Search

Laboratory innovation significantly affects program sustainability of HIV programs in low and middle income countries (LMICs) far beyond its immediate sphere of impact. Innovation in rapid development of diagnostic technologies, improved quality management systems, strengthened laboratory management, affordable external quality assurance and accreditation schemes, and building local capacity have reduced costs, brought quality improvement to point-of-care testing, increased access to testing services, reduced treatment and prevention costs and opened the door to the real possibility of ending the AIDS epidemic. However, for effectively implemented laboratory innovation to contribute to HIV quality program sustainability, it must be implemented within the overall context of the national strategic plan and HIV treatment programs. The high quality of HIV rapid diagnostic test was a breakthrough that made it possible for more persons to learn their HIV status, receive counseling, and if infected to receive treatment. Likewise, the use of dried blood spots made the shipment of samples easier for the assessment of different variables of HIV infection-molecular diagnosis, CD4+ cell counts, HIV antibodies, drug resistance surveillance, and even antiretroviral drug level measurements. Such advancement is critical for to reaching the UNAIDS target of 90-90-90 and for bringing the AIDS epidemic to an end, especially in LMICs.

Objective: The objective of the WHO/US President's Emergency Plan for AIDS Relief consultation was to discuss innovative strategies, offer guidance, and develop a comprehensive policy framework for implementing quality-assured HIV-related point-of-care testing (POCT)., Methods: The consultation was attended by representatives from international agencies (WHO, UNICEF, UNITAID, Clinton Health Access Initiative), United States Agency for International Development, Centers for Disease Control and Prevention/President's Emergency Plan for AIDS Relief Cooperative Agreement Partners, and experts from more than 25 countries, including policy makers, clinicians, laboratory experts, and program implementers., Main Outcomes: There was strong consensus among all participants that ensuring access to quality of POCT represents one of the key challenges for the success of HIV prevention, treatment, and care programs. The following four strategies were recommended: implement a newly proposed concept of a sustainable quality assurance cycle that includes careful planning; definition of goals and targets; timely implementation; continuous monitoring; improvements and adjustments, where necessary; and a detailed evaluation; the importance of supporting a cadre of workers [e.g. volunteer quality corps (Q-Corps)] with the role to ensure that the quality assurance cycle is followed and sustained; implementation of the new strategy should be seen as a step-wise process, supported by development of appropriate policies and tools; and joint partnership under the leadership of the ministries of health to ensure sustainability of implementing novel approaches., Conclusion: The outcomes of this consultation have been well received by program implementers in the field. The recommendations also laid the groundwork for developing key policy and quality documents for the implementation of HIV-related POCT.

Polymorphic Amplified Typing Sequences (PATS) is a PCR-based Escherichia coli O157 (O157) strain typing system. Here, we show that PATS compares excellently with Pulsed-Field Gel Electrophoresis (PFGE) in that both methods cluster geographically diverse O157 isolates similarly. Comparative analysis of the results obtained in this simulated "blind" study attests to the discriminating power and applicability of PATS to epidemiological/nosocomial situations.

Medical laboratory services are an essential, yet often neglected, component of health systems in developing countries. Their central role in public health, disease control and surveillance, and patient management is often poorly recognized by governments and donors. However, medical laboratory services in developing countries can be strengthened by leveraging funding from other sources of HIV/AIDS prevention, care, surveillance, and treatment programs. Strengthening these services will require coordinated efforts by national governments and partners and can be achieved by establishing and implementing national laboratory strategic plans and policies that integrate laboratory systems to combat major infectious diseases. These plans should take into account policy, legal, and regulatory frameworks; the administrative and technical management structure of the laboratories; human resources and retention strategies; laboratory quality management systems; monitoring and evaluation systems; procurement and maintenance of equipment; and laboratory infrastructure enhancement. Several countries have developed or are in the process of developing their laboratory plans, and others, such as Ethiopia, have implemented and evaluated their plan.

The risk of acquiring additional drug resistance in strains of multidrug-resistant tuberculosis (MDR-TB) during failure of empiric standardized retreatment regimens is poorly defined. We sought to estimate this risk by comparing drug susceptibility profiles and RFLP patterns of paired MDR-TB isolates collected from 27 patients before and after retreatment failure. Among 23 patients with paired isolates with concordant RFLP patterns, 19 (83%) had become resistant to at least one additional drug after failed retreatment. In this limited group of MDR-TB patients, acquisition of resistance was common during failure of empiric drug regimens. Further study is needed to confirm these findings.

In many developing countries and outside hospital settings, the characteristics of endemic Mycobacterium tuberculosis strains resistant to multiple drugs remain unknown. In a community-based referral and therapy program in northern Lima, Peru, beginning in 1996, patients found to be failures on standard regimens were referred for drug-susceptibility testing of their isolates, and those found to be infected with M. tuberculosis isolates resistant to at least rifampin were treated with individualized regimens based on their infecting strains. Isolates from 42 of these patients were subjected to DNA sequencing of the rpoB gene region responsible for rifampin resistance. We determined the frequency of types of mutations in the rpoB gene among these Peruvian isolates.

Setting: Lima, Peru., Objective: To describe drug resistance profiles of TB isolates from patients at risk for multidrug-resistant tuberculosis (MDR-TB), and to consider the implications of these findings for treatment., Design: Descriptive study of drug susceptibility testing (DST) results for TB isolates from 1680 patients referred for suspicion of MDR-TB between 1996 and 2001., Results: Of 1680 isolates tested, 1144 (68%) were resistant to at least one anti-tuberculosis drug and 926 (55%) were MDR-TB strains. Of 926 MDR isolates, 50 (5%) were resistant to INH and RMP alone, while 367 (40%) were resistant to at least five first-line drugs. We identified 146 unique drug resistance profiles, the most common of which accounted for 11% of drug-resistant isolates. The annual prevalence of isolates with resistance to at least five first-line drugs rose significantly during the study period, from 29% to 37% (P = 0.00086)., Conclusions: This is a group of patients with TB disease among whom the prevalence of a broad spectrum of often highly drug-resistant strains appears to be increasing over time. A single standardized retreatment regimen may be inadequate to cure most patients. Capacity for drug sensitivity testing is essential for development of multiple standardized retreatment or individualized treatment regimens and epidemiological surveillance for planning.

In a series of 116 Salmonella enterica Newport isolates that included 64 multidrug-resistant (MDR) isolates, automated ribotyping and pulsed-field gel electrophoresis (PFGE) discriminated MDR S. Newport with a sensitivity of 100% and 98% and specificity of 76% and 89%, respectively. Clustering of PFGE patterns (but not ribotyping) linked human and bovine cases. Automated ribotyping rapidly identified the MDR strain, and PFGE detected associations that aided epidemiologic investigations.

Objectives: This study evaluated the relation of housing policies to risk of subsequent lead exposure in addresses where lead-poisoned children had lived., Methods: Addresses where children with lead poisoning lived between May 1992 and April 1993 were selected from lead screening registries in 2 northeastern states differing in their enforcement of lead poisoning prevention statutes. Blood lead levels of subsequently resident children, exterior condition, tax value, age, and census tract characteristics were collected. The odds of elevated blood lead levels in subsequently resident children were calculated with logistic regression., Results: The risk of identifying 1 or more children with blood lead levels of 10 micrograms/dL or greater was 4 times higher in addresses with limited enforcement. Controlling for major confounders had little effect on the estimate., Conclusions: Enforcement of housing policies interrupts the cycle of repeated lead exposure.

A 4-year retrospective study showing that we isolated Bordetella holmesii, but not Bordetella pertussis, from patients with pertussis-like symptoms was performed. From 1995 through 1998, we isolated B. holmesii from 32 nasopharyngeal specimens that had been submitted from patients suspected of having pertussis. Previously, B. holmesii had been associated mainly with septicemia and was not thought to be associated with respiratory illness. A study was undertaken to describe the characteristics of the B. holmesii isolates recovered and why we were successful in detecting the organism in nasopharyngeal specimens. B. holmesii isolates were characterized for drug sensitivities and for genetic relatedness by pulsed-field gel electrophoresis (PFGE). These isolates, an additional strain of B. holmesii isolated from a blood culture and previously confirmed by the Centers for Disease Control and Prevention, Atlanta, Ga., and 14 other clinical isolates of Bordetella spp., including 4 of B. bronchiseptica, 5 of B. parapertussis, and 5 of B. pertussis, were studied. They were all separately inoculated on three Bordet Gengou (BG) selective media containing either 0.625 microgram of oxacillin per ml, 40 microgram of cephalexin per ml, or 2.5 microgram of methicillin per ml, on BG agar with no antibiotic (control), and on charcoal agar (CA) with and without 40 microgram of cephalexin per ml. We found that cephalexin, the antibiotic commonly incorporated in both CA and BG agar for the recovery of Bordetella spp., is inhibitory to the growth of B. holmesii. In addition, the genotypic analysis of the 32 B. holmesii isolates by PFGE following restriction with XbaI and SpeI identified the dominant strains circulating during the study period.

Setting: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru., Objective: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC)., Design: Case series., Results: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru., Conclusion: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.

An isocratic HPLC method for measuring pyrimethamine extracted from infant plasma is reported. The method is an improvement over previously published methods by requiring lower volumes of plasma (100 microL) and having increased sensitivity to pyrimethamine at 210 nm. The procedure, which entails a basic organic extraction and subsequent HPLC chromatography of the reconstituted extract, can detect 1.4 ng and quantify 4.0 ng of pyrimethamine per 40-microL injection, with two analyses per 100-microL sample. Analytical recovery of pyrimethamine added to plasma at 10, 50, and 125 ng/100 microL averaged 80%, 92%, and 101%, respectively (n = 20). Within- and between-day CVs were less than 7%. Studies of various plasma samples from adults and infants (n = 15) revealed no interference from other plasma peaks with the analyte of interest.

A study was conducted in the community of Greater New Bedford, Massachusetts, from 1984 through 1987 to assess the prevalence of elevated levels of polychlorinated biphenyls (PCBs) in the serum of individuals aged 18 to 64 years who had resided in the area for at least 5 years. Eight hundred and forty subjects were interviewed, examined, and tested in a cross-sectional sample of the towns of Acushnet, Dartmouth, and Fairhaven and the city of New Bedford. Serum PCBs were measured to estimate the extent of human exposure. Because of documented environmental contamination by PCBs in the New Bedford area, and the practice of recreational fishing in the harbor for food, a significant number of persons with elevated serum PCB levels were expected to be identified. Instead, the prevalence of elevated serum PCBs in the sample was found to be typical of "unexposed" urban populations in the United States. Only 1.3% of the subjects had serum PCB levels greater than 30 ppb. The same percentage was observed among males (n = 391) and females (n = 449). The geometric means of PCB levels were 4.3 ppb among males (Range = 0.50-60.9) and 4.2 ppb among females (Range = 0.38-154). We conclude that the prevalence of elevated serum PCBs is low in the population of Greater New Bedford.

To assess the validity of self-reported marijuana use during pregnancy, this study randomly allocated pregnant women into a group who were told their urine would be tested for marijuana, alcohol, and other drugs and another group not so tested. Women told they would be tested reported more marijuana use during pregnancy than did untested women. Moreover, urine assays identified more women who used marijuana during pregnancy than were willing to admit it in the interview even after being told their urine would be tested. No differences in reported drinking or cigarette smoking during pregnancy were found between tested and untested women.

Eighty-five samples of shellfish (50 soft shell clams, 21 hard shell clams and 14 oysters) were examined for the presence of human enteric viruses. In addition, bacterial contamination levels, both fecal coliform and standard plate count, were determined. Seventy-five samples were harvested from open shellfish areas and 10 samples from restricted shellfish areas during seasonal opening. Enteroviruses were not detected in any of the samples tested. In contrast, 33 (30 from open beds and 3 from restricted areas) of 82 shellfish samples had levels of bacterial contamination that exceed current regulatory limits for shellfish.