Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients

Background

A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre.

Methodology/Principal Findings

In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706–25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected.

Conclusions/Significance

A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study.     

Recombinant Antigens Expressed in Pichia pastoris for the Diagnosis of Sleeping Sickness Caused by Trypanosoma brucei gambiense

Background

Screening tests for gambiense sleeping sickness, such as the CATT/T. b. gambiense and a recently developed lateral flow tests, are hitherto based on native variant surface glycoproteins (VSGs), namely LiTat 1.3 and LiTat 1.5, purified from highly virulent trypanosome strains grown in rodents.

Methodology/Principal Findings

We have expressed SUMO (small ubiquitin-like modifier) fusion proteins of the immunogenic N-terminal part of these antigens in the yeast Pichia pastoris. The secreted recombinant proteins were affinity purified with yields up to 10 mg per liter cell culture.

Conclusions/Significance

The diagnostic potential of each separate antigen and a mixture of both antigens was confirmed in ELISA on sera from 88 HAT patients and 74 endemic non-HAT controls. Replacement of native antigens in the screening tests for sleeping sickness by recombinant proteins will eliminate both the infection risk for the laboratory staff during antigen production and the need for laboratory animals. Upscaling production of recombinant antigens, e.g. in biofermentors, is straightforward thus leading to improved standardisation of antigen production and reduced production costs, which on their turn will increase the availability and affordability of the diagnostic tests needed for the elimination of gambiense HAT.     

Health Access Livelihood Framework Reveals Potential Barriers in the Control of Schistosomiasis in the Dongting Lake Area of Hunan Province,China

Background

Access to health care is a major requirement in improving health and fostering socioeconomic development. In the People''s Republic of China (P.R. China), considerable changes have occurred in the social, economic, and health systems with a shift from a centrally planned to a socialist market economy. This brought about great benefits and new challenges, particularly for vertical disease control programs, including schistosomiasis. We explored systemic barriers in access to equitable and effective control of schistosomiasis.

Methodology

Between August 2002 and February 2003, 66 interviews with staff from anti-schistosomiasis control stations and six focus group discussions with health personnel were conducted in the Dongting Lake area, Hunan Province. Additionally, 79 patients with advanced schistosomiasis japonica were interviewed. The health access livelihood framework was utilized to examine availability, accessibility, affordability, adequacy, and acceptability of schistosomiasis-related health care.

Principal Findings

We found sufficient availability of infrastructure and human resources at most control stations. Many patients with advanced schistosomiasis resided in non-endemic or moderately endemic areas, however, with poor accessibility to disease-specific knowledge and specialized health services. Moreover, none of the patients interviewed had any form of health insurance, resulting in high out-of-pocket expenditure or unaffordable care. Reports on the adequacy and acceptability of care were mixed.

Conclusions/Significance

There is a need to strengthen health awareness and schistosomiasis surveillance in post-transmission control settings, as well as to reduce diagnostic and treatment costs. Further studies are needed to gain a multi-layered, in-depth understanding of remaining barriers, so that the ultimate goal of schistosomiasis elimination in P.R. China can be reached.     

The Role of Health Systems Factors in Facilitating Access to Psychotropic Medicines: A Cross-Sectional Analysis of the WHO-AIMS in 63 Low- and Middle-Income Countries

Background

Neuropsychiatric conditions comprise 14% of the global burden of disease and 30% of all noncommunicable disease. Despite the existence of cost-effective interventions, including administration of psychotropic medicines, the number of persons who remain untreated is as high as 85% in low- and middle-income countries (LAMICs). While access to psychotropic medicines varies substantially across countries, no studies to date have empirically investigated potential health systems factors underlying this issue.

Methods and Findings

This study uses a cross-sectional sample of 63 LAMICs and country regions to identify key health systems components associated with access to psychotropic medicines. Data from countries that completed the World Health Organization Assessment Instrument for Mental Health Systems (WHO-AIMS) were included in multiple regression analyses to investigate the role of five major mental health systems domains in shaping medicine availability and affordability. These domains are: mental health legislation, human rights implementations, mental health care financing, human resources, and the role of advocacy groups. Availability of psychotropic medicines was associated with features of all five mental health systems domains. Most notably, within the domain of mental health legislation, a comprehensive national mental health plan was associated with 15% greater availability; and in terms of advocacy groups, the participation of family-based organizations in the development of mental health legislation was associated with 17% greater availability. Only three measures were related with affordability of medicines to consumers: level of human resources, percentage of countries'' health budget dedicated to mental health, and availability of mental health care in prisons. Controlling for country development, as measured by the Human Development Index, health systems features were associated with medicine availability but not affordability.

Conclusions

Results suggest that strengthening particular facets of mental health systems might improve availability of psychotropic medicines and that overall country development is associated with affordability. Please see later in the article for the Editors'' Summary     

Energy Balance Related Behaviour: Personal,Home- and Friend-Related Factors among Schoolchildren in Europe Studied in the ENERGY-Project

Objective

To design interventions that target energy balance-related behaviours, knowledge of primary schoolchildren''s perceptions regarding soft drink intake, fruit juice intake, breakfast consumption, TV viewing and physical activity (PA) is essential. The current study describes personal beliefs and attitudes, home- and friend-related variables regarding these behaviours across Europe.

Design

Cross-sectional study in which personal, family and friend -related variables were assessed by validated questionnaires, and dichotomized as favourable versus unfavourable answers. Logistic regression analyses were conducted to estimate proportions of children giving unfavourable answers and test between-country differences.

Setting

A survey in eight European countries.

Subjects

A total of 7903 10–12 year old primary schoolchildren.

Results

A majority of the children reported unfavourable attitudes, preferences and subjective norms regarding soft drink, fruit juice intake and TV viewing accompanied with high availability and accessibility at home. Few children reported unfavourable attitudes and preferences regarding breakfast consumption and PA. Many children reported unfavourable health beliefs regarding breakfast consumption and TV viewing. Substantial differences between countries were observed, especially for variables regarding soft drink intake, breakfast consumption and TV viewing.

Conclusion

The surveyed children demonstrated favourable attitudes to some healthy behaviours (PA, breakfast intake) as well as to some unhealthy behaviours (soft drink consumption, TV viewing). Additionally, many children across Europe have personal beliefs and are exposed to social environments that are not supportive to engagement in healthy behaviours. Moreover, the large differences in personal, family and friend-related variables across Europe argue for implementing different strategies in the different European countries.     

Drug-Resistant Tuberculosis among HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

Objective

To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa.

Design

Cross-sectional cohort study.

Methods

Consecutive HIV-infected adults (≥18y/o) initiating HIV care were enrolled from May 2007–May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed.

Results

1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42–150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0–12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9–30.5) compared to 5.2% (95% CI 2.1–8.9) among those with no prior TB. 5.1% (95% CI 2.4–9.5) had rifampin or rifampin plus INH resistance.

Conclusions

The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.     

Modeling the impact of tuberculosis control strategies in highly endemic overcrowded prisons

Background

Tuberculosis (TB) in prisons is a major health problem in countries of high and intermediate TB endemicity such as Brazil. For operational reasons, TB control strategies in prisons cannot be compared through population based intervention studies.

Methodology/Principal Findings

A mathematical model is proposed to simulate the TB dynamics in prison and evaluate the potential impact on active TB prevalence of several intervention strategies. The TB dynamics with the ongoing program was simulated over a 10 year period in a Rio de Janeiro prison (TB prevalence 4.6 %). Then, a simulation of the DOTS strategy reaching the objective of 70 % of bacteriologically-positive cases detected and 85 % of detected cases cured was performed; this strategy reduced only to 2.8% the average predicted TB prevalence after 5 years. Adding TB detection at entry point to DOTS strategy had no major effect on the predicted active TB prevalence. But, adding further a yearly X-ray mass screening of inmates reduced the predicted active TB prevalence below 1%. Furthermore, according to this model, after applying this strategy during 2 years (three annual screenings), the TB burden would be reduced and the active TB prevalence could be kept at a low level by associating X-ray screening at entry point and DOTS.

Conclusions/Significance

We have shown that X-ray mass screenings should be considered to control TB in highly endemic prison. Prisons with different levels of TB prevalence could be examined thanks to this model which provides a rational tool for public health deciders.     

Transmission of MDR and XDR Tuberculosis in Shanghai,China

Background

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are global health problems. We sought to determine the characteristics, prevalence, and relative frequency of transmission of MDR and XDR TB in Shanghai, one of the largest cities in Asia.

Methods

TB is diagnosed in district TB hospitals in Shanghai, China. Drug susceptibility testing for first-line drugs was performed for all culture positive TB cases, and tests for second-line drugs were performed for MDR cases. VNTR-7 and VNTR-16 were used to genotype the strains, and prior treatment history and treatment outcomes were determined for each patient.

Results

There were 4,379 culture positive TB cases diagnosed with drug susceptibility test results available during March 2004 through November 2007. 247 (5.6%) were infected with a MDR strain of M. tuberculosis and 11 (6.3%) of the 175 MDR patients whose isolate was tested for susceptibility to second-line drugs, were XDR. More than half of the patients with MDR and XDR were newly diagnosed and had no prior history of TB treatment. Nearly 57% of the patients with MDR were successfully treated.

Discussion

Transmission of MDR and XDR strains is a serious problem in Shanghai. While a history of prior anti-TB treatment indicates which individuals may have acquired MDR or XDR TB, it does not accurately predict which TB patients have disease caused by transmission of MDR and XDR strains. Therefore, universal drug susceptibility testing is recommended for new and retreatment TB cases.     

Tuberculosis Treatment in HIV Infected Ugandans with CD4 Counts >350 Cells/mm3 Reduces Immune Activation with No Effect on HIV Load or CD4 Count

Background

Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.

Methodology

This prospective cohort study, composed of participants within a larger phase 3 open-label randomized controlled clinical trial, measured the impact of TB treatment on immune activation in persons with non-advanced HIV infection (CD4>350 cells/mm³) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB.

Results

Expression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period.

Conclusion

TB therapy leads to measurable decreases in immune activation in persons with HIV/TB co-infection and CD4 counts >350 cells/mm³.     

Linkage of Presumptive Multidrug Resistant Tuberculosis (MDR-TB) Patients to Diagnostic and Treatment Services in Cambodia

Setting

National Tuberculosis Programme, Cambodia.

Objective

In a cohort of TB patients, to ascertain the proportion of patients who fulfil the criteria for presumptive MDR-TB, assess whether they underwent investigation for MDR-TB, and the results of the culture and drug susceptibility testing (DST).

Methods

A cross sectional record review of TB patients registered for treatment between July-December 2011.

Results

Of 19,236 TB patients registered, 409 (2%) fulfilled the criteria of presumptive MDR-TB; of these, 187 (46%) were examined for culture. This proportion was higher among relapse, failure, return after default (RAD) and non-converters at 3 months of new smear positive TB patients (>60%) as compared to non-converters at 2 months of new TB cases (<20%). Nearly two thirds (n = 113) of the samples were culture positive; of these, three-fourth (n = 85) grew Mycobacterium tuberculosis complex (MTBc) and one-fourth (n = 28) grew non-tuberculous Mycobacteria. DST results were available for 96% of the MTBc isolates. Overall, 21 patients were diagnosed as MDR-TB (all diagnosed among retreatment TB cases and none from non-converters) and all of them were initiated on MDR-TB treatment.

Conclusion

There is a need to strengthen mechanisms for linking patients with presumptive MDR-TB to culture centers. The policy of testing non-converters for culture and DST needs to be reviewed.     

Patent and Exclusivity Status of Essential Medicines for Non-Communicable Disease

Objective

The threat of non-communicable diseases (“NCDs”) is increasingly becoming a global health crisis and are pervasive in high, middle, and low-income populations resulting in an estimated 36 million deaths per year. There is a need to assess intellectual property rights (“IPRs”) that may impede generic production and availability and affordability to essential NCD medicines.

Methods

Using the data sources listed below, the study design systematically eliminated NCD drugs that had no patent/exclusivity provisions on API, dosage, or administration route. The first step identified essential medicines that treat certain high disease burden NCDs. A second step examined the patent and exclusivity status of active ingredient, dosage and listed route of administration using exclusion criteria outlined in this study.

Materials

We examined the patent and exclusivity status of medicines listed in the World Health Organization’s (“WHO”) Model List of Essential Drugs (Medicines) (“MLEM”) and other WHO sources for drugs treating certain NCDs. i.e., cardiovascular and respiratory disease, cancers, and diabetes. We utilized the USA Food and Drug Administration Orange Book and the USA Patent and Trademark Office databases as references given the predominant number of medicines registered in the USA.

Results

Of the 359 MLEM medicines identified, 22% (79/359) address targeted NCDs. Of these 79, only eight required in-depth patent or exclusivity assessment. Upon further review, no NCD MLEM medicines had study patent or exclusivity protection for reviewed criteria.

Conclusions

We find that ensuring availability and affordability of potential generic formulations of NCD MLEM medicines appears to be more complex than the presence of IPRs with API, dosage, or administration patent or exclusivity protection. Hence, more sophisticated analysis of NCD barriers to generic availability and affordability should be conducted in order to ensure equitable access to global populations for these essential medicines.     

The impact of asymptomatic helminth co-infection in patients with newly diagnosed tuberculosis in north-west ethiopia

Background

Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls.

Methodology

Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment.

Results

Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV−/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well.

Conclusion

One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV−/TB group.     

Sensitivity of the Quantiferon-Gold In-Tube Assay in Sputum Smear Positive TB Cases in Indonesia

Background

As part of a formal evaluation of the Quantiferon-Gold in-tube assay (QFT-IT) for latent TB infection we compared its sensitivity to the tuberculin skin test (TST) in confirmed adult TB cases in Indonesia. Smear-positive TB disease was used as a proxy gold standard for latent TB infection.

Methods and Findings

We compared the sensitivity of QFT-IT and TST in 98 sputum smear and chest x-ray positive TB cases and investigated risk factors for negative and discordant results in both tests. Both tests showed high sensitivity; (QFT-IT; 88.7%: TST; 94.9%), not significantly different from each other (p value 0.11). Very high sensitivity was seen when tests were combined (98.9%). There were no variables significantly associated with discordant results or with a negative TST. For QFT-IT which particular staff member collected blood was significantly associated with test positivity (p value 0.01). Study limitations include small sample size and lack of culture confirmation or HIV test results.

Conclusions

The QFT-IT has similar sensitivity in Indonesian TB cases as in other locations. However, QFT-IT, like the TST cannot distinguish active TB disease from LTBI. In countries such as Indonesia, with high background rates of LTBI, test specificity for TB disease will likely be low. While our study was not designed to evaluate the QFT-IT in the diagnosis of active TB disease in TB suspects, the data suggest that a combination of TST and QFT-IT may prove useful for ruling out TB disease. Further research is required to explore the clinical role of QFT-IT in combination with other TB diagnostic tests.     

Control of (Multi)Drug Resistance and Tuberculosis Incidence over 23 Years in the Context of a Well-Supported Tuberculosis Programme in Rural Malawi

Background

The rise in tuberculosis (TB) incidence following generalized HIV epidemics can overwhelm TB control programmes in resource-limited settings, sometimes accompanied by rising rates of drug resistance. This has led to claims that DOTS-based TB control has failed in such settings. However, few studies have described the effect of a sustained and well-supported DOTS programme on TB incidence and drug resistance over a long period. We present long-term trends in incidence and drug resistance in rural Malawi.

Methods

Karonga District in northern Malawi has an adult HIV prevalence of ∼10%. A research group, the Karonga Prevention Study, collaborates with the National Tuberculosis Programme to support core TB control activities. Bacteriological, demographic and clinical (including HIV status) information from all patients starting TB treatment in the District have been recorded since 1988. During that period isolates from each culture-positive TB patient were exported for drug sensitivity testing. Antiretroviral therapy (ART) has been widely available since 2005.

Results

Incidence of new smear-positive adult TB peaked at 124/100,000/year in the mid-90s, but has since fallen to 87/100,000/year. Drug sensitivity information was available for 95% (3132/3307) of all culture-positive cases. Initial resistance to isoniazid was around 6% with no evidence of an increase. Fewer than 1% of episodes involved a multi-drug resistant strain.

Discussion

In this setting with a generalised HIV epidemic and medium TB burden, a well-supported DOTS programme enhanced by routine culture and drug sensitivity testing may well have reduced TB incidence and maintained drug resistance at low levels.     

Is IP-10 a Better Biomarker for Active and Latent Tuberculosis in Children than IFNγ?

Background

The blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-γ-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results.

Aim

To investigate this new biomarker for active TB and LTBI in paediatrics.

Method

We measured IP-10 levels using ELISA in supernatants of whole blood samples stimulated with TB-specific-antigens and negative control antigen.

Results

IP-10 is produced in high levels following mycobacterial antigen stimulation in active TB (n = 17) and LTBI (n = 16) compared to controls (n = 16) and to IFN-γ. The baseline levels of IP-10 are increased in active TB and in LTBI, but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI.

Conclusions

IP-10 is a biomarker for tuberculosis in children. However like IFNγ, IP-10 also does not distinguish between active TB and LTBI.     

Scaling up towards international targets for AIDS, tuberculosis, and malaria: contribution of global fund-supported programs in 2011-2015

Objective

The paper projects the contribution to 2011–2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries.

Design

Estimates, using past trends, for the period 2011–2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation.

Results

Global Fund-supported programs are projected to provide ARV treatment to 5.5–5.8 million people, providing 30%–31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%–63% of the international target for tuberculosis case detection and 30%–35% of the ITN distribution target in sub-Saharan Africa.

Conclusion

Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015.     

TB Incidence in an Adolescent Cohort in South Africa

Background

Tuberculosis (TB) is a major public health problem globally. Little is known about TB incidence in adolescents who are a proposed target group for new TB vaccines. We conducted a study to determine the TB incidence rates and risk factors for TB disease in a cohort of school-going adolescents in a high TB burden area in South Africa.

Methods

We recruited adolescents aged 12 to 18 years from high schools in Worcester, South Africa. Demographic and clinical information was collected, a tuberculin skin test (TST) performed and blood drawn for a QuantiFERON TB Gold assay at baseline. Screening for TB cases occurred at follow up visits and by surveillance of registers at public sector TB clinics over a period of up to 3.8 years after enrolment.

Results

A total of 6,363 adolescents were enrolled (58% of the school population targeted). During follow up, 67 cases of bacteriologically confirmed TB were detected giving an overall incidence rate of 0.45 per 100 person years (95% confidence interval 0.29–0.72). Black or mixed race, maternal education of primary school or less or unknown, a positive baseline QuantiFERON assay and a positive baseline TST were significant predictors of TB disease on adjusted analysis.

Conclusion

The adolescent TB incidence found in a high burden setting will help TB vaccine developers plan clinical trials in this population. Latent TB infection and low socio-economic status were predictors of TB disease.     

Access to Diagnostic Tests and Essential Medicines for Cardiovascular Diseases and Diabetes Care: Cost,Availability and Affordability in the West Region of Cameroon

Objective

To assess the availability and affordability of medicines and routine tests for cardiovascular disease (CVD) and diabetes in the West region of Cameroon, a low-income setting.

Methods

A survey was conducted on the availability and cost of twelve routine tests and twenty medicines for CVD and diabetes in eight health districts (four urban and four rural) covering over 60% of the population of the region (1.8 million). We analyzed the percentage of tests and medicines available, the median price against the international reference price (median price ratio) for the medicines, and affordability in terms of the number of days’ wages it would cost the lowest-paid unskilled government worker for initial investigation tests and procurement for one month of treatment.

Results

The availability of tests varied between 10% for the ECG to 100% for the fasting blood sugar. The average cost for the initial investigation using the minimum tests cost 29.76 days’ wages. The availability of medicines varied from 36.4% to 59.1% in urban and from 9.1% to 50% in rural settings. Only metformin and benzathine-benzylpenicilline had a median price ratio of ≤1.5, with statins being largely unaffordable (at least 30.51 days’ wages). One month of combination treatment for coronary heart disease costs at least 40.87 days’ wages.

Conclusion

The investigation and management of patients with medium-to-high cardiovascular risk remains largely unavailable and unaffordable in this setting. An effective non-communicable disease program should lay emphasis on primary prevention, and improve affordable access to essential medicines in public outlets.     

Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease

Background

We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results with short-term antigen stimulated and unstimulated culture supernatants.

Methods

We recruited 15 culture confirmed TB cases and 15 non-TB cases from a high-TB endemic community in Cape Town, South Africa into a pilot case-control study from an on-going larger study. Blood samples collected from study participants were stimulated with 4 M.tb antigens that were previously identified as promising (ESAT6/CFP10 (early secreted), Rv2029c (latency), Rv2032 (latency) and Rv2389c (rpf)) in a 7-day or overnight culture assay. Supernatants were also collected form the standard QuantiFERON In Tube (QFT-IT) test. The levels of 26 host markers were evaluated in the three culture supernatants using the Luminex platform.

Results

The unstimulated levels of CRP, Serum amyloid P (SAP) and serum amyloid A (SAA) and ESAT-6/CFP-10 specific IP-10 and SAA were amongst the best discriminatory markers in all 3 assays, ascertaining TB with AUC of 72–84%. Four-marker models accurately classified up to 92%, 100% and 100% of study participants in the overnight, 7-day and Quantiferon culture supernatants, respectively, after leave-one-out cross validation.

Conclusion

Unstimulated and antigen-specific levels of CRP, SAA, IP-10, MMP-2 and sCD40L hold promise as diagnostic candidates for TB disease in short-term stimulation assays. Larger studies are required to validate these findings but the data suggest that antigen-specific cytokine production and in particular mutimarker biosignatures might contribute to future diagnostic strategies.     

Retooling National TB Control Programmes (NTPs) with New Diagnostics: The NTP Perspective

Background

A delay is evident between the development of new policies on TB diagnostics and their implementation at country level. The Stop TB Partnership would benefit from information from national TB program (NTP) managers on progress towards implementation of new recommendations as well as the opportunities and challenges encountered in the process.

Methods and Findings

To solicit information on the introduction of new TB diagnostics at country level, questionnaires were sent out to NTP managers of high-burden TB countries and a subset of managers was interviewed. The results indicate that about 50% of high-burden TB countries are using the TB diagnostic tools newly recommended by the World Health Organization (WHO). Most NTP managers reported that new diagnostics would only be implemented when officially endorsed by the WHO. All countries have plans to adopt newly endorsed diagnostics at reference laboratory level, while approaches to optimize smear microscopy at lower levels of the health service are given less attention. NTP managers reported diverse challenges to the implementation of new diagnostics.

Conclusions

More information on the obstacles and advantages of introducing new diagnostic tools should be provided to NTP managers to ensure the rational adoption of new diagnostics. A single recommendation covering the introduction of a package of diagnostic tools might be preferable to NTP managers and facilitate implementation in high-burden TB countries.