INTRODUCTION: In 2018, Senegal introduced human papillomavirus (HPV) vaccine into its routine immunization program for all nine-year-old girls nationwide. We evaluated the costs of Senegal's introduction of HPV vaccine via this delivery approach. METHODS: We conducted a retrospective, incremental, ingredients-based cost evaluation from the provider perspective. The study timeframe included Senegal's first planning meeting in 2018 through data collection in early 2020. We collected costs from all involved units at the national and regional levels. A multi-stage cluster sampling approach was used to obtain a nationally representative sample of districts and health facilities. Weights were applied to costs from sampled units to estimate costs across all units. The cost evaluation was based on four dimensions: program activity, resource input, payer, and administrative level. Total costs were divided by the number of HPV doses administered to determine cost per dose and per dimension. RESULTS: Excluding vaccine program activity costs, the total financial and economic delivery costs of Senegal's HPV vaccination program were US$ 1,152,351 and US$ 2,838,466, respectively (US$ 3.07 and US$ 7.56 per dose, respectively). A total of 375,608 HPV vaccine doses were administered during the cost evaluation. Training and per diem represented the largest shares of financial costs. Service delivery and personnel time accounted for the largest shares of economic costs. By administrative level, district and health facility levels had the largest shares of financial and economic costs, respectively. Senegal's Ministry of Health accounted for the largest share of financial and economic costs. Including vaccine program activity costs (US$ 4.68/per dose), the total financial cost was US$ 2,911,343 (US$ 7.75 per dose). CONCLUSION: This cost evaluation can support Senegal's future vaccine introductions and inform other countries planning to introduce HPV vaccine nationwide. These findings support previous costing studies which anticipated potential economies of scale during the transition from HPV vaccine pilot demonstration projects to national introduction.

Radon is a naturally released radioactive carcinogenic gas. To estimate radon exposure, studies have examined various risk factors, but limited information exists pertaining to the confluent impact of housing characteristics and geology. This study evaluated the efficacy of housing and geological characteristics to predict radon risk in DeKalb County, Georgia, USA. Four major types of data were used: (1) three databases of indoor radon concentrations (n=6757); (2) geologic maps of rock types and fault zones; (3) a database of 402 in situ measurements of gamma emissions, and (4) two databases of housing characteristics. The Getis-Ord method was used to delineate hot spots of radon concentrations. Empirical Bayesian Kriging was used to predict gamma radiation at each radon test site. Chi-square tests, bivariate correlation coefficients, and logistic regression were used to examine the impact of geological and housing factors on radon. The results showed that indoor radon levels were more likely to exceed the action level-4 pCi/L (148Bq/m(3)) designated by the U.S. Environmental Protection Agency-in fault zones, were significantly positively correlated to gamma readings, but significantly negatively related to the presence of a crawlspace foundation and its combination with a slab. The findings suggest that fault mapping and in situ gamma ray measurements, coupled with analysis of foundation types and delineation of hot spots, may be used to prioritize areas for radon screening.

BACKGROUND: Approximately 5% of patients with drug-susceptible tuberculosis have a relapse after 6 months of first-line therapy, as do approximately 20% of patients after 4 months of short-course therapy. We postulated that by analyzing pretreatment isolates of Mycobacterium tuberculosis obtained from patients who subsequently had a relapse or were cured, we could determine any correlations between the minimum inhibitory concentration (MIC) of a drug below the standard resistance breakpoint and the relapse risk after treatment. METHODS: Using data from the Tuberculosis Trials Consortium Study 22 (development cohort), we assessed relapse and cure isolates to determine the MIC values of isoniazid and rifampin that were below the standard resistance breakpoint (0.1 mug per milliliter for isoniazid and 1.0 mug per milliliter for rifampin). We combined this analysis with clinical, radiologic, and laboratory data to generate predictive relapse models, which we validated by analyzing data from the DMID 01-009 study (validation cohort). RESULTS: In the development cohort, the mean (+/-SD) MIC of isoniazid below the breakpoint was 0.0334+/-0.0085 mug per milliliter in the relapse group and 0.0286+/-0.0092 mug per milliliter in the cure group, which represented a higher value in the relapse group by a factor of 1.17 (P=0.02). The corresponding MIC values of rifampin were 0.0695+/-0.0276 and 0.0453+/-0.0223 mug per milliliter, respectively, which represented a higher value in the relapse group by a factor of 1.53 (P<0.001). Higher MIC values remained associated with relapse in a multivariable analysis that included other significant between-group differences. In an analysis of receiver-operating-characteristic curves of relapse based on these MIC values, the area under the curve (AUC) was 0.779. In the development cohort, the AUC in a multivariable model that included MIC values was 0.875. In the validation cohort, the MIC values either alone or combined with other patient characteristics were also predictive of relapse, with AUC values of 0.964 and 0.929, respectively. The use of a model score for the MIC values of isoniazid and rifampin to achieve 75.0% sensitivity in cross-validation analysis predicted relapse with a specificity of 76.5% in the development cohort and a sensitivity of 70.0% and a specificity of 100% in the validation cohort. CONCLUSIONS: In pretreatment isolates of M. tuberculosis with decrements of MIC values of isoniazid or rifampin below standard resistance breakpoints, higher MIC values were associated with a greater risk of relapse than lower MIC values. (Funded by the National Institute of Allergy and Infectious Diseases.).

We thank the Journal for providing us the opportunity to respond to the letter from Goodman et al. [2017] regarding the conclusions of our mortality study among toluene diisocyanate (TDI)-exposed workers [Pinkerton et al., 2016]. | | Goodman et al. [2017] point out that exposure measurement error can result in a bias towards the null or away from the null. We agree and did not assert otherwise. Rather, in our paper, we pointed out that exposure measurement error is among several possible explanations for the lack of an observed positive association of cumulative TDI exposure, based on inhalation, with lung and larynx cancer [Pinkerton et al., 2016]. | | Goodman et al. [2017] also raise the possibility of positive confounding by smoking because our risk estimate for other smoking-related cancers in the overall cohort is imprecise and chronic obstructive pulmonary disease (COPD) mortality, which is more strongly related to smoking, was elevated in the cohort compared to the general population. The standardized mortality ratio for other smoking-related cancers was 1.06 (95% confidence interval, 0.85–1.31), which is evidence against large differences in smoking patterns between the cohort and general population. Although Goodman et al. [2017] state that even slight differences could account for an elevated number of respiratory deaths, other data indicate that smoking is unlikely to fully explain our findings [Siemiatycki et al., 1988]. We caution against using the findings for COPD mortality to assess potential differences in smoking between the cohort and general population because other investigators have reported associations of TDI exposure with chronic bronchitis [Jones et al., 1992] and decline in pulmonary function [Diem et al., 1982].

Accounting for as much as 14% of all lung cancers worldwide, cumulative radon progeny exposure is the leading cause of lung cancer among never-smokers both internationally and in the United States. To understand the risk of radon progeny exposure, studies have mapped radon potential using aircraft-based measurements of gamma emissions. However, these efforts are hampered in urban areas where the built environment obstructs aerial data collection. To address part of this limitation, this study aimed to evaluate the effectiveness of using in situ gamma readings (taken with a scintillation probe attached to a ratemeter) to assess radon potential in an urban environment: DeKalb County, part of the Atlanta metropolitan area, Georgia, USA. After taking gamma measurements at 402 survey sites, empirical Bayesian kriging was used to create a continuous surface of predicted gamma readings for the county. We paired these predicted gamma readings with indoor radon concentration data from 1351 residential locations. Statistical tests showed the interpolated gamma values were significantly but weakly positively related with indoor radon concentrations, though this relationship is decreasingly informative at finer geographic scales. Geology, gamma readings, and indoor radon were interrelated, with granitic gneiss generally having the highest gamma readings and highest radon concentrations and ultramafic rock having the lowest of each. Our findings indicate the highest geogenic radon potential may exists in the relatively undeveloped southeastern part of the county. It is possible that in situ gamma, in concert with other variables, could offer an alternative to aerial radioactivity measurements when determining radon potential, though future work will be needed to address this project's limitations.

BACKGROUND: Hepatitis B vaccine birth dose (HepB-BD) was introduced in Lao People's Democratic Republic to prevent perinatal hepatitis B virus transmission in 2008; high coverage is challenging since only 38% of births occur in a health facility. Healthcare workers report being unaware of home births and thus unable to conduct timely postnatal care (PNC) home visits. A quasi-experimental pilot study was conducted wherein mobile phones and phone credits were provided to village health volunteers (VHV) and healthcare workers (HCWs) to assess whether this could improve HepB-BD administration, as well as birth notification and increase home visits. METHODS: From April to September 2014, VHVs and HCWs in four selected intervention districts were trained, supervised, received outreach per diem for conducting home visits, and received mobile phones and phone credits. In three comparison districts, VHVs and HCWs were trained, supervised, and received outreach per diem for conducting home visits. A post-study survey compared HepB-BD coverage among children born during the study and children born one year before. HCWs and VHVs were interviewed about the study. FINDINGS: Among intervention districts, 463 study children and 406 pre-study children were enrolled in the survey; in comparison districts, 347 study children and 309 pre-study children were enrolled. In both arms, there was a significant improvement in the proportion of children reportedly receiving a PNC home visit (intervention p<0.0001, comparison p=0.04). The median difference in village level HepB-BD coverage (study cohort minus pre-study cohort), was 57% (interquartile range [IQR] 32-88%, p<0.0001) in intervention districts, compared with 20% (IQR 0-50%, p<0.0001) in comparison districts. The improvement in the intervention districts was greater than in the comparison districts (p=0.0009). CONCLUSION: Our findings suggest that the provision of phones and phone credits might be one important factor for increasing coverage. However, reasons for improvement in both arms are multifactorial and discussed.

Smallholder farmers in Sub-Saharan Africa (SSA) are not only dealing with decreased production from land degradation, but are also impacted heavily by climate variability. Farmers perceive decreased rainfall or shortened rainy seasons throughout SSA; however, the link between perceptions and climate variability is complex, especially in areas with increasing land degradation. Moreover, little is known about climate variability and farmers’ perceptions in central equatorial Africa. The purpose of this study is to quantify interannual rainfall variability from 1983 to 2014 in western Uganda and to relate the rainfall variability and associated changes in soil moisture to perceptions and coping strategies of local farmers. Surveys of 308 farming households and 14 group interviews were conducted near Kibale National Park, and daily satellite-based rainfall data for the region were extracted from the African Rainfall Climatology version 2 database. Results indicate a decrease in the long rains by approximately 3 weeks throughout much of the region; thus, soil-water deficits have intensified. Farmers perceived later onsets of both the short rains and long rains, while also reporting decreasing soil fertility and crop yields. Therefore, farmers’ perceptions of rainfall variability in the Kibale region may reflect more the decrease in soil fertility than the shortened rainy seasons and decreased soil moisture. Expanding croplands has been the farmers’ most prevalent coping strategy to decreased yields; however, nearly all the unfarmed land in western Uganda is now in protected areas. Consequently, western Uganda is facing a crisis at the nexus of population growth, land use change, and climate change.

INTRODUCTION: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis (TB) is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. SUBJECTS AND METHODS: To assess the GLC's impact, we followed adults with pulmonary MDRTB from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLD) in nine countries that volunteered to participate, five countries that met GLC criteria and four countries that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) TB, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLI). The relative risk (95% confidence interval) of acquired resistance was lower at GLC-approved sites: 0.27 (0.16,0.47) for XDRTB, 0.28 (0.17,0.45) for FQ, and 0.15 (0.06,0.39) to 0.60 (0.34,1.05) for three different SLI. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios were 0.21 (0.07,0.62) for acquired XDRTB and 0.23 (0.09,0.59) for acquired FQ resistance. CONCLUSIONS: Treatment of MDRTB involves substantial risk of acquired resistance to SLD, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.

BACKGROUND: Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. METHODS: In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. RESULTS: African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. CONCLUSIONS: Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved. TRIAL REGISTRATION: ClinicalTrials.gov NCT00144417.

OBJECTIVES: Broth-based culture (BBC) systems are increasingly being used to detect Mycobacterium tuberculosis complex (MTBC) in resource-limited. We evaluated the performance, time to detection and cost of the Capilia TB identification test from broth cultures positive for acid-fast bacilli (AFB) in Thailand. METHODS: From October-December 2007, broth cultures that grew AFB from specimens submitted by district TB clinics to the Bangkok city laboratory were tested for MTBC using Capilia TB and standard biochemical tests. Isolates that were identified as MTBC by biochemical tests but not by Capilia TB underwent repeat testing using Capilia TB, Accuprobe (Gen-Probe, San Diego, CA, USA) and sequencing. Costs of time, labour, infrastructure and consumables for all procedures were measured. RESULTS: Of 247 isolates evaluated, the sensitivity of Capilia TB was 97% and its true specificity 100% compared with biochemical testing. The median time from specimen receipt to confirmed MTBC identification was 20 days (range 7-53 days) for Capilia TB and 45 days (range 35-79 days) for biochemical testing (P < 0.01). Six isolates that were Capilia TB negative but positive by biochemical testing were confirmed as MTBC and mutations in the mpb64 gene were detected in all. The unit cost of using Capilia TB was 2.67 USD that of biochemical testing was 8.78 USD. CONCLUSIONS: In Thailand, Capilia TB had acceptable sensitivity and specificity, was lower in cost and had shorter turn-around times. Laboratories investing in BBC should consider Capilia TB for identification of MTBC, after validation of performance in their setting.

The role of microbial factors in outcomes of tuberculosis treatment has not been well studied. We performed a case-control study to evaluate the association between a Beijing strain and tuberculosis treatment outcomes. Isolates from patients with culture-positive treatment failure (n = 8) or relapse (n = 54) were compared with isolates from randomly selected controls (n = 296) by using spoligotyping. Patients with Beijing strains had a higher risk for relapse (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.0-4.0, p = 0.04) but not for treatment failure. Adjustment for factors previously associated with relapse had little effect on the association between Beijing strains and relapse. Beijing strains were strongly associated with relapse among Asian-Pacific Islanders (OR 11, 95% CI 1.1-108, p = 0.04). Active disease caused by a Beijing strain was associated with increased risk for relapse, particularly among Asian-Pacific Islanders.