Cost implications of delays to tuberculosis diagnosis among pulmonary tuberculosis patients in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Delays seeking care worsen the burden of tuberculosis and cost of care for patients, families and the public health system. This study investigates costs of tuberculosis diagnosis incurred by patients, escorts and the public health system in 10 districts of Ethiopia.</p> <p>Methods</p> <p>New pulmonary tuberculosis patients ≥ 15 years old were interviewed regarding their health care seeking behaviour at the time of diagnosis. Using a structured questionnaire patients were interviewed about the duration of delay at alternative care providers and the public health system prior to diagnosis. Costs incurred by patients, escorts and the public health system were quantified through patient interview and review of medical records.</p> <p>Results</p> <p>Interviews were held with 537 (58%) smear positive patients and 387 (42%) smear negative pulmonary patients. Of these, 413 (45%) were female; 451 (49%) were rural residents; and the median age was 34 years. The mean (median) days elapsed for consultation at alternative care providers and public health facilities prior to tuberculosis diagnosis was 5 days (0 days) and 3 (3 days) respectively. The total median cost incurred from first consultation to diagnosis was $27 per patient (mean =$59). The median costs per patient incurred by patient, escort and the public health system were $16 (mean =$29), $3 (mean =$23) and $3 (mean =$7) respectively. The total cost per patient diagnosed was higher for women, rural residents; those who received government food for work support, patients with smear negative pulmonary tuberculosis and patients who were not screened for TB in at least one district diagnostic centers.</p> <p>Conclusions</p> <p>The costs of tuberculosis diagnosis incurred by patients and escorts represent a significant portion of their monthly income. The costs arising from time lost in seeking care comprised a major portion of the total cost of diagnosis, and may worsen the economic position of patients and their families. Getting treatment from alternative sources and low index of suspicion public health providers were key problems contributing to increased cost of tuberculosis diagnosis. Thus, the institution of effective systems of referral, ensuring screening of suspects across the district public health system and the involvement of alternative care providers in district tuberculosis control can reduce delays and the financial burden to patients and escorts.</p

Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae

Abstract: Leprosy continues to be the belligerent public health hazard for the causation of high disability and eventual morbidity cases with stable prevalence rates, even with treatment by the on-going multidrug therapy (MDT). Today, dapsone (DDS) resistance has led to fear of leprosy in more unfortunate people of certain developing countries. Herein, DDS was chemically conjugated with five phytochemicals independently as dapsone-phytochemical conjugates (DPCs) based on azo-coupling reaction. Possible biological activities were verified with computational chemistry and quantum mechanics by molecular dynamics simulation program before chemical synthesis and spectral characterizations viz., proton-HNMR, FTIR, UV and LC-MS. The in vivo antileprosy activity was monitored using the ‘mouse-foot-pad propagation method’, with WHO recommended concentration 0.01% mg/kg each DPC for 12 weeks, and the host-toxicity testing of the active DPC4 was seen in cultured-human-lymphocytes in vitro. One-log bacilli cells in DDS-resistant infected mice footpads decreased by the DPC4, and no bacilli were found in the DDS-sensitive mice hind pads. Additionally, the in vitro host toxicity study also confirmed that the DCP4 up to 5,000 mg/L level was safety for oral administration, since a minor number of dead cells were found in red color under a fluorescent microscope. Several advanced bioinformatics tools could help locate the potential chemical entity, thereby reducing the time and resources required for in vitro and in vitro tests. DPC4 could be used in place of DDS in MDT, evidenced from in vivo antileprosy activity and in vitro host toxicity study

Predicting neuropathy and reactions in leprosy at diagnosis and before incident events. Results from the INFIR cohort study

BackgroundLeprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.Methodology/Principal FindingsThe study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.Conclusions/SignificanceThese findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability

A Comparison of Tools Used for Tuberculosis Diagnosis in Resource-Limited Settings: A Case Study at Mubende Referral Hospital, Uganda

This study compared TB diagnostic tools and estimated levels of misdiagnosis in a resource-limited setting. Furthermore, we estimated the diagnostic utility of three-TB-associated predictors in an algorithm with and without Direct Ziehl-Neelsen (DZM).Data was obtained from a cross-sectional study in 2011 conducted at Mubende regional referral hospital in Uganda. An individual was included if they presented with a two weeks persistent cough and or lymphadenitis/abscess. 344 samples were analyzed on DZM in Mubende and compared to duplicates analyzed on direct fluorescent microscopy (DFM), growth on solid and liquid media at Makerere University. Clinical variables from a questionnaire and DZM were used to predict TB status in multivariable logistic and Cox proportional hazard models, while optimization and visualization was done with receiver operating characteristics curve and algorithm-charts in Stata, R and Lucid-Charts respectively.DZM had a sensitivity and specificity of 36.4% (95% CI = 24.9-49.1) and 97.1%(95% CI = 94.4-98.7) compared to DFM which had a sensitivity and specificity of 80.3%(95% CI = 68.7-89.1) and 97.1%(95% CI = 94.4-98.7) respectively. DZM false negative results were associated with patient's HIV status, tobacco smoking and extra-pulmonary tuberculosis. One of the false negative cases was infected with multi drug resistant TB (MDR). The three-predictor screening algorithm with and without DZM classified 50% and 33% of the true cases respectively, while the adjusted algorithm with DZM classified 78% of the true cases.The study supports the concern that using DZM alone risks missing majority of TB cases, in this case we found nearly 60%, of who one was an MDR case. Although adopting DFM would reduce this proportion to 19%, the use of a three-predictor screening algorithm together with DZM was almost as good as DFM alone. It's utility is whoever subject to HIV screening all TB suspects