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Performance characteristics and costs of serological tests for brucellosis in a pastoralist community of northern Tanzania

Discussion

Our data show that all the rapid commercial plate assays evaluated had poor diagnostic accuracy. In comparison, the RBT 1:2 and RBT 1:8 assays both had high diagnostic accuracy and also had lower costs per sample when applied to diagnose brucellosis in this population of Tanzanian pastoralists. The cELISA had high diagnostic accuracy but a higher cost per sample when evaluated as a frontline test. This study provides a strong rationale for replacing the rapid commercial plate assays with the RBT for frontline brucellosis testing in Tanzanian health facilities.

Our findings in this Tanzanian pastoralist population corroborate the results of earlier studies carried out elsewhere, where excellent diagnostic performance of RBT 1:2 (high sensitivity and specificity estimates within the 85–100% interval) was reported24,27,29,61,62,63,64. RBT specificity estimates may be underestimated in contexts where a positive test can occur due to previous exposure to Brucella spp., rather than active infection, or an active infection caused by a cross-reacting pathogen (e.g. Y. enterocolitica O:9, Vibrio cholerae O:1, Francisella tularensis or Escherichia coli O157)20. Compared to our reference case standard (including SAT and blood culture results), RBT 1:2 and RBT 1:8 both displayed high specificity. With RBT 1:8, the point estimate for specificity increased from 96.6 to 99.0%. However, the 95% confidence intervals on these estimates overlap. Five out of the seven false positive test results observed with RBT 1:2 were classified as true negatives with RBT 1:8. This leads to an increase of 21.4% in the PPV (from 63.2% for RBT 1:2 to 84.6% for RBT 1:8) (Table 2). The precision of these estimates is limited by the relatively small sample size available for this study, but a true difference between the two RBT protocols is likely to be important in clinical practice. Particularly in contexts where access to confirmatory tests is limited, a high PPV is a crucial attribute of a frontline test. The PPV determines the confidence with which health practitioners start patients on targeted treatments. For brucellosis, high PPV is particularly important, given the long duration of recommended treatment regimens, adverse effects of these regimens for patients, frequent involvement of restricted drugs, and frequent treatment failures5,65,66. A full evaluation of the cut-off used for the RBT was not performed as part of this study, in part due to the small proportion of positive individuals and thus limited data to robustly compare results at different dilutions. However, the data for all RBT results at serial dilution are shown in the accompanying data file (see Data Availability section). Further evaluation of the field performance of the RBT with different dilution cut-offs at scale could resolve this query. Future studies could also aim to inform selection of a preferred testing protocol for this context and shed light on the impacts of current misdiagnosis.

Our results showed that the widely used commercial plate agglutination tests have significantly lower specificity and diagnostic accuracy as compared to the RBT protocols. These findings agree with the small number of published evaluations of similar tests16,17,18. We estimate that the PPV of each of the commercial plate agglutination tests is at least six times lower than that of the RBT 1:2 (63.2%) and RBT 1:8 (84.6%). Given the relatively small sample size and low brucellosis case prevalence in this sample set, the sensitivity estimates obtained in this study have wide confidence intervals. However, the point estimates for sensitivity indicate that between 28.6% (Fortress) and 64.3% (Arkray) of the pre-defined brucellosis cases were classified as positive by the commercially available plate agglutination tests. Estimating the performance of RBT 1:2 and RBT 1:8 using the commercial plate agglutination tests as reference further highlights the difference in performance between these tests: (1) if the Eurocell test (the rapid commercial plate assay with highest percentage of samples positive and lowest estimated accuracy) was used as the reference for true case status, the estimated accuracy of both RBT 1:2 and 1:8 would be 53.7% (95% CI 46.8–60.4); (2) if the Fortress test (the rapid commercial plate assay with lowest percentage of samples positive and highest estimated accuracy) was used as the reference for true case status instead, the accuracy of RBT 1:2 and RBT 1:8 would be 69.7% (95% CI 63.2–75.7) and 72.5% (95% CI 66.0–78.3), respectively. Given the considerable existing literature on the performance of the RBT (1:2 and 1:8), these accuracy estimates are not plausible. These data further illustrate that the results of the commercial plate agglutination tests cannot be regarded as accurate indicators of true brucellosis case status. The proportion of individuals testing positive by the four commercial plate agglutination tests (Table 1) are implausibly high, when evaluated alongside the other tests and the existing literature on the brucellosis prevalence expected in this and other comparable populations15,51,67. These estimates are unlikely to be explained by previous exposure in this population68,69,70,71, and are more likely due to the low specificity of these tests. The higher sensitivity of RBT protocols (as compared to these commercial plate agglutination tests) is likely to be explained, at least partially, by the standardization of the antigen to OIE specification and the acid buffer used to suspend Rose Bengal stained Brucella cells. The acid buffering improves the ability of RBT to detect agglutinating and non-agglutinating antibodies irrespective of the stage of disease evolution30. Information on the pH of the buffers used with the commercially available plate agglutination tests is not included in the test kits. Our data provide further rationale for replacement of the poorly performing plate agglutination tests that are currently used in Tanzanian health facilities with RBT (RBT 1:2 or RBT 1:8), as recommended in national and international guidelines6,7,9.

Using the estimated optimal cut-off for human testing, the cELISA evaluated in this study was highly sensitive and specific in this population. The kit recommended cut-off for this cELISA, which has been applied for human testing previously39,40,41 uses a cut-off value of 60% of the OD obtained with conjugate control wells. This threshold value was originally optimized for livestock testing, and its application to human samples requires formal evaluation33,34,72,73,74. The estimated cut-off point based on the assay readings for this population and the pre-defined brucellosis case status (56% of the conjugate blank OD) fell close to the kit recommended value (60%). The high estimates of sensitivity and specificity generated from a small sample set provide a strong justification for a full validation of the cELISA, specifically including cut-off evaluation in a larger dataset that ideally also includes well-characterized patient samples known to span the different clinical stages of presentation of human brucellosis.

There are no publicly available data on the per-sample running costs of the RBT or alternative test options in northern Tanzania75. The cost of a diagnostic test can negatively impact its utility20,37,46, especially in rural, low-resource settings5,8,20. Our data suggest that RBT 1:2 is the cheapest option for frontline use among the evaluated tests. The RBT 1:8 has marginally increased costs as compared to the RBT 1:2 due to the additional time and consumables required for serum dilution, but this cost difference is trivial (Fig. 2). In addition to the poor diagnostic performance of the commercially available plate agglutination tests, they also cost more per sample as compared to the RBT 1:2 or RBT 1:8 (Fig. 2). The cELISA costs more per sample than any of plate agglutination tests evaluated under the common assumptions specified. However, the costs per sample for the cELISA are substantially reduced when samples are batched for testing (Table 3). The application of the cELISA, with batching of samples, is more likely to occur when used as a frontline test in larger health facilities. In this study, our primary aim was to assess the suitability of available options specifically for frontline use in a clinical setting, hence, assuming a small number of samples per batch. Under these circumstances, RBT 1:2 and RBT 1:8 were more affordable (and accurate) than any of the other evaluated test options.

The availability and use of a rapid, cheap, and accurate test for the diagnosis of human brucellosis are vital to minimize some of the impacts of brucellosis. The higher the test accuracy in particular, the lower the risk of delays in diagnosing true cases and, consequently, the lower the multiple downstream impacts of missed diagnoses. Among the population of individuals tested for brucellosis but who are not true cases, a higher test accuracy could also contribute to faster exclusion of brucellosis as a likely cause of illness. The large-scale deployment of a cheap and accurate test for brucellosis would also be key to strengthening surveillance capacity, therefore improving the quality of the data needed to plan, design, and deliver brucellosis control strategies. Our findings indicate that the RBT is a good candidate for national roll-out in Tanzania. Further evaluation of RBT implementation at scale is needed to assess, among other factors, reliability of the reagent supply chain, ability to ensure and maintain antigen quality in field conditions76,77 and overall test performance under field conditions. A regional or national scale evaluation could also provide evidence to inform the selection of the best candidate test for confirmatory testing in this context.

This study has several limitations. First, given the limited sample size and proportion of brucellosis cases in the population used for this study, the confidence intervals on many of the estimates of test sensitivity are wide and overlap in many cases. Second, we used serum of febrile patients from a pastoralist community, some of whom may have had previous exposure to Brucella39,67,78. We evaluated the performance of the index tests in this study with reference to sample status defined by SAT and culture tests that are estimated to have lower sensitivity than the RBT and some cELISA assays20,31. As a consequence, our estimates of the specificity and PPV of the index tests evaluated might be underestimated in comparison to their unobserved true performance in this population. Third, for the commercial plate agglutination tests, we used the semi-quantitative dilution protocols described in the test kit materials in all cases. In practice, these dilution protocols are rarely applied in health facilities, and test results are performed with neat serum testing only51,52. For this reason, our data may well over-estimate the specificity of the commercial plate agglutination tests as compared to their common use in practice. Finally, all of the diagnostic test data presented were generated in a research laboratory, and we have not evaluated the field performance of these tests.

Conclusions

This evaluation of the diagnostic performance characteristics of tests for human brucellosis provides robust estimates of the markedly poor diagnostic performance of the commercial plate agglutination tests currently available and widely used in Tanzania. Our results suggest that data generated based on these currently used tests are likely to be highly inaccurate and that the systematic use of RBT (either RBT 1:2 or RBT 1:8) as the frontline test for human brucellosis in northern Tanzania would provide more accurate data on human brucellosis than is currently available. In addition, the per-sample costs of RBT 1:2 and RBT 1:8 were lower than any other test evaluated. Future studies to evaluate the feasibility and cost-effectiveness of national roll-out of RBT as the frontline brucellosis test in Tanzania are recommended. Standardized application of RBT for human brucellosis testing across Tanzania could have enormous value for both patient management and also for understanding the current distribution and burden of disease by improving disease surveillance data10,50.

Data availability

The datasets generated during and/or analysed during the current study are available in the Enlighten research data repository of the University of Glasgow (https://doi.org/10.5525/gla.researchdata.1119).

References

1. 1.

Dean, A. S., Crump, L., Greter, H., Schelling, E. & Zinsstag, J. Global burden of human brucellosis: A systematic review of disease frequency. PLoS Negl. Trop. Dis. 6, 66 (2012).

2. 2.

Franco, M. P., Mulder, M., Gilman, R. H. & Smits, H. L. Human brucellosis. Lancet Infect. Dis. 7, 775–786 (2007).

3. 3.

Al-Dahouk, S., Sprague, L. D. & Neubauer, H. New developments in the diagnostic procedures for zoonotic brucellosis in humans. Sci. Tech. Rev. Off. Int. des Epizoot. 32, 177–188 (2013).

4. 4.

Jamil, T. et al. Brucella abortus: Current research and future trends. Curr. Clin. Microbiol. Rep. 4, 1–10 (2017).

5. 5.

Rubach, P. M., Halliday, J. E. B., Cleaveland, S. & Crump, A. J. Brucellosis in low-income and middle-income countries. Curr. Opin. Infect. Dis. 26, 404–412 (2014).

6. 6.

Corbel, M. J., Food and Agriculture Organization of the United Nations, World Health Organization & World Organisation for Animal Health. Brucellosis in Humans and Animals. World Health Organization (WHO Press, 2006).

7. 7.

CDC. Brucellosis (Brucella spp.) 2010 Case Definition (2010).

8. 8.

Dean, A. S. et al. Clinical manifestations of human brucellosis: A systematic review and meta-analysis. PLoS Negl. Trop. Dis. 6, 67 (2012).

9. 9.

Center for Disease Control and Prevention. Brucellosis Reference Guide: Exposures, Testing and Prevention. 1–35 (2017).

10. 10.

United Republic of Tanzania (URT). Guidelines for Surveillance of Prioritized Zoonotic Diseases for Human and Animal Health in the United Republic of Tanzania. Government Report vol. 1 (2018).

11. 11.

The European Commission. Commission Implementing Decision 2018/945 On the communicable diseases and related special health issues to be covered by epidemiological surveillance as well as relevant case definitions. Annex II. Official Journal of the European Union 1–74 (2018).

12. 12.

Yagupsky, P., Morata, P. & Colmenero, J. D. Laboratory diagnosis of human Brucellosis Pablo. Clin. Microbiol. Rev. 33, 1–54 (2020).

13. 13.

Bouley, A. J. et al. Brucellosis among hospitalized febrile patients in northern Tanzania. Am. J. Trop. Med. Hyg. 87, 1105–1111 (2012).

14. 14.

Cash-Goldwasser, S. et al. Risk factors for human brucellosis in northern Tanzania. Am. J. Trop. Med. Hyg. 19, 135–140 (2017).

15. 15.

Bodenham, F. R. et al. Prevalence and speciation of acute brucellosis in febrile patients from a pastoralist community of Tanzania. Sci. Rep. 10, 1–10 (2020).

16. 16.

de Glanville, W. A. et al. Poor performance of the rapid test for human brucellosis in health facilities in Kenya. PLoS Negl. Trop. Dis. 11, 1–15. https://doi.org/10.1038/s41598-020-62849-4 (2017).

17. 17.

Kiambi, S. G., Fèvre, E. M., Omolo, J., Oundo, J. & de Glanville, W. A. Risk factors for acute human brucellosis in Ijara, north-eastern Kenya. PLoS Negl. Trop. Dis. 14, e0008108 (2020).

18. 18.

Alumasa, L. et al. Hospital-based evidence on cost-effectiveness of brucellosis diagnostic tests and treatment in Kenyan hospitals. PLoS Negl. Trop. Dis. 891, 1–19 (2021).

19. 19.

Diaz, R., Maravi Poma, E. & Rivero, A. Comparison of counter immunoelectrophoresis with other serological tests in the diagnosis of human brucellosis. Bull. World Health Organ. 53, 417–424 (1976).

20. 20.

Al Dahouk, S. & Nöckler, K. Implications of laboratory diagnosis on brucellosis therapy. Expert Rev. Anti. Infect. Ther. 9, 833–845 (2011).

21. 21.

Kunda, J. et al. Health-seeking behaviour of human brucellosis cases in rural Tanzania. BMC Public Health 7, 1–7 (2007).

22. 22.

Robertson, L. Diagnosis and treatment of infection with Brucella abortus, biotype 5. J. Clin. Pathol. 20, 199–203 (1967).

23. 23.

Roop, R. M., Preston-Moore, D., Bagchi, T. & Schurig, G. G. Rapid identification of smooth Brucella species with a monoclonal antibody. J. Clin. Microbiol. 25, 2090–2093 (1987).

24. 24.

Oomen, L. J. A. & Waghela, S. The Rose Bengal plate test in human brucellosis. Trop. Geogr. Med. 26, 300–302 (1974).

25. 25.

Caces, E., De Lauture, H., Vol, S., Tichet, J. & Boulard, P. The systematic detection of human brucellosis by the Rose Bengal test on agricultural people after a study in the middle west of France on 89000 workers. Comp. Immunol. Microbiol. Infect. Dis. 1, 107–114 (1978).

26. 26.

Cernyseva, M. I., Knjazeva, E. N. & Egorova, L. S. Study of the plate agglutination test with rose bengal antigen for the diagnosis of human brucellosis. Bull. World Health Organ. 55, 669–674 (1977).

27. 27.

Russell, A. O., Patton, C. M. & Kaufmann, A. F. Evaluation of the card test for diagnosis of human brucellosis. J. Clin. Microbiol. 7, 454–458 (1978).

28. 28.

Saz, J. V. et al. Enzyme-linked immunosorbent assay for diagnosis of brucellosis. Eur. J. Clin. Microbiol. 6, 71–74 (1987).

29. 29.

Maichomo, M. W., McDermott, J. J., Arimi, S. M. & Gathura, P. B. Assessment of the Rose-Bengal plate test for the diagnosis of human brucellosis in health facilities in Narok district, Kenya. East Afr. Med. J. 75, 219–222 (1998).

30. 30.

Alton, G. G., Jones, L. M. & Pietz, D. E. Laboratory techniques in brucellosis. Monogr. Ser. World Health Organ. 47, 1–163 (1975).

31. 31.

Díaz, R., Casanova, A., Ariza, J. & Moriyón, I. The rose Bengal test in human brucellosis: A neglected test for the diagnosis of a neglected disease. PLoS Negl. Trop. Dis. 5, 1–7 (2011).

32. 32.

Ruiz-Mesa, J. D. et al. Rose Bengal test: Diagnostic yield and use for the rapid diagnosis of human brucellosis in emergency departments in endemic areas. Clin. Microbiol. Infect. 11, 221–225 (2005).

33. 33.

Lucero, N. E., Foglia, L., Ayala, S. M., Gall, D. & Nielsen, K. Competitive enzyme immunoassay for diagnosis of human brucellosis. J. Clin. Microbiol. 37, 3245–3248 (1999).

34. 34.

Perrett, L. L., McGiven, J. A., Brew, S. D. & Stack, J. A. Evaluation of competitive ELISA for detection of antibodies to Brucella infection in domestic animals. Croat. Med. J. 51, 314–319 (2010).

35. 35.

Lucero, N. E. et al. Unusual clinical presentation of brucellosis caused by Brucella canis. J. Med. Microbiol. 54, 505–508 (2005).

36. 36.

Lucero, N. E., Escobar, G. I., Ayala, S. M., Paulo, P. S. & Nielsen, K. Fluorescence polarization assay for diagnosis of human brucellosis. J. Med. Microbiol. 52, 883–887 (2003).

37. 37.

Dieckhaus, K. D. & Kyebambe, P. S. Human Brucellosis in Rural Uganda: Clinical manifestations, diagnosis, and comorbidities at Kabale Regional Referral Hospital, Kabale, Uganda. Open Forum Infect. Dis. 4, 1–6 (2017).

38. 38.

United Republic of Tanzania (URT), United States Department of Defense (DoD), Defense Threat Reduction Agency (DTRA), Cooperative Threat Reduction (CTR) & Cooperative Biological Engagement Program (CBEP). The United Republic of Tanzania One Health Strategic Plan 2015–2020. http://www.tzdpg.or.tz/fileadmin/documents/dpg_internal/dpg_working_groups_clusters/cluster_2/health/Key_Sector_Documents/Tanzania_Key_Health_Documents/FINAL_URT_One_Health_Strategy_Plan_20151021.pdf (2015).

39. 39.

Shirima, G. M. & Kunda, J. S. Prevalence of brucellosis in the human, livestock and wildlife interface areas of Serengeti National Park, Tanzania. Onderstepoort J. Vet. Res. 83, 2–5 (2016).

40. 40.

John, K. et al. Quantifying risk factors for human brucellosis in Rural Northern Tanzania. PLoS ONE 5, 66 (2010).

41. 41.

Gabriel, S. M. The Epidemiology of Brucellosis in Animals and Humans in Arusha and Manyara Regions of Tanzania (The University of Glasgow, Glasgow, 2005).

42. 42.

Nasinyama, G. et al. Brucella sero-prevalence and modifiable risk factors among predisposed cattle keepers and consumers of un-pasteurized milk in Mbarara and Kampala districts, Uganda. Afr. Health Sci. 14, 790–796 (2014).

43. 43.

Šimundić, A.-M. Measures of diagnostic accuracy: Basic definitions. Ejifcc 19, 203–211 (2009).

44. 44.

Okeh, U. & Okoro, C. Evaluating measures of indicators of diagnostic test performance: Fundamental meanings and formulars. J. Biom. Biostat. 03, 1–10 (2012).

45. 45.

Metz, C. E. Basic principles of ROC analysis. Semin. Nucl. Med. 8, 283–298 (1978).

46. 46.

Chanda, P., Castillo-Riquelme, M. & Masiye, F. Cost-effectiveness analysis of the available strategies for diagnosing malaria in outpatient clinics in Zambia. Cost Eff. Resour. Alloc. 7, 1–12 (2009).

47. 47.

Wang, R., Wang, G., Zhang, N., Li, X. & Liu, Y. Clinical evaluation and cost-effectiveness analysis of serum tumor markers in lung cancer. Biomed Res. Int. 2013, 66 (2013).

48. 48.

Assefa, L. M. et al. Diagnostic accuracy and cost-effectiveness of alternative methods for detection of soil-transmitted helminths in a post-treatment setting in Western Kenya. PLoS Negl. Trop. Dis. 8, 66 (2014).

49. 49.

Rutjes, A. W. S. et al. Evidence of bias and variation in diagnostic accuracy studies. CMAJ 174, 469–476 (2006).

50. 50.

The United Republic of Tanzania (URT). National Strategy for Prevention and Control of Brucellosis in Humans and Animals 2018–2023. Prime Ministers Office vol. 56 (2018).

51. 51.

Orsel, K. et al. Brucellosis serology as an alternative diagnostic test for patients with malaria-like symptoms. Tanzan. J. Health Res. 17, 1–10 (2015).

52. 52.

Mngumi, E. B., Mirambo, M. M., Wilson, S. & Mshana, S. E. Predictors of specific anti-Brucella antibodies among humans in agro-pastoral communities in Sengerema district, Mwanza, Tanzania: The need for public awareness. Trop. Med. Health 44, 64 (2016).

53. 53.

APHA Scientific. COMPELISA 160 & 400 A Competitive ELISA Kit for the Detection of Antibodies Against Brucella in Serum Samples Instructions For Use (For In-Vitro and Animal Use Only). 1–4 (2014).

54. 54.

Greiner, M., Sohr, D. & Göbel, P. A modified ROC analysis for the selection of cut-off values and the definition of intermediate results of serodiagnostic tests. J. Immunol. Methods 185, 123–132 (1995).

55. 55.

Khan, M. R. A. & Brandenburger, T. ROCit: Performance Assessment of Binary Classifier with Visualization. R package version 2.1.1. 1–21 (2020).

56. 56.

R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. https://www.R-project.org/ (2019).

57. 57.

Clopper, C. J. & Pearson, E. S. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26, 404 (1934).

58. 58.

Perez-jaume, S., Pallares, N. & Skaltsa, K. Optimum Threshold Estimation. in Package ‘ThresholdROC’ F (R CRAN, 2019).

59. 59.

Stock, A. C., Hielscher, T. & Stock, M. C. Package ‘ DTComPair, Comparison of Binary Diagnostic Tests in a Paired Study Design’ (2015).

60. 60.

World Health Organization (WHO). Laboratory Test Costing Tool User Manual/Training Manual. 17 (2019).

61. 61.

Andriopoulos, P. et al. Prevalence of Brucella antibodies on a previously acute brucellosis infected population: sensitivity, specificity and predictive values of Rose Bengal and Wright standard tube agglutination tests. Infection 43, 325–330 (2015).

62. 62.

Rahman, A. K. M. A., Saegerman, C. & Berkvens, D. Latent class evaluation of three serological tests for the diagnosis of human brucellosis in Bangladesh. Trop. Med. Health 44, 1–6 (2016).

63. 63.

Ron-Román, J. et al. Bayesian evaluation of three serological tests for detecting antibodies against brucella spp. Among humans in the Northwestern Part of Ecuador. Am. J. Trop. Med. Hyg. 100, 1312–1320 (2019).

64. 64.

Konstantinidis, A. et al. Evaluation and comparison of fluorescence polarization assay with three of the currently used serological tests in diagnosis of human brucellosis. Eur. J. Clin. Microbiol. Infect. Dis. 26, 715–721 (2007).

65. 65.

Kazak, E. et al. Brucellosis: A retrospective evaluation of 164 cases. Singap. Med. J. 57, 624–629 (2016).

66. 66.

Pappas, G., Solera, J., Akritidis, N. & Tsianos, E. New approaches to the antibiotic treatment of brucellosis. Int. J. Antimicrob. Agents 26, 101–105 (2005).

67. 67.

Makala, R. et al. Seroprevalence of Brucella infection and associated factors among pregnant women receiving antenatal care around human, wildlife and livestock interface in Ngorongoro ecosystem, Northern Tanzania. A cross-sectional study. BMC Infect. Dis. 20, 1–7 (2020).

68. 68.

Ducrotoy, M. J. & Bardosh, K. L. How do you get the Rose Bengal Test at the point-of-care to diagnose brucellosis in Africa? The importance of a systems approach. Acta Trop. 165, 33–39 (2017).

69. 69.

Njeru, J. et al. Human brucellosis in febrile patients seeking treatment at remote hospitals, northeastern Kenya, 2014–2015. Emerg. Infect. Dis. 22, 2160–2164 (2016).

70. 70.

Muturi, M. et al. Risk factors for human brucellosis among a pastoralist community in South-West Kenya, 2015 11 Medical and Health Sciences 1117 Public Health and Health Services. BMC Res. Notes 11, 1–6 (2018).

71. 71.

Osoro, E. M. et al. Strong association between human and animal brucella seropositivity in a linked study in Kenya, 2012–2013. Am. J. Trop. Med. Hyg. 93, 224–231 (2015).

72. 72.

McGiven, J. A. et al. Validation of FPA and cELISA for the detection of antibodies to Brucella abortus in cattle sera and comparison to SAT, CFT, and iELISA. J. Immunol. Methods 278, 171–178 (2003).

73. 73.

Stack, J. A., Perrett, L. L. & Macmillan, A. P. Competitive ELISA for Bovine Brucellosis suitable for testing poor quality samples. Vet. Rec. 145, 735–736 (1999).

74. 74.

Organisation International Epizoonoses (OIE). Chapter 3.6.1—Development and optimisation of antibody detection assays. in OIE Validation Recommendations 1–13 (2014). https://doi.org/10.1787/c88edbcd-en.

75. 75.

Kunda, J. S. The Epidemiology of Human Brucellosis in the Context of Zoonotic Diseases in Tanzania (University of Edinburgh, Edinburgh, 2005).

76. 76.

Gall, D. & Nielsen, K. Serological diagnosis of bovine brucellosis: A review of test performance and cost comparison. OIE Rev. Sci. Technol. 23, 989–1002 (2004).

77. 77.

Ducrotoy, M. et al. Brucellosis in Sub-Saharan Africa: Current challenges for management, diagnosis and control. Acta Trop. 165, 179–193 (2017).

78. 78.

Assenga, J. A., Matemba, L. E., Muller, S. K., Malakalinga, J. J. & Kazwala, R. R. Epidemiology of Brucella infection in the human, livestock and wildlife interface in the Katavi-Rukwa ecosystem, Tanzania. BMC Vet. Res. 11, 1–11 (2015).

Acknowledgements

We thank the patients and staff at the Endulen Hospital for providing the samples used in this study, the field team for their assistance in data collection and the laboratory teams at Kilimanjaro Clinical Research Institute (KCRI) and Animal & Plant Health Agency (APHA), UK, for diagnostic analyses. We also thank the Ngorongoro Conservation Area Authority (NCAA) for approvals to collect data within the Ngorongoro Conservation Area. A.S.L, C.M and R.R.K are supported by the DELTAS Africa Initiative Afrique One-ASPIRE scholarship scheme (Afrique One-ASPIRE/DEL-15-008, http://afriqueoneaspire.org). Â.J.M is supported by The University of Glasgow’s Lord Kelvin/Adam Smith (LKAS) PhD scholarship. R.F.B received scholarship support from the UK Biotechnology and Biological Sciences Research Council (BBSRC), Department for International Development (DFID), the Economic & Social Research Council, the Medical Research Council, the Natural Environment Research Council and the Defence Science & Technology Laboratory, under the Zoonoses and Emerging Livestock Systems – Associated Studentship (ZELS-AS) programme (grant number BB/N503563/1). This study was also supported by the Zoonoses and Emerging Livestock Systems program grant numbers BB/L018845 and BB/L017679 http://www.bbsrc.ac.uk/).

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A.S.L., Â.J.M., R.F.B, J.A.M., C.M, V.P.M., N.A.M., M.P.R., G.M.S., C.J.K., R.R.K., J.E.B.H, B.T.M. designed the study. A.S.L., Â.J.M., R.F.B., J.A.M., D.D.S., M.P.R., P.S., K.M.T., J.E.B.H. performed data collection/generation. A.S.L, Â.J.M, J.A.M, J.E.B.H. performed data analysis. A.S.L., Â.J.M, J.A.M, J.E.B.H, B.T.M wrote the main manuscript. All authors reviewed the manuscript.

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Correspondence to AbdulHamid S. Lukambagire.

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Lukambagire, A.S., Mendes, Â.J., Bodenham, R.F. et al. Performance characteristics and costs of serological tests for brucellosis in a pastoralist community of northern Tanzania. Sci Rep 11, 5480 (2021). https://doi.org/10.1038/s41598-021-82906-w

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