Effects of an intervention program to improve mental health and epilepsy care in Madagascar.

BACKGROUND: Despite the high prevalence of mental disorders and epilepsy in low- and middle-income countries, nearly 80% of patients are not treated. In Madagascar, initiatives to improve access to epilepsy and mental health care, including public awareness and training of general practitioners (GPs), were carried out between 2013 and 2018. Our study's main objective was to assess the effectiveness of these initiatives, two to five years post-intervention. METHODS: This quasi-experimental study (intervention vs. control areas) included five surveys assessing: general population's Knowledge Attitudes and Practices (KAP), GPs' KAP , number of epilepsy and mental health consultations at different levels of the healthcare system, diagnostic accuracy, and treatments' availability. OUTCOMES: In the general population, KAP scores were higher in intervention areas for epilepsy (11.4/20 vs. 10.3/20; p = 0.003). For mental disorders, regardless of the area, KAP scores were low, especially for schizophrenia (1.1/20 and 0.1/20). Among GPs, KAP scores were higher in intervention areas for schizophrenia (6.0/10 vs. 4.5/10; p = 0.008) and epilepsy (6.9/10 vs. 6.2/10; p = 0.044). Overall, there was a greater proportion of mental health and epilepsy consultations in intervention areas (4.5% vs 2.3%). Although low, concordance between GPs' and psychiatrists' diagnoses was higher in intervention areas. There was a greater variety of anti-epileptic and psychotropic medications available in intervention areas. INTERPRETATION: This research has helped to better understand the effectiveness of initiatives implemented in Madagascar to improve epilepsy and mental health care and to identify barriers which will need to be addressed. FUNDING: Sanofi Global Health, as part of the Fight Against STigma Program.

Description of multiple myeloma cases and assessment of survival and mortality factors in Madagascar.

INTRODUCTION: In Madagascar, the epidemiologic, therapeutic, and evolutionary aspects of multiple myeloma remain poorly understood. Our objectives were to describe the cases, report factors associated with mortality, and estimate patient survival. PATIENTS AND METHOD: This was a retrospective descriptive and analytical study conducted in five teaching hospitals in Madagascar: HJRA and CENHOSOA (Antananarivo), CHUPZAGA (Mahajanga), CHUAT (Toamasina) and CHUT (Fianarantsoa). The study included patients diagnosed with multiple myeloma between January 1, 2010 and December 31, 2021. RESULTS: Of the 11,374 cancer patients, 75 (0.66%) had multiple myeloma. The mean age of the patients was 59.9 years (±8.9) and the sex ratio was 1.5. Arterial hypertension was observed in 32% of the patients. The most common symptom of myeloma was bone pain (n = 48; 64%). Forty-six patients (61%) were diagnosed with stage III myeloma and 28 patients (37.3%) with stage IIIA myeloma according to the Durie-Salmon classification. Anemia, renal failure, hypercalcemia and fractures were present in 53%, 37%, 21% and 28% of cases, respectively. Fifty-four patients received specific treatment. The combination of melphalan-prednisone-thalidomide was used in 79.63% of cases, and one patient had received autologous stem cell transplantation. Eleven patients (14.67%) died. Chronic kidney disease (p = 0.009), smoking (p = 0.028) and two associated comorbidities (p = 0.035) were associated with mortality. The median overall survival was 45.5 months. CONCLUSION: Patient survival is shorter than reported in the literature. The high mortality rate is due to comorbidities and limited access to recommended therapies.

Proactive community case management decreased malaria prevalence in rural Madagascar: results from a cluster randomized trial.

BACKGROUND: Malaria remains a leading cause of morbidity and mortality worldwide, with progress in malaria control stalling in recent years. Proactive community case management (pro-CCM) has been shown to increase access to diagnosis and treatment and reduce malaria burden. However, lack of experimental evidence may hinder the wider adoption of this intervention. We conducted a cluster randomized community intervention trial to assess the efficacy of pro-CCM at decreasing malaria prevalence in rural endemic areas of Madagascar. METHODS: Twenty-two fokontany (smallest administrative unit) of the Mananjary district in southeast Madagascar were selected and randomized 1:1 to pro-CCM (intervention) or conventional integrated community case management (iCCM). Residents of all ages in the intervention arm were visited by a community health worker every 2 weeks from March to October 2017 and screened for fever; those with fever were tested by a rapid diagnostic test (RDT) and treated if positive. Malaria prevalence was assessed using RDTs on all consenting study area residents prior to and following the intervention. Hemoglobin was measured among women of reproductive age. Intervention impact was assessed via difference-in-differences analyses using logistic regressions in generalized estimating equations. RESULTS: A total of 27,087 and 20,475 individuals participated at baseline and endline, respectively. Malaria prevalence decreased from 8.0 to 5.4% in the intervention arm for individuals of all ages and from 6.8 to 5.7% in the control arm. Pro-CCM was associated with a significant reduction in the odds of malaria positivity in children less than 15 years (OR = 0.59; 95% CI [0.38-0.91]), but not in older age groups. There was no impact on anemia among women of reproductive age. CONCLUSION: This trial suggests that pro-CCM approaches could help reduce malaria burden in rural endemic areas of low- and middle-income countries, but their impact may be limited to younger age groups with the highest malaria burden. TRIAL REGISTRATION: NCT05223933. Registered on February 4, 2022.

Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages.

BACKGROUND: Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours. METHODS: Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns. RESULTS: Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5-29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5-14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5-14-year-olds reported fever in the two weeks prior to survey (p = 0.044). CONCLUSIONS: The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.

How geographic access to care shapes disease burden: The current impact of post-exposure prophylaxis and potential for expanded access to prevent human rabies deaths in Madagascar.

BACKGROUND: Post-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning. METHODOLOGY & PRINCIPAL FINDINGS: We use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI): 790-1120), with PEP averting an additional 800 deaths (95% PI: 640-970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust. CONCLUSIONS & SIGNIFICANCE: PEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths.

Barriers inhibiting effective detection and management of postpartum hemorrhage during facility-based births in Madagascar: findings from a qualitative study using a behavioral science lens.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality in low-income countries, and is the most common direct cause of maternal deaths in Madagascar. Studies in Madagascar and other low-income countries observe low provider adherence to recommended practices for PPH prevention and treatment. Our study addresses gaps in the literature by applying a behavioral science lens to identify barriers inhibiting facility-based providers' consistent following of PPH best practices in Madagascar. METHODS: In June 2019, we undertook a cross-sectional qualitative research study in peri-urban and rural areas of the Vatovavy-Fitovinany region of Madagascar. We conducted 47 in-depth interviews in 19 facilities and five communities, with facility-based healthcare providers, postpartum women, medical supervisors, community health volunteers, and traditional birth attendants, and conducted thematic analysis of the transcripts. RESULTS: We identified seven key behavioral insights representing a range of factors that may contribute to delays in appropriate PPH management in these settings. Findings suggest providers' perceived low risk of PPH may influence their compliance with best practices, subconsciously or explicitly, and lead them to undervalue the importance of PPH prevention and monitoring measures. Providers lack clear feedback on specific components of their performance, which ultimately inhibits continuous improvement of compliance with best practices. Providers demonstrate great resourcefulness while operating in a challenging context with limited equipment, supplies, and support; however, overcoming these challenges remains their foremost concern. This response to chronic scarcity is cognitively taxing and may ultimately affect clinical decision-making. CONCLUSIONS: Our study reveals how perception of low risk of PPH, limited feedback on compliance with best practices and consequences of current practices, and a context of scarcity may negatively affect provider decision-making and clinical practices. Behaviorally informed interventions, designed for specific contexts that care providers operate in, can help improve quality of care and health outcomes for women in labor and childbirth.

Field assessment of dog as sentinel animal for plague in endemic foci of Madagascar.

The epidemiology of Yersinia pestis, the causative agent of plague, involves vectors and reservoirs in its transmission cycle. The passive plague surveillance in Madagascar targets mainly rodent and fleas. However, carnivores are routinely surveyed as sentinels of local plague activity in some countries. The aim of this study is to assess the use of domestic dog (Canis familiaris) as sentinel animal for field surveillance of plague in a highly endemic area in Madagascar. Cross-sectional surveys of plague antibody prevalence in C. familiaris were conducted in endemic areas with contrasting histories of plague cases in humans, as well as a plague free area. Rodent capture was done in parallel to evaluate evidence for Y. pestis circulation in the primary reservoirs. In 2 sites, dogs were later re-sampled to examine evidence of seroconversion and antibody persistence. Biological samplings were performed between March 2008 and February 2009. Plague antibody detection was assessed using anti-F1 ELISA. Our study showed a significant difference in dog prevalence rates between plague-endemic and plague-free areas, with no seropositive dogs detected in the plague free area. No correlation was found between rodents and dog prevalence rates, with an absence of seropositive rodents in some area where plague circulation was indicated by seropositive dogs. This is consistent with high mortality rates in rodents following infection. Re-sampling dogs identified individuals seropositive on both occasions, indicating high rates of re-exposure and/or persistence of plague antibodies for at least 9 months. Seroconversion or seropositive juvenile dogs indicated recent local plague circulation. In Madagascar, dog surveillance for plague antibody could be useful to identify plague circulation in new areas or quiescent areas within endemic zones. Within active endemic areas, monitoring of dog populations for seroconversion (negative to positive) or seropositive juvenile dogs could be useful for identifying areas at greatest risk of human outbreaks.

[Prevalence of sickle cell trait in blood donors at the regional blood transfusion center in the Haute Matsiatra Region, Madagascar]. / Prévalence du trait drépanocytaire chez les donneurs de sang au centre régional de transfusion sanguine de la région Haute Matsiatra, Madagascar.

INTRODUCTION: sickle cell trait is the heterozygous form of sickle-cell disease. Patients with sickle cell trait can synthesize normal hemoglobin A and hemoglobin S. This condition has no recognizable clinical signs; then subjects with sickle cell trait, ignoring their genetic status, can be found among blood donors. This can have severe impact on donors´ health status and on that of recipients, especially if these have sickle-cell trait. The purpose of our study is to determine the prevalence of sickle cell trait in blood donors. METHODS: we conducted a 4-month descriptive prospective study (January-May 2017) at the Haute Matsiatra Regional Blood Transfusion Center (RBTC). All donors were screened by Emmel test and positive cases were confirmed by hemoglobin electrophoresis. RESULTS: the study involved 427 donors, of whom 332 were men and 95 women (sex ratio 3.4). The average age of blood donors was 32.72, ranging from 18 to 64 years. Emmel test was positive in 5 donors (1.17%). These patients had the AS genotype confirmed by hemoglobin electrophoresis. CONCLUSION: the results of this study reveal the presence of sickle cell trait among blood donors at the CRTS. Most of them ignore their sickle cell status before blood donation. Quality and safety of blood and blood products are mandatory, hence the importance of screening among blood donors is a current relevant issue.

Diarrhea hospitalization costs among children <5 years old in Madagascar.

BACKGROUND: Following a recommendation by the World Health Organization, Madagascar introduced rotavirus vaccine in 2014. Though national rotavirus vaccine coverage has remained <80%, rotavirus hospitalizations declined by 78%. Gavi, the Vaccine Alliance, has provided financial support for rotavirus vaccine, however the Malagasy government has increasing responsibility for the financial cost. METHODS: In this evaluation, we describe the direct medical, direct non-medical, and indirect cost of illness due to diarrhea among children <5 years old at a public pediatric referral hospital. A 3-part structured questionnaire was administered during and following the hospitalization and the child's hospital record was reviewed. RESULTS: In total, 96 children were included in this analysis. The median total cost of the illness was $156.00 (IQR: 104.00, 210.86) and the median direct medical cost was $107.22. Service delivery costs represented a median of 44% of the inpatient costs; medications and diagnostic tests represented a median of 28% and 20% of the total costs of the hospitalization, respectively. The median percentage of the total illness costs paid by the household was 67%. Among households with income of <$61/month, the median costs of the illness paid by the household were $78.55, representing a median of 168% of the household's monthly expenses. Among households earning >$303/month, the median costs paid by the household were $147.30, representing a median of 53% of the household's monthly expenses. Among all household income levels, caregivers commonly paid these bills from savings, borrowed money, and donations. CONCLUSIONS: Our findings will be useful in assessing the cost-effectiveness of rotavirus vaccine by decisionmakers. These results may also help hospital administrators and healthcare providers better understand the financial constraints of families.

Drones and digital adherence monitoring for community-based tuberculosis control in remote Madagascar: A cost-effectiveness analysis.

BACKGROUND: Continuing tuberculosis control with current approaches is unlikely to reach the World Health Organization's objective to eliminate TB by 2035. Innovative interventions such as unmanned aerial vehicles (or drones) and digital adherence monitoring technologies have the potential to enhance patient-centric quality tuberculosis care and help challenged National Tuberculosis Programs leapfrog over the impediments of conventional Directly Observed Therapy (DOTS) implementation. A bundle of innovative interventions referred to for its delivery technology as the Drone Observed Therapy System (DrOTS) was implemented in remote Madagascar. Given the potentially increased cost these interventions represent for health systems, a cost-effectiveness analysis was indicated. METHODS: A decision analysis model was created to calculate the incremental cost-effectiveness of the DrOTS strategy compared to DOTS, the standard of care, in a study population of 200,000 inhabitants in rural Madagascar with tuberculosis disease prevalence of 250/100,000. A mixed top-down and bottom-up costing approach was used to identify costs associated with both models, and net costs were calculated accounting for resulting TB treatment costs. Net cost per disability-adjusted life years averted was calculated. Sensitivity analyses were performed for key input variables to identify main drivers of health and cost outcomes, and cost-effectiveness. FINDINGS: Net cost per TB patient identified within DOTS and DrOTS were, respectively, $282 and $1,172. The incremental cost per additional TB patient diagnosed in DrOTS was $2,631 and the incremental cost-effectiveness ratio of DrOTS compared to DOTS was $177 per DALY averted. Analyses suggest that integrating drones with interventions ensuring highly sensitive laboratory testing and high treatment adherence optimizes cost-effectiveness. CONCLUSION: Innovative technology packages including drones, digital adherence monitoring technologies, and molecular diagnostics for TB case finding and retention within the cascade of care can be cost effective. Their integration with other interventions within health systems may further lower costs and support access to universal health coverage.

Inequalities in cause-specific mortality in children and adolescents in the Moramanga health survey, Madagascar.

OBJECTIVES: One child or young adolescent dies every 10 min in Madagascar and large disparities in survival persist. We estimated cause-specific mortality in a cohort of children aged 0-14 in the Moramanga district and explored how causes of death shape these inequalities. METHODS: Children were followed prospectively between 2012 and 2017. Causes of death were established based on verbal autopsies. Incidence rate ratios were estimated in Poisson regression models. RESULTS: The risk of dying before age 15 was 68.1 per thousand live births. Risks of dying were highest in the first year of life (31.2‰) and lowest in children aged 10-14 (6.4‰). The male-to-female sex ratios of mortality increased with age and reached 2.3 among adolescents aged 10-14. Communicable, nutritional and neonatal causes accounted for 79.5% of deaths below age 5 and 47.0% above age 5. Mortality was positively associated with household poverty, lack of education of the household head, and rural residence. CONCLUSIONS: Interventions should be designed with an equity lens to reduce large disparities in survival and be tailored to the needs of each age-group.

A Mixed-Method Design Evaluation of the SAFE Obstetric Anaesthesia Course at 4 and 12-18 Months After Training in the Republic of Congo and Madagascar.

BACKGROUND: Maternal mortality in low- and middle-income countries (LMICs) is higher than in high-income countries (HICs), and poor anesthesia care is a contributing factor. Many anesthesia complications are considered preventable with adequate training. The Safer Anaesthesia From Education Obstetric Anaesthesia (SAFE-OB) course was designed as a refresher course to upgrade the skills of anesthesia providers in low-income countries, but little is known about the long-term impact of the course on changes in practice. We report changes in practice at 4 and 12-18 months after SAFE-OB courses in Madagascar and the Republic of Congo. METHODS: We used a concurrent embedded mixed-methods design based on the Kirkpatrick model for evaluating educational training courses. The primary outcome was qualitative determination of personal and organizational change at 4 months and 12-18 months. Secondary outcomes were quantitative evaluations of knowledge and skill retention over time. From 2014 to 2016, 213 participants participated in 5 SAFE-OB courses in 2 countries. Semistructured interviews were conducted at 4 and 12-18 months using purposive sampling and analyzed using thematic content analysis. Participants underwent baseline knowledge and skill assessment, with 1 cohort reevaluated using repeat knowledge and skills tests at 4 months and another at 12-18 months. RESULTS: At 4 months, 2 themes of practice change (Kirkpatrick level 3) emerged that were not present at 12-18 months: neonatal resuscitation and airway management. At 12-18 months, 4 themes emerged: management of obstetric hemorrhage, management of eclampsia, using a structured approach to assessing a pregnant woman, and management of spinal anesthesia. With respect to organizational culture change (Kirkpatrick level 4), the same 3 themes emerged at both 4 and 12-18 months: improved teamwork, communication, and preparation. Resistance from peers, lack of senior support, and lack of resources were cited as barriers to change at 4 months, but at 12-18 months, very few interviewees mentioned lack of resources. Identified catalysts for change were self-motivation, credibility, peer support, and senior support. Knowledge and skills tests both showed an immediate improvement after the course that was sustained. This supports the qualitative responses suggesting personal and organizational change. CONCLUSIONS: Participation at a SAFE-OB course in the Republic of Congo and in Madagascar was associated with personal and organizational changes in practice and sustained improvements in knowledge and skill at 12-18 months.

A Multicenter Cost-of-Illness and Long-term Socioeconomic Follow-up Study in the Severe Typhoid Fever in Africa Program: Study Protocol.

BACKGROUND: There are limited data on typhoid fever cost of illness (COI) and economic impact from Africa. Health economic data are essential for measuring the cost-effectiveness of vaccination or other disease control interventions. Here, we describe the protocol and methods for conducting the health economic studies under the Severe Typhoid Fever in Africa (SETA) program. METHODS: The SETA health economic studies will rely on the platform for SETA typhoid surveillance in 4 African countries-Burkina Faso, Ethiopia, Ghana, and Madagascar. A COI and long-term socioeconomic study (LT-SES) will be its components. The COI will be assessed among blood culture-positive typhoid fever cases, blood culture-negative clinically suspected cases (clinical cases), and typhoid fever cases with pathognomonic gastrointestinal perforations (special cases). Repeated surveys using pretested questionnaires will be used to measure out-of-pocket expenses, quality of life, and the long-term socioeconomic impact. The cost of resources consumed for diagnosis and treatment will be collected at health facilities. RESULTS: Results from these studies will be published in peer-reviewed journals and presented at scientific conferences to make the data available to the wider health economics and public health research communities. CONCLUSIONS: The health economic data will be analyzed to estimate the average cost per case, the quality of life at different stages of illness, financial stress due to illness, and the burden on the family due to caregiving during illness. The data generated are expected to be used in economic analysis and policy making on typhoid control interventions in sub-Saharan Africa.

Transmission Routes of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae in a Neonatology Ward in Madagascar.

The diffusion of extended-spectrum beta-lactamase (E-ESBL)-producing Enterobacteriaceae is a major concern worldwide, especially in low-income countries, where they may lead to therapeutic failures. In hospitals, where colonization is the highest, E-ESBL transmission is poorly understood, limiting the possibility of establishing effective control measures. We assessed E-ESBL-acquisition routes in a neonatalogy ward in Madagascar. Individuals from a neonatology ward were longitudinally followed-up (August 2014-March 2015). Newborns' family members' and health-care workers (HCWs) were stool-sampled and tested for E-ESBL colonization weekly. Several hypothetical acquisition routes of newborns-e.g. direct contact with family members and HCWs and indirect contact with other newborns through environmental contamination, colonization pressure, or transient hand carriage-were examined and compared using mathematical modeling and Bayesian inference. In our results, high E-ESBL acquisition rates were found, reaching > 70% for newborns, > 55% for family members, and > 75% for HCWs. Modeling analyses indicated transmission sources for newborn colonization to be species dependent. Health-care workers' route were selected for Klebsiella pneumoniae and Escherichia coli, with respective estimated transmission strengths of 0.05 (0.008; 0.14) and 0.008 (0.001; 0.021) ind-1 day-1. Indirect transmissions associated with ward prevalence, e.g. through hand carriage or environment, were selected for Enterobacter cloacae, E. coli, and K. pneumoniae (range 0.27-0.41 ind-1 day-1). Importantly, family members were not identified as transmission source. To conclude, E-ESBL acquisition sources are strongly species dependent. Escherichia coli and E. cloacae involve more indirect contamination, whereas K. pneumoniae also spreads through contact with colonized HCWs. These findings should help improve control measures to reduce in-hospital transmission.

Burden and epidemiology of influenza- and respiratory syncytial virus-associated severe acute respiratory illness hospitalization in Madagascar, 2011-2016.

BACKGROUND: Influenza and respiratory syncytial virus (RSV) infections are responsible for substantial global morbidity and mortality in young children and elderly individuals. Estimates of the burden of influenza- and RSV-associated hospitalization are limited in Africa. METHODS: We conducted hospital-based surveillance for laboratory-confirmed influenza- and RSV-associated severe acute respiratory illness (SARI) among patients of any age at one hospital and a retrospective review of SARI hospitalizations in five hospitals situated in Antananarivo during 2011-2016. We estimated age-specific rates (per 100 000 population) of influenza- and RSV-associated SARI hospitalizations for the Antananarivo region and then extrapolated these rates to the national level. RESULTS: Overall, the mean annual national number of influenza-associated SARI hospitalizations for all age groups was 6609 (95% CI: 5381-7835-rate: 30.0; 95% CI: 24.4-35.6), 4468 (95% CI: 3796-5102-rate: 127.6; 95% CI: 108.4-145.7), 2141 (95% CI: 1585-2734-rate: 11.6; 95% CI: 8.6-14.8), and 339 (95% CI: 224-459-rate: 50.0; 95% CI: 36.3-74.4) among individuals aged <5, ≥5, and ≥65 years, respectively. For these same age groups, the mean annual number of RSV-associated SARI hospitalizations was 11 768 (95% CI: 10 553-12 997-rate: 53.4; 95% CI: 47.9-59.0), 11 299 (95% CI: 10 350-12 214-rate: 322.7; 95% CI: 295.6-348.8), 469 (95% CI: 203-783-rate: 2.5;95% CI: 1.1-4.2), and 36 (95% CI: 0-84-rate: 5.8; 0.0-13.5), respectively. CONCLUSION: The burden of influenza- and RSV-associated SARI hospitalization was high among children aged <5 years. These first estimates for Madagascar will enable government to make informed evidence-based decisions when allocating scarce resources and planning intervention strategies to limit the impact and spread of these viruses.

Healthcare utilization, provisioning of post-exposure prophylaxis, and estimation of human rabies burden in Madagascar.

In Madagascar, dog-mediated rabies has been endemic for over a century, however there is little data on its incidence or impact. We collected data over a 16-month period on provisioning of post-exposure prophylaxis (PEP) at a focal clinic in the Moramanga District and determined the rabies status of biting animals using clinical and laboratory diagnosis. We find that animal rabies cases are widespread, and clinic-based triage and investigation are effective ways to increase detection of rabies exposures and to rule out non-cases. A high proportion of rabies-exposed persons from Moramanga sought (84%) and completed PEP (90% of those that initiated PEP), likely reflecting the access and free provisioning of PEP in the district. Current clinic vial sharing practices demonstrate the potential for intradermal administration of PEP in endemic African settings, reducing vaccine use by 50% in comparison to intramuscular administration. A high proportion of PEP demand was attributed to rabies cases, with approximately 20% of PEP administered to probable rabies exposures and an additional 20% to low-to-no risk contacts with confirmed/probable animal or human cases. Using a simplified decision tree and our data on rabies exposure status and health-seeking behavior, we estimated an annual incidence of 42-110 rabies exposures and 1-3 deaths per 100,000 persons annually. Extrapolating to Madagascar, we estimate an annual burden of 282-745 human rabies deaths with current PEP provisioning averting 1499-3958 deaths each year. Data from other clinics and districts are needed to improve these estimates, particularly given that PEP availability is currently limited to only 31 clinics in the country. A combined strategy of mass dog vaccination, enhanced surveillance, and expanded access to PEP along with more judicious guidelines for administration could effectively reduce and eventually eliminate the burden of rabies in Madagascar.