Changing Patterns of Disease Severity in Blastomyces dermatitidis Infection, Quebec, Canada.

This retrospective multicenter cohort study assessed temporal changes in the severity and mortality rate of blastomycosis in Quebec, Canada, and identified risk factors for death in patients with blastomycosis in 1988-2016. The primary outcome was 90-day all-cause deaths. Among 185 patients, 122 (66%) needed hospitalization and 30 (16%) died. We noted increases in the proportion of severe cases, in age at diagnosis and in the proportion of diabetic and immunocompromised patients over time. Independent risk factors for death were age (adjusted odds ratio [aOR] 1.04, 95% CI 1.00-1.07), immunosuppression (aOR 4.2, 95% CI 1.5-11.6), and involvement of >2 lung lobes (aOR 5.3, 95% CI 1.9-14.3). There was no association between the Blastomyces genotype group and all-cause mortality. The proportion of severe cases of blastomycosis has increased in Quebec over the past 30 years, partially explained by the higher number of immunosuppressed patients.

The epidemiology of hepatitis delta virus infection in Cameroon.

OBJECTIVE: To investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon. DESIGN: We tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies. RESULTS: Overall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15-49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude <4°N) while having rural/outdoor work (OR=15.2; 95% CI: 8.35 to 27.6, when compared with living on latitude ≥4°N and not having rural/outdoor work). CONCLUSION: We found evidence for effective intra-household transmission of HDV in Cameroon. We also identified large differences in prevalence between regions, with cases concentrated in forested areas close to the Equator, as described in other tropical areas. The reasons underlying these geographical variations in HDV prevalence deserve further investigation.

Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa Have Unknown Susceptibility to Direct-Acting Antiviral Treatments.

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub-Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population-based, nested case-control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next-generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR-positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well-resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.

Anosmia and dysgeusia associated with SARS-CoV-2 infection: an age-matched case-control study.

BACKGROUND: Anosmia and dysgeusia have been reported as potential symptoms of coronavirus disease 2019. This study aimed to confirm whether anosmia and dysgeusia are specific symptoms among those who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted an age-matched case-control study in the Eastern Townships region of Quebec between Mar. 10 and Mar. 23, 2020. We included adults (age ≥ 18 yr) who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction. Cases were matched (1:1) according to 5-year age groups with control patents selected randomly from among all patients who tested negative for SARS-CoV-2 during the same period. Demographic and laboratory information was collected from medical records. Clinical symptoms and comorbidities associated with anosmia and dysgeusia were obtained by telephone interview with a standardized questionnaire. RESULTS: Among 2883 people tested for SARS-CoV-2, we identified 134 positive cases (70 women [52.2%] and 64 men [47.8%]; median age 57.1 [interquartile range 41.2-64.5] yr). The symptoms independently associated with SARS-CoV-2 positivity in conditional logistic regression were anosmia or dysgeusia or both (adjusted odds ratio [OR] 62.9, 95% confidence interval [CI] 11.0-359.7), presence of myalgia (adjusted OR 7.6, 95% CI 1.9-29.9), blurred vision (adjusted OR 0.1, 95% CI 0.0-0.8) and chest pain (adjusted OR 0.1, 95% CI 0.0-0.6). INTERPRETATION: We found a strong association between olfactory and gustatory symptoms and SARS-CoV-2 positivity. These symptoms should be considered as common and distinctive features of SARS-CoV-2 infection and should serve as an indication for testing and possible retesting of people whose first test result is negative.

Multilocus Variable-Number Tandem-Repeat Analysis of Clostridioides difficile Clusters in Ribotype 027 Isolates and Lack of Association with Clinical Outcomes.

The epidemiology of Clostridioides difficile infection (CDI) has drastically changed since the emergence of the epidemic strain BI/NAP1/027, also known as ribotype 027 (R027). However, the relationship between the infecting C. difficile strain and clinical outcomes is still debated. We hypothesized that certain subpopulations of R027 isolates could be associated with unfavorable outcomes. We applied high-resolution multilocus variable-number tandem-repeat analysis (MLVA) to characterize C. difficile R027 isolates collected from confirmed CDI patients recruited across 10 Canadian hospitals from 2005 to 2008. PCR ribotyping was performed first to select R027 isolates that were then analyzed by MLVA (n = 450). Complicated CDI (cCDI) was defined by the occurrence of any of admission to an intensive care unit, colonic perforation, toxic megacolon, colectomy, and if CDI was the cause or contributed to death within 30 days after enrollment. Three major MLVA clusters were identified, MC-1, MC-3, and MC-10. MC-1 and MC-3 were exclusive to Quebec centers, while MC-10 was found only in Ontario. Fewer cases infected with MC-1 developed cCDI (4%) than those infected with MC-3 and MC-10 (15% and 16%, respectively), but a statistically significant difference was not reached. Our data did not identify a clear association between subpopulations of R027 and different clinical outcomes; however, the data confirmed the utility of MLVA's higher discrimination potential to better characterize CDI populations in an epidemiological analysis. For a patient with CDI, the progression toward an unfavorable outcome is a complex process that probably includes several interrelated strain and host characteristics.

An Efficient, Large-Scale Survey of Hepatitis C Viremia in the Democratic Republic of the Congo Using Dried Blood Spots.

Background: Efficient viral load testing is needed for hepatitis C (HCV) surveillance and diagnosis. HCV viral load testing using dried blood spots (DBSs), made with a single drop of finger-prick whole blood on filter paper, is a promising alternative to traditional serum- or plasma-based approaches. Methods: We adapted the Abbott Molecular m2000 instrument for high-throughput HCV viremia testing using DBSs with simple specimen processing and applied these methods to estimate the national burden of infection in the Democratic Republic of the Congo (DRC). We tested DBSs collected during the 2013-2014 DRC Demographic and Health Survey, including 1309 adults ≥40 years of age. HCV-positive samples underwent targeted sequencing, genotyping, and phylogenetic analyses. Results: This high-throughput screening approach reliably identified HCV RNA extracted from DBSs prepared using whole blood, with a 95% limit of detection of 1196 (95% confidence interval [CI], 866-2280) IU/mL for individual 6-mm punches and 494 (95% CI, 372-1228) IU/mL for larger 12-mm punches. Fifteen infections were identified among samples from the DRC Demographic and Health Survey; the weighted country-wide prevalence of HCV viremia was 0.9% (95% CI, 0.3%-1.6%) among adults ≥40 years of age and 0.7% (95% CI, .6%-.8%) among human immunodeficiency virus-infected subjects. All successfully genotyped cases were due to genotype 4 infection. Conclusions: DBS-based HCV testing represents a useful tool for the diagnosis and surveillance of HCV viremia and can easily be incorporated into specimen referral systems. Among adults ≥40 years of age in the DRC, 100000-200000 may have active infection and be eligible for treatment.

Sustained impact of a computer-assisted antimicrobial stewardship intervention on antimicrobial use and length of stay.

Objectives: : Prospective audit and feedback interventions are the core components of an antimicrobial stewardship programme. Herein, we describe the sustained impact of an antimicrobial stewardship programme, based on a novel clinical decision-support system (Antimicrobial Prescription Surveillance System; APSS), on antimicrobial use and costs, hospital length of stay (LOS) in days and the proportion of inappropriate antimicrobial prescriptions. Methods: A quasi-experimental, retrospective study was conducted using interrupted time series between 2008 and 2013. Data on all hospitalized adults receiving antimicrobials were extracted from the data warehouse of a 677 bed academic centre. The intervention started in August 2010. Prospective audit and feedback interventions, led by a pharmacist, were triggered by APSS based on deviations from published and local guidelines. Changes in outcomes before and after the intervention were compared using segmented regression analysis. Results: APSS reviewed 40 605 hospitalizations for 35 778 patients who received antimicrobials. The intervention was associated with a decrease in the average LOS (level change -0.92, P < 0.01; trend -0.08, P < 0.01; intercept 11.4 days), antimicrobial consumption in DDDs/1000 inpatient days (level change -32.4, P < 0.01; trend -1.12, P < 0.02; intercept 243 DDDs per 1000 days of hospitalization), antimicrobial spending in Canadian dollars (level change -19 649, P = 0.01; trend -1881, P < 0.01; intercept $74 683) and proportion of non-concordance with local guidelines for prescribing antimicrobials (level change -2.3, P = 0.04; intercept 41%). Conclusions: The implementation of the APSS-initiated strategy was associated with a positive impact on antimicrobial use and spending, LOS and inappropriate prescriptions. The high rate of accepted interventions may have contributed to these results.

Epidemic History and Iatrogenic Transmission of Blood-borne Viruses in Mid-20th Century Kinshasa.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) pandemic was ignited in Léopoldville (now known as Kinshasa), in the former Belgian Congo. Factors that jump-started its early expansion remain unclear. Nonlethal hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV-1) can be used to investigate past iatrogenic transmission. METHODS: We undertook a cross-sectional study of elderly inhabitants of Kinshasa, with serological assays, amplification, and sequencing. Risk factors were assessed through logistic regression. Phylogenetic methods reconstructed the genetic history of HCV. RESULTS: A total of 217 of 839 participants (25.9%) were HCV seropositive; 26 (3.1%) were HTLV-1-seropositive. Amplification products were obtained from 118 HCV-seropositive participants; subtypes 4k (in 47 participants) and 4r (in 38) were most common. Independent risk factors for HCV subtype 4r seropositivity were intramuscular tuberculosis therapy, intravenous injections at hospital A, intravenous injections before 1960, and injections at a colonial-era venereology clinic. Intravenous injections at hospital B and antimalarials were associated with HCV subtype 4k seropositivity. Risk factors for HTLV-1 seropositivity included intravenous injections at hospitals C or D and transfusions. Evolutionary analysis of viral sequences revealed independent exponential amplification of HCV subtypes 4r and 4k from the 1950s onward. CONCLUSIONS: Iatrogenic transmission of HCV and HTLV-1 occurred in mid-20th century Kinshasa, at the same time and place HIV-1 emerged. Iatrogenic routes may have contributed to the early establishment of the pandemic.

Clinical and Healthcare Burden of Multiple Recurrences of Clostridium difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI. METHODS: This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode. RESULTS: We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences. CONCLUSIONS: This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management.

Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections.

OBJECTIVES: Patients with Clostridium difficile infection (CDI) who are re-exposed to antibiotics have a high likelihood of recurrence. We aimed to determine whether oral vancomycin as secondary prophylaxis reduces the risk of recurrence in patients recently diagnosed with CDI who undergo subsequent antibiotic exposure (CDI-AE). METHODS: We conducted a retrospective cohort study of patients diagnosed with CDI (initial episode or recurrence) between 2003 and 2011 in two tertiary care centers in Quebec, Canada and who received antibiotics not targeted against CDI within 90 days after their CDI diagnosis. Risk factors for subsequent recurrence after this exposure to antibiotics were assessed through Cox regression analyses. RESULTS: We included 551 episodes of CDI-AE (379 initial episodes, 172 recurrences). Recurrence occurred after exposure to antibiotics in 181 episodes (32.9%). Recurrence was more likely in older patients (for each additional year of age: adjusted hazard ratio (AHR), 1.01; 95% confidence interval (CI), 1.00-1.03; P=0.02) and among cases where the CDI-AE episode was itself a first (AHR, 3.59; 95% CI, 2.52-5.13; P<0.0001) or a second recurrence (AHR, 4.88; 95% CI, 3.38-7.06; P<0.0001). Oral vancomycin prophylaxis decreased the risk of further recurrence in patients whose CDI-AE itself was a recurrence (AHR, 0.47; 95% CI, 0.32-0.69; P<0.0001) but not in those whose CDI-AE was an initial episode (AHR, 0.91; 95% CI, 0.57-1.45; P=0.68). CONCLUSIONS: Oral vancomycin appears as an effective strategy for decreasing the risk of further CDI recurrence in patients with a history of recurrent CDI who are re-exposed to antibiotics.

Factors Associated With Complications of Clostridium difficile Infection in a Multicenter Prospective Cohort.

BACKGROUND: Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and may result in severe complications including death. We conducted a prospective study to identify risk factors for complications of CDI (cCDI). METHODS: Adult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and followed for 90 days. Potential risk factors were measured within 24 hours of diagnosis. Isolates were typed by polymerase chain reaction ribotyping. cCDI was defined as 1 or more of the following: colonic perforation, toxic megacolon, colectomy, admission to an intensive care unit for cCDI, or if CDI contributed to death within 30 days of enrollment. Risk factors for cCDI were investigated by logistic regression. RESULTS: A total of 1380 patients were enrolled. cCDI was observed in 8% of patients. The ribotype was identified in 922 patients, of whom 52% were infected with R027. Age ≥ 80 years, heart rate >90/minute, respiratory rate >20/minute, white cell count <4 × 10(9)/L or ≥ 20 × 10(9)/L, albumin <25 g/L, blood urea nitrogen >7 mmol/L, and C-reactive protein ≥ 150 mg/L were independently associated with cCDI. A higher frequency of cCDI was observed among R027-infected patients (10.9% vs 7.2%), but the association was not significant in adjusted analysis. CONCLUSIONS: CDI complications were associated with older age, abnormal blood tests, and abnormal vital signs. These factors, which are readily available to clinicians at the time of diagnosis, could be used for outcome prediction and risk stratification to select patients who may need closer monitoring or more aggressive therapy.

Characterization of Hepatitis C Virus Recombination in Cameroon by Use of Nonspecific Next-Generation Sequencing.

The importance of recombination in the evolution and genetic diversity of the hepatitis C virus (HCV) is currently uncertain. Only a small number of intergenotypic recombinants have been identified so far, and each has core and envelope genes classified as belonging to genotype 2. Here, we investigated two putative genotype 4/1 recombinants from southern Cameroon using a number of approaches, including standard Sanger sequencing, genotype-specific PCR amplification, and non-HCV-specific Illumina RNA sequencing (RNA-seq). Recombination between genotypes 1 and 4 was confirmed in both samples, and the parental lineages of each recombinant belong to HCV subtypes that are cocirculating at a high prevalence in Cameroon. Using the RNA-seq approach, we obtained a complete genome for one sample, which contained a recombination breakpoint at the E2/P7 gene junction. We developed and applied a new method, called Deep SimPlot, which can be used to visualize and identify viral recombination directly from the short sequence reads created by next-generation sequencing in conjunction with a consensus sequence.

Anosmie et dysgueusie associées à l'infection au SRAS-CoV-2: étude cas­témoins appariée selon l'âge.

CONTEXTE: On a signalé l'anosmie et la dysgueusie comme symptômes potentiels de la maladie à coronavirus 2019. Cette étude visait à confirmer si ces symptômes sont caractéristiques chez les personnes ayant eu un résultat positif au dépistage du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2). MÉTHODES: Nous avons réalisé une étude cas­témoins appariée selon l'âge dans la région des Cantons-de-l'Est, au Québec, entre le 10 et le 23 mars 2020. Nous avons inclus les adultes (18 ans et plus) ayant obtenu un résultat positif au dépistage du SRAS-CoV-2 par test d'amplification en chaîne par polymérase couplée à une transcription inverse. Les cas ont été appariés (1:1) par tranche d'âge de 5 ans avec des témoins sélectionnés aléatoirement parmi tous les patients ayant eu un résultat négatif au dépistage pendant la même période. Les données démographiques et de laboratoire ont été récupérées dans les dossiers médicaux. Les symptômes cliniques et les comorbidités associés à l'anosmie et à la dysgueusie ont été notés lors d'entrevues téléphoniques faites au moyen d'un questionnaire standardisé. RÉSULTATS: Parmi les 2883 personnes soumises au dépistage du SRAS-CoV-2, nous avons recensé 134 cas positifs (70 femmes [52,2 %] et 64 hommes [47,8 %]; âge médian 57,1 ans [intervalle interquartile 41,2­64,5 ans]). Les symptômes indépendamment associés à l'infection confirmée au SRAS-CoV-2 dans une analyse de régression logistique conditionnelle étaient les suivants : anosmie et/ou dysgueusie (rapport de cotes [RC] ajusté 62,9; intervalle de confiance [IC] de 95 % 11,0­359,7), myalgie (RC ajusté 7,6; IC de 95 % 1,9­29,9), vision trouble (RC ajusté 0,1; IC de 95 % 0,0­0,8) et douleur thoracique (RC ajusté 0,1; IC de 95 % 0,0­0,6). INTERPRÉTATION: Nous avons observé un lien étroit entre les symptômes olfactifs et gustatifs et la positivité au SRAS-CoV-2. Ces symptômes devraient être considérés comme une caractéristique fréquente et distinctive de l'infection au SRAS-CoV-2 et devraient servir d'indication de dépistage, et même de répétition du dépistage chez les personnes dont le résultat initial est négatif.

Characterization of full-length hepatitis C virus sequences for subtypes 1e, 1h and 1l, and a novel variant revealed Cameroon as an area in origin for genotype 1.

In this study, we characterized the full-length genome sequences of seven hepatitis C virus (HCV) isolates belonging to genotype 1. These represent the first complete genomes for HCV subtypes 1e, 1h, 1l, plus one novel variant that qualifies for a new but unassigned subtype. The genomes were characterized using 19-22 overlapping fragments. Each was 9400-9439 nt long and contained a single ORF encoding 3019-3020 amino acids. All viruses were isolated in the sera of seven patients residing in, or originating from, Cameroon. Predicted amino acid sequences were inspected and unique patterns of variation were noted. Phylogenetic analysis using full-length sequences provided evidence for nine genotype 1 subtypes, four of which are described for the first time here. Subsequent phylogenetic analysis of 141 partial NS5B sequences further differentiated 13 subtypes (1a-1m) and six additional unclassified lineages within genotype 1. As a result of this study, there are now seven HCV genotype 1 subtypes (1a-1c, 1e, 1g, 1h, 1l) and two unclassified genotype 1 lineages with full-length genomes characterized. Further analysis of 228 genotype 1 sequences from the HCV database with known countries is consistent with an African origin for genotype 1, and with the hypothesis of subsequent dissemination of some subtypes to Asia, Europe and the Americas.

Human parvovirus 4 infection, Cameroon.

In a post hoc analysis of samples collected in 2009, we determined seroprevalence of parvovirus 4 (PARV4) among elderly Cameroonians. PARV4 seropositivity was associated with receipt of intravenous antimalarial drugs, intramuscular streptomycin, or an intramuscular contraceptive, but not hepatitis C virus seropositivity. Findings suggest parenteral acquisition of some PARV4 infections.

High seroprevalence of enterovirus infections in apes and old world monkeys.

To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.

The expansion of HIV-1 in colonial Leopoldville, 1950s: driven by STDs or STD control?

OBJECTIVES: To understand the factors that drove the exponential spread of HIV-1 in Léopoldville (Kinshasa) in the 1950s. METHODS: A review of colonial and post-colonial health service reports, medical publications, and demographic and social science research in Léopoldville. RESULTS: Sex work appeared early in the history of Léopoldville, driven by a strong gender imbalance. Throughout the colonial era, sex work was of a low-risk type, with 'free women' having a few regular clients. This sufficed for the persistence of HIV-1, but probably not for the dramatic expansion that occurred in the 1950s. During that decade, genital ulcerative diseases were uncommon and their effect on HIV-1 transmission must have been modest. Circumstantial evidence indicates that this expansion may have been related to parenteral transmission of HIV-1 in the city's sexually transmitted disease clinic, where up to 500 injections were administered daily using syringes and needles that were merely rinsed between patients. Most intravenous injections were given to treat syphilis in patients who never had any clinical evidence of this disease but only had a positive non-treponemal serology, often because of prior yaws infection. An outbreak of 'inoculation hepatitis' was reported among these patients in 1951-1952. It is only after the Congo's independence (1960) that, in a context of pauperisation, a pattern of sex work appeared in Léopoldville wherein women had sex with more than 1000 clients each year, allowing the sexual amplification of the virus. CONCLUSIONS: It is plausible that the exponential amplification of HIV-1 in Léopoldville occurred mostly parenterally in the 1950s and sexually in the 1960s.

Periodical antibiotic treatment for the control of gonococcal and chlamydial infections among sex workers in Benin and Ghana: a cluster-randomized placebo-controlled trial.

BACKGROUND: In resource-poor settings, control of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) among female sex workers (FSWs) is difficult. We sought to determine whether periodical antibiotic treatment (PAT) might be effective in controlling these infections among West African FSWs. Secondary objectives were to determine the impact of PAT on human immunodeficiency virus (HIV) incidence among FSWs and on NG/CT prevalence among their clients. METHODS: Cluster-randomized, double-blind, placebo-controlled trial among FSW communities in Benin and Ghana. Within each of 9 pairs of clusters of FSW communities, one was allocated to receive, during 9 months, a monthly antibiotic (alternatively ciprofloxacin or azithromycin, n = 296 FSWs) and the other a placebo (n = 340 FSWs). Prevalence of NG/CT infections was measured at 3-month intervals using the polymerase chain reaction. HIV status was determined at the beginning and at the end of the study. RESULTS: After adjusting for age, HIV status, duration of prostitution, price per intercourse and condom use, and accounting for prevalence at enrollment and cluster-pairing effect, prevalence ratios (intervention vs. placebo) of NG infection were 0.77 (P = NS), 1.07 (P = NS), and 0.49 (P = 0.05) at the first, second, and third follow-up visits, respectively. PAT neither reduced significantly CT prevalence or HIV incidence among FSWs nor NG/CT prevalence among their clients. CONCLUSION: The only beneficial impact of PAT was on the prevalence of gonococcal infections among FSWs 9 months after the beginning of the intervention. Although PAT could be more effective in other circumstances, for instance, in the early stages of a program for FSWs, it can not be recommended at present as a routine strategy to control cervical infections among FSWs.

In the footsteps of Albert Calmette: an ecological study of TB, leprosy and potential exposure to wild-type Mycobacterium bovis.

BACKGROUND: One hundred years ago, Albert Calmette developed an avirulent strain of Mycobacterium bovis, but there is no evidence that his BCG strain was more immunogenic than wild-type M. bovis. Geographic variations in BCG efficacy remain ill-understood. We hypothesized that exposure to M. bovis through unpasteurized milk might protect against Mycobacterium tuberculosis and Mycobacterium leprae. METHODS: After excluding high-income countries (with universal milk pasteurization) and microstates, an ecological study comprising 113 countries was conducted. National data were obtained from United Nations agencies and international organizations about milk production per capita (1980-1999) as a proxy for exposure to wild-type M. bovis, TB (2000-2019) and leprosy (2005-2019) incidence, HIV prevalence (2000-2019), human development index (2010), global hunger index (2010), neonatal BCG coverage (1980-1999), urbanization (2000) and temperature (1990-2020). Multiple linear regression analyses were performed using log-transformed variables. RESULTS: For TB, the association differed by region. An inverse association with milk production was seen in regions outside, but not within, sub-Saharan Africa, after adjustment for confounders. The incidence of leprosy was inversely associated with milk production when combining all countries, but the association was stronger in sub-Saharan Africa. CONCLUSIONS: Exposure to wild-type M. bovis through unpasteurized milk may provide cross-protection against M. tuberculosis and M. leprae and contribute to geographic disparities in BCG efficacy. This needs to be confirmed by individual-level studies.

Impact and benefit-cost ratio of a program for the management of latent tuberculosis infection among refugees in a region of Canada.

INTRODUCTION: The identification and treatment of latent tuberculosis infection (LTBI) among immigrants from high-incidence regions who move to low-incidence countries is generally considered an ineffective strategy because only ≈14% of them comply with the multiple steps of the 'cascade of care' and complete treatment. In the Estrie region of Canada, a refugee clinic was opened in 2009. One of its goals is LTBI management. METHODS: Key components of this intervention included: close collaboration with community organizations, integration within a comprehensive package of medical care for the whole family, timely delivery following arrival, shorter treatment through preferential use of rifampin, and risk-based selection of patients to be treated. Between 2009-2020, 5131 refugees were evaluated. To determine the efficacy and benefit-cost ratio of this intervention, records of refugees seen in 2010-14 (n = 1906) and 2018-19 (n = 1638) were reviewed. Cases of tuberculosis (TB) among our foreign-born population occurring before (1997-2008) and after (2009-2020) setting up the clinic were identified. All costs associated with TB or LTBI were measured. RESULTS: Out of 441 patients offered LTBI treatment, 374 (85%) were compliant. Adding other losses, overall compliance was 69%. To prevent one case of TB, 95.1 individuals had to be screened and 11.9 treated, at a cost of $16,056. After discounting, each case of TB averted represented $32,631, for a benefit-cost ratio of 2.03. Among nationals of the 20 countries where refugees came from, incidence of TB decreased from 68.2 (1997-2008) to 26.3 per 100,000 person-years (2009-2020). Incidence among foreign-born persons from all other countries not targeted by the intervention did not change. CONCLUSIONS: Among refugees settling in our region, 69% completed the LTBI cascade of care, leading to a 61% reduction in TB incidence. This intervention was cost-beneficial. Current defeatism towards LTBI management among immigrants and refugees is misguided. Compliance can be enhanced through simple measures.