Biomedical subjects

Christopher Dye

Publications and source records attributed to Christopher Dye.

15 recordsLinked to original sources

PubMed2003

Tuberculosis epidemics driven by HIV: is prevention better than cure?

OBJECTIVE: To compare the benefits of tuberculosis (TB) treatment with TB and HIV prevention for the control of TB in regions with high HIV prevalence. DESIGN AND METHODS: A compartmental difference equation model of TB and HIV has been developed and fitted to time series and other published data using Bayesian methods. The model is used to compare the effectiveness of TB chemotherapy with three strategies for prevention: highly active antiretroviral therapy (HAART), the treatment of latent TB infection (TLTI) and the reduction of HIV transmission. RESULTS: Even where the prevalence of HIV infection is high, finding and curing active TB is the most effective way to minimize the number of TB cases and deaths over the next 10 years. HAART can be as effective, but only with very high levels of coverage and compliance. TLTI is comparatively ineffective over all time scales. Reducing HIV incidence is relatively ineffective in preventing TB and TB deaths over 10 years but is much more effective over 20 years. CONCLUSIONS: In countries where the spread of HIV has led to a substantial increase in the incidence of TB, TB control programmes should maintain a strong emphasis on the treatment of active TB. To ensure effective control of TB in the longer term, methods of TB prevention should be carried out in addition to, but not as a substitute for, treating active cases.

AIDS-Related Opportunistic Infections↗

PubMed2003

Tuberculosis.

Among communicable diseases, tuberculosis is the second leading cause of death worldwide, killing nearly 2 million people each year. Most cases are in less-developed countries; over the past decade, tuberculosis incidence has increased in Africa, mainly as a result of the burden of HIV infection, and in the former Soviet Union, owing to socioeconomic change and decline of the health-care system. Definitive diagnosis of tuberculosis remains based on culture for Mycobacterium tuberculosis, but rapid diagnosis of infectious tuberculosis by simple sputum smear for acid-fast bacilli remains an important tool, and more rapid molecular techniques hold promise. Treatment with several drugs for 6 months or more can cure more than 95% of patients; direct observation of treatment, a component of the recommended five-element DOTS strategy, is judged to be the standard of care by most authorities, but currently only a third of cases worldwide are treated under this approach. Systematic monitoring of case detection and treatment outcomes is essential to effective service delivery. The proportion of patients diagnosed and treated effectively has increased greatly over the past decade but is still far short of global targets. Efforts to develop more effective tuberculosis vaccines are under way, but even if one is identified, more effective treatment systems are likely to be required for decades. Other modes of tuberculosis control, such as treatment of latent infection, have a potentially important role in some contexts. Until tuberculosis is controlled worldwide, it will continue to be a major killer in less-developed countries and a constant threat in most of the more-developed countries.

Adolescent↗

PubMed2003

Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS.

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has dramatically increased the incidence of tuberculosis (TB) in subSaharan Africa, where up to 60% of TB patients are coinfected with HIV and each year 200,000 TB deaths are attributable to HIV coinfection. Now HIV threatens control of TB in Asia, Eastern Europe, and Latin America. Antiretroviral (ARV) drugs can prevent TB by preserving immunity, but cohort analysis shows that early therapy, plus high levels of coverage and compliance, will be needed to avert a significant fraction of TB cases. However, ARV drugs could enhance the treatment of TB, and TB programs provide an important entry point for the treatment of HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Effects of human immunodeficiency virus infection on recurrence of tuberculosis after rifampin-based treatment: an analytical review.

We reviewed 47 prospective studies of recurrence of pulmonary tuberculosis (TB) after cure to assess the influence of human immunodeficiency virus (HIV) infection and rifampin treatment. Multivariate regression revealed that the recurrence rate for HIV-uninfected persons increased with decreasing duration of therapy: it was 1.4 cases per 100 person-years for recipients of >or=7 months of rifampin therapy and 2.0 and 4.0 cases per 100 person-years for recipients of 5-6 and 2-3 months of rifampin therapy, respectively (trend P=.00014), over a mean follow-up duration of 34 months, at a TB incidence of 250 cases per 100,000 person-years. Relative risks of recurrence associated with HIV infection at these 3 treatment durations were 2.2, 2.1, and 3.4, respectively, with a significant interaction between HIV infection status and treatment duration (P=.025). The recurrence rate increased with the background TB incidence (P=.048), and it decreased over time since completion of treatment in HIV-uninfected but not in HIV-infected patients (overall trend, P=.00008; difference by HIV infection status, P=.025). In countries where HIV infection is endemic, TB recurrence may be reduced by administration of rifampin-based treatment for at least 6 months, in accordance with World Health Organization recommendations.

Antitubercular Agents↗

PubMed2003

The growing burden of tuberculosis: global trends and interactions with the HIV epidemic.

BACKGROUND: The increasing global burden of tuberculosis (TB) is linked to human immunodeficiency virus (HIV) infection. METHODS: We reviewed data from notifications of TB cases, cohort treatment outcomes, surveys of Mycobacterium tuberculosis infection, and HIV prevalence in patients with TB and other subgroups. Information was collated from published literature and databases held by the World Health Organization (WHO), the Joint United Nations Programme on HIV/Acquired Immunodeficiency Syndrome (UNAIDS), the US Census Bureau, and the US Centers for Disease Control and Prevention. RESULTS: There were an estimated 8.3 million (5th-95th centiles, 7.3-9.2 million) new TB cases in 2000 (137/100,000 population; range, 121/100,000-151/100,000). Tuberculosis incidence rates were highest in the WHO African Region (290/100,000 per year; range, 265/100,000-331/100,000), as was the annual rate of increase in the number of cases (6%). Nine percent (7%-12%) of all new TB cases in adults (aged 15-49 years) were attributable to HIV infection, but the proportion was much greater in the WHO African Region (31%) and some industrialized countries, notably the United States (26%). There were an estimated 1.8 million (5th-95th centiles, 1.6-2.2 million) deaths from TB, of which 12% (226 000) were attributable to HIV. Tuberculosis was the cause of 11% of all adult AIDS deaths. The prevalence of M tuberculosis-HIV coinfection in adults was 0.36% (11 million people). Coinfection prevalence rates equaled or exceeded 5% in 8 African countries. In South Africa alone there were 2 million coinfected adults. CONCLUSIONS: The HIV pandemic presents a massive challenge to global TB control. The prevention of HIV and TB, the extension of WHO DOTS programs, and a focused effort to control HIV-related TB in areas of high HIV prevalence are matters of great urgency.

AIDS-Related Opportunistic Infections↗

PubMed2003

Susceptibility to visceral leishmaniasis in the domestic dog is associated with MHC class II polymorphism.

Zoonotic visceral leishmaniasis (VL) is a disease of dogs, humans and other animals caused by the intracellular macrophage parasite Leishmania infantum. We examined the relationship between DLA class II alleles ( DRB1, DQA1, DQB1) and the course of infection in a cohort of Brazilian mongrel dogs exposed to natural L. infantum infection. DLA alleles were typed by sequence-based typing. DLA-DRB1 genotype was significantly associated with levels of anti- Leishmania IgG and parasite status assessed by PCR. Dogs with DLA-DRB1*01502 had higher levels of specific IgG and an increased risk of being parasite positive compared with dogs without this allele, controlling for other alleles and significant variables. No significant associations were seen for DLA-DQA1 or DLA-DQB1 alleles. These results suggest that the DLA-DRB1 locus plays a role in determining susceptibility to canine VL. As the domestic dog is the main reservoir for human infection, the identification of genetic factors influencing canine resistance or susceptibility to VL may provide insights into the immunology and potential control through vaccination of VL.

Alleles↗

PubMed2003

What is the limit to case detection under the DOTS strategy for tuberculosis control?

In year 2000, the WHO DOTS strategy for tuberculosis (TB) control had been adopted by 148 out of 212 countries, but only 27% of all estimated sputum smear-positive patients were notified under DOTS in that year. Here we investigate the way in which gains in case detection under DOTS were made up until 2000 in an attempt to anticipate future progress towards the global target of 70% case detection. The analysis draws on annual reports of DOTS geographical coverage and case notifications, and focuses on the 22 high-burden countries (HBCs) that account for about 80% of new TB cases arising globally each year. Our principal observation is that, as TB programmes in the 22 HBCs have expanded geographically, the fraction of the estimated number of sputum smear-positive cases detected within designated DOTS areas has remained constant at 40-50% although there are significant differences between countries. This fraction is about the same as the percentage of all smear-positive cases notified annually to WHO via public health systems worldwide. The implication is that, unless the DOTS strategy can reach beyond traditional public health reporting systems, or unless these systems can be improved, case detection will not rise much above 40% in the 22 HBCs, or in the world as a whole, even when the geographical coverage of DOTS is nominally 100%. We estimate that, under full DOTS coverage, three-quarters of the undetected smear-positive cases will be living in India, China, Indonesia, Nigeria, Bangladesh and Pakistan. But case detection could also remain low in countries with smaller populations: in year 2000, over half of all smear-positive TB cases were living in 49 countries that detected less than 40% of cases within DOTS areas. Substantial efforts are therefore needed (a) to develop new case finding and management methods to bridge the gap between current and target case detection, and (b) to improve the accuracy of national estimates of TB incidence, above all by reinforcing and expanding routine surveillance.

Antitubercular Agents↗

PubMed2003

Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy.

Reduction of deaths associated with malaria in children is a primary goal of malaria control programmes in Africa, but there has been little discussion about how changes in mortality will be measured. This paper assesses recent historical changes in the contribution of malaria to child survival in Africa by examining data from demographic surveillance systems (DSS) in 25 mainly rural settings. The data were adjusted for the varying sensitivity and specificity of verbal autopsies (VA) in different ranges of malaria mortality and for varying parasite prevalences. Average malaria mortality in the DSS sites in west Africa was 7.8 per 1000 child-years between 1982 and 1998; the rate did not change significantly over this period. In the sites in east and southern Africa combined, malaria mortality was 6.5 per 1000 child-years between 1982 and 1989, but it increased to 11.9 per 1000 child-years between 1990 and 1998. All-cause child mortality and non-malaria mortality, by contrast, decreased significantly over time in both regions; consequently, the proportion of deaths due to malaria rose from 18% to 23% in west African sites and from 18% to 37% in east and southern African sites between 1982-89 and 1990-98. If malaria mortality fell at a rate consistent with the Roll Back Malaria target of halving malaria mortality by the year 2010, an individual DSS of a total population of 63 500 could with adequate VA adjustment detect this reduction after 7 years.

Africa↗

PubMed2003

Monitoring mosquito net coverage for malaria control in Africa: possession vs. use by children under 5 years.

OBJECTIVES: To investigate the strengths and weaknesses of the indicators 'proportion of households possessing mosquito net(s)' and 'proportion of children under 5 years of age who slept under a net the preceding night' for monitoring malaria control. METHODS: Review of data from household surveys including demographic and health surveys in sub-Saharan African countries. RESULTS: Net possession ranged among 14 surveyed regions from 0.1% to 28.5% for insecticide-treated nets (ITNs) and among 69 regions from 3.6% to 79.7% for any net. Reported use during the preceding night by children under 5 years of age was between 0% and 16% for ITNs and between 0.7% and 74.5% for any net. On average, in households owning ITN(s), 55% of children slept under it (R2 = 0.97, P < 0.001). For any net, use was -4.2% + 0.875 x possession (R2 = 0.89, P < 0.001); the use of nets, however, also varied somewhat among the surveyed countries (P = 0.003). In-depth surveys suggested that use was lower than possession because: (i). nets were scarce (mean 1.8 per possessing household); (ii). nets were not always used for children and (iii). use was lower during hot, dry months than during cool rainy months, and many surveys had been conducted in the dry season. CONCLUSIONS: Not all mosquito nets owned by African households are being used for young children. Household education on the consistent use of nets for this vulnerable group is called for in malaria control programmes. Regular, district-level rapid assessments of household possession of nets should complement ongoing in-depth surveys. Data on 'use during the preceding night' must be interpreted taking the survey season into account.

Adult↗

PubMed2002

Infectiousness in a cohort of brazilian dogs: why culling fails to control visceral leishmaniasis in areas of high transmission.

The elimination of seropositive dogs in Brazil has been used to control zoonotic visceral leishmaniasis but with little success. To elucidate the reasons for this, the infectiousness of 50 sentinel dogs exposed to natural Leishmania chagasi infection was assessed through time by xenodiagnosis with the sandfly vector, Lutzomyia longipalpis. Eighteen (43%) of 42 infected dogs became infectious after a median of 333 days in the field (105 days after seroconversion). Seven highly infectious dogs (17%) accounted for >80% of sandfly infections. There were positive correlations between infectiousness and anti-Leishmania immunoglobulin G, parasite detection by polymerase chain reaction, and clinical disease (logistic regression, r2=0.08-0.18). The sensitivity of enzyme-linked immunosorbent assay to detect currently infectious dogs was high (96%) but lower in the latent period (<63%), and specificity was low (24%). Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling.

Animals↗

PubMed2002

Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru.

BACKGROUND: There are no data on the feasibility and cost-effectiveness of using second-line drugs to treat patients with chronic tuberculosis, many of whom are infected with multidrug resistant (MDR) strains of Mycobacterium tuberculosis, in low or middle-income countries. METHODS: A national programme to treat chronic tuberculosis patients with a directly observed standardised 18-month daily regimen, consisting of kanamycin (3 months only), ciprofloxacin, ethionamide, pyrazinamide, and ethambutol, was established in Peru in 1997. Compliance and treatment outcomes were analysed for the cohort started on treatment between October, 1997, and March, 1999. Total and average costs were assessed. Cost-effectiveness was estimated as the cost per DALY gained. FINDINGS: 466 patients were enrolled; 344 were tested for drug susceptibility and 298 (87%) had MDR tuberculosis. 225 patients (48%) were cured, 57 (12%) died, 131 (28%) did not respond to treatment, and 53 (11%) defaulted. Of the 413 (89%) patients who complied with treatment, 225 (55%) were cured. Among MDR patients, resistance to five or more drugs was significantly associated with an unfavourable outcome (death, non-response to treatment, or default; odds ratio 3.37, 95% CI 1.32-8.60; p=0.01). The programme cost US $0.6 million per year, 8% of the National Tuberculosis Programme budget, and US $2381 per patient for those who completed treatment. The mean cost per DALY gained was $211 ($165 at drug prices projected for 2002). INTERPRETATION: Treating chronic tuberculosis patients with high levels of MDR with second-line drugs can be feasible and cost-effective in middle-income countries, provided a strong tuberculosis control programme is in place.

Adolescent↗

PubMed2002

Worldwide incidence of multidrug-resistant tuberculosis.

Planning for tuberculosis (TB) control requires an assessment of the number and distribution of drug-resistant cases. This study used results of resistance surveys from 64 countries, together with data predictive of resistance rates from 72 others, to estimate the number of new multidrug-resistant (MDR) TB cases that occurred in 2000. By these methods, an estimated 273,000 (95% confidence limits, 185,000 and 414,000) new cases of MDR TB occurred worldwide in 2000, 3.2% of all new TB cases. The analysis provides the first comprehensive set of estimates of the MDR TB burden by country and globally.

Humans↗

PubMed2002

Erasing the world's slow stain: strategies to beat multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR) is perceived as a growing hazard to human health worldwide. Judgments about the true scale of the problem, and strategies for containing it, need to come from a balanced appraisal of the epidemiological evidence. We conclude in this review that MDR is, and will probably remain, a locally severe problem; that epidemics can be prevented by fully exploiting the potential of standard short-course chemotherapy (SCC) based on cheap and safe first-line drugs; and that best-practice SCC may even reduce the incidence of MDR where it has already become endemic. On the basis of the available, imperfect data, we recommend a three-part response to the threat of MDR: widespread implementation of SCC as the cornerstone of good tuberculosis control, improved resistance testing and surveillance, and the careful introduction of second-line drugs after a sound evaluation of cost, effectiveness, and feasibility.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Estimates of world-wide distribution of child deaths from acute respiratory infections.

Acute respiratory infections (ARI) are among the leading causes of childhood mortality. Estimates of the number of children worldwide who die from ARI are needed in setting priorities for health care. To establish a relation between deaths due to ARI and all-cause deaths in children under 5 years we show that the proportion of deaths directly attributable to ARI declines from 23% to 18% and then 15% (95% confidence limits range from +/- 2% to +/- 3%) as under-5 mortality declines from 50 to 20 and then to 10/1000 per year. Much of the variability in estimates of ARI in children is shown to be inherent in the use of verbal autopsies. This analysis suggests that throughout the world 1.9 million (95% CI 1.6-2.2 million) children died from ARI in 2000, 70% of them in Africa and southeast Asia.

Acute Disease↗

PubMed2002

Low access to a highly effective therapy: a challenge for international tuberculosis control.

OBJECTIVE: To determine the scale of the tuberculosis (TB) problem facing the international Stop TB Partnership by measuring the gap between present rates of case detection and treatment success, and the global targets (70% and 85%, respectively) to be reached by 2005 under the WHO DOTS strategy. METHODS: We analysed case notifications submitted annually to WHO from up to 202 (of 210) countries and territories between 1980 and 2000, and the results of treatment for patients registered between 1994 and 1999. FINDINGS: Many of the 148 national DOTS programmes in existence by the end of 2000 have shown that they can achieve high treatment success rates, close to or exceeding the target of 85%. However, we estimate that only 27% of all the new smear-positive cases that arose in 2000 were notified under DOTS, and only 19% were successfully treated. The increment in case-finding has been steady at about 133 000 additional smear-positive cases in each year since 1994. In the interval 1999- 2000, more than half of the extra cases notified under DOTS were in Ethiopia, India, Myanmar, the Philippines, and South Africa. CONCLUSION: With the current rate of progress in DOTS expansion, the target of 70% case detection will not be reached until 2013. To reach this target by 2005, DOTS programmes must find an additional 333 000 cases each year. The challenge now is to show that DOTS expansion in the major endemic countries can significantly accelerate case finding while maintaining high cure rates.

Antitubercular Agents↗