Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.

Suboptimal Bacteriological Quality of Household Water in Municipal Ibadan, Nigeria.

Access to potable water is difficult for many African residents. This study evaluated the bacteriological quality of household water collected in the dry and wet seasons across five municipal local government areas (LGAs) in Ibadan, a large city in southwest Nigeria. A total of 447 water samples (dry season, n = 250; wet season, n = 197) were aseptically collected from a random sample of mapped households within Ibadan's five municipal LGAs. The pH values and total aerobic and coliform bacterial counts were measured, and samples were screened for Escherichia coli, Salmonella, Shigella, and Yersinia by standard phenotypic techniques and multiplex polymerase chain reaction. The most common source of water was well (53.2%), followed by borehole (34%). None of the households used municipal tap water. Cumulatively, aerobic (P = 0.0002) and coliform (P = 0.0001) counts as well as pH values (P = 0.0002) changed significantly between seasons, with increasing and decreasing counts depending on the LGA. Nonpotable water samples were found to be very common during the dry (86.8%) and wet (74.1%) seasons. Escherichia coli spp., as indicators of recent fecal contamination, were isolated from 115 (25.7%) of the household water sources. Thirty three Salmonella, four enteroaggregative E. coli, and four enterotoxigenic E. coli isolates but no Shigella or Yersinia isolates were identified. This study revealed the absence of treated tap water and the poor quality of alternative sources with detectable pathogens in municipal Ibadan. Addressing the city-wide lack of access to potable water is an essential priority for preventing a high prevalence of feco-orally transmitted infections.

Evaluating Quality Management and Diagnostics Microbiology Performance Within an International External Quality Assessment (EQA) Program Serving National One Health Sector Reference Laboratories Across Asia: Experience Amid the Coronavirus Disease 2019 (COVID-19) Pandemic.

BACKGROUND: Strengthening external quality assessment (EQA) services across the One Health sector supports implementation of effective antimicrobial resistance (AMR) control strategies. Here we describe and compare 2 different approaches for conducting virtual laboratory follow-up assessments within an EQA program to evaluate quality management system (QMS) and procedures for pathogen identification and antimicrobial susceptibility testing (AST). METHODS: During the coronavirus disease 2019 (COVID-19) pandemic in 2021 and 2022, 2 laboratory assessment approaches were introduced: virtual-based and survey-based methodologies. The evaluation of 2 underperforming Animal Health laboratories through a virtual-based approach occurred between May and August 2021. This evaluation encompassed the utilization of 3 online meetings and document reviews, performed subsequent to the execution of EQA procedures. Within a distinct group of laboratories, the survey-based assessment was implemented from December 2021 to February 2022, also following EQA procedures. This phase encompassed the dissemination of an online survey to 31 participating laboratories, alongside a sole online consultation meeting involving 4 specific underperforming laboratories. RESULTS: The virtual-based assessment post-EQA aimed to identify gaps and areas for improvement in the laboratory's practices for pathogen identification and AST. This approach was, however, time-intensive, and, hence, only 2 laboratories were assessed. In addition, limited interactions in virtual platforms compromised the assessment quality. The survey-based post-EQA assessment enabled evaluation of 31 laboratories. Despite limitations for in-depth analysis of each procedure, gaps in QMS across multiple laboratories were identified and tailored laboratory-specific recommendations were provided. CONCLUSIONS: Reliable internet and plans for efficient time management, post-EQA virtual laboratory follow-up assessments are an effective alternative when conducting onsite evaluation is infeasible as observed during the COVID-19 pandemic, although the successful implementation of remediation plans will likely require in person assessments. We advocate application of hybrid approaches (both onsite and virtual) for targeted capacity building of AMR procedures with the ability to implement and oversee the process.

Mortality patterns over a 10-year period in Kibera, an urban informal settlement in Nairobi, Kenya, 2009-2018.

BACKGROUND: Reliable mortality data are important for evaluating the impact of health interventions. However, data on mortality patterns among populations living in urban informal settlements are limited. OBJECTIVES: To examine the mortality patterns and trends in an urban informal settlement in Kibera, Nairobi, Kenya. METHODS: Using data from a population-based surveillance platform we estimated overall and cause-specific mortality rates for all age groups using person-year-observation (pyo) denominators and using Poisson regression tested for trends in mortality rates over time. We compared associated mortality rates across groups using incidence rate ratios (IRR). Assignment of probable cause(s) of death was done using the InterVA-4 model. RESULTS: We registered 1134 deaths from 2009 to 2018, yielding a crude mortality rate of 4.4 (95% Confidence Interval [CI]4.2-4.7) per 1,000 pyo. Males had higher overall mortality rates than females (incidence rate ratio [IRR], 1.44; 95% CI, 1.28-1.62). The highest mortality rate was observed among children aged < 12 months (41.5 per 1,000 pyo; 95% CI 36.6-46.9). All-cause mortality rates among children < 12 months were higher than that of children aged 1-4 years (IRR, 8.5; 95% CI, 6.95-10.35). The overall mortality rate significantly declined over the period, from 6.7 per 1,000 pyo (95% CI, 5.7-7.8) in 2009 to 2.7 (95% CI, 2.0-3.4) per 1,000 pyo in 2018. The most common cause of death was acute respiratory infections (ARI)/pneumonia (18.1%). Among children < 5 years, the ARI/pneumonia deaths rate declined significantly over the study period (5.06 per 1,000 pyo in 2009 to 0.61 per 1,000 pyo in 2018; p = 0.004). Similarly, death due to pulmonary tuberculosis among persons 5 years and above significantly declined (0.98 per 1,000 pyo in 2009 to 0.25 per 1,000 pyo in 2018; p = 0.006). CONCLUSIONS: Overall and some cause-specific mortality rates declined over time, representing important public health successes among this population.

Characterization of Typhoid Intestinal Perforation in Africa: Results From the Severe Typhoid Fever Surveillance in Africa Program.

Background: Typhoid intestinal perforation (TIP) remains the most serious complication of typhoid fever. In many countries, the diagnosis of TIP relies on intraoperative identification, as blood culture and pathology capacity remain limited. As a result, many cases of TIP may not be reported as typhoid. This study demonstrates the burden of TIP in sites in Burkina Faso, Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Methods: Patients with clinical suspicion of nontraumatic intestinal perforation were enrolled and demographic details, clinical findings, surgical records, blood cultures, tissue biopsies, and peritoneal fluid were collected. Participants were then classified as having confirmed TIP, probable TIP, possible TIP, or clinical intestinal perforation based on surgical descriptions and cultures. Results: A total of 608 participants were investigated for nontraumatic intestinal perforation; 214 (35%) participants had surgically-confirmed TIP and 33 participants (5%) had culture-confirmed typhoid. The overall proportion of blood or surgical site Salmonella enterica subspecies enterica serovar Typhi positivity in surgically verified TIP cases was 10.3%. TIP was high in children aged 5-14 years in DRC, Ghana, and Nigeria. We provide evidence for correlation between monthly case counts of S. Typhi and the occurrence of intestinal perforation. Conclusions: Low S. Typhi culture positivity rates, as well as a lack of blood and tissue culture capability in many regions where typhoid remains endemic, significantly underestimate the true burden of typhoid fever. The occurrence of TIP may indicate underlying typhoid burden, particularly in countries with limited culture capability.

Dynamic Incidence of Typhoid Fever over a 10-Year Period (2010-2019) in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting.

Restoring non-COVID-19 clinical research and surveillance in Oyo state, Nigeria during the SARS-CoV-2pandemic.

Background: Many sub-Saharan African patients receive clinical care from extramurally-supported research and surveillance. Dur- ing the COVID-19 pandemic, pausing these activities reduces pa- tient care, surveillance, and research staff employment, increasing pandemic losses. In Oyo State, Nigeria, we paused a multi-country invasive salmonellosis surveillance initiative and a rural clinical bac- teriology project. Objective: Working with research partners raises health facility con- cerns about SARS-CoV-2 transmission risks and incurs infection pre- vention costs, so we developed and implemented re-opening plans to protect staff and patients and help health facilities deliver care. Methods: Our reopening plan included appointing safety and per- sonal protective equipment (PPE) managers from existing project staff cadres, writing new standard operating procedures, implement- ing extensive assessed training, COVID-19 testing for staff, procuring and managing PPE, and providing secondary bacteraemia blood culture support for COVID-19 patients in State isolation facilities. Results: Surveillance data showed that the pandemic reduced care access and negatively affected patient unsupervised antibacterial use. The re-opening plan repurposed human and material resources from national and international extramurally-supported programs to mitigate these effects on public health. Conclusions: A structured reopening plan restarted care, surveil- lance, and infection prevention and control.

Mapping the coverage, availability and uptake of External Quality Assessment programmes across One Health sectors in Asia.

INTRODUCTION: Establishing effective external quality assessment (EQA) programmes is an important element in ensuring the quality of, and building capacity for, antimicrobial resistance (AMR) laboratory surveillance. OBJECTIVES: To understand the current coverage of, and challenges to participation in, EQAs in National Reference Laboratories (NRLs) across One Health (OH) sectors in Asia. METHODS: Current EQA coverage was evaluated through desktop review, online surveys and interviews of both EQA participants and providers. EQA coverage was mapped and summarized by laboratory type and 'readiness' level and identified challenges evaluated qualitatively. RESULTS: Of the 31 identified NRLs [16 Human Health (HH) and 15 Animal/Food Safety laboratories (A/FS)], 14 HH and 7 A/FS laboratories currently participated in international EQA schemes and several participated in two or more different schemes. Seven laboratories were currently not participating in any EQA scheme and two of these (one HH and one A/FS) do not currently perform microbiology; six HH NRLs provided national EQAs. Of the eight surveyed international EQA providers, three were based in Asia and all offered varying programmes in terms of pathogens, frequency and support mechanisms for reporting and follow-up. Only one provider currently served laboratories across all OH sectors. CONCLUSIONS: The current coverage of EQA programmes for AMR in Asia was heterogeneous across countries but especially across OH sectors. This updated overview of the coverage and challenges associated with participation in, and provision of, EQAs for AMR suggest the benefit and relevance of introducing one comprehensive and high-quality EQA programme across OH sectors in Asia.

The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries.

BACKGROUND: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent. METHODS: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010-2014) and a fever study in Ghana (2007-2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site. RESULTS: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries. CONCLUSIONS: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.

No Evidence of Acute Dengue Virus Infections at a Rural Site in Western Kenya, 2011 and 2013.

The incidence and spread of dengue virus (DENV) have increased rapidly in recent decades. Dengue is underreported in Africa, but recent outbreaks and seroprevalence data suggest that DENV is widespread there. A lack of ongoing surveillance limits knowledge about its spatial reach and hinders disease control planning. We sought to add data on dengue distribution in Kenya through diagnostic testing of serum specimens from persons with an acute febrile illness (AFI) attending an outpatient clinic in rural western Kenya (Asembo) during rainy seasons. Patients with symptoms not likely to be misclassified as dengue (e.g., diarrhea and anemia), those with a positive diagnostic laboratory results which explained their febrile illness, or those with serum collected more than 5 days after fever onset were excluded. However, febrile patients with a positive malaria smear were included in the study. We used reverse transcription polymerase chain reaction (RT-PCR) to test for DENV and IgM anti-DENV to test for recent infection. Of the 615 serum specimens available for testing, none were dengue positive by either RT-PCR or IgM anti-DENV testing. Dengue did not appear to be a cause of febrile illness in this area of western Kenya, although our relatively small sample size may not have identified DENV infections occurring at low incidence. A more widespread AFI surveillance system that includes dengue diagnostic testing by RT-PCR and antibody-based methods is required to more definitively gauge the size and geographic distribution of DENV infection in western Kenya.

The epidemiology of dengue outbreaks in 2016 and 2017 in Ouagadougou, Burkina Faso.

BACKGROUND: Dengue is prevalent in as many as 128 countries with more than 100 million clinical episodes reported annually and four billion people estimated to be at risk. While dengue fever is systematically diagnosed in large parts of Asia and South America, the disease burden in Africa is less well investigated. This report describes two consecutive dengue outbreaks in Ouagadougou, Burkina Faso in 2016 and 2017. METHODS: Blood samples of febrile patients received at Schiphra laboratory in Ouagadougou, Burkina Faso, were screened for dengue infection using SD Bioline Dengue Duo rapid diagnostic test kits (Standard Diagnostics, Suwon, Republic of Korea). RESULTS: A total of 1,397 and 1,882 cases were reported by a single laboratory in 2016 and 2017, respectively. Most cases were at least 15 years of age and the results corroborated reports from WHO indicating the circulation of three dengue virus serotypes in Burkina Faso. CONCLUSION: This study complements data from other, simultaneously conducted surveillance efforts, and indicates that the dengue disease burden might be underestimated in sub-Saharan African nations. Dengue surveillance should be enhanced in African settings to determine the burden more accurately, and accelerated efforts towards a dengue vaccine should be put in place.

Impact of 10-Valent Pneumococcal Conjugate Vaccine Introduction on Pneumococcal Carriage and Antibiotic Susceptibility Patterns Among Children Aged <5 Years and Adults With Human Immunodeficiency Virus Infection: Kenya, 2009-2013.

BACKGROUND: Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1-4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults. METHODS: During 2009-2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1-4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009-2010 as baseline. RESULTS: We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV-). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1-4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1-4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV-). Approximately 80% of isolates were PNSP, both in 2009 and 2013. CONCLUSIONS: PCV10-type carriage declined in children <5 years and adults post-PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination.

How Can the Typhoid Fever Surveillance in Africa and the Severe Typhoid Fever in Africa Programs Contribute to the Introduction of Typhoid Conjugate Vaccines?

BACKGROUND: The World Health Organization now recommends the use of typhoid conjugate vaccines (TCVs) in typhoid-endemic countries, and Gavi, the Vaccine Alliance, added TCVs into the portfolio of subsidized vaccines. Data from the Severe Typhoid Fever in Africa (SETA) program were used to contribute to TCV introduction decision-making processes, exemplified for Ghana and Madagascar. METHODS: Data collected from both countries were evaluated, and barriers to and benefits of introduction scenarios are discussed. No standardized methodological framework was applied. RESULTS: The Ghanaian healthcare system differs from its Malagasy counterpart: Ghana features a functioning insurance system, antimicrobials are available nationwide, and several sites in Ghana deploy blood culture-based typhoid diagnosis. A higher incidence of antimicrobial-resistant Salmonella Typhi is reported in Ghana, which has not been identified as an issue in Madagascar. The Malagasy people have a low expectation of provided healthcare and experience frequent unavailability of medicines, resulting in limited healthcare-seeking behavior and extended consequences of untreated disease. CONCLUSIONS: For Ghana, high typhoid fever incidence coupled with spatiotemporal heterogeneity was observed. A phased TCV introduction through an initial mass campaign in high-risk areas followed by inclusion into routine national immunizations prior to expansion to other areas of the country can be considered. For Madagascar, a national mass campaign followed by routine introduction would be the introduction scenario of choice as it would protect the population, reduce transmission, and prevent an often-deadly disease in a setting characterized by lack of access to healthcare infrastructure. New, easy-to-use diagnostic tools, potentially including environmental surveillance, should be explored and improved to facilitate identification of high-risk areas.

Bacteremia Among Febrile Patients Attending Selected Healthcare Facilities in Ibadan, Nigeria.

BACKGROUND: The relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia. METHODS: Febrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion. RESULTS: A total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant. CONCLUSIONS: The study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality.

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.

Multicountry Distribution and Characterization of Extended-spectrum ß-Lactamase-associated Gram-negative Bacteria From Bloodstream Infections in Sub-Saharan Africa.

BACKGROUND: Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum ß-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa. METHODS: Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for ß-lactamase were performed on all pathogens. RESULTS: Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity. CONCLUSIONS: Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.

A Systematic Review of Typhoid Fever Occurrence in Africa.

BACKGROUND: Our current understanding of the burden and distribution of typhoid fever in Africa relies on extrapolation of data from a small number of population-based incidence rate estimates. However, many other records on the occurrence of typhoid fever are available, and those records contain information that may enrich our understanding of the epidemiology of the disease as well as secular trends in reporting by country and over time. METHODS: We conducted a systematic review of typhoid fever occurrence in Africa, published in PubMed, Embase, and ProMED (Program for Monitoring Emerging Diseases). RESULTS: At least one episode of culture-confirmed typhoid fever was reported in 42 of 57 African countries during 1900-2018. The number of reports on typhoid fever has increased over time in Africa and was highly heterogeneous between countries and over time. Outbreaks of typhoid fever were reported in 15 countries, with their frequency and size increasing over time. CONCLUSIONS: Efforts should be made to leverage existing typhoid data, for example, by incorporating them into models for estimating the burden and distribution of typhoid fever.

The Monitoring and Evaluation of a Multicountry Surveillance Study, the Severe Typhoid Fever in Africa Program.

BACKGROUND: There is limited information on the best practices for monitoring multicountry epidemiological studies. Here, we describe the monitoring and evaluation procedures created for the multicountry Severe Typhoid Fever in Africa (SETA) study. METHODS: Elements from the US Food and Drug Administration (FDA) and European Centre for Disease Prevention and Control (ECDC) recommendations on monitoring clinical trials and data quality, respectively were applied in the development of the SETA monitoring plan. The SETA core activities as well as the key data and activities required for the delivery of SETA outcomes were identified. With this information, a list of key monitorable indicators was developed using on-site and centralized monitoring methods, and a dedicated monitoring team was formed. The core activities were monitored on-site in each country at least twice per year and the SETA databases were monitored centrally as a collaborative effort between the International Vaccine Institute and study sites. Monthly reports were generated for key indicators and used to guide risk-based monitoring specific for each country. RESULTS: Preliminary results show that monitoring activities have increased compliance with protocol and standard operating procedures. A reduction in blood culture contamination following monitoring field visits in two of the SETA countries are preliminary results of the impact of monitoring activities. CONCLUSIONS: Current monitoring recommendations applicable to clinical trials and routine surveillance systems can be adapted for monitoring epidemiological studies. Continued monitoring efforts ensure that the procedures are harmonized across sites. Flexibility, ongoing feedback, and team participation yield sustainable solutions.

The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis.

BACKGROUND: Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. METHODS: A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. RESULTS: Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. CONCLUSIONS: SETA supports public health policy on typhoid immunization strategy in Africa.

Occurrence of Typhoid Fever Complications and Their Relation to Duration of Illness Preceding Hospitalization: A Systematic Literature Review and Meta-analysis.

BACKGROUND: Complications from typhoid fever disease have been estimated to occur in 10%-15% of hospitalized patients, with evidence of a higher risk in children and when delaying the implementation of effective antimicrobial treatment. We estimated the prevalence of complications in hospitalized patients with culture-confirmed typhoid fever and the effects of delaying the implementation of effective antimicrobial treatment and age on the prevalence and risk of complications. METHODS: A systematic review and meta-analysis were performed using studies in the PubMed database. We rated risk of bias and conducted random-effects meta-analyses. Days of disease at hospitalization (DDA) was used as a surrogate for delaying the implementation of effective antimicrobial treatment. Analyses were stratified by DDA (DDA <10 versus ≥10 mean/median days of disease) and by age (children versus adults). Differences in risk were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity and publication bias were evaluated with the I2 value and funnel plot analysis, respectively. RESULTS: The pooled prevalence of complications estimated among hospitalized typhoid fever patients was 27% (95% CI, 21%-32%; I2 = 90.9%, P < .0001). Patients with a DDA ≥ 10 days presented higher prevalence (36% [95% CI, 29%-43%]) and three times greater risk of severe disease (OR, 3.00 [95% CI, 2.14-4.17]; P < .0001) than patients arriving earlier (16% [95% CI, 13%- 18%]). Difference in prevalence and risk by age groups were not significant. CONCLUSIONS: This meta-analysis identified a higher overall prevalence of complications than previously reported and a strong association between duration of symptoms prior to hospitalization and risk of serious complications.