Trends of Zambia’s tuberculosis burden over the past two decades

Objectives:  To study trends in Zambia’s TB notification rates between 1990 and 2010 and to ascertain progress made towards TB control. Methods:  Retrospective review of TB notification returns and TB programme reports for the period from 1990 to 2010. Results:  Two distinct TB trend periods were identified: a period of rising trends up to a peak between 1990 and 2004 and a period of moderately declining trends between 2004 and 2010. Treatment outcomes improved over the two decades. Data on trends in paediatric TB, TB in prisoners and TB in pregnant women remain scanty and unreliable owing to poor diagnostic capability. There were no data available on trends on drug-resistant TB because of the lack of laboratory services to perform drug sensitivity testing. Conclusions:  The period of increasing TB between 1990 and 2000 coincided with an increase in HIV/AIDS. The period of slightly decreasing TB between 2004 and 2010 can be attributed to improved TB care, sustained DOTS implementation and improvement in TB diagnostic services. Newer diagnostics technologies for the rapid diagnosis of active TB cases and for drug-resistant testing, recently endorsed by the WHO, need to be implemented into the national TB programmes to detect more cases and to provide epidemiological and surveillance data from which to obtain an evidence base for guided investments for TB control. Alignment of TB and HIV services is required to achieve improved management outcomes

Seasonality of childhood tuberculosis cases in Kampala, Uganda, 2010-2015.

BackgroundSeasonality in tuberculosis (TB) has been described, especially in children. However, few studies have assessed seasonality of TB in the equatorial region, and none in children.ObjectivesTo assess for seasonality of childhood TB cases in Kampala, Uganda, and determine the role of temperature, rainfall patterns, and influenza cases on TB diagnoses.MethodsWe retrospectively analyzed demographic and clinical data of children (under 15 years) diagnosed with TB at a pediatric TB clinic in Kampala, Uganda from 2010 to 2015. We performed decomposition analysis of the monthly case time series to assess seasonality. We compared monthly mean plots and performed Poisson regression to assess any association between TB diagnoses and temperature, rainfall, and influenza.ResultsOf the 713 childhood TB cases diagnosed at the clinic, 609 (85%) were clinically diagnosed and 492 (69%) were pulmonary cases. There were minimal monthly variations in TB cases, with a trough in December and peaks in July and October, but there was no significant seasonality. Temperature variations did not show a clear pattern with TB diagnoses. Rainfall alternated with TB diagnoses in the first half of the year, but then overlapped in the second half and was significantly associated with TB diagnoses. Influenza cases were significantly related to TB diagnoses with (β = 0.05, 95% CI 0.01 to 0.09, p = 0.01) or without (β = 0.06, 95% CI 0.01 to 0.1, p = 0.01) rainfall, and had particular overlap with pulmonary TB cases.ConclusionsSeasonal variations in childhood TB diagnoses were non-significant. Temperature did not have a clear pattern with TB diagnoses, but rainfall and influenza cases correlated with the primarily clinically diagnosed childhood TB cases

The age-specific burden and household and school-based predictors of child and adolescent tuberculosis infection in rural Uganda.

BackgroundThe age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection.MethodsFrom 2015-2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5-11 years old) and adolescents (12-19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors.ResultsThe adjusted prevalence of TB infection was 8.5% (95%CI: 6.9-10.4) in children and 16.7% (95% CI:14.0-19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7-16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8-7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0-2.9) fold higher odds of TB infection than those who attended school in the community.ConclusionChildren and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth

Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa.

The WHO recommends integrating interventions to address the devastating TB/HIV co-epidemics in South Africa, yet integration has been poorly implemented and TB/HIV control efforts need strengthening. Identifying infected individuals is particularly difficult in rural settings. We used mathematical modeling to predict the impact of community-based, integrated TB/HIV case finding and additional control strategies on South Africa's TB/HIV epidemics. We developed a model incorporating TB and HIV transmission to evaluate the effectiveness of integrating TB and HIV interventions in rural South Africa over 10 years. We modeled the impact of a novel screening program that integrates case finding for TB and HIV in the community, comparing it to status quo and recommended TB/HIV control strategies, including GeneXpert, MDR-TB treatment decentralization, improved first-line TB treatment cure rate, isoniazid preventive therapy, and expanded ART. Combining recommended interventions averted 27% of expected TB cases (95% CI 18-40%) 18% HIV (95% CI 13-24%), 60% MDR-TB (95% CI 34-83%), 69% XDR-TB (95% CI 34-90%), and 16% TB/HIV deaths (95% CI 12-29). Supplementing these interventions with annual community-based TB/HIV case finding averted a further 17% of TB cases (44% total; 95% CI 31-56%), 5% HIV (23% total; 95% CI 17-29%), 8% MDR-TB (68% total; 95% CI 40-88%), 4% XDR-TB (73% total; 95% CI 38-91%), and 8% TB/HIV deaths (24% total; 95% CI 16-39%). In addition to increasing screening frequency, we found that improving TB symptom questionnaire sensitivity, second-line TB treatment delays, default before initiating TB treatment or ART, and second-line TB drug efficacy were significantly associated with even greater reductions in TB and HIV cases. TB/HIV epidemics in South Africa were most effectively curtailed by simultaneously implementing interventions that integrated community-based TB/HIV control strategies and targeted drug-resistant TB. Strengthening existing TB and HIV treatment programs is needed to further reduce disease incidence

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

Review of multidrug-resistant and extensively drug-resistant TB: global perspectives with a focus on sub-Saharan Africa

Tuberculosis (TB) remains a global emergency and is responsible for 1.7 million deaths annually. Widespread global misuse of isoniazid and rifampicin over three decades has resulted in emergence of the ominous spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) globally. These difficult to treat resistant forms of TB are increasingly seen in Asia, Eastern Europe, South America and sub-Saharan Africa, disrupting TB and HIV control programmes. We review the latest available global epidemiological and clinical evidence on drug-resistant TB in HIV-infected and uninfected populations, with focus on Africa where data are scanty because of poor diagnostic and reporting facilities. The difficult management and infection control problems posed by drug-resistant TB in HIV-infected patients are discussed. Given the increasing current global trends in MDR-TB, aggressive preventive and management strategies are urgently required to avoid disruption of global TB control efforts. The data suggest that existing interventions, public health systems and TB and HIV programmes must be strengthened significantly. Political and funder commitment is essential to curb the spread of drug-resistant TB

Improvement of Tuberculosis Laboratory Capacity on Pemba Island, Zanzibar: A Health Cooperation Project.

Low-income countries with high Tuberculosis burden have few reference laboratories able to perform TB culture. In 2006, the Zanzibar National TB Control Programme planned to decentralize TB diagnostics. The Italian Cooperation Agency with the scientific support of the "L. Spallanzani" National Institute for Infectious Diseases sustained the project through the implementation of a TB reference laboratory in a low-income country with a high prevalence of TB. The implementation steps were: 1) TB laboratory design according to the WHO standards; 2) laboratory equipment and reagent supplies for microscopy, cultures, and identification; 3) on-the-job training of the local staff; 4) web- and telemedicine-based supervision. From April 2007 to December 2010, 921 sputum samples were received from 40 peripheral laboratories: 120 TB cases were diagnosed. Of all the smear-positive cases, 74.2% were culture-positive. During the year 2010, the smear positive to culture positive rate increased up to 100%. In March 20, 2010 the Ministry of Health and Social Welfare of Zanzibar officially recognized the Public Health Laboratory- Ivo de Carneri as the National TB Reference Laboratory for the Zanzibar Archipelago. An advanced TB laboratory can represent a low cost solution to strengthen the TB diagnosis, to provide capacity building and mid-term sustainability

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

Background Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. Methods This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. Results In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Conclusion Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold

Discriminating active from latent tuberculosis in patients presenting to community clinics.

BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings