Four years of case-based surveillance of meningitis following the introduction of MenAfriVac in Moissala, Chad: lessons learned.

OBJECTIVE: Case-based surveillance of bacterial meningitis in sentinel districts has been recommended after the introduction of the conjugated vaccine against Neisseria meningitidis serogroup A (NmA), MenAfriVac, in the African meningitis belt. Here we report data and lessons learnt from four years of surveillance in the district of Moissala, Chad. METHODS: All suspected cases of meningitis were referred free of charge to the district hospital for lumbar puncture and treatment. Cerebrospinal fluid samples were tested with Pastorex latex agglutination in Moissala, and inoculated trans-isolate media were used for culture and PCR at the national reference laboratory and/or at the Norwegian Institute of Public Health. RESULTS: From July 2012 to December 2016, 237 suspected cases of meningitis were notified, and a specimen was collected from 224. Eighty-three samples were positive for a bacterial pathogen by culture, PCR or Pastorex, including 58 cases due to Streptococcus pneumoniae with only 28 of 49 pneumococcal meningitis confirmed by culture or PCR correctly identified by Pastorex. Four cases of NmA were detected by Pastorex, but none were confirmed by PCR. CONCLUSION: Implementation of case-based surveillance for meningitis is feasible in Chad, but has required political and technical engagement. Given the high proportion of S. pneumoniae and its poor detection by Pastorex, continued use of PCR is warranted for surveillance outside of outbreaks, and efforts to accelerate the introduction of pneumococcal conjugate vaccines are needed. Introduction of MenAfriVac in routine immunisation and future availability of a pentavalent meningococcal conjugate vaccine will be key elements for the sustained reduction in meningitis outbreaks in the area.

Continuing effectiveness of serogroup A meningococcal conjugate vaccine, Chad, 2013.

In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted.

A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain.

BACKGROUND: In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in "Controlled Temperature Chain" (CTC; up to 40 °C for <30 days before administration), compared to standard cold chain (SCC; 2-8 °C). Prior to the study, stability parameters of TT-CTC were shown to meet international requirements. METHODS: A cluster randomized, non-inferiority trial was conducted in Moïssala district, Chad, December 2012-March 2013. Thirty-four included clusters were randomized to CTC or SCC. Women aged 14-49 years, eligible for TT vaccination and with a history of ≤1 TT dose, received two TT doses 4 weeks apart. Participants were blinded to allocation strategy. Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations (GMC). Non-inferiority was by seroconversion difference (TTSCC-TTCTC) <5% and ratio of GMCs (TTSCC/TTCTC) <1.5. Adverse events were monitored at health centers and at next contact with participants. RESULTS: A total of 2128 women (CTC=1068; SCC=1060) were recruited. Primary intention to vaccinate analysis included 1830 participants; 272 of these were included in the seroconversion analysis. Seroconversion was reached by >95% of participants; upper 95%CI of the difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI of GMC ratio was 1.36 in the adjusted analysis. Few adverse events were recorded. CONCLUSIONS: This study demonstrates the immunogenicity and safety of TT in CTC at <40 °C for <30 days. The high proportion of participants protected at baseline results in a reduction of power to detect a 5% non-inferiority margin. However, results at a 10% non-inferiority margin, the comparable GMC increases and vaccine's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain cannot be maintained.

Time is (still) of the essence: quantifying the impact of emergency meningitis vaccination response in Katsina State, Nigeria.

BACKGROUND: In 2009, a large meningitis A epidemic affected a broad region of northern Nigeria and southern Niger, resulting in more than 75 000 cases and 4000 deaths. In collaboration with state and federal agencies, Médecins Sans Frontières (MSF) intervened with a large-scale vaccination campaign using polysaccharide vaccine. Here the authors analyze the impact (cases averted) of the vaccination response as a function of the timing and coverage achieved. METHODS: Phenomenological epidemic models were fitted to replicate meningitis surveillance data from the Nigerian Ministry of Health/WHO surveillance system and from reinforced surveillance conducted by MSF in both vaccinated and unvaccinated areas using a dynamic, state-space framework to account for under-reporting of cases. RESULTS: The overall impact of the vaccination campaigns (reduction in meningitis cases) in Katsina State, northern Nigeria, ranged from 4% to 12%. At the local level, vaccination reduced cases by as much as 50% when campaigns were conducted early in the epidemic. CONCLUSIONS: Reactive vaccination with polysaccharide vaccine during meningitis outbreaks can significantly reduce the case burden when conducted early and comprehensively. Introduction of the conjugate MenAfriVac vaccine has reduced rates of disease caused by serogroup A Neisseria meningitidis in the region. Despite this, reactive campaigns with polysaccharide vaccine remain a necessary and important tool for meningitis outbreak response.

Global practices of meningococcal vaccine use and impact on invasive disease.

A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs.

Local discrepancies in measles vaccination opportunities: results of population-based surveys in Sub-Saharan Africa.

BACKGROUND: The World Health Organization recommends African children receive two doses of measles containing vaccine (MCV) through routine programs or supplemental immunization activities (SIA). Moreover, children have an additional opportunity to receive MCV through outbreak response immunization (ORI) mass campaigns in certain contexts. Here, we present the results of MCV coverage by dose estimated through surveys conducted after outbreak response in diverse settings in Sub-Saharan Africa. METHODS: We included 24 household-based surveys conducted in six countries after a non-selective mass vaccination campaign. In the majority (22/24), the survey sample was selected using probability proportional to size cluster-based sampling. Others used Lot Quality Assurance Sampling. RESULTS: In total, data were collected on 60,895 children from 2005 to 2011. Routine coverage varied between countries (>95% in Malawi and Kirundo province (Burundi) while <35% in N'Djamena (Chad) in 2005), within a country and over time. SIA coverage was <75% in most settings. ORI coverage ranged from >95% in Malawi to 71.4% [95% CI: 68.9-73.8] in N'Djamena (Chad) in 2005.In five sites, >5% of children remained unvaccinated after several opportunities. Conversely, in Malawi and DRC, over half of the children eligible for the last SIA received a third dose of MCV. CONCLUSIONS: Control pre-elimination targets were still not reached, contributing to the occurrence of repeated measles outbreak in the Sub-Saharan African countries reported here. Although children receiving a dose of MCV through outbreak response benefit from the intervention, ensuring that programs effectively target hard to reach children remains the cornerstone of measles control.

Measles outbreak response immunization is context-specific: insight from the recent experience of Médecins Sans Frontières.

Andrea Minetti and colleagues compare measles outbreak responses from the Democratic Republic of the Congo and Malawi and argue that outbreak response strategies should be tailored to local measles epidemiology. Please see later in the article for the Editors' Summary.

Global epidemiology of invasive meningococcal disease.

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.

Measles in Democratic Republic of Congo: an outbreak description from Katanga, 2010-2011.

BACKGROUND: The Democratic Republic of Congo experiences regular measles outbreaks. From September 2010, the number of suspected measles cases increased, especially in Katanga province, where Medecins sans Frontieres supported the Ministry of Health in responding to the outbreak by providing free treatment, reinforcing surveillance and implementing non-selective mass vaccination campaigns. Here, we describe the measles outbreak in Katanga province in 2010-2011 and the results of vaccine coverage surveys conducted after the mass campaigns. METHODS: The surveillance system was strengthened in 28 of the 67 health zones of the province and we conducted seven vaccination coverage surveys in 2011. RESULTS: The overall cumulative attack rate was 0.71% and the case fatality ratio was 1.40%. CONCLUSIONS: Early investigation of the age distribution of cases is a key to understanding the epidemic, and should guide the vaccination of priority age groups.

Performance of small cluster surveys and the clustered LQAS design to estimate local-level vaccination coverage in Mali.

BACKGROUND: Estimation of vaccination coverage at the local level is essential to identify communities that may require additional support. Cluster surveys can be used in resource-poor settings, when population figures are inaccurate. To be feasible, cluster samples need to be small, without losing robustness of results. The clustered LQAS (CLQAS) approach has been proposed as an alternative, as smaller sample sizes are required. METHODS: We explored (i) the efficiency of cluster surveys of decreasing sample size through bootstrapping analysis and (ii) the performance of CLQAS under three alternative sampling plans to classify local VC, using data from a survey carried out in Mali after mass vaccination against meningococcal meningitis group A. RESULTS: VC estimates provided by a 10 × 15 cluster survey design were reasonably robust. We used them to classify health areas in three categories and guide mop-up activities: i) health areas not requiring supplemental activities; ii) health areas requiring additional vaccination; iii) health areas requiring further evaluation. As sample size decreased (from 10 × 15 to 10 × 3), standard error of VC and ICC estimates were increasingly unstable. Results of CLQAS simulations were not accurate for most health areas, with an overall risk of misclassification greater than 0.25 in one health area out of three. It was greater than 0.50 in one health area out of two under two of the three sampling plans. CONCLUSIONS: Small sample cluster surveys (10 × 15) are acceptably robust for classification of VC at local level. We do not recommend the CLQAS method as currently formulated for evaluating vaccination programmes.

A long-lasting measles epidemic in Maroua, Cameroon 2008-2009: mass vaccination as response to the epidemic.

BACKGROUND: A measles outbreak occurred in Maroua, Cameroon, from January 2008 to April 2009. In accordance with recent World Health Organization guidelines, an outbreak-response immunization (ORI) was conducted in January 2009. The aim of this study was to investigate the causes of the epidemic in order to guide vaccination strategies. METHODS: We performed a stratified household-based survey using cluster sampling to determine measles vaccination coverage in children aged 9 months to 15 years. We defined 3 strata based on measles incidence. Next, we performed a case-control study to measure vaccine effectiveness (VE). Cases were obtained from health center registries. Controls were selected among respondents to the coverage survey. RESULTS: The vaccination-coverage survey included 2963 children in total. The overall routine vaccination coverage was 74.1% (95% confidence interval [CI]: 70.0%-78.3%). Measles incidence was inversely proportional to routine vaccination coverage, with high incidence associated with coverage of 71% and low incidence associated with coverage of 84%. The overall VE was 94% (95% CI, 86.7%-97.4%). After the ORI in January 2009, the coverage was >90% in all strata and measles incidence declined rapidly. DISCUSSION: Our results confirm that insufficient vaccination coverage was the main reason for this epidemic. The ORI conducted in January 2009 contributed both to control the epidemic and to increase the vaccination coverage to desirable levels.

Outbreak of beriberi in a prison in Côte d'Ivoire.

BACKGROUND: A beriberi outbreak occurred in the Maison d'Arrêt et de Correction d'Abidjan (MACA), a detention center in Abidjan, Côte d'Ivoire, between October 2002 and April 2003. OBJECTIVE: A retrospective investigation was conducted to document the outbreak in April 2003. METHODS: A descriptive analysis and a case-control study were performed. A probable case patient was defined as a person detained in the center between October 2002 and April 2003 with at least two of the following symptoms: bilateral leg edema, dyspnea, positive squat test, motor deficiencies, and paresthesia. A definite case patient was defined as a probable case patient who showed clinical improvement under thiamin treatment. RESULTS: Of 712 cases reported, 115 (16%) were probable and 597 (84%) were definite. The overall attack rate was 14.1%, and the case fatality rate was 1.0% (7/712). The highest attack rate was reported in the building housing prisoners with long-term sentences (16.9%). All patients were male, and the mean age was 28 years. During the period studied, the penal ration provided a fifth of the quantity of thiamin recommended by international standards. After adjustment for potential confounders, a history of cholera infection (adjusted odds ratio [OR(a)], 12.9; 95% confidence interval [CI], 2.9 to 54.1) and incarceration in the building for severe penalties (OR(a), 4.8; 95% CI, 1.3 to 18.5) were associated with the disease. CONCLUSIONS: Beriberi has been underreported among prisoners. Further attention should be given to its risk factors, especially a history of acute diarrhea. Systematic food supplementation with vitamins and micronutrients should be discussed when the penal ration does not provide the necessary nutrient intake recommended according to international standards.

Late vaccination reinforcement during a measles epidemic in Niamey, Niger (2003-2004).

Low measles vaccination coverage (VC) leads to recurrent epidemics in many African countries. We describe VC before and after late reinforcement of vaccination activities during a measles epidemic in Niamey, Niger (2003-2004) assessed by Lot Quality Assurance Sampling (LQAS). Neighborhoods of Niamey were grouped into 46 lots based on geographic proximity and population homogeneity. Before reinforcement activities, 96% of lots had a VC below 70%. After reinforcement, this proportion fell to 78%. During the intervention 50% of children who had no previous record of measles vaccination received their first dose (vaccination card or parental recall). Our results highlight the benefits and limitations of vaccine reinforcement activities performed late in the epidemic.

Adherence to the combination of sulphadoxine-pyrimethamine and artesunate in the Maheba refugee settlement, Zambia.

Artemisinin-based combination therapy (ACT) is one strategy recommended to increase cure rates in malaria and to contain resistance to Plasmodium falciparum. In the Maheba refugee settlement, children aged 5 years or younger with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulphadoxine-pyrimethamine (1 day) and artesunate (3 days). To measure treatment adherence, home visits were carried out the day after the last treatment dose. Patients who had any treatment dose left were considered certainly non-adherent. Other patients' classification was based on the answers to the questionnaire: patients whose caretakers stated the child had received the treatment regimen exactly as prescribed were considered probably adherent; all other patients were considered probably non-adherent. Reasons for non-adherence were assessed. We found 21.2% (95% CI [15.0-28.4]) of the patients to be certainly non-adherent, 39.4% (95% CI [31.6-47.6]) probably non-adherent, and 39.4% (95% CI [31.6-47.6]) probably adherent. Insufficient explanation by the dispenser was identified as an important reason for non-adherence. When considering the use of ACT, the issue of patient adherence remains challenging. However, it should not be used as an argument against the introduction of ACT. For these treatment regimens to remain efficacious on a long-term basis, specific and locally adapted strategies need to be implemented to ensure completion of the treatment.

Refugee Health: An approach to emergency situations

Ce livre est une réalisation collective des différentes sections de Médecins Sans Frontières (MSF), et a été écrit pour consolider la vaste expérience de MSF dans les programmes de réfugiés. Ce document traite des réfugiés et des personnes déplacées, et de ce quÆun organisme de santé peut faire pour soulager leurs souffrances. Il met l'accent sur ​​les politiques plutôt que sur les aspects pratiques, et vise à servir de guide aux décideurs.