Helena Huerga

Lessons and Challenges for Measles Control from Unexpected Large Outbreak, Malawi

Supplementary immunization activities are crucial to reduce the number of susceptible children.

Nutrition outcomes of HIV-infected malnourished adults treated with ready-to-use therapeutic food in sub-Saharan Africa: a longitudinal study

BackgroundAmong people living with HIV/AIDS, nutritional support is increasingly recognized as a critical part of the essential package of care, especially for patients in sub-Saharan Africa. The objectives of the study were to evaluate the outcomes of HIV-positive malnourished adults treated with ready-to-use therapeutic food and to identify factors associated with nutrition programme failure.MethodsWe present results from a retrospective cohort analysis of patients aged 15 years or older with a body mass index of less than 17 kg/m2 enrolled in three HIV/AIDS care programmes in Africa between March 2006 and August 2008. Factors associated with nutrition programme failure (patients discharged uncured after six or more months of nutritional care, defaulting from nutritional care, remaining in nutritional care for six or more months, or dead) were investigated using multiple logistic regression.ResultsOverall, 1340 of 8685 (15.4%) HIV-positive adults were enrolled in the nutrition programme. At admission, median body mass index was 15.8 kg/m2 (IQR 14.9-16.4) and 12% received combination antiretroviral therapy (ART). After a median of four months of follow up (IQR 2.2-6.1), 524 of 1106 (47.4%) patients were considered cured. An overall total of 531 of 1106 (48.0%) patients failed nutrition therapy, 132 (11.9%) of whom died and 250 (22.6%) defaulted from care. Men (OR = 1.5, 95% CI 1.2-2.0), patients with severe malnutrition at nutrition programme enrolment (OR = 2.2, 95% CI 1.7-2.8), and those never started on ART (OR = 4.5, 95% CI 2.7-7.7 for those eligible; OR = 1.6, 95% CI 1.0-2.5 for those ineligible for ART at enrolment) were at increased risk of nutrition programme failure. Diagnosed tuberculosis at nutrition programme admission or during follow up, and presence of diarrhoeal disease or extensive candidiasis at admission, were unrelated to nutrition programme failure.ConclusionsConcomitant administration of ART and ready-to-use therapeutic food increases the chances of nutritional recovery in these high-risk patients. While adequate nutrition is necessary to treat malnourished HIV patients, development of improved strategies for the management of severely malnourished patients with HIV/AIDS are urgently needed.

Performance of the 2007 WHO Algorithm to Diagnose Smear-Negative Pulmonary Tuberculosis in a HIV Prevalent Setting

Background The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya. Methods PTB smear-negative adult suspects were included in a prospective diagnostic study (2009–2011). In addition, program data (2008–2009) were retrospectively analysed. At the first consultation, clinical examination, chest X-ray, and sputum culture (Thin-Layer-Agar and Lowenstein-Jensen) were performed. Patients not started on TB treatment were clinically re-assessed after antibiotic course. The algorithm performance was calculated using culture as reference standard. Results 380 patients were included prospectively and 406 analyzed retrospectively. Culture was positive for MTB in 17.5% (61/348) and 21.8% (72/330) of cases. Sensitivity of the clinical-radiological algorithm was 55.0% and 31.9% in the prospective study and the program data analysis, respectively. Specificity, positive and negative predictive values were 72.9%, 29.7% and 88.6% in the prospective study and 79.8%, 30.7% and 80.8% in the program data analysis. Performing culture increased the number of confirmed TB patients started on treatment by 43.3% in the prospective study and by 44.4% in the program data analysis. Median time to treatment of confirmed TB patients was 6 days in the prospective study and 27 days in the retrospective study. Inter-reader agreement for X-ray interpretation between the study clinician and a radiologist was low (Kappa coefficient = 0.11, 95%CI: 0.09–0.12). In a multivariate logistic analysis, past TB history, number of symptoms and signs at the clinical exam were independently associated with risk of overtreatment. Conclusion The clinical-radiological algorithm is suboptimal to diagnose smear-negative PTB. Culture increases significantly the proportion of confirmed TB cases started on treatment. Better access to rapid MTB culture and development of new diagnostic tests is necessary.

Adherence to Self-Administered Tuberculosis Treatment in a High HIV-Prevalence Setting: A Cross-Sectional Survey in Homa Bay, Kenya

Background Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools. Methods We conducted a cross-sectional survey amongst a series of new TB patients receiving 6 months of standard TB chemotherapy with FDC under SAT. Adherence was assessed at home with urine testing for Isoniazid (INH), pill count, interviewer-administered questionnaire and visual analogue scale (VAS). Results In November 2008 and in June 2009, 212 of 279 eligible patients were assessed for adherence. Overall, 95.2% [95%CI: 91.3–97.7] of the patients reported not having missed a tablet in the last 4 days. On the VAS, complete adherence was estimated at 92.5% [95%CI: 88.0–95.6]. INH urine test was positive for 97.6% [95%CI: 94.6–99.2] of the patients. Pill count could be assessed among only 70% of the interviewed patients. Among them, it was complete for 82.3% [95%CI: 75.1–88.1]. Among the 212 surveyed patients, 193 (91.0%) were successfully treated (cured or treatment completed). The data suggest a fair agreement between the questionnaire and the INH urine test (k = 0.43) and between the questionnaire and the VAS (k = 0.40). Agreement was poor between the other adherence tools. Conclusion These results suggest that SAT, together with the FDC, allows achieving appropriate adherence to antituberculosis treatment in a high TB and HIV burden area. The use of a combination of a VAS and a questionnaire can be an adequate approach to monitor adherence to TB treatment in routine program conditions.

Adult and paediatric mortality patterns in a referral hospital in Liberia 1 year after the end of the war

The aim of this study was to describe and analyse hospital mortality patterns after the Liberian war. Data were collected retrospectively from January to July 2005 in a referral hospital in Monrovia, Liberia. The overall fatality rate was 17.2% (438/2543) of medical admissions. One-third of deaths occurred in the first 24h. The adult fatality rate was 23.3% (241/1034). Non-infectious diseases accounted for 56% of the adult deaths. The main causes of death were meningitis (16%), stroke (14%) and heart failure (10%). Associated fatality rates were 48%, 54% and 31% respectively. The paediatric fatality rate was 13.1% (197/1509). Infectious diseases caused 66% of paediatric deaths. In infants <1 month old, the fatality rate was 18% and main causes of death were neonatal sepsis (47%), respiratory distress (24%) and prematurity (18%). The main causes of death in infants > or =1 month old were respiratory infections (27%), malaria (23%) and severe malnutrition (16%). Associated fatality rates were 12%, 10% and 19%. Fatality rates were similar to those found in other sub-Saharan countries without a previous conflict. Early deaths could decrease through recognition and early referral of severe cases from health centres to the hospital and through assessment and priority treatment of these patients at arrival.

Incremental Yield of Including Determine-TB LAM Assay in Diagnostic Algorithms for Hospitalized and Ambulatory HIV-Positive Patients in Kenya.

Background Determine-TB LAM assay is a urine point-of-care test useful for TB diagnosis in HIV-positive patients. We assessed the incremental diagnostic yield of adding LAM to algorithms based on clinical signs, sputum smear-microscopy, chest X-ray and Xpert MTB/RIF in HIV-positive patients with symptoms of pulmonary TB (PTB). Methods Prospective observational cohort of ambulatory (either severely ill or CD4<200cells/μl or with Body Mass Index<17Kg/m2) and hospitalized symptomatic HIV-positive adults in Kenya. Incremental diagnostic yield of adding LAM was the difference in the proportion of confirmed TB patients (positive Xpert or MTB culture) diagnosed by the algorithm with LAM compared to the algorithm without LAM. The multivariable mortality model was adjusted for age, sex, clinical severity, BMI, CD4, ART initiation, LAM result and TB confirmation. Results Among 474 patients included, 44.1% were severely ill, 69.6% had CD4<200cells/μl, 59.9% had initiated ART, 23.2% could not produce sputum. LAM, smear-microscopy, Xpert and culture in sputum were positive in 39.0% (185/474), 21.6% (76/352), 29.1% (102/350) and 39.7% (92/232) of the patients tested, respectively. Of 156 patients with confirmed TB, 65.4% were LAM positive. Of those classified as non-TB, 84.0% were LAM negative. Adding LAM increased the diagnostic yield of the algorithms by 36.6%, from 47.4% (95%CI:39.4–55.6) to 84.0% (95%CI:77.3–89.4%), when using clinical signs and X-ray; by 19.9%, from 62.2% (95%CI:54.1–69.8) to 82.1% (95%CI:75.1–87.7), when using clinical signs and microscopy; and by 13.4%, from 74.4% (95%CI:66.8–81.0) to 87.8% (95%CI:81.6–92.5), when using clinical signs and Xpert. LAM positive patients had an increased risk of 2-months mortality (aOR:2.7; 95%CI:1.5–4.9). Conclusion LAM should be included in TB diagnostic algorithms in parallel to microscopy or Xpert request for HIV-positive patients either ambulatory (severely ill or CD4<200cells/μl) or hospitalized. LAM allows same day treatment initiation in patients at higher risk of death and in those not able to produce sputum.

Implementation and Operational Research: Feasibility of Using Tuberculin Skin Test Screening for Initiation of 36-Month Isoniazid Preventive Therapy in HIV-Infected Patients in Resource-Constrained Settings.

Introduction:The tuberculin skin test (TST) can be used to identify HIV-infected people who would benefit the most from long-term isoniazid preventive therapy (IPT). However, in resource-constrained settings, implementation of the TST can be challenging. The objectives of this study were to assess the feasibility of implementing the TST for IPT initiation and to estimate the proportion of TST-positive incidence among HIV-positive patients in 2 high tuberculosis and HIV burden settings. Methods:Two prospective observational cohort studies were conducted under programmatic conditions in Mathare, an urban slum of Nairobi, Kenya, and in rural Shiselweni, Swaziland. HIV-positive adults with negative tuberculosis symptomatic screening underwent the TST. Those testing positive were started on 36-month IPT. Results:Of 897 and 1021 patients screened in Mathare and Shiselweni, 550 and 696, respectively, were included. Median age was 38 years, 67.7% were female, and 86.8% were on antiretroviral therapy. Among TST-eligible participants, 88.0% (491/558) and 81.8% (694/848) accepted TST and 74.2% (414/558) and 77.1% (654/858) returned for test reading in Mathare and Shiselweni, respectively. The TST was positive in 49.8% (95% confidence interval: 44.9 to 54.6) in Mathare and 33.2% (95% confidence interval: 29.6 to 36.8) in Shiselweni. The 36-month IPT was accepted by 96.1% (198/206) patients in Mathare and 99.5% (216/217) in Shiselweni. IPT implementation at the clinics was managed with no additional staff or extra space. Conclusion:Implementing the TST for IPT initiation was feasible and acceptable in both urban and rural resource-constrained settings. This strategy allows patients who can benefit the most to receive long-term IPT and avoids unnecessarily treating a significant number of patients who do not stand to benefit.

Shortened multidrug-resistant tuberculosis treatment in settings with a high prevalence of ofloxacin resistance

We read with interest the research letter by Javaid et al. [1] in a recent issue of the European Respiratory Journal. The authors aptly note some uncertainty in current World Health Organization (WHO) guidelines [2]. Nevertheless, we question the authors’ main assertion that “high prevalence of ofloxacin resistance should not limit the applicability of the new shorter regimen”. The shortened regimen has indeed produced promising results in a number of settings, albeit in populations carefully selected for their limited exposure and resistance to second-line drugs [3–5]. That this should be extended to settings with a high prevalence of fluoroquinolone resistance, without individual, rapid molecular testing for such resistance, is not supported by data or the WHO. Shortened MDR-TB treatment requires individual, rapid resistance testing for fluoroquinolone resistance http://ow.ly/sufM30cjQYM

Population-level HIV incidence estimates using a combination of synthetic cohort and recency biomarker approaches in KwaZulu-Natal, South Africa

Introduction There is a notable absence of consensus on how to generate estimates of population-level incidence. Incidence is a considerably more sensitive indicator of epidemiological trends than prevalence, but is harder to estimate. We used a novel hybrid method to estimate HIV incidence by age and sex in a rural district of KwaZulu-Natal, South Africa. Methods Our novel method uses an ‘optimal weighting’ of estimates based on an implementation of a particular ‘synthetic cohort’ approach (interpreting the age/time structure of prevalence, in conjunction with estimates of excess mortality) and biomarkers of ‘recent infection’ (combining Lag-Avidity, Bio-Rad Avidity and viral load results to define recent infection, and adapting the method for age-specific incidence estimation). Data were obtained from a population-based cross-sectional HIV survey conducted in Mbongolwane and Eshowe health service areas in 2013. Results Using the combined method, we find that age-specific HIV incidence in females rose rapidly during adolescence, from 1.33 cases/100 person-years (95% CI: 0.98,1.67) at age 15 to a peak of 5.01/100PY (4.14,5.87) at age 23. In males, incidence was lower, 0.34/100PY (0.00-0.74) at age 15, and rose later, peaking at 3.86/100PY (2.52-5.20) at age 30. Susceptible population-weighted average incidence in females aged 15-29 was estimated at 3.84/100PY (3.36-4.40), in males aged 15-29 at 1.28/100PY (0.68-1.50) and in all individuals aged 15-29 at 2.55/100PY (2.09-2.76). Using the conventional recency biomarker approach, we estimated HIV incidence among females aged 15-29 at 2.99/100PY (1.79-4.36), among males aged 15-29 at 0.87/100PY (0.22-1.60) and among all individuals aged 15-59 at 1.66/100PY (1.13-2.27). Discussion HIV incidence was very high in women aged 15-30, peaking in the early 20s. Men had lower incidence, which peaked at age 30. The estimates obtained from the hybrid method are more informative than those produced by conventional analysis of biomarker data, and represents a more optimal use of available data than either the age-continuous biomarker or synthetic cohort methods alone. The method is mainly useful at younger ages, where excess mortality is low and uncertainty in the synthetic cohort estimates is reasonably small. Conclusion Application of this method to large-scale population-based HIV prevalence surveys is likely to result in improved incidence surveillance over methods currently in wide use. Reasonably accurate and precise age-specific estimates of incidence are important to target better prevention, diagnosis and care strategies.

Bedaquiline and Repurposed Drugs for Fluoroquinolone-Resistant MDR-TB: How Much Better Are They?

on grouping and outcomes. Am J Respir Crit Care Med 2018;197: 463–469. 6. Wong ES, Rinne ST, Hebert PL, Cook MA, Liu CF. Hospital distance and readmissions among VA-Medicare dual-enrolled veterans. J Rural Health 2016;32:377–386. 7. Rinne ST, Elwy AR, Bastian LA, Wong ES, Wiener RS, Liu CF. Impact of multisystem health care on readmission and follow-up among veterans hospitalized for chronic obstructive pulmonary disease. Med Care 2017;55(Suppl 7 Suppl 1):S20–S25. 8. Darnell K, Dwivedi AK, Weng Z, Panos RJ. Disproportionate utilization of healthcare resources among veterans with COPD: a retrospective analysis of factors associated with COPD healthcare cost. Cost Eff Resour Alloc 2013;11:13. 9. Garvin JH, Redd A, Bolton D, Graham P, Roche D, Groeneveld P, et al. Exploration of ICD-9-CM coding of chronic disease within the Elixhauser comorbidity measure in patients with chronic heart failure. Perspect Health Inf Manag 2013; 10:1b. 10. Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA 2012;307: 1801–1802.