Health and demographic surveillance systems (HDSSs) provide a foundation for characterizing and defining priorities and strategies for improving population health. The Child Health and Mortality ...Prevention Surveillance (CHAMPS) project aims to inform policy to prevent child deaths through generating causes of death from surveillance data combined with innovative diagnostic and laboratory methods. Six of the 7 sites that constitute the CHAMPS network have active HDSSs: Mozambique, Mali, Ethiopia, Kenya, Bangladesh, and South Africa; the seventh, in Sierra Leone, is in the early planning stages. This article describes the network of CHAMPS HDSSs and their role in the CHAMPS project. To generate actionable health and demographic data to prevent child deaths, the network depends on reliable demographic surveillance, and the HDSSs play this crucial role.
is a common cause of sepsis and is particularly associated with healthcare-associated infections. New strategies are needed to prevent or treat infections due to the emergence of multi-drug resistant
.... The goal of this study was to determine the diversity and distribution of O (lipopolysaccharide) and K (capsular polysaccharide) antigens on a large (>500) global collection of
strains isolated from blood to inform vaccine development efforts. A total of 645
isolates were collected from the blood of patients in 13 countries during 2005-2017. Antibiotic susceptibility was determined using the Kirby-Bauer disk diffusion method. O antigen types including the presence of modified O galactan types were determined by PCR. K types were determined by multiplex PCR and
capsular typing. Sequence types of isolates were determined by multilocus sequence typing (MLST) targeting seven housekeeping genes. Among 591 isolates tested for antimicrobial resistance, we observed that 19.3% of isolates were non-susceptible to carbapenems and 62.1% of isolates were multidrug resistant (from as low as 16% in Sweden to 94% in Pakistan). Among 645 isolates, four serotypes, O1, O2, O3, and O5, accounted for 90.1% of
strains. Serotype O1 was associated with multidrug resistance. Fifty percent of 199 tested O1 and O2 strains were
-positive, indicating the presence of the modified polysaccharide subunit D-galactan III. The most common K type was K2 by both multiplex PCR and
capsular typing. Of 39 strains tested by MLST, 36 strains were assigned to 26 known sequence types of which ST14, ST25, and ST258 were the most common. Given the limited number of O antigen types, diverse K antigen types and the high multidrug resistance, we believe that an O antigen-based vaccine would offer an excellent prophylactic strategy to prevent
invasive infection.
Background. In 2002, following establishment of a clinical microbiology laboratory in the government hospital that admits children with severe illnesses in Bamako, Mali, surveillance to identify ...pathogens causing invasive bacterial infections (septicemia, bacteremia, meningitis, etc) was initiated. Methods. Parents/guardians of children aged <16 years admitted to l'Hôpital Gabriel Touré with high fever or clinical syndromes compatible with focal invasive bacterial disease were asked for consent to culture their child's blood/body fluid. Standard bacteriologic techniques speciated isolates; Salmonella serovars were determined. Results. From July 2002 through June 2014, 687 nontyphoidal Salmonella (NTS) isolates were obtained from 667 children; 667 yielded a single serovar and 20 grew 2 Salmonella serovars, 1 being NTS. Four serovars accounted for 87% of the 687 NTS isolates, including Salmonella Enteritidis (n = 244 35.5%), Salmonella Typhimurium (n = 221 32.2%), I:4,5,12:i:- (n = 42 6.1%), and Salmonella Dublin (n = 89 13.0%). Of 553 patients with invasive NTS from whom 1 of the 4 predominant serovars was isolated in pure culture, 448 (81.0%) were aged <5 years and case fatality was 20.3%; Salmonella Enteritidis case fatality (27.8%) was higher than for other serovars (P = .0009). NTS disease showed a seasonal peak following the rainy season and into the cool, dry season. Since 2010, Salmonella Enteritidis cases have risen and Salmonella Typhimurium fallen. Conclusions. NTS has become the predominant invasive pathogen as Haemophilus influenzae type b and pneumococcal vaccine use in Mali has diminished invasive disease due to those pathogens. The age distribution and limited serovars involved make control of NTS disease by vaccines epidemiologically feasible, if products under development prove safe and efficacious.
Abstract
Background
Salmonella enterica bloodstream infections are an important cause of childhood morbidity and mortality, including in Mali. We report 17 years of surveillance for nontyphoidal and ...typhoidal S. enterica infections among inpatients and outpatients at l’Hôpital Gabriel Touré, the main source of pediatric tertiary care in Bamako, Mali.
Methods
Between June 2002 and December 2018, a blood culture was collected from 54 748 children aged ≤15 years with fever and/or suspected invasive bacterial infection who provided consent (38 152 inpatients, 16 596 outpatients). Bacterial pathogens were identified using standard microbiological techniques and serovars of S. enterica were determined by PCR and/or agglutination with antisera.
Results
Nontyphoidal Salmonella (NTS) was identified in 671 enrolled inpatients (1.8% of all enrolled inpatients, 13.8% of enrolled inpatients with a positive culture). S. Enteritidis, the most common NTS serovar, accounted for 38.5% of all NTS isolates (n = 258), followed by S. Typhimurium (31.7%, n = 213). The median (SD) age of children with a culture positive for NTS was 1.8 (3) years. Overall case fatality was 20.9%. An additional 138 inpatients (0.4%) had a positive culture for typhoidal Salmonella. NTS was identified in 11 outpatients (0.07%), while typhoidal Salmonella was found in 49 outpatients (0.3%). The annual incidence of invasive NTS disease decreased over the study period, but case fatality remained high.
Conclusions
Although incidence decreased, NTS remained a major cause of invasive bacterial infection and mortality among hospitalized children in Bamako, while typhoidal Salmonella was uncommon. Because 87% of NTS belonged to only 4 serovars, a multivalent vaccine may be an effective strategy to reduce the burden and mortality of invasive NTS.
•New RSV prevention products can substantially reduce disease burden.•Longer-actingmonoclonal antibodies, priced affordably, are likely cost-effective.•Maternal vaccines meeting preferred product ...characteristicswould be cost-effective.•RSV prevention productscanprovide good valuein low-income countries.
Low- and middle-income countries have a high burden of respiratory syncytial virus lower respiratory tract infections. A monoclonal antibody administered monthly is licensed to prevent these infections, but it is cost-prohibitive for most low- and middle-income countries. Long-acting monoclonal antibodies and maternal vaccines against respiratory syncytial virus are under development.
We estimated the likelihood of respiratory syncytial virus preventive interventions (current monoclonal antibody, long-acting monoclonal antibody, and maternal vaccine) being cost-effective in Mali.
We modeled age-specific and season-specific risks of respiratory syncytial virus lower respiratory tract infections within monthly cohorts of infants from birth to six months. We parameterized with respiratory syncytial virus data from Malian cohort studies, as well as product efficacy from clinical trials. Integrating parameter uncertainty, we simulated health and economic outcomes for status quo without prevention, intra-seasonal monthly administration of licensed monoclonal antibody, pre-seasonal birth dose administration of a long-acting monoclonal antibody, and maternal vaccination. We then calculated the incremental cost-effectiveness ratio of each intervention compared to status quo from the perspectives of the government, donor, and society.
At a price of $3 per dose and from the societal perspective, current monoclonal antibody, long-acting monoclonal antibody, and maternal vaccine would have incremental cost-effectiveness ratios of $4280 (95% CI $1892 to $122,434), $1656 (95% CI $734 to $9091), and $8020 (95% CI $3501 to $47,047) per disability-adjusted life-year averted, respectively.
In Mali, long-acting monoclonal antibody is likely to be cost-effective from both the government and donor perspectives at $3 per dose. Maternal vaccine would need higher efficacy over that measured by a recent trial in order to be considered cost-effective.
Rotavirus vaccines given to infants are safe and efficacious. A booster dose of rotavirus vaccine could extend protection into the second year of life in low-resource countries.
We conducted an ...open-label, individual-randomized trial in Bamako, Mali. We assigned 600 infants aged 9-11 months to receive measles vaccine (MV), yellow fever vaccine (YFV), and meningococcal A conjugate vaccine (MenAV) with or without pentavalent rotavirus vaccine (PRV). We assessed the noninferiority (defined as a difference of ≤10%) of seroconversion and seroresponse rates to MV, YFV, and MenAV. We compared the seroresponse to PRV.
Seroconversion to MV occurred in 255 of 261 PRV recipients (97.7%) and 246 of 252 control infants (97.6%; difference, 0.1% 95% confidence interval {CI}, -4.0%-4.2%). Seroresponse to YFV occurred in 48.1% of PRV recipients (141 of 293), compared with 52.2% of controls (153 of 293; difference, -4.1% 95% CI, -12.2%-4.0%). A 4-fold rise in meningococcus A bactericidal titer was observed in 273 of 292 PRV recipients (93.5%) and 276 of 293 controls (94.2%; difference, -0.7% 95% CI, -5.2%-3.8%). Rises in geometric mean concentrations of immunoglobulin A and immunoglobulin G antibodies to rotavirus were higher among PRV recipients (118 95% CI, 91-154 and 364 95% CI, 294-450, respectively), compared with controls (68 95% CI, 50-92 and 153 95% CI, 114-207, respectively).
PRV did not interfere with MV and MenAV; this study could not rule out interference with YFV. PRV increased serum rotavirus antibody levels.
NCT02286895.
In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis) has revealed non-typhoidal Salmonella (NTS) to be a major ...pathogen exhibiting high case fatality (~20%). Where infant vaccination against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged <5 years. While NTS is believed to be acquired orally via contaminated food/water, epidemiologic studies have failed to identify the reservoir of infection or vehicles of transmission. This has precluded targeting food chain interventions to diminish disease transmission but conversely has fostered the development of vaccines to prevent invasive NTS (iNTS) disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako.
A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged <5 years and assuming vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children <5 years, with and without a Salmonella Enteritidis/Salmonella Typhimurium vaccine, were the model's outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age <8 weeks.
The public health impact of NTS vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for use elsewhere in Africa where NTS epidemiologic patterns, serovar prevalence, and immunization schedules differ from Bamako.
We present findings from the Pneumonia Etiology Research for Child Health (PERCH) site in Bamako, Mali.
Cases were patients 28 days to 59 months of age, admitted to hospital with severe or very ...severe pneumonia (2005 World Health Organization definition). Community controls were frequency matched by age. Both provided nasopharyngeal and oropharyngeal swabs for multiplex polymerase chain reaction and Streptococcus pneumoniae culture. Cases underwent blood culture and induced sputum culture for Mycobacterium tuberculosis. A subset had pleural fluid and lung aspirates collected for culture and polymerase chain reaction. Primary analyses included participants with negative or unknown HIV status (HIV-) and cases with abnormal chest radiographs (CXR+). Cases and controls were compared using logistic regression adjusting for age. Etiologic fractions were calculated by a Bayesian nested partially latent class analysis, the PERCH integrated analysis.
Between January 1, 2012, and January 14, 2014, we enrolled 241 CXR+/HIV- cases and 725 HIV- controls. Compared with controls, cases were more likely to have moderate-to-severe wasting (43.1% vs. 14.1%, P < 0.001) and stunting (26.6% vs. 9.4%, P < 0.001). Predominant etiologies were respiratory syncytial virus 24.0%; 95% credible interval (CrI): 18.3%-31.1%, S. pneumoniae (15.2%; 95% CrI: 9.5-21.6), human metapneumovirus (11.8%; 95% CrI: 8.3%-16.2%) and parainfluenza virus type 3 (9.0%; 95% CrI: 5.8%-13.3%). Case fatality was 13.3%, with Staphylococcus aureus, Pneumocystis jirovecii and Haemophilus influenzae type b predominating (40% of fatal cases).
PERCH uncovered high case fatality among children with severe pneumonia in Mali, highlighting a role for new interventions (eg, respiratory syncytial virus vaccines) and a need to improve vaccine coverage and strengthen healthcare delivery.
Abstract
Pentavalent rotavirus vaccine has been associated with a small increase in intussusception, but pre- and post-introduction data are lacking in many low-resource settings. Using chart review ...and prospective surveillance data, intussusception incidence was estimated in Bamako, Mali. The mean annual intussusception incidence post-introduction was not significantly different from that of pre-introduction.
The association between rotavirus vaccines and intussusception has raised concern about the risk-benefit ratio of these vaccines in low-resource settings. We describe rates of intussusception among infants in Bamako, Mali, before and after the introduction of pentavalent rotavirus vaccine.
In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We ...analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model.
PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2.
Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76).
Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community.
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