Scoring tools to identify TB patients facing catastrophic costs in the Philippines.

BACKGROUND: This study was to meet a practical need to design a simple tool to identify TB patients who may potentially be facing catastrophic costs while seeking TB care in the public sector. Such a tool may help prevent and address catastrophic costs among individual patients. METHODS: We used data from the national TB patient cost survey in the Philippines. We randomly allocated TB patients to either the derivation or validation sample. Using adjusted odds ratios (ORs) and ß coefficients of logistic regression, we developed four scoring systems to identify TB patients who may be facing catastrophic costs from the derivation sample. We validated each scoring system in the validation sample. RESULTS: We identified a total of 12 factors as predictive indicators associated with catastrophic costs. Using all 12 factors, the ß coefficients-based scoring system (area under the curve [AUC] 0.783, 95% CI 0.754-0.812) had a high validity. Even with seven selected factors with OR > 2.0, the validity remained in the acceptable range (ß coefficients-based: AUC 0.767, 95% CI 0.737-0.798). CONCLUSION: The ß coefficients-based scoring systems in this analysis can be used to identify those at high risk of facing catastrophic costs due to TB in the Philippines. Operational feasibility needs to be investigated further to implement this in routine TB surveillance.

CONTEXTE: Cette étude visait à répondre à un besoin pratique de concevoir un outil simple pour identifier les patients atteints de TB qui pourraient potentiellement être confrontés à des coûts catastrophiques lorsqu'ils recherchent des soins de TB dans le secteur public. Un tel outil pourrait aider à prévenir et à traiter les coûts catastrophiques chez les patients individuels. MÉTHODES: Nous avons utilisé des données de l'enquête nationale sur les coûts des patients atteints de TB aux Philippines. Nous avons réparti aléatoirement les patients atteints de TB dans l'échantillon de dérivation ou de validation. À l'aide des odds ratio (OR) ajustés et des coefficients ß de la régression logistique, nous avons développé quatre systèmes de notation pour identifier les patients atteints de TB qui pourraient être confrontés à des coûts catastrophiques à partir de l'échantillon de dérivation. Nous avons validé chaque système de notation dans l'échantillon de validation. RÉSULTATS: Nous avons identifié un total de 12 facteurs en tant qu'indicateurs prédictifs associés à des coûts catastrophiques. En utilisant les 12 facteurs, le système de notation basé sur les coefficients ß (aire sous la courbe [AUC] 0,783 ; IC 95% 0,754­0,812) avait une validité élevée. Même avec sept facteurs sélectionnés avec OR > 2,0, la validité est restée dans la plage acceptable (basée sur les coefficients ß : AUC 0,767 ; IC 95% 0,737­0,798). CONCLUSION: Les systèmes de notation basés sur les coefficients ß dans cette analyse peuvent être utilisés pour identifier les personnes à haut risque de faire face à des coûts catastrophiques liés à la TB aux Philippines. La faisabilité opérationnelle doit être étudiée plus avant pour mettre en œuvre cela dans la surveillance de routine de la TB.

ScreenTB: a tool for prioritising risk groups and selecting algorithms for screening for active tuberculosis.

SETTING AND OBJECTIVES: There is an urgent need to improve tuberculosis (TB) case detection globally. This would require greater focus on the implementation of TB screening programs. However, to be productive, cost-effective, and ethical, TB screening efforts should be tailored to their local context, targeted to the populations most likely to benefit and utilizing diagnostic tools with sufficient accuracy.DESIGN AND RESULTS: We have developed an online tool, ScreenTB to help National TB Programmes (NTPs) and their partners plan TB screening activities by modeling the potential outcomes of screening programs, including yield of TB cases diagnosed (true- and false-positives), costs, and cost-effectiveness, specific to the populations screened and the diagnostic algorithms used. In Myanmar, ScreenTB was used to assist the NTP in prioritizing risk groups for screening efforts and selecting appropriate screening algorithms to maximize case detection and minimize false-positive diagnoses.CONCLUSION: The ScreenTB tool can help facilitate the prioritization of risk groups for screening and the selection of appropriate screening algorithms. This is useful when used as part of a larger planning process that considers feasibility of screening, vulnerability of risk groups, potential impact of screening on TB transmission, human rights implications of screening and equity in health care access.

Policies and practices on the programmatic management of latent tuberculous infection: global survey.

SETTING: Global survey among low tuberculosis (TB) burden countries, which are primary target countries for the World Health Organization (WHO) guidelines on the programmatic management of latent tuberculous infection (LTBI). OBJECTIVE: To perform a baseline assessment of policies and practices for the programmatic management of LTBI. DESIGN: Online and paper-based pre-tested questionnaire filled out by national TB programme managers or their equivalents from 108 countries. RESULTS: Of 74 respondent countries, 75.7% (56/74) had a national policy on LTBI. The majority of the countries (67/74, 90.5%) provided LTBI testing and treatment for child contacts of TB cases, while almost two thirds (49/74, 66%) reported provision of LTBI testing and treatment to people living with the human immunodeficiency virus (PLHIV). Six countries (8.1%) did not report providing LTBI management to child contacts and PLHIV. Among countries that reported both the availability of policy and practice of testing and treatment of LTBI for at-risk populations, a system for recording and reporting data was available in 62% (33/53) for child contacts and in 53% (21/40) for PLHIV. CONCLUSION: Countries need to ensure that national LTBI policies and a standardised monitoring and evaluation system are in place to promote the programmatic management of LTBI.

Outcomes of Category I and II regimens in mono- and polyresistant tuberculosis cases in the Philippines.

SETTING: National Tuberculosis Programme, the Philippines. OBJECTIVE: To compare treatment outcomes of Category I and Category II regimens among mono- and/or polyresistant tuberculosis (TB) cases under programme conditions. DESIGN: Retrospective cohort analysis of pulmonary TB patients from two data sets from the National Drug Resistance Survey and the Programmatic Management of Drug-resistant Tuberculosis by linking drug resistance patterns with treatment outcomes. RESULTS: Of 288 Category I patients, 193 were isoniazid (INH) resistant, 42 were either ethambutol (EMB) or streptomycin (SM) resistant, and 53 were resistant to a combination of two or all three TB drugs. Of 138 Category II patients, 92 were INH-resistant, 9 were either EMB- or SM-resistant, and 37 were poly-resistant. Respectively 206 (87.7%) and 41 (77.4%) mono- and poly-resistant patients treated with the Category I regimen achieved significantly higher successful treatment outcomes, in comparison to respectively 60 (59.4%) and 15 (40.5%) mono- and poly-resistant patients treated with the Category II regimen. CONCLUSION: The Category II regimen produced poor outcomes, whereas the Category I regimen achieved a treatment success rate of more than 85% among new patients with the same drug resistance patterns. The poor outcomes of the Category II regimen could be attributed to other factors such as patient behaviour and comorbidities, rather than drug resistance.

Western Pacific Regional Green Light Committee: progress and way forward.

The Western Pacific Regional Green Light Committee (rGLC WPR) was established in 2011 to promote the rational scale-up of programmatic management of drug-resistant tuberculosis (PMDT). We reflect on its achievements, consider the challenges faced, and explore its potential future role. Achievements include the supervision and support of national PMDT action plans, increased local ownership, contextualized guidance, and a strong focus on regional capacity building, as well as a greater awareness of regional challenges. Future rGLC activities should include (1) advocacy for high-level political commitment; (2) monitoring, evaluation, and supervision; (3) technical support and contextualized guidance; and (4) training, capacity building, and operational research. Regional activities require close collaboration with both national and global efforts, and should be an important component of the new Global Drug-resistant TB Initiative.

Reduction of tuberculosis burden among prisoners in Mongolia: review of case notification, 2001-2010.

Documentation on the TB situation in prisons in developing countries is limited, and very few studies have quantitatively evaluated TB control programmes in prisons. This study aimed to evaluate TB control in Mongolian prisons by analysing routine programmatic data. The TB caseload in prisons has significantly diminished in the last decade, synchronised with policy and programmatic development, including systematic entry screening on detention and after conviction, and improved living conditions. Improved case detection during entry screening may have contributed to the significant reduction of the TB caseload in prisons.

Loss of biological activity of human chorionic gonadotropin (hCG) by the amino acid substitution on the "CMGCC" region of the alpha-subunit.

In order to study the bioactive sites of the glycoprotein hormones, we have prepared five point mutants on the CMGCC (Cys28-Met29-Gly30-Cys31-Cys32) region of the human alpha-subunit by using site-directed mutagenesis. Each mutant human chorionic gonadotropin (hCG) agr; cDNA and a wild-type hCG beta cDNA were transcribed by T3 RNA polymerase, and the mixture of the hCG alpha mRNA and hCG beta mRNA was microinjected into Xenopus laevis oocytes. All five mutant hCGs produced in oocyte culture supernatants were detected as immunoreactive forms by enzyme immunoassay. In contrast, four mutants (Cys28-->Tyr28, Gly30-->Arg30, Ala30, Asp30) were devoid of biological activity in vitro bioassay using the production of testosterone with mouse Leydig cells. These results indicate that the CMGCC region in the alpha-subunit, particularly the cysteine residue at position 28 and the glycine residue at position 30, plays an important role in the biosynthesis of glycoprotein hormones.

Membrane-spanning Fc gamma receptor III isoform expressed on human placental trophoblasts.

PROBLEM: Fc receptor for immunoglobulin (Fc gamma R) is an important mediator of immunological functions in the feto-maternal relationship. We have demonstrated by immunohistochemical means that three distinct classes of Fc gamma Rs are expressed in the different cell components of the human placenta. METHOD: In this study, Fc gamma RIII isoform expressed on placental trophoblasts (PTs) was investigated by indirect immunofluorescence and cDNA cloning. PTs, isolated from human term placenta by digestion with proteolytic enzyme, were reacted with monoclonal antibodies (MAb) against the Fc gamma Rs and other surface markers of leukocytes and subjected to flow cytometric analysis. RESULTS: PTs were positively stained with 3G8 and Leu1 1b against Fc gamma RIII, partially stained with MAb against MHC class I, but not with 32.2 (Fc gamma RI), IV3 (Fc gamma RII), or MAbs against CD4, CD19, or CD56, indicating that only low affinity receptor, Fc gamma RIII, is expressed on PTs. The DNA sequence of cloned Fc gamma RIII CDNA from PTs by PCR was identical to that of natural killer (NK) cell isoform, including the position of the stop codon that differs from the granulocyte isoform by several nucleotide substitutions. We further analyzed the susceptibility of PTs against phosphatidylinositol specific phospholipase C (PI-PLC) to determine the structural topology of PT isoform. While the reactivity with 3G8 on PTs was not influenced by treatment with PI-PLC, that on granulocytes was significantly diminished with PI-PLC. CONCLUSIONS: This result confirmed that Fc gamma RIII on PTs is a membrane-spanning molecule, and that it is distinctive from PI anchoring Fc gamma RIII on granulocytes.

Differential mRNA expression of three distinct classes of Fc gamma receptor at the feto-maternal interface.

Heterogeneous expression of three classes of Fc gamma receptor (Fc gamma RI, IIa, IIb, and III) in the human placenta and decidua was examined by Northern blot hybridization and cDNA amplification analysis by polymerase chain reaction. Messenger RNA of Fc gamma RI, IIa and III genes were consistently expressed in the human placenta in all trimesters of gestation. The transcripts of the Fc gamma RIIb gene, on the other hand, dramatically increased in placentae at the second and third trimesters. This characteristic expression of Fc gamma RIIb after 20 gestational weeks was confirmed by sequential cDNA amplification analysis. Fc gamma RI, IIa and III mRNAs, but not Fc gamma RIIb, were also detected in the human decidua. Interestingly, while Fc gamma R mRNA could be induced in uterine endometrium by pseudopregnancy therapy using estrogen and progesterone, there was no detectable mRNA in hormone-unprimed normal endometrium. These findings suggest that Fc gamma Rs expressed at the feto-maternal interface can be transcriptionally regulated by sex steroid hormones as multifunctional molecules. In addition, the Fc gamma RIIb molecule is predominantly produced by placental tissues after the mid-trimester of gestation and possibly plays an important role in the transport of IgG molecules from mother to fetus.