Second-line drug-resistant TB and associated risk factors in Karakalpakstan, Uzbekistan.

BACKGROUND: Drug-resistant TB (DR-TB) remains a major public health threat. In 2022, Uzbekistan reported 2,117 cases of DR-TB, with 69% tested for fluoroquinolone resistance. Limited information is available on the prevalence of resistance to bedaquiline, linezolid, and fluoroquinolone, which are key components of the all-oral treatment regimen for rifampicin-resistant TB in Uzbekistan. METHODS: A retrospective study was conducted using extensive programmatic data from 2019 to 2023 in Uzbekistan. We assessed second-line drug-resistant TB (SLDR-TB) rates using phenotypic drug susceptibility testing (pDST). Demographic and clinical characteristics associated with SLDR-TB were analysed using multivariable logistic regression models based on the Allen-Cady approach. RESULTS: In total, 2,405 patients with TB who had undergone pDST were included (median age 40 years, 47% female). The overall SLDR-TB resistance rate was 24% (95% CI 22-26). Prevalence of resistance to bedaquiline, linezolid, moxifloxacin, levofloxacin, and amikacin were respectively 3.1%, 0.8%, 15%, 13%, and 12%. Risk factors for SLDR-TB were resistance to rifampicin and/or isoniazid, exposure to clofazimine, retreatment status, contact with drug-susceptible TB case or DR-TB case, and diabetes. CONCLUSIONS: The high prevalence of SLDR-TB is of major concern, emphasising the need for baseline pDST in RR-TB treatment. Identified risk factors can aid early detection of at-risk individuals and inform clinical practice.

CONTEXTE: La TB résistante aux médicaments (DR-TB) reste une menace majeure pour la santé publique. En 2022, l'Ouzbékistan a signalé 2 117 cas de DR-TB, dont 69% ont été testés pour la résistance aux fluoroquinolones. Les informations sur la prévalence de la résistance à la bédaquiline, au linézolide et aux fluoroquinolones, qui sont des composants clés du traitement entièrement oral de la TB résistante à la rifampicine en Ouzbékistan, sont limitées. MÉTHODES: Une étude rétrospective a été menée en utilisant des données programmatiques exhaustives de 2019 à 2023 en Ouzbékistan. Nous avons évalué les taux de TB résistante aux médicaments de deuxième ligne (SLDR-TB, pour l'anglais, « second-line drug-resistant TB ¼) en utilisant des tests de sensibilité phénotypique aux médicaments (pDST). Les caractéristiques démographiques et cliniques associées à la SLDR-TB ont été analysées à l'aide de modèles de régression logistique multivariés basés sur l'approche Allen-Cady. RÉSULTATS: Au total, 2 405 patients atteints de TB ayant subi un pDST ont été inclus (âge médian de 40 ans, 47% de femmes). Le taux global de résistance à la SLDR-TB était de 24% (CI à 95% 22­26). La prévalence de la résistance à la bédaquiline, au linézolide, à la moxifloxacine, à la lévofloxacine et à l'amikacine était respectivement de 3,1%, 0,8%, 15%, 13% et 12%. Les facteurs de risque de SLDR-TB comprenaient la résistance à la rifampicine et/ou à l'isoniazide, l'exposition à la clofazimine, le statut de retraitement, le contact avec un cas de TB sensible aux médicaments ou de DR-TB, et le diabète. CONCLUSIONS: La prévalence élevée de la SLDR-TB est une source de préoccupation majeure, soulignant la nécessité de réaliser des pDST de base dans le traitement de la TB résistante à la rifampicine. Les facteurs de risque identifiés peuvent aider à la détection précoce des individus à risque et à informer la pratique clinique.

A 10-year review of isoniazid-resistant TB management in Uzbekistan 2009-2020.

BACKGROUND: Isoniazid (INH, H) resistance is the most common drug-resistant TB pattern, with treatment success rates lower than those in drug-susceptible TB. The WHO recommends a 6-month regimen of rifampicin (RIF, R), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (Lfx) (6REZLfx) for INH-resistant, RIF-susceptible TB (HRRS-TB). Uzbekistan has a high burden of TB (62/100,000 population) and multidrug-resistant TB (12/100,000 population). METHODS: We conducted a retrospective, descriptive study of microbiologically confirmed HRRS-TB using routinely collected programmatic data from 2009 to 2020. RESULTS: We included 854 HRRS-TB cases. Treatment success was 80.2% overall. For REZLfx, the treatment success rate was 92.0% over a short treatment duration, with no amplifications to RIF or second-line anti-TB drug resistance. We documented 46 regimens with REZLfx plus linezolid (success 87.0%) and 539 regimens using kanamycin or capreomycin (success 76.6%). We identified 37 treatment failures (4.3%), 30 deaths (3.5%), 25 resistance amplifications (2.9%), including eight to RIF (0.9%), and 99 lost to follow-up (LTFU) cases (11.6%). Unsuccessful outcomes were more common with older age, diabetes, chest X-ray cavities, smear positivity, smear-positive persistence, and male sex. LTFU was more common with injection-containing regimens. CONCLUSIONS: REZLfx is a safe and effective first-line treatment for INH-resistant, RIF-susceptible TB. Treatment success was lower and LTFU was higher for injection-containing regimens.

CONTEXTE: La résistance à l'isoniazide (INH, H) est la forme de TB pharmacorésistante la plus courante, avec des taux de réussite thérapeutique inférieurs à ceux de la TB pharmacosensible. L'OMS recommande un traitement de six mois à base de rifampicine (RIF, R), d'éthambutol (EMB, E), de pyrazinamide (PZA, Z) et de lévofloxacine (LFx) (6REZLfx) pour la TB résistante à l'INH et sensible au RIF (HRRS-TB). En Ouzbékistan, la prévalence de la TB est élevée, avec un taux de 62 cas pour 100 000 habitants, ainsi que de la TB multirésistante, avec un taux de 12 cas pour 100 000 habitants. MÉTHODES: Une étude rétrospective et descriptive de la HRRS-TB confirmée microbiologiquement a été réalisée en utilisant des données programmatiques collectées de manière routinière de 2009 à 2020. RÉSULTATS: Nous avons inclus 854 cas de HRRS-TB. Le taux de réussite du traitement global était de 80,2%. Pour le traitement avec REZLfx, le taux de réussite était de 92,0% sur une courte durée, sans résistance au RIF ni aux médicaments antituberculeux de deuxième ligne. Nous avons observé 46 schémas thérapeutiques associant REZLfx et linézolide avec un taux de réussite de 87,0%, ainsi que 539 schémas thérapeutiques utilisant la kanamycine ou la capréomycine avec un taux de réussite de 76,6 %. Nous avons enregistré 37 échecs thérapeutiques (4,3%), 30 décès (3,5%), 25 cas de résistance amplifiée (2,9%), dont huit au RIF (0,9%), et 99 cas de perte de suivi (LTFU, pour l'anglais « loss to follow-up ¼) (11,6%). Les échecs étaient plus fréquents chez les patients âgés, diabétiques, présentant des cavités à la radiographie thoracique, un frottis positif persistant et de sexe masculin. La prolongation de la durée d'utilisation était plus fréquente avec les schémas contenant des injections. CONCLUSIONS: REZLfx est un traitement de première intention sûr et efficace contre la TB résistante à l'INH et sensible aux RIF. Le succès du traitement était plus faible et le nombre de LTFU était plus élevé pour les schémas contenant des injections.

Household drug-resistant TB contact tracing in Tajikistan.

BACKGROUND: Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently.METHODS: We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis.RESULTS: We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years.CONCLUSION: RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan.

BACKGROUND: Bedaquiline (BDQ) is widely used in the treatment of rifampicin-resistant TB (RR-TB). However, resistance to BDQ is now emerging. There are no standardised regimens for BDQ-resistant TB. This study aims to share experience in managing primary BDQ-resistant TB.METHODS: We performed a retrospective study of patients treated for RR-TB in Karakalpakstan, Uzbekistan, from January 2017 to March 2022. We identified patients with resistance to BDQ with no history of BDQ exposure. We describe baseline characteristics, treatment and follow-up of these patients.RESULTS: Twelve of the 1,930 patients (0.6%) had baseline samples resistant to BDQ with no history of BDQ exposure, 75% (9/12) of whom had been previously treated for TB. Ten (83.3%) were resistant to fluoroquinolones; respectively 66% and 50% had culture conversion by Month 3 and Month 6. The interim treatment outcomes were as follows: unfavourable treatment outcomes (3/12, 25%), favourable outcomes (2/12, 17%); the remaining seven (58%) were continuing treatment.CONCLUSIONS: A large proportion of the cases had previously been treated for TB and had TB resistant to quinolone. Both patients who had not experienced culture conversion by Month 3 had an unfavourable treatment outcome. Therefore, we recommend monthly monitoring of culture status for patients on treatment regimens for BDQ resistance.

Epidemiology of chlamydial infection: are we losing ground?

Are we losing ground in our efforts to control sexually transmitted Chlamydia trachomatis infection? Before we can answer this question, we must first consider recent trends in Chlamydia from around the world to establish a baseline for understanding the possible explanations underlying these data.

Incorporating a social networking approach to enhance contact tracing in a heterosexual outbreak of syphilis.

OBJECTIVE: This report describes the outcomes of a social networking approach (SNA) in a heterosexually transmitted syphilis epidemic by street nurses in British Columbia, Canada. METHODS: Street nurses used SNA interviewing cues, environmental observation, peer outreach, serial interviewing, conducted blood tests, and offered treatment on the street. Rates of cases of syphilis identified by outreach nurses and cases linked to another case were compared before and after adoption of an SNA. RESULTS: SNA resulted in a significantly increased proportion of cases identified by the street nurses (p = 0.01) and increased the percentage of cases linked to a previous case (p = 0.03). CONCLUSION: This preliminary study confirms that SNA can increase the number of cases and contacts identified in an epidemic of a sexually transmitted disease in a vulnerable, hard to reach population.

Heterosexual outbreak of infectious syphilis: epidemiological and ethnographic analysis and implications for control.

This study describes the epidemiology and ethnography of an outbreak of infectious syphilis in Vancouver, British Columbia. Between 1996 and 1999, British Columbias's rate of infectious syphilis rose from 0.5 to 3.4 per 100,000, with a dense concentration of cases among sex trade workers, their clients, and street-involved people in the downtown eastside area of Vancouver. Sexual networks were imported cases with secondary spread (dyads and triads), large densely connected dendritic networks of sex trade workers and clients, or occasional starburst networks among gay men. Only 232 of 429 partners were documented as having been treated (54% of those named, or 0.9 per case). The geographical and demographic concentration of this outbreak led to consideration of a programme of focused mass treatment with single dose azithromycin.

Sex in the city: sexual behaviour, societal change, and STDs in Saigon.

HIV infection is increasing among sex workers and injection drug users in southern Vietnam. Vietnamese sex workers returning from Cambodia are an important factor. This phase I growth stage is being accelerated by widespread prostitution and escalating heroin use. Sexually transmitted disease (STD) rates are significant in sex workers but low in the general population. STD epidemics in developing countries may not follow the dynamic topology that is common in developed countries. Vietnam has the potential for significant HIV and STD epidemics but also the capacity to respond to these threats.

Incidence of hepatitis C virus infection among injection drug users during an outbreak of HIV infection.

BACKGROUND: Beginning in 1994, Vancouver experienced an explosive outbreak of HIV infection among injection drug users (IDUs). The objectives of this study were to measure the prevalence and incidence of hepatitis C virus (HCV) infection in this context and to examine factors associated with HCV seroconversion among IDUs. METHODS: IDUs recruited through a study site and street outreach completed interviewer-administered questionnaires covering subjects' characteristics, behaviour, health status and service utilization and underwent serologic testing for HIV and HCV at baseline and semiannually thereafter. A Cox proportional hazards model was used to identify independent correlates of HCV seroconversion. RESULTS: As of Nov. 30, 1999, 1345 subjects had been recruited into the study cohort. The prevalence of anti-HCV antibodies was 81.6% (95% confidence interval [CI] 79.6% to 83.6%) at enrollment. Sixty-two HCV seroconversions occurred among 155 IDUs who were initially HCV negative and who returned for follow-up, for an overall incidence density rate of 29.1 per 100 person-years (95% CI 22.3 to 37.3). The HCV incidence remained above 16 per 100 person-years over 3 years of observation (December 1996 to November 1999), whereas HIV incidence declined from more than 19 to less than 5 per 100 person-years. Independent correlates of HCV seroconversion included female sex, cocaine use, injecting at least daily and frequent attendance at a needle exchange program. INTERPRETATION: Because of high transmissibility of HCV among those injecting frequently and using cocaine, the harm reduction initiatives deployed in Vancouver during the study period proved insufficient to eliminate hepatitis C transmission in this population.

Antenatal seroprevalence of herpes simplex virus type 2 (HSV-2) in Canadian women: HSV-2 prevalence increases throughout the reproductive years.

BACKGROUND: This study sought to provide the first population estimates of herpes simplex type 2 (HSV-2) seroprevalence in Canada. GOAL: To measure the antenatal seroprevalence of HSV-2 antibodies in reproductive age women. STUDY DESIGN: An anonymous unlinked seroprevalence study used stored sera collected from pregnant women in British Columbia during 1999. Randomized sampling within age strata selected a total of 1215 subjects, ages 15 to 44 years. Serologic testing used the Gull Meridian Test. Overall prevalence was directly standardized to the 1999 Canadian female population. RESULTS: The age-adjusted prevalence for HSV-2 was 17.3% (95% CI, 15.2-19.4). Prevalence ranged from 7.1% (ages, 15-19 years) to 28.1% (ages, 40-44 years), with the largest increases after the age of 24 years. CONCLUSIONS: The HSV-2 seroprevalence among pregnant women in British Columbia is similar to that in the United States and other countries. Seroprevalence continues to rise through the later reproductive years. This observation may relate to continued transmission, an age cohort effect, or both.

Non-nominal HIV surveillance: preserving privacy while tracking an epidemic.

OBJECTIVE: To enhance HIV surveillance within a non-nominal provincial testing system. METHODS: Confirmatory HIV tests from a provincial laboratory were analyzed during 1995 and 1996. Enhancements included elimination of repeat positive tests for the same individual using automated matching of non-nominal identifiers and nurse call-back of health care providers, completion of missing information through call-back and connection of providers with resources for patient care. RESULTS: Forty-seven percent of 2,683 reactive HIV tests were identified as duplicates for the same individual, meaning that 1,401 people tested positive for the first time. From laboratory test data to enhanced unduplicated data after call-back, the proportion of tests for which risk and ethnic information was unknown dropped from 37% to 11% and from 64% to 18% respectively (p < 0.0001). CONCLUSIONS: Enhanced non-nominal surveillance for HIV is a practical means of marrying the needs of public health for epidemiological information and the rights of patients to privacy.

Do needle exchange programmes increase the spread of HIV among injection drug users?: an investigation of the Vancouver outbreak.

OBJECTIVE: An association between needle exchange attendance and higher HIV prevalence rates among injecting drug users (IDU) in Vancouver has been interpreted by some to suggest that needle exchange programmes (NEP) may exacerbate HIV spread. We investigated this observed association to determine whether needle exchange was causally associated with the spread of HIV. DESIGN AND METHOD: Prospective cohort study of 694 IDU recruited in the downtown eastside of Vancouver. Subjects were HIV-negative at the time of recruitment and had injected illicit drugs within the previous month. RESULTS: Of 694 subjects, the 15-month cumulative HIV incidence was significantly elevated in frequent NEP attendees (11.8+/-1.7 versus 6.2+/-1.5%; log-rank P = 0.012). Frequent attendees (one or more visits per week) were younger and were more likely to report: unstable housing and hotel living, the downtown eastside as their primary injecting site, frequent cocaine injection, sex trade involvement, injecting in 'shooting galleries', and incarceration within the previous 6 months. The Cox regression model predicted 48 seroconversions among frequent attendees; 47 were observed. Although significant proportions of subjects reported obtaining needles, swabs, water and bleach from the NEP, only five (0.7%) reported meeting new friends or people there. When asked where subjects had met their new sharing partners, only one out of 498 respondents cited the needle exchange. Paired analysis of risk variables at baseline and the first follow-up visit did not reveal any increase in risk behaviours among frequent attendees, regardless of whether they had initiated drug injection after establishment of the NEP. CONCLUSIONS: We found no evidence that this NEP is causally associated with HIV transmission. The observed association should not be cited as evidence that NEP may promote the spread of HIV. By attracting higher risk users, NEP may furnish a valuable opportunity to provide additional preventive/support services to these difficult-to-reach individuals.

Use of incentives to increase compliance for TB screening in a population of intravenous drug users. Vancouver Injection Drug Use Study Group.

SETTING: Intravenous drug users (IDUs) represent a high risk group for dual human immunodeficiency virus (HIV) and tuberculosis (TB) infection. Screening with TB skin testing has therefore been suggested in this group. Subjects' compliance for returning to have TB skin test results read is a major problem. In the setting of a needle exchange program we evaluated the role of financial incentives to increase compliance. METHODS: We evaluated the role of giving a small financial incentive of Can $5 to subjects if they returned to have their purified protein derivative (PPD) skin test read. IDUs who had previously been skin-tested were compared with IDUs drawn from a similar population who, prospectively, were offered a financial incentive. RESULTS: During the initial period 558 subjects were evaluated and no incentive was offered. During the second phase of the study 549 IDUs were assessed but were also offered Can $5 if they returned to have their skin test read. Use of incentives increased compliance from 43% to 78% (P = 0.001). During the same period three active cases of TB were also diagnosed. CONCLUSIONS: We suggest that use of financial incentives can increase the return of IDUs to have their skin tests read. Further studies are required to assess the efficacy of follow-up interventions, especially the use of isoniazid chemoprophylaxis.

Routine prenatal screening for HIV in a low-prevalence setting.

BACKGROUND: The objectives of this study were to assess the effect of British Columbia's June 1994 guidelines for prenatal HIV screening on the rate of maternal-fetal HIV transmission and to estimate the cost-effectiveness of such screening. METHODS: The authors conducted a retrospective review of pregnancy and delivery statistics, HIV screening practices, laboratory testing volume, prenatal and labour management decisions of HIV-positive women, maternal-fetal transmission rates and associated costs. RESULTS: Over 1995 and 1996, 135,681 women were pregnant and 92,645 carried to term. The rate of HIV testing increased from 55% to 76% of pregnancies on chart review at one hospital between November 1995 and November 1996. On the basis of seroprevalence studies, an estimated 50.2 pregnancies and 34.3 (95% confidence interval 17.6 to 51.0) live births to HIV-positive women were expected. Of 42 identified mother-infant pairs with an estimated date of delivery during 1995 or 1996, 25 were known only through screening. Of these 25 cases, there were 10 terminations, 1 spontaneous abortion and 14 cases in which the woman elected to carry the pregnancy to term with antiretroviral therapy. There was one stillbirth. One instance of maternal-fetal HIV transmission occurred among the 13 live births. The net savings attributable to prevented infections among babies carried to term were $165,586, with a saving per prevented case of $75,266. INTERPRETATION: A routine offer of pregnancy screening for HIV in a low-prevalence setting reduces the rate of maternal-fetal HIV transmission and may rival other widely accepted health care expenditures in terms of cost-effectiveness.

Factors associated with frequent needle exchange program attendance in injection drug users in Vancouver, Canada.

The objective of this study was to identify factors associated with frequent needle exchange program (NEP) attendance by injection drug users (IDUs) in Vancouver, Canada. Data were examined from a case control study of recent HIV infection. IDUs with documented HIV seroconversion after January 1, 1994 (n = 89) and seronegative controls with two documented HIV-negative test results in the same period (n = 192) were asked about demographic and social information, drug injection and sexual behavior, and NEP attendance. Logistic regression was used to examine the effect of multiple variables on NEP attendance while adjusting for HIV status and other potential confounders. Frequent (> 1 time/week) versus nonfrequent (< or = 1 time/week) NEP attenders did not differ with respect to gender, age, ethnicity, education, or HIV serostatus. For men, multivariate analysis showed that frequent cocaine injection was the only variable independently associated with NEP attendance (adjusted odds ratio [AOR] = 3.9; 95% confidence interval [CI] = 1.8-8.3); for women, independently associated variables were frequency of any drug injection (AOR = 5.5; 95% CI = 1.7-17), shooting gallery attendance (AOR = 11.5; 95% CI = 2.2-66), and having a nonlegal source of income (AOR = 3.4; 95% CI = 1.0-12). Borrowing used needles was associated with frequent NEP attendance in the univariate analysis. The NEP in Vancouver attracts IDUs who are frequent injectors (especially men using cocaine) and who have high-risk behaviors or an unstable lifestyle. This finding reinforces the role of NEPs as potential focal points for intervention in this hard-to-reach population.

Determinants of HIV seroconversion in injection drug users during a period of rising prevalence in Vancouver.

To identify determinants of HIV seroconversion among injection drug users (IDUs) during a period of rising prevalence, a case-control investigation was conducted. Cases were IDUs with a new positive test after 1 January 1994, and a negative test within the prior 18 months. Controls required 2 negative tests during the same period. Subjects completed a questionnaire on demographic, psychosocial, and behavioural factors. Eighty-nine cases and 192 controls were similar with respect to gender, age, ethnicity and inter-test interval. Multivariate analyses of events during the inter-test interval showed borrowing syringes (adj. OR = 2.96; P < 0.006), unstable housing (adj. OR = 2.01; P = 0.03) and injecting > or = 4 times daily (adj. OR = 1.71; P = 0.06) to be independently associated with seroconversion. Protective associations were demonstrated for sex with opposite gender (adj. OR = 0.36; P = 0.001) and tetrahydrocannabinol use (adj. OR = 0.41; P = 0.001). There is a need to evaluate programmes dealing with addiction, housing and the social underpinnings of risk behaviours in this population.