Feasibility of antiretroviral therapy initiation under the treat‐all policy under routine conditions: a prospective cohort study from Eswatini Kerschberger, B; Jobanputra, K; Schomaker, M; Kabore, SM; Teck, R; Mabhena, E; Lukhele, N; Rusch, B; Boulle, A; Ciglenecki, I Introduction The World Health Organization recommends the Treat‐All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource‐poor settings. We assessed the feasibility of Treat‐All compared with standard of care (SOC) under routine conditions. Methods This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat‐All was offered in one health zone and SOC according to the CD4 350 and 500 cells/mm3 treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan–Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions. Results Of the 1726 (57.3%) patients enrolled under Treat‐All and 1287 (42.7%) under SOC, cumulative three‐month ART initiation was higher under Treat‐All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat‐All, ART initiation was higher in pregnant women (vs. non‐pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV‐positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/mm3 (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3‐month ART initiation was similar in both interventions (91% to 92%) although Treat‐All initiated patients more quickly during the first month after HIV care enrolment. Conclusions ART initiation was high under Treat‐All and without evidence of de‐prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long‐term impact of Treat‐All on patient outcomes.
Pneumococcal conjugate vaccine use during humanitarian crises van Zandvoort, K; Checchi, F; Diggle, E; Eggo, RM; Gadroen, K; Mulholland, K; McGowan, CR; le Polain de Waroux, O; Rao, VB; Satzke, C; Flasche, S Streptococcus pneumoniae is a common human commensal that causes a sizeable part of the overall childhood mortality in low income settings. Populations affected by humanitarian crises are at especially high risk, because a multitude of risk factors that are enhanced during crises increase pneumococcal transmission and disease severity. Pneumococcal conjugate vaccines (PCVs) provide effective protection and have been introduced into the majority of routine childhood immunisation programmes globally, though several barriers have hitherto limited their uptake during humanitarian crises. When PCV coverage cannot be sustained during crises or when PCV has not been part of routine programmes, mass vaccination campaigns offer a quick acting and programmatically feasible bridging solution until services can be restored. However, we currently face a paucity of evidence on which to base the structure of such campaigns. We believe that, now that PCV can be procured at a substantially reduced price through the Humanitarian Mechanism, this lack of information is a remaining hurdle to PCV use in humanitarian crises. Considering the difficulties in conducting research in crises, we propose an evidence generation pathway consisting of primary data collection in combination with mathematical modelling followed by quasi-experimental evaluation of a PCV intervention, which can inform on optimal vaccination strategies that consider age targeting, dosing regimens and impact duration.
Challenges and controversies in childhood tuberculosis Reuter, A; Hughes, J; Furin, J 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.
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 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.
Global oral cholera vaccine use Pezzoli, L; Cavailler, P; Mengel, M; Matzger, H; Lorenson, T; Sur, D; Luquero, F; Grais, R; Ko, M; Soble, A; Rouzier, V; Pape, JW; Buckee, C; Qadri, F; Mahoney, F; Kall, JJ; Landegger, J; Gayer, M; Lynch, J; Azman, AS; Sack, D; Henkens, M; Ciglenecki, I; Hall, R; Ivers, LI; Diggle, E; Weiss, M; Hinman, A; Maina, K; Mirza, I; Papowitz, H; Gimeno, G; Ramos, M; Levine, MM; Date, K; Sreenivasan, N Vaccination is a key intervention to prevent and control cholera in conjunction with water, sanitation and hygiene activities. An oral cholera vaccine (OCV) stockpile was established by the World Health Organization (WHO) in 2013. We reviewed its use from July 2013 to all of 2018 in order to assess its role in cholera control. We computed information related to OCV deployments and campaigns conducted including setting, target population, timelines, delivery strategy, reported adverse events, coverage achieved, and costs. In 2013–2018, a total of 83,509,941 OCV doses have been requested by 24 countries, of which 55,409,160 were approved and 36,066,010 eventually shipped in 83 deployments, resulting in 104 vaccination campaigns in 22 countries. OCVs had in general high uptake (mean administrative coverage 1st dose campaign at 90.3%; 2nd dose campaign at 88.2%; mean survey-estimated two-dose coverage at 69.9%, at least one dose at 84.6%) No serious adverse events were reported. Campaigns were organized quickly (five days median duration). In emergency settings, the longest delay was from the occurrence of the emergency to requesting OCV (median: 26 days). The mean cost of administering one dose of vaccine was 2.98 USD. The OCV stockpile is an important public health resource. OCVs were generally well accepted by the population and their use demonstrated to be safe and feasible in all settings. OCV was an inexpensive intervention, although timing was a limiting factor for emergency use. The dynamic created by the establishment of the OCV stockpile has played a role in the increased use of the vaccine by setting in motion a virtuous cycle by which better monitoring and evaluation leads to better campaign organization, better cholera control, and more requests being generated. Further work is needed to improve timeliness of response and contextualize strategies for OCV delivery in the various settings.
Declining blood lead levels among small-scale miners participating in a safer mining pilot programme in Nigeria Gottesfeld, P; Meltzer, G; Costello, S; Greig, J; Thurtle, N; Bil, K; Mwangombe, BJ; Nota, MM Objectives Our objective was to monitor blood lead levels (BLLs) of miners and ore processors participating in a pilot programme to reduce lead poisoning and take-home exposures from artisanal small-scale gold mining. A medical surveillance programme was established to assess exposures as new methods aimed at reducing lead exposures from ore were introduced in a community in Nigeria where children experienced substantial lead-related morbidity and mortality. Methods Extensive outreach and education were offered to miners, and investments were made to adopt wet methods to reduce exposures during mining and processing. We conducted medical surveillance, including a physical exam and repeated blood lead testing, for 61 miners selected from among several hundred who participated in the safer mining pilot programme and consented to testing. Venous blood lead concentrations were analysed using the LeadCare II device at approximately 3-month intervals over a period of 19 months. Results Overall geometric mean (GM) BLLs decreased by 32% from 31.6 to 21.5 µg/dL during the 19-month project. Women had a somewhat lower reduction in GM BLLs (23%) compared with men (36%). There was a statistically significant reduction in log BLLs from baseline to the final test taken by each participant (p<0.001). Conclusions The observed reductions in GM BLLs during the pilot intervention among this representative group of miners and ore processors demonstrated the effectiveness of the safer mining programme in this community. Such measures are feasible, cost-effective and can greatly improve health outcomes in mining communities.
Dual screen and confirm rapid test does not reduce overtreatment of syphilis in pregnant women living in a non-venereal treponematoses endemic region: a field evaluation among antenatal care attendees in Burkina Faso. Langendorf, C; Lastrucci, C; Sanou-Bicaba, I; Blackburn, K; Koudika, MH; Crucitti, T OBJECTIVES: In resource-limited settings, screening pregnant women for syphilis using rapid diagnostic tests (RDTs) is a key tool in the prevention of congenital syphilis. However, most syphilis RDTs detect only treponemal antibodies (T-RDT), meaning antibiotics may be provided unnecessarily to previously treated pregnant women, particularly in non-venereal treponematoses endemic regions. We estimated the potential reduction in overtreatment when comparing T-RDT (SD Bioline) to a newer rapid test (Dual Path Platform (DPP) Screen and Confirm Assay, Chembio) detecting both treponemal and non-treponemal antibodies. METHODS: Pregnant women in Déou, Burkina Faso, screened for syphilis during antenatal care (ANC) visits were prospectively enrolled in the study after providing consent. DPP and T-RDT tests were performed on whole blood specimens. Plasma was tested in an international reference laboratory by Treponema pallidum passive particle agglutination (TPPA) and quantitative rapid plasma reagin (RPR). Presumptive active syphilis was defined as a result that was both TPPA and RPR reactive. RESULTS: Of the 242 pregnant women included in the study, 91 (37.6%) had presumptive active syphilis and 19.0% had RPR titres ≥8. DPP testing did not reduce the number of pregnant women who would have been overtreated compared with T-RDT (0.0% vs 2.5%; p=0.218) and had a higher proportion of underdiagnosis (48.4% vs 2.2%; p<0.001). Seven women with high RPR titres ≥8 would not have received treatment had only DPP testing been used. CONCLUSION: In the first evaluation comparing DPP with traditional screening methods in pregnant women, we saw no reduction in unnecessarily treated syphilis and an underestimation of those needing treatment. High seroprevalence in the population may indicate the presence of other treponemal infections in the area, and further study of DPP in a variety of Sahelian and other contexts is warranted.
Field Suitability and Diagnostic Accuracy of the Biocentric Open Real-Time PCR Platform for Dried Blood Spot-Based HIV Viral Load Quantification in Eswatini. Kerschberger, B; Ntshalintshali, N; Mpala, Q; Diaz Uribe, PA; Maphalala, G; Kalombola, S; Telila, AB; Chawinga, T; Maphalala, M; Jani, A; Phugwayo, N; de la Tour, R; Nyoni, N; Goiri, J; Dlamini, S; Ciglenecki, I; Fajardo, E BACKGROUND: To assess the performance and suitability of dried blood spot (DBS) sampling using filter paper to collect blood for viral load (VL) quantification under routine conditions. METHODS: We compared performance of DBS VL quantification using the Biocentric method with plasma VL quantification using Roche and Biocentric as reference methods. Adults (≥18 years) were enrolled at 2 health facilities in Eswatini from October 12, 2016 to March 1, 2017. DBS samples were prepared through finger-prick by a phlebotomist (DBS-1), and through the pipetting of whole venous blood by a phlebotomist (DBS-2) and by a laboratory technologist (DBS-3). We calculated the VL-testing completion rate, correlation, and agreement, as well as diagnostic accuracy estimates at the clinical threshold of 1000 copies/mL. RESULTS: Of 362 patients enrolled, 1066 DBS cards (DBS-1: 347; DBS-2: 359; DBS-3: 360) were tested. Overall, test characteristics were comparable between DBS-sampling methods, irrespective of the reference method. The Pearson correlation coefficients ranged from 0.67 to 0.82 (P < 0.001) for different types of DBS sampling using both reference methods, and the Bland-Altman difference ranged from 0.15 to 0.30 log10 copies/mL. Sensitivity estimates were from 85.3% to 89.2% and specificity estimates were from 94.5% to 98.6%. The positive predictive values were between 87.0% and 96.5% at a prevalence of 30% VL elevations, and negative predictive values were between 93.7% and 95.4%. CONCLUSIONS: DBS VL quantification using the newly configured Biocentric method can be part of contextualized VL-testing strategies, particularly for remote settings and populations with higher viral failure rates.
Feasibility of Training Clinical Officers in Point-of-Care Ultrasound for Pediatric Respiratory Diseases in Aweil, South Sudan. Nadimpalli, A; Tsung, JW; Sanchez, R; Shah, S; Zelikova, E; Umphrey, L; Hurtado, N; Gonzalez, A; Teicher, C Lower respiratory tract infections (LRTIs) are the leading cause of deaths in children < 5 years old worldwide, particularly affecting low-resource settings such as Aweil, South Sudan. In these settings, diagnosis can be difficult because of either lack of access to radiography or clinical algorithms that overtreat children with antibiotics who only have viral LRTIs. Point-of-care ultrasound (POCUS) has been applied to LRTIs, but not by nonphysician clinicians, and with limited data from low-resource settings. Our goal was to examine the feasibility of training the mid-level provider cadre clinical officers (COs) in a Médecins Sans Frontières project in South Sudan to perform a POCUS algorithm to differentiate among causes of LRTI. Six COs underwent POCUS training, and each subsequently performed 60 lung POCUS studies on hospitalized pediatric patients < 5 years old with criteria for pneumonia. Two blinded experts, with a tiebreaker expert adjudicating discordant results, served as a reference standard to calculate test performance characteristics, assessed image quality and CO interpretation. The COs performed 360 studies. Reviewers rated 99.1% of the images acceptable and 86.0% CO interpretations appropriate. The inter-rater agreement (κ) between COs and experts for lung consolidation with air bronchograms was 0.73 (0.63-0.82) and for viral LRTI/bronchiolitis was 0.81 (0.74-0.87). It is feasible to train COs in South Sudan to use a POCUS algorithm to diagnose pneumonia and other pulmonary diseases in children < 5 years old.
Duty of care and health worker protections in the age of Ebola: lessons from Médecins Sans Frontières McDiarmid, M; Crestani, R Health workers were differentially infected during the 2014 to 2016 Ebola outbreak with an incidence rate of 30 to 44/1000 depending on their job duties, compared to the wider population’s rate of 1.4/1000, according to the WHO. Médecins Sans Frontières (MSF) health workers had a much lower incidence rate of 4.3/1000, explained as the result of MSF’s ‘duty of care’ toward staff safety. Duty of care is defined as an obligation to conform to certain standards of conduct for the protection of others against an unreasonable risk of harm. The duty of care was operationalised through four actions: performing risk assessments prior to deployment, organising work and work practices to minimise exposure, providing extensive risk communication and training of staff and providing medical follow-up for staff exposures. Adopting and consistently enforcing these broader, duty of care safety policies in deployed teams augments and fortifies standard infection prevention practices, creating a more protective, comprehensive safety programme. Prioritising staff safety by taking such actions will help avoid the catastrophic loss of the health work force and assist in building resilient health systems.
Lassa fever in pregnancy with a positive maternal and fetal outcome: A case report. Agboeze, J; Nwali, MI; Nwakpakpa, E; Ogah, OE; Onoh, R; Eze, J; Ukaegbe, C; Ajayi, N; Nnadozie, UU; Orji, ML; Ojide, CK; Unigwe, US; Chika-Igwenyi, N; Nwidi, UD; Clement, UC; Kalombo, C; Makwe, C; Tshiang, J BACKGROUND: The signs and symptoms of Lassa fever are initially indistinguishable from other febrile illnesses common in the tropics and complications of pregnancy. Surviving Lassa fever during pregnancy is rare. Only few cases have been documented. The antiviral drug of choice is ribavirin. CASE DESCRIPTION: A 25-year-old multigravida farmer with fever who was initially thought to have malaria in pregnancy at 29 weeks gestation. Further changes in her clinical state and laboratory tests led to a confirmation of Lassa fever. The Liver enzymes were markedly deranged and the packed cell volume was 27%. She commenced on ribavirin and subsequently was delivered of a live male neonate who was RT PCR negative for Lassa fever virus. Her clinical state improved, repeat RT PCR on day 15 was negative and she made full recovery. DISCUSSION: The case reported had similar clinical features of fever and abdominal pain and resulted in the initial diagnoses of Malaria in pregnancy. When she failed to respond to antimalarial and antibiotics treatments, a strong suspicion of viral hemorrhagic fever was made. At this time the patient was in advanced stage of the disease with bleeding from vagina and puncture sites. On the third day of admission she was delivered of a live male neonate who remained negative after 2 consecutive RT PCR tests for Lassa fever virus. Lassa fever carries a high risk of death to the fetus throughout pregnancy and to the mother in the third trimester. Mothers with Lassa fever improved rapidly after evacuation of the uterus by spontaneous abortion, or normal delivery. She was clinically stable following delivery. Her laboratory investigations were essentially normal. Throughout her management transmission based precautions were observed. None of the six close contacts developed symptoms after been followed up for 21 days. CONCLUSION: This report adds to the body of literature that individuals can survive Lassa fever during pregnancy with good maternal and fetal outcome.
Comparison of Operative Logbook Experience of Australian General Surgical Trainees With Surgeons Deployed on Humanitarian Missions: What Can Be Learnt for the Future? Coventry, CA; Dominguez, L; Read, DJ; Trelles, M; Ivers, RQ; Montazerolghaem, M; Holland, AJA OBJECTIVE: General surgical training in Australia has undergone considerable change in recent years with less exposure to other areas of surgery. General surgeons from many high-income countries have played important roles in assisting with the provision of surgical care in low- and middle-income countries during sudden-onset disasters (SODs) as part of emergency medical teams (EMTs). It is not known if contemporary Australian general surgeons are receiving the broad surgical training required for work in EMTs. DESIGN: Logbook data on the surgical procedures performed by Australian general surgical trainees were obtained from General Surgeons Australia (GSA) for the time period February 2008 to February 2017. Surgical procedures performed by Médecins sans Frontières (MSF) surgeons during 5 projects in 3 SODs (the 2010 Haiti earthquake, the 2013 Philippines typhoon and the 2015 Nepal earthquake) were obtained from previously published data for 6 months following each disaster. SETTING AND PARTICIPANTS: This was carried out at the University of Sydney with input from MSF Operational Centre Brussels and GSA. RESULTS: Australian general surgical trainees performed a mean of 2107 surgical procedures (excluding endoscopy) during their training (10 6-month rotations). Common procedures included abdominal wall hernia repairs (268, 12.7%), cholecystectomies (247, 11.8%), and specialist colorectal procedures (242, 11.5%). MSF surgeons performed a total of 3542 surgical procedures across the 5 projects analyzed. Common procedures included Caesarean sections (443, 12.5%), wound debridement (1115, 31.5%), and other trauma-related procedures (472, 13.3%). CONCLUSIONS: Australian general surgical trainees receive exposure to both essential and advanced general surgery but lack exposure to specialty procedures including the obstetric and orthopedic procedures commonly performed by MSF surgeons after SODs. Further training in these areas would likely be beneficial for general surgeons prior to deployment with an EMT.
Measles seroprevalence after reactive vaccination campaigns during the 2015 measles outbreak in four health zones of the former Katanga Province, Democratic Republic of Congo. Keating, P; Carrion Martin, AI; Blake, A; Lechevalier, P; Uzzeni, F; Gignoux, E; Okonta, C; Langendorf, C; Smit, S; Ahuka, S; Suchard, M; Pukuta, E; Degail, MA; Hansen, L; Kibanza-Kyungu, J; Ciglenecki, I; Cohuet, S BACKGROUND: Measles continues to circulate in the Democratic Republic of Congo, and the country suffered from several important outbreaks over the last 5 years. Despite a large outbreak starting in the former province of Katanga in 2010 and the resulting immunization activities, another outbreak occurred in 2015 in this same region. We conducted measles seroprevalence surveys in four health zones (HZ) in the former Katanga Province in order to assess the immunity against measles in children 6 months to 14 years after the 2015 outbreak. METHODS: We conducted multi-stage cluster surveys stratified by age group in four HZs, Kayamba, Malemba-Nkulu, Fungurume, and Manono. The age groups were 6-11 months, 12-59 months, and 5-14 years in Kayamba and Malemba-Nkulu, 6-59 months and 5-14 years in Manono and Fungurume. The serological status was measured on dried capillary blood spots collected systematically along with vaccination status (including routine Extended Program of Immunization (EPI), and supplementary immunization activities (SIAs)) and previous self-reported history of suspected measles. RESULTS: Overall seroprevalence against measles was 82.7% in Kayamba, 97.6% in Malemba-Nkulu, 83.2% in Manono, and 74.4% in Fungurume, and it increased with age in all HZs. It was 70.7 and 93.8% in children 12-59 months in Kayamba and Malemba-Nkulu, and 49.8 and 64.7% in children 6-59 months in Fungurume and Manono. The EPI coverage was low but varied across HZ. The accumulation of any type of vaccination against measles resulted in an overall vaccine coverage (VC) of at least 85% in children 12-59 months in Kayamba and Malemba-Nkulu, 86.1 and 74.8% in children 6-59 months in Fungurume and Manono. Previous measles infection in 2015-early 2016 was more frequently reported in children aged 12-59 months or 6-59 months (depending on the HZ). CONCLUSION: The measured seroprevalence was consistent with the events that occurred in these HZs over the past few years. Measles seroprevalence might prove a valuable source of information to help adjust the timing of future SIAs and prioritizing support to the EPI in this region as long as the VC does not reach a level high enough to efficiently prevent epidemic flare-ups.