Outcomes of Multidrug-Resistant Tuberculosis Treatment with Early Initiation of Antiretroviral Therapy for HIV Co-Infected Patients in Lesotho

Background: Although the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure. Methods: We reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes. Results: Of 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p = 0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27–5.93; HR 5.50, 95% CI 2.38–12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24–4.52). Conclusions: Favorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly

Rainfall variation and child health: effect of rainfall on diarrhea among under 5 children in Rwanda, 2010

BACKGROUND:Diarrhea among children under 5 years of age has long been a major public health concern. Previous studies have suggested an association between rainfall and diarrhea. Here, we examined the association between Rwandan rainfall patterns and childhood diarrhea and the impact of household sanitation variables on this relationship.METHODS:We derived a series of rain-related variables in Rwanda based on daily rainfall measurements and hydrological models built from daily precipitation measurements collected between 2009 and 2011. Using these data and the 2010 Rwanda Demographic and Health Survey database, we measured the association between total monthly rainfall, monthly rainfall intensity, runoff water and anomalous rainfall and the occurrence of diarrhea in children under 5 years of age.RESULTS:Among the 8601 children under 5 years of age included in the survey, 13.2 % reported having diarrhea within the 2 weeks prior to the survey. We found that higher levels of runoff were protective against diarrhea compared to low levels among children who lived in households with unimproved toilet facilities (OR?=?0.54, 95 % CI: [0.34, 0.87] for moderate runoff and OR?=?0.50, 95 % CI: [0.29, 0.86] for high runoff) but had no impact among children in household with improved toilets.CONCLUSION:Our finding that children in households with unimproved toilets were less likely to report diarrhea during periods of high runoff highlights the vulnerabilities of those living without adequate sanitation to the negative health impacts of environmental events

Assessing Early Access to Care and Child Survival during a Health System Strengthening Intervention in Mali: A Repeated Cross Sectional Survey

Background: In 2012, 6.6 million children under age five died worldwide, most from diseases with known means of prevention and treatment. A delivery gap persists between well-validated methods for child survival and equitable, timely access to those methods. We measured early child health care access, morbidity, and mortality over the course of a health system strengthening model intervention in Yirimadjo, Mali. The intervention included Community Health Worker active case finding, user fee removal, infrastructure development, community mobilization, and prevention programming. Methods and Findings: We conducted four household surveys using a cluster-based, population-weighted sampling methodology at baseline and at 12, 24, and 36 months. We defined our outcomes as the percentage of children initiating an effective antimalarial within 24 hours of symptom onset, the percentage of children reported to be febrile within the previous two weeks, and the under-five child mortality rate. We compared prevalence of febrile illness and treatment using chi-square statistics, and estimated and compared under-five mortality rates using Cox proportional hazard regression. There was a statistically significant difference in under-five mortality between the 2008 and 2011 surveys; in 2011, the hazard of under-five mortality in the intervention area was one tenth that of baseline (HR 0.10, p<0.0001). After three years of the intervention, the prevalence of febrile illness among children under five was significantly lower, from 38.2% at baseline to 23.3% in 2011 (PR = 0.61, p = 0.0009). The percentage of children starting an effective antimalarial within 24 hours of symptom onset was nearly twice that reported at baseline (PR = 1.89, p = 0.0195). Conclusions: Community-based health systems strengthening may facilitate early access to prevention and care and may provide a means for improving child survival

Rainfall variation and child health: effect of rainfall on diarrhea among under 5 children in Rwanda, 2010

Background: Diarrhea among children under 5 years of age has long been a major public health concern. Previous studies have suggested an association between rainfall and diarrhea. Here, we examined the association between Rwandan rainfall patterns and childhood diarrhea and the impact of household sanitation variables on this relationship. Methods: We derived a series of rain-related variables in Rwanda based on daily rainfall measurements and hydrological models built from daily precipitation measurements collected between 2009 and 2011. Using these data and the 2010 Rwanda Demographic and Health Survey database, we measured the association between total monthly rainfall, monthly rainfall intensity, runoff water and anomalous rainfall and the occurrence of diarrhea in children under 5 years of age. Results: Among the 8601 children under 5 years of age included in the survey, 13.2 % reported having diarrhea within the 2 weeks prior to the survey. We found that higher levels of runoff were protective against diarrhea compared to low levels among children who lived in households with unimproved toilet facilities (OR = 0.54, 95 % CI: [0.34, 0.87] for moderate runoff and OR = 0.50, 95 % CI: [0.29, 0.86] for high runoff) but had no impact among children in household with improved toilets. Conclusion: Our finding that children in households with unimproved toilets were less likely to report diarrhea during periods of high runoff highlights the vulnerabilities of those living without adequate sanitation to the negative health impacts of environmental events

Targeted Drug-Resistance Testing Strategy for Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008

Running head: Targeted Drug-Resistance Testing Strategy for MDR T

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: a prospective cohort study

Background: Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting. Methods: We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment. Results: Of 1701 participants treated for tuberculosis, 136 (8.0 %) died during tuberculosis treatment. HIV-positive patients constituted 11.0 % of the cohort and contributed to 34.6 % of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9 %, P < 0.001) and less likely to be cured (28.3 vs. 39.4 %, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95 % confidence interval [CI], 3.96–9.27), unemployment (HR = 2.24; 95 % CI, 1.55–3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95 % CI, 1.10–3.31) were significantly associated with a higher hazard of death. Conclusions: We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality

Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study.

Rationale: Bedaquiline and delamanid offer the possibility of more effective and less toxic treatment for multidrug-resistant (MDR) tuberculosis (TB). With this treatment, however, some patients remain at high risk for an unfavorable treatment outcome. The endTB Observational Study is the largest multicountry cohort of patients with rifampin-resistant TB or MDR-TB treated in routine care with delamanid- and/or bedaquiline-containing regimens according to World Health Organization guidance.Objectives: We report the frequency of sputum culture conversion within 6 months of treatment initiation and the risk factors for nonconversion.Methods: We included patients with a positive baseline culture who initiated a first endTB regimen before April 2018. Two consecutive negative cultures collected 15 days or more apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.Measurements and Main Results: A total of 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%), or both (10%). Of these, 939 (85%) experienced culture conversion within 6 months. In adjusted analyses, patients with HIV had a lower probability of conversion (0.73; 95% confidence interval [CI], 0.62-0.84) than patients without HIV (0.84; 95% CI, 0.79-0.90; P = 0.03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0.68; 95% CI, 0.57-0.79) relative to patients without either (0.89; 95% CI, 0.84-0.95; P = 0.0004). Hepatitis C infection, diabetes mellitus or glucose intolerance, and baseline resistance were not associated with conversion.Conclusions: Frequent sputum conversion in patients with rifampin-resistant TB or MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease

DHS_U5M: A flexible SAS macro to calculate childhood mortality estimates and standard errors from birth histories

This SAS macro generates childhood mortality estimates (neonatal, post-neonatal, infant (1q0), child (4q1) and under-five (5q0) mortality) and standard errors based on birth histories reported by women during a household survey. We have made the SAS macro flexible enough to accommodate a range of calculation specifications including multi-stage sampling frames, and simple random samples or censuses. Childhood mortality rates are the component death probabilities of dying before a specific age. This SAS macro is based on a macro built by Keith Purvis at MeasureDHS. His method is described in Estimating Sampling Errors of Means, Total Fertility, and Childhood Mortality Rates Using SAS (www.measuredhs.com/pubs/pdf/OD17/OD17.pdf, section 4). More information about Childhood Mortality Estimation can also be found in the Guide to DHS Statistics (www.measuredhs.com/pubs/pdf/DHSG1/Guide_DHS_Statistics.pdf, page 93). We allow the user to specify whether childhood mortality calculations should be based on 5 or 10 years of birth histories, when the birth history window ends, and how to handle age of death with it is reported in whole months (rather than days). The user can also calculate mortality rates within sub-populations, and take account of a complex survey design (unequal probability and cluster samples). Finally, this SAS program is designed to read data in a number of different formats

Geographical guide to floras of the world : an annotated list with special reference to useful plants and common plant names : Part 1. Africa, Australia, North America, South America, and islands of Atlantic, Pacific, and Indian oceans / by S.F. Blake and Alice C. Atwood.

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