Modeling Optimal Laboratory Testing Strategies for Bacterial Meningitis Surveillance in Africa.

Since 2010, the introduction of an effective serogroup A meningococcal conjugate vaccine has led to the near-elimination of invasive Neisseria meningitidis serogroup A disease in Africa's meningitis belt. However, a significant burden of disease and epidemics due to other bacterial meningitis pathogens remain in the region. High-quality surveillance data with laboratory confirmation is important to monitor circulating bacterial meningitis pathogens and design appropriate interventions, but complete testing of all reported cases is often infeasible. Here, we use case-based surveillance data from 5 countries in the meningitis belt to determine how accurately estimates of the distribution of causative pathogens would represent the true distribution under different laboratory testing strategies. Detailed case-based surveillance data was collected by the MenAfriNet surveillance consortium in up to 3 seasons from participating districts in 5 countries. For each unique country-season pair, we simulated the accuracy of laboratory surveillance by repeatedly drawing subsets of tested cases and calculating the margin of error of the estimated proportion of cases caused by each pathogen (the greatest pathogen-specific absolute error in proportions between the subset and the full set of cases). Across the 12 country-season pairs analyzed, the 95% credible intervals around estimates of the proportion of cases caused by each pathogen had median widths of ±0.13, ±0.07, and ±0.05, respectively, when random samples of 25%, 50%, and 75% of cases were selected for testing. The level of geographic stratification in the sampling process did not meaningfully affect accuracy estimates. These findings can inform testing thresholds for laboratory surveillance programs in the meningitis belt.

Increasing rabies data availability: The example of a One Health research project in Chad, Côte d'Ivoire and Mali.

Rabies is a fatal but preventable disease that remains notoriously underreported. Weak data availability hampers advocacy, constitutes a barrier to resource allocation and inhibits effective prevention and control. To gain better insight into the global rabies burden and human vaccine demand several studies were funded through the Vaccine Alliance (GAVI) learning agenda. With the help of this funding, Swiss TPH and local in country partner organizations implemented a One Health research project in Chad, Côte d'Ivoire and Mali to collect data at household, public health facility and veterinary level. This paper describes the implementation of this research project and evaluates its success on amount of information gained, achieved capacity building, impact on knowledge creation and influence on national and international policies. The project was based on the One Health concept and guided by the principles of transboundary research partnerships formulated by the Swiss Academy of Sciences. Data was collected on bite incidents and health seeking from over 24'000 households, on access to treatment of over 8'800 bite cases registered in public health facilities and on the status of over 1'800 rabies suspect animals. Selected country specific datasets have contributed to more than 10 scientific articles so far. On the international level, the multi-level data collection provided a unique set of indicators to inform, along with results from other studies, new WHO rabies immunization recommendations and a vaccine investment case scenario to prevent human rabies. New rabies burden estimates based on the data gathered are published for Mali and will be modelled for the whole West and Central African region. On the national level, the project facilitated communication between animal health and human health workers catalyzing creation of local and national committees and formulation of national action plans for Mali and Côte D'Ivoire. Major challenges arose from lack of data collection and documentation experience of human health and veterinary workers and weak infrastructural capacities of the veterinary and human health systems of the project countries. Through adherence to the principles of transboundary research partnerships, project team members acquired valuable research and networking skills despite language barriers, enabling them to play key roles in the future agenda towards national, regional and global canine rabies elimination. Project external collaborations with local public institutions was facilitated through long-term local partnerships. Both factors enabled success in project implementation and outcomes by identifying and mitigating risks in advance, resolving challenges amiably and enabling mutual knowledge creation as a fructuous ground for sustained commitment. Lack of immediate follow-up funding did not allow to maintain activities beyond the project timeframe. However, the national and international policy changes triggered, as well as the strengthened local disease control and research capacities provides sustainable basis for the elimination of dog transmitted human rabies.

Implementation of Case-Based Surveillance and Real-time Polymerase Chain Reaction to Monitor Bacterial Meningitis Pathogens in Chad.

BACKGROUND: Meningococcal serogroup A conjugate vaccine (MACV) was introduced in Chad during 2011-2012. Meningitis surveillance has been conducted nationwide since 2003, with case-based surveillance (CBS) in select districts from 2012. In 2016, the MenAfriNet consortium supported Chad to implement CBS in 4 additional districts and real-time polymerase chain reaction (rt-PCR) at the national reference laboratory (NRL) to improve pathogen detection. We describe analysis of bacterial meningitis cases during 3 periods: pre-MACV (2010-2012), pre-MenAfriNet (2013-2015), and post-MenAfriNet (2016-2018). METHODS: National surveillance targeted meningitis cases caused by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae. Cerebrospinal fluid specimens, inoculated trans-isolate media, and/or isolates from suspected meningitis cases were tested via culture, latex, and/or rt-PCR; confirmed bacterial meningitis was defined by a positive result on any test. We calculated proportion of suspected cases with a specimen received by period, and proportion of specimens with a bacterial meningitis pathogen identified, by period, pathogen, and test. RESULTS: The NRL received specimens for 6.8% (876/12813), 46.4% (316/681), and 79.1% (787/995) of suspected meningitis cases in 2010-2012, 2013-2015, and 2016-2018, respectively, with a bacterial meningitis pathogen detected in 33.6% (294/876), 27.8% (88/316), and 33.2% (261/787) of tested specimens. The number of N. meningitidis serogroup A (NmA) among confirmed bacterial meningitis cases decreased from 254 (86.4%) during 2010-2012 to 2 (2.3%) during 2013-2015, with zero NmA cases detected after 2014. In contrast, proportional and absolute increases were seen between 2010-2012, 2013-2015, and 2016-2018 in cases caused by S. pneumoniae (5.1% [15/294], 65.9% [58/88], and 52.1% [136/261]), NmX (0.7% [2/294], 1.1% [1/88], and 22.2% [58/261]), and Hib (0.3% [1/294], 11.4% [10/88], and 14.9% [39/261]). Of specimens received at the NRL, proportions tested during the 3 periods were 47.7% (418), 53.2% (168), and 9.0% (71) by latex; 81.4% (713), 98.4% (311), and 93.9% (739) by culture; and 0.0% (0), 0.0% (0), and 90.5% (712) by rt-PCR, respectively. During the post-MenAfriNet period (2016-2018), 86.1% (678) of confirmed cases were tested by both culture and rt-PCR, with 12.5% (85) and 32.4% (220) positive by culture and rt-PCR, respectively. CONCLUSIONS: CBS implementation was associated with increased specimen referral. Increased detection of non-NmA cases could reflect changes in incidence or increased sensitivity of case detection with rt-PCR. Continued surveillance with the use of rt-PCR to monitor changing epidemiology could inform the development of effective vaccination strategies.

Bottlenecks in the provision of antenatal care: rural settled and mobile pastoralist communities in Chad.

OBJECTIVE: To assess antenatal care (ANC) coverage and analyse constraining factors for service delivery to rural settled and mobile populations in two districts in Chad. METHOD: Data from cross-sectional household and health facility surveys in the two Chadian rural health districts were analysed. First, contact coverage of ANC services in the study area was estimated from household data as the proportion of women who visited health facilities to obtain ANC during their last pregnancy. Second, bottlenecks in the provision of this service were explored by calibrating a multiplicative model of ANC contact coverage to household and health facility data. The model allowed quantification of the magnitude by which coverage decreased as it progressed through the health system. Sensitivity analysis was applied to account for uncertainty around the estimated coverage factors. RESULTS: Direct estimates revealed that ANC contact coverage decreased as the number of required visits increased: 79% of rural settled mothers and 46% of mobile pastoralist mothers visited a health facility to obtain ANC at least once (ANC 1). Among mobile pastoralists, only 20% of pregnant women attended ANC at least three times compared to 63% of rural settled women. Availability, accessibility, affordability and acceptability contributed to reductions in service coverage in both populations. For mobile pastoralists, acceptability was clearly the most important factor. ANC 1 contact coverage resulting from the model is 50% for rural settled and 30% for mobile pastoralists. CONCLUSION: Antenatal care coverage was low in rural districts of Chad, particularly for mobile pastoralists. Acceptability largely explained the prevailing difference between the two population groups.

[Evaluation of Knowledge-Attitudes-Practices of the populations in the health districts of Benoye, Laoukassy, Moundou and South N'Djamena towards canine rabies in Chad]. / Evaluation des Connaissances-Attitudes-Pratiques des populations des districts sanitaires de Benoye, Laoukassy, Moundou et N'Djaména Sud sur la rage canine au Tchad.

INTRODUCTION: Canine rabies remains a concern in Africa as well as in Chad. Our study aimed to evaluate the knowledge, attitudes and practices of the populations towards the appropriate management of people exposed to canine rabies and effective fight against it. METHODS: We conducted a cross-sectional, descriptive study in four health districts in Chad in July and in September 2015. Data were collected from households recruited by three-stage random sampling by means of a questionnaire. RESULTS: We conducted a survey of 2428 individuals having completed at least primary education level (54,12%). The average age was 36 ± 13.50 years. Surveyed individuals were farmers (35,17%), merchants (18,04%), households (12.81%). Rabies was defined as a disease transmitted from the dog to the man (41.43%), an alteration in brain function (41.27%), an undernourishment (10.26%). The cat was little-known to be a reservoir(13.84%) and a vector (19,77%) as well as licking was little-known to be a transmission medium (4.61%) and cat vaccination to be a preventive measure (0.49%). First aid for a bite at home was the traditional practice (47,69%), wounds washing (19.48%) or no action undertaken (20.43%). Households consulted the Health Service (78.50%), the Animal Health Service (5.35%) and the traditional healers (27%). CONCLUSION: A communication campaing for implementing first aid at home in the event of a bite, knowledge about the cat as a reservoir and a vector and licking as a transmission medium as well as the promotion of the consultation of veterinary services in the event of a bite are necessary.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad.

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N'Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general.

The Importance of a Participatory and Integrated One Health Approach for Rabies Control: The Case of N'Djaména, Chad.

This study compares data on animal rabies cases from the Chadian national rabies laboratory, hosted at the Insitut de Recherche en Elevage pour le Developpement (IRED), with bite case reporting from health facilities. The data collection accompanied a mass dog vaccination intervention over two years in N'Djaména, Chad. This allowed for a comparison of the dynamics of the incidence of animal rabies cases, human bite exposure incidence and post-exposure prophylaxis (PEP) demand during a dog rabies elimination attempt. Following the mass vaccination, the monthly animal rabies incidence dropped from 1.1/10,000 dogs, as observed prior to the campaign in 2012, to 0.061/10,000 dogs in 2014. However, the PEP demand was found to be largely unaffected. The suspicion of the rabies exposure as reported by health personnel in most cases did not reflect the status of the biting animal but rather the severity of the bite wound, resulting in inappropriate PEP recommendations. In addition, the levels of reporting dead or killed animals to the rabies laboratory was found to be very low. These results reveal a profound lack of communication between health facilities and veterinary structures and the absence of an integrated bite case management (IBCM) approach. Improved communication between human health and veterinary workers is imperative to prevent human rabies deaths through the appropriate use of PEP and to further translate success in animal rabies control into cost savings for the public health sector through a lower PEP demand. Improved training of health and veterinary personnel and the sensitisation of the public are needed to achieve good IBCM practice, to increase the rate of diagnostic testing, to provide adequate and timely PEP, and to reduce the wastage of scarce vaccine resources.

Cost-estimate and proposal for a development impact bond for canine rabies elimination by mass vaccination in Chad.

Close to 69,000 humans die of rabies each year, most of them in Africa and Asia. Clinical rabies can be prevented by post-exposure prophylaxis (PEP). However, PEP is commonly not available or not affordable in developing countries. Another strategy besides treating exposed humans is the vaccination of vector species. In developing countries, the main vector is the domestic dog, that, once infected, is a serious threat to humans. After a successful mass vaccination of 70% of the dogs in N'Djaména, we report here a cost-estimate for a national rabies elimination campaign for Chad. In a cross-sectional survey in four rural zones, we established the canine : human ratio at the household level. Based on human census data and the prevailing socio-cultural composition of rural zones of Chad, the total canine population was estimated at 1,205,361 dogs (95% Confidence interval 1,128,008-1,736,774 dogs). Cost data were collected from government sources and the recent canine mass vaccination campaign in N'Djaména. A Monte Carlo simulation was used for the simulation of the average cost and its variability, using probability distributions for dog numbers and cost items. Assuming the vaccination of 100 dogs on average per vaccination post and a duration of one year, the total cost for the vaccination of the national Chadian canine population is estimated at 2,716,359 Euros (95% CI 2,417,353-3,035,081) for one vaccination round. A development impact bond (DIB) organizational structure and cash flow scenario were then developed for the elimination of canine rabies in Chad. Cumulative discounted cost of 28.3 million Euros over ten years would be shared between the government of Chad, private investors and institutional donors as outcome funders. In this way, the risk of the investment could be shared and the necessary investment could be made available upfront - a key element for the elimination of canine rabies in Chad.

Operational performance and analysis of two rabies vaccination campaigns in N'Djamena, Chad.

Transmission of rabies from animals to people continues despite availability of good vaccines for both human and animal use. The only effective strategy to achieve elimination of dog rabies and the related human exposure is to immunize dogs at high coverage levels. We present the analysis of two consecutive parenteral dog mass vaccination campaigns conducted in N'Djamena in 2012 and 2013 to advocate the feasibility and effectiveness for rabies control through proof of concept. The overall coverage reached by the intervention was >70% in both years. Monthly reported rabies cases in dogs decreased by more than 90% within one year. Key points were a cooperative collaboration between the three partner institutions involved in the control program, sufficient information and communication strategy to access local leaders and the public, careful planning of the practical implementation phase and the effective motivation of staff. The dynamic and semi to non-restricted nature of dog populations in most rabies endemic areas is often considered to be a major obstacle to achieve sufficient vaccination coverage. However, we show that feasibility of dog mass vaccination is highly dependent on human determinants of dog population accessibility and the disease awareness of dog owners. Consequently, prior evaluation of the human cultural and socio-economic context is an important prerequisite for planning dog rabies vaccination campaigns.

The use of mobile phones for demographic surveillance of mobile pastoralists and their animals in Chad: proof of principle.

BACKGROUND: Demographic information is foundational for the planning and management of social programmes, in particular health services. The existing INDEPTH network surveillance sites are limited to coverage of sedentary populations. Including mobile populations in this approach would be expensive, time consuming and possibly low in accuracy. Very little is known about the demography of mobile pastoralists and their animals, so innovative approaches are urgently needed. OBJECTIVE: To test and evaluate a mobile demographic surveillance system for mobile pastoralist households, including livestock herds, using mobile phones. DESIGN: Mobile pastoralist camps were monitored (10 for 12 months and 10 for 18 months) using biweekly mobile phone calls with camp leaders and their wives to conduct interviews about the households and livestock. The collected information was validated through personal visits, GPS data and a livestock demographic model. RESULTS: The study showed the feasibility of mobile phone surveillance for mobile pastoralist camps, providing usable, valid information on human and livestock population structures, pregnancy outcomes and herd dynamics, as well as migration patterns. The approach was low-cost and applicable with the existing local resources. CONCLUSION: Demographic surveillance in mobile populations is feasible using mobile phones. Expansion of the small-scale system into a full mobile demographic surveillance system is warranted and would likely lead to improved planning and provision of human and animal health care.

Polio outbreak among nomads in Chad: outbreak response and lessons learned.

BACKGROUND: In response to the 2011 and 2012 polio epidemic in Chad, Chad's Ministry of Public Health, with support from Global Polio Eradication Initiative partners, took steps to increase vaccination coverage of nomadic children with targeted polio campaigns. This article describes the strategies we used to vaccinate nomads in 3 districts of Chad. METHODS: Our targeted interventions involved using mobile vaccination teams, recruiting local nomads to identify settlements, using social mobilization, and offering vaccinations to children, women, and animals. RESULTS: Vaccination coverage of nomadic children 0-59 months of age increased, particularly among those never before vaccinated against polio. These increases occurred mostly in the intervention districts of Dourbali, from 2956 to 8164 vaccinated children, and Kyabe, from 7319 to 15 868. The number of first-time vaccinated nomadic children also increased the most in these districts, from 60 to 131 in Dourbali and from 1302 to 2973 in Kyabe. Coverage in the Massaguet district was only 37.7%. CONCLUSIONS: Our success was probably due to (1) appointment of staff to oversee implementation, (2) engagement of the national government and its partners, (3) participation of nomadic community leaders, (4) intersectoral collaboration between human and animal health services, and (5) flexibility and capacity of vaccinators to vaccinate when and where nomads were available.

Priorities for research on meningococcal disease and the impact of serogroup A vaccination in the African meningitis belt.

For over 100 years, large epidemics of meningococcal meningitis have occurred every few years in areas of the African Sahel and sub-Sahel known as the African meningitis belt. Until recently, the main approach to the control of these epidemics has been reactive vaccination with a polysaccharide vaccine after an outbreak has reached a defined threshold and provision of easy access to effective treatment but this approach has not prevented the occurrence of new epidemics. Meningococcal conjugate vaccines, which can prevent meningococcal carriage and thus interrupt transmission, may be more effective than polysaccharide vaccines at preventing epidemics. Because the majority of African epidemics have been caused by serogroup A meningococci, a serogroup A polysaccharide/tetanus toxoid protein conjugate vaccine (PsA-TT) has recently been developed. Results from an initial evaluation of the impact of this vaccine on meningococcal disease and meningococcal carriage in Burkina Faso have been encouraging. To review how the research agenda for meningococcal disease in Africa has been changed by the advent of PsA-TT and to define a new set of research priorities for study of meningococcal infection in Africa, a meeting of 41 scientists was held in Dakar, Senegal on April 24th and 25th 2012. The research recommendations developed during the course of this meeting are presented in this paper. The need for enhanced surveillance for meningitis in defined populations with good diagnostic facilities in African countries at risk of epidemics was identified as the highest priority. This is needed to determine the duration of protection against serogroup A meningococcal disease provided by PsA-TT and to determine the risk of disease and carriage caused by meningococci of other serogroups. Other research areas given high priority included identification and validation of serological correlates of protection against meningococcal disease and carriage, development of improved methods for detecting carriage and epidemiological studies aimed at determining the reasons underlying the peculiar epidemiology of meningococcal disease in the African meningitis belt. Minutes and working papers from the meeting are provided in supplementary tables and some of the presentations made at the meeting are available on the MenAfriCar consortium website (www.menafricar.org) and on the web site of the Centers for Disease Control (www.cdc.gov).