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Biomedical subjects

C Dye

Publications and source records attributed to C Dye.

At least 19 recordsLinked to original sources
PubMed2005

The impact of HIV/AIDS on the control of tuberculosis in India.

Epidemics of HIV/AIDS have increased the tuberculosis (TB) case-load by five or more times in East Africa and southern Africa. As HIV continues to spread, warnings have been issued of disastrous AIDS and TB epidemics in "new-wave" countries, including India, which accounts for 20% of all new TB cases arising in the world each year. Here we investigate whether, in the face of the HIV epidemic, India's Revised National TB Control Program (RNTCP) could halve TB prevalence and death rates in the period 1990-2015, as specified by the United Nations Millennium Development Goals. Using a mathematical model to capture the spatial and temporal variation in TB and HIV in India, we predict that, without the RNTCP, HIV would increase TB prevalence (by 1%), incidence (by 12%), and mortality rates (by 33%) between 1990 and 2015. With the RNTCP, however, we expect substantial reductions in prevalence (by 68%), incidence (by 41%), and mortality (by 39%) between 1990 and 2015. In India, 29% of adults but 72% of HIV-positive adults live in four large states in the south where, even with the RNTCP, mortality is expected to fall by only 15% between 1990 and 2015. Nationally, the RNTCP should be able to reverse the increases in TB burden due to HIV but, to ensure that TB mortality is reduced by 50% or more by 2015, HIV-infected TB patients should be provided with antiretroviral therapy in addition to the recommended treatment for TB.

AIDS-Related Opportunistic Infections↗
PubMed2005

Preliminary study using an indirect ELISA for the detection of serum antibodies to Alternaria in domestic cats.

Alternaria is a saprophytic fungus that is widespread in the environment; it is an opportunistic pathogen and causes disease in human beings and domestic animals. Fungal spores gain entry to the host through skin lesions and cause slow-growing, soft to firm, subcutaneous swellings, either with or without ulcers. An indirect ELISA was developed for the detection of anti-Alternaria immunoglobulin G (IgG) antibodies in serum to determine the prevalence of Alternaria exposure in domestic cats. Fifty-two of 63 cats had detectable levels of anti-Alternaria IgG antibody. There were no correlations between the concentration of antibody and the sex, breed or living environment of the cats, but cats less than two years of age had significantly lower concentrations than older cats. The cats with disease caused by culture-confirmed Alternaria infections did not have significantly higher concentrations of antibody than the healthy cats or cats with other diseases.

Alternaria↗
PubMed2005

Tuberculosis deaths in countries with high HIV prevalence: what is their use as an indicator in tuberculosis programme monitoring and epidemiological surveillance?

Although the reduction of tuberculosis deaths is one of the aims of tuberculosis control, it has not always been a priority for National Tuberculosis Programmes (NTPs). The usual explanation is that death as a treatment outcome not associated with ongoing tuberculosis transmission is not relevant to the public health objective of cutting the cycle of disease transmission. However, death as an adverse outcome for tuberculosis patients and their families is an important indicator in NTP monitoring. Global health targets agreed as part of the Millennium Development Goals include the reduction of tuberculosis deaths. Tuberculosis deaths as an indicator of the impact of tuberculosis control measures are therefore important in the epidemiological surveillance of progress towards these targets. These considerations are particularly important in countries with high human immunodeficiency virus (HIV) prevalence where HIV has exacerbated the tuberculosis epidemic and is now the single best predictor of tuberculosis incidence. Tuberculosis deaths are also closely linked to HIV prevalence. Routine NTP data on tuberculosis cohort deaths are important in programme monitoring, and improvements in recording and reporting of deaths would help to overcome limitations in their accuracy. As routine NTP data on tuberculosis cohort deaths are insufficient as an indicator in epidemiological surveillance regarding the impact of NTPs on tuberculosis mortality, measuring progress towards targets for reduced tuberculosis deaths depends on improved national vital registration systems for a more accurate determination of tuberculosis mortality.

Environmental Monitoring↗
PubMed2003

IgG subclass responses in a longitudinal study of canine visceral leishmaniasis.

Visceral leishmaniasis (VL), caused by Leishmania infantum, is an important disease of domestic dogs. Here, we present data on the IgG subclass antibody response to crude L. infantum antigen in a cohort of naturally infected Brazilian dogs. Specific IgG1-IgG4 responses could be detected in 98, 58, 70 and 82%, respectively of 57 dogs that were seropositive for specific IgG. Levels of all IgG subclasses were strongly inter-correlated. Levels of all IgG subclasses increased at the time of seroconversion, before reaching a plateau after several months. Levels of all IgG subclasses were higher in sick dogs than healthy dogs, and levels of all except IgG2 were higher in parasite-positive (by PCR) than parasite-negative dogs. However, levels of IgG2 relative to IgG1 were lower in sick or parasite-positive dogs compared to healthy or parasite-negative infected dogs. In contrast to previous studies, the results suggest that canine VL is associated with upregulation of specific antibody of all IgG subclasses, particularly IgG1, IgG3 and IgG4.

Animals↗
PubMed2002

Low infectiousness of a wildlife host of Leishmania infantum: the crab-eating fox is not important for transmission.

The epidemiological role of the crab-eating fox Cerdocyon thous in the transmission of Leishmania infantum is assessed in a longitudinal study in Amazon Brazil. A total of 37 wild-caught foxes were immunologically and clinically monitored, and 26 foxes exposed to laboratory colonies of the sandfly vector Lutzomyia longipalpis, over a 15-month period. In total 78% (29/37) of foxes were seropositive for anti-Leishmania IgG on at least 1 occasion, and 38% (8/37) had infections confirmed by PCR and/or by culture. Point prevalences were 74% (serology), 15% (PCR), and 26% (culture). No signs of progressive disease were observed. None of the foxes were infectious to the 1469 sandflies dissected from 44 feeds. A conservative estimate of the possible contribution of foxes to transmission was 9% compared to 91% by sympatric domestic dogs. These results show that crab-eating fox populations do not maintain a transmission cycle independently of domestic dogs. The implication is that they are unlikely to introduce the parasite into Leishmania-free dog populations.

Aging↗
PubMed2002

Comparison of vaccination strategies for the control of dog rabies in Machakos District, Kenya.

Demographic and epidemiological field data were used in a deterministic model to describe dog rabies transmission in Machakos District, Kenya and to predict the impact of potential vaccination strategies for its control. The basic reproduction number (R0) was estimated to be 2.44 (1.52-3.36, 95% confidence limits). There were three key model predictions. The first was that a threshold dog density (K(T)) of 4.5 dogs km(-2) (3.8-5.2 dogs km(-2), 95% confidence limits) was required to maintain transmission. The second was that the estimated annual vaccination rate of 24% failed to decrease incidence and actually increased the stability of transmission and may be counter-productive. Thirdly, to control rabies, it was predicted that 59% (34%-70%, 95% confidence limits) of dogs should be vaccinated at any one time. This requires approximately 70% coverage for annual but only 60% coverage for semi-annual vaccination campaigns. Community-level vaccination trials are needed to test these predictions.

Animals↗
PubMed2001

The resurgence of tuberculosis in Russia.

This paper documents and attempts to explain the epidemic spread of tuberculosis (TB) in Russia during the 1990s. After several decades of decline, the notification rate of all new TB cases among permanent residents increased by 7.5% per year from 1991-1999 and the death rate by 11% per year. Growth was quickest from 1993-1995 but increased again after the economic crisis of August 1998. Approximately 120 000 new cases and 30 000 deaths were reported in 1999. Case detection and cure rates have fallen in Russia since the mid-1980s; the fall has been accompanied by a higher frequency of severe disease among cases, and higher death and case fatality rates. With a mathematical model describing the deterioration in case finding and cure rates we could replicate the average rate of increase in incidence 1991-1999 but not the precise timing of the observed changes. Other factors that probably helped to shape the observed rise in caseload include enhanced transmission due to the mixing of prison and civilian populations, an increase in susceptibility to disease, and changes in the proportion of cases detected by surveillance. Although our explanation for the resurgence of TB is incomplete, we have identified a set of measures that can be implemented now to cut transmission, incidence and deaths.

Humans↗
PubMed2001

The dynamics of tuberculosis in response to 10 years of intensive control effort in Peru.

Improved tuberculosis (TB) case detection and cure rates are expected to accelerate the decline in incidence of TB and to reduce TB-associated deaths. Time series analyses of case reports in Peru showed that the per capita TB incidence rate was probably steady before 1991. Case reports increased between 1990 and 1992 as a result of improved case detection. Although diagnostic efforts have continued to increase since 1993, the incidence of new pulmonary TB cases has declined in every department of the country, with a national rate of decline > or =5.8% per year (range, 1.9%-9.7%). This elevated rate of decline suggests that 27% (19%-34%) of cases (158,000) and 70% (63%-77%) of deaths (91,000) among smear-positive patients were averted between 1991 and 2000. This is the first demonstration that a significant number of TB cases can be prevented through intensive short-course chemotherapy in a high-burden country.

Humans↗
PubMed2001

Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance.

BACKGROUND: Data on global trends in resistance to antituberculosis drugs are lacking. METHODS: We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. RESULTS: Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from 9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of multidrug resistance among new cases of tuberculosis was only 1.0 percent, but the prevalence was much higherin Estonia (14.1 percent), Henan Province in China (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0 percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in China (4.5 percent). There were significant decreases in multidrug resistance in France and the United States. In Estonia, the prevalence in all cases increased from 11.7 percent in 1994 to 18.1 percent in 1998 (P<0.001). CONCLUSIONS: Multidrug-resistant tuberculosis continues to be a serious problem, particularly among some countries of eastern Europe. Our survey also identified areas with a high prevalence of multidrug-resistant tuberculosis in such countries as China and Iran.

Antitubercular Agents↗
PubMed2001

Tissue cytokine responses in canine visceral leishmaniasis.

To elucidate the local tissue cytokine response of dogs infected with Leishmania chagasi, cytokine mRNA levels were measured in bone marrow aspirates from 27 naturally infected dogs from Brazil and were compared with those from 5 uninfected control animals. Interferon-gamma mRNA accumulation was enhanced in infected dogs and was positively correlated with humoral (IgG1) but not with lymphoproliferative responses to Leishmania antigen in infected dogs. Increased accumulation of mRNA for interleukin (IL)-4, IL-10, and IL-18 was not observed in infected dogs, and mRNA for these cytokines did not correlate with antibody or proliferative responses. However, infected dogs with detectable IL-4 mRNA had significantly more severe symptoms. IL-13 mRNA was not detectable in either control or infected dogs. These data suggest that clinical symptoms are not due to a deficiency in interferon-gamma production. However, in contrast to its role in human visceral leishmaniasis, IL-10 may not play a key immunosuppressive role in dogs.

Actins↗
PubMed2001

Will tuberculosis become resistant to all antibiotics?

The discovery of high prevalences of antibiotic resistance in some pathogens, in some parts of the world, has provoked fears of a widespread loss of drug efficacy. Here, we use a mathematical model to investigate the evolution of resistance to four major anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and streptomycin) in 47 sites around the world. The model provides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients who develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemic spread of isoniazid resistance over the past 50 years. The predicted median prevalence of resistance among new cases today was 7.0% (range 0.9-64.3%), close to the 6.3% (range 0-28.1%) observed. Predicted and observed prevalences of resistance to isoniazid plus rifampicin (multidrug-resistant or MDR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1-5.9%) and 1.0% (range 0-14.1%), respectively. With current data, and under prevailing treatment practices, it appears that MDR-TB will remain a localized problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relative fitness of drug-resistant strains.

Antitubercular Agents↗
PubMed2001

Detection of Leishmania infantum by PCR, serology and cellular immune response in a cohort study of Brazilian dogs.

The sensitivity and specificity of PCR, serology (ELISA) and lymphoproliferative response to Leishmania antigen for the detection of Leishmania infantum infection were evaluated in a cohort of 126 dogs exposed to natural infection in Brazil. For PCR, Leishmania DNA from bone-marrow was amplified with both minicircle and ribosomal primers. The infection status and time of infection of each dog were estimated from longitudinal data. The sensitivity of PCR in parasite-positive samples was 98%. However, the overall sensitivity of PCR in post-infection samples, from dogs with confirmed infection, was only 68%. The sensitivity of PCR varied during the course of infection, being highest (78-88%) 0-135 days post-infection and declining to around 50% after 300 days. The sensitivity of PCR also varied between dogs, and was highest in sick dogs. The sensitivity of serology was similar in parasite-positive (84%), PCR-positive (86%) and post-infection (88%) samples. The sensitivity of serology varied during the course of infection, being lowest at the time of infection and high (93-100%) thereafter. Problems in determining the specificity of serology are discussed. The sensitivity and specificity of cellular responsiveness were low. These data suggest that PCR is most useful in detecting active or symptomatic infection, and that serology can be a more sensitive technique for the detection of all infected dogs.

Animals↗
PubMed2001

Knowledge transfer, policymaking and community empowerment: a consensus model approach for providing public mental health and substance abuse services.

An important problem in creating new programs and policies is how to encourage the transfer of knowledge in non-hierarchical ways so that new, relevant and specific knowledge is co-created by all interested parties. In this paper, we suggest that a consensus model of policymaking is one response and identify four key structural elements thought necessary for creating such a consensus infrastructure. These are a) a leadership and facilitating capacity for initiating and promoting such an endeavor, b) a network or consortium of key researchers, practitioners, consumers, and policymakers to empower community ownership of the endeavor, c) a process for consensus building and strategic problem-solving for such a consortium, and d) the continued creation of a multi-directional dialogue through information dissemination. We examine these elements in action by describing a particular problem solving and consensus building model for developing and implementing a program, resolving group differences, and evaluating the group's process and products.

Community Mental Health Services↗
PubMed2000

Climate change and malaria: temperatures without fevers?

As the world gets warmer, the predictions about the spread of vector-based diseases such as malaria get gloomier. However, in their timely Perspective, Dye and Reiter explain the implications of a new climate model (Randolph and Rogers), which predicts that the distribution of malaria is unlikely to change dramatically in the next 50 years even if the world does get hotter.

Animals↗
PubMed2000

Criteria for the control of drug-resistant tuberculosis.

Antibiotic resistance is a growing impediment to the control of infectious diseases worldwide, tuberculosis (TB) being among them. TB kills two million people each year and foci of multidrug-resistant TB (MDR-TB) have been identified in Eastern Europe, Africa, Asia, and Latin America. A critical question for health policy is whether standardized short-course chemotherapy for TB, based on cheap first-line drugs, can prevent and reverse the spread of drug resistance. Here we use mathematical modeling, in conjunction with treatment results from six countries, to show that best-practice short-course chemotherapy is highly likely to bring strains resistant to either of the two key drugs isoniazid and rifampicin under control and to prevent the emergence of MDR-TB. However, it is not certain to contain MDR-TB once it has emerged, partly because cure rates are too low. We estimate that approximately 70% of prevalent, infectious MDR-TB cases should be detected and treated each year, and at least 80% of these cases should be cured, in order to prevent outbreaks of MDR-TB. Poor control programs should aim to increase case detection and cure rates together for three reasons: (i) these variables act synergistically; (ii) when either is low, the other cannot succeed alone; and (iii) the second-line drugs needed to raise MDR-TB cure rates are few and extremely costly. We discuss the implications of these results for World Health Organization policy on the management of antibiotic resistance.

Antitubercular Agents↗
PubMed2000

Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries.

CONTEXT: No large-scale study has investigated the impact of multidrug-resistant tuberculosis (TB) on the outcome of standard short-course chemotherapy under routine countrywide TB control program conditions in the World Health Organization's (WHO) directly observed treatment short-course strategy for TB control. OBJECTIVE: To assess the results of treatment with first-line drugs for patients enrolled in the WHO and the International Union Against Tuberculosis and Lung Disease's global project on drug-resistance surveillance. DESIGN AND SETTING: Retrospective cohort study of patients with TB in the Dominican Republic, Hong Kong Special Administrative Region (People's Republic of China), Italy, Ivanovo Oblast (Russian Federation), the Republic of Korea, and Peru. PATIENTS: New and retreatment TB cases who received short-course chemotherapy with isoniazid, rifampicin, pyrazinamide, and either ethambutol or streptomycin between 1994 and 1996. MAIN OUTCOME MEASURE: Treatment response according to WHO treatment outcome categories (cured; died; completed, defaulted, or failed treatment; or transferred). RESULTS: Of the 6402 culture-positive TB cases evaluated, 5526 (86%) were new cases and 876 (14%) were retreatment cases. A total of 1148 (20.8%) new cases and 390 (44.5%) retreatment cases were drug resistant, including 184 and 169 cases of multidrug-resistant TB, respectively. Of the new cases 4585 (83%) were treated successfully, 138 (2%) died, and 151 (3%) experienced short-course chemotherapy failure. Overall, treatment failure (relative risk [RR], 15.4; 95% confidence interval [CI], 10.6-22.4; P<.001) and mortality (RR, 3.73; 95% CI, 2.13-6.53; P<.001) were higher among new multidrug-resistant TB cases than among new susceptible cases. Even in settings using 100% direct observation, cases with multidrug resistance had a significantly higher failure rate than those who were susceptible (9/94 [10%] vs 8/1410 [0.7%]; RR, 16.9; 95% CI, 6.6-42.7; P<.001). Treatment failure was also higher among patients with any rifampicin resistance (n=115) other than multidrug resistance (RR, 5.48; 95% CI, 3.04-9.87; P<.001), any isoniazid resistance (n=457) other than multidrug resistance (RR, 3. 06; 95% CI, 1.85-5.05; P<.001), and among patients with TB resistant to rifampicin only (n=76) (RR, 5.47; 95% CI, 2.68-11.2; P<.001). Of the retreatment cases, 497 (57%) were treated successfully, 51 (6%) died, and 124 (14%) failed short-course chemotherapy treatment. Failure rates among retreatment cases were higher in those with multidrug-resistant TB, with any isoniazid resistance other than multidrug resistance, and in cases with TB resistant to isoniazid only. CONCLUSIONS: These data suggest that standard short-course chemotherapy, based on first-line drugs, is an inadequate treatment for some patients with drug-resistant TB. Although the directly observed treatment short-course strategy is the basis of good TB control, the strategy should be modified in some settings to identify drug-resistant cases sooner, and to make use of second-line drugs in appropriate treatment regimens. JAMA. 2000;283:2537-2545

Antitubercular Agents↗