Missed opportunities for vaccination (MOV) in children up to 5 years old in 19 Médecins Sans Frontières-supported health facilities: a cross-sectional survey in six low-resource countries.

OBJECTIVE: To describe missed opportunities for vaccination (MOV) among children visiting Médecins Sans Frontières (MSF)-supported facilities, their related factors, and to identify reasons for non-vaccination. DESIGN: Cross-sectional surveys conducted between 2011 and 2015. SETTING AND PARTICIPANTS: Children up to 59 months of age visiting 19 MSF-supported facilities (15 primary healthcare centres and four hospitals) in Afghanistan, Democratic Republic of the Congo, Mauritania, Niger, Pakistan and South Sudan. Only children whose caregivers presented their vaccination card were included. OUTCOME MEASURES: We describe MOV prevalence and reasons for no vaccination. We also assess the association of MOV with age, type of facility and reason for visit. RESULTS: Among 5055 children's caregivers interviewed, 2738 presented a vaccination card of whom 62.8% were eligible for vaccination, and of those, 64.6% had an MOV. Presence of MOV was more likely in children visiting a hospital or a health facility for a reason other than vaccination. MOV occurrence was significantly higher among children aged 12-23 months (84.4%) and 24-59 months (88.3%) compared with children below 12 months (56.2%, p≤0.001). Main reasons reported by caregivers for MOV were lack of vaccines (40.3%), reason unknown (31.2%) and not being informed (17.6%). CONCLUSIONS: Avoiding MOV should remain a priority in low-resource settings, in line with the new 'Immunization Agenda 2030'. Children beyond their second year of life are particularly vulnerable for MOV. We strongly recommend assessment of eligibility for vaccination as routine healthcare practice regardless of the reason for the visit by screening vaccination card. Strengthening implementation of 'Second year of life' visits and catch-up activities are proposed strategies to reduce MOV.

Effectiveness of typhoid conjugate vaccine in Zimbabwe used in response to an outbreak among children and young adults: A matched case control study.

BACKGROUND: Zimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare. METHODS: A matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls. FINDINGS: Of 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls. The adjusted VE against confirmed TF was 75% (95%CI: 1-94, p = 0.049) compared to facility controls, and 84% (95%CI: 57-94, p < 0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26-77, p = 0.153) compared to facility controls, and 67% (95%CI: 35-83, p = 0.002) compared to community controls six months to 45 years old. INTERPRETATION: This study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.

'When you welcome well, you vaccinate well': a qualitative study on improving vaccination coverage in urban settings in Conakry, Republic of Guinea.

BACKGROUND: Recurrent measles outbreaks followed by mass vaccination campaigns (MVCs) occur in urban settings in sub-Saharan countries. An understanding of the reasons for this is needed to improve future vaccination strategies. The 2017 measles outbreak in Guinea provided an opportunity to qualitatively explore suboptimal vaccination coverage within an MVC among participants through their perceptions, experiences and challenges. METHODS: We conducted focus group discussions with caregivers (n=68) and key informant interviews (n=13) with health professionals and religious and community leaders in Conakry. Data were audio-recorded, transcribed verbatim from Susu and French, coded and thematically analysed. RESULTS: Vaccinations were widely regarded positively and their preventive benefits noted. Vaccine side effects and the subsequent cost of treatment were commonly reported concerns, with further knowledge requested. Community health workers (CHWs) play a pivotal role in MVCs. Caregivers suggested recruiting CHWs from local neighbourhoods and improving their attitude, knowledge and skills to provide information about vaccinations. Lack of trust in vaccines, CHWs and the healthcare system, particularly after the 2014-2016 Ebola epidemic, were also reported. CONCLUSIONS: Improving caregivers' knowledge of vaccines, potential side effects and their management are essential to increase MVC coverage in urban settings. Strengthening CHWs' capacities and appropriate recruitment are key to improving trust through a community involvement approach.

Diphtheria Antitoxin Administration, Outcomes, and Safety: Response to a Diphtheria Outbreak in Cox's Bazar, Bangladesh.

BACKGROUND: Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment for diphtheria. The 2017-2018 outbreak among Rohingya refugees in Bangladesh was the largest in decades. We determined the outcomes of DAT-treated patients and describe the occurrence and risk factors associated with adverse reactions to DAT. METHODS: We conducted a retrospective study at the Médecins Sans Frontières Rubber Garden Diphtheria Treatment Center from December 2017-September 2018. Diphtheria was diagnosed based on the World Health Organization clinical case criteria. High-acuity patients were eligible for DAT. Safety precautions were meticulously maintained. We calculated the presence of adverse events by age, duration of illness, and DAT dosage using bivariate comparisons. RESULTS: We treated 709 patients with DAT; 98% (n = 696) recovered and were discharged. One-fourth (n = 170) had at least 1 adverse reaction. Common reactions included cough (n = 115, 16%), rash (n = 66, 9%), and itching (n = 37, 5%). Three percent (n = 18) had severe hypersensitivity reactions. Five patients died during their DAT infusion or soon afterwards, but no deaths were attributed to DAT. CONCLUSIONS: Outcomes for DAT-treated patients were excellent; mortality was <1%. Adverse reactions occurred in one-quarter of all patients, but most reactions were mild and resolved quickly. DAT can be safely administered in a setting with basic critical care, provided there is continuous patient monitoring during the infusion, staff training on management of adverse effects, and attention to safety precautions.

Evaluation of the stability of measles vaccine out of the cold chain under extended controlled temperature conditions.

Measles outbreaks occur periodically in remote and difficult to reach areas in countries such as the Democratic Republic of Congo. The possibility to keep measles vaccines at temperatures outside the cold chain for a limited period prior to administration would be an advantage for organizations such as Médecins Sans Frontières, which repeatedly respond to measles outbreaks in difficult contexts. Using stability data at 37 °C and 40 °C provided by Serum Institute of India Private Limited we applied the product release model for Extended Controlled Temperature Conditions (ECTC) to evaluate the possibility of an out of the cold chain excursion. Measles vaccine in the lyophilized form remains above the minimum required potency at the end of the shelf-life for up to 6 days at 37 °C or for 2 days at 40 °C. This evaluation supports the use of a monodose presentation of measles vaccine in ECTC. This could be an advantage for outbreak response in isolated and difficult to reach areas. However the operational advantages of this approach need to be established.

High cholera vaccination coverage following emergency campaign in Haiti: Results from a cluster survey in three rural Communes in the South Department, 2017.

Oral cholera vaccine (OCV) has increasingly been used as an outbreak control measure, but vaccine shortages limit its application. A two-dose OCV campaign targeting residents aged over 1 year was launched in three rural Communes of Southern Haiti during an outbreak following Hurricane Matthew in October 2016. Door-to-door and fixed-site strategies were employed and mobile teams delivered vaccines to hard-to-reach communities. This was the first campaign to use the recently pre-qualified OCV, Euvichol. The study objective was to estimate post-campaign vaccination coverage in order to evaluate the campaign and guide future outbreak control strategies. We conducted a cluster survey with sampling based on random GPS points. We identified clusters of five households and included all members eligible for vaccination. Local residents collected data through face-to-face interviews. Coverage was estimated, accounting for the clustered sampling, and 95% confidence intervals calculated. 435 clusters, 2,100 households and 9,086 people were included (99% response rate). Across the three communes respectively, coverage by recall was: 80.7% (95% CI:76.8-84.1), 82.6% (78.1-86.4), and 82.3% (79.0-85.2) for two doses and 94.2% (90.8-96.4), 91.8% (87-94.9), and 93.8% (90.8-95.9) for at least one dose. Coverage varied by less than 9% across age groups and was similar among males and females. Participants obtained vaccines from door-to-door vaccinators (53%) and fixed sites (47%). Most participants heard about the campaign through community 'criers' (58%). Despite hard-to-reach communities, high coverage was achieved in all areas through combining different vaccine delivery strategies and extensive community mobilisation. Emergency OCV campaigns are a viable option for outbreak control and where possible multiple strategies should be used in combination. Euvichol will help alleviate the OCV shortage but effectiveness studies in outbreaks should be done.

Prospective evaluation of diagnostic accuracy of dried blood spots from finger prick samples for determination of HIV-1 load with the NucliSENS Easy-Q HIV-1 version 2.0 assay in Malawi.

HIV-1 viral load (VL) testing is not widely available in resource-limited settings. The use of finger prick dried blood spot (FP-DBS) samples could remove barriers related to sample collection and transport. Measurement of VL using DBS from EDTA venous blood (VB-DBS) in place of plasma has previously been validated using the NucliSENS Easy-Q HIV-1 v2.0 assay, but information on the accuracy of FP-DBS samples for measuring VL is limited. This prospective study, conducted at Thyolo District Hospital in southern Malawi, compared VL levels measured on FP-DBS samples and plasma using the NucliSENS Easy-Q HIV-1 v2.0 assay. Comparability was assessed by means of agreement and correlation (131 patients with VLs of ≥100 copies/ml), sensitivity, and specificity (612 patients on antiretroviral treatment [ART]). Samples of EDTA venous blood and FP-DBS from 1,009 HIV-infected individuals were collected and prepared in the laboratory. Bland-Altman analysis found good agreement between plasma and FP-DBS VL levels, with a mean difference of -0.35 log10, and 95% limits of agreement from -1.26 to 0.55 log10. FP-DBS had a sensitivity of 88.7% (95% confidence interval [CI], 81.1 to 94.4%) and a specificity of 97.8% (95% CI, 96.1 to 98.9%) using a 1,000-copies/ml cut point and a sensitivity of 83.0% (95% CI, 73.4 to 90.1%) and a specificity of 100% (95% CI, 99.3 to 100%) using a 5,000-copies/ml cut point. This study shows that FP-DBS is an acceptable alternative to plasma for measuring VL using the NucliSENS Easy-Q HIV-1 v2.0. We are conducting a second study to assess the proficiency of health workers at preparing FP-DBS in primary health care clinics.

Feasibility of using teleradiology to improve tuberculosis screening and case management in a district hospital in Malawi.

PROBLEM: Malawi has one of the world's highest rates of human immunodeficiency virus (HIV) infection (10.6%), and southern Malawi, where Thyolo district is located, bears the highest burden in the country (14.5%). Tuberculosis, common among HIV-infected people, requires radiologic diagnosis, yet Malawi has no radiologists in public service. This hinders rapid and accurate diagnosis and increases morbidity and mortality. APPROACH: Médecins Sans Frontières, in collaboration with Malawi's Ministry of Health, implemented teleradiology in Thyolo district to assist clinical staff in radiologic image interpretation and diagnosis. LOCAL SETTING: Thyolo district's 600 000 inhabitants are mostly subsistence-level or migrant farmers living in extreme poverty. Health facilities include one public hospital and 38 primary health centres. Understaffing and the absence of a radiologist make the diagnosis of tuberculosis difficult in a population where this disease affects 66% of patients with HIV infection. RELEVANT CHANGES: From September 2010-2011, 159 images (from 158 patients) were reviewed by teleradiology. Teleradiology changed patient management in 36 cases (23.5%). Two (1.3%) of them were cases of pulmonary tuberculosis not previously suspected by clinical staff. In addition, the radiologist's review corrected the misdiagnosis of tuberculosis and averted inappropriate treatment in 16 patients (10.5%). LESSONS LEARNT: Teleradiology can improve tuberculosis diagnosis and case management, especially if criteria to identify the patients most suitable for referral are developed and the radiologist is conversant with local resources and health problems. Designating a clinical focal point for teleradiology ensures sustainability. Staff need time to adapt to a new teleradiology programme.

Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique.

As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care.In Tete City, Mozambique, patients on antiretrovirals were rapidly down referred from a provincial hospital to four urban clinics in large numbers without careful planning, resulting in a number of patients being lost to follow-up.We outline some key lessons learned to support down referral, including the need to improve process management, clinic infrastructure, monitoring systems, and patient preparation. Down referral can be avoided by initiating patients' antiretroviral treatment at clinic level from the outset.