Economic evaluation of laparoscopic and open inguinal herniorrhaphies: the effect of cost-containment measures and internal hospital policy decisions on costs and charges.

BACKGROUND: Totally extraperitoneal (TEP) repairs of inguinal hernias, despite having a favorable clinical outcome are often criticized due to higher costs and charges associated with this approach. We, therefore, present a comparison of direct costs and charges between TEP and open tension-free (OPN) repairs, emphasizing the effect of cost-containment measures on the part of surgeons and the hospital's charging (rate-setting) policies on these measurements. METHODS: Itemized direct costs, charges, and reimbursements were determined for 41 TEP and 44 OPN unilateral repairs done between January 1997 and December 1999. Multiple sensitivity analyses were done to evaluate the effect of cost-containment measures and the hospital's rate-setting policies on the differences in costs and charges between the two procedures. The hospital's profits were expressed as profit-cost ratios. RESULTS: The mean direct cost for a TEP repair was $128.58 more than the OPN repair ($795.07[+/-65] vs 666.49 [+/-52]). However, mean charges and hospital reimbursement were $2,139.80 and $1,679.87, respectively, more for the TEP repairs. The profit-cost ratio was significantly higher in the TEP group (2.85:1 vs 1.07:1, P<.001). We found that 79.8% of the difference in direct costs vs 29% of the difference in charges between the two procedures was sensitive to cost-containment measures. Forty-five percent of the difference in charges was due to the hospital's nonuniform rate-setting policies. Long-term follow-up (38 months) showed no recurrence for either procedure. CONCLUSIONS: The direct cost of TEP repairs with the minimal use of disposable instruments in a high-volume center is comparable to the OPN repair. However, due to differences in the hospital's charging policies, TEP repair would appear to be an expensive alternative from the payer's point of view.

Value of chest radiography in a tuberculosis prevention programme for HIV-infected people, Botswana.

To exclude tuberculosis, WHO/UNAIDS recommends considering medical history, symptom screen, and chest radiograph before starting tuberculosis prevention in people infected with HIV. The value of a chest radiograph for this purpose is unknown. We prospectively assessed 935 HIV-infected outpatients seeking isoniazid preventive therapy. Of 935 patients, 692 (74%) had no signs or symptoms of tuberculosis. Of these 692, 123 (18%) were lost during the chest radiograph process, and one (0.2%) of the remaining 563 was diagnosed with tuberculosis on the basis of the chest radiograph. A screening chest radiograph should not be required routinely for asymptomatic people taking isoniazid as preventive treatment in settings able to screen for signs and symptoms of tuberculosis.

Cost-effectiveness of home-based care versus hospital care for chronically ill tuberculosis patients, Francistown, Botswana.

SETTING: Francistown, Botswana, 1999. OBJECTIVE: To determine the affordability and cost-effectiveness of home-based directly observed therapy (DOT) compared to hospital-based DOT for chronically ill tuberculosis (TB) patients, and to describe the characteristics of patients and their caregivers. DESIGN: Costs for each alternative strategy were analysed from the perspective of the health system and caregivers, in 1998 US dollars. Caregiver costs were assessed using a structured questionnaire administered to a sample of 50 caregivers. Health system costs were assessed using interviews with relevant staff and documentary data such as medical records and expenditure files. These data were used to calculate the average cost of individual components of care, and, for each alternative strategy, the average cost per patient treated. Cost-effectiveness was calculated as the cost per patient compliant with treatment. The characteristics of caregivers and patients were assessed using demographic and socio-economic data collected during interviews, and medical records. RESULTS: Overall, home-based care reduced the cost per patient treated by 44% compared with hospital-based treatment (dollars 1657 vs. dollars 2970). The cost to the caregiver was reduced by 23% (dollars 551 vs. dollars 720), while the cost to the health system was reduced by 50% (dollars 1106 vs. dollars 2206). The cost per patient complying with treatment was dollars 1726 for home-based care and dollars 2970 for hospitalisation. Caregivers were predominantly female relatives (88%), unemployed (48%), with primary school education or less (82%), and with an income of less than dollars 1000 per annum (71%). Of those patients with an HIV test result, 98% were HIV-positive. CONCLUSION: Home-based care is more affordable and cost-effective than hospital-based care for chronically ill TB patients, although costs to caregivers remain high in relation to their incomes. Structured home-based DOT should be included as a component of the National Tuberculosis Control Programme in Botswana.

The validity of HIV testing using sputum from suspected tuberculosis patients, Botswana, 2001.

SETTING: The World Health Organization recommends that sentinel HIV surveillance be conducted on tuberculosis patients. However, serum HIV testing is complicated in the TB clinic context, and may not be acceptable to patients. DESIGN: To determine the utility of the OraQuick HIV-1/2 Assay for the detection of HIV antibodies in sputum, we consecutively enrolled adult in-patients in Botswana who had sputum sent for acid-fast bacilli testing and serum sent for HIV ELISA testing. OraQuick HIV-1/2 Assay was applied to gingival secretions according to manufacturer's guidelines, and was also dipped into sputum specimens. A subset of 60 sputum specimens was also serially tested up to 72 hours after collection. RESULTS: Of 377 patients, 84% were HIV-positive by serum ELISA. Compared with serum ELISA, the OraQuick HIV-1/2 Assay detected HIV in gingival secretions with 98.4% sensitivity and 98.3% specificity (95%CI 97-99 and 92-100, respectively), and 97.1% sensitivity and 98.3% specificity on initial sputum specimens (95%CI 95-99 and 92-100, respectively). OraQuick HIV-1/2 Assay performance on sputum declined slightly when tested up to 72 hours after collection. CONCLUSIONS: When applied to sputum specimens, the OraQuick HIV-1/2 Assay demonstrates sensitivity and specificity comparable to its intended application on gingival secretions. This novel testing method will be valuable in anonymous sentinel HIV surveillance surveys among tuberculosis patients.

Etiology of pulmonary infections in predominantly HIV-infected adults with suspected tuberculosis, Botswana.

SETTING: In countries with high HIV rates, diagnosis of lower respiratory disease etiology is both challenging and clinically important. OBJECTIVE: To determine the etiology of lower respiratory tract disease among persons with suspected tuberculosis (TB) and abnormal chest X-rays in a setting with very high HIV seroprevalence. DESIGN: Cross-sectional prevalence data from a prospective cohort of predominantly hospitalized adults with suspected TB in Botswana, January-December 1997. RESULTS: Of 229 patients, 86% were HIV-positive and 71% had a pathogen identified. TB was confirmed in 52%, 17% had acute mycoplasma pneumonia, 3% had Pneumocystis carinii, 27% grew a bacterial pathogen from sputum and 8% from blood. Ninety-four per cent of TB diagnoses were made through expectorated sputum and only 5% of TB cases were diagnosed by sputum induction alone. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis had positive and negative predictive values of 94% and 59%, respectively. Male sex, cough < 2 weeks, and tuberculin skin test > or = 5 mm were independently associated with culture-positive TB among persons with negative acid-fast bacilli smears. Co-infection with two or more pathogens occurred in 25%. CONCLUSIONS: Mycoplasma pneumoniae infection was quite common despite clinical suspicion of TB, and sputum induction and PCR did not significantly improve our ability to diagnose TB, although clinical presentation had some predictive value.

Control of anti-tuberculosis drug resistance in Botswana.

SETTING: Botswana, where in 2000 the prevalence of human immunodeficiency virus (HIV) infection among adults was 38%, and the tuberculosis (TB) rate was 591/100,000. A 1995-1996 survey demonstrated low levels of anti-tuberculosis drug resistance. OBJECTIVE: Because TB drug resistance may increase rapidly in HIV-infected populations, a second survey was undertaken in 1999 to determine any increase in anti-tuberculosis drug resistance. DESIGN: Sputum specimens positive for acid-fast bacilli from patients without prior TB treatment (new patients), and all sputum specimens from patients reporting prior TB treatment (retreatment patients) were collected nationwide. Specimens were cultured for Mycobacterium tuberculosis and tested for resistance to isoniazid, rifampicin, ethambutol, and streptomycin. RESULTS: From January to May 1999, 783 patients were consecutively enrolled from all districts. Of these, 483 (61.7%) were male, the median age was 33 years, and 82% were new patients. Drug resistance occurred in 6.3% of new patients (95 % confidence interval [CI] 4.6-8.6) and 22.8% of retreatment patients (95% CI 16.5-30.1). Resistance to at least isoniazid and rifampicin was found in 0.5% of new (95% CI 0.1-1.3) and 9.0% of retreatment patients (95% CI 5.1-14.5). CONCLUSION: Anti-tuberculosis drug resistance remains relatively low in Botswana, probably as a result of a well-functioning TB program. Periodic surveys will be essential to adequately determine any significant trend.

Comparison of varicella-zoster virus ORF47 protein kinase and casein kinase II and their substrates.

ORF47, a serine/threonine protein kinase encoded by varicella-zoster virus (VZV), has often been compared to the ubiquitous cellular kinase, casein kinase II (CKII). However, no direct comparison of the two protein kinases has been carried out. Herein, we show that the ORF47 kinase was resistant to heparin, while CKII activity is profoundly inhibited by the acidic molecule in vitro. ORF47 required the presence of polyamines (aliphatic, positively-charged molecules) for in vitro activity. When polyamines were depleted from MeWo cells prior to VZV infection by pretreatment with D,L-alpha-difluoromethylornithine, VZV replication was reduced by 80%. Finally, the substrate specificity of the ORF47 kinase was defined using an in vitro assay. The ORF47 kinase phosphorylated maltose-binding protein, the mouse IgG2A heavy chain, the rabbit IgG heavy chain, casein, VZV ORF62, and VZV ORF63. The ORF47 kinase failed to phosphorylate an ORF62 truncation mutant, glutathione-S-transferase, or VZV gB. In contrast, CKII weakly phosphorylated VZV gB in vitro. By analyzing the sequences of these substrates, the minimal ORF47 consensus sequence was deduced to be the following motif: S/T-X-D/E-D/E, with a marked preference for additional acidic amino acids in the -1 and +1 position.

Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana.

OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana. DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection. METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results. Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed. A positive test was defined as > or = 10 mm induration. Skin test results were compared with results obtained from a population survey of children of similar age from the same community. RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005). Of the infected children, 22 (78.6%) were contacts of a close female relative. The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001). In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006). CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M. tuberculosis during the era of HIV. However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS.

Phosphorylation by the varicella-zoster virus ORF47 protein serine kinase determines whether endocytosed viral gE traffics to the trans-Golgi network or recycles to the cell membrane.

Like all alphaherpesviruses, varicella-zoster virus (VZV) infection proceeds by both cell-cell spread and virion production. Virions are enveloped within vacuoles located near the trans-Golgi network (TGN), while in cell-cell spread, surface glycoproteins fuse cells into syncytia. In this report, we delineate a potential role for serine/threonine phosphorylation of the cytoplasmic tail of the predominant VZV glycoprotein, gE, in these processes. The fact that VZV gE (formerly called gpI) is phosphorylated has been documented (E. A. Montalvo and C. Grose, Proc. Natl. Acad. Sci. USA 83:8967-8971, 1986), although respective roles of viral and cellular protein kinases have never been delineated. VZV ORF47 is a viral serine protein kinase that recognized a consensus sequence similar to that of casein kinase II (CKII). During open reading frame 47 (ORF47)-specific in vitro kinase assays, ORF47 phosphorylated four residues in the cytoplasmic tail of VZV gE (S593, S595, T596, and T598), thus modifying the known phosphofurin acidic cluster sorting protein 1 domain. CKII phosphorylated gE predominantly on the two threonine residues. In wild-type-virus-infected cells, where ORF47-mediated phosphorylation predominated, gE endocytosed and relocalized to the TGN. In cells infected with a VZV ORF47-null mutant, internalized VZV gE recycled to the plasma membrane and did not localize to the TGN. The mutant virus also formed larger syncytia than the wild-type virus, linking CKII-mediated gE phosphorylation with increased cell-cell spread. Thus, ORF47 and CKII behaved as "team players" in the phosphorylation of VZV gE. Taken together, the results showed that phosphorylation of VZV gE by ORF47 or CKII determined whether VZV infection proceeded toward a pathway likely involved with either virion production or cell-cell spread.

Pathology and causes of death in a group of 128 predominantly HIV-positive patients in Botswana, 1997-1998.

BACKGROUND: Little is known about causes of death in countries of southern Africa seriously affected by the HIV/AIDS epidemic. METHODS: After obtaining informed consent, autopsies were performed on 128 mainly hospitalised adults in Francistown, Botswana, between July 1997 and June 1998. Criteria for case selection included those who died before a diagnosis could be established, those whose condition deteriorated unexpectedly during hospitalization, and those who had respiratory disease. This represented 14% of adult medical patients who died in hospital during the study period. RESULTS: Of the 128 patients, 104 (81%) were HIV-positive. Among HIV-positive patients, the most common pathologic findings were tuberculosis (TB) (40%), bacterial pneumonia (23%), Pneumocystis carinii pneumonia (11%), and Kaposi's sarcoma (11%); these conditions were the cause of death in 38%, 14%, 11%, and 6%, respectively. Of the 40 pulmonary TB cases, 90% also had disseminated extra-pulmonary TB. Chest radiology could not reliably distinguish the pathologies pre-mortem. CONCLUSIONS: TB was the leading cause of death in our series of HIV-positive adults in Botswana, selected towards those with chest disease; in most, it was widely disseminated. Bacterial pneumonia also played an important role in mortality. Pneumocystis carinii pneumonia was present, but relatively uncommon.

Use of a computerized tuberculosis register for automated generation of case finding, sputum conversion, and treatment outcome reports.

SETTING: Tuberculosis (TB) rates in southern Africa have increased dramatically in recent years. Provision of accurate data for surveillance, program management, and supervision is increasingly essential. OBJECTIVE: To develop software that would provide more efficient collection, compilation, and analysis of TB data on an ongoing basis. DESIGN: The 'Electronic TB Register' is a user-friendly, Epi-Info based software program based on the WHO/IUATLD format of recording and reporting. Individual records from the TB registry are entered in a program that provides interactive support. The software provides several patient management and supervision functions, such as lists of defaulters. Finally, it generates standard quarterly and annual reports on case-finding, sputum conversion, and cohort analysis, and provides graphs of trends and maps of TB indicators. RESULTS: The 'Electronic TB Register' software has been successfully implemented in five pilot projects in southern Africa. User acceptance has been high and quality of data has improved, although timeliness remains unchanged. Factors critical for success include a functioning, paper-based system, involvement of staff from the TB program, health information systems, and health facilities, ongoing training, and backup support. CONCLUSIONS: The 'Electronic TB Register' is a potentially powerful tool for surveillance, management, and supervision for countries with well-functioning paper-based recording and reporting systems.

Dedicated minimally invasive surgery suites increase operating room efficiency.

BACKGROUND: The rapid adoption of laparoscopic surgery since the late 1980s added tremendous complexity into the operating room (OR) environment. For each case, a plethora of additional equipment-including monitors, video equipment, wiring, tubing, and cords-had to be set up, prolonging OR turnover time and decreasing OR efficiency. In 1993, the concept of designated minimally invasive surgery (MIS) suites was introduced. MIS suites integrated monitors and video equipment into the OR on ceiling-mounted columns and moved the controls to a centralized nursing station. The overall effect of this innovation on OR efficiency has not been measured. METHODS: Five RNs with varying degrees of MIS experience were instructed on video setup and put-away criteria and then timed while performing a set of standardized tasks. Each set of tasks was performed twice using a standardized surgery model. Differences in setup and put-away times between MIS suites and standard ORs were tested using the t-test for paired comparisons. RESULTS: The mean +/- standard deviation (SD) video setup times were 27.9 +/- 5.3 sec (MIS) and 254.3 +/- 54.0 sec (standard); the put-away times were 19.8 +/- 2.7 sec (MIS) and 222.3 +/- 26.0 sec (standard). The mean difference +/- standard error (SE) in both the setup (226.4 +/- 16.9 sec, p = 0.0001) and put-away times (202.5 +/- 8.6, p = 0.0001) were large and statistically significant. CONCLUSION: Using a simulation model, we have demonstrated that the use of a MIS suite reduces video setup and put-away time significantly, with the potential for significant associated cost savings. This provides just one justification for the high cost of building such "ORs of the future."

Varicella-zoster virus ORF47 protein serine kinase: characterization of a cloned, biologically active phosphotransferase and two viral substrates, ORF62 and ORF63.

Varicella-zoster virus (VZV) codes for a protein serine kinase called ORF47; the herpes simplex virus (HSV) homolog is UL13. No recombinant alphaherpesvirus serine kinase has been biologically active in vitro. We discovered that preservation of the intrinsic kinase activity of recombinant VZV ORF47 required unusually stringent in vitro conditions, including physiological concentrations of polyamines. In this assay, ORF47 phosphorylated two VZV regulatory proteins: the ORF62 protein (homolog of HSV ICP4) and the ORF63 protein (homolog of HSV ICP22). Of interest, ORF47 kinase also coprecipitated ORF63 protein from the kinase assay supernatant.

Risk factors for positive mantoux tuberculin skin tests in children in San Diego, California: evidence for boosting and possible foodborne transmission.

OBJECTIVES: Source case finding in San Diego, California, rarely detects the source for children with tuberculosis (TB) infection or disease. One third of all pediatric TB isolates in San Diego are Mycobacterium bovis, a strain associated with raw dairy products. This study was conducted to determine risk factors for TB infection in San Diego. DESIGN: Case-control study of children /=10 mm) Mantoux skin test (TST) were matched by age to 1 to 2 children with negative TST from the same clinic. We assessed risk factors for TB infection through parental interview and chart review. RESULTS: A total of 62 cases and 97 controls were enrolled. Eleven cases and 25 controls were excluded from analysis because of previous positive skin tests. Compared with controls, cases were more likely to have received BCG vaccine (73% vs 7%, odds ratio [OR] 44), to be foreign born (35% vs 11%, OR 4.3), and to have eaten raw milk or cheese (21% vs 8%, OR 3.76). The median time between the most recent previous TST and the current test was 12 months for cases and 25 months for controls. Other factors associated with a positive TST included foreign travel, staying in a home while out of the country, and having a relative with a positive TST. There was no association between contact with a known TB case. In a multivariable model, receipt of BCG, contact with a relative with a positive TST, and having a previous TST within the past year were independently associated with TB infection. CONCLUSIONS: We identified several new or reemerging associations with positive TST including cross border travel, staying in a foreign home, and eating raw dairy products. The strong associations with BCG receipt and more recent previous TST may represent falsely positive reactions, booster phenomena, or may be markers for a population that is truly at greater risk for TB infection. Unlike studies conducted in nonborder areas, we found no association between positive TB skin tests and contact with a TB case or a foreign visitor. Efforts to control pediatric TB in San Diego need to address local risk factors including consumption of unpasteurized dairy products and cross-border travel. The interpretation of a positive TST in a young child in San Diego who has received BCG is problematic.

The minimally invasive surgical suite enters the 21st century. A discussion of critical design elements.

Most minimally invasive surgical procedures are now performed in operating rooms that were originally designed for traditional open surgery. Laparoscopic instrumentation such as insufflators, light sources, and camera control units must be placed on one or more equipment carts. After the cart has been moved into place, insufflation tubing, video cables, light cords, cautery lines, and foot controls must be positioned and connected. This cart-based paradigm restricts the ergonomic configuration of the operating room and creates potential mechanical, electrical, and biological hazards to the patient and operating room staff. In order to decrease clutter, ease personnel movement, improve ergonomics, maintain the sterile field, and facilitate the use of advanced imaging, communication, and display devices, an appropriately designed operating environment is essential. Herein we detail both the theoretical and practical aspects of the design and describe the implementation and utilization of such a suite in our hospital. These design elements may prove to be critical to the next generation of minimally invasive surgical suites and will facilitate future advanced laparoscopic procedures.

Substandard tuberculosis drugs on the global market and their simple detection.

SETTING: The prevalence of substandard anti-tuberculosis drugs is unknown. To maximize the effectiveness of tuberculosis (TB) control efforts, simple, inexpensive drug quality screening methods are needed. DESIGN: Isoniazid (INH) and rifampin (RMP) single- and fixed-dose combination (FDC) formulations were collected from selected TB programs and pharmacies in Colombia, Estonia, India, Latvia, Russia and Vietnam. Samples were screened using a recently developed thin-layer chromatography (TLC) kit. All abnormal samples and a 40% random sample of normal formulations were further analyzed using confirmatory techniques. Samples outside of 85% to 115% of stated content, and/or containing compounds other than the stated drug, were defined as being substandard. RESULTS: Overall, 10% (4/40) of all samples, including 13% (4/30) RMP samples, contained <85% of stated content. More FDCs (5/24, 21%) than single-drug samples (2/16, 13%) were substandard. A comparison of TLC with the confirmatory analysis for RMP analysis showed a sensitivity of 100% (4/4), a specificity of 92% (24/26), a positive predictive value (PPV) of 67% (4/6), and a negative predictive value (NPV) of 100% (24/24). An analysis of INH showed a specificity of 90% (9/10). However, sensitivity, PPV, and NVP could not be determined. CONCLUSION: A substantial number of anti-tuberculosis drugs from several countries, in particular FDCs, were found to be substandard. Such drugs may contribute to the creation of drug-resistant TB. TLC is an effective, convenient, and inexpensive method for the detection of substandard drugs.

Risk factors for latent tuberculosis infection among children in New York City.

OBJECTIVE: Although identification and appropriate treatment of children with latent tuberculosis (TB) infection (LTBI) is considered critical to the control and elimination of TB in the United States, there are limited data on risk factors for LTBI in pediatric populations. METHODS: To further improve targeted screening for LTBI, we performed a matched case-control study from September 1996 to December 1998. We actively surveyed 24 primary care clinics serving Northern Manhattan and Harlem twice monthly for case participants 1 to 5 years old with LTBI, defined as a child with a Mantoux tuberculin skin test (TST) >/=10 mm and a normal chest radiograph. Two age- and clinic-matched control participants with TSTs equal to 0 mm were enrolled per case. To determine risk factors for LTBI, a bilingual research worker reviewed the medical records of study participants and administered a questionnaire to the parents of participants. RESULTS: We enrolled 96 cases and 192 controls whom did not differ by age, gender, ethnicity, and race; overall, the mean age of participants was 2.9 years, 51% were male, 80% were Hispanic, and 9% black. Logistic regression analysis demonstrated that contact with an adult with active TB, foreign birth, foreign travel, and a relative with a positive TST were predictive of case status. In contrast, a history of a previous negative TST proved protective and BCG immunization was not an independent risk factor for a positive TST, suggesting that boosting was not important in this population. CONCLUSIONS: We identified several risk factors for LTBI in children that can be used to refine targeted surveillance for TB among Hispanic immigrant populations in the United States.

Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients.

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.

Completeness and timeliness of treatment initiation after laboratory diagnosis of tuberculosis in Gaborone, Botswana.

SETTING: Gaborone, the capital of Botswana. OBJECTIVE: To determine the time from positive sputum smear microscopy for acid-fast bacilli (AFB) to initiation of therapy, and to identify risk factors for delays. DESIGN: Retrospective cohort study of medical records and surveillance data for patients with positive smear microscopy and newly diagnosed tuberculosis (TB) from January to May 1997. Treatment delay was defined as more than 2 weeks from the first positive sputum smear to the initiation of TB treatment. RESULTS: Of 127 patients identified, 15 (11.8%) had treatment delay, 13 (10.2%) had an incomplete workup (only one smear performed) and were not registered for TB treatment, and six (4.5%) had two or more positive smears but were not registered for TB treatment. Risk factors for treatment delay or non-registration included TB patients who had been diagnosed in a hospital outpatient setting vs. a clinic (RR 2.9, 95% CI 1.2-3.6, P = 0.02), or in a high volume vs. low volume clinic (RR 2.2, 95% CI 1.2-5.3, P = 0.01). CONCLUSION: More than a quarter of the smear-positive TB patients identified had treatment delay or no evidence of treatment initiation. Proper monitoring of laboratory sputum results and suspect TB patient registers could potentially reduce treatment delays and patient loss.

Transmission of Mycobacterium tuberculosis among employees in a US government office, Gaborone, Botswana.

SETTING: A US government office located in Botswana where two office employees, one negative and one positive for the human immunodeficiency virus (HIV), were diagnosed with pulmonary tuberculosis (TB) in January 1998. One employee had been symptomatic with untreated laryngeal TB for 8 months. OBJECTIVE: To determine the extent of and risk factors for TB transmission in the office. METHODS: Office contacts were interviewed and a tuberculin skin test (TST) was performed. A positive TST was defined as > or = 10 mm induration for employees from countries where TB is highly endemic, and as > or = 5 mm induration for those from low prevalence counties. RESULTS: Of 79 office contacts investigated, 54/57 (94.7%) born in high TB prevalence countries had a positive TST compared with 4/22 (18.2%) from low prevalence countries (RR 5.1, 95% CI 2.1-12.7, P < 0.001). Of 20 US-born contacts, three (15%) had documented TST conversion, two of whom were co-workers of the employee with laryngeal TB. Isolates of Mycobacterium tuberculosis from the TB cases had matching DNA fingerprints. CONCLUSION: Delayed diagnosis in a setting of high TB prevalence may have contributed to transmission within a US government office located in Botswana. Transmission may have been underestimated due to the high background prevalence of tuberculous infection in the population. Recent tuberculous transmission to persons living with HIV infection may be playing an important role in the escalating TB epidemic in Africa.