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PubMed2006

Enhancement of treatment completion for latent tuberculosis infection with 4 months of rifampin.

BACKGROUND: Isoniazid is the standard medication used to treat latent tuberculosis infection (LTBI). The lengthy treatment with isoniazid, its perceived hepatotoxicity, and the increasing influx of foreign-born persons from countries with a higher prevalence of isoniazid resistance have compromised this regimen. In 2000, the Centers for Disease Control and Prevention guidelines recommended 4 months of rifampin (4R) as an acceptable alternative regimen to 9 months of isoniazid (9H). In a county chest clinic in northern New Jersey, a self-administered 9H regimen for patients with LTBI was generally prescribed until the year 2002. After recognizing poor completion rates, LTBI treatment was shifted predominantly to the alternative 4R regimen. METHODS: Medical records of patients placed on LTBI treatment during 2000 (predominantly a 9H regimen) and 2003 (predominantly a 4R regimen) were reviewed. A total of 474 patients were included in the study. chi(2), Fishers exact, two-sample t, and Wilcoxon rank-sum tests and logistic regression were used to analyze the data. The main outcome variable was treatment completion. RESULTS: A total of 80.5% of patients receiving 4R and 53.1% receiving 9H completed treatment (p < 0.0001); 34.7% of patients receiving 9H were unavailable for follow-up, compared to 12.6% receiving 4R (p = <0.0001). Fewer drug reactions were observed in the group receiving 4R compared to the group receiving 9H (3.1% vs 5.8%), although this was not statistically significant. Logistic regression analysis identified treatment regimen as a significant predictor for treatment completion (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3 to 8.1). Employment was negatively associated with treatment completion in the same model (OR, 0.54; 95% CI, 0.34 to 0.94). CONCLUSIONS: Patients receiving 4R were significantly more likely to complete therapy than those receiving 9H.

Adolescent↗

PubMed2003

The histamine H2-receptor antagonist, cimetidine, inhibits the articular osteopenia in rats with adjuvant-induced arthritis by suppressing the osteoclast differentiation induced by histamine.

The effects of cimetidine on rat adjuvant arthritis (AA) and rat osteoclast differentiation were studied. For the in vivo experiments, AA was induced by injections of Mycobacterium tuberculosis H37RA either subcutaneously into the base of the tail or into the right hind paw. The osteoclast differentiation was assessed by estimating the number of tartrate-resistant acid phosphatase-positive multinuclear cells in the bone marrow culture. Cimetidine, at the dose of 25 mg/kg body weight, reduced the paw swelling by 70% (P<0.01). Cimetidine, at 10 microM concentration, inhibited 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) and histamine mediated osteoclast differentiations by 40% (P<0.01) and 60% (P<0.001), respectively. Dimaprit, at 0.3 microM, stimulated the cell differentiation by 100% (P<0.01). Mepyramine reduced osteoclast differentiation, but the reduction was not statistically significant. Measurements of bone mineral density of the femur indicated that 5 mg/kg of cimetidine treated animals had 30% (P<0.01) higher mineral density in comparison with that of the AA control group that received no cimetidine. These results suggest that histamine is a potent inducer of osteoclast differentiation, at least in part, through the histamine H(2)-receptor, and cimetidine has a preventive effect on articular destruction and accompanying inflammation in arthritic rats. These observations may provide critical insights into the pathogenesis of the bone pathology seen in patients with RA.

Animals↗

PubMed2002

[Immune response and anergy. Study in tuberculosis patients from the Universitary Hospital, Maracaibo, Venezuela ].

With the aim of evaluate the anergy in Mycobacterium tuberculosis individuals infected we study 57 patients and 15 healthy controls, both sex and with different age, which to practice Sputum Bacteriology culture (BK) and the la reaction intradermic with PDD. The test of tuberculine on skin was achieve inoculate 0.1 ml de PPD intradérmic vía, the results were obtained at 72 h. 28 patient total result BK+ and 29 BK-. The Group BK+, 15 result PPD+ and 13 PPD-, the lastet were classify as anergic patients (BK+ PPD-). From the 29 patient residual (BK-), 20 was PPD+ and 9 PPD-. All the controls resulted BK- PPD-. Only the anergy in patient BK was evaluated + (28 individuals) patient. Was classified from the point of clinical view in three series: N series: 27 patient TBC+ BK-, P Series: 28 patient TBC+ BK+ and EP Series: 2 patient with extra pulmonary TBC. According to the grade of pulmonary complication, the patient separated in two groups, according to the extension and type of lesion found in the evaluation with X. rays The "group 1" with 9 patient (32.14%) it introduced lesions on one side with or without caverns and the "group 2" with 19 patient (67.85%) with bilateral lesions with or without caverns. Was carried out the Lymphoblastic Transformation Test (TTL) stimulating with PHA and PPD, for which patterns of outlying blood with heparina were gathered. The concentrations of IL-4, IL-6 and INF-gamma was gotten inmunoenzimatic in supernatants of cultivations for rehearsals and in plasm, hind to the stimulation with the PPD. The statistical analysis was carried out utilizing the Test T of Student in pair, Varianza Analysis and the square Chi. Only the controls and the patient BK-, they showed normal response to the PHA, in contrast, the patient BK+ PPD+ they introduced a suppression of the response opposite the PHA of aprox. 90%. The patient PPD+ they showed a superior response in cultivation that the patient PPD-. The concentration of IL-4 in the plasm of the anergic patient (PPD-) showed a significant difference (P < 0.05) with concerning the PPD group+. The concentration of INF-gamma was lower in the anergic patient significantly different to the of the patient PPD+. Similar result was gotten in the mensuration of IL-4 and INF-gamma in supernatants of cultivation. One could observe the presence of patient with IL-4+ INF-gamma, and INF-gamma or IL-4 only. In the patient classified clinical like series "P", the concentration of IL-4 was old in the "group 2" with concerning the "group 1." the opposite occurred with the concentrations of the INF-gamma which were old in the "group 1" (both differences were not significant statistical). The increase of IL-4 next to low concentrations of INF-gamma in anergic patient and committed clinical, it suggest a prevalence of the pattern Th2 (T2) in the immune response.

Adolescent↗

PubMed1993

Six months versus nine months chemotherapy for tuberculosis of lymph nodes: final results.

Of 199 patients treated for peripheral lymph node tuberculosis, 157 completed treatment as planned. Fifty received E2H9R9, 56 Z2 H9R9 and 51 Z2H6R6 regimens (E = Ethambutol; H = Isoniazid; R = Rifampicin; Z = pyrazinamide: numbers denote duration of therapy in months). In follow-up from 9 to 30 months, there were no significant differences between the regimens in enlargement of existing nodes, development of new glands or sinuses, in the need for new operative procedures, or in the percentage with measurable nodes at 30 months. Nine patients were felt to have had a clinical relapse (4 E2H9R9; 2 Z2H9R9; 3 Z2H6R6) although this was not confirmed bacteriologically in the five cases where material was sent for culture. These differences were not statistically different. The 6 month Z2H6R6 regimen performs just as well as the 9 month regimens Z2H9R9 and E2H9R9 in patients with fully sensitive organisms, and has the additional benefits of convenience and reduced cost.

Adolescent↗

PubMed1999

Tuberculin skin testing: determinants and reaction.

Mantoux purified protein derivative (PPD) skin testing was performed in schoolchildren who were grouped according to positive (Group I, n = 205) and negative (Group II, n = 79) exposure to recent acid-fast bacilli (AFB) smear-positive tuberculosis (TB) family contact. A prospective case-control study was undertaken to evaluate whether repeat bacille Calmette-Guérin (BCG) vaccination, nutritional state, presence/absence of BCG scar, and degree of AFB positivity of sputum of adult TB cases affect PPD skin reactivity in these two groups. Group I with TB contacts had larger induration (13.00 +/- 11.29 mm) than the Group II control group of 4.52 +/- 6.20; P = 0.000. Purified protein derivative reaction as to the number of BCG vaccination(s) received showed an increase in size as the BCG vaccination is repeated with significantly larger induration in Group I than in Group II (P = 0.048). The nutritional status was subgrouped into A (weight < 10 percentile), B (weight 50-75 percentile), and C (weight > 90 percentile), which were comparable for both groups. The mean PPD induration of subgroup A in Groups I and II was not statistically different. However, the mean PPD induration was highly significant between Groups I and II in subgroup B (12.46 +/- 10.70 vs 3.80 +/- 5.71 mm; P = 0.000) and subgroup C (14.31 +/- 11.54 vs 5.42 +/- 6.70 mm; P = 0.000). Children in group I with the BCG scar were noted to have significantly greater PPD induration size than in group II (14.14 +/- 11.23 vs 5.05 +/- 6.24 mm; P = 0.000). The degree of AFB positivity of sputum of TB adult cases (1+ to 4+ and cavitary TB) has no effect on PPD size (P = 0.766). Close contact with individuals with active TB (AFB smear positive) is a very important factor for PPD skin conversion. Repeat BCG vaccination, malnutrition, and BCG with scars present difficulties in making a diagnosis of TB infection but did not affect PPD reactivity and did highlight the need for thorough clinical evaluation.

BCG Vaccine↗

PubMedDate not supplied

Analysis of status of surgery in thoracic tuberculosis.

A retrospective analysis of the surgical procedure in 1655 patients in twenty years in a university hospital for thoracic tuberculosis revealed that the varieties of procedures were necessary in 2.2% cases only. They can be grouped as tubercular empyema with or without bronchopleural fistula in 1507 (91%), complicated pulmonary tuberculosis in 78 (4.7%), cold abscess in the chest wall with or without lymphadenitis in 54 (3.2%) and osteomyelitis of the ribs and sternum in 16 cases (0.9%). This is statistically significant with a confidence interval of 0.1248 to 0.2348. In tubercular empyema 222 procedures were performed of which 162 were minor procedures, intercostal drainage with irrigation: 89 cases, thoracostoma: 56 cases and continuous chest wall tube 17 cases and 60 were major procedures (decortication in 45 cases, thoracoplasty [modified] in 14 cases and muscle transfer in one case). All the above procedures were preceded by an intercostal drainage. In complicated pulmonary tuberculosis the operative procedures were as follows: lobectomy in 33 cases, pneumonectomy in 35 cases and thoracoplasty in 10 cases. Drainage of cold abscess with or without lymphnode resection was performed in 54 cases and in 16 cases of osteomyelitis of the ribs and sternum resection were necessary. All procedures were performed under the cover of antitubercular therapy and supportive treatment with the aim of resolution of process, obliteration of the empyema space, control of sepsis and improvement of activity performance. The morbidity was extensive and mortality was high in major procedures. Good results could be obtained in over 92% cases, and only 66.2% on major surgery cases.

Humans↗

PubMed1975

[Changes in pediatrics (author's transl)].

The decrease of infant mortality and the dramatic reduction of infectious diseases including Tuberculosis and Poliomyelitis have changed the problems in pediatrics. Today, sick children, who formerly had to be hospitalised are treated by the practitioner. In the hospitals, physicians are more dealing with chronic and malign diseases, where in addition, problems of psychological guidance of these children and their parents are of importance. Pediatrics should deal with all aspects of child welfare and development directly or indirectly related to health.

Child↗

PubMed1992

A multidimensional autoantibody analysis specifying systemic lupus erythematosus patients with neuropsychiatric symptomatology.

Utilizing a newly perfected multiple-response permutation procedure, we analyzed the autoantibody titer of systemic lupus erythematosus (SLE) patients during active and convalescent periods of disease, SLE patients without neurological involvement, and three other comparison groups (patients with active tuberculosis, patients with multiple sclerosis, and healthy normal controls). The multidimensional analysis we used distinguished those SLE patients with neurological involvement from the other SLE patients. Differences were noted by a univariate analysis measuring antibodies to single- and double-stranded DNA, poly (G), Sm, RNP, Ro, La, and gangliosides. Elevated concentrations of the common anti-DNA idiotype 16/6 were also noted among SLE patients with neuropsychiatric illness. This report stresses that increased disease activity in SLE patients with neuropsychiatric phenomena is reflected by their autoantibody profile.

Antibodies, Antinuclear↗

PubMed1978

Vitamin A deficiency in the Philippines: a study of xerophthalmia in Cebu.

An investigation of xerophthalmia was undertaken in four ecological zones in Cebu in the Philippines. One thousand seven hundred fifteen children aged 1 to 16 years were examined in 12 barrios. Clinical, biochemical and anthropometric data were collected from the children. Dietary and socioeconomic information was obtained from the households. Multivariate statistical techniques were used to examine factors possibly associated with xerophthalmia. Of children 47% had deficient or low serum vitamin A levels and 4.5% had clinical signs of xerophthalmia. Approximately 2% had both low serum vitamin A levels and clinical eye signs and were then defined as having active xerophthalmia. Vitamin A deficiency was more prevalent in males than females. Xerophthalmia was most common in the 4 to 6 year old age group. Diarrhea, roundworm infestation and measles were not positively correlated with xerophthalmia but whooping cough and tuberculosis were. Low intakes of carotene and vitamin A were associated with xerophthalmia but protein and fat intakes were not. A higher incidence of xerophthalmia occurred in children of working than nonworking mothers. Data on home production and use of vegetables and fruits are presented. The results of this study are being used to introduce three alternate intervention strategies to control xerophthalmia.

Adolescent↗

PubMed1998

Epidemiology of tuberculosis in Europe.

The regular decline in tuberculosis (TB) notification rates observed in several industrialized countries over the past two decades has levelled off or reversed in recent years. The aim of the present study is to review the epidemiological situation in Europe (updated to 1996), focusing on the annual risk of TB infection, mortality, notifications and age distribution of new smear-positive cases. Epidemiological data were obtained from national statistical reports produced by the Ministry of Health, the Global Tuberculosis Programme and Monitoring Project of the World Health Organization and the Euro TB Report on the feasibility study of Surveillance of Tuberculosis in Europe. The increasingly high mortality rates notified by the Baltic States, Romania, the Russian Federation and the countries previously belonging to the USSR and a few countries of the former Yugoslavia have been attributed to late patient detection and low cure rates, compounded, in some cases, with a lack of first-line drugs, resulting in the use of suboptimal regimens. In addition, higher death rates than in the general population have been described in risk groups, including prisoners and exprisoners, alcohol addicts and the unemployed. The analysis of notification rates and trends in Europe indicates that a stabilization in the number of notified cases or even a new decline had been achieved where efficient TB control programmes had been established or revitalized (e.g. in the majority of Western European and in several Central European countries).

Disease Notification↗

PubMed1997

The association between the bovine tuberculosis status of herds in the East Offaly Project Area, and the distance to badger setts, 1988-1993.

The proximity of farms to badger setts was compared between farms that had experienced a tuberculosis breakdown and those that had not, over the 6 year period from 1988 to 1993. The data were derived from a badger removal study conducted in East Offaly County in the Republic of Ireland. Badger removal began in 1989 and continued through 1993; by the end of 1990, approximately 80% of all badgers caught in the 6 year period had been removed. All badgers were examined, grossly, for evidence of tuberculosis. Tuberculosis status of the approximately 900 study herds was based on the results of the single intradermal comparative skin test and/or lesions of bovine tuberculosis. All herds were tested at least once annually. The number of herds experiencing bovine tuberculosis declined over the period, particularly in the years 1992 and 1993. The data on farm and badger sett location were stored and analysed, initially, in a geographical information system. Owing to the badger removal programme, the distance between the barn yard of a typical farm and the nearest occupied badger sett increased, by about 300 m year-1, and by about 600 m year-1 to the closest infected sett. In bivariate analyses, in the years 1988 and 1989, the risk of tuberculosis declined with increasing distance to a badger sett containing one or more tuberculous badgers. In multivariable logistic regression analyses, year and the average number of cattle tested per farm per year were controlled. A second identical analysis was conducted to control for the repeated observations on the same herds using generalised estimating equations. In both analyses, the risk of a multiple reactor tuberculosis breakdown decreased for herds at least 1000 m away from an infected badger sett, and increased as the number of infected badgers per infected sett increased. Despite the significantly reduced risk of a breakdown with increasing distance to infected badger setts, the relationship was not strong (sensitivity and specificity of the model in the low 70% range) and explained only 9-19% of tuberculosis breakdowns.

Animals↗

PubMed1998

Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy.

Increased levels of interleukin-6 (IL-6) and IL-8 are found in various immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3 +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml-1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8: 450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/- 1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of active disease. The low levels of sIL-6R in the presence of high levels of IL-6 in pleural effusions, and the high levels of sIL-6R in the presence of low levels of IL-6 in serum suggest that the expression or shedding of sIL-6R may be downregulated in the presence of excessive amounts of IL-6.

Adult↗

PubMed1997

Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 1. Newly-diagnosed pulmonary disease.

In this study, 206 previously untreated patients with sputum culture positive pulmonary tuberculosis were randomized to receive an injection of killed Mycobacterium vaccae as immunotherapy, or of saline as placebo, after 1 month of a 6-month chemotherapeutic regime. Not surprisingly in a disease for which there is good chemotherapy, the difference in numbers which were culture negative at the end of treatment was small, and the final outcome at the latest post-treatment follow-up did not reach statistical significance between the two arms of the study. Nonetheless, those receiving immunotherapy showed better progression in every parameter measured, suggesting faster and more complete cure. Whereas seven of 97 patients receiving immunotherapy required a course of re-treatment and five still had active disease after a mean follow-up of 2 yr, 13 of 109 placebo recipients required re-treatment and nine still had active disease at the end of the study. Only one patient receiving M. vaccae plus chemotherapy died of tuberculosis, compared with four of those receiving chemotherapy alone. A degree of drug resistance was shown by the bacilli cultured from 25 of 175 (14%) patients, and seven of them (4.0%) were multi-drug resistant. Fourteen patients received immunotherapy of whom 13 were cured, including all three of those showing multi-drug resistance. Of the 11 patients with drug resistance in the control group, eight were cured, and one patient with multi-drug-resistant disease died of tuberculosis during re-treatment.

Adolescent↗

PubMed2004

Cryptosporidiosis and other intestinal parasitic infections in patients with chronic diarrhea.

OBJECTIVE: To consider the relationship of the parasitic infections including cryptosporidium with chronic diarrhea. Also the effect of chronic disease as pulmonary tuberculosis (TB) and nosocomial infection on the occurrence rate of parasites in cases of chronic diarrhea. METHODS: Stool samples were collected from 205 patients in teaching, general, child and maternity hospitals in Basrah, Iraq, suffering from chronic diarrhea during 2000. Out of these patients, there were 40 patients with pulmonary TB and 50 inpatients with nosocomial infection. Also 175 apparently healthy individuals who have no episodes of diarrhea for at least 2-months were served as a control group. Direct smear method and then formalin ether sedimentation method were carried out for stool samples to detect intestinal parasites. Fecal smears were prepared from the sediment and stained by the modified Ziehl Neelsen stain for the recovery of red pink oocysts of cryptosporidium. RESULTS: Out of the 205 examined patients, cryptosporidium oocysts were found to be excreted in 20 (9.7%) patients in comparing to 1.1% of the control group. The difference is statistically significant. There were 109 (53.2%) patients found to be positive for intestinal parasitic infections compared to 26 (14.8%) of the control group. The difference is also statistically significant. Out of the 40 TB patients, 2 (5%) were found to excrete cryptosporidium oocysts and also 27 (67.3%) were positive for intestinal parasites. In addition, there were 4 (8%) excreting cryptosporidium oocysts and 23 (46%) infecting by intestinal parasites among the in patients with nosocomial infection. CONCLUSION: Both acid and non-acid fast parasites should be considered in the differential diagnosis of undiagnosed chronic diarrhea especially among patients with pulmonary TB or nosocomial infection.

Adolescent↗

PubMed1991

[A report of the state of health in Zimbabwe].

The health state in Zimbabwe is reported in terms of currently significant diseases, health statistics and hygiene and health care system in conjunction with the author's experiences as a visiting doctor in the country between June and September in 1989. Since independence in 1980 the government has transformed the colonial and racial health system and attempted to redistribute health care resources to the rural population. Similar to many countries in Central and East Africa, the accumulative number of AIDS cases in Zimbabwe is increasing rapidly despite the vigorous governmental campaigns launched in the early stage. The incidence of tuberculosis has also been rising since 1986 apparently in association with HIV spread in the country. On the other hand Zimbabwe is unique among the countries in Africa because rural clinics and preventive medicine such as immunization, basic sanitation and health education have been well-established throughout the country. As a result various communicable diseases common to the tropics and subtropics have been successfully controlled. The country now needs to improve quality and quantity of hospital medicine. While hospital facilities are available, the number of doctors, particularly in the district, is far below demand. Zimbabwe is one of the few countries in Africa where doctors trained in Japan could work efficiently and therefore it is suggested that it be considered as a country amenable to international medical cooperation.

Delivery of Health Care↗

PubMedDate not supplied

Influence of pre-treatment bacillary load on treatment outcome of pulmonary tuberculosis patients receiving DOTS under revised national tuberculosis control programme.

OBJECTIVE: To study the influence of initial bacillary load on sputum conversion rates and treatment outcome of new smear positive pulmonary tuberculosis patients. METHODS: A retrospective study was done among 2938 new smear positive pulmonary tuberculosis patients, registered at the peripheral centres, covering a population of 1.6 million in Delhi, India. The patients pre-treatment sputum smears were graded as 1+, 2+ or 3+ based on three samples. Patients were given intermittent short-course chemotherapy under supervision and the treatment outcome was analysed. RESULTS: Sputum conversion rates among patients graded as sputum 3+ and rest of the patients (combined graded sputum 1+ and 2+) at the end of two months were 62.2% and 76.8% respectively (p<0.001), and at the end of three months were 81.3% and 89.5% respectively (p<0.001). Cure rates among same group of patients were 76.6% and 85.1% respectively (p<0.001), and failure rates were 7.7% and 4.5% respectively (p<0.001). CONCLUSIONS: Under field conditions even with directly observed treatment (DOT) new smear positive patients with heavy bacillary load showed statistically significant poor sputum conversion rates at two and three months and higher failure rates as compared to patients with lesser bacillary load. To investigate possible reasons for this poor response and possible solutions further studies are needed.

Adolescent↗

PubMed2005

Correlates of Mycobacterium tuberculosis infection in a prison population.

Prisons represent a crucial setting for tuberculosis control. Currently, there is scarce information concerning Mycobacterium tuberculosis (MT) infection in European prisons, and no data are available for Italy. This study aims to describe the prevalence and correlates of MT infection in an Italian prison population. In this multicentre cross-sectional study, 1,247 inmates from nine prisons were recruited and asked to undergo questioning regarding socio-economic and demographic variables, tuberculin skin testing (TST), chest radiographs and testing for HIV, hepatitis B and hepatitis C virus infection. TST was positive in 17.9% of the 448 evaluable subjects. With multivariate logistic regression (performed among male inmates), MT infection was correlated with age (adjusted odds ratio (OR) 4.12 for inmates aged 31-40 yrs; 3.78 for those aged >40 yrs), being foreign-born (OR = 4.9), education < or =5 yrs (OR = 1.88) and length of detention (increased risk per yr: 11%). As with elsewhere in the world, the prison system in Italy features a population with an increased rate of Mycobacterium tuberculosis infection and at-risk rate for Mycobacterium tuberculosis transmission. Improved tuberculosis surveillance and control measures are deemed necessary in correctional facilities nationwide, especially for subjects with the above risk factors and those who are HIV infected, in whom the tuberculin skin testing can be misleading. The screening of entrants is particularly important to avoid undiagnosed smear-positive tuberculosis cases.

Adult↗

PubMed2026

Spatial clustering and transmission networks of multidrug-resistant tuberculosis in Rwanda: a national retrospective genomic and spatial epidemiological study.

BACKGROUND: Approximately 96% of rifampicin resistance/multidrug-resistant tuberculosis (RR/MDR-TB) cases in Rwanda result from direct transmission rather than acquired resistance. However, the nationwide spatial distribution and transmission dynamics of RR/MDR-TB remain poorly characterised. This study aims to analyse spatial patterns of RR/MDR-TB in Rwanda and explore relationships between spatial proximity and RR/MDR-TB strains' genetic relatedness. METHODS: We conducted a retrospective analysis of 249 confirmed RR-TB cases across Rwanda from 2017 to 2024, using the known geolocations of patients' residences. Spatial and space-time clustering was assessed using Kulldorff's scan statistics. Demographic and socioeconomic determinants were evaluated using multivariable regression. For 201 cases with whole-genome sequencing data, we performed transmission analysis using a 5-SNP threshold to define recent transmission clusters and investigated spatial relationships within genetically related strains. RESULTS: Significant spatial clustering of RR/MDR-TB was identified in 21 sectors, mainly in Nyarugenge, southern Gasabo and western Kicukiro (relative risk: 10.06; p<0.001). Our multivariable analysis showed that population density is positively associated with case notification rates. Molecular analysis revealed 88.5% of cases belonged to genotype clusters defined using a 12-SNP threshold, with 73.6% forming clusters at a strict 5-SNP threshold. Spatial K-function analysis of the six major clusters revealed heterogeneous transmission patterns, characterised by both tightly clustered outbreaks and regional transmission networks that spanned administrative boundaries. Most clusters (5/6) extended beyond Kigali, indicating that transmission networks operate across administrative divides. CONCLUSION: RR/MDR-TB in Rwanda shows significant spatial clustering with transmission occurring through both localised and regional networks. Integrating genomic and spatial data reveals transmission patterns that extend beyond household contacts and administrative boundaries. These findings underscore the need to implement geographically targeted interventions that address community-level transmission to control RR/MDR-TB in Rwanda effectively.

Rwanda↗