Now showing items 1-20 of 2258

    • "If we miss this chance, it's futile later on" - late antenatal booking and its determinants in Bhutan: a mixed-methods study.

      Dorji, T; Das, M; Van den Bergh, R; Oo, MM; Gyamtsho, S; Tenzin, K; Tshomo, T; Ugen, S (BioMed Central, 2019-05-07)
      BACKGROUND: To achieve the Sustainable Development Goal related to maternal and neonatal outcomes, the World Health Organization advocates for a first antenatal care (ANC) contact before 12 weeks of gestation. In order to guide interventions to achieve early ANC in the lower middle-income setting of Bhutan, we conducted an assessment of the magnitude and determinants of late ANC in this context. METHODS: This was a mixed-methods study with quantitative (cross-sectional study) and qualitative (in-depth interviews with pregnant women and ANC providers) component in a concurrent triangulation design. The quantitative component retrospectively analysed the socio-demographic and clinical characteristics, and the gestational age at booking of women who were provided care for delivery or miscarriages at the three tertiary hospitals in Bhutan from May-August 2018. The qualitative component involved thematic analysis of in-depth interviews with ten women attending ANC visits and four healthcare workers involved in ANC provision. RESULTS: Among 868 women studied, 67% (n = 584) had a late booking (after 12 weeks), and 1% (n = 13) had no booking. Women with only primary education and those residing in rural areas were more likely to have a late first ANC booking. While many women achieved the recommended eight ANC visits, this did not necessarily reflect early booking. Late booking was common among multigravida women. The interviews illustrated a general understanding and recognition of the importance of early ANC. Support from peers, family and co-workers, and male participation in accessing ANC were seen as enablers. The outreach clinics (ORCs) at the primary healthcare level were an important means of reaching the ANC services to women in rural areas where geographical accessibility was a barrier. Specific barriers to early ANC were gender insensitivity in providing care through male health workers, cost/time in ANC visits, and the inability to produce the documents of the father for booking ANC. CONCLUSION: Late ANC booking was common in Bhutan, and appeared to be associated with educational, geographic, socio-cultural and administrative characteristics. A comprehensive information package on ANC needs to be developed for pregnant mothers, and the quality of ANC coverage needs to be measured in terms of early ANC booking.
    • Association Between Gender, Surgery and Mortality for Patients Treated at Médecins Sans Frontières Trauma Centre in Kunduz, Afghanistan.

      Tounsi, LL; Daebes, HL; Warnberg, MG; Jaweed, M; Mamozai, BA; Nasim, M; Drevin, G; Trelles, M; von Schreeb, J (Springer, 2019-05-07)
      INTRODUCTION: There is paucity of literature describing type of injury and care for females in conflicts. This study aimed to describe the injury pattern and outcome in terms of surgery and mortality for female patients presenting to Médecins Sans Frontières Trauma Centre in Kunduz, Afghanistan, and compare them with males. MATERIALS AND METHODS: This study retrospectively analysed patient data from 17,916 patients treated at the emergency department in Kunduz between January and September 2015, before its destruction by aerial bombing in October the same year. Routinely collected data on patient characteristics, injury patterns, triage category, time to arrival and outcome were retrieved and analysed. Comparative analyses were conducted using logistic regression. RESULTS: Females constituted 23.6% of patients. Burns and back injuries were more common among females (1.4% and 3.3%) than among males (0.6% and 2.0%). In contrast, open wounds and thoracic injuries were more common among males (10.1% and 0.6%) than among females (5.2% and 0.2%). Females were less likely to undergo surgery (OR 0.60, CI 0.528-0.688), and this remained significant after adjustment for age, nature of injury, triage category, multiple injuries and delay to arrival (OR 0.80, CI 0.690-0.926). Females also had lower unadjusted odds of mortality (OR 0.49, CI 0.277-0.874), but this was not significant in the adjusted analysis (OR 0.81, CI 0.446-1.453). CONCLUSION: Our main findings suggest that females seeking care at Kunduz Trauma Centre arrived later, had different injury patterns and were less likely to undergo surgery as compared to males.
    • Novel Approaches to Control Malaria in Forested Areas of Southeast Asia.

      von Seidlein, L; Peto, TJ; Tripura, R; Pell, C; Yeung, S; Kindermans, JM; Dondorp, A; Maude, R (Elsevier, 2019-05-07)
      The emergence and spread of drug resistance in the Greater Mekong Subregion (GMS) have added urgency to accelerate malaria elimination while reducing the treatment options. The remaining foci of malaria transmission are often in forests, where vectors tend to bite during daytime and outdoors, thus reducing the effectiveness of insecticide-treated bed nets. Limited periods of exposure suggest that chemoprophylaxis could be a promising strategy to protect forest workers against malaria. Here we discuss three major questions in optimizing malaria chemoprophylaxis for forest workers: which antimalarial drug regimens are most appropriate, how frequently the chemoprophylaxis should be delivered, and how to motivate forest workers to use, and adhere to, malaria prophylaxis.
    • Trends of and factors associated with cesarean section related surgical site infections in Guinea

      Delamou, A; Camara, BS; Sidibe, S; Camara, A; Dioubate, N; Ayadi, AME; Tayler-Smith, K; Beavogui, AH; Balde, MD; Zachariah, R (Page Press, 2019-05-03)
      Since the adoption of free obstetric care policy in Guinea in 2011, no study has examined the surgical site infections in maternity facilities. The objective of this study was to assess the trends of and factors associated with surgical site infection following cesarean section in Guinean maternity facilities from 2013 to 2015. This was a retrospective cohort study using routine medical data from ten facilities. Overall, the incidence of surgical site infections following cesarean section showed a declining trend across the three periods (10% in 2013, 7% in 2014 and 5% in 2015, P<0.001). Women who underwent cesarean section in 2014 (AOR: 0.70; 95%CI: 0.57-0.84) and 2015 (AOR: 0.43; 95%CI: 0.34-0.55) were less likely to develop surgical site infections during hospital stay than women operated in 2013. In the contrary, women with comorbidities were more likely to experience surgical site infection (AOR: 1.54; 95% CI: 1.25-1.90) than those who did not have comorbidities. The reductions achieved in 2014 and 2015 (during the Ebola outbreak) should be sustained in the post-Ebola context.
    • Bedaquiline and delamanid in combination for treatment of drug-resistant tuberculosis

      Mohr, E; Ferlazzo, G; Hewison, C; De Azevedo, V; Isaakidis, P (Elsevier, 2019-05-01)
      Here we report on the final outcomes for the cohort of 28 patients from Armenia, India, and South Africa who initiated regimens containing the combination of bedaquiline and delamanid from January to August, 2016, for the treatment of multidrug-resistant tuberculosis in our cohort study.1 The median duration on combination treatment was 12 months (interquartile range [IQR] 5·9–20·0); 17 (61%) of 28 patients received the combination for more than 6 months.
    • Diagnostic value of the urine lipoarabinomannan assay in HIV-positive, ambulatory patients with CD4 below 200 cells/μl in 2 low-resource settings: A prospective observational study.

      Huerga, H; Mathabire Rucker, SC; Cossa, L; Bastard, M; Amoros, I; Manhica, I; Mbendera, K; Telnov, A; Szumilin, E; Sanchez-Padilla, E; Molfino, L (Public Library of Science, 2019-04-30)
      BACKGROUND: Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB. METHODS AND FINDINGS: We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results. CONCLUSIONS: LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.
    • Female Genital Schistosomiasis and HIV: Research Urgently Needed to Improve Understanding of the Health Impacts of This Important Coinfection

      O'Brien, D; Ford, N; Djirmay, AG; Calmy, A; Vitoria, M; Jensen, TO; Christinet, V (Lippincott Williams and Wilkins, 2019-04-15)
      Evidence suggests that there are important interactions between HIV and female genital schistosomiasis (FGS) that may have significant effects on individual and population health. However, the exact way they interact and the health impacts of the interactions are not well understood. In this article, we discuss what is known about the interactions between FGS and HIV, and the potential impact of the interactions. This includes the likelihood that FGS is an important health problem for HIV-positive women in Schistosoma-endemic areas potentially associated with an increased risk of mortality, cancer, and infertility. In addition, it may be significantly impacting the HIV epidemic in sub-Saharan Africa by making young women more susceptible to HIV. We call for immediate action and argue that research is urgently required to address these knowledge gaps and propose a research agenda to achieve this.
    • Female Genital Schistosomiasis and HIV: Research Urgently Needed to Improve Understanding of the Health Impacts of This Important Coinfection.

      O'Brien, DP; Ford, Nathan; Djirmay, AG; Calmy, A; Vitoria, M; Jensen, TO; Christinet, V (Lippincott Williams and Wilkins, 2019-04-15)
      Evidence suggests that there are important interactions between HIV and female genital schistosomiasis (FGS) that may have significant effects on individual and population health. However, the exact way they interact and the health impacts of the interactions are not well understood. In this article, we discuss what is known about the interactions between FGS and HIV, and the potential impact of the interactions. This includes the likelihood that FGS is an important health problem for HIV-positive women in Schistosoma-endemic areas potentially associated with an increased risk of mortality, cancer, and infertility. In addition, it may be significantly impacting the HIV epidemic in sub-Saharan Africa by making young women more susceptible to HIV. We call for immediate action and argue that research is urgently required to address these knowledge gaps and propose a research agenda to achieve this.
    • High incidence of intended partner pregnancy among men living with HIV in rural Uganda: Implications for safer conception services.

      Kaida, A; Kabakyenga, J; Bwana, M; Bajunirwe, F; Mayindike, W; Bennett, K; Kembabazi, A; Haberer, JE; Boum, Y; Martin, JN; Hunt, PW; Bangsberg, DR; Matthews, LT (Lippincott Williams and Wilkins, 2019-04-15)
      Many men with HIV express fertility intentions and nearly half have HIV-uninfected sexual partners. We measured partner pregnancy among a cohort of men accessing antiretroviral therapy (ART) in Uganda. Self-reported partner pregnancy incidence and bloodwork (CD4, HIV-RNA) were collected quarterly. Interviewer-administered questionnaires assessed men's sexual and reproductive health annually and repeated at time of reported pregnancy (2011-2015). We measured partner pregnancy incidence overall, by pregnancy intention, and by reported partner HIV-serostatus. We assessed viral suppression (≤400 copies/mL) during the peri-conception period. Cox proportional hazard regression with repeated events identified predictors of partner pregnancy. Among 189 men, baseline median age was 39.9 years [IQR:34.7,47.0], years on ART was 3.9 [IQR:0.0,5.1], and 51% were virally suppressed. Over 530.2 person-years of follow-up, 63 men reported 85 partner pregnancies (incidence=16.0/100 person-years); 45% with HIV-serodifferent partners. By three years of follow-up, 30% of men reported a partner pregnancy, with no difference by partner HIV-serostatus (p=0.75). 69% of pregnancies were intended, 18% wanted but mis-timed, and 8% unwanted. 78% of men were virally suppressed prior to pregnancy report. Men who were younger (aHR:0.94/year;95%CI:0.89-0.99), had incomplete primary education (aHR:2.95;95%CI:1.36-6.40), and reported fertility desires (aHR:2.25;95%CI:1.04-4.85) had higher probability of partner pregnancy. A high incidence of intended partner pregnancy highlights the need to address men's reproductive goals within HIV care. Nearly half of pregnancy partners were at-risk for HIV and one-quarter of men were not virally suppressed during peri-conception. Safer conception care provides opportunity to support men's health and reproductive goals, while preventing HIV transmission to women and infants.
    • A screening tool for psychological difficulties in children aged 6 to 36 months: cross-cultural validation in Kenya, Cambodia and Uganda.

      Nackers, F; Roederer, T; Marquer, C; Ashaba, S; Maling, S; Mwanga-Amumpaire, J; Muny, S; Sokeo, C; Shom, V; Palha, M; Lefebvre, P; Kirubi, BW; Kamidigo, G; Falissard, B; Moro, MR; Grais, RF (BioMed Central, 2019-04-12)
      In low-resource settings, the lack of mental health professionals and cross-culturally validated screening instruments complicates mental health care delivery. This is especially the case for very young children. Here, we aimed to develop and cross-culturally validate a simple and rapid tool, the PSYCa 6-36, that can be administered by non-professionals to screen for psychological difficulties among children aged six to 36 months. A primary validation of the PSYCa 6-36 was conducted in Kenya (n = 319 children aged 6 to 36 months; 2014), followed by additional validations in Kenya (n = 215; 2014) Cambodia (n = 189; 2015) and Uganda (n = 182; 2016). After informed consent, trained interviewers administered the PSYCa 6-36 to caregivers participating in the study. We assessed the psychometric properties of the PSYCa 6-36 and external validity was assessed by comparing the results of the PSYCa 6-36 against a clinical global impression severity [CGIS] score rated by an independent psychologist after a structured clinical interview with each participant. The PSYCa 6-36 showed satisfactory psychometric properties (Cronbach's alpha > 0.60 in Uganda and > 0.70 in Kenya and Cambodia), temporal stability (intra-class correlation coefficient [ICC] > 0.8), and inter-rater reliability (ICC from 0.6 in Uganda to 0.8 in Kenya). Psychologists identified psychological difficulties (CGIS score > 1) in 11 children (5.1%) in Kenya, 13 children (8.7%) in Cambodia and 15 (10.5%) in Uganda, with an area under the receiver operating characteristic curve of 0.65 in Uganda and 0.80 in Kenya and Cambodia. The PSYCa 6-36 allowed for rapid screening of psychological difficulties among children aged 6 to 36 months among the populations studied. Use of the tool also increased awareness of children's psychological difficulties and the importance of early recognition to prevent long-term consequences. The PSYCa 6-36 would benefit from further use and validation studies in popula`tions with higher prevalence of psychological difficulties.
    • Patient and health-care worker experiences of an HIV viral load intervention using SMS: A qualitative study.

      Venables, E; Ndlovu, Z; Munyaradzi, D; Martinez-Perez, G; Mbofana, E; Nyika, P; Chidawanyika, H; Bygrave, H; Garone, D (Public Library of Science, 2019-04-11)
      Mobile Health or mHealth interventions, including Short Message Service (SMS), can help increase access to care, enhance the efficiency of health service delivery and improve diagnosis and treatment for HIV. Text messaging, or SMS, allows for the low cost transmission of information, and has been used to send appointment reminders, information about HIV counselling and treatment, messages to encourage adherence and information on nutrition and side-effects. HIV Viral Load (VL) monitoring is recommended by the WHO and has been progressively adopted in many settings. In Zimbabwe, implementation of VL is routine and has been rolled out with support of Médecins Sans Frontières (MSF) since 2012. An SMS intervention to assist with the management of VL results was introduced in two rural districts of Zimbabwe. After completion of the HIV VL testing at the National Microbiology Reference Laboratory in Harare, results were sent to health facilities via SMS. Consenting patients were also sent an SMS informing them that their viral load results were ready for collection at their nearest health facilities. No actual VL results were sent to patients. A qualitative study was conducted in seven health-care facilities using in-depth interviews (n = 32) and focus group discussions (n = 5) to explore patient and health-care worker experiences of the SMS intervention. Purposive sampling was used to select participants to ensure that male and female patients, as well as those with differing VL results and who lived differing distances from the clinics were included. Data were transcribed, translated from Shona into English, coded and thematically analysed using NVivo software. The VL SMS intervention was considered acceptable to patients and health-care workers despite some challenges in implementation. The intervention was perceived by health-care workers as improving adherence and well-being of patients as well as improving the management of VL results at health facilities. However, there were some concerns from participants about the intervention, including challenges in understanding the purpose and language of the messages and patients coming to their health facility unnecessarily. Health-care workers were more concerned than patients about unintentional HIV disclosure relating to the content of the messages or phone-sharing. This was an innovative intervention in Zimbabwe, in which SMS was used to send VL results to health-care facilities, and notifications of the availability of VL results to patients. Interventions such as this have the potential to reduce unnecessary clinic visits and ensure patients with high VL results receive timely support, but they need to be properly explained, alongside routine counselling, for patients to fully benefit. The findings of this study also have potential policy implications, as if implemented well, such an SMS intervention has the potential to help patients adopt a more active role in the self-management of their HIV disease, become more aware of the importance of adherence and VL monitoring and seek follow-up at clinics when results are high.
    • Lessons learned: Retrospective assessment of outcomes and management of patients with advanced HIV disease in a semi-urban polyclinic in Epworth, Zimbabwe.

      Blankley, S; Gashu, T; Ahmad, B; Belaye, AK; Ringtho, L; Mesic, A; Zizhou, S; Casas, EC (Public Library of Science, 2019-04-10)
      HIV continues to be one of the leading causes of infectious death worldwide and presentation with advanced HIV disease is associated with increased morbidity and mortality. Recommendations for the management of advanced HIV disease include prompt screening and treatment of opportunistic infections, rapid initiation of ART and intensified adherence support. We present treatment outcomes of a cohort of patients presenting with advanced HIV disease in a semi-urban Zimbabwean polyclinic. Retrospective cohort analysis of adult patients enrolled for care at Epworth polyclinic, Zimbabwe between 2007 and end June 2016. Treatment outcomes at 6 and 12 months were recorded. Multivariate logistical regression analysis was undertaken to identify risk factors for presentation with advanced HIV Disease (CD4 count less than 200 cells/mm3 or WHO stage 3 or 4) and risks for attrition at 12 months. 16,007 anti-retroviral therapy naive adult patients were included in the final analysis, 47.4% of whom presented with advanced HIV disease. Patients presenting with advanced HIV disease had a higher mortality rate at 12 months following enrollment compared to early stage patients (5.11% vs 0.45%). Introduction of a package of differentiated care for patients with a CD4 count of less than 100 cells/mm3 resulted in diagnosis of cryptococcal antigenaemia in 7% of patients and a significant increase in the diagnosis of TB, although there was no significant difference in attrition at 6 or 12 months for these patients compared to those enrolled prior to the introduction of the differentiated care. The burden of advanced HIV disease remained high over the study period in this semi-urban polyclinic in Zimbabwe. Introduction of a package of differentiated care for those with advanced HIV disease increased the diagnosis of opportunistic infections and represents a model of care which can be replicated in other polyclinics in the resource constrained Zimbabwean context.
    • An Epidemic of Suspicion - Ebola and Violence in the DRC

      Nguyen, VK (Massachusetts Medical Society, 2019-04-04)
      Until the 2014 Ebola epidemic in West Africa, Ebola outbreaks had been sporadic, small, and largely confined to isolated rural villages in Central Africa. But the 2014 epidemic broke all the rules and killed more than 15,000 people; since then, more outbreaks have been reaching larger urban centers, sometimes resulting in uncontrolled spread. The current epidemic in the Democratic Republic of Congo (DRC) has triggered a massive international response, which has been met by violence, culminating in attacks at the end of February that partially destroyed Ebola treatment units in the regional hub of Butembo and its township, Katwa. This area is the epicenter of the epidemic, which is likely to be fueled by any breakdown of isolation and treatment efforts.
    • 2017 Outbreak of Ebola Virus Disease in Northern Democratic Republic of Congo

      Nsio, J; Kapetshi, J; Makiala, S; Raymond, F; Tshapenda, G; Boucher, N; Corbeil, J; Okitandjate, A; Mbuyi, G; Kiyele, M; Mondonge, V; Kikoo, MJ; Van Herp, M; Barboza, P; Petrucci, R; Benedetti, G; Formenty, P; Muzinga, BM; Kalenga, OI; Ahuka, S; Fausther-Bovendo, H; Ilunga, BK; Kobinger, GP; Muyembe, JJT (Oxford University Press, 2019-04-03)
      Background In 2017, the Democratic Republic of the Congo (DRC) recorded its eighth Ebola virus disease (EVD) outbreak, approximately 3 years after the previous outbreak. Methods Suspect cases of EVD were identified on the basis of clinical and epidemiological information. Reverse transcription–polymerase chain reaction (RT-PCR) analysis or serological testing was used to confirm Ebola virus infection in suspected cases. The causative virus was later sequenced from a RT-PCR–positive individual and assessed using phylogenetic analysis. Results Three probable and 5 laboratory-confirmed cases of EVD were recorded between 27 March and 1 July 2017 in the DRC. Fifty percent of cases died from the infection. EVD cases were detected in 4 separate areas, resulting in > 270 contacts monitored. The complete genome of the causative agent, a variant from the Zaireebolavirus species, denoted Ebola virus Muyembe, was obtained using next-generation sequencing. This variant is genetically closest, with 98.73% homology, to the Ebola virus Mayinga variant isolated from the first DRC outbreaks in 1976–1977. Conclusion A single spillover event into the human population is responsible for this DRC outbreak. Human-to-human transmission resulted in limited dissemination of the causative agent, a novel Ebola virus variant closely related to the initial Mayinga variant isolated in 1976–1977 in the DRC.
    • Screening of asymptomatic rheumatic heart disease among refugee/migrant children and youths in Italy.

      Condemi, F; Rossi, G; Miguel, L; Pagano, A; Zamatto, F; Marini, S; Romeo, F; De Maio, G (BioMed Central, 2019-04-02)
      Rheumatic heart disease (RHD) is a chronic condition responsible of congestive heart failure, stroke and arrhythmia. Almost eradicated in high-income countries (HIC), it persists in low- and middle-income countries. The purpose of the study was to assess the feasibility and meaningfulness of ultrasound-based RHD screening among the population of unaccompanied foreign minors in Italy and determine the burden of asymptomatic RHD among this discrete population. From February 2016 to January 2018, Médecins Sans Frontières conducted a weekly mobile screening by echocardiography in reception centers and family houses for unaccompanied foreign minors in Rome, followed by fix echocardiographic retesting for those resulting positive at screening. 'Definite' and 'borderline' cases were defined according to the World Hearth Federation criteria. Six hundred fifty-three individuals (13-26 years old) were screened; 95.6% were below 18 years old (624/653). Six 'definite RHD' were identified at screening, yielding a detection rate of 9.2‰ (95% CI 4.1-20.3‰), while 285 (436.4‰) were defined as 'borderline' (95% CI 398.8-474.9‰). Out of 172 "non-negative borderline" cases available for being retested (113 "non-negative borderline" lost in follow-up), additional 11 were categorized as 'definite RHD', for a total of 17 'definite RHD', yielding a final prevalence of 26.0‰ (95% CI 16.2-41.5‰) (17/653), and 122 (122/653) were confirmed as 'borderline' (final prevalence of 186.8‰, 95% CI 158.7-218.7). In multivariate logistic regression analysis the presence of systolic murmur was a strong predictor for both 'borderline' (OR 4.3 [2.8-6.5]) and 'definite RHD' (OR 5.2 [1.7-15.2]), while no specific country/geographic area of origin was statistically associated with an increased risk of latent, asymptomatic RHD. Screening for RHD among the unaccompanied migrant minors in Italy proved to be feasible. The burden of 'definite RHD' was similar to that identified in resource-poor settings, while the prevalence of 'borderline' cases was higher than reported in other studies. In view of these findings, the health system of high-income countries, hosting migrants and asylum seekers, are urged to adopt screening for RHD in particular among the silent and marginalized population of refugee and migrant children.
    • Bedaquiline overdose: A case report

      Telnov, O; Alvarez, V; Gragila, E; Molfino, L; du Cros, P; Rich, M (Elsevier, 2019-04-02)
      We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed.
    • Programmatic outcomes and impact of rapid public sector antiretroviral therapy expansion in adults prior to introduction of the WHO treat-all approach in rural Eswatini.

      Boulle, A; Teck, R; Lukhele, N; Rusch, B; Telnov, A; Mabhena, E; Pasipamire, L; Ciglenecki, I; Schomaker, M; Kerschberger, B (John Wiley & Sons, 2019-04-01)
      To assess long-term antiretroviral therapy (ART) outcomes during rapid HIV programme expansion in the public sector of Eswatini (formerly Swaziland). This is a retrospectively established cohort of HIV-positive adults (≥16 years) who started first-line ART in 25 health facilities in Shiselweni (Eswatini) between 01/2006 and 12/2014. Temporal trends in ART attrition, treatment expansion and ART coverage were described over 9 years. We used flexible parametric survival models to assess the relationship between time to ART attrition and covariates. Of 24 772 ART initiations, 6% (n = 1488) occurred in 2006, vs. 13% (n = 3192) in 2014. Between these years, median CD4 cell count at ART initiation increased (113-265 cells/mm Programmatic outcomes improved during large expansion of the treatment cohort and increased ART coverage. Changes in ART programming may have contributed to better outcomes.
    • Risk score for predicting mortality including urine lipoarabinomannan detection in hospital inpatients with HIV-associated tuberculosis in sub-Saharan Africa: Derivation and external validation cohort study.

      Gupta-Wright, A; Corbett, EL; Wilson, D; van Oosterhout, JJ; Dheda, K; Huerga, H; Peter, J; Bonnet, M; Alufandika-Moyo, M; Grint, D; Lawn, SD; Fielding, K (Public Library of Science, 2019-04-01)
      The prevalence of and mortality from HIV-associated tuberculosis (HIV/TB) in hospital inpatients in Africa remains unacceptably high. Currently, there is a lack of tools to identify those at high risk of early mortality who may benefit from adjunctive interventions. We therefore aimed to develop and validate a simple clinical risk score to predict mortality in high-burden, low-resource settings. A cohort of HIV-positive adults with laboratory-confirmed TB from the STAMP TB screening trial (Malawi and South Africa) was used to derive a clinical risk score using multivariable predictive modelling, considering factors at hospital admission (including urine lipoarabinomannan [LAM] detection) thought to be associated with 2-month mortality. Performance was evaluated internally and then externally validated using independent cohorts from 2 other studies (LAM-RCT and a Médecins Sans Frontières [MSF] cohort) from South Africa, Zambia, Zimbabwe, Tanzania, and Kenya. The derivation cohort included 315 patients enrolled from October 2015 and September 2017. Their median age was 36 years (IQR 30-43), 45.4% were female, median CD4 cell count at admission was 76 cells/μl (IQR 23-206), and 80.2% (210/262) of those who knew they were HIV-positive at hospital admission were taking antiretroviral therapy (ART). Two-month mortality was 30% (94/315), and mortality was associated with the following factors included in the score: age 55 years or older, male sex, being ART experienced, having severe anaemia (haemoglobin < 80 g/l), being unable to walk unaided, and having a positive urinary Determine TB LAM Ag test (Alere). The score identified patients with a 46.4% (95% CI 37.8%-55.2%) mortality risk in the high-risk group compared to 12.5% (95% CI 5.7%-25.4%) in the low-risk group (p < 0.001). The odds ratio (OR) for mortality was 6.1 (95% CI 2.4-15.2) in high-risk patients compared to low-risk patients (p < 0.001). Discrimination (c-statistic 0.70, 95% CI 0.63-0.76) and calibration (Hosmer-Lemeshow statistic, p = 0.78) were good in the derivation cohort, and similar in the external validation cohort (complete cases n = 372, c-statistic 0.68 [95% CI 0.61-0.74]). The validation cohort included 644 patients between January 2013 and August 2015. Median age was 36 years, 48.9% were female, and median CD4 count at admission was 61 (IQR 21-145). OR for mortality was 5.3 (95% CI 2.2-9.5) for high compared to low-risk patients (complete cases n = 372, p < 0.001). The score also predicted patients at higher risk of death both pre- and post-discharge. A simplified score (any 3 or more of the predictors) performed equally well. The main limitations of the scores were their imperfect accuracy, the need for access to urine LAM testing, modest study size, and not measuring all potential predictors of mortality (e.g., tuberculosis drug resistance). This risk score is capable of identifying patients who could benefit from enhanced clinical care, follow-up, and/or adjunctive interventions, although further prospective validation studies are necessary. Given the scale of HIV/TB morbidity and mortality in African hospitals, better prognostic tools along with interventions could contribute towards global targets to reduce tuberculosis mortality.
    • Further evidence of Mycobacterium tuberculosis in the sputum of culture-negative pulmonary tuberculosis suspects using an ultrasensitive molecular assay.

      Guillermo, M; Solange, V; Orr, B; White, L; Gaeddert, M; Miller, NS; Mpeirwe, M; Orikiriza, P; Mwanga-Amumpaire, J; Boum, Y; Palaci, M; Dietze, R; Jones-Lopez, EC (Elsevier, 2019-03-23)
      BACKGROUND: Rapid diagnosis of pulmonary tuberculosis (TB) is critical to TB control. However, many patients with paucibacillary TB disease remain undiagnosed. Current TB elimination goals require new tools to diagnose early disease. We evaluated performance of the Totally Optimized PCR (TOP) TB assay, a novel ultrasensitive molecular test. METHODS: We assessed analytical specificity against nontuberculous mycobacteria (NTM), and estimated the diagnostic accuracy of TOP in a pilot study in Brazil (n = 46) and a cross-sectional study in Boston (n = 60). We compared TOP results to culture and a composite reference standard (CRS). RESULTS: TOP exhibited no cross-reactivity against NTM. We tested 132 respiratory specimens from 106 patients with suspected pulmonary TB. The pilot demonstrated feasibility and 100% (95% CI 85-100) sensitivity in predominantly smear-positive specimens; TOP's specificity against solid media culture was low (58%, 37-77) but improved against a CRS (93%, 68-100). Similarly, when using the CRS in the Boston study, TOP (88%, 1-99) had greater sensitivity than solid or liquid media culture (25%, 3-65) and similar specificity (both 100%, 93-100). CONCLUSIONS: The TOP assay enables detection of M. tuberculosis in culture-negative paucibacillary disease. While the use of TOP for the diagnosis of paucibacillary disease will require further clinical validation, its high sensitivity indicate a more immediate utility as a rule out TB test.