• 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.
    • Bedaquiline overdose: A case report

      Telnov, O; Alvarez, V; Graglia, E; Molfino, L; du Cros, P; Rich, M (Elsevier, 2019-07)
      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.
    • 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.
    • Behavioural characteristics, prevalence of Chlamydia trachomatis and antibiotic susceptibility of Neisseria gonorrhoeae in men with urethral discharge in Thyolo, Malawi.

      Zachariah, R; Harries, A D; Nkhoma, W; Arendt, V; Nchingula, D; Chantulo, A; Chimtulo, F; Kirpach, P; Médecins sans Frontières-Luxembourg, Thyolo District, Malawi. zachariah@internet.lu (Elsevier, 2008-01-25)
      A study was carried out in 2000/2001 in a rural district of Malawi among men presenting with urethral discharge, in order to (a) describe their health-seeking and sexual behaviour, (b) determine the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis, and (c) verify the antibiotic susceptibility of N. gonorrhoeae. A total of 114 patients were entered into the study; 61% reported having taken some form of medication before coming to the sexually transmitted infections clinic. The most frequent alternative source of care was traditional healers. Sixty-eight (60%) patients reported sexual encounters during the symptomatic period, the majority (84%) not using condoms. Using ligase chain reaction on urine, N. gonorrhoeae was detected in 91 (80%) and C. trachomatis in 2 (2%) urine specimens. Forty five of 47 N. gonorrhoeae isolates produced penicillinase, 89% showing multi-antimicrobial resistance. This study emphasizes the need to integrate alternative care providers and particularly traditional healers in control activities, and to encourage their role in promoting safer sexual behaviour. In patients presenting with urethral discharge in our rural setting, C. trachomatis was not found to be a major pathogen. Antimicrobial susceptibility surveillance of N. gonorrhoeae is essential in order to prevent treatment failures and control the spread of resistant strains.
    • Better Treatment of XDR Tuberculosis Needed in South Africa

      Cox, H; van Cutsem, G; Cox, V (Elsevier, 2014-08-16)
    • Beyond wasted and stunted—a major shift to fight child undernutrition

      Wells, JCK; Briend, A; Boyd, EM; Berkely, JA; Hall, A; Isanaka, S; Webb, P; Khara, T; Dolan, C (Elsevier, 2019-09-11)
      Child undernutrition refers broadly to the condition in which food intake is inadequate to meet a child's needs for physiological function, growth, and the capacity to respond to illness. Since the 1970s, nutritionists have categorised undernutrition in two major ways, either as wasted (ie, low weight for height, or small mid-upper arm circumference) or stunted (ie, low height for age). This approach, although useful for identifying populations at risk of undernutrition, creates several problems: the focus is on children who have already become undernourished, and this approach draws an artificial distinction between two idealised types of undernourished children that are widely interpreted as indicative of either acute or chronic undernutrition. This distinction in turn has led to the separation of programmatic approaches to prevent and treat child undernutrition. In the past 3 years, research has shown that individual children are at risk of both conditions, might be born with both, pass from one state to the other over time, and accumulate risks to their health and life through their combined effects. The current emphasis on identifying children who are already wasted or stunted detracts attention from the larger number of children undergoing the process of becoming undernourished. We call for a major shift in thinking regarding how we assess child undernutrition, and how prevention and treatment programmes can best address the diverse causes and dynamic biological processes that underlie undernutrition.
    • Biological diagnosis of meningococcal meningitis in the African meningitis belt: current epidemic strategy and new perspectives.

      Chanteau, S; Rose, A; Djibo, S; Nato, F; Boisier, P; CERMES, Réseau International Institut Pasteur, PO Box 10887, Niamey, Niger. schanteau@cermes.org (Elsevier, 2007-09-03)
      Laboratory diagnosis is an essential component in surveillance of meningococcal epidemics, as it can inform decision-makers of the Neisseria meningitidis serogroup(s) involved and the most appropriate vaccine to be selected for mass vaccination. However, countries most affected face real limitations in laboratory diagnostics, due to lack of resources. We describe current diagnostic tools and examine their cost-effectiveness for use in an epidemic context. The conclusion is that current WHO recommendations to use only the latex agglutination assay (Pastorex) at epidemic onset is cost-effective, but recently developed rapid diagnostic tests for the major epidemic-causing meningococcal serogroups may prove a breakthrough for the future.
    • The burden of diabetes and use of diabetes care in humanitarian crises in low-income and middle-income countries

      Kehlenbrink, S; Smith, J; Ansbro, E; Fuhr, D; Cheung, A; Ratnayake, R; Boulle, P; Jobanputra, K; Perel, P; Roberts, B (Elsevier, 2019-03-13)
      Human suffering as a result of natural disasters or conflict includes death and disability from non-communicable diseases, including diabetes, which have largely been neglected in humanitarian crises. The objectives of this Series paper were to examine the evidence on the burden of diabetes, use of health services, and access to care for people with diabetes among populations affected by humanitarian crises in low-income and middle-income countries, and to identify research gaps for future studies. We reviewed the scientific literature on this topic published between 1992 and 2018. The results emphasise that the burden of diabetes in humanitarian settings is not being captured, clinical guidance is insufficient, and diabetes is not being adequately addressed. Crisis-affected populations with diabetes face enormous constraints accessing care, mainly because of high medical costs. Further research is needed to characterise the epidemiology of diabetes in humanitarian settings and to develop simplified, cost-effective models of care to improve the delivery of diabetes care during humanitarian crises.
    • Calling tuberculosis a social disease--an excuse for complacency?

      Isaakidis, P; Smith, S; Majumdar, S; Furin, J; Reid, T (Elsevier, 2014-09-20)
    • Care of Non-Communicable Diseases in Emergencies

      Slama, S; Kim, HJ; Roglic, G; Boulle, P; Hering, H; Varghese, C; Rasheed, S; Tonelli, M (Elsevier, 2016-09-13)
    • Carriage Prevalence and Serotype Distribution of Streptococcus Pneumoniae Prior to 10-Valent Pneumococcal Vaccine Introduction: A Population-Based Cross-Sectional Study in South Western Uganda, 2014

      Nackers, F; Cohuet, S; le Polain de Waroux, O; Langendorf, C; Nyehangane, D; Ndazima, D; Nanjebe, D; Karani, A; Tumwesigye, E; Mwanga-Amumpaire, J; et al. (Elsevier, 2017-08-04)
      Information on Streptococcus pneumoniae nasopharyngeal (NP) carriage before the pneumococcal conjugate vaccine (PCV) introduction is essential to monitor impact. The 10-valent PCV (PCV10) was officially introduced throughout Ugandan national childhood immunization programs in 2013 and rolled-out countrywide during 2014. We aimed to measure the age-specific Streptococcus pneumoniae carriage and serotype distribution across all population age groups in the pre-PCV10 era in South Western Uganda.
    • Case management of a multidrug-resistant Shigella dysenteriae serotype 1 outbreak in a crisis context in Sierra Leone, 1999-2000.

      Guerin, P J; Brasher, C; Baron, E; Mic, D; Grimont, F; Ryan, M; Aavitsland, P; Legros, D; Epicentre, 8 rue Saint Sabin, 75011 Paris, France. philippe.guerin@epicentre.msf.org (Elsevier, 2004-11)
      From December 1999 to the end of February 2000, 4218 cases of dysentery were reported in Kenema district, southeastern Sierra Leone, by a Médecins Sans Frontières team operating in this region. Shigella dysenteriae serotype 1 was isolated from the early cases. The overall attack rate was 7.5% but higher among children under 5 years (11.2%) compared to the rest of the population (6.8%) (RR = 1.6; 95% CI 1.5-1.8). The case fatality ratio was 3.1%, and higher for children under 5 years (6.1% vs. 2.1%) (RR = 2.9; 95% CI 2.1-4.1). A case management strategy based on stratification of affected cases was chosen in this resource-poor setting. Patients considered at higher risk of death were treated with a 5 day ciprofloxacin regimen in isolation centres. Five hundred and eighty-three cases were treated with a case fatality ratio of 0.9%. Patients who did not have signs of severity when seen by health workers were given hygiene advice and oral rehydration salts. This strategy was effective in this complex emergency.
    • Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study.

      Nathan, N; Borel, T; Djibo, A; Evans, D; Djibo, S; Corty, J F; Guillerm, M; Alberti, K P; Pinoges, L; Guerin, P J; et al. (Elsevier, 2008-04-14)
      BACKGROUND: In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis. METHODS: In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses. FINDINGS: Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported. INTERPRETATION: Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.
    • Chagas disease knocks on our door: a cross-sectional study among Latin American immigrants in Milan, Italy.

      Antinori, S; Galimberti, L; Grande, R; Bianco, R; Oreni, L; Traversi, L; Ricaboni, D; Bestetti, G; Lai, A; Mileto, D; et al. (Elsevier, 2018-12-01)
      OBJECTIVES: We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability. METHODS: A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information. RESULTS: Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%). CONCLUSIONS: CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment.
    • Challenges and controversies in childhood tuberculosis

      Reuter, A; Hughes, J; Furin, J (Elsevier, 2019-09-14)
      Children bear a substantial burden of suffering when it comes to tuberculosis. Ironically, they are often left out of the scientific and public health advances that have led to important improvements in tuberculosis diagnosis, treatment, and prevention over the past decade. This Series paper describes some of the challenges and controversies in paediatric tuberculosis, including the epidemiology and treatment of tuberculosis in children. Two areas in which substantial challenges and controversies exist (ie, diagnosis and prevention) are explored in more detail. This Series paper also offers possible solutions for including children in all efforts to end tuberculosis, with a focus on ensuring that the proper financial and human resources are in place to best serve children exposed to, infected with, and sick from all forms of tuberculosis.
    • Challenges associated with providing diabetes care in humanitarian settings

      Boulle, P; Kehlenbrink, S; Smith, J; Beran, D; Jobanputra, K (Elsevier, 2019-03-13)
      The humanitarian health landscape is gradually changing, partly as a result of the shift in global epidemiological trends and the rise of non-communicable diseases, including diabetes. Humanitarian actors are progressively incorporating care for diabetes into emergency medical response, but challenges abound. This Series paper discusses contemporary practical challenges associated with diabetes care in humanitarian contexts in low-income and middle-income countries, using the six building blocks of health systems described by WHO (information and research, service delivery, health workforce, medical products and technologies, governance, and financing) as a framework. Challenges include the scarcity of evidence on the management of diabetes and clinical guidelines adapted to humanitarian contexts; unavailability of core indicators for surveillance and monitoring systems; and restricted access to the medicines and diagnostics necessary for adequate clinical care. Policy and system frameworks do not routinely include diabetes and little funding is allocated for diabetes care in humanitarian crises. Humanitarian organisations are increasingly gaining experience delivering diabetes care, and interagency collaboration to coordinate, improve data collection, and analyse available programmes is in progress. However, the needs around all six WHO health system building blocks are immense, and much work needs to be done to improve diabetes care for crisis-affected populations.
    • Challenges associated with providing diabetes care in humanitarian settings

      Boulle, P; Kehlenbrink, S; Smith, J; Beran, D; Jobanputra, K (Elsevier, 2019-03-13)
      The humanitarian health landscape is gradually changing, partly as a result of the shift in global epidemiological trends and the rise of non-communicable diseases, including diabetes. Humanitarian actors are progressively incorporating care for diabetes into emergency medical response, but challenges abound. This Series paper discusses contemporary practical challenges associated with diabetes care in humanitarian contexts in low-income and middle-income countries, using the six building blocks of health systems described by WHO (information and research, service delivery, health workforce, medical products and technologies, governance, and financing) as a framework. Challenges include the scarcity of evidence on the management of diabetes and clinical guidelines adapted to humanitarian contexts; unavailability of core indicators for surveillance and monitoring systems; and restricted access to the medicines and diagnostics necessary for adequate clinical care. Policy and system frameworks do not routinely include diabetes and little funding is allocated for diabetes care in humanitarian crises. Humanitarian organisations are increasingly gaining experience delivering diabetes care, and interagency collaboration to coordinate, improve data collection, and analyse available programmes is in progress. However, the needs around all six WHO health system building blocks are immense, and much work needs to be done to improve diabetes care for crisis-affected populations.
    • Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.

      Zachariah, R; Harries, A D; Spielmann M P; Arendt, V; Nchingula, D; Mwenda, R; Courteille, O; Kirpach, P; Mwale, B; Salaniponi, F M L; et al. (Elsevier, 2008-01-31)
      In Thyolo district, Malawi, an operational research study is being conducted on the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths in HIV-positive patients with tuberculosis (TB). A series of cross-sectional studies were carried out in 1999 and 2001 to determine (i) whether faecal Escherichia coli resistance to co-trimoxazole in TB patients changed with time, and (ii) whether the resistance pattern was different in HIV-positive TB patients who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E. coli isolates in TB patients at the time of registration was 60% in 1999 and 77% in 2001 (P < 0.01). Resistance was 89% among HIV-infected TB patients (receiving cotrimoxazole), while in HIV-negative patients (receiving anti-TB therapy alone) it was 62% (P < 0.001). The study shows a significant increase of E. coli resistance to co-trimoxazole in TB patients which is particularly prominent in HIV-infected patients on co-trimoxazole prophylaxis. Since a high degree of plasmid-mediated transfer of resistance exists between E. coli and the Salmonella species, these findings could herald limitations on the short- and long-term benefits to be expected from the use of co-trimoxazole prophylaxis in preventing non-typhoid Salmonella bacteraemia and enteritis in HIV-infected TB patients in Malawi.