• Paediatric Buruli ulcer in Australia

      Walker, G; Friedman, D; Cooper, C; O'Brien, M; McDonald, A; Callan, P; O'Brien, D; MSF UK Manson Unit (2019-12-10)
      AIM: This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients. METHODS: Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age. RESULTS: A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery. CONCLUSIONS: Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.
    • Paediatric Care in Relation to the 2014-2015 Ebola Outbreak and General Reporting of Deaths in Sierra Leone

      Sesay, T; Denisiuk, O; Shringarpure, K; Wurie, B; George, P; Sesay, M; Zachariah, R (International Union Against Tuberculosis and Lung Disease, 2017-06-21)
      Setting: All peripheral health units countrywide in Sierra Leone and one hospital in Port Loko. Objectives: Sierra Leone was severely affected by the 2014-2015 Ebola outbreak, whose impact on paediatric care and mortality reports merits assessment. We sought to compare the periods before, during and after the Ebola outbreak, the countrywide trend in morbidities in children aged < 5 years and exit outcomes in one district hospital (Port Loko). During the Ebola outbreak period, gaps in district death reporting within the routine Health Management Information System (HMIS) were compared with the Safe and Dignified Burials (SDB) database in Port Loko. Design: This was a retrospective records analysis. Results: The average number of monthly consultations during the Ebola outbreak period declined by 27% for malaria and acute respiratory infections and 38% for watery diarrhoea, and did not recover to the pre-Ebola levels. For measles, there was an 80% increase during Ebola, which multiplied by 6.5-fold post-Ebola. The number of unfavourable hospital exit outcomes was 52/397 (13%) during Ebola, which was higher than pre-Ebola (47/496, 9%, P = 0.04). Of 6565 deaths reported in the Port Loko SDB database, only 2219 (34%) appeared in the HMIS, a reporting deficit of 66%. Conclusion: The Ebola disease outbreak was associated with reduced utilisation of health services, and appears to have triggered a measles epidemic. Almost 70% of deaths were missed by the HMIS during the Ebola outbreak period. These findings could guide health system responses in future outbreaks.
    • Paediatric HIV care in sub-Saharan Africa: clinical presentation and 2-year outcomes stratified by age group

      Ben-Farhat, Jihane; Gale, Marianne; Szumilin, Elisabeth; Balkan, Suna; Poulet, Elisabeth; Pujades-Rodríguez, Mar (John Wiley & Sons Ltd, 2013-09)
      To examine age differences in mortality and programme attrition amongst paediatric patients treated in four African HIV programmes.
    • Paediatric HIV testing beyond the context of prevention of mother-to-child transmission: a systematic review and meta-analysis.

      Cohn, Jennifer; Whitehouse, Katherine; Tuttle, Julia; Lueck, Kristin; Tran, Trang (2016-10)
      Many HIV-positive children in low-income and middle-income countries remain undiagnosed. Although HIV testing in children at health facilities is recommended by WHO, it is not well implemented. This systematic review and meta-analysis examines the case-finding benefit of HIV screening in children aged 0-5 years in low-income and middle-income countries.
    • Paediatric HIV Treatment Failure: A Silent Epidemic

      Bernheimer, Jonathan M; Patten, Gem; Makeleni, Thembisa; Mantangana, Nompumelelo; Dumile, Nombasa; Goemaere, Eric; Cox, Vivian (International AIDS Society, 2015-07-23)
      Paediatric antiretroviral treatment (ART) failure is an under-recognized issue that receives inadequate attention in the field of paediatrics and within HIV treatment programmes. With paediatric ART failure rates ranging from 19.3% to over 32% in resource limited settings, a comprehensive evaluation of the causes of failure along with approaches to address barriers to treatment adherence are urgently needed. In partnership with the local Department of Health, a pilot programme has been established by Medecins Sans Frontieres (MSF) in Khayelitsha, South Africa, to identify and support paediatric HIV patients with high viral loads and potential treatment failure. Through detailed clinical and psychosocial evaluations and adherence support with an innovative counselling model, treatment barriers are identified and addressed. Demographic and clinical characteristics from the cohort show a delayed median start date for ART, prolonged viraemia including a large number of patients who have never achieved viral load (VL) suppression, a low rate of regimen changes despite failure, and a high percentage of pre-adolescent and adolescent patients who have not gone through the disclosure process. Stemming this epidemic of paediatric treatment failure requires programmatic responses to high viral loads in children, starting with improved "case finding" of previously undiagnosed HIV-infected children and adolescents. Viral load testing needs to be prioritized over CD4 count monitoring, and flagging systems to identify high VL results should be developed in clinics. Clinicians must understand that successful treatment begins with good adherence, and that simple adherence support strategies can often dramatically improve adherence. Moreover, appropriate adherence counselling should begin not when the child fails to respond to treatment. Establishing good adherence from the beginning of treatment, and supporting ongoing adherence during the milestones in these children's lives is key to sustaining treatment success in this vulnerable HIV-infected patient population.
    • Paediatric in-patient care in a conflict-torn region of Somalia: are hospital outcomes of acceptable quality?

      Ngoy, B B; Zachariah, R; Hinderaker, S G; Khogali, M; Manzi, M; van Griensven, J; Ayada, L; Jemmy, J P; Maalim, A; Amin, H (International Union Against Tuberculosis and Lung Disease, 2014-03-25)
    • Paediatric in-patient care in a conflict-torn region of Somalia: are hospital outcomes of acceptable quality? [Short communication]

      Ngoy, B B; Zachariah, R; Hinderaker, S G; Khogali, M; Manzi, M; van Griensven, J; Ayada, L; Jemmy, J P; Maalim, A; Amin, H (2013-06)
    • Paediatric pharmacovigilance: use of pharmacovigilance data mining algorithms for signal detection in a safety dataset of a paediatric clinical study conducted in seven african countries

      Kajungu, D K; Erhart, A; Talisuna, A O; Bassat, Q; Karema, C; Nabasumba, C; Nambozi, M; Tinto, H; Kremsner, P; Meremikwu, M; et al. (Public Library of Science, 2014-05)
      Pharmacovigilance programmes monitor and help ensuring the safe use of medicines which is critical to the success of public health programmes. The commonest method used for discovering previously unknown safety risks is spontaneous notifications. In this study we examine the use of data mining algorithms to identify signals from adverse events reported in a phase IIIb/IV clinical trial evaluating the efficacy and safety of several Artemisinin-based combination therapies (ACTs) for treatment of uncomplicated malaria in African children.
    • Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

      Andronikou, S; McHugh, K; Abdurahman, N; Khoury, B; Mngomezulu, V; Brant, W E; Cowan, I; McCulloch, M; Ford, N; Radiology Department, University of Witwatersrand, Johannesburg Gauteng, South Africa; Radiology Department, Great Ormond Street Hospital for Children, London, UK; Radiology Department, University of Cape Town, Cape Town, South Africa; Radiology Department, University of Virginia, Charlottesville, VA, USA; Radiology Department, Christchurch Hospital, Christchurch, New Zealand; Evelyna Children's Hospital, London, UK; Public Health/Access, Medecins Sans Frontieres, Cape Town, South Africa (Springer, 2011-06-09)
      Paediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children.
    • Pain in traumatic upper limb amputees in Sierra Leone.

      Lacoux, P; Crombie, I K; Macrae, W A; Medecins Sans Frontieres, 8, Rue St Sabin, Paris XI, France. (2002-09)
      Data on 40 upper limb amputees (11 bilateral) with regard to stump pain, phantom sensation and phantom pain is presented. All the patients lost their limbs as a result of violent injuries intended to terrorise the population and were assessed 10-48 months after the injury. All amputees reported stump pain in the month prior to interview and ten of the 11 bilateral amputees had bilateral pain. Phantom sensation was common (92.5%), but phantom pain was only present in 32.5% of amputees. Problems in translation and explanation may have influenced the low incidence of phantom pain and high incidence of stump pain. In the bilateral amputees phantom sensation, phantom pain and telescoping all showed bilateral concordance, whereas stump pain and neuromas did not show concordance. About half the subjects (56%) had lost their limb at the time of injury (primary) while the remainder had an injury, then a subsequent amputation in hospital (secondary). There was no association between the incidence of phantom pain and amputation irrespective of being primary or secondary.
    • Paracheck-Pf accuracy and recently treated Plasmodium falciparum infections: is there a risk of over-diagnosis?

      Swarthout, T D; Counihan, H; Senga, R K K; van den Broek, I; Médecins Sans Frontières, London, UK. toddswarth@yahoo.com (Elsevier, 2007)
      BACKGROUND: An assessment of the accuracy of Paracheck Pf, a malaria rapid diagnostic test (RDT) detecting histidine rich protein 2 was undertaken amongst children aged 6-59 months in eastern Democratic Republic of Congo. METHODS: This RDT assessment occurred in conjunction with an ACT efficacy trial. Febrile children were simultaneously screened with both RDT and high quality microscopy and those meeting inclusion criteria were followed for 35 days. RESULTS: 358 febrile children were screened with 180 children recruited for five weeks follow-up. On screening, the RDT accurately diagnosed all 235 true malaria cases, indicating 100% RDT sensitivity. Of the 123 negative slides, the RDT gave 59 false-positive results, indicating 52.0% (64/123) RDT specificity. During follow-up after treatment with an artemisinin-based combination therapy, 98.2% (110/112), 94.6% (106/112), 92.0% (103/112) and 73.5% (50/68) of effectively treated children were still false-positive by RDT at days 14, 21, 28 and 35, respectively. CONCLUSION: Results show that though the use of Paracheck-Pf is as sensitive as microscopy in detecting true malaria cases, a low specificity did present a high frequency of false-positive RDT results. What's more, a duration of RDT false-positivity was found that significantly surpassed the 'fortnight' after effective treatment reported by its manufacturer. Though further research is needed in assessing RDT accuracy, study results showing the presence of frequent false positivity should be taken into consideration to avoid clinicians inappropriately focusing on malaria, not identifying the true cause of illness, and providing unnecessary treatment.
    • Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome after early initiation of antiretroviral therapy in a randomized clinical trial

      Laureillard, D; Marcy, O; Madec, Y; Chea, S; Chan, S; Borand, L; Fernandez, M; Prak, N; Kim, C; Dim, B; et al. (Lippincott Williams & Wilkins, 2013-10-23)
      To analyze cases of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the CAMbodian Early versus Late Introduction of Antiretrovirals (CAMELIA) randomized trial designed to compare early (2 weeks) versus late (8 weeks) antiretroviral therapy (ART) initiation after tuberculosis treatment onset in Cambodia (NCT00226434).
    • "Paradoxical" immune-mediated reactions to Mycobacterium ulcerans during antibiotic treatment: a result of treatment success, not failure.

      O'Brien, D P; Robson, M E; Callan, P P; McDonald, A H; Barwon Health, Geelong, VIC, Australia. daniel.obrien@amsterdam.msf.org. (2009-11-16)
      We present the first clinical descriptions of immune-mediated paradoxical reactions to effective antibiotic treatment for Mycobacterium ulcerans infection, which result in clinical deterioration after initial improvement. Recognition of this phenomenon could prevent unnecessary changes to antibiotic regimens, and might obviate the need for, or reduce the extent of, further surgery. (MJA 2009; 191: 564-566).
    • Paragonimiasis in Tuberculosis Patients in Nagaland, India

      Das, M; Doleckova, K; Shenoy, R; Mahanta, J; Narain, K; Devi, KR; Konyak, T; Mansoor, H; Isaakidis, P (Co-Action Publishing, 2016-09-23)
      One of the infections that mimic tuberculosis (TB) is paragonimiasis (PRG), a foodborne parasitic disease caused by lung flukes of the genus Paragonimus. In the northeastern states of India, TB and PRG are endemic; however, PRG is rarely included in the differential diagnosis of TB.
    • The Partec CyFlow Counter could provide an option for CD4+ T-cell monitoring in the context of scaling-up antiretroviral treatment at the district level in Malawi.

      Fryland, M; Chaillet, P; Zachariah, R; Barnaba, A; Bonte, L; Andereassen, R; Charrondière, S; Teck, R; Didakus, O; Médecins sans Frontières-Luxembourg, Thyolo District, Malawi. (Elsevier, 2006-10)
      A study was conducted in rural Malawi to verify (a) whether the Partec CyFlow Counter((R)) for CD4+ T-cell lymphocyte counting in HIV-positive individuals could be introduced into a district hospital laboratory and (b) whether it would produce CD4 counts of acceptable quality. CD4+ cell counting was performed using the Partec CyFlow Counter and the results were compared with a reference method (FACsCount). A total of 311 blood samples were analysed and the correlation coefficient for the CyFlow Counter was 0.92 (95% CI 0.89-0.95). Mean CD4 counts using the Partec and the reference methods were 308.2 cells/microl and 316.9 cells/microl, respectively. The mean difference in CD4 count values was -8.68 cells/microl (95% CI -18.8 to 1.4). Mean intra-run variation was -6.84 cells/microl (95% CI -12.9 to 0.79). In the district laboratory setting, the instrument could accommodate up to 75 blood samples per technician per day. After being trained, local laboratory staff found the CyFlow Counter procedures simple to run and the instrument easy to manipulate. The Partec CyFlow Counter produces sufficiently reliable results and the instrument appears robust under field conditions. It could provide a new option for introducing routine CD4+ cell monitoring at the district level in the context of scaling-up antiretroviral therapy in Malawi.
    • Partnerships, Not Parachutists, for Zika Research

      Heymann, DL; Liu, J; Lillywhite, L (Massachusetts Medical Society, 2016-03-09)
    • Passive Versus Active Tuberculosis Case Finding and Isoniazid Preventive Therapy Among Household Contacts in a Rural District of Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Gomani, P; Graham, S; Bakali, E; Humblet, P; Operational Research (HIV/TB), Medical Department, Médecins sans Frontières-Brussels Operational Centre, Brussels, Belgium. zachariah@internet.lu (International Union Against TB and Lung Disease, 2003-11)
      SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis.
    • Patch-Testing for the Management of Hypersensitivity Reactions to Second-Line Anti-Tuberculosis Drugs: A Case Report

      Khan, S; Andries, A; Pherwani, A; Saranchuk, P; Isaakidis, P (BioMed Central (Springer Science), 2014-08-15)
      The second-line anti-tuberculosis drugs used in the treatment of multidrug-resistant tuberculosis often cause adverse events, especially in patients co-infected with the human immunodeficiency virus. Severe hypersensitivity reactions due to these drugs are rare and there is little published experience to guide their management.
    • Patent dispute: Delhi High Court gives a boost to access to affordable medicines

      Menghaney, Leena; Medecins Sans Frontieres-Campaign for Access to Essential Medicines, C 236 Defence Colony, New Delhi, India (Forum for Medical Ethics Society, 2010-04-01)
      The Delhi High Court has rejected the petition filed by Bayer Corporation seeking to stop the Drugs Controller of India (DCGI) from registering a generic version of a patented cancer drug. The case was filed in 2008 by Bayer to try and introduce "patent linkage" which involves linking the registration (marketing approval) of drugs with their patent status. If Bayer's plea for "patent linkage" had been accepted by the court, it would have undermined public health safeguards contained in India's patent legislation. This comment discusses the Bayer case in the context of efforts by multinational pharmaceutical companies to introduce barriers to generic competition, the only proven means of reducing the prices of medicines to make them affordable to those in need. Bayer has filed an appeal in the Supreme Court, indicating that it does not intend to give up.