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Biomedical subjects

C Lienhardt

Publications and source records attributed to C Lienhardt.

At least 19 recordsLinked to original sources
PubMed2004

Traditional healers participate in tuberculosis control in The Gambia.

SETTING: Twenty-three Gambian villages. OBJECTIVE: To evaluate the feasibility of involving traditional healers in tuberculosis diagnosis and treatment in The Gambia. DESIGN: Twenty-eight traditional healers were educated in the recognition of signs and symptoms of tuberculosis and indications for referral. They administered medications to confirmed cases, and were revisited after 1 year to assess knowledge retention. RESULTS: Over 6 months, the traditional healers referred 66 suspects, from whom eight cases were diagnosed. All were successfully treated. Twenty-three of 24 traditional healers re-interviewed retained appropriate knowledge; 16 continued to refer suspects. CONCLUSIONS: Traditional healers can play a positive role in tuberculosis control.

Adult↗
PubMed2003

Surveillance of drug-resistant Mycobacterium tuberculosis in The Gambia.

To determine the rates of drug-resistant tuberculosis in The Gambia, Mycobacterium tuberculosis isolates obtained from 225 patients during a nationwide survey were tested against isoniazid, rifampicin, ethambutol and streptomycin using the resistance ratio method. Only nine (4%) of the patients had strains that were resistant to one or more drugs. None of the patients with drug-resistant M. tuberculosis had previously been treated for tuberculosis. Drug-resistant tuberculosis is, as yet, not common in The Gambia. Periodic surveys for drug-resistant tuberculosis are recommended to monitor changes that may emerge over time.

Adolescent↗
PubMed2003

Clinical and radiological presentation of 340 adults with smear-positive tuberculosis in The Gambia.

SETTING: Four clinics in The Gambia. OBJECTIVE: To document clinical and radiographic presentations of sputum smear-positive tuberculosis in adults. DESIGN: Newly diagnosed acid-fast bacilli (AFB) smear, culture-positive tuberculosis patients aged > or = 15 years were interviewed and examined, and underwent tuberculin skin testing, HIV testing and chest X-ray reviewed by a chest physician using set criteria. RESULTS: Of 340 patients enrolled (median age 29 years; males 73%), 8.3% were HIV-positive. One-third reported haemoptysis, > 90% reported weight loss and fever, and wasting was the most common sign (69%). Crepitations were the most frequent auscultatory finding (41%). The most common radiological lesion was a patchy infiltrate (> 90%). Cavitation was present in 206 patients (60.6%), most frequently occurred in the upper lung fields, was associated with increasing bacterial load in the sputum, and was less prevalent in HIV-positive patients (45% vs. 62%; P = 0.07). Auscultatory and chest X-ray findings matched only one-third of the time. CONCLUSION: In our setting, wasting is the most common clinical sign of sputum smear-positive tuberculosis. Auscultatory findings correlate poorly with radiological abnormalities. Cavitation is associated with increasing bacterial load in the sputum, and is therefore a strong indicator for early treatment.

Adolescent↗
PubMed2002

Investigation of environmental and host-related risk factors for tuberculosis in Africa. I. Methodological aspects of a combined design.

Host-related and environmental factors for tuberculosis have usually been investigated separately using different study designs. Joint investigation of the genetic, immunologic, and environmental factors at play in susceptibility to tuberculosis represents an innovative goal for obtaining a better understanding of the pathogenesis of the disease. In this paper, the authors describe methods being used to investigate these points in a West African study combining several designs. Patients with newly diagnosed smear-positive cases of tuberculosis are recruited. The effect of host-related factors is assessed by comparing each case with a healthy control from the case's household. The role of environmental factors is estimated by comparing cases with randomly selected community controls. The frequencies of candidate gene variants are compared between cases and community controls, and results are validated through family-based association studies. Members of the households of cases and community controls are being followed prospectively to determine the incidence of "secondary" tuberculosis and to evaluate the influence of geographic and genetic proximity to the index case. This type of design raises important methodological issues that may be useful to consider in studies investigating the natural history of infectious diseases and in attempts to disentangle the effects of environmental and genetic factors in response to infection.

Africa, Western↗
PubMed2002

Investigation of environmental and host-related risk factors for tuberculosis in Africa. II. Investigation of host genetic factors.

In an accompanying paper (Am. J. Epidemiol. 2002;155:1066-73), the authors describe the design of a large multicenter study being carried out in three West African countries for investigation of the roles of environmental and host-related factors in the development of tuberculosis. In this paper, the authors review some evidence that host genetic factors play a role in susceptibility to tuberculosis. They describe the three components of the study that are designed to investigate the effect of host genetic factors on the development of tuberculosis: case-control and family-based association studies of candidate genes and analysis of affected relative pairs to screen the human genome for areas of linkage to the disease. The authors also address a number of methodological issues that arise, such as the effects of consanguinity, half-siblings, and nonpaternity. Lastly, they review opportunities to assess gene-environment interaction in the framework of the study, in light of current methodological knowledge. Consideration of these issues may be useful in the design of other studies of genetic susceptibility to infectious diseases, particularly those to be carried out in developing countries.

Africa, Western↗
PubMed2001

Tuberculosis contacts but not patients have higher gamma interferon responses to ESAT-6 than do community controls in The Gambia.

The Mycobacterium tuberculosis antigen ESAT-6 has been proposed for tuberculosis immunodiagnosis. In The Gambia, 30% of community controls produced gamma interferon (IFN-gamma) in response to ESAT-6. Increased proportions of responders and intensities of responses were found in household contacts. Responses that were initially low in tuberculosis patients increased after treatment. An ESAT-6 IFN-gamma assay will be of limited use in the diagnosis of tuberculosis in countries where tuberculosis is endemic. Its role in contact tracing should be evaluated further.

Adolescent↗
PubMed2001

Polarization of PPD-specific T-cell response of patients with tuberculosis from Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12.

The T helper (Th) 1/Th2 balance in the T-lymphocyte response to purified protein derivative (PPD) was evaluated at the clonal level in six Italian and five Gambian patients with pulmonary tuberculosis (TB) before and after antimycobacterial therapy, as well as in five Gambian and four Italian healthy immune control subjects. In untreated patients, most PPD-specific clones derived from either peripheral blood or pleural effusions showed a Th0 cytokine profile (production of both interferon [IFN]-gamma and interleukin [IL]-4/IL-5). After 6 mo of therapy and clinical healing, most PPD-specific clones showed a polarized Th1 profile (production of IFN-gamma but not IL-4/IL-5) in both Italian and Gambian patients. The Th1 polarization was less marked in Gambian than in Italian patients and failed to occur in another group of four Italian patients who experienced treatment failure. The cytokine profile observed after successful therapy in patients with TB was similar to that found in healthy control subjects. T-cell clones of undefined specificity generated from PPD-stimulated cultures showed a similar Th0/Th2 bias in Gambian individuals and Italian patients with treatment failure. The Th0/Th2-biased responses in Gambian patients before therapy could be modulated in vitro by IFN-alpha or IL-12, which induced a Th1 polarization of both PPD-specific and bystander T cells. Our data show that active TB associates with a predominant Th0 response to mycobacterial antigens that could play a role in the pathogenesis of the disease. Adjunctive immunotherapy using Th1-polarizing cytokines could increase host defense against mycobacteria and accelerate healing.

Adult↗
PubMed2001

Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans.

Twin and family studies indicate that host genetic factors influence susceptibility to leprosy and, possibly, leprosy type. Murine studies have suggested a role for the natural resistance-associated macrophage protein 1 (Nramp1) gene, which can influence cellular immune responses to intracellular pathogens. We evaluated a variation in the human homolog, NRAMP1, recently associated with tuberculosis susceptibility in West Africa. A total of 273 patients with leprosy and 201 controls from Mali were genotyped for NRAMP1 polymorphisms previously associated with tuberculosis. No association was found with leprosy per se (P = 0.83), but the NRAMP1 3'-untranslated region 4-bp insertion/deletion polymorphism was associated with leprosy type (P = 0.007). Heterozygotes were more frequent among multibacillary than paucibacillary leprosy cases. Thus, variation in or near the NRAMP1 gene may exert an influence on the clinical presentation of leprosy, possibly by influencing cellular immune response type.

Adult↗
PubMed2001

Factors affecting time delay to treatment in a tuberculosis control programme in a sub-Saharan African country: the experience of The Gambia.

SETTING: Rural and urban health centres in The Gambia, West Africa. OBJECTIVES: To estimate the time delay between onset of symptoms and initiation of treatment and identify the risk factors influencing the delay in patients with tuberculosis (TB). DESIGN: Structured interviews with newly diagnosed TB patients aged over 15 years presenting to TB control staff in four health centres. RESULTS: A total of 152 TB patients were interviewed. The median delay from onset of symptoms to commencement of treatment was 8.6 weeks (range 5-17). Delay to treatment was independent of sex, but was shorter in young TB patients. The median delay was longer in rural than in urban areas (12 weeks [range 8.5-17] vs. 8 [4-12], P < 0.01) and in those who did not attend school, but this effect disappeared after adjusting for age and area of residence. Patients who reported haemoptysis as one of their initial symptoms had shorter delays to treatment. There was no relation between duration of delay to treatment and cure rate, but longer delay did increase the risk of death. CONCLUSION: Starting TB patients on treatment as early as possible plays a major role in reducing disease transmission in the community. Key to this is increasing awareness of the signs and symptoms of TB and ensuring easy access to diagnostic facilities and treatment.

Adolescent↗
PubMed1998

Bactericidal activity of a single-dose combination of ofloxacin plus minocycline, with or without rifampin, against Mycobacterium leprae in mice and in lepromatous patients.

To develop a fully supervisable, monthly administered regimen for treatment of leprosy, the bactericidal effect of a single-dose combination of ofloxacin (OFLO) and minocycline (MINO), with or without rifampin (RMP), against Mycobacterium leprae was studied in the mouse footpad system and in previously untreated lepromatous leprosy patients. Bactericidal activity was measured by the proportional bactericidal method. In mouse experiments, the activity of a single dose of the combination OFLO-MINO was dosage related; the higher dosage of the combination displayed bactericidal activity which was significantly inferior to that of a single dose of RMP, whereas the lower dosage did not exhibit a bactericidal effect. In the clinical trial, 20 patients with previously untreated lepromatous leprosy were treated with a single dose consisting of either 600 mg of RMP plus 400 mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of MINO. The OFLO-MINO combination exhibited definite bactericidal activity in 7 of 10 patients but was less bactericidal than the RMP-OFLO-MINO combination. Both combinations were well tolerated. Because of these promising results, a test of the efficacy of multiple doses of ROM in a larger clinical trial appears justified.

Adolescent↗
PubMed1998

Factors determining the outcome of treatment of adult smear-positive tuberculosis cases in The Gambia.

SETTING: Health centres in The Gambia, West Africa. OBJECTIVES: To identify factors determining the outcome of treatment of adult tuberculosis cases in a Tuberculosis Control Programme using directly observed treatment. DESIGN: Information on the outcome of treatment was collected on all tuberculosis cases registered with the Tuberculosis Control Programme in 1994 and 1995 and treated under supervision by tuberculosis control staff, nurses or village health workers. Treatment outcome was recorded as cured, completed treatment, failed, defaulted or died. Transferred-out patients were traced and their treatment outcome recorded at the health centre where they had last been seen. RESULTS: Data were analysed for 1357 adult smear-positive tuberculosis cases. Sputum smear conversion 2 months after the start of treatment was observed in 90% of smear-positive cases and was more likely to occur if the initial bacterial load in the sputum was low. The total cure rate was 74.6%. Female tuberculosis patients were more likely to achieve cure than males. Adjusting for sex, the cure rate was higher when treatment was provided by tuberculosis control staff in the main health centres rather than by nurses or village health workers at the peripheral level (odds ratio [OR] = 1.60, 95% confidence interval [CI] 1.23-2.09). The absence of sputum smear conversion after 2 months of chemotherapy was associated with defaulting later during treatment (OR = 2.0, 95% CI 1.15-3.57). Adjusting for age and sex, the death rate during treatment was higher in human immunodeficiency virus (HIV) positive than in HIV-negative tuberculosis patients. CONCLUSION: Directly observed treatment is an effective intervention for improving adherence of tuberculosis patients to treatment in a resource-poor country, provided that drugs are effectively delivered to the most peripheral level, and that health staff are adequately trained and regularly supervised. Patients with high bacterial load in initial sputum smears need to be closely supervised, as they are more likely to default from treatment.

Adult↗
PubMed1997

Comparison of bacillary indexes in slit-skin smears, skin and nerve biopsies; a study from Malawi.

Data analyzed in this paper were collected within the framework of the Lepra Evaluation Project, an epidemiological study of leprosy in Karonga District, northern Malawi. For 212 patients information on the number of skin lesions, slit-skin smear and skin biopsy results were available. Among 61 patients with a single lesion none were slit-skin-smear positive and two had bacilli detected in skin biopsies. In contrast, among 119 patients with four or more lesions 34 (28.6%) versus 59 (49.6%) had bacilli detectable in slit-skin smears or skin biopsies, respectively. In a further 47 patients skin biopsy results could be compared with split-nerve biopsy results. In 20 of 47 patients the bacterial indexes (BIs) were identical in skin and nerve biopsies, while in 26 of 47 patients the BIs were higher in nerve than in skin biopsies. This difference, which is consistent with several other studies in the literature, provides an insight into the pathogenesis of leprosy.

Adult↗
PubMed1997

Estimation of the impact of the human immunodeficiency virus infection on tuberculosis: tuberculosis risks re-visited?

The human immunodeficiency virus (HIV) infection has both a direct and an indirect effect on the incidence of tuberculosis. The direct effect is due to the increased number of cases among HIV-infected individuals because of their enhanced susceptibility to the disease. The indirect effect is increased transmission of Mycobacterium tuberculosis infection in a community with high levels of dual infection, as a consequence of infectious cases occurring in HIV-infected persons. The risk of infection by M. tuberculosis in the population will then increase, as will the number of tuberculosis cases in the general population. According to the World Health Organization, over 4 million people are estimated to be dually infected with HIV and M. tuberculosis world-wide. In 1990, it was estimated that 300,000 new TB cases (4% of total new cases) were attributable to HIV infection; around 1.4 million cases are expected per year by 2000 (equivalent to about 14% of expected cases), thus increasing the reservoir of tuberculosis patients capable of transmitting the infection to others, and increasing the burden on the already overstretched National Tuberculosis Control Programmes, especially in resource-poor countries. This paper is a review of methods suggested to quantify the effect of the interaction between HIV infection and tuberculosis at population level, and more particularly the effect of HIV on the risk of tuberculosis infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Bactericidal activity of single dose of clarithromycin plus minocycline, with or without ofloxacin, against Mycobacterium leprae in patients.

Fifty patients with newly diagnosed lepromatous leprosy were allocated randomly to one of five groups and treated with either a month-long standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a single dose of 600 mg of rifampin, a month-long regimen with the dapsone (DDS) and clofazimine (CLO) components of the standard MDT, or a single dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline (MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the end of 1 month, clinical improvement accompanied by significant decreases of morphological indexes in skin smears was observed in about half of the patients of each group. A significant bactericidal effect was demonstrated in the great majority of patients in all five groups by inoculating the footpads of mice with organisms recovered from biopsy samples obtained before and after treatment. Rifampin proved to be a bactericidal drug against Mycobacterium leprae more potent than any combination of the other drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a degree of bactericidal activity similar to that of a regimen daily of doses of DDS-CLO for 1 month, suggesting that it may be possible to replace the DDS and CLO components of the MDT with a monthly dose of CLARI-MINO, with or without OFLO. However, gastrointestinal adverse events were quite frequent among patients treated with CLARI-MINO, with or without OFLO, and may be attributed to the higher dosage of CLARI or MINO or to the combination of CLARI-MINO plus OFLO. In future trials, therefore, we propose to reduce the dosages of the drugs to 1,000 mg of CLARI, 100 mg of MINO, and 400 mg of OFLO.

Adolescent↗
PubMed1996

Mycetomas in Mali: causative agents and geographic distribution.

Although Mali is situated in the African zone endemic for mycetomas, no report has been published on the characteristics of the disease in this country. We report a series of 54 cases observed in Bamako. The causative agents were Madurella mycetomatis in 20 patients, Leptosphaeria sp. in one patients, Actinomadura madurae in 12 patients, A. pelletieri in 15 patients, and Streptomyces somaliensis in three patients. In this series, the observed geographic distribution of the causative agents was in agreement with data on the causative agents and their geographic distribution in neighboring countries, and with those suggesting a relationship between the type of infectious agent and the annual rainfall.

Adult↗
PubMed1996

Determination of the minimal effective dosages of ofloxacin and sparfloxacin against M. leprae in the mouse foot pad system.

The minimal effective dosages (MEDs) of ofloxacin (OFLO) and sparfloxacin (SPFX) against 10 isolates of Mycobacterium leprae were measured in the mouse foot pad system. The drugs were administered either by gavage or by incorporation into the mouse diet in a range of concentrations. The results demonstrated that the MEDs of OFLO were 4 to 5 times higher than those of SPFX, thus confirming that, on a weight-to-weight basis, the anti-M. leprae activity of SPFX was significantly greater than that of OFLO. The MEDs of OFLO/SPFX measured by gavage were 20 times lower than those measured by incorporating the drug into the mouse diet.

Animals↗