C-Reactive Protein as a Triage Test in Guiding Who Should Get a Confirmatory Test for Pulmonary Tuberculosis Diagnosis among Adults: A Case-Control Proof-of-Concept Study from Urban Tanzania

Background: The current screening tools for tuberculosis (TB) are inadequate resulting in insufficient TB case detection and continued community transmission of TB. As the world is geared into finding missing TB cases, new strategies are called for to aid in rapid identification of TB cases. This study aimed to evaluate the role C-reactive protein (CRP) in triaging patients to get a definitive test for active pulmonary TB diagnosis in urban Tanzania. Methods: A case-control study was conducted among pulmonary TB (PTB) patients and contacts without active PTB. The diagnosis of PTB was performed using GeneXpert MTB/RIF assay and culture. Blood was collected from cases and controls for measuring CRP levels during recruitment. We compared socio-demographic characteristics, clinical and laboratory parameters obtained during recruitment and performed diagnostic accuracy analyses for CRP. Results: Out of all 193 study participants who were involved in final analysis, 147 (76.2%) were males. Pulmonary TB cases had significantly lower median BMI than controls (median 17.4 kg/m2 [IQR: 15.8 - 19.2 kg/m2] vs., 24.9 kg/m2 [IQR: 22.1 - 28.5 kg/m2), p < 0.001). There was no statistical difference in prevalence of HIV between PTB cases and controls i.e., 13.33% vs., 11.7%, p = 0.48. CRP was significantly higher in PTB cases vs., controls (median 67.8 mg/L, [IQR: 36.5 - 116.9 mg/L] vs., 1.55 mg/L, [IQR: 0.59 - 6.0 mg/L], p = 0.003). Furthermore, CRP at cut-off ≥10 mg/L was associated with best combination of sensitivity, specificity and area under the curve of 89.9%, 95% CI: 82.2 - 95.0, 80.9%, CI: 71.4 - 88.2 and 0.85, 95% CI: 0.80 - 0.90 respectively. A multivariate logistic regression model adjusted for fever, night sweats and body mass index showed that CRP above 10 mg/L was significantly associated with PTB, aOR 5.2, 95% CI 1.2 - 22.8. Conclusions: CRP at cut-off ≥10 mg/L can be used to screen pulmonary TB. These findings can be used to improve TB screening algorithm by incorporating CRP in combination with TB symptoms to identify patients who need further confirmatory TB tests. However, additional prospective studies are required to support our findings and contribute into policy recommendations on use of CRP in a screening algorithm for pulmonary TB.

Distinct clinical characteristics and helminth co-infections in adult tuberculosis patients from urban compared to rural Tanzania

Background:Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis(TB).We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania.Methods:Adult patients(≥18 years)with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam,with~4.4 million inhabitants(urban),and Ifakara in the sparsely populated Kilombero District with~400000 inhabitants(rural).Clinical data were obtained at recruitment.Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz,Baermann,urine filtration,and circulating cathodic antigen tests.Differences between groups were assessed byχ2,Fisher’s exact,and Wilcoxon rank sum tests.Logistic regression models were used to determine associations.Results:Between August 2015 and February 2017,668 patients were enrolled,460(68.9%)at the urban and 208(31.1%)at the rural site.Median patient age was 35 years(interquartile range[IQR]:27-41.5 years),and 454(68%)were males.Patients from the rural setting were older(median age 37 years vs.34 years,P=0.003),had a lower median body mass index(17.5 kg/m2 vs.18.5 kg/m2,P<0.001),a higher proportion of recurrent TB cases(9%vs.1%,P<0.001),and in HIV/TB co-infected patients a lower median CD4 cell counts(147 cells/μl vs.249 cells/μl,P=0.02)compared to those from urban Tanzania.There was no significant difference in frequencies of HIV infection,diabetes mellitus,and haemoglobin concentration levels between the two settings.The overall prevalence of helminth co-infections was 22.9%(95%confidence interval[CI]:20.4-27.0%).The significantly higher prevalence of helminth infections at the urban site(25.7%vs.17.3%,P=0.018)was predominantly driven by Strongyloides stercoralis(17.0%vs.4.8%,P<0.001)and Schistosoma mansoni infection(4.1%vs.16.4%,P<0.001).Recurrent TB was associated with living in a rural setting(adjusted odds ratio[aOR]:3.97,95%CI:1.16-13.67)and increasing age(aOR:1.06,95%CI:1.02-1.10).Conclusions:Clinical characteristics and helminth co-infections pattern differ in TB patients in urban and rural Tanzania.The differences underline the need for setting-specific,tailored public health interventions to improve clinical management of TB and comorbidities.