were block-randomized from two sites (107 PACTS, reporting 418 contacts; and 107 SOC, reporting 420 contacts). Overall, 62.8% of index TB participants were HIV-positive and 52.1% were TB culture-positive. 250 otherwise eligible TB patients declined participation and 6 households (10 PACTS, 6 SOC) were lost to follow-up and were not included in the analysis. By three months, nine contacts (PACTS: 6, [1.4%]; SOC: 3, [0.7%]) had TB diagnosed, with no difference between groups (adjusted odds ratio [aOR]: 2.18, 95% CI: 0.60–7.95). Eligible PACTS contacts (37/96, 38.5%) were more likely to initiate TPT by 3-months compared to SOC contacts (27/101, 26.7%; aOR 2.27, 95% CI: 1.04–4.98). U5Y children in the PACTS arm (47/81 58.0%) were more likely to have initiated TPT before the 3-month visit compared to SOC children (36/89, 41.4%; aOR: 2.31, 95% CI: 1.05–5.06). Conclusions and relevance A household-centred patient-delivered symptom screen and IPT eligibility assessment significantly increased timely TPT uptake among U5Y children, but did not significantly increase TB diagnosis. This model needs to be optimized for acceptability, given low participation, and investigated in other low resource settings. Clinical trial registration TRIAL REGISTRATION NUMBER: ISRCTN81659509 https://www.isrctn.com/ISRCTN81659509?q=&filters=conditionCategory:Respiratory,recruitmentCountry:Malawi,ageRange:Mixed&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search. 19 July 2012.
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- 2022
3. Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study
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Meiring, JE, Shakya, M, Khanam, F, Voysey, M, Phillips, MT, Tonks, S, Thindwa, D, Darton, TC, Dongol, S, Karkey, A, Zaman, K, Baker, S, Dolecek, C, Dunstan, SJ, Dougan, G, Holt, KE, Heyderman, RS, Qadri, F, Pitzer, VE, Basnyat, B, Gordon, MA, Clemens, J, Pollard, AJ, Meiring, JE, Shakya, M, Khanam, F, Voysey, M, Phillips, MT, Tonks, S, Thindwa, D, Darton, TC, Dongol, S, Karkey, A, Zaman, K, Baker, S, Dolecek, C, Dunstan, SJ, Dougan, G, Holt, KE, Heyderman, RS, Qadri, F, Pitzer, VE, Basnyat, B, Gordon, MA, Clemens, J, and Pollard, AJ
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BACKGROUND: Enteric fever is a serious public health concern in many low-income and middle-income countries. Numerous data gaps exist concerning the epidemiology of Salmonella enterica serotype Typhi (S Typhi) and Salmonella enterica serotype Paratyphi (S Paratyphi), which are the causative agents of enteric fever. We aimed to determine the burden of enteric fever in three urban sites in Africa and Asia. METHODS: In this multicentre population-based study, we did a demographic census at three urban sites in Africa (Blantyre, Malawi) and Asia (Kathmandu, Nepal and Dhaka, Bangladesh) between June 1, 2016, and Sept 25, 2018. Households were selected randomly from the demographic census. Participants from within the geographical census area presenting to study health-care facilities were approached for recruitment if they had a history of fever for 72 h or more (later changed to >48 h) or temperature of 38·0°C or higher. Facility-based passive surveillance was done between Nov 11, 2016, and Dec 31, 2018, with blood-culture collection for febrile illness. We also did a community-based serological survey to obtain data on Vi-antibody defined infections. We calculated crude incidence for blood-culture-confirmed S Typhi and S Paratyphi infection, and calculated adjusted incidence and seroincidence of S Typhi blood-culture-confirmed infection. FINDINGS: 423 618 individuals were included in the demographic census, contributing 626 219 person-years of observation for febrile illness surveillance. 624 S Typhi and 108 S Paratyphi A isolates were collected from the blood of 12 082 febrile patients. Multidrug resistance was observed in 44% S Typhi isolates and fluoroquinolone resistance in 61% of S Typhi isolates. In Blantyre, the overall crude incidence of blood-culture confirmed S Typhi was 58 cases per 100 000 person-years of observation (95% CI 48-70); the adjusted incidence was 444 cases per 100 000 person-years of observation (95% credible interval [CrI] 347-717). The corres
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- 2021
4. A Bayesian approach for estimating typhoid fever incidence from large-scale facility-based passive surveillance data
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Phillips, MT, Meiring, JE, Voysey, M, Warren, JL, Baker, S, Basnyat, B, Clemens, JD, Dolecek, C, Dunstan, SJ, Dougan, G, Gordon, MA, Thindwa, D, Heyderman, RS, Holt, KE, Qadri, F, Pollard, AJ, Pitzer, VE, Phillips, MT, Meiring, JE, Voysey, M, Warren, JL, Baker, S, Basnyat, B, Clemens, JD, Dolecek, C, Dunstan, SJ, Dougan, G, Gordon, MA, Thindwa, D, Heyderman, RS, Holt, KE, Qadri, F, Pollard, AJ, and Pitzer, VE
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Decisions about typhoid fever prevention and control are based on estimates of typhoid incidence and their uncertainty. Lack of specific clinical diagnostic criteria, poorly sensitive diagnostic tests, and scarcity of accurate and complete datasets contribute to difficulties in calculating age-specific population-level typhoid incidence. Using data from the Strategic Typhoid Alliance across Africa and Asia program, we integrated demographic censuses, healthcare utilization surveys, facility-based surveillance, and serological surveillance from Malawi, Nepal, and Bangladesh to account for under-detection of cases. We developed a Bayesian approach that adjusts the count of reported blood-culture-positive cases for blood culture detection, blood culture collection, and healthcare seeking-and how these factors vary by age-while combining information from prior published studies. We validated the model using simulated data. The ratio of observed to adjusted incidence rates was 7.7 (95% credible interval [CrI]: 6.0-12.4) in Malawi, 14.4 (95% CrI: 9.3-24.9) in Nepal, and 7.0 (95% CrI: 5.6-9.2) in Bangladesh. The probability of blood culture collection led to the largest adjustment in Malawi, while the probability of seeking healthcare contributed the most in Nepal and Bangladesh; adjustment factors varied by age. Adjusted incidence rates were within or below the seroincidence rate limits of typhoid infection. Estimates of blood-culture-confirmed typhoid fever without these adjustments results in considerable underestimation of the true incidence of typhoid fever. Our approach allows each phase of the reporting process to be synthesized to estimate the adjusted incidence of typhoid fever while correctly characterizing uncertainty, which can inform decision-making for typhoid prevention and control.
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- 2021
5. Completion of isoniazid preventive therapy among human immunodeficiency virus positive adults in urban Malawi
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Thindwa, D, MacPherson, P, Choko, AT, Khundi, M, Sambakunsi, R, Ngwira, LG, Kalua, T, Webb, EL, and Corbett, EL
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sub-Saharan Africa ,AFRICA ,qv_268.5 ,Respiratory System ,wc_503_6 ,wc_503 ,PLACEBO-CONTROLLED TRIAL ,1102 Cardiovascular Medicine And Haematology ,Microbiology ,wa_110 ,DOUBLE-BLIND ,ANTIRETROVIRAL THERAPY ,HIV-INFECTION ,LATENT TUBERCULOSIS INFECTION ,parasitic diseases ,risk factors ,loss to follow-up ,SITES ,wa_30 ,Science & Technology ,prospective ,Infectious Diseases ,TANZANIA ,tuberculosis ,qv_268 ,Life Sciences & Biomedicine - Abstract
SETTING: \ud Despite worldwide scale-up of human immunodeficiency virus (HIV) care services, relatively few countries have implemented isoniazid preventive therapy (IPT). Among other programmatic concerns, IPT completion tends to be low, especially when not fully integrated into HIV care clinics.\ud OBJECTIVE: \ud To estimate non-completion of 6-month IPT and its predictors among HIV-positive adults aged 16 years.\ud DESIGN: \ud A prospective cohort study nested within a cluster-randomised trial of TB prevention was conducted between February 2012 and June 2014. IPT for 6 months was provided with pyridoxine at study clinics. Non-completion was defined as loss to follow-up (LTFU), death, active/presumptive TB or stopping IPT for any other reason. Random-effects logistic regression was used to determine predictors of non-completion.\ud RESULTS: \ud Of 1284 HIV-positive adults initiated on IPT, 885/1280 (69.1%) were female; the median CD4 count was 337 cells/μl (IQR 199-511); 320 (24.9%) did not complete IPT. After controlling for antiretroviral treatment status, IPT initiation year, age and sex, non-completion of IPT was associated with World Health Organization stage 3/4 (aOR 1.76, 95%CI 1.22-2.55), CD4 count 100-349 cells/μl (aOR 1.93, 95%CI 1.10-3.38) and any reported side effects (aOR 22.00, 95%CI 9.45-46.71).\ud CONCLUSION: \ud Completion of IPT was suboptimal. Interventions to further improve retention should target immunosuppressed HIV-positive adults and address side effects.
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- 2018
6. The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys
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Darton, T.C., Meiring, J.E., Tonks, S., Khan, M.A., Khanam, F., Shakya, M., Thindwa, D., Baker, S., Basnyat, B., Clemens, J.D., Dougan, G., Dolecek, C., Dunstan, S.J., Gordon, M.A., Heyderman, R.S., Holt, K.E., Pitzer, V.E., Qadri, F., Zaman, K., Pollard, A.J., STRATAA Study Consortium, ., Meiring, James E [0000-0001-9183-5174], and Apollo - University of Cambridge Repository
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Male ,healthcare utilisation ,Malawi ,Adolescent ,diagnosis ,febrile illness ,education ,infection transmission ,enteric fever ,resource-limited setting ,salmonella typhi ,Cost of Illness ,Nepal ,Seroepidemiologic Studies ,Surveys and Questionnaires ,Humans ,Typhoid Fever ,Child ,Bangladesh ,vaccination programme ,Incidence ,Infant, Newborn ,Infant ,Censuses ,Models, Theoretical ,Patient Acceptance of Health Care ,asia ,salmonella paratyphi a ,serosurveillance ,africa ,Research Design ,Child, Preschool ,Population Surveillance ,Carrier State ,Health Resources ,Female ,seroepidemiology - Abstract
Introduction Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12–27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics.\ud \ud The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies.\ud \ud Methods/design Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers.\ud \ud Ethics and dissemination This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences.\ud \ud Trial registration number ISRCTN 12131979.\ud \ud Ethics references Oxford (Oxford Tropical Research Ethics Committee 39-15).\ud \ud Bangladesh (icddr,b Institutional Review Board PR-15119).\ud \ud Malawi (National Health Sciences Research Committee 15/5/1599).\ud \ud Nepal (Nepal Health Research Council 306/2015).
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- 2017
7. The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys
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Darton, TC, Meiring, JE, Tonks, S, Khan, MA, Khanam, F, Shakya, M, Thindwa, D, Baker, S, Basnyat, B, Clemens, JD, Dougan, G, Dolecek, C, Dunstan, SJ, Gordon, MA, Heyderman, RS, Holt, KE, Pitzer, VE, Qadri, F, Zaman, K, and Pollard, AJ
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SALMONELLA-TYPHI CARRIERS ,healthcare utilisation ,diagnosis ,febrile illness ,infection transmission ,VACCINE ,enteric fever ,CHILDREN ,resource-limited setting ,IMMUNOGENICITY ,salmonella typhi ,Medicine, General & Internal ,VI CONJUGATE ,General & Internal Medicine ,INFECTION ,EPIDEMIOLOGY ,Science & Technology ,vaccination programme ,GLOBAL BURDEN ,asia ,salmonella paratyphi a ,serosurveillance ,africa ,ENDEMIC AREA ,STRATAA Study Consortium ,seroepidemiology ,Life Sciences & Biomedicine ,RESISTANCE - Abstract
Introduction Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12–27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics. The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies. Methods/design Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers. Ethics and dissemination This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences.
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- 2017
8. Initial Accuracy of HIV Rapid Test Kits Stored in Suboptimal Conditions and Validity of Delayed Reading of Oral Fluid Tests
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Choko, AT, Taegtmeyer, M, MacPherson, P, Cocker, D, Khundi, M, Thindwa, D, Sambakunsi, RS, Kumwenda, MK, Chiumya, K, Malema, O, Makombe, SD, Webb, EL, and Corbett, EL
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RNA viruses ,Male ,Research Facilities ,Physiology ,Systems Engineering ,Health Care Providers ,Nurses ,lcsh:Medicine ,HIV Infections ,wc_503 ,Pathology and Laboratory Medicine ,Workflow ,Immunodeficiency Viruses ,Medicine and Health Sciences ,Mass Screening ,Public and Occupational Health ,lcsh:Science ,HIV diagnosis and management ,Hematology ,Vaccination and Immunization ,Body Fluids ,Multidisciplinary Sciences ,Professions ,Blood ,Medical Microbiology ,Viral Pathogens ,Viruses ,Science & Technology - Other Topics ,Engineering and Technology ,Female ,Pathogens ,Anatomy ,Research Laboratories ,Research Article ,Adult ,wc_503_1 ,General Science & Technology ,Immunology ,HIV prevention ,Antiretroviral Therapy ,wa_395 ,Research and Analysis Methods ,Microbiology ,Sensitivity and Specificity ,26bc6fb8 ,Antiviral Therapy ,MD Multidisciplinary ,Retroviruses ,Humans ,ASSAYS ,ALGORITHM ,Saliva ,Microbial Pathogens ,Science & Technology ,HIV-1/2 ,Lentivirus ,lcsh:R ,Organisms ,Biology and Life Sciences ,HIV ,Reproducibility of Results ,Diagnostic medicine ,Health Care ,People and Places ,Population Groupings ,lcsh:Q ,Preventive Medicine ,Reagent Kits, Diagnostic ,Quality Assurance ,Government Laboratories ,wb_200 - Abstract
OBJECTIVES\ud To evaluate the effect of storing commonly used rapid diagnostic tests above manufacturer-recommended temperature (at 37°C), and the accuracy of delayed reading of oral fluid kits with relevance to HIV self-testing programmes.\ud \ud DESIGN\ud A quality assurance study of OraQuick (OraSure), Determine HIV 1/2™ (Alere) and Uni-Gold™ (Recombigen®).\ud \ud METHODS\ud Consecutive adults (≥18y) attending Ndirande Health Centre in urban Blantyre, Malawi in January to April 2012 underwent HIV testing with two of each of the three rapid diagnostic test kits stored for 28 days at either 18°C (optimally-stored) or at 37°C (pre-incubated). Used OraQuick test kits were stored in a laboratory for delayed day 1 and subsequent monthly re-reading was undertaken for one year.\ud \ud RESULTS\ud Of 378 individuals who underwent parallel testing, 5 (1.3%) were dropped from the final analysis due to discordant or missing reference standard results (optimally-stored Determine and Uni-Gold). Compared to the diagnostic reference standard, OraQuick had a sensitivity of 97.2% (95% CI: 93.6-99.6). There were 7 false negative results among all test kits stored at 37°C and three false negatives among optimally stored kits. Excellent agreement between pre-incubated tests and optimally-stored tests with Kappa values of 1.00 for Determine and Uni-Gold; and 0.97 (95% CI: 0.95; 1.00) for OraQuick were observed. There was high visual stability on re-reading of OraQuick, with only 1/375 pre-incubated and 1/371 optimally-stored OraQuick kits changing from the initial result over 12 months.\ud \ud CONCLUSION\ud Erroneous results observed during HIV testing in low income settings are likely to be due to factors other than suboptimal storage conditions. Re-reading returned OraQuick kits may offer a convenient and accurate quality assurance approach, including in HIV self-testing programmes.
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- 2016
9. Development and Validation of a Global Positioning System-based 'Map Book' System for Categorizing Cluster Residency Status of Community Members Living in High-Density Urban Slums in Blantyre, Malawi
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MacPherson, Peter, Choko, A. T., Webb, E. L., Thindwa, D., Squire, Bertie, Sambakunsi, R., van Oosterhout, J. J., Chunda, T., Chavula, K., Makombe, S. D., Lalloo, David, and Corbett, E. L.
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wa_950 ,qv_771 ,wa_395 - Abstract
A significant methodological challenge in implementing community-based cluster-randomized trials is how to accurately categorize cluster residency when data are collected at a site distant from households. This study set out to validate a map book system for use in urban slums with no municipal address systems, where classification has been shown to be inaccurate when address descriptions were used. Between April and July 2011, 28 noncontiguous clusters were demarcated in Blantyre, Malawi. In December 2011, antiretroviral therapy initiators were asked to identify themselves as cluster residents (yes/no and which cluster) by using map books. A random sample of antiretroviral therapy initiators was used to validate map book categorization against Global Positioning System coordinates taken from participants' households. Of the 202 antiretroviral therapy initiators, 48 (23.8%) were categorized with the map book system as in-cluster residents and 147 (72.8%) as out-of-cluster residents, and 7 (3.4%) were unsure. Agreement between map books and the Global Positioning System was 100% in the 20 adults selected for validation and was 95.0% (κ = 0.96, 95% confidence interval: 0.84, 1.00) in an additional 20 in-cluster residents (overall κ = 0.97, 95% confidence interval: 0.90, 1.00). With map books, cluster residents were classified rapidly and accurately. If validated elsewhere, this approach could be of widespread value in that it would enable accurate categorization without home visits.
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- 2013
10. Estimating pneumococcal carriage dynamics in adults living with HIV in a mature infant pneumococcal conjugate vaccine programme in Malawi, a modelling study.
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Phiri J, Sibale L, Mlongoti L, Mitole N, Kusakala A, Khwiya M, Kayembe T, Lisimba E, Kapwata P, Malisita K, Chaguza C, Ferreira DM, Thindwa D, and Jambo K
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- Humans, Malawi epidemiology, Female, Adult, Male, Young Adult, Middle Aged, Adolescent, Infant, Vaccines, Conjugate administration & dosage, Longitudinal Studies, HIV Infections epidemiology, Pneumococcal Vaccines administration & dosage, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control, Carrier State epidemiology, Carrier State microbiology, Streptococcus pneumoniae isolation & purification, Nasopharynx microbiology, Nasopharynx virology
- Abstract
Background: Adults living with human immunodeficiency virus (ALWHIV) receiving antiretroviral therapy (ART) exhibit higher pneumococcal carriage prevalence than adults without HIV (HIV-). To assess factors influencing high pneumococcal carriage in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting at least 10 years after introducing infant PCV13 in routine immunisation., Methods: We collected longitudinal nasopharyngeal swabs from individuals aged 18-45 in Blantyre, Malawi. The study group included both HIV- individuals and those living with HIV, categorised based on ART duration as either exceeding 1 year (ART > 1y) or less than 3 months (ART < 3 m). Samples were collected at baseline and then weekly for 16 visits. To detect pneumococcal carriage, we used classical culture microbiology, and to determine pneumococcal serotypes, we used latex agglutination. We modelled trajectories of serotype colonisation using multi-state Markov models to capture pneumococcal carriage dynamics, adjusting for age, sex, number of under 5 year old (< 5y) children, social economic status (SES), and seasonality., Results: We enrolled 195 adults, 65 adults in each of the study groups. 51.8% were females, 25.6% lived with more than one child under 5 years old, and 41.6% lived in low socioeconomic areas. The median age was 33 years (IQR 25-37 years). The baseline pneumococcal carriage prevalence of all serotypes was 31.3%, with non-PCV13 serotypes (NVT) at 26.2% and PCV13 serotypes (VT) at 5.1%. In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (hazard ratio [HR], NVT [1.53]; VT [1.96]). It was also higher in low than high SES (NVT [1.38]; VT [2.06]), in adults living with 2 + than 1 child < 5y (VT [1.78]), and in ALWHIV on ART > 1y than HIV- adults (NVT [1.43]). Moreover, ALWHIV on ART > 1y cleared pneumococci slower than HIV- adults ([0.65]). Residual VT 19F and 3 were highly acquired, although NVT remained dominant., Conclusions: The disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART > 1y is likely due to impaired nasopharyngeal clearance, which results in prolonged carriage. Our findings provide baseline estimates for comparing pneumococcal carriage dynamics after implementing new PCV strategies in ALWHIV., (© 2024. The Author(s).)
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- 2024
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11. Modelling Salmonella Typhi in high-density urban Blantyre neighbourhood, Malawi, using point pattern methods.
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Khaki JJ, Meiring JE, Thindwa D, Henrion MYR, Jere TM, Msuku H, Heyderman RS, Gordon MA, and Giorgi E
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- Humans, Adolescent, Child, Malawi epidemiology, Adult, Child, Preschool, Male, Female, Young Adult, Incidence, Infant, Risk Factors, Sanitation, Urban Population, Typhoid Fever epidemiology, Typhoid Fever microbiology, Salmonella typhi isolation & purification
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Salmonella Typhi is a human-restricted pathogen that is transmitted by the faecal-oral route and causative organism of typhoid fever. Using health facility data from 2016 to 2020, this study focuses on modelling the spatial variation in typhoid risk in Ndirande township in Blantyre. To pursue this objective, we developed a marked inhomogeneous Poisson process model that allows us to incorporate both individual-level and environmental risk factors. The results from our analysis indicate that typhoid cases are spatially clustered, with the incidence decreasing by 54% for a unit increase in the water, sanitation, and hygiene (WASH) score. Typhoid intensity was also higher in children aged below 18 years than in adults. However, our results did not show evidence of a strong temporal variation in typhoid incidence. We also discuss the inferential benefits of using point pattern models to characterise the spatial variation in typhoid risk and outline possible extensions of the proposed modelling framework., (© 2024. The Author(s).)
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- 2024
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12. Global patterns of rebound to normal RSV dynamics following COVID-19 suppression.
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Thindwa D, Li K, Cooper-Wootton D, Zheng Z, Pitzer VE, and Weinberger DM
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- Humans, Seasons, Respiratory Syncytial Virus, Human, Pandemics, COVID-19 epidemiology, Respiratory Syncytial Virus Infections epidemiology, SARS-CoV-2, Global Health
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Background: Annual epidemics of respiratory syncytial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting in April 2020, RSV seasonal activity declined due to COVID-19 non-pharmaceutical interventions (NPIs) before re-emerging after relaxation of NPIs. We described the unusual patterns of RSV epidemics that occurred in multiple subsequent waves following COVID-19 in different countries and explored factors associated with these patterns., Methods: Weekly cases of RSV from twenty-eight countries were obtained from the World Health Organisation and combined with data on country-level characteristics and the stringency of the COVID-19 response. Dynamic time warping and regression were used to cluster time series patterns and describe epidemic characteristics before and after COVID-19 pandemic, and identify related factors., Results: While the first wave of RSV epidemics following pandemic suppression exhibited unusual patterns, the second and third waves more closely resembled typical RSV patterns in many countries. Post-pandemic RSV patterns differed in their intensity and/or timing, with several broad patterns across the countries. The onset and peak timings of the first and second waves of RSV epidemics following COVID-19 suppression were earlier in the Southern than Northern Hemisphere. The second wave of RSV epidemics was also earlier with higher population density, and delayed if the intensity of the first wave was higher. More stringent NPIs were associated with lower RSV growth rate and intensity and a shorter gap between the first and second waves., Conclusion: Patterns of RSV activity have largely returned to normal following successive waves in the post-pandemic era. Onset and peak timings of future epidemics following disruption of normal RSV dynamics need close monitoring to inform the delivery of preventive and control measures., (© 2024. The Author(s).)
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- 2024
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13. The role of viral interference in shaping RSV epidemics following the 2009 H1N1 influenza pandemic.
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Li K, Thindwa D, Weinberger DM, and Pitzer VE
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Respiratory syncytial virus (RSV) primarily affects infants, young children, and older adults, with seasonal outbreaks in the United States (US) peaking around December or January. Despite the limited implementation of non-pharmaceutical interventions, disrupted RSV activity was observed in different countries following the 2009 influenza pandemic, suggesting possible viral interference from influenza. Although interactions between the influenza A/H1N1 pandemic virus and RSV have been demonstrated at an individual level, it remains unclear whether the disruption of RSV activity at the population level can be attributed to viral interference. In this work, we first evaluated changes in the timing and intensity of RSV activity across 10 regions of the US in the years following the 2009 influenza pandemic using dynamic time warping. We observed a reduction in RSV activity following the pandemic, which was associated with intensity of influenza activity in the region. We then developed an age-stratified, two-pathogen model to examine various hypotheses regarding viral interference mechanisms. Based on our model estimates, we identified three mechanisms through which influenza infections could interfere with RSV: 1) reducing susceptibility to RSV coinfection; 2) shortening the RSV infectious period in coinfected individuals; and 3) reducing RSV infectivity in coinfection. Our study offers statistical support for the occurrence of atypical RSV seasons following the 2009 influenza pandemic. Our work also offers new insights into the mechanisms of viral interference that contribute to disruptions in RSV epidemics and provides a model-fitting framework that enables the analysis of new surveillance data for studying viral interference at the population level., Competing Interests: Competing interests: DMW has been principal investigator on grants from Pfizer and Merck to Yale University for work unrelated to this manuscript and has received consulting and/or speaking fees from Pfizer, Merck, and GSK/Affinivax. The other authors declare no competing interests.
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- 2024
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14. Cost-effectiveness analysis of typhoid conjugate vaccines in an outbreak setting: a modeling study.
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Phillips MT, Antillon M, Bilcke J, Bar-Zeev N, Limani F, Debellut F, Pecenka C, Neuzil KM, Gordon MA, Thindwa D, Paltiel AD, Yaesoubi R, and Pitzer VE
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- Humans, Adolescent, Cost-Effectiveness Analysis, Vaccines, Conjugate, Cost-Benefit Analysis, Typhoid Fever epidemiology, Typhoid Fever prevention & control, Typhoid-Paratyphoid Vaccines
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Background: Several prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks., Methodology: We developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak., Results: Assuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15-60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0-300 per DALY averted. For WTP values > $300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and > $140 per DALY averted if implemented after the outbreak has already occurred., Conclusions: Countries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2023
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15. Optimal age targeting for pneumococcal vaccination in older adults; a modelling study.
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Thindwa D, Clifford S, Kleynhans J, von Gottberg A, Walaza S, Meiring S, Swarthout TD, Miller E, McIntyre P, Andrews N, Amin-Chowdhury Z, Fry N, Jambo KC, French N, Almeida SCG, Ladhani SN, Heyderman RS, Cohen C, de Cunto Brandileone MC, and Flasche S
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- Infant, Humans, Aged, Middle Aged, Pneumococcal Vaccines, Vaccination, Serogroup, Incidence, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control
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Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries., (© 2023. The Author(s).)
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- 2023
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16. Unmasking Pneumococcal Carriage in a High Human Immunodeficiency Virus (HIV) Prevalence Population in two Community Cohorts in South Africa, 2016-2018: The PHIRST Study.
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Carrim M, Tempia S, Thindwa D, Martinson NA, Kahn K, Flasche S, Hellferscee O, Treurnicht FK, McMorrow ML, Moyes J, Mkhencele T, Mathunjwa A, Kleynhans J, Lebina L, Mothlaoleng K, Wafawanaka F, Gómez-Olivé FX, Cohen C, von Gottberg A, and Wolter N
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- Child, Humans, Infant, Middle Aged, Aged, Streptococcus pneumoniae, HIV, South Africa epidemiology, Prevalence, Nasopharynx, Pneumococcal Vaccines, Carrier State epidemiology, Carrier State prevention & control, Pneumococcal Infections prevention & control, HIV Infections complications, HIV Infections epidemiology
- Abstract
Background: Longitudinal pneumococcus colonization data in high human immunodeficiency virus (HIV) prevalence settings following pneumococcal conjugate vaccine introduction are limited., Methods: In 327 randomly selected households, 1684 individuals were enrolled and followed-up for 6 to 10 months during 2016 through 2018 from 2 communities. Nasopharyngeal swabs were collected twice weekly and tested for pneumococcus using quantitative lytA real-time polymerase chain reaction. A Markov model was fitted to the data to define the start and end of an episode of colonization. We assessed factors associated with colonization using logistic regression., Results: During the study period, 98% (1655/1684) of participants were colonized with pneumococcus at least once. Younger age (<5 years: adjusted odds ratio [aOR], 14.1; 95% confidence [CI], 1.8-111.3, and 5-24 years: aOR, 4.8, 95% CI, 1.9-11.9, compared with 25-44 years) and HIV infection (aOR, 10.1; 95% CI, 1.3-77.1) were associated with increased odds of colonization. Children aged <5 years had fewer colonization episodes (median, 9) than individuals ≥5 years (median, 18; P < .001) but had a longer episode duration (<5 years: 35.5 days; interquartile range, 17-88) vs. ≥5 years: 5.5 days (4-12). High pneumococcal loads were associated with age (<1 year: aOR 25.4; 95% CI, 7.4-87.6; 1-4 years: aOR 13.5, 95% CI 8.3-22.9; 5-14 years: aOR 3.1, 95% CI, 2.1-4.4 vs. 45-65 year old patients) and HIV infection (aOR 1.7; 95% CI 1.2-2.4)., Conclusions: We observed high levels of pneumococcus colonization across all age groups. Children and people with HIV were more likely to be colonized and had higher pneumococcal loads. Carriage duration decreased with age highlighting that children remain important in pneumococcal transmission., Competing Interests: Potential conflicts of interest. M. C. has received the Robert Austrian Award sponsored by Pfizer as well as received funding as part of the South Africa-Pittsburgh Public Health Genomic Epidemiology (SAPPHGenE) training program and reports support for attending meetings and/or travel paid to the institution from Bill and Melinda Gates Foundation. D. T. received funding from the UK National Institute of Health Research Mucosal Pathogen Research 336 Unit (NIHR-MPRU) at University College London. C. C. has received grant support from Sanofi Pasteur, Advanced Vaccine Initiative, CDC, Wellcome Trust, PATH, Bill and Melinda Gates Foundation, and South African Medical Research Council (SA-MRC). A. v. G. has received grant support from Sanofi Pasteur, Pfizer related to pneumococcal vaccine, CDC, and the Bill and Melinda Gates Foundation and reports being chairperson at their local NiTAG. N. W. report grants from Sanofi Pasteur and the Bill and Melinda Gates Foundation paid to the institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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17. Omicron B.1.1.529 variant infections associated with severe disease are uncommon in a COVID-19 under-vaccinated, high SARS-CoV-2 seroprevalence population in Malawi.
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Mseka UL, Mandolo J, Nyoni K, Divala O, Kambalame D, Mapemba D, Kamzati M, Chibwe I, Henrion MYR, Manda K, Thindwa D, Mvula M, Odala B, Kamng'ona R, Dzinza N, Jere KC, Feasey N, Ho A, Amoah AS, Gordon M, Swarthout TD, Crampin A, Heyderman RS, Kagoli M, Chitsa-Banda E, Mitambo C, Phuka J, Chilima B, Kasambara W, Jambo KC, and Chauma-Mwale A
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Background: The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the fourth COVID-19 pandemic wave across the southern African region, including Malawi. The seroprevalence of SARS-CoV-2 antibodies and their association with epidemiological trends of hospitalisations and deaths are needed to aid locally relevant public health policy decisions., Methods: We conducted a population-based serosurvey from December 27, 2021 to January 17, 2022, in 7 districts across Malawi to determine the seroprevalence of SARS-CoV-2 antibodies. Serum samples were tested for antibodies against SARS-CoV-2 receptor binding domain using WANTAI SARS-CoV-2 Receptor Binding Domain total antibody commercial enzyme-linked immunosorbent assay (ELISA). We also evaluated COVID-19 epidemiologic trends in Malawi, including cases, hospitalisations and deaths from April 1, 2021 through April 30, 2022, collected using the routine national COVID-19 reporting system. A multivariable logistic regression model was developed to investigate the factors associated with SARS-CoV-2 seropositivity., Findings: Serum samples were analysed from 4619 participants (57% female; 60% aged 18-50 years), of whom 878/3794 (23%) of vaccine eligible adults had received a single dose of any COVID-19 vaccine. The overall assay-adjusted seroprevalence was 83.7% (95% confidence interval (CI), 79.3%-93.4%). Seroprevalence was lowest among children <13 years of age (66%) and highest among adults 18-50 years of age (82%). Seroprevalence was higher among vaccinated compared to unvaccinated participants (1 dose, 94% vs. 77%, adjusted odds ratio 4.89 [95% CI, 3.43-7.22]; 2 doses, 97% vs. 77%, aOR 6.62 [95% CI, 4.14-11.3]). Urban residents were more likely to be seropositive than those from rural settings (91% vs. 78%, aOR 2.76 [95% CI, 2.16-3.55]). There was at least a two-fold reduction in the proportion of hospitalisations and deaths among the reported cases in the fourth wave compared to the third wave (hospitalisations, 10.7% (95% CI, 10.2-11.3) vs. 4.86% (95% CI, 4.52-5.23), p < 0.0001; deaths, 3.48% (95% CI, 3.18-3.81) vs. 1.15% (95% CI, 1.00-1.34), p < 0.0001)., Interpretation: We report reduction in proportion of hospitalisations and deaths from SARS-CoV-2 infections during the Omicron variant dominated wave in Malawi, in the context of high SARS-CoV-2 seroprevalence and low COVID-19 vaccination coverage. These findings suggest that COVID-19 vaccination policy in high seroprevalence settings may need to be amended from mass campaigns to targeted vaccination of reported at-risk populations., Funding: Supported by the Bill and Melinda Gates Foundation (INV-039481)., Competing Interests: All authors declare no conflict of interest., (© 2022 The Author(s).)
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- 2023
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18. Waning of antibody levels induced by a 13-valent pneumococcal conjugate vaccine, using a 3 + 0 schedule, within the first year of life among children younger than 5 years in Blantyre, Malawi: an observational, population-level, serosurveillance study.
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Swarthout TD, Henrion MYR, Thindwa D, Meiring JE, Mbewe M, Kalizang'Oma A, Brown C, Msefula J, Moyo B, Mataya AA, Barnaba S, Pearce E, Gordon M, Goldblatt D, French N, and Heyderman RS
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- Child, Humans, Infant, Adolescent, Child, Preschool, Vaccines, Conjugate, Malawi epidemiology, Prospective Studies, Pneumococcal Vaccines, Immunoglobulin G, Antibodies, Bacterial, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control
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Background: Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi., Methods: For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age <3 months to 57-59 months)., Findings: We evaluated 638 plasma samples: 556 primary samples and 82 unique secondary samples (each linked to one primary sample). Immunogenicity profiles revealed a consistent pattern among vaccine serotypes except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3, we observed no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination nadir (from 11·2 months [19A] to 27·3 months [7F]). The age at peak IgG titre ranged from 2·69 months (5) to 6·64 months (14). Titres dropped below CoPs against IPD among nine vaccine serotypes (1, 3, 4, 5, 6B, 7F, 9V, 18C, and 23F) and below CoPs against carriage for ten vaccine serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F). Increasing antibody concentrations among older children and seroincident events were consistent with ongoing vaccine-serotype exposure., Interpretation: A 3 + 0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several vaccine serotypes, potentially contributing to persistent vaccine-serotype carriage and residual vaccine-serotype IPD in Malawi and other similar settings. Policy decisions should consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody titres, and thus control., Funding: Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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19. Quality of antibody responses by adults and young children to 13-valent pneumococcal conjugate vaccination and Streptococcus pneumoniae colonisation.
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Wolf AS, Mitsi E, Jones S, Jochems SP, Roalfe L, Thindwa D, Meiring JE, Msefula J, Bonomali F, Makhaza Jere T, Mbewe M, Collins AM, Gordon SB, Gordon MA, Ferreira DM, French N, Goldblatt D, Heyderman RS, and Swarthout TD
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- Humans, Child, Infant, Adult, Child, Preschool, Antibody Formation, Pneumococcal Vaccines, Vaccines, Conjugate, Vaccination, Immunoglobulin G, Nasopharynx, Streptococcus pneumoniae, Pneumococcal Infections prevention & control
- Abstract
Childhood pneumococcal conjugate vaccine (PCV) protects against invasive pneumococcal disease caused by vaccine-serotype (VT) Streptococcus pneumoniae by generating opsonophagocytic anti-capsular antibodies, but how vaccination protects against and reduces VT carriage is less well understood. Using serological samples from PCV-vaccinated Malawian individuals and a UK human challenge model, we explored whether antibody quality (IgG subclass, opsonophagocytic killing, and avidity) is associated with protection from carriage. Following experimental challenge of adults with S. pneumoniae serotype 6B, 3/21 PCV13-vaccinees were colonised with pneumococcus compared to 12/24 hepatitis A-vaccinated controls; PCV13-vaccination induced serotype-specific IgG, IgG1, and IgG2, and strong opsonophagocytic responses. However, there was no clear relationship between antibody quality and protection from carriage or carriage intensity after vaccination. Similarly, among PCV13-vaccinated Malawian infants there was no relationship between serotype-specific antibody titre or quality and carriage through exposure to circulating serotypes. Although opsonophagocytic responses were low in infants, antibody titre and avidity to circulating serotypes 19F and 6A were maintained or increased with age. These data suggest a complex relationship between antibody-mediated immunity and pneumococcal carriage, and that PCV13-driven antibody quality may mature with age and exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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20. Risk factors for pneumococcal carriage in adults living with HIV on antiretroviral therapy in the infant pneumococcal vaccine era in Malawi.
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Thindwa D, Mwalukomo TS, Msefula J, Jambo KC, Brown C, Kamng'ona A, Mwansambo C, Ojal J, Flasche S, French N, Heyderman RS, and Swarthout TD
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- Adult, Female, Humans, Infant, Male, Carrier State epidemiology, Cross-Sectional Studies, Malawi epidemiology, Nasopharynx, Pneumococcal Vaccines, Prevalence, Risk Factors, Streptococcus pneumoniae, Infant, Newborn, Child, Preschool, HIV Infections complications, HIV Infections drug therapy, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control
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Objective: Adults living with HIV (ALWHIV) on antiretroviral therapy (ART) are at high risk of pneumococcal carriage and disease. To help evaluate carriage risk in African ALWHIV at least 4 years after infant pneumococcal conjugate vaccination introduction in 2011, we assessed association between pneumococcal carriage and potential risk factors., Methods: Nasopharyngeal swabs were collected from adults aged 18-40 years attending an ART clinic during rolling, cross-sectional surveys in Blantyre, Malawi between 2015 and 2019. We fitted generalized additive models to estimate the risk of sex, social economic status (SES), living with a child less than 5 years, and ART duration on carriage., Results: Of 2067 adults, median age was 33 years (range 28-37), 1427 (69.0%) were women, 1087 (61.4%) were in low-middle socioeconomic-status (SES), 910 (44.0%) were living with a child less than 5 years, and median ART duration was 3 years (range 0.004-17). We estimated 38.2 and 60.6% reductions in overall and vaccine-serotype carriage prevalence. Overall carriage was associated with low SES, living with a child less than 5 years and shorter duration on ART. By contrast, vaccine-type carriage was associated with living without a child less than 5 years and male sex., Conclusion: Despite temporal reductions in overall and vaccine-serotype carriage, there is evidence of incomplete vaccine-serotype indirect protection. A targeted-vaccination campaign should be considered for ALWHIV, along with other public health measures to further reduce vaccine-serotype carriage and therefore disease., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2022
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21. Hepatitis B Vaccination Impact and the Unmet Need for Antiviral Treatment in Blantyre, Malawi.
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Stockdale AJ, Meiring JE, Shawa IT, Thindwa D, Silungwe NM, Mbewe M, Kachala R, Kreuels B, Patel P, Patel P, Henrion MYR, Bar-Zeev N, Swarthout TD, Heyderman RS, Gordon SB, Maria Geretti A, and Gordon MA
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- Adolescent, Adult, Antiviral Agents therapeutic use, Child, Female, Hepatitis B Surface Antigens, Hepatitis B Vaccines therapeutic use, Hepatitis B virus, Humans, Infant, Malawi epidemiology, Male, Seroepidemiologic Studies, Vaccination, HIV Infections drug therapy, HIV Infections epidemiology, Hepatitis B drug therapy, Hepatitis B epidemiology, Hepatitis B prevention & control
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Background: Hepatitis B is the leading cause of cirrhosis and liver cancer in sub-Saharan Africa. To reduce mortality, antiviral treatment programs are needed. We estimated prevalence, vaccine impact, and need for antiviral treatment in Blantyre, Malawi., Methods: We conducted a household study in 2016-2018. We selected individuals from a census using random sampling and estimated age-sex-standardized hepatitis B surface antigen (HBsAg) seroprevalence. Impact of infant hepatitis B vaccination was estimated by binomial log-linear regression comparing individuals born before and after vaccine implementation. In HBsAg-positive adults, eligibility for antiviral therapy was assessed., Results: Of 97386 censused individuals, 6073 (median age 18 years; 56.7% female) were sampled. HBsAg seroprevalence was 5.1% (95% confidence interval [CI], 4.3%-6.1%) among adults and 0.3% (95% CI, .1%-.6%) among children born after vaccine introduction. Estimated vaccine impact was 95.8% (95% CI, 70.3%-99.4%). Of HBsAg-positive adults, 26% were HIV-positive. Among HIV-negative individuals, 3%, 6%, and 9% were eligible for hepatitis B treatment by WHO, European, and American hepatology association criteria, respectively., Conclusions: Infant HBV vaccination has been highly effective in reducing HBsAg prevalence in urban Malawi. Up to 9% of HBsAg-positive HIV-negative adults are eligible, but have an unmet need, for antiviral therapy., Competing Interests: Potential conflicts of interest. N. B.-Z. reports grants from Merck-Sharp-Dohme, Johnson & Johnson, and Serum Institute of India, outside the submitted work. A. M. G. reports grants and personal fees from Roche Pharma Research and Early Development, ViiV Healthcare, and Gilead; personal fees from Janssen; and consulting fees from GSK, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
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22. Effect of patient-delivered household contact tracing and prevention for tuberculosis: A household cluster-randomised trial in Malawi.
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Kaswaswa K, MacPherson P, Kumwenda M, Mpunga J, Thindwa D, Nliwasa M, Mwapasa M, Odland J, Tomoka T, Chipungu G, Mukaka M, and Corbett EL
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- Adolescent, Adult, Child, Child, Preschool, Family Characteristics, Humans, Isoniazid therapeutic use, Malawi epidemiology, Contact Tracing, Tuberculosis diagnosis, Tuberculosis epidemiology, Tuberculosis prevention & control
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Background: Household contact tracing provides TB screening and TB preventive therapy (TPT) to contacts at high risk of TB disease. However, it is resource intensive, inconvenient, and often poorly implemented. We investigated a novel model aiming to improve uptake., Methods: Between May and December 2014, we randomised patient with TB who consented to participate in the trial to either standard of care (SOC) or intervention (PACTS) arms. Participants randomised to PACTS received one screening/triage tool (adapted from WHO integrated management of adolescent and adult illnesses [IMAI] guidelines) and sputum pots for each reported household contact. The tool guided participants through symptom screening; TPT (6-months of isoniazid) eligibility; and sputum collection for contacts. Patients randomised to SOC were managed in accordance with national guidelines, that is, they received verbal instruction on who to bring to clinics for investigation using national guidelines., Main Outcome and Measures: The primary outcome was the proportion of adult contacts receiving treatment for TB within 3 months of randomisation. Secondary outcomes were the proportions of child contacts under age 5 years (U5Y) who were commenced on, and completed, TPT. Data were analyzed by logistic regression with random effects to adjust for household clustering., Results: Two hundred and fourteen index TB participants were block-randomized from two sites (107 PACTS, reporting 418 contacts; and 107 SOC, reporting 420 contacts). Overall, 62.8% of index TB participants were HIV-positive and 52.1% were TB culture-positive. 250 otherwise eligible TB patients declined participation and 6 households (10 PACTS, 6 SOC) were lost to follow-up and were not included in the analysis. By three months, nine contacts (PACTS: 6, [1.4%]; SOC: 3, [0.7%]) had TB diagnosed, with no difference between groups (adjusted odds ratio [aOR]: 2.18, 95% CI: 0.60-7.95). Eligible PACTS contacts (37/96, 38.5%) were more likely to initiate TPT by 3-months compared to SOC contacts (27/101, 26.7%; aOR 2.27, 95% CI: 1.04-4.98). U5Y children in the PACTS arm (47/81 58.0%) were more likely to have initiated TPT before the 3-month visit compared to SOC children (36/89, 41.4%; aOR: 2.31, 95% CI: 1.05-5.06)., Conclusions and Relevance: A household-centred patient-delivered symptom screen and IPT eligibility assessment significantly increased timely TPT uptake among U5Y children, but did not significantly increase TB diagnosis. This model needs to be optimized for acceptability, given low participation, and investigated in other low resource settings., Clinical Trial Registration: TRIAL REGISTRATION NUMBER: ISRCTN81659509 https://www.isrctn.com/ISRCTN81659509?q=&filters=conditionCategory:Respiratory,recruitmentCountry:Malawi,ageRange:Mixed&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search. 19 July 2012., Competing Interests: The authors have declared that no competing interests exit.
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23. Social mixing patterns relevant to infectious diseases spread by close contact in urban Blantyre, Malawi.
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Thindwa D, Jambo KC, Ojal J, MacPherson P, Dennis Phiri M, Pinsent A, Khundi M, Chiume L, Gallagher KE, Heyderman RS, Corbett EL, French N, and Flasche S
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- Adolescent, Adult, Child, Female, Humans, Infant, Malawi epidemiology, Male, Schools, COVID-19 epidemiology, Communicable Diseases epidemiology, HIV Infections epidemiology
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Introduction: Understanding human mixing patterns relevant to infectious diseases spread through close contact is vital for modelling transmission dynamics and optimisation of disease control strategies. Mixing patterns in low-income countries like Malawi are not well known., Methodology: We conducted a social mixing survey in urban Blantyre, Malawi between April and July 2021 (between the 2nd and 3rd wave of COVID-19 infections). Participants living in densely-populated neighbourhoods were randomly sampled and, if they consented, reported their physical and non-physical contacts within and outside homes lasting at least 5 min during the previous day. Age-specific mixing rates were calculated, and a negative binomial mixed effects model was used to estimate determinants of contact behaviour., Results: Of 1201 individuals enroled, 702 (58.5%) were female, the median age was 15 years (interquartile range [IQR] 5-32) and 127 (10.6%) were HIV-positive. On average, participants reported 10.3 contacts per day (range: 1-25). Mixing patterns were highly age-assortative, particularly those within the community and with skin-to-skin contact. Adults aged 20-49 y reported the most contacts (median:11, IQR: 8-15) of all age groups; 38% (95%CI: 16-63) more than infants (median: 8, IQR: 5-10), who had the least contacts. Household contact frequency increased by 3% (95%CI: 2-5) per additional household member. Unemployed participants had 15% (95%CI: 9-21) fewer contacts than other adults. Among long range (>30 m away from home) contacts, secondary school children had the largest median contact distance from home (257 m, IQR 78-761). HIV-positive status in adults >=18 years-old was not associated with changed contact patterns (rate ratio: 1.01, 95%CI: (0.91-1.12)). During this period of relatively low COVID-19 incidence in Malawi, 301 (25.1%) individuals stated that they had limited their contact with others due to COVID-19 precautions; however, their reported contacts were 8% (95%CI: 1-13) higher., Conclusion: In urban Malawi, contact rates, are high and age-assortative, with little reported behavioural change due to either HIV-status or COVID-19 circulation. This highlights the limits of contact-restriction-based mitigation strategies in such settings and the need for pandemic preparedness to better understand how contact reductions can be enabled and motivated., Competing Interests: Conflict of Interest The authors have declared that no conflict of interest or competing interests exist., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
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24. A clinical and molecular epidemiological survey of hepatitis C in Blantyre, Malawi, suggests a historic mechanism of transmission.
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Stockdale AJ, Kreuels B, Shawa IT, Meiring JE, Thindwa D, Silungwe NM, Chetcuti K, Joekes E, Mbewe M, Mbale B, Patel P, Kachala R, Patel PD, Malewa J, Finch P, Davis C, Shah R, Tong L, da Silva Filipe A, Thomson EC, Geretti AM, and Gordon MA
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- Adolescent, Adult, Aged, Hepacivirus genetics, Hepatitis C Antibodies, Humans, Liver Cirrhosis complications, Malawi epidemiology, Middle Aged, Prevalence, Prospective Studies, RNA, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular epidemiology, Hepatitis C complications, Hepatitis C epidemiology, Liver Neoplasms complications
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Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. There are no previous representative community HCV prevalence studies from Southern Africa, and limited genotypic data. Epidemiological data are required to inform an effective public health response. We conducted a household census-based random sampling serological survey, and a prospective hospital-based study of patients with cirrhosis and hepatocellular carcinoma (HCC) in Blantyre, Malawi. We tested participants with an HCV antigen/antibody ELISA (Monolisa, Bio-Rad), confirmed with PCR (GeneXpert, Cepheid) and used line immunoassay (Inno-LIA, Fujiribio) for RNA-negative participants. We did target-enrichment whole-genome HCV sequencing (NextSeq, Illumina). Among 96,386 censused individuals, we randomly selected 1661 people aged ≥16 years. Population-standardized HCV RNA prevalence was 0.2% (95% CI 0.1-0.5). Among 236 patients with cirrhosis and HCC, HCV RNA prevalence was 1.9% and 5.0%, respectively. Mapping showed that HCV RNA+ patients were from peri-urban areas surrounding Blantyre. Community and hospital HCV RNA+ participants were older than comparator HCV RNA-negative populations (median 53 vs 30 years for community, p = 0.01 and 68 vs 40 years for cirrhosis/HCC, p < 0.001). Endemic HCV genotypes (n = 10) were 4v (50%), 4r (30%) and 4w (10%). In this first census-based community serological study in Southern Africa, HCV was uncommon in the general population, was centred on peri-urban regions and was attributable for <5% of liver disease. HCV infection was observed only among older people, suggesting a historic mechanism of transmission. Genotype 4r, which has been associated with treatment failure with ledipasvir and daclatasvir, is endemic., (© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)
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- 2022
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25. Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016-2018: A hidden Markov modelling study.
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Thindwa D, Wolter N, Pinsent A, Carrim M, Ojal J, Tempia S, Moyes J, McMorrow M, Kleynhans J, Gottberg AV, French N, Cohen C, and Flasche S
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- Adolescent, Adult, Algorithms, Carrier State epidemiology, Carrier State transmission, Child, Child, Preschool, Computational Biology, Female, Humans, Male, Markov Chains, Middle Aged, Models, Statistical, South Africa epidemiology, Streptococcus pneumoniae, Young Adult, HIV Infections complications, HIV Infections epidemiology, Pneumococcal Infections complications, Pneumococcal Infections epidemiology, Pneumococcal Infections transmission
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Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant's age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9-80.5%) than older children (5-17 years-old) (31.7-50.0%) or adults (11.5-23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7-15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91-1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2-12.8 vs 6.0 days, 95%CI: 5.6-6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507-714 vs 389, 95%CI: 311.1-435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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26. Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study.
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Meiring JE, Shakya M, Khanam F, Voysey M, Phillips MT, Tonks S, Thindwa D, Darton TC, Dongol S, Karkey A, Zaman K, Baker S, Dolecek C, Dunstan SJ, Dougan G, Holt KE, Heyderman RS, Qadri F, Pitzer VE, Basnyat B, Gordon MA, Clemens J, and Pollard AJ
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- Anti-Bacterial Agents therapeutic use, Bangladesh epidemiology, Census Tract, Humans, Malawi epidemiology, Nepal epidemiology, Population Density, Risk Factors, Seasons, Seroepidemiologic Studies, Typhoid Fever drug therapy, Urban Population statistics & numerical data, Population Surveillance methods, Typhoid Fever epidemiology, Typhoid Fever transmission
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Background: Enteric fever is a serious public health concern in many low-income and middle-income countries. Numerous data gaps exist concerning the epidemiology of Salmonella enterica serotype Typhi (S Typhi) and Salmonella enterica serotype Paratyphi (S Paratyphi), which are the causative agents of enteric fever. We aimed to determine the burden of enteric fever in three urban sites in Africa and Asia., Methods: In this multicentre population-based study, we did a demographic census at three urban sites in Africa (Blantyre, Malawi) and Asia (Kathmandu, Nepal and Dhaka, Bangladesh) between June 1, 2016, and Sept 25, 2018. Households were selected randomly from the demographic census. Participants from within the geographical census area presenting to study health-care facilities were approached for recruitment if they had a history of fever for 72 h or more (later changed to >48 h) or temperature of 38·0°C or higher. Facility-based passive surveillance was done between Nov 11, 2016, and Dec 31, 2018, with blood-culture collection for febrile illness. We also did a community-based serological survey to obtain data on Vi-antibody defined infections. We calculated crude incidence for blood-culture-confirmed S Typhi and S Paratyphi infection, and calculated adjusted incidence and seroincidence of S Typhi blood-culture-confirmed infection., Findings: 423 618 individuals were included in the demographic census, contributing 626 219 person-years of observation for febrile illness surveillance. 624 S Typhi and 108 S Paratyphi A isolates were collected from the blood of 12 082 febrile patients. Multidrug resistance was observed in 44% S Typhi isolates and fluoroquinolone resistance in 61% of S Typhi isolates. In Blantyre, the overall crude incidence of blood-culture confirmed S Typhi was 58 cases per 100 000 person-years of observation (95% CI 48-70); the adjusted incidence was 444 cases per 100 000 person-years of observation (95% credible interval [CrI] 347-717). The corresponding rates were 74 (95% CI 62-87) and 1062 (95% CrI 683-1839) in Kathmandu, and 161 (95% CI 145-179) and 1135 (95% CrI 898-1480) in Dhaka. S Paratyphi was not found in Blantyre; overall crude incidence of blood-culture-confirmed S Paratyphi A infection was 6 cases per 100 000 person-years of observation (95% CI 3-11) in Kathmandu and 42 (95% CI 34-52) in Dhaka. Seroconversion rates for S Typhi infection per 100 000 person-years estimated from anti-Vi seroconversion episodes in serological surveillance were 2505 episodes (95% CI 1605-3727) in Blantyre, 7631 (95% CI 5913-9691) in Kathmandu, and 3256 (95% CI 2432-4270) in Dhaka., Interpretation: High disease incidence and rates of antimicrobial resistance were observed across three different transmission settings and thus necessitate multiple intervention strategies to achieve global control of these pathogens., Funding: Wellcome Trust and the Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests VEP is a member of the WHO Immunization and Vaccine-related Implementation Research Advisory Committee. AJP chairs the UK Department of Health Joint Committee on Vaccination and Immunisation (JCVI) and is a member of the WHO Strategic Advisory Group of Experts. RSH is supported by the National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens using UK aid from the UK Government. The views expressed in this publication are those of the authors and not necessarily those of the UK Department of Health, JCVI, WHO, NIHR, or the Department of Health and Social Care. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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27. A Bayesian approach for estimating typhoid fever incidence from large-scale facility-based passive surveillance data.
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Phillips MT, Meiring JE, Voysey M, Warren JL, Baker S, Basnyat B, Clemens JD, Dolecek C, Dunstan SJ, Dougan G, Gordon MA, Thindwa D, Heyderman RS, Holt KE, Qadri F, Pollard AJ, and Pitzer VE
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- Bayes Theorem, Humans, Incidence, Malawi epidemiology, Nepal, Typhoid Fever diagnosis, Typhoid Fever epidemiology, Typhoid Fever prevention & control
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Decisions about typhoid fever prevention and control are based on estimates of typhoid incidence and their uncertainty. Lack of specific clinical diagnostic criteria, poorly sensitive diagnostic tests, and scarcity of accurate and complete datasets contribute to difficulties in calculating age-specific population-level typhoid incidence. Using data from the Strategic Typhoid Alliance across Africa and Asia program, we integrated demographic censuses, healthcare utilization surveys, facility-based surveillance, and serological surveillance from Malawi, Nepal, and Bangladesh to account for under-detection of cases. We developed a Bayesian approach that adjusts the count of reported blood-culture-positive cases for blood culture detection, blood culture collection, and healthcare seeking-and how these factors vary by age-while combining information from prior published studies. We validated the model using simulated data. The ratio of observed to adjusted incidence rates was 7.7 (95% credible interval [CrI]: 6.0-12.4) in Malawi, 14.4 (95% CrI: 9.3-24.9) in Nepal, and 7.0 (95% CrI: 5.6-9.2) in Bangladesh. The probability of blood culture collection led to the largest adjustment in Malawi, while the probability of seeking healthcare contributed the most in Nepal and Bangladesh; adjustment factors varied by age. Adjusted incidence rates were within or below the seroincidence rate limits of typhoid infection. Estimates of blood-culture-confirmed typhoid fever without these adjustments results in considerable underestimation of the true incidence of typhoid fever. Our approach allows each phase of the reporting process to be synthesized to estimate the adjusted incidence of typhoid fever while correctly characterizing uncertainty, which can inform decision-making for typhoid prevention and control., (© 2021 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)
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- 2021
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28. Tuberculosis case notifications in Malawi have strong seasonal and weather-related trends.
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Kirolos A, Thindwa D, Khundi M, Burke RM, Henrion MYR, Nakamura I, Divala TH, Nliwasa M, Corbett EL, and MacPherson P
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- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Child, Preschool, Disease Notification statistics & numerical data, Female, HIV Infections complications, Humans, Infant, Malawi epidemiology, Male, Middle Aged, Models, Statistical, Population Surveillance, Rain, Seasons, Sex Factors, Temperature, Tuberculosis, Pulmonary etiology, Weather, Young Adult, Tuberculosis, Pulmonary epidemiology
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Seasonal trends in tuberculosis (TB) notifications have been observed in several countries but are poorly understood. Explanatory factors may include weather, indoor crowding, seasonal respiratory infections and migration. Using enhanced citywide TB surveillance data collected over nine years in Blantyre, Malawi, we set out to investigate how weather and seasonality affect temporal trends in TB case notification rates (CNRs) across different demographic groups. We used data from prospective enhanced surveillance between April 2011 and December 2018, which systematically collected age, HIV status, sex and case notification dates for all registering TB cases in Blantyre. We retrieved temperature and rainfall data from the Global Surface Summary of the Day weather station database. We calculated weekly trends in TB CNRs, rainfall and temperature, and calculated 10-week moving averages. To investigate the associations between rainfall, temperature and TB CNRs, we fitted generalized linear models using a distributed lag nonlinear framework. The estimated Blantyre population increased from 1,068,151 in April 2011 to 1,264,304 in December 2018, with 15,908 TB cases recorded. Overall annual TB CNRs declined from 222 to 145 per 100,000 between 2012 and 2018, with the largest declines seen in HIV-positive people and adults aged over 20 years old. TB CNRs peaks occurred with increasing temperature in September and October before the onset of increased rainfall, and later in the rainy season during January-March, after sustained rainfall. When lag between a change in weather and TB case notifications was accounted for, higher average rainfall was associated with an equivalent six weeks of relatively lower TB notification rates, whereas there were no changes in TB CNR associated with change in average temperatures. TB CNRs in Blantyre have a seasonal pattern of two cyclical peaks per year, coinciding with the start and end of the rainy season. These trends may be explained by increased transmission at certain times of the year, by limited healthcare access, by patterns of seasonal respiratory infections precipitating cough and care-seeking, or by migratory patterns related to planting and harvesting during the rainy season.
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- 2021
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29. Electronic data capture for large scale typhoid surveillance, household contact tracing, and health utilisation survey: Strategic Typhoid Alliance across Africa and Asia.
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Thindwa D, Farooq YG, Shakya M, Saha N, Tonks S, Anokwa Y, Gordon MA, Hartung C, Meiring JE, Pollard AJ, and Heyderman RS
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Electronic data capture systems (EDCs) have the potential to achieve efficiency and quality in collection of multisite data. We quantify the volume, time, accuracy and costs of an EDC using large-scale census data from the STRATAA consortium, a comprehensive programme assessing population dynamics and epidemiology of typhoid fever in Malawi, Nepal and Bangladesh to inform vaccine and public health interventions. A census form was developed through a structured iterative process and implemented using Open Data Kit Collect running on Android-based tablets. Data were uploaded to Open Data Kit Aggregate, then auto-synced to MySQL-defined database nightly. Data were backed-up daily from three sites centrally, and auto-reported weekly. Pre-census materials' costs were estimated. Demographics of 308,348 individuals from 80,851 households were recorded within an average of 14.7 weeks range (13-16) using 65 fieldworkers. Overall, 21.7 errors (95% confidence interval: 21.4, 22.0) per 10,000 data points were found: 13.0 (95% confidence interval: 12.6, 13.5) and 24.5 (95% confidence interval: 24.1, 24.9) errors on numeric and text fields respectively. These values meet standard quality threshold of 50 errors per 10,000 data points. The EDC's total variable cost was estimated at US$13,791.82 per site. In conclusion, the EDC is robust, allowing for timely and high-volume accurate data collection, and could be adopted in similar epidemiological settings., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Thindwa D et al.)
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- 2020
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30. Vaccine strategies to reduce the burden of pneumococcal disease in HIV-infected adults in Africa.
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Thindwa D, Pinsent A, Ojal J, Gallagher KE, French N, and Flasche S
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- Adult, Africa, Anti-HIV Agents administration & dosage, HIV Infections drug therapy, Humans, Immunization Schedule, Infant, Streptococcus pneumoniae isolation & purification, Vaccines, Conjugate administration & dosage, HIV Infections complications, Pneumococcal Infections prevention & control, Pneumococcal Vaccines administration & dosage
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Introduction: Streptococcus pneumoniae is the leading cause of invasive bacterial disease, globally. Despite antiretroviral therapy, adults infected with human immunodeficiency virus (HIV) are also at high risk of pneumococcal carriage and disease. Pneumococcal conjugate vaccines (PCVs) provide effective protection against vaccine serotype (VT) carriage and disease in children, and have been introduced worldwide, including most HIV-affected low- and middle-income countries. Unlike high-income countries, the circulation of VT persists in the PCV era in some low-income countries and results in a continued high burden of pneumococcal disease in HIV-infected adults. Moreover, no routine vaccination that directly protects HIV-infected adults in such settings has been implemented., Areas Covered: Nonsystematic review on the pneumococcal burden in HIV-infected adults and vaccine strategies to reduce this burden., Expert Opinion: We propose and discuss the relative merit of changing the infant PCV program to use (1a) a two prime plus booster dose schedule, (1b) a two prime plus booster dose schedule with an additional booster dose at school entry, to directly vaccinate (2a) HIV-infected adults or vaccinating (2b) HIV-infected pregnant women for direct protection, with added indirect protection to the high-risk neonates. We identify key knowledge gaps for such an evaluation and propose strategies to overcome them.
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- 2020
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31. Use of seasonal influenza and pneumococcal polysaccharide vaccines in older adults to reduce COVID-19 mortality.
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Thindwa D, Garcia Quesada M, Liu Y, Bennett J, Cohen C, Knoll MD, von Gottberg A, Hayford K, and Flasche S
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- Aged, COVID-19, Coronavirus Infections prevention & control, Humans, Influenza Vaccines administration & dosage, Pandemics prevention & control, Pneumococcal Vaccines administration & dosage, Pneumonia, Viral prevention & control, Respiratory Tract Infections mortality, Risk Assessment, Vaccination, Vaccines, Conjugate administration & dosage, Coronavirus Infections complications, Coronavirus Infections mortality, Influenza Vaccines supply & distribution, Pneumococcal Vaccines supply & distribution, Pneumonia, Viral complications, Pneumonia, Viral mortality, Respiratory Tract Infections complications, Respiratory Tract Infections prevention & control, Seasons
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2020
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32. Distinct climate influences on the risk of typhoid compared to invasive non-typhoid Salmonella disease in Blantyre, Malawi.
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Thindwa D, Chipeta MG, Henrion MYR, and Gordon MA
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- Algorithms, Geography, Medical, Humans, Incidence, Malawi epidemiology, Models, Theoretical, Public Health Surveillance, Rain, Risk Assessment, Risk Factors, Temperature, Climate, Salmonella Infections epidemiology, Salmonella Infections microbiology, Typhoid Fever epidemiology, Typhoid Fever microbiology
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Invasive Salmonella diseases, both typhoid and invasive non-typhoidal Salmonella (iNTS), are seasonal bloodstream infections causing important morbidity and mortality globally in Africa. The reservoirs and transmission of both are not fully understood. We hypothesised that differences in the time-lagged relationships of rainfall or temperature with typhoid and iNTS incidence might infer differences in epidemiology. We assessed the dynamics of invasive Salmonella incidence over a 16-year period of surveillance, quantifying incidence peaks, seasonal variations, and nonlinear effects of rainfall and temperature exposures on the relative risks of typhoid and iNTS, using monthly lags. An increased relative risk of iNTS incidence was short-lasting but immediate after the onset of the rains, whereas that of typhoid was long-lasting but with a two months delayed start, implying a possible difference in transmission. The relative-risk function of temperature for typhoid was bimodal, with higher risk at both lower (with a 1 month lag) and higher (with a ≥4 months lag) temperatures, possibly reflecting the known patterns of short and long cycle typhoid transmission. In contrast, the relative-risk of iNTS was only increased at lower temperatures, suggesting distinct transmission mechanisms. Environmental and sanitation control strategies may be different for iNTS compared to typhoid disease.
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- 2019
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33. Correction: Pregnancy intention and contraceptive use among HIV-positive Malawian women at 4-26 weeks post-partum: A nested cross-sectional study.
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Thindwa D, Landes M, van Lettow M, Kanyemba A, Nkhoma E, Phiri H, Kalua T, van Oosterhout JJ, Kim EJ, and Tippett Barr BA
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[This corrects the article DOI: 10.1371/journal.pone.0215947.].
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- 2019
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34. Pregnancy intention and contraceptive use among HIV-positive Malawian women at 4-26 weeks post-partum: A nested cross-sectional study.
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Thindwa D, Landes M, van Lettow M, Kanyemba A, Nkhoma E, Phiri H, Kalua T, van Oosterhout JJ, Kim EJ, and Barr BAT
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- Adult, Female, HIV, HIV Infections physiopathology, HIV Infections transmission, HIV Infections virology, Humans, Infectious Disease Transmission, Vertical, Logistic Models, Malawi epidemiology, Postpartum Period physiology, Pregnancy, Religion, Young Adult, Contraception, Family Planning Services, HIV Infections epidemiology, Reproductive Techniques, Assisted
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Background: Avoiding unintended pregnancies through family planning is a WHO strategy for preventing mother to child transmission of HIV (PMTCT) and maternal morbidity/mortality. We investigated factors associated with unintended index pregnancy, unmet contraceptive need, future pregnancy intention and current contraceptive use among Malawian women living with HIV in the Option B+ era., Methods: Women who tested HIV positive at 4-26 weeks postpartum were enrolled into a cross-sectional study at high-volume Under-5 clinics. Structured baseline interviews included questions on socio-demographics, HIV knowledge, partner's HIV status/disclosure, ART use, pregnancy intention and contraceptive use. Logistic regression was used to determine factors associated with outcomes., Results: We enrolled 578 HIV-positive women between May 2015-May 2016; median maternal age was 28 years (y) (interquartile-range [IQR]: 23-32), median parity was 3 deliveries (IQR: 2-4) and median infant age was 7 weeks (IQR: 6-12). Overall, 41.8% women reported unintended index pregnancy, of whom 35.0% reported unmet contraceptive need and 65.0% contraceptive failure. In multivariable analysis, unintended index pregnancy was higher in ≥35y vs. 14-24y (adjusted Odds Ratio [aOR]: 2.1, 95% Confidence Interval [95%CI]: 1.0-4.2) and in women with parity ≥3 vs. primiparous (aOR: 2.9, 95%CI: 1.5-5.6). Unmet contraceptive need at conception was higher in 14-24y vs. ≥35y (aOR: 4.2, 95%CI: 1.8-9.9), primiparous vs. ≥3 (aOR: 8.3, 95%CI: 1.8-39.5), and women with a partner of unknown HIV-status (aOR: 2.2, 95%CI: 1.2-4.0). Current contraceptive use was associated with being on ART in previous pregnancy (aOR: 2.5, 95%CI: 1.5-3.9)., Conclusions: High prevalence of unintended index pregnancy and unmet contraceptive need among HIV-positive women highlight the need for improved access to contraceptives. To help achieve reproductive goals and elimination of MTCT of HIV, integration of family planning into HIV care should be strengthened to ensure women have timely access to a wide range of family planning methods with low failure risk., Competing Interests: The authors have declared that no competing interests exist.
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- 2019
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35. Completion of isoniazid preventive therapy among human immunodeficiency virus positive adults in urban Malawi.
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Thindwa D, MacPherson P, Choko AT, Khundi M, Sambakunsi R, Ngwira LG, Kalua T, Webb EL, and Corbett EL
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- Adolescent, Adult, Anti-Retroviral Agents therapeutic use, Antitubercular Agents adverse effects, CD4 Lymphocyte Count, Female, HIV Seropositivity, Humans, Isoniazid adverse effects, Logistic Models, Malawi epidemiology, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Tuberculosis epidemiology, Young Adult, Antitubercular Agents administration & dosage, HIV Infections drug therapy, Isoniazid administration & dosage, Medication Adherence statistics & numerical data, Tuberculosis prevention & control
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Setting: Despite worldwide scale-up of human immunodeficiency virus (HIV) care services, relatively few countries have implemented isoniazid preventive therapy (IPT). Among other programmatic concerns, IPT completion tends to be low, especially when not fully integrated into HIV care clinics., Objective: To estimate non-completion of 6-month IPT and its predictors among HIV-positive adults aged 16 years., Design: A prospective cohort study nested within a cluster-randomised trial of TB prevention was conducted between February 2012 and June 2014. IPT for 6 months was provided with pyridoxine at study clinics. Non-completion was defined as loss to follow-up (LTFU), death, active/presumptive TB or stopping IPT for any other reason. Random-effects logistic regression was used to determine predictors of non-completion., Results: Of 1284 HIV-positive adults initiated on IPT, 885/1280 (69.1%) were female; the median CD4 count was 337 cells/μl (IQR 199-511); 320 (24.9%) did not complete IPT. After controlling for antiretroviral treatment status, IPT initiation year, age and sex, non-completion of IPT was associated with World Health Organization stage 3/4 (aOR 1.76, 95%CI 1.22-2.55), CD4 count 100-349 cells/μl (aOR 1.93, 95%CI 1.10-3.38) and any reported side effects (aOR 22.00, 95%CI 9.45-46.71)., Conclusion: Completion of IPT was suboptimal. Interventions to further improve retention should target immunosuppressed HIV-positive adults and address side effects.
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- 2018
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36. The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys.
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Darton TC, Meiring JE, Tonks S, Khan MA, Khanam F, Shakya M, Thindwa D, Baker S, Basnyat B, Clemens JD, Dougan G, Dolecek C, Dunstan SJ, Gordon MA, Heyderman RS, Holt KE, Pitzer VE, Qadri F, Zaman K, and Pollard AJ
- Subjects
- Adolescent, Bangladesh epidemiology, Child, Child, Preschool, Cost of Illness, Female, Humans, Incidence, Infant, Infant, Newborn, Malawi epidemiology, Male, Models, Theoretical, Nepal epidemiology, Patient Acceptance of Health Care statistics & numerical data, Research Design, Seroepidemiologic Studies, Surveys and Questionnaires, Typhoid Fever transmission, Carrier State epidemiology, Censuses, Health Resources statistics & numerical data, Population Surveillance methods, Typhoid Fever epidemiology
- Abstract
Introduction: Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12-27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics.The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies., Methods/design: Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers., Ethics and Dissemination: This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences., Trial Registration Number: ISRCTN 12131979., Ethics References: Oxford (Oxford Tropical Research Ethics Committee 39-15).Bangladesh (icddr,b Institutional Review Board PR-15119).Malawi (National Health Sciences Research Committee 15/5/1599).Nepal (Nepal Health Research Council 306/2015)., Competing Interests: Competing interests: AJP chairs the UK Department of Health’s (DH) Joint Committee on Vaccination an Immunisation (JCVI) and the European Medicines Agency (EMA) Scientific Advisory Group on Vaccines and is a member of WHO’s SAGE. The views expressed in this manuscript do not necessarily reflect those of JCVI, DH, EMA or WHO. AJP has previously conducted clinical trials on behalf of the University of Oxford funded by vaccine manufacturers but has no personal financial interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
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- 2017
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37. Initial Accuracy of HIV Rapid Test Kits Stored in Suboptimal Conditions and Validity of Delayed Reading of Oral Fluid Tests.
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Choko AT, Taegtmeyer M, MacPherson P, Cocker D, Khundi M, Thindwa D, Sambakunsi RS, Kumwenda MK, Chiumya K, Malema O, Makombe SD, Webb EL, and Corbett EL
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- Adult, Female, HIV classification, Humans, Male, Mass Screening, Reproducibility of Results, Sensitivity and Specificity, Workflow, HIV genetics, HIV Infections diagnosis, HIV Infections virology, Reagent Kits, Diagnostic standards, Saliva virology
- Abstract
Objectives: To evaluate the effect of storing commonly used rapid diagnostic tests above manufacturer-recommended temperature (at 37°C), and the accuracy of delayed reading of oral fluid kits with relevance to HIV self-testing programmes., Design: A quality assurance study of OraQuick (OraSure), Determine HIV 1/2™ (Alere) and Uni-Gold™ (Recombigen®)., Methods: Consecutive adults (≥18y) attending Ndirande Health Centre in urban Blantyre, Malawi in January to April 2012 underwent HIV testing with two of each of the three rapid diagnostic test kits stored for 28 days at either 18°C (optimally-stored) or at 37°C (pre-incubated). Used OraQuick test kits were stored in a laboratory for delayed day 1 and subsequent monthly re-reading was undertaken for one year., Results: Of 378 individuals who underwent parallel testing, 5 (1.3%) were dropped from the final analysis due to discordant or missing reference standard results (optimally-stored Determine and Uni-Gold). Compared to the diagnostic reference standard, OraQuick had a sensitivity of 97.2% (95% CI: 93.6-99.6). There were 7 false negative results among all test kits stored at 37°C and three false negatives among optimally stored kits. Excellent agreement between pre-incubated tests and optimally-stored tests with Kappa values of 1.00 for Determine and Uni-Gold; and 0.97 (95% CI: 0.95; 1.00) for OraQuick were observed. There was high visual stability on re-reading of OraQuick, with only 1/375 pre-incubated and 1/371 optimally-stored OraQuick kits changing from the initial result over 12 months., Conclusion: Erroneous results observed during HIV testing in low income settings are likely to be due to factors other than suboptimal storage conditions. Re-reading returned OraQuick kits may offer a convenient and accurate quality assurance approach, including in HIV self-testing programmes.
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- 2016
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38. Effect of optional home initiation of HIV care following HIV self-testing on antiretroviral therapy initiation among adults in Malawi: a randomized clinical trial.
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MacPherson P, Lalloo DG, Webb EL, Maheswaran H, Choko AT, Makombe SD, Butterworth AE, van Oosterhout JJ, Desmond N, Thindwa D, Squire SB, Hayes RJ, and Corbett EL
- Subjects
- Adolescent, Adult, Female, HIV Seropositivity, Humans, Malawi, Male, Mass Screening, Middle Aged, Patient Compliance, Self Care, Young Adult, Anti-Retroviral Agents administration & dosage, HIV Infections diagnosis, HIV Infections drug therapy, Home Care Services
- Abstract
Importance: Self-testing for HIV infection may contribute to early diagnosis of HIV, but without necessarily increasing antiretroviral therapy (ART) initiation., Objective: To investigate whether offering optional home initiation of HIV care after HIV self-testing might increase demand for ART initiation, compared with HIV self-testing accompanied by facility-based services only., Design, Setting, and Participants: Cluster randomized trial conducted in Blantyre, Malawi, between January 30 and November 5, 2012, using restricted 1:1 randomization of 14 community health worker catchment areas. Participants were all adult (≥16 years) residents (n = 16,660) who received access to home HIV self-testing through resident volunteers. This was a second-stage randomization of clusters allocated to the HIV self-testing group of a parent trial., Interventions: Clusters were randomly allocated to facility-based care or optional home initiation of HIV care (including 2 weeks of ART if eligible) for participants reporting positive HIV self-test results., Main Outcomes and Measures: The preplanned primary outcome compared between groups the proportion of all adult residents who initiated ART within the first 6 months of HIV self-testing availability. Secondary outcomes were uptake of HIV self-testing, reporting of positive HIV self-test results, and rates of loss from ART at 6 months., Results: A significantly greater proportion of adults in the home group initiated ART (181/8194, 2.2%) compared with the facility group (63/8466, 0.7%; risk ratio [RR], 2.94, 95% CI, 2.10-4.12; P < .001). Uptake of HIV self-testing was high in both the home (5287/8194, 64.9%) and facility groups (4433/8466, 52.7%; RR, 1.23; 95% CI, 0.96-1.58; P = .10). Significantly more adults reported positive HIV self-test results in the home group (490/8194 [6.0%] vs the facility group, 278/8466 [3.3%]; RR, 1.86; 95% CI, 1.16-2.97; P = .006). After 6 months, 52 of 181 ART initiators (28.7%) and 15 of 63 ART initiators (23.8%) in the home and facility groups, respectively, were lost from ART (adjusted incidence rate ratio, 1.18; 95% CI, 0.62-2.25, P = .57)., Conclusions and Relevance: Among Malawian adults offered HIV self-testing, optional home initiation of care compared with standard HIV care resulted in a significant increase in the proportion of adults initiating ART., Trial Registration: clinicaltrials.gov Identifier: NCT01414413.
- Published
- 2014
- Full Text
- View/download PDF
39. A novel community health worker tool outperforms WHO clinical staging for assessment of antiretroviral therapy eligibility in a resource-limited setting.
- Author
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Macpherson P, Lalloo DG, Thindwa D, Webb EL, Squire SB, Chipungu GA, Desmond N, Makombe SD, Taegtmeyer M, Choko AT, and Corbett EL
- Subjects
- Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count methods, Developing Countries, Female, HIV Infections immunology, HIV Infections pathology, Humans, Malawi, Male, Middle Aged, Predictive Value of Tests, Pregnancy, Sensitivity and Specificity, Anti-Retroviral Agents therapeutic use, Clinical Medicine methods, Community Health Workers, HIV Infections diagnosis, HIV Infections drug therapy
- Abstract
The accuracy of a novel community health worker antiretroviral therapy eligibility assessment tool was examined in community members in Blantyre, Malawi. Nurses independently performed World Health Organization (WHO) staging and CD4 counts. One hundred ten (55.6%) of 198 HIV-positive participants had a CD4 count of <350 cells per cubic millimeter. The community health worker tool significantly outperformed WHO clinical staging in identifying CD4 count of <350 cells per cubic millimeter in terms of sensitivity (41% vs. 19%), positive predictive value (75% vs. 68%), negative predictive values (53% vs. 47%), and area under the receiver-operator curve (0.62 vs. 0.54; P = 0.017). Reliance on WHO staging is likely to result in missed and delayed antiretroviral therapy initiation.
- Published
- 2014
- Full Text
- View/download PDF
40. Development and validation of a global positioning system-based "map book" system for categorizing cluster residency status of community members living in high-density urban slums in Blantyre, Malawi.
- Author
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MacPherson P, Choko AT, Webb EL, Thindwa D, Squire SB, Sambakunsi R, van Oosterhout JJ, Chunda T, Chavula K, Makombe SD, Lalloo DG, and Corbett EL
- Subjects
- Humans, Malawi, Geographic Information Systems, Maps as Topic, Poverty Areas, Residence Characteristics, Urban Population
- Abstract
A significant methodological challenge in implementing community-based cluster-randomized trials is how to accurately categorize cluster residency when data are collected at a site distant from households. This study set out to validate a map book system for use in urban slums with no municipal address systems, where classification has been shown to be inaccurate when address descriptions were used. Between April and July 2011, 28 noncontiguous clusters were demarcated in Blantyre, Malawi. In December 2011, antiretroviral therapy initiators were asked to identify themselves as cluster residents (yes/no and which cluster) by using map books. A random sample of antiretroviral therapy initiators was used to validate map book categorization against Global Positioning System coordinates taken from participants' households. Of the 202 antiretroviral therapy initiators, 48 (23.8%) were categorized with the map book system as in-cluster residents and 147 (72.8%) as out-of-cluster residents, and 7 (3.4%) were unsure. Agreement between map books and the Global Positioning System was 100% in the 20 adults selected for validation and was 95.0% (κ = 0.96, 95% confidence interval: 0.84, 1.00) in an additional 20 in-cluster residents (overall κ = 0.97, 95% confidence interval: 0.90, 1.00). With map books, cluster residents were classified rapidly and accurately. If validated elsewhere, this approach could be of widespread value in that it would enable accurate categorization without home visits.
- Published
- 2013
- Full Text
- View/download PDF
41. Determinants and consequences of failure of linkage to antiretroviral therapy at primary care level in Blantyre, Malawi: a prospective cohort study.
- Author
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MacPherson P, Corbett EL, Makombe SD, van Oosterhout JJ, Manda E, Choko AT, Thindwa D, Squire SB, Mann GH, and Lalloo DG
- Subjects
- Adolescent, Adult, Africa South of the Sahara, Anti-HIV Agents therapeutic use, CD4-Positive T-Lymphocytes virology, Cohort Studies, Female, Humans, Malawi, Male, Middle Aged, Program Evaluation, Prospective Studies, Risk, Anti-Retroviral Agents pharmacology, HIV Infections drug therapy, Primary Health Care organization & administration
- Abstract
Background: Poor rates of linkage from HIV diagnosis to ART initiation are a major barrier to universal coverage of ART in sub-Saharan Africa, with reasons for failure poorly understood. In the first study of this kind at primary care level, we investigated the pathway to care in the Malawian National Programme, one of the strongest in Africa., Methods and Findings: A prospective cohort study was undertaken at two primary care clinics in Blantyre, Malawi. Newly diagnosed HIV-positive adults (>15 years) were followed for 6-months to assess completion of eligibility assessments, initiation of ART and death. Two hundred and eighty participants were followed for 82.6 patient-years. ART eligibility assessments were problematic: only 134 (47.9%) received same day WHO staging and 121 (53.2%) completed assessments by 6-months. Completion of CD4 measurement (stage 1/2 only) was 81/153 (52.9%). By 6-months, 87/280 (31.1%) had initiated ART with higher uptake in participants who were ART eligible (68/91, 74.7%), and among participants who received same-day staging (52/134 [38.8%] vs. 35/146 [24.0%] p = 0.007). Non-completion of ART eligibility assessments (adjusted hazard ratio: 0.11, 95% CI: 0.06-0.21) was associated with failure to initiate ART. Retention in pre-ART care for non-ART initiators was low (55/193 [28.5%]). Of the 15 (5.4%) deaths, 11 (73.3%) occurred after ART initiation., Conclusions: Although uptake of ART was high and prompt for patients with known eligibility, there was frequent failure to complete eligibility assessment and poor retention in pre-ART care. HIV care programmes should urgently evaluate the way patients are linked to ART. In particular, there is a critical need for simplified, same-day ART eligibility assessments, reduced requirements for hospital visits, and active defaulter follow-up.
- Published
- 2012
- Full Text
- View/download PDF
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