Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.

Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.

Alcohol use, drunkenness and tobacco smoking in rural western Kenya.

OBJECTIVES: To describe the prevalence of smoking and alcohol use and abuse in an impoverished rural region of western Kenya. METHODS: Picked from a population-based longitudinal database of demographic and health census data, 72 292 adults (≥18 years) were asked to self-report their recent (within the past 30 days) and lifetime use of tobacco and alcohol and frequency of recent 'drunkenness'. RESULTS: Overall prevalence of ever smoking was 11.2% (11.0-11.5) and of ever drinking, 20.7% (20.4-21.0). The prevalence of current smoking was 6.3% (6.1-6.5); 5.7% (5.5-5.9) smoked daily. 7.3% (7.1-7.5) reported drinking alcohol within the past 30 days. Of these, 60.3% (58.9-61.6) reported being drunk on half or more of all drinking occasions. The percentage of current smokers rose with the number of drinking days in a month (P < 0.0001). Tobacco and alcohol use increased with decreasing socio-economic status and amongst women in the oldest age group (P < 0.0001). CONCLUSIONS: Tobacco and alcohol use are prevalent in this rural region of Kenya. Abuse of alcohol is common and likely influenced by the availability of cheap, home-manufactured alcohol. Appropriate evidence-based policies to reduce alcohol and tobacco use should be widely implemented and complemented by public health efforts to increase awareness of their harmful effects.

What are the most sensitive and specific sign and symptom combinations for influenza in patients hospitalized with acute respiratory illness? Results from western Kenya, January 2007-July 2010.

Influenza causes severe illness and deaths, and global surveillance systems use different clinical case definitions to identify patients for diagnostic testing. We used data collected during January 2007-July 2010 at hospital-based influenza surveillance sites in western Kenya to calculate sensitivity, specificity, positive predictive value, and negative predictive value for eight clinical sign/symptom combinations in hospitalized patients with acute respiratory illnesses, including severe acute respiratory illness (SARI) (persons aged 2-59 months: cough or difficulty breathing with an elevated respiratory rate or a danger sign; persons aged ≥5 years: temperature ≥38 °C, difficulty breathing, and cough or sore throat) and influenza-like illness (ILI) (all ages: temperature ≥38 °C and cough or sore throat). Overall, 4800 persons aged ≥2 months were tested for influenza; 416 (9%) had laboratory-confirmed influenza infections. The symptom combination of cough with fever (subjective or measured ≥38 °C) had high sensitivity [87·0%, 95% confidence interval (CI) 83·3-88·9], and ILI had high specificity (70·0%, 95% CI 68·6-71·3). The case definition combining cough and any fever is a simple, sensitive case definition for influenza in hospitalized persons of all age groups, whereas the ILI case definition is the most specific. The SARI case definition did not maximize sensitivity or specificity.

Successful use of rifampicin for Hispanic foreign-born patients with latent tuberculosis infection.

SETTING: Four months of rifampicin (4R) is recommended for the treatment of latent tuberculosis infection (LTBI), although data regarding its use are limited. The majority of tuberculosis (TB) cases in the USA occur among foreign-born persons. OBJECTIVE: To determine tolerability, hepatotoxicity and completion rates associated with 4R among foreign-born persons. DESIGN: We retrospectively evaluated 4R treatment among a cohort of predominantly Hispanic foreign-born LTBI patients in four Middle-Tennessee public health clinics from February 2000 to February 2004. Patients' charts were reviewed to abstract demographic, social and clinical data. 4R completion rates, new symptoms and hepatotoxicity (serum aminoalanine transferase >or=120U/l with gastrointestinal symptoms or >or=200 regardless of symptoms) were evaluated. RESULTS: Of 749 patients treated, 571 (76%) completed 4R. Among all subjects, Hispanics had a lower risk of non-completion (OR 0.6, 95%CI 0.4-0.7) than non-Hispanics. Among non-Hispanic subjects, the risk of non-completion was higher for Blacks than non-Blacks (adjusted OR 2.6, 95%CI 1.5-4.7), but was lower for foreign-born than non-foreign-born subjects (adjusted OR 0.5, 95%CI 0.2-0.9). During treatment, 85 subjects (11%) developed new symptoms, and hepatotoxicity occurred in three patients. CONCLUSION: With high completion rates and minimal side effects, 4R is a favorable LTBI treatment regimen for Hispanic and other foreign-born patients.

Using program evaluation to improve the performance of a TB-HIV project in Banteay Meanchey, Cambodia.

SETTING: Cambodia has the highest human immunodeficiency virus (HIV) prevalence (1.9%) and tuberculosis (TB) incidence (508/100000) in Asia. Banteay Meanchey, a province with high HIV prevalence of 1.9%, established a pilot project in 2003 to enhance TB-HIV activities. We evaluated this project to improve performance. METHODS: In March 2005, we analyzed 17 months of data on all persons diagnosed with HIV or TB at 11 participating clinics. We determined barriers to HIV testing and TB screening, modified the program to reduce these barriers and assessed whether our interventions improved testing and screening rates. RESULTS: Among 952 patients newly diagnosed with TB disease, 138 (14%) had known HIV infection at the time of TB diagnosis. Of the 814 TB patients with unknown HIV status, 432 (53%) were HIV tested. Of 1228 persons newly diagnosed with HIV infection, 450 (37%) were screened for TB disease. We found and addressed barriers to HIV testing and TB screening. In the 9 months after the interventions, 240/322 (71%) TB patients were HIV tested, an increase of 34% (P < 0.01); 426/751 (57%) HIV-infected patients were screened for TB, an increase of 54% (P < 0.01). CONCLUSION: Evaluations of TB-HIV collaborative activities can lead to increased TB screening and HIV testing rates.

Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992-2002.

SETTING: Brooklyn Chest Hospital, Western Cape, South Africa. OBJECTIVE: To evaluate the treatment outcome and 2- and 5-year follow-up of patients treated for multidrug-resistant tuberculosis (MDR-TB) with individualized regimens. DESIGN: Retrospective cohort study of all MDR-TB patients starting treatment during 1992-2002. Patients were evaluated every 6 months for 2 years after treatment and at 5 years when possible. RESULTS: Over 11 years, 491 (66%) of 747 MDR-TB patients received treatment with two or more second-line drugs; 239 (49%) were cured or completed treatment, 68 (14%) died, 144 (29%) defaulted from treatment, 27 (5%) failed, 10 (2%) transferred out and 3 (<1%) remained on treatment. Only 176 (36%) were tested for human immunodeficiency virus and 15 were positive. The proportion with a successful MDR-TB treatment outcome declined over time, while the proportion who defaulted remained stable. Among 410 patients who had not transferred out or died, 281 (69%) had 2-year data available: 185 (66%) were cured or completed treatment, 32 (11%) were retreated for TB and 64 (23%) died. CONCLUSIONS: Under program conditions in the West Coast/Winelands District, default rates were high and treatment success rates low. Outreach strategies for MDR-TB treatment should only be implemented if adequate resources are committed to the program.

The epidemiology of HIV-associated tuberculosis in rural Cambodia.

SETTING: Banteay Meanchey Province, Cambodia. OBJECTIVE: The World Health Organization recommends human immunodeficiency virus (HIV) testing for all tuberculosis (TB) patients and TB screening for all HIV-infected persons in countries with a TB-HIV syndemic. We sought to determine whether evidence supports implementing these recommendations in South-East Asia. DESIGN: We conducted a cross-sectional survey and retrospective cohort study of patients newly diagnosed with HIV or TB from October 2003 to February 2005 to identify risk factors for HIV infection and TB, and for death during TB treatment. RESULTS: HIV infection was diagnosed in 216/574 (38%) TB patients. TB disease was found in 124/450 (24%) HIV-infected persons. No sub-groups of patients had a low risk of HIV infection or TB. Of 180 TB patients with HIV infection and a recorded treatment outcome, 49 (27%) died compared to 17/357 (5%) without HIV infection (relative risk [RR] 5.2, 95% confidence interval [CI] 3.1-8.7). HIV-infected TB patients with smear-negative pulmonary disease died less frequently than those with smear-positive pulmonary disease (RR 0.39, 95%CI 0.16-0.93). CONCLUSIONS: No sub-groups of patients had low risk for HIV infection or TB, and mortality among HIV-infected TB patients was high. These data justify using the WHO global TB-HIV recommendations in South-East Asia. Urgent interventions are needed to reduce the high mortality rate in HIV-infected TB patients.

Risk factors associated with default from multidrug-resistant tuberculosis treatment, South Africa, 1999-2001.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment centers in five provinces, South Africa. OBJECTIVES: To estimate the mortality and evaluate risk factors associated with default from MDR-TB treatment. DESIGN: Using registries and a standardized questionnaire, we conducted a case-control study among patients diagnosed and treated for MDR-TB. Cases were defined as patients who began MDR-TB treatment between 1 October 1999 and 30 September 2001 and defaulted from treatment for more than 2 months; controls were defined as patients who began MDR-TB treatment during the same time and were cured, completed or failed. RESULTS: After initial identification and reclassification, 269 cases and 401 controls were confirmed eligible for interview. Further investigation revealed that 74 (27%) cases and 44 (10%) controls had died. Among 96 cases located who consented and were interviewed, 70% had defaulted after receiving at least 6 months of treatment. In a multivariate model, the strongest individual risk factors for default included reporting smoking marijuana or mandrax during treatment, and having an unsatisfactory opinion about the attitude of health care workers. CONCLUSION: Mortality among MDR-TB defaulters was high. Interventions to reduce default from MDR-TB treatment should center on substance abuse treatment, patient education and support and improving provider-patient relationships.

A multicenter evaluation of tuberculin skin test positivity and conversion among health care workers in Brazilian hospitals.

SETTING: Four general Brazilian hospitals. OBJECTIVE: To assess the occupational risk of Mycobacterium tuberculosis (TB) in participating hospitals. DESIGN: In phase one of this longitudinal study, a cross-sectional survey documented baseline tuberculin skin test (TST) positivity rates. In phase two, TST conversion rates were evaluated in participants with an initial negative two-step TST. TST conversion data were analyzed to determine risk factors for TB infection using an increase of > or = 10 mm compared to baseline TST. RESULTS: The initial TST positivity rate was 63.1%; the follow-up TST conversion rate was 10.7 per 1000 person-months (p-m). Hospital of employment, recent bacille Calmette-Guerin (BCG) vaccination, nosocomial TB exposure, and employment as a nurse were independent risk factors for TST conversion. Hospitals without TB infection control measures had higher conversion rates than those with control measures (16.0 vs. 7.8/ 1000 p-m, P < 0.001). CONCLUSIONS: This study indicates an important occupational risk of infection in health care settings with a high TB incidence. Longitudinal TST studies are a valuable tool to assess the occupational risk of TB, even in BCG-vaccinated populations, and should be used to direct limited resources for infection control.

TST reversion in a BCG-revaccinated population of nursing and medical students, São Paulo, Brazil, 1997-2000.

SETTING: A major university in São Paulo, Brazil, where vaccination against tuberculosis (TB) with bacille Calmette-Guerin (BCG) was routinely offered to first-year medical and nursing students. OBJECTIVES: To estimate the probability of negative tuberculin skin test (TST) results over a 4-year period following BCG revaccination, and to evaluate the effect of factors associated with reversion. DESIGN: Students were enrolled in 1997, initially given a two-step TST, and were retested annually or biannually for the duration of the study. Data on TB exposures and potential risk factors for TST negativity and reversion were collected through annual surveys. A linear mixture survival model was used to estimate the probability of negative TST results over time. RESULTS: Of 159 students, an estimated 20% had a negative TST result despite revaccination, and a further 31% reverted to negative over 4 years of follow-up. No cofactors significantly affected the probability of reversion. CONCLUSION: Overall, in the absence of reported exposure to Mycobacterium tuberculosis, 51% of students revaccinated upon entering nursing or medical school would have a negative TST result by the time they begin their internships. In this recently vaccinated population, reversion was common, suggesting that annual TST screening may remain a useful tool.

Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis.

SETTING: Globally it is estimated that 273000 new cases of multidrug-resistant tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000. To address MDR-TB management in the context of the DOTS strategy, the World Health Organization and partners have been promoting an expanded treatment strategy called DOTS-Plus. However, standard definitions for MDR-TB patient registration and treatment outcomes do not exist. OBJECTIVE: To propose a standardized set of case registration groups and treatment outcome definitions for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus strategy. DESIGN: Using published definitions for drug-susceptible TB as a guide, a 2-year-long series of meetings, conferences, and correspondence was undertaken to review published literature and country-specific program experience, and to develop international agreement. RESULTS: Definitions were designed for MDR-TB patient categorization, smear and culture conversion, and treatment outcomes (cure, treatment completion, death, default, failure, transfer out). Standards for conducting outcome analyses were developed to ensure comparability between programs. CONCLUSION: Optimal management strategies for MDR-TB have not been evaluated in controlled clinical trials. Standardized definitions and cohort analyses will facilitate assessment and comparison of program performance. These data will contribute to the evidence base to inform decision makers on approaches to MDR-TB control.

Capacity building for international tuberculosis control through operations research training.

SETTING: In resource-poor countries, few tuberculosis (TB) program staff at the national, provincial, and even district levels have the basic analytical and epidemiological skills necessary for collecting and analyzing quality data pertaining to national TB control program (NTP) improvements. This includes setting program priorities, operations planning, and implementing and evaluating program activities. OBJECTIVES: To present a model course for building capacity in basic epidemiology and operations research (OR). DESIGN: A combination of didactic lectures and applied field exercises were used to achieve the main objectives of the 6-day OR course. These were to increase the understanding of quantitative and qualitative research concepts, study design, and analytic methods, and to increase awareness of how these methods apply to the epidemiology and control of TB; and to demonstrate the potential uses of OR in answering practical questions on NTP effectiveness. As a final outcome, course participants develop OR proposals that are funded and later implemented. RESULTS: Since 1997, this OR course has been conducted nine times in five countries; 149 key NTP and laboratory staff have been trained in OR methods, and 44 OR protocols have been completed or are underway. CONCLUSION: This low-cost model course can be adapted to a wide range of public health issues.

Effect of chemotherapy on malaria transmission among Yanomami Amerindians: simulated consequences of placebo treatment.

To determine whether chemotherapy effectively reduces Plasmodium falciparum malaria transmission in isolated human populations, we followed two abrupt sequential outbreaks of malaria infection among Yanomami Amerindians and modeled the effect of chemotherapy and the consequences if no drug was available. A Macdonald-type mathematical model demonstrated that both outbreaks comprised a single epidemic event linked by an invisible outbreak in vector mosquitoes. The basic reproductive number, R0, from fitted values based on the treated epidemic was 2 during the initial phase of the epidemic, and waned as vector density decreased with the onset of the dry season. In the observed epidemic, 60 (45%) of 132 village residents were affected, and the treated outbreak ended after two months. Although the initial chemotherapy regimen was only marginally effective, the duration of human infectivity was reduced from an expected nine months to two weeks. In the absence of this intervention, the initial R0 value would have been 40, more than 60% of the population would have been infected, and more than 30% would have remained parasitemic until the next rainy season (about six months later). Another outbreak would then have ensued, and malaria probably would have remained endemic in this village. Our simulated placebo treatment permits us to conclude that even partially effective chemotherapeutic interventions, such as those in our study, interrupt serial transmission of P. falciparum among isolated human populations that are exposed to infection seasonally.

Differential perpetuation of malaria species among Amazonian Yanomami Amerindians.

To determine whether malaria perpetuates within isolated Amerindian villages in the Venezuelan Amazon, we surveyed malaria infection and disease among 1,311 Yanomami in three communities during a 16-month period. Plasmodium vivax was generally present in each of these small, isolated villages; asymptomatic infection was frequent, and clinical disease was most evident among children less than five years of age (odds ratio [OR] = 6.3, 95% confidence interval [CI] = 1.4-29.2) and among persons experiencing parasitemias > or = 1,000 parasites/mm3 of blood (OR = 45.0, 95% CI = 5.5-370.7). Plasmodium falciparum, in contrast, was less prevalent, except during an abrupt outbreak in which 72 infections resulted in symptoms in all age groups and at all levels of parasitemia, and occasionally were life-threatening. The observed endemic pattern of P. vivax infection may derive from the capacity of this pathogen to relapse, while the epidemic pattern of P. falciparum infection may reflect occasional introductions of strains carried by immigrants or residents of distant villages and the subsequent disappearance of this non-relapsing pathogen.

Use of the polymerase chain reaction to directly detect malaria parasites in blood samples from the Venezuelan Amazon.

We have examined the reproducibility, sensitivity, and specificity of detecting Plasmodium falciparum using the polymerase chain reaction (PCR) and the species-specific probe pPF14 under field conditions in the Venezuelan Amazon. Up to eight samples were field collected from each of 48 consenting Amerindians presenting with symptoms of malaria. Sample processing and analysis was performed at the Centro Amazonico para la Investigacion y Control de Enfermedades Tropicales Simon Bolivar. A total of 229 samples from 48 patients were analyzed by PCR methods using four different P. falciparum-specific probes. One P. vivax-specific probe and by conventional microscopy. Samples in which results from PCR and microscopy differed were reanalyzed at a higher sensitivity by microscopy. Results suggest that microscopy-negative, PCR-positive samples are true positives, and that microscopy-positive and PCR-negative samples are true negatives. The sensitivity of the DNA probe/PCR method was 78% and its specificity was 97%. The positive predictive value of the PCR method was 88%, and the negative predictive value was 95%. Through the analysis of multiple blood samples from each individual, the DNA probe/PCR methodology was found to have an inherent reproducibility that was highly statistically significant.

Substandard tuberculosis drugs on the global market and their simple detection.

SETTING: The prevalence of substandard anti-tuberculosis drugs is unknown. To maximize the effectiveness of tuberculosis (TB) control efforts, simple, inexpensive drug quality screening methods are needed. DESIGN: Isoniazid (INH) and rifampin (RMP) single- and fixed-dose combination (FDC) formulations were collected from selected TB programs and pharmacies in Colombia, Estonia, India, Latvia, Russia and Vietnam. Samples were screened using a recently developed thin-layer chromatography (TLC) kit. All abnormal samples and a 40% random sample of normal formulations were further analyzed using confirmatory techniques. Samples outside of 85% to 115% of stated content, and/or containing compounds other than the stated drug, were defined as being substandard. RESULTS: Overall, 10% (4/40) of all samples, including 13% (4/30) RMP samples, contained <85% of stated content. More FDCs (5/24, 21%) than single-drug samples (2/16, 13%) were substandard. A comparison of TLC with the confirmatory analysis for RMP analysis showed a sensitivity of 100% (4/4), a specificity of 92% (24/26), a positive predictive value (PPV) of 67% (4/6), and a negative predictive value (NPV) of 100% (24/24). An analysis of INH showed a specificity of 90% (9/10). However, sensitivity, PPV, and NVP could not be determined. CONCLUSION: A substantial number of anti-tuberculosis drugs from several countries, in particular FDCs, were found to be substandard. Such drugs may contribute to the creation of drug-resistant TB. TLC is an effective, convenient, and inexpensive method for the detection of substandard drugs.

Clinical and programmatic mismanagement rather than community outbreak as the cause of chronic, drug-resistant tuberculosis in Buenaventura, Colombia, 1998.

SETTING: Buenaventura, Colombia. OBJECTIVE: To assess whether antituberculosis drug resistance was generated by poor management or community transmission. DESIGN: Treatment-failure and new tuberculosis (TB) patients identified between May 1997 and June 1998 were interviewed and their treatment histories reviewed. Bacteriologic testing, including drug susceptibility profiles (DSP) and DNA fingerprinting by restriction fragment length polymorphism (RFLP), was performed and human immunodeficiency virus (HIV) testing was offered. RESULTS: DSP and RFLP fingerprints were obtained for isolates from 34 of 64 treatment-failure patients; 25 (74%) were resistant to > or = one drug. Fifteen of the 25 patients consented to HIV testing; none were positive. An average of 2.8 major treatment errors per patient was identified. RFLP from the treatment-failure patients revealed 20 unique isolates and six clusters (isolates with identical RFLP); 4/6 clusters contained isolates with different DSP. Analysis of the RFLP from both treatment-failure and new patients revealed that 44/111 (40%) isolates formed 18 clusters. Four of 47 (9%) new patients had multidrug-resistant TB (MDR-TB). Eleven isolates belonged to the Beijing family, related to the MDR strain W. CONCLUSION: Drug resistance in Buenaventura results from both poor management and community transmission. Dependence on DSP to identify TB transmission is inadequate when programmatic mismanagement is common.

Antiretroviral therapy uptake among adult tuberculosis patients newly diagnosed with HIV in Nyanza Province, Kenya.

SETTING: In 2008, the Kenya tuberculosis (TB) program reported low (31%) antiretroviral therapy (ART) uptake among human immunodeficiency virus (HIV) infected TB patients. OBJECTIVE: To confirm ART coverage and identify factors associated with HIV clinic enrollment and ART initiation among TB patients. DESIGN: Retrospective chart abstraction of adult TB patients newly diagnosed with HIV and eligible for ART at 58 Nyanza Province TB clinics between October 2006 and April 2008. TB data were linked to HIV clinic data at 50 facilities that provided ART. Associations with HIV clinic enrollment and ART were evaluated. RESULTS: Among 1137 ART-eligible TB patient records sampled, 32% documented HIV clinic enrollment and 29% ART. Date fields were largely incomplete; 11% of the patient records included HIV testing dates and ≤1% had dates for cotrimoxazole prophylaxis, HIV clinic enrollment and ART initiation. Adding HIV clinic data increased HIV clinic enrollment and ART documentation to respectively 62% and 44%. Among TB patients in HIV care, female sex, older age group and baseline CD4 documentation were associated with ART initiation. CONCLUSION: Linking data increased documentation of HIV clinic enrollment and ART uptake. Continued efforts are required to improve the documentation of HIV service delivery, especially in TB clinics. Interventions to increase ART uptake are needed for younger patients and men.

Concordance of programmatic and laboratory-based multidrug-resistant tuberculosis treatment outcomes in Peru.

BACKGROUND: Confirmation of cure for multidrug-resistant tuberculosis (MDR-TB) patients requires laboratory tests for Mycobacterium tuberculosis growth on culture media. Outcome decisions dictate patient management, and inaccuracies place patients at an increased risk of morbidity and mortality, and may contribute to continued transmission of MDR-TB. OBJECTIVE: To examine concordance between programmatic and laboratory-based MDR-TB treatment outcomes. METHODS: The study population included 1658 MDR-TB patients in Peru treated between 1996 and 2002 with both program and laboratory-based outcomes. Laboratory-based outcomes were assigned according to international standards requiring at least five consecutive negative cultures in the last 12 months of treatment to confirm cure. RESULTS: Compared to the global culture-defined standard classification, only 1.1% of treatment successes, but 54.3% of failures, were misclassified programmatically. Overall, 10.4% of patients identified by a clinician as having a successful treatment outcome still had cultures positive for MDR-TB. CONCLUSION: Most patients with successful treatment outcomes by strict culture definitions were also classified by clinicians as having successful outcomes. However, many culture-confirmed failures were missed. In light of delays and incomplete access to culture in MDR-TB programs, efforts should be made to improve the accuracy of programmatically determined treatment outcomes.