Transmission Of Drug-resistant Strains Research Articles

Default from Anti-Retroviral Treatment Programme in Sagamu, Nigeria

To determine the rate and reason for default from antiretroviral treatment (ART) program in Sagamu Nigeria, a cohort of 100 patients on ART was followed up for 12 months at the centre for special studies Olabisi Onabanjo University Teaching Hospital Sagamu between July 2000 and September 2003. The patient chart at the clinic were reviewed to collect the socio-demographic data of patients who defaulted ART treatment (defined as PLWA who refused to come back to collect ART medications for at least 6 months from the last visit). The patients were traced to their place of residence with the address given on the clinic chart. Where such patients were found at home, a reason for default from treatment was inquired from them. For those who were not met at home proxy interviewees such as a neighbour or a family member were asked if they were available. Of the 100 patients who had enrolled in the ART treatment programme during the study period, 36% of the study population defaulted treatment, 18% had died while 46% were alive and well. Major reasons for default includes: opting for spiritual/faith/alternative healing ( 8%), lost of interest in the programme/financial (7%), moved to home town of origin (6%), changed address (5%), untraceable home address or name (5%), side effects of ART (2%), widowhood rites (1%). Two individuals were not met at home after repeated visits by the Community health extension workers. About a third of PLWA defaulted from treatment. The major reasons for default were psychosocial factors unrelated to the treatment regimen. Ensuring adherence to therapy in communities must take into consideration the psychosocial and cultural practices and norms of the people to avert the emergence and transmission of drug-resistant strains. (Afr. J. Biomed. Res. 11: 221 - 224) Key Words: HAART, Defaulters, factors, psychosocial

ScreenTape as a tool for the rapid differentiation of Mycobacterium tuberculosis isolates

Abstract The emergence of difficult to treat multi drug-resistant tuberculosis currently threatens control efforts in all regions of the world. Genotyping of M. tuberculosis strains using molecular markers has the potential to identify outbreaks and track transmission of drug resistant strains. To be of value to the public health practitioner genotyping must be discriminatory, rapid and readily available. The preferred method of typing M. tuberculosis is MIRU-VNTR where 15 loci are examined by PCR. However, implementation requires the ability to accurately size the resulting amplicons. Analysis by traditional gel electrophoresis is tedious and slow and MIRU typing has so far been largely restricted to laboratories with sophisticated high throughput analytical facilities. ScreenTape (LAB901, Loanhead, Scotland) is a fully automated electophoretic device for rapid analysis of nucleic acids. It is simple to use and provides accurate sizing of amplicons in under 10 min. When applied to MIRU-VNTR analysis of 20 drug resistant M. tuberculosis isolates, the assignment of alleles was in agreement with results obtained from a commercial genotyping company on 97.1% occasions, compared to 93.4% for traditional gel electrophoresis. Correlation coefficients for predicted fragment length were 0.9911 and 0.9919 for ScreenTape and gel electrophoresis, respectively. Whereas the 20 isolates had previously been identified as having two spoligotype patterns, 14 MIRU patterns were observed demonstrating the superior discriminatory power of MIRU-VNTR typing for M. tuberculosis. ScreenTape appears to offer rapid discriminatory genotyping and may prove an attractive option for public health laboratories charged with controlling infectious tuberculosis disease.

Emergency of Primary NNRTI Resistance Mutations without Antiretroviral Selective Pressure in a HAART-Treated Child

ObjectiveThe use of antiretrovirals (ARV) during pregnancy has drastically reduced the rate of the human immunodeficiency virus perinatal transmission (MTCT). As a consequence of widespread ARV use, transmission of drug resistant strains from mothers to their babies is increasing. Ultra-sensitive PCR techniques have permitted the quantification of minority viral populations, but little is known about the transmission of drug-resistant HIV-1 minority population in the setting of MTCT.Methodology/Principal FindingsWe describe the case of a female child born to an HIV-infected mother, which had not taken any ARV during the pregnancy. The child's first genotype demonstrated a minor non-nucleoside reverse transcriptase inhibitor (K101E), and during her treatment with reverse transcriptase and protease inhibitors full resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) emerged (G190A). Phenotypic/genotypic analysis of variant quasispecies through yeast TyHRT assay was conducted to characterize minority resistant viral strains circulating in both mother and child. Maximum likelihood and Bayesian MCMC phylogenetic analyses were performed with samples from the pair to assess genetic relatedness among minor viral strains. The analysis showed that the child received a minor NNRTI resistant variant, containing the mutation K101E that was present in less than 1% of the mother's quasispecies. Phylogenetic analyses have suggested common ancestry between the mother's virus strain carrying K101E with the viral sequences from the child.ConclusionThis is the first documentation of MTCT of a minority resistant strain of HIV-1. The transmission of minor resistant variants carries the threat of emergence of multi-drug primary mutations without identified specific selective pressures.

Surveillance of antituberculosis drug resistance among children from the Western Cape Province of South Africa--an upward trend.

We assessed the prevalence of antituberculosis drug resistance among children with tuberculosis (TB) in the Western Cape Province of South Africa. Drug susceptibility testing for isoniazid and rifampin was prospectively done on all children with culture-confirmed TB at Tygerberg Children's Hospital, Cape Town, from March 2005 through February 2007. Survey results were compared with results from 2 previous surveys. We found 291 children had culture-confirmed TB. Resistance to isoniazid or rifampin increased from 21 of 306 (6.9%) to 41 of 319 (12.9%) and 43 of 285 (15.1%) in the first to third surveys (P = .005) and multidrug resistance from 7 of 306 (2.3%) to 18 of 319 (5.6%) and 19 of 285 (6.7%; P = .033). Although previously treated children had significantly more drug resistance than did new TB cases (19 of 66 [28.8%] vs 24 of 225 [10.7%]; odds ratio = 3.39; 95% confidence interval = 1.62, 7.05), evidence suggests transmission rather than acquisition of resistance. HIV infection was not significantly associated with drug resistance. Results indicate a high and rising prevalence of anti-TB drug resistance among children in the Western Cape, which suggests ongoing transmission of drug-resistant strains within the community. Improved control of TB in adults, including early identification and treatment of drug-resistant cases, is necessary to reduce transmission to children.

Modeling the effects of drug resistant influenza virus in a pandemic

Neuraminidase inhibitors (NI) play a major role in plans to mitigate future influenza pandemics. Modeling studies suggested that a pandemic may be contained at the source by early treatment and prophylaxis with antiviral drugs. Here, we examine the influence of NI resistant influenza strains on an influenza pandemic. We extend the freely available deterministic simulation program InfluSim to incorporate importations of resistant infections and the emergence of de novo resistance. The epidemic with the fully drug sensitive strain leads to a cumulative number of 19,500 outpatients and 258 hospitalizations, respectively, per 100,000 inhabitants. Development of de novo resistance alone increases the total number of outpatients by about 6% and hospitalizations by about 21%. If a resistant infection is introduced into the population after three weeks, the outcome dramatically deteriorates. Wide-spread use of NI treatment makes it highly likely that the resistant strain will spread if its fitness is high. This situation is further aggravated if a resistant virus is imported into a country in the early phase of an outbreak. As NI-resistant influenza infections with high fitness and pathogenicity have just been observed, the emergence of drug resistance in treated populations and the transmission of drug resistant strains is an important public health concern for seasonal and pandemic influenza.

Lessons from Molecular Epidemiology and Comparative Genomics

Molecular biology has revolutionized the field of tuberculosis (TB) research. Comparative genomics and molecular epidemiology are providing revelations about the evolutionary origins of MYCOBACTERIUM TUBERCULOSIS and phylogenetic relationships between different strains and strain families. Accumulating evidence indicates that distinct strains of M. TUBERCULOSIS (genotype) may be associated with differential transmissibility, virulence, and/or clinical manifestations (phenotype). As advances in our understanding of the relationships between genotype and phenotype progress, this knowledge will have important ramifications for TB control and the development of novel vaccines and improved diagnostics. Some of the greatest advantages of molecular epidemiological methods include our abilities to follow transmission of particular strains within communities, track epidemics, and recognize the presence of historic outbreaks. Moreover, there are critical questions about TB that are essentially unanswerable in the absence of molecular techniques. These include our capacity to distinguish exogenous reinfection from endogenous reactivation in recurrent TB cases and to recognize primary transmission of drug resistant strains versus the acquisition of drug resistance via de novo mutations. Finally, an elucidation of the phylogenetic structure and evolutionary history of M. TUBERCULOSIS provides a necessary background for understanding the underlying mechanisms responsible for the continued success of this deadly pathogen.

Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study

Mycobacterium tuberculosis strains that cause untreatable drug-resistant disease are a threat worldwide. We describe the treatment, management, and outcomes of patients with extensively drug-resistant tuberculosis in Tomsk, Russia. We undertook a retrospective cohort study of 608 patients with multidrug resistant tuberculosis who had treatment in civilian or prison services, between Sept 10, 2000, and Nov 1, 2004, according to the treatment strategy recommended by WHO. Clinical characteristics, management practices, and treatment outcomes of patients with extensively drug-resistant (XDR) tuberculosis and non-extensively drug-resistant (non-XDR) tuberculosis are described. The main outcome was the frequency of poor and favourable outcomes at the end of treatment. Of 608 patients with multidrug resistant tuberculosis, 29 (4.8%) patients had baseline XDR tuberculosis. Treatment failure was more common in patients with XDR tuberculosis than in those with non-XDR tuberculosis (31%vs 8.5%, p=0.0008). 48.3% of patients with XDR tuberculosis and 66.7% of patients with non-XDR tuberculosis had treatment cure or completion (p=0.04). The frequency and management of adverse events did not differ between patients with XDR and non-XDR tuberculosis. The chronic features of tuberculosis in these patients suggest that extensively drug-resistant tuberculosis may be acquired through previous treatments that include second-line drugs. Aggressive management of this infectious disease is feasible and can prevent high mortality rates and further transmission of drug-resistant strains of Mycobacterium tuberculosis.

Epidemiological features of drug resistant tuberculosis in Harare, 1994 to 1996.

To characterise the prevalence, clinical and radiological features of drug resistant tuberculosis in selected patients with pulmonary tuberculosis in Harare between 1994 and 1996. A retrospective review of medical and microbiological records. Beatrice Road Infectious Diseases Hospital, Harare, Zimbabwe. 381 smear-positive tuberculosis patients who had samples submitted to the National Tuberculosis Reference Laboratory for culture and susceptibility testing. Prevalence of resistance of isolated cultures of Mycobacterium tuberculosis to anti-tuberculosis drugs; clinical, radiological and microbiological response to treatment with recommended anti-tuberculosis regimens. Resistance to one or more drugs was detected in 16 isolates (16/165, 9.7%), single drug resistance in five (3.0%) and resistance to two or more drugs in 11 (6.7%). There were no distinctive clinical or radiological features of drug-resistant tuberculosis, although a higher percent of drug resistant cases had evidence of pleural disease (25% vs 2.5%, p = 0.005). Neither past history of tuberculosis or known or suspected HIV infection was associated with the presence of drug resistance. In spite of the resurgence of tuberculosis and the high prevalence of HIV infection in Zimbabwe, the rates of drug resistance have remained relatively low, even among a selected population at high risk of resistance. A significant proportion of cases of drug-resistant tuberculosis appear to be due to new transmission of drug resistant strains, which reinforces the importance of maintaining a surveillance system for the monitoring of drug susceptibility. Ongoing prospective studies should provide more reliable estimates of the prevalence and determinants of drug resistance in Zimbabwe.

The Emergence of HIV Transmitted Resistance in Botswana: “When Will the WHO Detection Threshold Be Exceeded?”

BackgroundThe Botswana antiretroviral program began in 2002 and currently treats 42,000 patients, with a goal of treating 85,000 by 2009. The World Health Organization (WHO) has begun to implement a surveillance system for detecting transmitted resistance that exceeds a threshold of 5%. However, the WHO has not determined when this threshold will be reached. Here we model the Botswana government's treatment plan and predict, to 2009, the likely stochastic evolution of transmitted resistance.MethodsWe developed a model of the stochastic evolution of drug-resistant strains and formulated a birth-death Master equation. We analyzed this equation to obtain an analytical solution of the probabilistic evolutionary trajectory for transmitted resistance, and used treatment and demographic data from Botswana. We determined the temporal dynamics of transmitted resistance as a function of: (i) the transmissibility (i.e., fitness) of the drug-resistant strains that may evolve and (ii) the rate of acquired resistance.ResultsTransmitted resistance in Botswana will be unlikely to exceed the WHO's threshold by 2009 even if the rate of acquired resistance is high and the strains that evolve are half as fit as the wild-type strains. However, we also found that transmission of drug-resistant strains in Botswana could increase to ∼15% by 2009 if the drug-resistant strains that evolve are as fit as the wild-type strains.ConclusionsTransmitted resistance will only be detected by the WHO (by 2009) if the strains that evolve are extremely fit and acquired resistance is high. Initially after a treatment program is begun a threshold lower than 5% should be used; and we advise that predictions should be made before setting a threshold. Our results indicate that it may be several years before the WHO's surveillance system is likely to detect transmitted resistance in other resource-poor countries that have significantly less ambitious treatment programs than Botswana.

Overview of HIV drug resistance and its implications for China

At the end of 2005 an estimated 650 000 people in China were infected with HIV among whom 75 000 were in need of ART. The Division of Treatment and Care at the National Center for AIDS/STD Control and Prevention (NCAIDS) Chinese Center for Disease Control (CCDC) has been responsible for the overall scale up of the National Free ART Program. As of December 2005 a total of 20 453 patients in 28 provinces autonomous regions and special municipalities had benefited from this national program and received free ART. The increase in access to ART however is accompanied by the risk of drug resistance development. A small body of literature already documents HIV drug resistance in China in these treated populations. These preliminary findings are consistent with the development of drug resistance observed in developed countries soon after the initiation of wide-scale HIV treatment. Therefore it is imperative that clinicians understand the causes and implications of HIV resistance in both patientcare and in the public health perspective. (excerpt)

Drug Resistance inMycobacterium tuberculosis

Anti-tuberculosis drugs are a two-edged sword. While they destroy pathogenic M. tuberculosis they also select for drug resistant bacteria against which those drugs are then ineffective. Global surveillance has shown that drug resistant Tuberculosis is widespread and is now a threat to tuberculosis control programs in many countries. Application of molecular methods during the last decade has greatly changed our understanding of drug resistance in tuberculosis. Application of molecular epidemiological methods was also central to the description of outbreaks of drug resistance in Tuberculosis. This review describes recommendations for Tuberculosis treatment according to the WHO guidelines, the drug resistance problem in the world, mechanisms of resistance to first line and second line drugs and applications of molecular methods to detect resistance causing gene mutations. It is envisaged that molecular techniques may be important adjuncts to traditional culture based procedures to rapidly screen for drug resistance. Prospective analysis and intervention to prevent transmission may be particularly helpful in areas with ongoing transmission of drug resistant strains as recent mathematical modeling indicate that the burden of MDR-TB cannot be contained in the absence of specific efforts to limit transmission.

Frequency of Drug‐Resistant Variants of HIV‐1 Coexistent With Wild‐Type in Treatment‐Naive Patients of India

ContextOver the past few years, reports of emergence and transmission of drug-resistant strains of HIV have increased, especially in western countries. In the context of increased widespread use of zidovudine- and lamivudine-based combinations in India, coupled with the genetic diversity of HIV, it is essential to generate preliminary data on the frequency of zidovudine- and lamivudine-resistant variants of HIV-1 in North India.ObjectivesIn the present study, the authors screened for mutations in the pol gene of HIV-1 associated with resistance to zidovudine and lamivudine in HIV-infected treatment-naive patients from North India.Design and PatientsThe mutations were screened at codons 70 and 215 (conferring resistance to zidovudine) and at codon 184 (conferring resistance to lamivudine) by using a nested amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) approach from the proviral DNA of 60 patients.ResultsMost of the patients showed a mixture of both wild-type and mutant virus. In all but 1 patient, wild-type virus was observed with respect to each codon. Mutant variants were also observed in many patients, especially at codon 70 (48 patients [80%]) and codon 184 (19 patients [31.67%]). In contrast, the frequency of mutation at codon 215 was found to be very low (1 patient [1.67%]).ConclusionIn this sample of treatment-naive HIV-1-infected patients in North India, a high proportion of mutant variants harbored mutations in the pol gene at codons- 70 and 184 coexisting with wild-type HIV-1.

The Effect of Initial Drug Resistance on Treatment Response and Acquired Drug Resistance during Standardized Short-Course Chemotherapy for Tuberculosis

In Tomsk Oblast, Russian Federation, during the period of 1996-2000, most previously untreated patients with tuberculosis received standardized short-course chemotherapy, irrespective of drug-susceptibility testing results. A retrospective analysis was done to determine the effect of initial drug resistance on treatment outcome and acquired drug resistance in new patients receiving standardized short-course chemotherapy. During the period of 1 November 1996 through 31 December 2000, a total of 2194 patients received a category 1 treatment regimen. Drug susceptibility test results for 1681 patients were available for analysis. Drug resistance patterns before and during treatment were compared for 73 patients whose culture results were persistently positive during treatment. Acquired resistance was defined as new drug resistance (during or at the end of treatment) that was not present at the beginning of treatment. Pretreatment drug resistance was strongly associated with treatment failure. In patients who had strains with pretreatment resistance patterns that included isoniazid or rifampin resistance, but not resistance to both, 17 (70.8%) of 24 cases involving treatment failures acquired new multidrug resistance. In patients with pretreatment pan-susceptible or streptomycin-monoresistant strains, 13 (41.9%) of 31 cases involving treatment failures acquired new multidrug resistance. Early diagnosis of drug-resistant tuberculosis and judicious use of second-line drugs is recommended to decrease transmission of drug-resistant strains and to prevent the creation of multidrug-resistant strains. Finally, if drug susceptibility tests are not available or results are delayed, physicians should recognize that patients who do not respond to directly observed empirical short-course chemotherapy are at high risk of having multidrug-resistant tuberculosis and should be treated accordingly.

Declining trend in transmission of drug-resistant HIV-1 in Amsterdam.

Symptomatic primary HIV infections are over-represented in the mainly hospital-based studies on transmission of resistant HIV-1. We examined a more general population for the prevalence of resistant HIV-1 strains among primary infections. From 1994 to 2002 primary infections were identified within the Amsterdam Cohort Studies (ACS) among homosexual men and drug users, and at the Academic Medical Center (AMC). Whereas primary HIV-1-infected AMC patients, often presented with symptoms of acute retroviral syndrome, ACS participants largely seroconverted during follow-up and thus brought also asymptomatic primary infections to our study. Reverse transcriptase (RT) and protease sequences were obtained by population-based nucleotide sequence analysis of the first HIV RNA-positive sample available. Subtypes were identified by phylogenetic analysis. Mutations were identified based on the IAS-USA resistance table. A total of 100 primary HIV-1 infections were identified (32 AMC and 68 ACS). Transmission of drug-resistant strains decreased over calendar time, with 20% [95% confidence interval (CI), 10-34%] of infections bearing drug-resistant mutations before 1998 versus only 6% (95% CI, 1-17%) after 1998. No multi-drug resistance pattern was observed. The median plasma HIV-1 RNA level of the first RNA positive sample was significantly lower for the individuals infected with a resistant strain versus those infected with wild-type, suggesting a fitness-cost to resistance. Four of seven non-B subtypes corresponded with the prevalent subtype in the presumed country of infection, and none showed resistance mutations. The transmission of drug-resistant HIV-1 strains in Amsterdam has decreased over time. Monitoring should be continued as this trend might change.

Transmission of HIV-1 drug resistance.

The use of highly-active anti-retroviral therapy (HAART) for treating HIV infections is increasing. Recent studies have demonstrated that HAART is improving both the length and quality of life in HIV-infected patients. Resistant strains of HIV arise when drug adherence is poor. This can lead to the transmission of drug-resistant strains of HIV to susceptible individuals. This can lead to suboptimal first-line therapy, if the resistance profile of the transmitted virus is unknown. To review the mechanisms of how drug resistance arises; the methods used to characterise drug resistance; the problems arising with compliance leading to the development of drug-resistant HIV strains; the evidence for the incidence, prevalence and trends in the transmission of resistant HIV strains in different risk groups; and the evidence of suboptimal response to first-line therapy where transmission of a resistant HIV strain has occurred. On the basis of this, a case is presented for the routine resistance testing of all newly diagnosed HIV-infected individuals. Literature review. There is evidence, though limited at present, that transmission of drug-resistant HIV strains can lead to suboptimal response to first-line therapy in newly diagnosed HIV-infected individuals. As the use of HAART can only increase in the future, and compliance will always be a problem in such HAART-treated patients, baseline resistance testing should become a routine part of their management.

Adherence to antiretroviral therapy among patients with HIV: a critical link between behavioral and biomedical sciences.

Rapid advances in biomedical science, such as pharmaceutical developments for HIV disease, must be integrated with advances in behavioral science to further our understanding of medication adherence. This article evaluates the current state of the science in adherence to antiretroviral therapy for persons with HIV. The primary objectives are to 1) identify critical determinants of adherence, and 2) describe interventions to improve adherence. Adherence is a complex dynamic behavior influenced by characteristics of the patient, treatment regimen, disease, patient-provider relationship, and clinical setting. Therefore, the most promising interventions are multifaceted and target different locations in this matrix simultaneously. Unfortunately, nonadherence remains a formidable barrier in the management of HIV, resulting in the development of resistance and drug failure. Moreover, adherence is a public health concern, with implications for the transmission of HIV in general and the transmission of drug-resistant strains of HIV specifically. Despite substantial attention to adherence in recent years, much more remains to be done to better understand and promote adherence to antiretroviral therapy through effective interventions. From this integration of biomedical and behavioral science, effective clinical interventions can be developed and implemented to enhance the health of patients with HIV.

Issues in the treatment of Mycobacterium tuberculosis in patients with human immunodeficiency virus infection.

The HIV/AIDS pandemic has led to a rise in the incidence of tuberculosis and an epidemic of co-infection in many developing countries. Treatment of Mycobacterium tuberculosis in persons with HIV infection presents several challenges to the clinician particularly in resource-poor countries. As will be discussed in this paper diagnosis of latent tuberculosis relies on tuberculin skin testing which has poor sensitivity and reproducibility in immunocompromised patients. The World Health Organization (WHO) recommends treatment of active tuberculosis as the primary means of global tuberculosis control. In practice treatment of active tuberculosis typically requires that a symptomatic patient self-report to a health service for evaluation and management. Even if this approach to tuberculosis control were sufficient many logistic and clinical problems remain involving tuberculosis diagnosis and therapy in the patient with HIV/AIDS. Recognizing the significant clinical and public health challenges surrounding the treatment of tuberculosis in patients with HIV infection this paper will address a number of issues relevant to the care of co-infected patients. These include current guidelines for the treatment of active tuberculosis as well as the diagnosis and treatment of latent tuberculosis in HIV-positive patients. The paper concludes with a discussion of promising new drugs for tuberculosis treatment. (excerpt)

Classification of drug-resistant tuberculosis in an epidemic area

Traditionally, patients with drug-resistant tuberculosis are classified as having acquired drug-resistant or primary drug-resistant disease on the basis of a history of previous tuberculosis treatment. Only cases of primary drug resistance are assumed to be due to transmission of drug-resistant strains. This descriptive study of 63 patients with drug-resistant tuberculosis assessed the relative contribution of transmission of drug-resistant strains in a high-incidence community of Cape Town, South Africa, by restriction-fragment length polymorphism (RFLP). The RFLP results were compared with the results obtained by traditional classification methods. According to RFLP definitions, 52% (33 cases) of drug-resistant tuberculosis was caused by transmission of a drug-resistant strain. The proportion of cases due to transmission was higher for multidrug-resistant (64%; 29 cases) than for single-drug-resistant (no cases) tuberculosis. By the clinical classification, only 18 (29%) patients were classified as having primary drug-resistant tuberculosis (implying transmission). The clinical classification was thus misleading in 25 patients. The term acquired drug resistance includes patients infected with strains that truly acquired drug resistance during treatment and patients who were initially infected with or reinfected with a drug-resistant strain. This definition could lead to misinterpretation of surveillance studies, incorrect evaluation of tuberculosis programmes, and delayed diagnosis and treatment of patients with multidrug-resistant disease. The clinical term acquired drug resistance should be replaced with the term "drug resistance in previously treated cases", which includes cases with drug resistance due to true acquisition as well as that due to transmitted drug-resistant strains.

Drug-resistant tuberculosis: what do we do now?

Drug-resistant tuberculosis (TB) represents a threat to TB control programmes. Erratic and inappropriate use of currently available medications, HIV-TB co-infection, and concern about transmission of drug-resistant strains in the general population all contribute to a worrying picture. What do we do now? In the last few years, there has been considerable progress in the understanding of mechanisms of action and resistance to antituberculosis agents, and in establishing the value of directly observed therapy in preventing treatment failure. However, a limited effort has been devoted to the development of new active compounds or of rapid diagnostic tests, and their relevance to global tuberculosis control has been questioned.

Transmission of drug-resistant strains of HIV-1: unfortunate, but inevitable

The US Food and Drug Administration has licensed 15 antiretroviral drugs for the treatment of HIV-1 infection, 11 of these in the past 3·5 years. How best to use these agents is a complex issue, although guidelines developed by expert panels have been extremely helpful.1,2 Combinations of these drugs are capable of profound suppression of HIV-1 replication for long periods and have been referred to as highly active antiretroviral therapy (HAART). Among patients with access to HAART, HIV-1-related morbidity and mortality have declined sharply.