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Objectives To assess hypertension prevalence and the extent and associated factors of hypertension diagnosis, follow‐up, treatment and control gaps in low‐income urban Medellin, Colombia. Methods We randomly sampled 1873 adults aged 35 or older. Unaware hypertensive individuals were defined as those without previous diagnosis whose average blood pressure was equal to or above 140/90 mmHg. For aware hypertensive patients, control was delimited as average blood pressure below 140/90 if under 59 years old or diabetic, and as less than 150/90 otherwise. We used logistic regression to identify care gap‐associated factors. Results Hypertension prevalence was 43.5% (95% CI 41.2–45.7). We found 28.2% aware and 15.3% unaware hypertensive individuals, which corresponds to a 35.1% (95% CI 31.9–38.5) underdiagnosis. This gap was determined by age, sex, education and lifestyle factors. 14.4% (95% CI 11.6–17.6) of aware hypertensive patients presented a follow‐up gap, 93.4% (95% CI 90.9–95.2) were prescribed antihypertensive drugs, but 38.9% (95% CI 34.7–43.3) were not compliant. The latter was strongly associated with follow‐up. The hypertension control gap in aware hypertensive patients, 39.0% (95% CI: 34.9–43.2), was associated with being older, having diabetes, weakly adhering to pharmacological treatment and receiving poor non‐pharmacological advice. Overall, 60.4% (95% CI 57.0–63.8) of aware and unaware hypertensive participants had either diagnosed but uncontrolled or undiagnosed hypertension. Conclusions We found high hypertension prevalence coupled with, from an international perspective, encouraging awareness and control figures. Still, there remains ample room for improvement. Our findings can assist in designing integrated primary healthcare measures that further strengthen equitable and effective access to hypertension care and control.

BackgroundA recurrent tuberculosis (TB) episode results from exogenous reinfection or relapse after cure. The use of genotyping allows the distinction between both.MethodsWe did a systematic review and meta-analysis, using four databases to search for studies in English, French and Spanish published between 1 January 1980 and 30 September 2020 that assessed recurrences after TB treatment success and/or differentiated relapses from reinfections using genotyping. We calculated person years of follow-up and performed random-effects model meta-analysis for estimating pooled recurrent TB incidence rates and proportions of relapses and reinfections. We performed subgroup analyses by clinical–epidemiological factors and by methodological study characteristics.FindingsThe pooled recurrent TB incidence rate was 2.26 per 100 person years at risk (95% CI 1.87 to 2.73; 145 studies). Heterogeneity was high (I2=98%). Stratified pooled recurrence rates increased from 1.47 (95% CI 0.87 to 2.46) to 4.10 (95% CI 2.67 to 6.28) per 100 person years for studies conducted in low versus high TB incidence settings. Background HIV prevalence, treatment drug regimen, sample size and duration of follow-up contributed too. The pooled proportion of relapses was 70% (95% CI 63% to 77%; I²=85%; 48 studies). Heterogeneity was determined by background TB incidence, as demonstrated by pooled proportions of 83% (95% CI 75% to 89%) versus 59% (95% CI 42% to 74%) relapse for studies from settings with low versus high TB incidence, respectively.InterpretationThe risk of recurrent TB is substantial and relapse is consistently the most frequent form of recurrence. Notwithstanding, with increasing background TB incidence the proportion of reinfections increases and the predominance of relapses among recurrences decreases.PROSPERO registration numberCRD42018077867

Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those5 years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines.We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models.A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts5 and 98.1% (558/569) of contacts aged 5-19 years. Of 191 eligible contacts5 years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19 years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts5 years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19 year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7 years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for5 year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19 years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for5 year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19 years old), and, only for those 5-19 years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2).We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.Les contacts des cas de tuberculose (TB) pulmonaire présentent un risque élevé d'infection à la TB et d'évolution vers la maladie. Les contacts étroits et familiaux et ceux de moins de 5 ans sont les plus à risque. Le traitement préventif à l'isoniazide (TPI) peut largement prévenir la maladie TB chez les personnes infectées. Nous avons mené une étude à Lima, au Pérou, pour déterminer le nombre de contacts proches et familiaux qui ont été évalués, qui ont commencé le TPI et qui l'ont achevé, ainsi que les facteurs associés au respect des directives nationales. MÉTHODES: Etude longitudinal rétrospective de tous les cas de TB diagnostiqués entre janvier 2015 et juillet 2016 dans 13 établissements de santé dans le sud de Lima. Les cartes de traitement, les registres de TB et les dossiers cliniques ont été examinés et des données sur les cas indice, l’investigation des contacts et les établissements de santé ont été extraites. Nous avons tabulé les fréquences d'évaluation des contacts par les caractéristiques des contacts et des cas indice. Pour étudier les déterminants de l'initiation et de l'achèvement du TPI, nous avons utilisé des modèles linéaires mixtes généralisés. RÉSULTATS: Au total, 2.323 contacts ont été rapportés par 662 cas indice; 70,2% des contacts âgés de moins de 5 ans ont commencé le TPI et 31,4% l'ont terminé, tandis que 36,7% des contacts âgés de 5 à 19 ans ont commencé le TPI et 32,4% l'ont terminé. Les facteurs associés au fait de ne pas commencer ou de terminer le TPI étaient: être un parent de second degré du cas indice, ne pas avoir reçu le test tuberculinique, être le contact d'un cas indice à frottis négatif et fréquenter un établissement de santé à faible charge de travail pour les moins de cinq ans contre fréquenter un établissement de santé à charge de travail élevée pour les contacts plus âgés.Nous avons constaté une compliance partielle à l'enquête sur les contacts de la TB, et avons identifié les facteurs liés aux contacts, aux cas indice et aux établissements de santé associés au début et à la fin du TPI qui peuvent guider le programme de TB dans l'augmentation de sa couverture et de sa qualité.

Objectives: To assess a multicomponent intervention to improve private practitioners (PPs) involvement in referral of presumptive pulmonary TB (PTB) cases to the Revised National TB Control Programme (RNTCP) for sputum examination. Methods: Randomised controlled trial. We randomly allocated all 189 eligible PPs in Tumkur city, South India, to intervention or control arm. The intervention, implemented between December 2014 and January 2016, included two sets of activities, one targeted at health system strengthening (building RNTCP staff capacity to collaborate with PPs, provision of feedback on referrals through SMS) and one targeted at intervention PPs (training in RNTCP, provision of referral pads and education materials and monthly visits to PPs by RNTCP staff). Crude and adjusted referral and PTB case-finding rate ratios were calculated with negative binomial regression. Results: PPs referred 836 individuals (548 from intervention and 169 from control arm PPs) of whom 176 were diagnosed with bacteriologically confirmed PTB. The proportion (95% confidence interval) of referring PPs [0.59 (0.49, 0.68) vs. 0.42 (0.32, 0.52) in the intervention and control arm, respectively], mean referral rate per PP-year [(5.7 (3.8, 8.7) vs. 1.8 (1.2, 2.8)] and smear-positive PTB case-finding rate per PP-year [(1.5 (0.9, 2.2) vs. 0.6 (0.3, 0.9)] were significantly higher in the intervention than the control arm. Stratifying by qualification, a statistically significant difference in the above indicators remained only among GPs and internists. Overall, surgeons, paediatricians and gynaecologists referred few patients. PP referrals contributed to 20% of the sputum smear positive PTB cases detected by RNTCP in Tumkur city (14% were from intervention arm PPs). Conclusions: We demonstrated the effectiveness of a health system-oriented intervention to improve PP's referrals of presumptive PTB cases to RNTCP.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. Objectives: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. Methods: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. Results: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. Conclusion: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT. Revisión por pares

Background India’s Revised National Tuberculosis (TB) Control Programme (RNTCP) offers free TB diagnosis and treatment. But more than 50% of TB patients seek care from private practitioners (PPs), where TB is managed sub-optimally. In India, there is dearth of studies capturing experiences of TB patients when they navigate through health facilities to seek care. Also, there is less information available on how PPs make decisions to refer TB cases to RNTCP. We conducted this study to understand the factors influencing TB patient’s therapeutic itineraries to RNTCP and PP’s cross referral practices linked to RNTCP. Methods We conducted in-depth interviews on a purposive sample of 33 TB patients and 38 PPs. Patients were categorised into three groups: those who reached RNTCP directly, those who were referred by PPs to RNTCP and patients who took DOT from PPs. We assessed patient’s experiences in each category and documented their journey from initial symptoms until they reached RNTCP, where they were diagnosed and started on treatment. PPs were categorised into three groups based on their TB case referrals to RNTCP: actively-referring, minimally-referring and non-referring. Results Patients had limited awareness about TB. Patients switched from one provider to the other, since their symptoms were not relieved. A first group of patients, self-medicated by purchasing get rid drugs from private chemists over the counter, before seeking care. A second group sought care from government facilities and had simple itineraries. A third group who sought care from PPs, switched concurrently and/or iteratively from public and private providers in search for relief of symptoms causing important diagnostic delays. Eventually all patients reached RNTCP, diagnosed and started on treatment. PP’s cross-referral practices were influenced by patient’s paying capacity, familiarity with RNTCP, kickbacks from private labs and chemists, and even to get rid of TB patients. These trade-offs by PPs complicated patient’s itineraries to RNTCP. Conclusions India aims to achieve universal health care for TB. Our study findings help RNTCP to develop initiatives to promote early detection of TB, by involving PPs and private chemists and establish effective referral systems from private sectors to RNTCP.

Objectives: To develop a clinical prediction rule (CPR) for the diagnosis of pleural tuberculosis (PT) in patients with pleural exudates in Peru. Methods: Clinical and laboratory information was collected from patients with exudative pleural effusion attending two reference hospitals in Lima, Peru. Predictive findings associated with PT in a multiple logistic regression model were used to develop the CPR. A definite diagnosis of PT was based on a composite reference standard including bacteriological and/or histological analysis of pleural fluid and pleural biopsy specimens. Results: A total of 238 patients were included in the analysis, of whom 176 had PT. Age, sex, previous contact with a TB patient, presence of lymphadenopathy, and pleural adenosine deaminase (ADA) levels were found to be independently associated with PT. These predictive findings were used to construct a CPR, for which the area under the receiver operating characteristics curve (AUC) was 0.92. The single best cut-off point was a score of >= 60 points, which had a sensitivity of 88%, specificity of 92%, a positive likelihood ratio of 10.9, and a negative likelihood ratio of 0.13. Conclusions: The CPR is accurate for the diagnosis of PT and could be useful for treatment initiation while avoiding pleural biopsy. A prospective evaluation is needed before its implementation in different settings. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Background Since 2006, the Peruvian National TB program (NTP) recommends voluntary counseling and testing (VCT) for all tuberculosis (TB) patients. Responding to the differential burden of both diseases in Peru, TB is managed in peripheral health facilities while HIV is managed in referral centers. This study aims to determine the coverage of HIV screening among TB patients and the characteristics of persons not screened. Methods From March 2010 to December 2011 we enrolled new smear-positive pulmonary TB adults in 34 health facilities in a district in Lima. NTP staff offered VCT to all TB patients. Patients with an HIV positive result were referred for confirmation tests and management. We interviewed patients to collect their demographic and clinical characteristics and registered if patients opted in or out of the screening. Results Of the 1295 enrolled TB patients, nine had a known HIV diagnosis. Of the remaining, 76.1% (979) were screened for HIV. Among the 23.9% (307) not screened, 38.4% (118) opted out of the screening. TB patients at one of the health care facilities of the higher areas of the district (OR = 3.38, CI 95% 2.17–5.28 for the highest area and OR = 2.82, CI 95% 1.78–4.49 for the high area) as well as those reporting illegal drug consumption (OR = 1.65, CI 95% 1.15–2.37) were more likely not to be screened. Twenty-four were HIV positive (1.9% of all patients 1295, or 2.4% of those screened). Of 15 patients diagnosed with HIV during the TB episode, ten were enrolled in an HIV program. The median time between the result of the HIV screening and the first consultation at the HIV program was 82 days (IQR, 32–414). The median time between the result of the HIV screening and antiretroviral initiation was 148.5 days (IQR 32–500). Conclusions An acceptable proportion of TB patients were screened for HIV in Lima. Referral systems of HIV positive patients should be strengthened for timely ART initiation.

Objectives: Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed t developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic. Methods: We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model, we developed a score-based CPR. We assessed its internal validity and diagnostic performance. Results: Of 155 analysed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10-500 cells in CSF and adenosine deaminase 6 U/l in CSF. It classifies patients into high-, moderate- or low-score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high- or the low-score group, permitting prompt decision-making. In patients in the high-score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores, a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity. Conclusion: This CPR could support decision-making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact are necessary before application in other settings.

Objectives To estimate the proportion of tuberculosis cases attributable to recent transmission and the risk factors possibly associated with tuberculosis clustering. Methods Population-based study combining information from epidemiological investigation of tuberculosis cases notified to the National Tuberculosis Control Program in Havana, Cuba, in 2009 with the results of genotyping of Mycobacterium tuberculosis isolates with variable number tandem repeat of mycobacterial interspersed repetitive units (MIRU-VNTR) typing. Results Of 186 cases, 61 were genotyped: 33 patterns and five clusters with 19, 7, 3, 2 and 2 cases were found. The proportion of cases due to recent transmission was 45% (95% confidence interval 33–58%). Routine contact investigation failed to identify a substantial number of epidemiological links. A history of living in a closed setting was strongly associated with clustering. Conclusions The proportion of cases due to recent transmission in Havana in 2009 is high. The existing control measures in closed settings should be strengthened. A study on a larger number of cases and for a longer time period should be carried out to obtain more precise estimates. Further studies on the utility and cost-effectiveness of the addition of molecular epidemiology techniques to support the progress towards tuberculosis elimination in Cuba, a low-incidence resource-limited setting, are also needed. Objectifs Estimer la proportion de cas de tuberculose (TB) attribuables a une transmission recente et les facteurs de risque pouvant etre associes au regroupement de la TB. Methodes Etude basee sur la population, combinant les informations provenant d'une enquete epidemiologique des cas de TB notifies au programme national de lutte contre la TB a La Havane, a Cuba, en 2009, avec des resultats du genotypage des isolats de Mycobacterium tuberculosis par la methode MIRU-VNTR. Resultats Sur 186 cas, 61 ont ete genotypes: 33 profils et 5 regroupements avec 19, 7, 3, 2 et 2 cas ont ete trouves. La proportion des cas dus a une transmission recente etait de 45% (IC95%: 33 a 58). L'investigation systematique des contacts n'a pas permis d'identifier un nombre important de liens epidemiologiques. Le fait de vivre dans une zone fermee a ete fortement associe au regroupement. Conclusions La proportion de cas dus a une transmission recente a La Havane en 2009 est elevee. Les mesures de controle existantes dans les zones fermees devraient etre renforcees. Une etude portant sur un plus grand nombre de cas et sur une periode plus longue devrait etre effectuee afin d'obtenir des estimations plus precises. Des etudes supplementaires sur l'utilite et le rapport cout-efficacite de l'adoption des techniques d’epidemiologie moleculaire pour soutenir le progres vers l’elimination de la TB a Cuba, une zone a ressources limitees et a faible incidence sont egalement necessaires. Objetivos Calcular la proporcion de casos de tuberculosis atribuibles a una transmision reciente y los factores de riesgo posiblemente asociados con los conglomerados de tuberculosis. Metodos Estudio poblacional que combina informacion de estudios epidemiologicos de casos de tuberculosis notificados al programa nacional de control de la tuberculosis en La Habana, Cuba, en el 2009 con los resultados de genotipar aislados de Mycobacterium tuberculosis mediante el metodo MIRU-VNTR (numero variable de repeticiones en tandem de unidades repetitivas interespaciadas de micobacterias). Resultados De 186 casos, 61 fueron genotipados: se encontraron 33 patrones y 5 conglomerados con 19, 7, 3, 2 y 2 casos. La proporcion de casos debido a una transmision reciente era del 45% (intervalo de confianza del 95%: 33%-58%). La investigacion rutinaria de contactos no consiguio identificar un numero sustancial de conexiones epidemiologicas. El historial de vivir en un lugar cerrado estaba fuertemente relacionado con los conglomerados. Conclusiones La proporcion de casos por una transmision reciente en La Habana en el 2009 era alta. Las actuales medidas de control en lugares cerrados deberian mejorarse. Deberia llevarse a cabo un estudio con un mayor numero de casos y por un mayor periodo de tiempo para conseguir estimaciones mas precisas. Tambien son necesarios mas estudios sobre la utilidad y costo-efectividad de anadir tecnicas de epidemiologia molecular para apoyar el progreso hacia la eliminacion de la tuberculosis en Cuba, un lugar con baja incidencia y recursos limitados.

Background Aedes control interventions are considered the cornerstone of dengue control programmes, but there is scarce evidence on their effect on disease. We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-domiciliary residual insecticide (deltamethrin) treatment (RIT) and long lasting insecticide treated curtains (ITC). Methodology/Principal findings Sixty three clusters (around 250 households each) were randomly allocated to two intervention (RIT and ITC) and one control arm. Routine Aedes control activities (entomological surveillance, source reduction, selective adulticiding, health education) were applied in the whole study area. The outcome measures were clinical dengue case incidence and immature Aedes infestation. Effectiveness of tools was evaluated using a generalized linear regression model with a negative binomial link function. Despite significant reduction in Aedes indices (Rate Ratio (RR) 0.54 (95%CI 0.32–0.89) in the first month after RIT, the effect faded out over time and dengue incidence was not reduced. Overall, in this setting there was no protective effect of RIT or ITC over routine in the 17months intervention period, with for house index RR of 1.16 (95%CI 0.96–1.40) and 1.25 (95%CI 1.03–1.50) and for dengue incidence RR of 1.43 (95%CI 1.08–1.90) and 0.96 (95%CI 0.72–1.28) respectively. The monthly dengue incidence rate (IR) at cluster level was best explained by epidemic periods (Incidence Rate Ratio (IRR) 5.50 (95%CI 4.14–7.31)), the IR in bordering houseblocks (IRR 1.03 (95%CI 1.02–1.04)) and the IR pre-intervention (IRR 1.02 (95%CI 1.00–1.04)). Conclusions Adding RIT to an intensive routine Aedes control programme has a transient effect on the already moderate low entomological infestation levels, while ITC did not have any effect. For both interventions, we didn’t evidence impact on disease incidence. Further studies are needed to evaluate impact in settings with high Aedes infestation and arbovirus case load., Author summary This is the first cluster randomized controlled trial providing evidence on the effect of applying residual insecticide treatment and deploying insecticide treated curtains on clinical dengue case incidence. In a context of intensive routine control activities, low Aedes infestation and moderate transmission, we did not observe an entomological nor epidemiological effect of these interventions. Besides the epidemiological context, we hypothesized two factors to explain our results: the counteracting effect of multiple insecticides applied in the same place at the same time and the importance of human mobility in dengue transmission dynamics. The specific impact of residual insecticide treatment and insecticide treated curtains on dengue transmission should be unambiguously demonstrated in settings with more intense arbovirus transmission and/or with less intensive routine control measures in place, before making recommendations for their implementation in local vector control programs in such contexts.

Background Yaws is a non-venereal treponemal infection caused by Treponema pallidum subspecies pertenue. The disease is targeted by WHO for eradication by 2020. Rapid diagnostic tests (RDTs) are envisaged for confirmation of clinical cases during treatment campaigns and for certification of the interruption of transmission. Yaws testing requires both treponemal (trep) and non-treponemal (non-trep) assays for diagnosis of current infection. We evaluate a sequential testing strategy (using a treponemal RDT before a trep/non-trep RDT) in terms of cost and cost-effectiveness, relative to a single-assay combined testing strategy (using the trep/non-trep RDT alone), for two use cases: individual diagnosis and community surveillance. Methods We use cohort decision analysis to examine the diagnostic and cost outcomes. We estimate cost and cost-effectiveness of the alternative testing strategies at different levels of prevalence of past/current infection and current infection under each use case. We take the perspective of the global yaws eradication programme. We calculate the total number of correct diagnoses for each strategy over a range of plausible prevalences. We employ probabilistic sensitivity analysis (PSA) to account for uncertainty and report 95% intervals. Results At current prices of the treponemal and trep/non-trep RDTs, the sequential strategy is cost-saving for individual diagnosis at prevalence of past/current infection less than 85% (81–90); it is cost-saving for surveillance at less than 100%. The threshold price of the trep/non-trep RDT (below which the sequential strategy would no longer be cost-saving) is US$ 1.08 (1.02–1.14) for individual diagnosis at high prevalence of past/current infection (51%) and US$ 0.54 (0.52–0.56) for community surveillance at low prevalence (15%). Discussion We find that the sequential strategy is cost-saving for both diagnosis and surveillance in most relevant settings. In the absence of evidence assessing relative performance (sensitivity and specificity), cost-effectiveness is uncertain. However, the conditions under which the combined test only strategy might be more cost-effective than the sequential strategy are limited. A cheaper trep/non-trep RDT is needed, costing no more than US$ 0.50–1.00, depending on the use case. Our results will help enhance the cost-effectiveness of yaws programmes in the 13 countries known to be currently endemic. It will also inform efforts in the much larger group of 71 countries with a history of yaws, many of which will have to undertake surveillance to confirm the interruption of transmission., Author summary Yaws is a non-venereal treponemal infection. The disease is targeted by WHO for eradication by 2020. Testing is envisaged for diagnosis to confirm of clinical cases during treatment campaigns and for surveillance to certify the interruption of transmission. However resources available to the global eradication programme are severely limited and the cost of testing must be contained. Testing requires simultaneous detection of antibodies to both treponemal and non-treponemal antigens for diagnosis of active infection. Currently, there is one commercially available rapid diagnostic test for yaws that can do just that. However, it is considerably more expensive than the available syphilis tests detecting treponemal antibodies only. We evaluate the cost and cost-effectiveness of a sequential testing strategy (using the treponemal test first, before the combined test), relative to a combined testing strategy (using only the combined test). We consider the two use cases: individual diagnosis and community surveillance. We find that the sequential strategy is cost-saving for both diagnosis and surveillance in most relevant settings. Yaws eradication programme should consider adopting the sequential strategy. Still, a cheaper trep/non-trep RDT is needed, costing no more than US$ 0.50–1.00. Our results will help enhance the cost-effectiveness of yaws programmes in the 13 countries known to be currently endemic. It will also inform efforts in the much larger group of 71 countries with a history of yaws, many of which will have to undertake surveillance to confirm the interruption of transmission.

BACKGROUND: There have been few studies of the natural history of Mycoplasma genitalium in women. We investigated patterns of clearance and recurrence of untreated M. genitalium infection in a cohort of female sex workers in Uganda. METHODS: Women diagnosed as having M. genitalium infection at enrollment were retested for the infection at 3-month intervals. Clearance of infection was defined as testing negative after having a previous positive result: persistence was defined as testing positive after a preceding positive test result, and recurrence as testing positive after a preceding negative test result. Adjusted hazard ratios for M. genitalium clearance were estimated using Cox proportional hazards regression. RESULTS: Among 119 participants infected with M. genitalium at enrollment (prevalence, 14%), 55% had spontaneously cleared the infection within 3 months; 83%, within 6; and 93%, within 12 months. The overall clearance rate was 25.7/100 person-years (pyr; 95% confidence interval, 21.4-31.0). HIV-positive women cleared M. genitalium infection more slowly than did HIV-negative women (20.6/100 pyr vs. 31.3/100 pyr, P = 0.03). The clearance rate was slower among HIV-positive women with CD4 counts less than 350/mL than among those with higher CD4 counts (9.88/100 pyr vs. 29.5/100 pyr, P

Avaliamos o rendimento diagnóstico da fibrobroncoscopia óptica no diagnóstico de tuberculose pulmonar com baciloscopia negativa em pacientes atendidos em um hospital de referência em Lima, Peru. Dos 611 pacientes submetidos ao procedimento, 140 (23%) foram diagnosticados com tuberculose com base nas amostras de LBA. Ser mais jovem e do sexo masculino foi associado a culturas positivas. Além disso, 287 pacientes realizaram baciloscopia de escarro após a broncoscopia, e os resultados aumentaram o rendimento diagnóstico em 22% em relação às amostras de LBA. Concluímos que amostras de LBA e de escarro pós-broncoscopia tiveram um bom rendimento diagnóstico nos pacientes com suspeita de tuberculose pulmonar com baciloscopia negativa. We evaluated the diagnostic yield of fiberoptic bronchoscopy for the diagnosis of smear-negative pulmonary tuberculosis in patients treated at a referral hospital in Lima, Peru. Of the 611 patients who underwent the procedure, 140 (23%) were diagnosed with tuberculosis based on the analysis of BAL samples. Being young and being male were significantly associated with positive cultures. In addition, 287 patients underwent post-bronchoscopic sputum smear testing for AFB, the results of which increased the diagnostic yield by 22% over that obtained through the analysis of BAL samples alone. We conclude that the analysis of BAL samples and post-bronchoscopic sputum samples provides a high diagnostic yield in smear-negative patients suspected of having pulmonary tuberculosis.

Objective To assess the economic cost of routine Aedes aegypti control in an at-risk environment without dengue endemicity and the incremental costs incurred during a sporadic outbreak. Methods The study was conducted in 2006 in the city of Guantanamo, Cuba. We took a societal perspective to calculate costs in months without dengue transmission (January–July) and during an outbreak (August–December). Data sources were bookkeeping records, direct observations and interviews. Results The total economic cost per inhabitant (p.i.) per month. (p.m.) increased from 2.76 USD in months without dengue transmission to 6.05 USD during an outbreak. In months without transmission, the routine Aedes control programme cost 1.67 USD p.i. p.m. Incremental costs during the outbreak were mainly incurred by the population and the primary/secondary level of the healthcare system, hardly by the vector control programme (1.64, 1.44 and 0.21 UDS increment p.i. p.m., respectively). The total cost for managing a hospitalized suspected dengue case was 296.60 USD (62.0% direct medical, 9.0% direct non-medical and 29.0% indirect costs). In both periods, the main cost drivers for the Aedes control programme, the healthcare system and the community were the value of personnel and volunteer time or productivity losses. Conclusions Intensive efforts to keep A. aegypti infestation low entail important economic costs for society. When a dengue outbreak does occur eventually, costs increase sharply. In-depth studies should assess which mix of activities and actors could maximize the effectiveness and cost-effectiveness of routine Aedes control and dengue prevention. Objectif: Evaluer le cout economique du controle de routine de l’Aedes aegypti dans un environnement a risque sans endemicite pour la dengue et les couts marginaux encourus lors d’une epidemie sporadique. Methodes: L’etude a ete menee en 2006 dans la ville de Guantanamo, a Cuba. Nous avons adopte une perspective societale pour calculer les couts dans les mois sans transmission de la dengue (janvier a juillet) et lors d’une epidemie (aout a decembre). Les sources des donnees etaient les registres, des observations directes et des interviews. Resultats: Le cout financier total par habitant (ph) par mois (pm) a augmente de 2,76 USD au cours des mois sans transmission de la dengue a 6,05 USD au cours d’une epidemie. Au cours des mois sans transmission, le programme de controle de routine de l’Aedes coutait 1,67 USD ph.pm. Les couts marginaux lors de l’epidemie ont ete engages principalement par la population et le secteur primaire/secondaire du systeme de soins de sante, et a peine par le programme de lutte antivectorielle (increments de 1,64; 1,44 et 0,21 UDS ph.pm, respectivement). Le cout total pour la prise en charge d’un cas de dengue hospitalise a ete estimea 296,60 USD (62,0% en couts directs medicaux, 9,0% en couts directs non medicaux et 29,0% en couts indirects). Dans les deux periodes, les principaux facteurs determinant les couts pour le programme de controle du genre Aedes, le systeme de soins de sante et la communauteetaient la valeur du personnel et le temps des benevoles ou les pertes en productivite. Conclusions: Des efforts intensifs pour maintenir basse l’infestation par Aedes aegypti entrainent d’importants couts economiques pour la societe. Lorsqu’une epidemie de dengue arrive eventuellement, les couts augmentent fortement. Des etudes approfondies doivent evaluer quels types de combinaisons d’activites et d’acteurs peuvent maximiser l’efficacite et la rentabilite du controle de routine de l’Aedes et la prevention de la dengue. Objetivo: Evaluar el coste economico del control rutinario de Aedes aegypti en un ambiente de riesgo sin dengue endemico y los costes incrementales incurridos durante un brote esporadico. Metodos: El estudio se realizo en el 2006 en la ciudad de Guantanamo, Cuba. Se utilizo una perspectiva social para calcular los costes en meses sin transmision del dengue (Enero a Julio) y duriante el brote (Agosto-Diciembre). Las fuentes de datos fueron libros de registro, la observacion directa y entrevistas. Resultados: El coste economico total por habitante (p.h.) por mes (p.m.) aumento de 2.76 USD en meses sin transmision del dengue al 6.05 USD durante un brote. En meses sin transmision el programa de control rutinario de Aedes cuesta 1.67 USD p.i. p.m. Los costes incrementales durante el brote eran principalmente para la poblacion y para los niveles primario/secundario del sistema sanitario, casi nunca para el programa de control vectorial (1.64, 1.44 y 0.21 UDS aumento p.h. p.m., respectivamente). El coste total de manejar un caso hospitalizado con sospecha de dengue era de 296.60 USD (62.0% costes medicos directos, 9.0% costes directos no medicos y 29.0% costes indirectos). En ambos periodos, los principales factores de coste para el programa de control de Aedes, para el sistema de cuidados sanitarios y para la comunidad eran el coste del personal y el tiempo de voluntarios, o perdidas de productividad. Conclusiones: Los intensos esfuerzos para mantener bajos los niveles de infestacion de Aedes aegypti conllevan a importantes costes economicos para la sociedad. Cuando eventualmente ocurre un brote de dengue, los costes aumentan considerablemente. Estudios en profundidad deberian evaluar cual mezcla de actividades y actores podria maximizar la efectividad y la costo-efectividad del control rutinario de Aedes y de la prevencion del dengue.

During the dengue outbreak that struck Santiago de Cuba in 2006-2007, we conducted an observational study in the Mariana Grajales district, the former setting of a community trial for Aedes aegypti control. In the trial, community working groups (CWG) had been created in 29 randomly selected intervention house blocks, and routine vector control activities alone were conducted in the remaining 30 control blocks. The CWG elaborated and implemented with the population plans and activities to reduce Aedes infestation. They were still functional in 2006 and continued organizing community-based environmental management activities. The attack rate of dengue fever during the outbreak was 8.5 per 1000 inhabitants in the former intervention blocks and 38.1 per 1000 inhabitants in the control blocks, which corresponds to a relative risk of 4.5 (95% CI 3.1-6.5). There was a significantly higher proportion of unaffected intervention blocks, and affected blocks had on average substantially less cases than affected control blocks. This study indicates that community-based environmental management inserted in the routine A. aegypti control programme can not only sustainably curb vector infestation but also have an impact on dengue transmission.

Background : Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes. Methods : A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Lowenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment. Results : Of 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1-4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95% CI: 1.9-47.8). Isoniazid mono-resistant patients had a higherrisk of poor treatment outcomes including treatment failure (2/85, 2%, p-value

Background Household contacts (HHCs) of TB cases are at increased risk for TB disease compared to the general population but the risk may be modified by individual or household factors. We conducted a study to determine incident TB among HHCs over two years after exposure and to identify individual and household level risk factors. Methods Adults newly diagnosed with a first episode of smear-positive pulmonary TB (index cases) between March 2010 and December 2011 in eastern Lima, were interviewed to identify their HHC and household characteristics. TB registers were reviewed for up to two years after the index case diagnosis and house visits were made to ascertain TB cases among HHC. The TB incidence rate ratio among HHCs as a function of risk factors was determined using generalized linear mixed models. Results The 1178 index cases reported 5466 HHCs. In 402/1178 (34.1 %) households, at least one HHC had experienced a TB episode ever. The TB incidence among HHCs was 1918 (95%CI 1669–2194) per 100,000 person-years overall, and was 2392 (95%CI 2005–2833) and 1435 (95%CI 1139–1787) per 100,000 person-years in the first and second year, respectively. Incident TB occurred more than six months following the index case’s TB diagnosis in 121/205 (59.0 %) HHCs. In HHCs, bacillary load and time between symptoms and treatment initiation in the index case, as well as the relationship to the index case and the sex of the HHC all had a significant association with TB incidence in HHCs. Conclusions Incidence of TB among HHCs was more than ten times higher than in the general population. Certain HHC and households were at higher risk of TB, we recommend studies to compare HHC investigation to households at highest risk versus current practice, in terms of efficiency. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1616-x) contains supplementary material, which is available to authorized users.

Background In India, the Revised National TB control programme (RNTCP) offers free diagnosis and treatment for tuberculosis (TB), based on the Directly Observed Treatment Short course (DOTS) strategy. We conducted a qualitative study to explore the experience and consequences of having TB on patients enrolled in DOTS and their caretakers in Tumkur district, located in a southern state of India, Karnataka. Methods We conducted 33 in-depth interviews on a purposive sample of TB patients from three groups: (1) patients who reached RNTCP directly on their own and took DOTS at RNTCP; (2) patients who were referred by private practitioners (PPs) to RNTCP and took DOTS at RNTCP; and (3) patients diagnosed by RNTCP and took DOTS from PPs. Data was analyzed using a thematic approach with the support of NVivo9. Results The study revealed that TB and DOTS have a large impact on patient’s lives, which is often extended to the family and caretakers. The most vulnerable patients faced the most difficulty in accessing and completing DOTS. The family was the main source of support during patient’s recovery. Patients residing in rural areas and, taking DOTS from the government facilities had to overcome many barriers to adhere to the DOTS therapy, such as long travelling distance to DOTS centers, inconvenient timings and unfavorable attitude of the RNTCP staff, when compared to patients who took DOTS from PPs. Advantages of taking DOTS from PPs cited by the patients were privacy, flexibility in timings, proximity and more immediate access to care. Patients and their family had to cope with stigmatization and fear and financial hardships that surfaced from TB and DOTS. Young patients living in urban areas were more worried about stigmatisation, than elderly patients living in rural areas. Patients who were referred by PPs experienced more financial problems compared to those who reached RNTCP services directly. Conclusion Our study provided useful information about patient’s needs and expectations while taking DOTS. The development of mechanisms within RNTCP towards patient centered care is needed to enable patients and caretakers cope with disease condition and adhere to DOTS. Electronic supplementary material The online version of this article (doi:10.1186/s12913-016-1545-9) contains supplementary material, which is available to authorized users.

Summary Background Indonesia has a high tuberculosis (TB) prevalence and a large private health sector. Objectives To explore the potential of private practitioners (PP) in TB control in Jogjakarta by assessing their load of TB suspects and case-management practices. Methods We conducted a cross-sectional telephone survey of a random sample of 164 PP, weighted to the local proportions of specialists, general practitioners (GP), nurses and midwives. We investigated their knowledge of directly observed treatment, short-course (DOTS), whether they see TB suspects, whether they refer such patients and how they possibly diagnose and treat TB. Results We sampled 174 PP, of which 164 (94.3%) completed the interview. Most PP (63.4%) reported to have seen TB suspects in their private practice, and 62.8% were also employed in a DOTS facility. Specialists saw on average 18 suspects, GP 11 suspects, and nurses–midwives three suspects in a year. Many PP (45.2%) always relied on National Tuberculosis Control Programme (NTP) services for diagnosis. Fewer PP (41.5%) used, by themselves, diagnostic procedures complying with the NTP guidelines. The majority (63.6%) always referred confirmed cases for treatment, mainly (71.4%) to NTP services. Most PP (72.7%) who treated TB patients themselves did not prescribe the NTP standard regimen. Conclusion The study shows that the TB case load per PP is low in Jogjakarta, where the NTP already involves public and private hospitals besides public health centres. Initiatives to engage all PP might only marginally contribute in increasing the TB case detection. Donnees de base L’Indonesie a une prevalence elevee de tuberculose (TB) et un vaste secteur prive de sante. Objectifs Explorer le potentiel des praticiens prives (PP) dans le controle de la TB a Jogjakarta en evaluant la charge de suspects TB dans leur clientele et les pratiques de gestion des cas de TB. Methodes Nous avons mene une surveillance transversale par telephone sur un echantillon aleatoire de 164 PP ponderes aux proportions locales de specialistes, de medecins generalistes, d’infirmieres et de sages-femmes. Nous avons investigue leur connaissance du DOTS (administration du schema court de traitement sous observation), s’ils voyaient des suspects TB, s’ils referaient de tels patients et comment ils diagnostiquaient et traitaient la TB. Resultats Sur un echantillons de 174 PP, 164 (94,3%) ont accompli l’entretien. La plupart des PP (63,4%) ont rapporte avoir vu des suspects TB dans leur cabinet prive et 62,8%etaient egalement employes dans un service DOTS. Les specialistes avaient vu en moyenne 18 suspects, les medecins generalistes 11 suspects et les infirmieres/sages-femmes, 3 suspects en une annee. Beaucoup de PP (45,2%) se sont toujours bases sur les services des programmes nationaux de controle de la tuberculose (PNT) pour le diagnostic. Peu de PP (41,5%) ont employe par eux-memes des procedures de diagnostic conformes aux directives des PNT. La majorite (63,6%) des PP ont toujours refere les cas confirmes de TB pour traitement, principalement (71,4%) dans les services de PNT. La plupart des PP (72,7%) qui ont eux-memes traite des patients TB n’ont pas prescrit le regime standard du PNT. Conclusion L’etude montre que la charge de cas de TB par pp est faible a Jogjakarta ou le PNT implique deja les hopitaux publics et prives autant que les centres de sante publique. Les initiatives pour engager tout les PP pourraient contribuer, mais seulement marginalement, a augmenter la detection de cas de TB. Antecedentes Indonesia tiene una alta prevalencia de tuberculosis (TB) y un amplio sector sanitario privado. Objetivos Explorar el potencial que los medicos con consultas privadas (MPs) tendrian en el control de la TB en Yogyakarta, evaluando su papel en la carga de sospecha de TB y practica de manejo de casos. Metodos Se realizo un estudio telefonico croseccional a una muestra de 164 MPs elegida al azar y ponderada por la proporcion de especialistas, medicos generales, enfermeras y comadronas. Se evaluo su conocimiento de DOTS (terapia de observacion directa), si atiendian pacientes con sospecha de TB, si refierian a dichos pacientes y como podrian diagnosticarse y tratarse la TB. Resultados De una muestra de 174 MPs, 164 (94.3%) completaron la entrevista. La mayoria de los MPs (63.4%) reportaron haber visto casos con sospecha de TB en sus consultas privadas y 62.8% estaban tambien empleados en un centro que utilizaba DOTS. En promedio, los especialistas veian 18 sospechosos por ano, los medicos generales 11, y las enfermeras y comadronas 3. Muchos MPs (45.2%) dependian siempre del Programa Nacional de Tuberculosis (PNT) para servicios de diagnostico. Un menor numero de MPs (41.5%) utilizaban, ellos solos, procedimientos diagnosticos que cumpliesen con las guias del PNT. La mayoria (63.6%) siempre referia los casos confirmados para tratamiento, principalmente (71.4%) a los servicios del PNT. La mayoria de los MPs (72.7%) que trataban ellos mismos a los pacientes con TB no prescribian el regimen estandar del PNT. Conclusion El estudio muestra que la carga de casos de TB por MP es baja en Yogyakarta, en donde el PNT ya involucra hospitales publicos y privados ademas de centros sanitarios publicos. Las iniciativas para implicar a todos los MPs podria contribuir a aumentar solo marginalmente la deteccion de casos de TB.

BACKGROUND: Although tuberculosis (TB) is usually curable with antibiotics, poor adherence to medication can lead to increased transmission, drug resistance, and death. Prior research has shown several factors to be associated with poor adherence, but this problem remains a substantial barrier to global TB control. We studied patients in a high-incidence district of Lima, Peru to identify factors associated with premature termination of treatment (treatment default). METHODS: We conducted a prospective cohort study of adult smear-positive TB patients enrolled between January 2010 and December 2011 with no history of TB disease. Descriptive statistics and multivariable logistic regression analyses were performed to determine risk factors associated with treatment default. RESULTS: Of the 1233 patients studied, 127 (10%) defaulted from treatment. Patients who defaulted were more likely to have used illegal drugs (OR = 4.78, 95% CI: 3.05-7.49), have multidrug-resistant TB (OR = 3.04, 95% CI: 1.58-5.85), not have been tested for HIV (OR = 2.30, 95% CI: 1.50-3.54), drink alcohol at least weekly (OR = 2.22, 95% CI: 1.40-3.52), be underweight (OR = 2.08, 95% CI: 1.21-3.56), or not have completed secondary education (OR = 1.55, 95% CI: 1.03-2.33). CONCLUSIONS: Our study identified several factors associated with defaulting from treatment, suggesting a complex set of causes that might lead to default. Addressing these factors individually would be difficult, but they might help to identify certain high-risk patients for supplemental intervention prior to treatment interruption. Treatment adherence remains a barrier to successful TB care and reducing the frequency of default is important for both the patients' health and the health of the community.

An exploratory study was conducted in the rural Estie district of Ethiopia in 1997 to identify the role of ABO blood group, rhesus factor, and type of grass pea (Lathyrus sativus) diet in the susceptibility to neurolathyrism. Five-hundred study subjects (250 cases and 250 controls) were examined and interviewed, and had their ABO and rhesus blood groups determined. The majority (86%) of the cases were males. Blood group O was the most common in the patients and controls followed by groups A, B, and AB. The vast majority of the study subjects were rhesus-positive. The gravy (Shiro) grass pea preparation was consumed by 91.6% of the study population, boiled (Nifiro) by 86%, and roasted (Kollo) by 56.4%. Almost half (48%) of the cases had consumed grass pea for > 4 months compared to 8% of controls (P < 0.001). There was a significant association between the risk for neurolathyrism and the consumption of boiled (adjusted odds ratio [AOR] = 98.4) and roasted (AOR = 55.62) forms of grass pea. There was no risk of paralysis associated with consumption of the gravy form of grass pea (AOR = 0.40, 95% confidence interval 0.1-2.0). Blood group O remained significantly associated with the disease after adjusting for age, type of grass pea preparation consumed, and duration of consumption (AOR = 2.90).

The objective of this study was to test the potential of routine vitamin A supplementation at admission to speed up recovery during hospitalization for acute lower respiratory tract infections (ALRI) and to decrease the levels of morbidity at 6 weeks after discharge. The study was conducted in the Central Hospital of Maputo (CHM), Mozambique, from 1995 to 1997.Children aged 6-72 months with ALRI admitted to the paediatric wards of the CHM were assigned to a supplementation group (n = 71, receiving 200000 IU of vitamin A) or a control group (n = 93, receiving a placebo).The prevalence of vitamin A deficiency was very high and similar between the two groups. The median number of inpatient days for the supplementation group was 3, for the placebo group 4 days. On day 5 the rate of clinical discharge was 88.4% (n = 61/69) in the experimental intervention group and 73.9% (n = 65/88) in the placebo group (P = 0.023). CONCLUSION We found a statistically significant reduction in duration of admission among vitamin A-supplemented children with ALRI. This effect is in line with what is known about the role of vitamin A in human defence and immune mechanisms and with the serological evidence of the extent of vitamin A deficiency among the children in this trial.

Evidence on the effectiveness of insecticide-treated curtains (ITCs) for reducing densities of Aedes mosquitoes, the principal vectors of dengue, is scarce. In Laem Chabang southeast of Bangkok, Thailand, the Breteau Index (BI) (number of positive containers/100 houses) was 45 in October 2006. In March 2007, we distributed long-lasting ITCs in 22 clusters (2,032 houses) and selected 66 control clusters (661 houses). Routine control activities continued in all clusters. Six months after distribution, the BI was 25.8 and 77.6 in intervention and control areas, respectively (P < 0.001). Eighteen months after distribution, the BI was 21.8 and 23.8, respectively (P = 0.28). The average number of ITCs/house at cluster level was associated with the BI (P < 0.01) after six months, when 70.5% of households still used ITCs, but not at 18 months, when ITC coverage had decreased to 33.2%. Deployment of ITCs can result in considerable reductions in Aedes infestation levels, but the effect is coverage dependent.

The efficacy of insecticide-treated window curtains (ITCs) for dengue vector control was evaluated in Thailand in a cluster-randomized controlled trial. A total of 2,037 houses in 26 clusters was randomized to receive the intervention or act as control (no treatment). Entomological surveys measured Aedes infestations (Breteau index, house index, container index, and pupae per person index) and oviposition indices (mean numbers of eggs laid in oviposition traps) immediately before and after intervention, and at 3-month intervals over 12 months. There were no consistent statistically significant differences in entomological indices between intervention and control clusters, although oviposition indices were lower (P < 0.01) in ITC clusters during the wet season. It is possible that the open housing structures in the study reduced the likelihood of mosquitoes making contact with ITCs. ITCs deployed in a region where this house design is common may be unsuitable for dengue vector control.

Background Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. Methods We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Results Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. Conclusions The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.

Objective: To evaluate the results obtained though intersectoral coordination and community empowerment in one study carried out during 6 years in Playa Municipality, Cuba. Methods: A longitudinal assessment comparing one intervention and one control area was conducted. The intervention encompasses two main stages separated by two dengue outbreaks. The first stage, focused on strengthening intersectoral coordination, was initiated in January 2000. In August 2003, a complementary strategy, focused on community empowerment and was initiated in half of the intervention area. In the control area, routine dengue control activities continued without additional input. We used entomologic surveillance data from January 1999 to December 2005 to assess the effectiveness. We computed the Breteau index (BI) per health area and the 95% confidence interval for the difference between the BIs at each time point. A semiparametric mixed model to capture the evolution in time of Aedes aegypti larval densities was fitted. Results: The BI in the control area showed the lowest value before starting the intervention. This was reversed 1 year after launching intersectoral activities for dengue control in the intervention area. In spite of spraying actions in all areas, the differences in BI between intervention and control areas remain significant until December 2002. Although for the next 2 years no differences were observed, they become significant again in December 2004, which corresponds with the implementation of the complementary community-based vector control strategy in the intervention area. Conclusions: The model fitted identified monotonous trends over time and reversal trends at particular moments. The confidence bands indicate sections with significant differences between areas. Our data increase the evidence that the intersectoral coordination and community empowerment strategy for A. aegypti control is effective.

IntroductionIn high multidrug resistant (MDR) tuberculosis (TB) prevalence areas, drug susceptibility testing (DST) at diagnosis is recommended for patients with risk factors for MDR. However, this approach might miss a substantial proportion of MDR-TB in the general population. We studied primary MDR in patients considered to be at low risk of MDR-TB in Lima, Peru.MethodsWe enrolled new sputum smear-positive TB patients who did not report any MDR-TB risk factor: known exposure to a TB patient whose treatment failed or who died or who was known to have MDR-TB; immunosuppressive co-morbidities, ex prison inmates; prison and health care workers; and alcohol or drug abuse. A structured questionnaire was applied to all enrolled participants to confirm the absence of these factors and thus minimize underreporting. Sputum from all participants was cultured on Löwenstein-Jensen media and DST for first line drugs was performed using the 7H10 agar method.ResultsOf 875 participants with complete data, 23.2% (203) had risk factors for MDR-TB elicited after enrolment. Among the group with no reported risk factors who had a positive culture, we found a 6.3% (95%CI 4.4-8.3) (37/584) rate of MDR-TB. In this group no epidemiological characteristics were associated with MDR-TB. Thus, in this group, multidrug resistance occurred in patients with no identifiable risk factors.ConclusionsWe found a high rate of primary MDR-TB in a general population with no identifiable risk factors for MDR-TB. This suggests that in a high endemic area targeting patients for MDR-TB based on the presence of risk factors is an insufficient intervention.

Objective To assess the operational effectiveness of long-lasting insecticide treated materials (ITMs), when used at household level, for the control of Aedes aegypti in moderately infested urban and suburban areas. Methods In an intervention study, ITMs consisting of curtains and water jar-covers (made from PermaNet) were distributed under routine field conditions in 10 clusters (5 urban and 5 suburban), with over 4000 houses, in Trujillo, Venezuela. Impact of the interventions were determined by comparing pre-and post-intervention measures of the Breteau index (BI, number of positive containers/100 houses) and pupae per person index (PPI), and by comparison with indices from untreated areas of the same municipalities. The effect of ITM coverage was modeled. Results At distribution, the proportion of households with ≥1 ITM curtain was 79.7% in urban and 75.2% in suburban clusters, but decreased to 32.3% and 39.0%, respectively, after 18 months. The corresponding figures for the proportion of jars using ITM covers were 34.0% and 50.8% at distribution and 17.0% and 21.0% after 18 months, respectively. Prior to intervention, the BI was 8.5 in urban clusters and 42.4 in suburban clusters, and the PPI was 0.2 and 0.9, respectively. In both urban and suburban clusters, the BI showed a sustained 55% decrease, while no discernable pattern was observed at the municipal level. After controlling for confounding factors, the percentage ITM curtain coverage, but not ITM jar-cover coverage, was significantly associated with both entomological indices (Incidence Rate Ratio = 0.98; 95%CI 0.97–0.99). The IRR implied that ITM curtain coverage of at least 50% was necessary to reduce A. aegypti infestation levels by 50%. Conclusion Deployment of insecticide treated window curtains in households can result in significant reductions in A. aegypti levels when dengue vector infestations are moderate, but the magnitude of the effect depends on the coverage attained, which itself can decline rapidly over time., Author Summary An estimated 40% of the world's population lives at risk of contracting dengue, and it inflicts a significant health, economic and social burden on the populations of endemic areas. In the absence of a vaccine, vector control is the only available strategy to prevent transmission. Some control methods against Aedes aegypti (the main dengue vector) have been successful in reducing vector infestation levels, but rarely sustained the reductions for a prolonged period. We report here on the first effectiveness trial of insecticide treated curtains and jar covers against A. aegypti implemented under ‘real-life’ conditions. The coverage of tools was high at distribution, but declined quickly over the 18 months of follow up. The vector infestation levels showed a sustained 55% decrease in the intervention clusters, while no discernable pattern was observed at the municipal level. At least 50% curtain coverage was needed to reduce A. aegypti infestation levels by 50%. We concluded that deployment of insecticide treated window curtains in households can result in significant reductions in dengue vector levels, which are related to dengue transmission risk. The magnitude of the effect depends on the curtain coverage attained, which itself can decline rapidly over time.

Background. In the framework of hospital infection control, various clinical prediction rules (CPRs) for respiratory isolation of patients with suspected pulmonary tuberculosis (PTB) have been developed. Our aim was to evaluate their performance in an emergency department setting with a high prevalence of PTB. Methods. We searched the MEDLINE and OVID databases to identify CPRs to predict PTB. We used a previously collected database containing clinical, radiographical, and microbiological information on patients attending an emergency department with respiratory complaints, and we applied each CPR to every patient and compared the result with culture for Mycobacterium tuberculosis as the reference standard. We also simulated the proportion of isolated suspects and missed cases for PTB prevalences of 5% and 30%. Results. We withheld 13 CPRs for evaluation. We had complete data on 345 patients. Most CPRs achieved a high sensitivity but very low specificity and very low positive predictive value. Mylotte’s score, which includes results of sputum smear as a predictive finding, was the best-performing CPR. It attained a sensitivity of 88.9% and a specificity of 63.9%. However, at a 30% PTB prevalence, 498 of 1000 individuals with suspected PTB would have to be isolated; 267 of these cases would be true PTB cases, and 33 cases would be missed. Two consecutive sputum smears had a sensitivity of 75.6% and a specificity of 99.7%. Conclusions. In a setting with a high prevalence of PTB, only 1 of the 13 assessed CPRs demonstrated high sensitivity combined with satisfactory specificity. Our results highlight the need for local validation of CPRs before their application. BACKGROUND

Background: Clinical suspects of pulmonary tuberculosis in which the sputum smears are negative for acid fast bacilli represent a diagnostic challenge in resource constrained settings. Our objective was to validate an existing clinical-radiographic score that assessed the probability of smear-negative pulmonary tuberculosis (SNPT) in high incidence settings in Peru. Methodology/Principal Findings: We included in two referral hospitals in Lima patients with clinical suspicion of pulmonary tuberculosis and two or more negative sputum smears. Using a published but not externally validated score, patients were classified as having low, intermediate or high probability of pulmonary tuberculosis. The reference standard for the diagnosis of tuberculosis was a positive sputum culture in at least one of 2 liquid (MGIT or Middlebrook 7H9) and 1 solid (Ogawa) media. Prevalence of tuberculosis was calculated in each of the three probability groups. 684 patients were included. 184 (27.8%) had a diagnosis of pulmonary tuberculosis. The score did not perform well in patients with a previous history of pulmonary tuberculosis. In patients without, the prevalence of tuberculosis was 5.1%, 31.7% and 72% in the low, intermediate and high probability group respectively. The area under de ROC curve was 0.76 (95% CI 0.72-0.80) and scores >= 6 had a positive LR of 10.9. Conclusions/Significance: In smear negative suspects without previous history of tuberculosis, the clinical-radiographic score can be used as a tool to assess the probability of pulmonary tuberculosis and to guide the decision to initiate or defer treatment or to requesting additional tests.

We aimed to evaluate the incremental cost-effectiveness of engaging private practitioners (PPs) to refer tuberculosis (TB) suspects to public health centers in Jogjakarta, Indonesia. Effectiveness was assessed for TB suspects notified between May 2004 and April 2005. Private practitioners referred 1,064 TB suspects, of which 57.5% failed to reach a health center. The smear-positive rate among patients reaching a health center was 61.8%. Two hundred eighty (280) out of a total of 1,306 (21.4%) new smear-positive cases were enrolled through the PPs strategy. The incremental cost-effectiveness ratio per smear-positive case successfully treated for the PPs strategy was US$351.66 (95% CI 322.84–601.33). On the basis of an acceptability curve using the National TB control program's willingness-to-pay threshold (US$448.61), we estimate the probability that the PPs strategy is cost-effective at 66.8%. The strategy of engaging PPs was incrementally cost-effective, although under specific conditions, most importantly a well-functioning public directly observed treatment, short-course (DOTS) program.

Background HIV and HIV-TB co-infection are slowly increasing in Indonesia. WHO recommends HIV testing among TB patients as a key response to the dual HIV-TB epidemic. Concerns over potential negative impacts to TB control and lack of operational clarity have hindered progress. We investigated the barriers and opportunities for introducing HIV testing perceived by TB patients and providers in Jogjakarta, Indonesia. Methods We offered Voluntary Counselling and Testing (VCT) to TB patients in parallel to a HIV prevalence survey. We conducted in-depth interviews with 33 TB patients, 3 specialist physicians and 3 disease control managers. We also conducted 4 Focus Group Discussions (FGDs) with nurses. All interviews and FGDs were recorded and data analysis was supported by the QSR N6® software. Results Patients' and providers' knowledge regarding HIV was poor. The main barriers perceived by patients were: burden for accessing VCT and fear of knowing the test results. Stigma caused concerns among providers, but did not play much role in patients' attitude towards VCT. The main barriers perceived by providers were communication, patients feeling offended, stigmatization and additional burden. Conclusion Introduction of HIV testing among TB patients in Indonesia should be accompanied by patient and provider education as well as providing conditions for effective communication.

Summary We aimed to establish HIV prevalence and uptake of unlinked anonymous testing and voluntary counselling and testing (VCT) among tuberculosis (TB) patients in Jogjakarta, Indonesia. We introduced unlinked anonymous HIV testing for TB patients attending directly observed treatment, short-course services between April and December 2006. Patients were additionally offered VCT services. Of 1269 TB patients who were offered unlinked anonymous testing, 989 (77.9%; 95% CI 75.6–80.1%) accepted. HIV prevalence was 1.9% (95% CI 1.6–2.2%). HIV infections were less frequently diagnosed among TB patients who attended a public health centre [odds ratio (OR) 0.15; 95% CI 0.03–0.70] rather than public hospital. They were more frequent in TB patients with a university education background (OR 5.16; 95% CI 1.01–26.63) or a history of HIV testing (OR 57.87; 95% CI 9.42–355.62). Of the 989 patients who accepted unlinked anonymous testing, only 133 (13.4%; 95% CI 11.5–15.7%) expressed interest in VCT. Of these, 52 (39.1%; 95% CI 31.2–47.6%) attended VCT, but interest was higher among students and those offered VCT by public health centres. The HIV prevalence in Jogjakarta is higher than expected and needs to be monitored cautiously. Unlinked anonymous HIV testing is well accepted and can be implemented with modest additional efforts.

Objectives To rationalise the use of hospital emergency units, the Cuban health system developed from 1996 onwards an extra muros first line emergency system (FLES). We analyse the use of the FLES and its determinants, in order to develop proposals to channel inappropriate users to their family doctor. Methods In the FLES of an urban (Cerro) and a rural (Baracoa) municipality we collected, from July 1999 to June 2001, data on the moment of consultation, age and sex of the patient, referral status, motive of consultation, emergency classification, diagnosis and medical conduct. A variable “inappropriate use” was constructed. We used multivariate logistic regression to quantify the strength of the associations between patient characteristics, the night-time use, medical procedures, referral, and inappropriate use of the FLES. Results Over the 2 years observation period, 24 879 and 59 795 patient contacts were registered with the principal emergency policlinic in Baracoa and Cerro, respectively. In both municipalities the overall “inappropriate” use was almost 60%. There was no correlation with age and gender but inappropriate use was 50% more frequent during the day. Referred patients in both localities were up to 12 times more frequently hospitalized. Conclusion Cuba's FLES attract patients that would be better attended by their family doctor. To strengthen his central position in the health system, one should strengthen the family doctor's technical platform, increase his permanence at the cabinet, and improve communication with the community on the rationale of the family doctor—FLES set up.

This study developed a clinical score based on clinical and radiographic data for the diagnosis of smear-negative pulmonary tuberculosis (SNPT). SNPT was defined as a positive culture in Ogawa in a patient with two negative sputum smears. Data from patients admitted to the emergency ward with respiratory symptoms and negative acid-fast bacilli (AFB) smears was analyzed by means of logistic regression to develop the predictive score.Two hundred and sixty two patients were included. Twenty patients had SNPT. The variables included in the final model were hemoptysis, weight loss, age > 45 years old, productive cough, upper-lobe infiltrate, and miliary infiltrate. With those, a score was constructed. The score values ranged from -2 to 6. The area under the curve for the ROC curve was 0.83 (95% CI 0.74-0.90). A score of value 0 or less was associated with a sensitivity of 93% and a score of more than 4 points was associated with a specificity of 92% for SNPT. Fifty-two point twenty-nine percent of patients had scores of less than one or more than four, what provided strong evidence against and in favor, respectively, for the diagnosis of SNPT. The score developed is a cheap and useful clinical tool for the diagnosis of SNPT and can be used to help therapeutic decisions in patients with suspicion of having SNPT.

Background Over the last decades hospital at home (HaH) programmes have been set up in many, mainly European, countries. The Cuban HaH programme is not hospital driven, but the responsibility of the first line health services, and family doctors play a pivotal role. Methods We analyse the structure and functioning of the Cuban programme. In this descriptive study, information was prospectively collected on HaH patients admitted between July 1st 2001 and June 30th 2002. Results Admission rates varied between areas from 0.014 to 0.035 per person per year (ppy). The < 1y and 1–4y age groups had the highest admission rates. In one area the follow-up of pregnancy problems led to high 15–24y and 25–49y female admission rates (0,070 and 0,058 respectively). Respiratory affections were the most frequent reason for admission (32,6%), followed by early hospital discharge (16,0%) and gynaeco-obstetrical problems (10.8%). The median length of stay varied from 5 to 7 days between regions and from 5 days (early discharge) to 7 days (gynaeco-obstetrical problems) in function of the reason for admission. On average an HaH episode entailed 1.4 and 1.6 contacts per patient-day with the family doctor and nurse respectively. Conclusion Difference in admission criteria in function of geography, distance to the hospital, transport facilities, and staff factors, as well as differences in hospital policy on early discharge explain the observed variability. The programme plays an important role in the integrated approach to quality care in the Cuban health system, but could benefit from more uniform admission criteria.

The definitive version is available at www3.interscience.wiley.com, OBJECTIVE: To document the frequency of Leishmania donovani infection at community level in a highly endemic region in southeastern Nepal, and to assess socioeconomic and environmental risk factors. METHODS: A random cross-sectional population survey was held in two visceral leishmaniasis (VL) foci in Morang District in April to May 2003, enrolling individuals 2 years or older and residing in the endemic area for at least 12 months. Leishmania infection was defined as a direct agglutination test (DAT) titre equal to or higher than 1:3200. Risk factors were identified by logistic regression. RESULTS: The direct agglutination test was positive in 7.5% (95% CI: 5.1-10.8) and the leishmanin skin test (LST) in 13.2% (95% CI: 9.9-17.2) of the 373 study participants. No case of current kala-azar was found, but 5.1 % (95% CI: 3.1-7.8) reported having suffered from VL. Independent risk factors for Leishmania infection were proximity of the house to ponds [odds ratio (OR) 3.7, 95% CI: 1.6-8.5], family size (OR 4.4, 95% CI: 1.6-12.6), age > or =15 years (OR 5.5, 95% CI: 1.2-25.0) and house constructed in mud (OR 3.0, 95% CI: 1.1-7.6). Bednets, not impregnated and in poor condition, were used by 95.2% (95% CI: 92.3-97.0) of the population, but did not show any protective effect. CONCLUSION: This study shows that there is a serious problem of transmission of VL in this area of Nepal. The risk factors identified are linked with the socioeconomic level and the environment. The population would benefit from a community intervention to improve the environmental and housing conditions in the villages.

BACKGROUND: This study aims at obtaining unbiased estimates of the sensitivity and specificity of existing screening tests for Trypanosoma cruzi and at simulating the effectiveness of alternative screening strategies at different prevalence rates. STUDY DESIGN AND METHODS: A systematic random sample of 400 was taken from 1200 banked serum samples of donors screened between August 1998 and January 1999 in Santa Cruz, Bolivia. Samples were tested with indirect hemagglutination test (IHA), indirect immunofluorescence assay (IFA), and four enzyme-linked immunosorbent assays (ELISAs). Sensitivity and specificity of tests were estimated through latent class analysis. RESULTS: The sensitivity of individual tests ranged from 96.5 to 100 percent, and their specificity from 87.0 to 98.9 percent. Combinations of two tests used in parallel would, even at 40 percent prevalence, only miss approximately 1 infected unit per 10,000 screened. At 5 percent prevalence, however, they would yield 75 to 120 false-positive units per 1000 units screened. Parallel testing with IHA plus ELISA or with IHA plus IFA is marginally more cost-effective, compared to single IHA testing, than single ELISA or single IFA testing, regardless of the T. cruzi prevalence. CONCLUSIONS: Routine blood donor screening for T. cruzi with a single test results in unacceptable numbers of false-negative samples in highly endemic areas or in at risk population groups. Adding a second test seems mandatory, but which one to choose depends on local cost components and feasibility.

To measure HIV prevalence in various subpopulations in Bolivia.In 2002 in Cochabamba, we offered voluntary counseling and testing to homeless street youths, registered and unregistered commercial sex workers, truck drivers, and prisoners. We examined surveillance data of pregnant women and blood donors.Among street youths over 15, overall HIV prevalence was 3.5% (11/313), higher among those recruited in the street, lower among those recruited in centers for homeless; prevalence was 0.6% (2/334) and 0.5% (1/189) in female registered and nonregistered sex workers, respectively, and below 0.3% in all other groups. All HIV cases were attributed to sexual transmission.In a low-prevalence setting where intravenous drug use is uncommon, street youths are a threat for the expansion of the HIV epidemic. We argue that HIV prevention in this population requires a comprehensive approach to their health and social problems.

The definitive version is available at www3.interscience.wiley.com, Objective To study an array of household individual and dietary risk factors for neurolathyrism. Method Case–control study using recent cases in a district highly affected by the recent neurolathyrism epidemic in Ethiopia: 108 households with cases and 104 households with no cases; 170 neurolathyrism cases, 370 intra-family controls and 170 community controls frequency matched for age and sex. Results A history of acute illness was associated with a two- and threefold increased risk of paralysis in community and intra-family controls, respectively. Soaking grass pea in water before cooking roughly halved the risk of neurolathyrism but cooking in clay utensils more than quadrupled it. Consumption of grass pea in the green unripe and boiled forms increased the risk 10 times or more. Mixing the food with gravy that contains condiments with antioxidant activity reduced it by a factor of 4. The consumption of grass pea mixed with cereals rich in sulphur amino acids was also highly protective, but the magnitude of the effect depended on the grass pea preparation consumed. Conclusion Consumption of pure grass pea, especially in the green unripe and boiled forms, should be avoided. Communities at risk of neurolathyrism during famine crises should be encouraged to combine and use grass pea with cereals before the household cereal stock is fully depleted. Breeding programmes, alongside traditional attempts to reduce the toxin content, should enhance the content of sulphur amino acids and antioxidants in grass pea.

The definitive version is available at www3.interscience.wiley.com, Background The human African trypanosomiasis (HAT) control programme of the Democratic Republic of Congo (DRC) uses mass screening with the card agglutination test for trypanosomes (CATT). We looked at the contribution of CATT and improved parasitological confirmation to the effectiveness of screening and treatment. Method The effectiveness of the screening and treatment process is measured by the percentage of HAT cases that is effectively cured after a single round of screening. The process is analysed in five steps: (i) the attendance at the screening, (ii) the sensitivity of the screening procedure, (iii) the sensitivity of the parasitological confirmation, (iv) the proportion of the confirmed cases that effectively receive treatment and (v) the cure rate of the treatment. We used a simplified model that multiplies proportions of infected persons that go through each step. We estimated these parameters using a combination of routine data collected by the national control programme over the period January 1997 to December 1998 and published data. For varying attendance rates we compared the effectiveness of screening strategies based on CATT or on CATT combined with improved parasitological confirmation by mini anion exchange column technique (mAECT) with the previously used strategy based on palpation of neck glands and microscopy alone. Results The model shows that overall effectiveness of the active case detection and treatment strategy is

Summary The importance of reinfection as a cause for recurrence of tuberculosis is unclear and has potential public-health implications. We systematically searched published material for studies using DNA fingerprinting to provide data on the issue. Very few studies were designed for that particular research objective and/or report on a sufficient number of observations. Differences in methods—eg, case-definitions—seriously hamper comparisons between studies. The proportion of recurrences due to reinfection ranged between 0% and 100%; however, this figure cannot be a useful indicator since the two causes of recurrence— relapse and reinfection—are essentially independent. Only one study provides an estimate of the incidence of recurrence due to reinfection, indicating its importance for HIV-infected patients in an environment with an unusually high tuberculosis incidence. We argue that apart from extreme situations like this one the problem of recurrence of tuberculosis due to reinfection has few implications for tuberculosis-control programmes.

We argue that tuberculosis control cannot reach its proposed global targets without investment in an adequate network of accessible, effective and comprehensive health services. Lessons from the past are reviewed. They underscore that passive case-detection and adequate case management is the central technical strategy for tuberculosis control. There is no compelling evidence to support active case-detection in the general population. We elaborate on why a strong health care system is a prerequisite in the framework of case-detection and treatment. The necessity to improve quality and accessibility of general health services for ensuring early detection and subsequent cure is demonstrated. It is argued why the need for strong public health care system becomes even more eminent in the light of the tuberculosis/HIV dual epidemics and of the rapid growth of unregulated private-for-profit services. We finally examine the financial gaps for tuberculosis control and discuss the need for allocating more resources to the strengthening of general health care systems. Copyright © 2003 John Wiley & Sons, Ltd.

The Global Fund to fight AIDS, Tuberculosis, and Malaria (GFTAM) has generated passionate debates since the UN Secretary General called for its creation in April 2001 [The Global Fund to fight AIDS, Tuberculosis, and Malaria (GFTAM) 2002].The debates concentrated on issues such as the gap between required funds and funds pledged (US$ 2 billion so far – some of it one-off contributions – where US$ 22 billion would be needed from donors annually to ensure universal coverage of essential interventions, WHO 2002b), the Fund’s administrative structure and countries’ processes for disbursement of money, but also – not least – on its scope and the types of activities eligible for funding through it. Not all strategies to fight the three targeted diseases rely primarily on the health services for their implementation – promoting the use of condoms or impregnated bednets, for instance – but most of them do, case management in particular. The Fund claims it will ‘address the three diseases in ways that will contribute to strengthening health systems’ (GFTAM 2002). This is a virtuous goal, because disease-specific control programmes do indeed have the potential to weaken fragile health systems, by diverting resources and staff from other activities. But how will this strengthening be paid for? Decades of underfunding have taken their toll in terms of derelict infrastructures, poorly motivated staff, chronic shortages of drugs, etc. In the poorest countries of sub-Saharan Africa, per capita government spending on health has fallen to US$ 8 a year in 2001. This amounts only to 20% – 40% of the cost of what the World Bank describes as the minimum package of health and environmental services (WHO et al. 2002). Accessible and effective health services are a necessary (but, admittedly, not sufficient) requirement to fight the three diseases. One-third of the world’s population lacks regular access to essential drugs, and in some parts of Africa and Asia, this figure exceeds 50% (WHO 2000). What could any strategy of case-detection/treatment be expected to achieve in such a situation? Despite a tenfold increase in external financing for tuberculosis (TB) control in the less-developed countries during the last decade (Raviglione & Pio 2002), only 27% of the world’s smearpositive cases of pulmonary TB have access to the DOTS strategy package (WHO 2002a). WHO estimated the costs of expanding DOTS coverage to control TB in the 22 countries that account for 80% of the TB incidence worldwide. For the period 2001–2005, funds required for health care services (US$ 2.9 billion) amount to more than twice those required for specific TB programme costs (US$ 1.28 billion) (STOP TB 2001). How much ‘strengthening of health services’ can be achieved simply as the welcome consequence of GFTAM increased funding for specific disease control activities? More ample resources and improved drug supply systems can have ripple benefits for controlling other health problems, and hopefully ‘when more doctors, nurses, and other health providers are trained and posted to rural areas, they will not confine their work to AIDS, TB, and malaria (WHO et al. 2002).’ But will the Fund finance the new health centres to be built in these rural areas? Or their rehabilitation? The other drugs? Recurrent costs? Salaries? Basic, multipurpose training? If not, who will? Beyond the ideological debate between advocates of comprehensive health services and advocates of specific programmes, when it comes to achieving targets set for disease control, there are also technical arguments to question the efficacy of health services reduced to the sum of a few priority programmes. Take TB control. Early diagnosis and treatment of smear-positive pulmonary TB cases are the key to interrupting the chain of transmission. If the TB programme is good but the overall quality of services is poor, patients are likely to consult late in the Tropical Medicine and International Health

The definitive version is available at www3.interscience.wiley.com, Summary Glucose-6-phosphate dehydrogenase (G6PD) deficiency was evaluated in 1676 schoolboys in northern Vietnam. The trait was nearly absent in boys of the Kinh (0.5%) and the Mong (0.7%) ethnic groups that traditionally have lived outside malaria transmission areas. Prevalences among ethnic groups living in the foothills, the breeding area of the main malaria vector Anopheles minimus, ranged from 9.7% to 31%. These findings support the hypothesis of a selective advantage of the trait in Plasmodium falciparum-endemic areas.

Summarybackground Substantial uncertainty surrounds the specificity of the Direct Agglutination Test (DAT) for visceral leishmaniasis (VL) in clinical suspects, since no good gold standard exists for unequivocally identifying diseased subjects. We explored the Latent Class Analysis (LCA) modelling technique to circumvent this problem. patients and methods Data on 149 clinical suspects recruited in 1993–96 during a multicentre study in Sudan were re-examined. Clinical data, lymph node and bone marrow aspirate and DAT results were available. IFAT was performed in 1997 on stored filter paper blood of 80 individuals. Classical Validity Analysis (CVA) in a 2 × 2 contingency table with parasitology as a gold standard was compared with the parameter estimates produced by the best fitting LCA model. results The sensitivity estimates of DAT produced by CVA (98% (89%-100%)) were almost exactly reproduced by LCA. The specificity estimates by LCA were substantially higher than those obtained in CVA. Specificity of DAT depended, however, on whether the subject was treated for VL before. In subjects without prior treatment, CVA estimated DAT specificity at 68% (56%– 79%), whereas LCA estimated it at 85% (63%– 100%). conclusion LCA modelling proved a useful tool, as it gave consistent estimates of test characteristics and allowed for control of confounding factors and interaction effects. Since VL is a life-threatening disease for which expensive but effective and safe treatment exists, a clinical suspect in an endemic area should be treated on the basis of a positive DAT result.