Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 150 Records) |
Query Trace: Verani JR[original query] |
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Age-dependent acquisition of IgG antibodies to Shigella serotypes-a retrospective analysis of seroprevalence in Kenyan children with implications for infant vaccination
Kapulu MC , Muthumbi E , Otieno E , Rossi O , Ferruzzi P , Necchi F , Acquaviva A , Martin LB , Orindi B , Mwai K , Kibet H , Mwanzu A , Bigogo GM , Verani JR , Mbae C , Nyundo C , Agoti CN , Nakakana UN , Conti V , Bejon P , Kariuki S , Scott JAG , Micoli F , Podda A . Front Immunol 2024 15 1340425 BACKGROUND: Shigellosis mainly affects children under 5 years of age living in low- and middle-income countries, who are the target population for vaccination. There are, however, limited data available to define the appropriate timing for vaccine administration in this age group. Information on antibody responses following natural infection, proxy for exposure, could help guide vaccination strategies. METHODS: We undertook a retrospective analysis of antibodies to five of the most prevalent Shigella serotypes among children aged <5 years in Kenya. Serum samples from a cross-sectional serosurvey in three Kenyan sites (Nairobi, Siaya, and Kilifi) were analyzed by standardized ELISA to measure IgG against Shigella sonnei and Shigella flexneri 1b, 2a, 3a, and 6. We identified factors associated with seropositivity to each Shigella serotype, including seropositivity to other Shigella serotypes. RESULTS: A total of 474 samples, one for each participant, were analyzed: Nairobi (n = 169), Siaya (n = 185), and Kilifi (n = 120). The median age of the participants was 13.4 months (IQR 7.0-35.6), and the male:female ratio was 1:1. Geometric mean concentrations (GMCs) for each serotype increased with age, mostly in the second year of life. The overall seroprevalence of IgG antibodies increased with age except for S. flexneri 6 which was high across all age subgroups. In the second year of life, there was a statistically significant increase of antibody GMCs against all five serotypes (p = 0.01-0.0001) and a significant increase of seroprevalence for S. flexneri 2a (p = 0.006), S. flexneri 3a (p = 0.006), and S. sonnei (p = 0.05) compared with the second part of the first year of life. Among all possible pairwise comparisons of antibody seropositivity, there was a significant association between S. flexneri 1b and 2a (OR = 6.75, 95% CI 3-14, p < 0.001) and between S. flexneri 1b and 3a (OR = 23.85, 95% CI 11-54, p < 0.001). CONCLUSION: Children living in low- and middle-income settings such as Kenya are exposed to Shigella infection starting from the first year of life and acquire serotype-specific antibodies against multiple serotypes. The data from this study suggest that Shigella vaccination should be targeted to infants, ideally at 6 or at least 9 months of age, to ensure children are protected in the second year of life when exposure significantly increases. |
Risk factors of adverse birth outcomes among a cohort of pregnant women in Coastal Kenya, 2017-2019
Mirieri H , Nduati R , Dawa J , Okutoyi L , Osoro E , Mugo C , Wamalwa D , Jin H , Mwaengo D , Otieno N , Marwanga D , Shabibi M , Munyua P , Kinuthia J , Clancey E , Widdowson MA , Njenga MK , Verani JR , Inwani I . BMC Pregnancy Childbirth 2024 24 (1) 127 INTRODUCTION: Adverse birth outcomes particularly preterm births and congenital anomalies, are the leading causes of infant mortality globally, and the burden is highest in developing countries. We set out to determine the frequency of adverse birth outcomes and the risk factors associated with such outcomes in a cohort of pregnant women in Kenya. METHODS: From October 2017 to July 2019, pregnant women < 28 weeks gestation were enrolled and followed up until delivery in three hospitals in coastal Kenya. Newborns were examined at delivery. Among women with birth outcome data, we assessed the frequency of congenital anomalies defined as gastroschisis, umbilical hernia, limb abnormalities and Trisomy 21, and adverse birth outcomes, defined as either stillbirth, miscarriage, preterm birth, small for gestational age, or microcephaly. We used log-binomial regression to identify maternal characteristics associated with the presence of at least one adverse outcome. RESULTS: Among the 2312 women enrolled, 1916 (82.9%) had birth outcome data. Overall, 402/1916 (20.9%; 95% confidence interval (CI): 19.1-22.8) pregnancies had adverse birth outcomes. Specifically, 66/1916 (3.4%; 95% CI: 2.7-4.4) were stillbirths, 34/1916 (1.8%; 95% CI: 1.2-2.4) were miscarriages and 23/1816 (1.2%; 95% CI: 0.8-1.9) had congenital anomalies. Among the participants with anthropometric measurements data, 142/1200 (11.8%; 95% CI: 10.1 - 13.8) were small for gestational age and among the participants with ultrasound records, 143/1711 (8.4%; 95% CI: 7.1-9.8) were preterm. Febrile illnesses in current pregnancy (adjusted risk ratio (aRR): 1.7; 95% CI: 1.1-2.8), a history of poor birth outcomes in prior pregnancy (aRR: 1.8; 95% CI: 1.3-2.4) and high blood pressure in pregnancy (aRR: 3.9, 95% CI: (1.7-9.2) were independently associated with adverse birth outcomes in a model that included age, education, human immunodeficiency virus status and high blood pressure at enrolment. CONCLUSION: We found similar rates of overall adverse birth outcomes, congenital anomalies, and small for gestational age but higher rates of stillbirths and lower rates of prematurity compared to the rates that have been reported in the sub-Saharan Africa region. However, the rates of adverse birth outcomes in this study were comparable to other studies conducted in Kenya. Febrile illnesses during the current pregnancy, previous history of poor birth outcomes and high blood pressure in pregnancy are predictive of an increased risk of adverse birth outcomes. |
Post-mortem investigation of deaths due to pneumonia in children aged 1-59 months in sub-Saharan Africa and South Asia from 2016 to 2022: an observational study
Mahtab S , Blau DM , Madewell ZJ , Ogbuanu I , Ojulong J , Lako S , Legesse H , Bangura JS , Bassat Q , Mandomando I , Xerinda E , Fernandes F , Varo R , Sow SO , Kotloff KL , Tapia MD , Keita AM , Sidibe D , Onyango D , Akelo V , Gethi D , Verani JR , Revathi G , Scott JAG , Assefa N , Madrid L , Bizuayehu H , Tirfe TT , El Arifeen S , Gurley ES , Islam KM , Alam M , Zahid Hossain M , Dangor Z , Baillie VL , Hale M , Mutevedzi P , Breiman RF , Whitney CG , Madhi SA . Lancet Child Adolesc Health 2024 BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network. METHODS: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards. FINDINGS: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus. INTERPRETATION: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens. FUNDING: Bill & Melinda Gates Foundation. |
Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data
Verani JR , Blau DM , Gurley ES , Akelo V , Assefa N , Baillie V , Bassat Q , Berhane M , Bunn J , Cossa ACA , El Arifeen S , Gunturu R , Hale M , Igunza A , Keita AM , Kenneh S , Kotloff KL , Kowuor D , Mabunda R , Madewell ZJ , Madhi S , Madrid L , Mahtab S , Miguel J , Murila FV , Ogbuanu IU , Ojulong J , Onyango D , Oundo JO , Scott JAG , Sow S , Tapia M , Traore CB , Velaphi S , Whitney CG , Mandomando I , Breiman RF . Lancet Microbe 2024 BACKGROUND: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. METHODS: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). FINDINGS: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. INTERPRETATION: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. FUNDING: Bill & Melinda Gates Foundation. |
Long-term surveillance of invasive pneumococcal disease: The impact of 10-valent pneumococcal conjugate vaccine in the metropolitan region of Salvador, Brazil
Reis JN , Azevedo J , de Oliveira AML , Menezes APO , Pedrosa M , Dos Santos MS , Ribeiro LC , Freitas HF , Gouveia EL , Teles MB , Carvalho MDG , Reis MG , Nascimento-Carvalho C , Verani JR . Vaccine 2024 BACKGROUND: In 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10) in the national infant immunization program. Limited data on the long-term impact of PCV10 are available from lower-middle-income settings. We examined invasive pneumococcal disease (IPD) in Salvador, Bahia, over 11 years. METHODS: Prospective laboratory-based surveillance for IPD was carried out in 9 hospitals in the metropolitan region of Salvador from 2008 to 2018. IPD was defined as Streptococcus pneumoniae cultured from a normally sterile site. Serotype was determined by multiplex polymerase chain reaction and/or Quellung reaction. Incidence rates per 100,000 inhabitants were calculated for overall, vaccine-type, and non-vaccine-type IPD using census data as the denominator. Incidence rate ratios (IRRs) were calculated to compare rates during the early (2010-2012), intermediate (2013-2015), and late (2016-2018) post-PCV10 periods in comparison to the pre-PCV10 period (2008-2009). RESULTS: Pre-PCV10, overall IPD incidence among all ages was 2.48/100,000. After PCV10 introduction, incidence initially increased (early post-PCV10 IRR 3.80, 95% CI 1.18-1.99) and then declined to 0.38/100,000 late post-PCV10 (IRR 0.15; 95% CI 0.09-0.26). The greatest reductions in the late post-PCV10 period were observed in children aged ≤2 years, with no cases (IRR not calculated) and those ≥60 years (IRR 0.11, 95% CI 0.03-0.48). Late post-PCV10, significant reductions were observed for both PCV10 serotypes (IRR 0.02; 95% CI 0.0-0.15) and non-PCV10 serotypes (IRR 0.27; 95%CI 0.14-0.53). Non-PCV10 serotypes 15B, 12F, 3, 17F, and 19A became predominant late post-PCV10 without a significant increase in serotype-specific IPD incidence compared to pre-PCV10. CONCLUSION: Significant declines in IPD, including among adults not eligible for vaccination, suggest direct and indirect protection up to nine years after PCV10 introduction, without evidence of significant replacement disease. Continued surveillance is needed to monitor changes in non-vaccine serotypes and inform decisions about introducing higher valent PCVs. |
Prevalence and missed cases of respiratory distress syndrome disease amongst neonatal deaths enrolled in the Kenya Child Health and Mortality Prevention Surveillance Network (CHAMPS) Program Between 2017 and 2021
Owuor HO , Akelo V , Murila F , Onyango D , Kuria M , Rogena E , Revathi G , Mitei P , Sava S , Were J , Igunza A , Khagayi S , Zielinski-Gutierrez E , Hawi S , Gethi D , Verani JR , Onyango C , Blau DM , Tippett Barr BA . Glob Pediatr Health 2023 10 2333794x231212819 Objectives. To describe RDS in neonatal deaths at the CHAMPS-Kenya site between 2017 and 2021. Methods. We included 165 neonatal deaths whose their Causes of death (COD) were determined by a panel of experts using data from post-mortem conducted through minimally invasive tissue specimen testing, clinical records, and verbal autopsy. Results. Twenty-six percent (43/165) of neonatal deaths were attributable to RDS. Most cases occurred in low birthweight and preterm neonates. From these cases, less than half of the hospitalizations were diagnosed with RDS before death, and essential diagnostic tests were not performed in most cases. Most cases received suboptimal levels of supplemental oxygen, and critical interventions like surfactant replacement therapy and mechanical ventilation were not adequately utilized when available. Conclusion. The study highlights the urgent need for improved diagnosis and management of RDS, emphasizing the importance of increasing clinical suspicion and enhancing training in its clinical management to reduce mortality rates. |
The epidemiology of fecal carriage of nontyphoidal Salmonella among healthy children and adults in three sites in Kenya
Muthumbi EM , Mwanzu A , Mbae C , Bigogo G , Karani A , Mwarumba S , Verani JR , Kariuki S , Scott JAG . PLoS Negl Trop Dis 2023 17 (10) e0011716 BACKGROUND: Despite the importance of non-Typhoidal Salmonella (NTS) disease in Africa, epidemiologic data on carriage and transmission are few. These data are important to understand the transmission of NTS in Africa and to design control strategies. METHOD: Ethics statementThe study was approved by the KEMRI Scientific and Ethics Research Unit (SERU No. 3221). This activity was reviewed by CDC and was conducted in a manner consistent with applicable federal law and CDC policy [Project ID: 0900f3eb81e92cdd]. To estimate the prevalence of stool carriage of NTS in Kenya, we conducted a cross-sectional study in Kilifi, Nairobi, and Siaya, sites with a low, moderate and high incidence of invasive NTS disease, respectively. At each site, we randomly selected 100 participants in each age-group of 0-11 months, 12-59 months, 5-14 years, 15-54 years and ≥55 years. We collected stool, venous blood (for hemoglobin and malaria rapid tests), anthropometric measurements, and administered a questionnaire on Water Access Sanitation and Hygiene (WASH) practices. Stool samples were cultured on selective agar for Salmonella; suspect isolates underwent serotyping and antimicrobial susceptibility testing. RESULT: Overall, 53 (3.5%) isolates of NTS were cultured from 1497 samples. Age-adjusted prevalence was 13.1% (95%CI 8.8-17.4) in Kilifi, 0.4% (95%CI 0-1.3) in Nairobi, and 0.9% (95%CI 0-2.0) in Siaya. Prevalence was highest among those aged 15-54 years (6.2%). Of 53 isolates; 5 were S. Enteritidis, 1 was S. Typhimurium. No S. Typhi was isolated. None of the risk factors were associated with carriage of NTS. All isolates were susceptible to all antibiotics tested, including ampicillin, chloramphenicol, ciprofloxacin and co-trimoxazole. CONCLUSION: Prevalence of fecal carriage was high in Kilifi, an area of low incidence of invasive NTS disease and was low in areas of higher incidence in Nairobi and Siaya. The age-prevalence, risk factors, geographical and serotype distribution of NTS in carriage differs from invasive disease. |
Correcting for measurement error in assessing gestational age in a low-resource setting: a regression calibration approach
Agogo GO , Verani JR , Otieno NA , Nyawanda BO , Widdowson MA , Chaves SS . Front Med (Lausanne) 2023 10 1222772 INTRODUCTION: Measurement error in gestational age (GA) may bias the association of GA with a health outcome. Ultrasound-based GA is considered the gold standard and is not readily available in low-resource settings. We corrected for measurement error in GA based on fundal height (FH) and date of last menstrual period (LMP) using ultrasound from the sub-cohort and adjusted for the bias in associating GA with neonatal mortality and low birth weight (< 2,500 grams, LBW). METHODS: We used data collected from 01/2015 to 09/2019 from pregnant women enrolled at two public hospitals in Siaya county, Kenya (N = 2,750). We used regression calibration to correct for measurement error in FH- and LMP-based GA accounting for maternal and child characteristics. We applied logistic regression to associate GA with neonatal mortality and low birth weight, with and without calibrating FH- and LMP-based GA. RESULTS: Calibration improved the precision of LMP (correlation coefficient, ρ from 0.48 to 0.57) and FH-based GA (ρ from 0.82 to 0.83). Calibrating FH/LMP-based GA eliminated the bias in the mean GA estimates. The log odds ratio that quantifies the association of GA with neonatal mortality increased by 29% (from -0.159 to -0.205) by calibrating FH-based GA and by more than twofold (from -0.158 to -0.471) by calibrating LMP-based GA. CONCLUSION: Calibrating FH/LMP-based GA improved the accuracy and precision of GA estimates and strengthened the association of GA with neonatal mortality/LBW. When assessing GA, neonatal public health and clinical interventions may benefit from calibration modeling in settings where ultrasound may not be fully available. |
Stillbirths and neonatal deaths caused by group B streptococcus in Africa and South Asia identified through Child Health and Mortality Prevention Surveillance (CHAMPS)
Mahtab S , Madewell ZJ , Madhi SA , Wise A , Swart PJ , Velaphi S , Mandomando I , Bramugy J , Mabunda R , Xerinda E , Scott AG , Assefa N , Madrid L , Bweihun M , Temesgen F , Onyango D , Akelo V , Oliech R , Otieno P , Verani JR , Arifeen SE , Gurley ES , Alam M , Rahman A , Hossain MZ , Sow S , Kotloff K , Tapia M , Keita AM , Sanogo D , Ogbuanu I , Ojulong J , Lako S , Ita O , Kaluma E , Wilson T , Mutevedzi P , Barr BAT , Whitney CG , Blau DM , Bassat Q . Open Forum Infect Dis 2023 10 (9) ofad356 BACKGROUND: Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). METHODS: Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. RESULTS: We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). CONCLUSIONS: Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs. |
Theoretical framework for retrospective studies of the effectiveness of SARS-CoV-2 vaccines (preprint)
Lewnard JA , Patel MM , Jewell NP , Verani JR , Kobayashi M , Tenforde MW , Dean NE , Cowling BJ , Lopman BA . medRxiv 2021 2021.01.21.21250258 Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. These are now in planning amid the ongoing rollout of SARS-CoV-2 vaccines globally. While traditional case-control (TCC) and test-negative design (TND) studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here we review the theoretical basis for estimation of vaccine direct effects under TCC and TND frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, non-specific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The TCC may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The TND reduces but may not eliminate this confounding, for instance if individuals who receive vaccination seek care or testing for less-severe infection. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.Competing Interest StatementJAL has received grants and consulting fees from Pfizer, Inc. unrelated to this research.Funding StatementThis work was supported by grants R01-AI14812701 from the National Institute for Allergy and Infectious Diseases to NPJ and JAL, and R01-AI139761 from the National Institute for Allergy and Infectious Diseases to NED.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThis is a theoretical study without patient data; equations used to generate the figures appear in the manuscript. |
mRNA Vaccine Effectiveness against COVID-19 among Symptomatic Outpatients Aged ≥16 Years in the United States, February – May 2021 (preprint)
Kim SS , Chung JR , Belongia EA , McLean HQ , King JP , Nowalk MP , Zimmerman RK , Balasubramani GK , Martin ET , Monto AS , Lamerato LE , Gaglani M , Smith ME , Dunnigan KM , Jackson ML , Jackson LA , Tenforde MW , Verani JR , Kobayashi M , Schrag S , Patel MM , Flannery B . medRxiv 2021 2021.07.20.21260647 Evaluations of vaccine effectiveness (VE) are important to monitor as COVID-19 vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or SARS-CoV-2 testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, VE of mRNA vaccines against COVID-19 was 91% (95% CI: 83-95) for full vaccination and 75% (95% CI: 55-87) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.Competing Interest StatementMPN reports grants from Merck & Co. outside the submitted work. RKZ reports grants from Sanofi Pasteur outside the submitted work. GKB reports grants from Merck & Co outside the submitted work and consulting fees from New World Medical, LLC. ETM reports grants from Merck & Co. outside the submitted work and consulting fees from Pfizer. ASM reports consulting fees from Sanofi Pasteur and Seqirus. LEL reports grants from Xcenda, Inc., eMAXHealth, AstraZeneca, Pfizer, Evidera outside the submitted work. MLJ reports grants from Sanofi Pasteur. All other authors report nothing to disclose.Funding StatementThis work was supported by the US Centers for Disease Control and Prevention through cooperative agreements U01IP001034-U01IP001039. At Pittsburgh, the project was also supported by the National Institutes of Health through grant ULTR001857.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Centers for Disease Control and Prevention IRB project determination numbers for included projects: 0900f3eb81c2e791, 0900f3eb81c52dc5; 0900f3eb81c52420, 0900f3eb81bc746b, 6238All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesDe-identified dataset can be made available upon request |
Effectiveness of COVID-19 Vaccines among Incarcerated People in California State Prisons: A Retrospective Cohort Study (preprint)
Chin ET , Leidner D , Zhang Y , Long E , Prince L , Schrag SJ , Verani JR , Wiegand RE , Alarid-Escudero F , Goldhaber-Fiebert JD , Studdert DM , Andrews JR , Salomon JA . medRxiv 2021 BACKGROUND: Prisons and jails are high-risk settings for COVID-19 transmission, morbidity, and mortality. COVID-19 vaccines may substantially reduce these risks, but evidence is needed of their effectiveness for incarcerated people, who are confined in large, risky congregate settings. METHODS: We conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination status, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates that adjusted for resident characteristics and infection rates across prisons. FINDINGS: Among 60,707 residents in the cohort, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable (74% [95% CI, 62-82%] and 92% [95% CI, 74-98%] from 14 days after first and second doses, respectively), as well as among the subset of residents who received the mRNA-1273 vaccine (71% [95% CI, 58-80%] and 96% [95% CI, 67-99%]). CONCLUSIONS: Consistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population. FUNDING: Horowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices. |
Identifying and alleviating bias due to differential depletion of susceptible people in post-marketing evaluations of COVID-19 vaccines (preprint)
Kahn R , Schrag SJ , Verani JR , Lipsitch M . medRxiv 2021 2021.07.15.21260595 Recent studies have provided key information about SARS-CoV-2 vaccines’ efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptibles between vaccinated and unvaccinated groups. Here we examine the extent to which biases occur under different scenarios and assess whether serologic testing has the potential to correct this bias. By identifying non-vaccine antibodies, these tests could identify individuals with prior infection. We find in scenarios with high baseline VE, differential depletion of susceptibles creates minimal bias in VE estimates, suggesting that any observed declines are likely not due to spurious waning alone. However, if baseline VE is lower, the bias for leaky vaccines (that reduce individual probability of infection given contact) is larger and should be corrected by excluding individuals with past infection if the mechanism is known to be leaky. Conducting analyses both unadjusted and adjusted for past infection could give lower and upper bounds for the true VE. Studies of VE should therefore enroll individuals regardless of prior infection history but also collect information, ideally through serologic testing, on this critical variable.Competing Interest StatementDr. Lipsitch reports consulting/honoraria from Bristol Myers Squibb, Sanofi Pasteur, and Merck, as well as a grant through his institution, unrelated to COVID-19, from Pfizer. He has served as an unpaid advisor related to COVID-19 to Pfizer, One Day Sooner, Astra-Zeneca, Janssen, and COVAX (United Biomedical). Dr. Kahn discloses consulting fees from Partners In Health.Funding StatementThis work was supported by the U.S. National Cancer Institute Seronet cooperative agreement U01CA261277. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesCode is available on github. https://github.com/rek160/spurious-waning |
Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States (preprint)
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . medRxiv 2020 2020.04.27.20081901 Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request. |
Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States (preprint)
Tenforde MW , Patel MM , Ginde AA , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CT , Busse L , Lohuis CCT , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Gershengorn HB , Babcock HM , Kwon JH , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Olson SM , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Self WH . medRxiv 2021 BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population. |
Mortality patterns over a 10-year period in Kibera, an urban informal settlement in Nairobi, Kenya, 2009-2018
Oduor C , Omwenga I , Ouma A , Mutinda R , Kiplangat S , Mogeni OD , Cosmas L , Audi A , Odongo GS , Obor D , Breiman R , Montgomery J , Agogo G , Munywoki P , Bigogo G , Verani JR . Glob Health Action 2023 16 (1) 2238428 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. |
Dynamic incidence of typhoid fever over a 10-year period (2010-2019) in Kibera, an urban informal settlement in Nairobi, Kenya
Ng'eno E , Lind M , Audi A , Ouma A , Oduor C , Munywoki PK , Agogo GO , Odongo G , Kiplangat S , Wamola N , Osita MP , Mugoh R , Ochieng C , Omballa V , Mogeni OD , Mikoleit M , Fields BS , Montgomery JM , Gauld J , Breiman RF , Juma B , Hunsperger E , Widdowson MA , Bigogo G , Mintz ED , Verani JR . Am J Trop Med Hyg 2023 109 (1) 22-31 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. |
Effectiveness of booster doses of monovalent mRNA COVID-19 vaccine against symptomatic severe acute respiratory syndrome coronavirus 2 infection in children, adolescents, and adults during omicron subvariant BA.2/BA.2.12.1 and BA.4/BA.5 predominant periods
Ciesla AA , Wiegand RE , Smith ZR , Britton A , Fleming-Dutra KE , Miller J , Accorsi EK , Verani JR , Shang N , Derado G , Pilishvili T , Link-Gelles R . Open Forum Infect Dis 2023 10 (5) ofad187 BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2/BA.2.12.1 and BA.4/BA.5 subvariants have mutations associated with increased capacity to evade immunity when compared with prior variants. We evaluated mRNA monovalent booster dose effectiveness among persons ≥5 years old during BA.2/BA.2.12.1 and BA.4/BA.5 predominance. METHODS: A test-negative, case-control analysis included data from 12 148 pharmacy SARS-CoV-2 testing sites nationwide for persons aged ≥5 years with ≥1 coronavirus disease-2019 (COVID-19)-like symptoms and a SARS-CoV-2 nucleic acid amplification test from April 2 to August 31, 2022. Relative vaccine effectiveness (rVE) was estimated comparing 3 doses of COVID-19 mRNA monovalent vaccine to 2 doses; for tests among persons ≥50 years, rVE estimates also compared 4 doses to 3 doses (≥4 months since third dose). RESULTS: A total of 760 986 test-positive cases and 817 876 test-negative controls were included. Among individuals ≥12 years, rVE of 3 versus 2 doses ranged by age group from 45% to 74% at 1-month post vaccination and waned to 0% by 5-7 months post vaccination during the BA.4/BA.5 period.Adults aged ≥50 years (fourth dose eligible) who received 4 doses were less likely to have symptomatic SARS-CoV-2 infection compared with those with 3 doses; this rVE remained >0% through at least 3 months since last dose. For those aged ≥65 years, rVE of 4 versus 3 doses 1-month post vaccination was higher during BA.2/BA.2.12.1 (rVE = 49%; 95% confidence interval [CI], 43%-53%) than BA.4/BA.5 (rVE = 40%; 95% CI, 36%-44%). In 50- to 64-year-olds, rVE estimates were similar. CONCLUSIONS: Monovalent mRNA booster doses provided additional protection against symptomatic SARS-CoV-2 infection during BA.2/BA.2.12.1 and BA.4/BA.5 subvariant circulation, but protection waned over time. |
Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021.
Tenforde MW , Self WH , Naioti EA , Ginde AA , Douin DJ , Olson SM , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Exline MC , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Patel MM , IVY Network Investigators . MMWR Morb Mortal Wkly Rep 2021 70 (34) 1156-1162 Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination. |
Effectiveness of BNT162b2 COVID-19 Vaccination in Children and Adolescents.
Klein NP , Demarco M , Fleming-Dutra KE , Stockwell MS , Kharbanda AB , Gaglani M , Rao S , Lewis N , Irving SA , Hartmann E , Natarajan K , Dalton AF , Zerbo O , DeSilva MB , Konatham D , Stenehjem E , Rowley EAK , Ong TC , Grannis SJ , Sloan-Aagard C , Han J , Verani JR , Raiyani C , Dascomb K , Reese SE , Barron MA , Fadel WF , Naleway AL , Nanez J , Dickerson M , Goddard K , Murthy K , Grisel N , Weber ZA , Dixon BE , Patel P , Fireman B , Arndorfer J , Valvi NR , Griggs EP , Hallowell C , Embi PJ , Ball SW , Thompson MG , Tenforde MW , Link-Gelles R . Pediatrics 2023 151 (5) OBJECTIVES: We assessed BNT162b2 vaccine effectiveness (VE) against mild to moderate and severe coronavirus disease 2019 (COVID-19) in children and adolescents through the Omicron BA.4/BA.5 period. METHODS: Using VISION Network records from April 2021 to September 2022, we conducted a test-negative, case-control study assessing VE against COVID-19-associated emergency department/urgent care (ED/UC) encounters and hospitalizations using logistic regression, conditioned on month and site, adjusted for covariates. RESULTS: We compared 9800 ED/UC cases with 70 232 controls, and 305 hospitalized cases with 2612 controls. During Delta, 2-dose VE against ED/UC encounters at 12 to 15 years was initially 93% (95% confidence interval 89 to 95), waning to 77% (69% to 84%) after ≥150 days. At ages 16 to 17, VE was initially 93% (86% to 97%), waning to 72% (63% to 79%) after ≥150 days. During Omicron, VE at ages 12 to 15 was initially 64% (44% to 77%), waning to 13% (3% to 23%) after ≥150 days; at ages 16 to 17 VE was 31% (10% to 47%) during days 60 to 149, waning to 7% (-8 to 20%) after 150 days. A monovalent booster increased VE to 54% (40% to 65%) at ages 12 to 15 and 46% (30% to 58%) at ages 16 to 17. At ages 5 to 11, 2-dose VE was 49% (33% to 61%) initially and 41% (29% to 51%) after 150 days. During Delta, VE against hospitalizations at ages 12 to 17 was high (>97%), and at ages 16 to 17 remained 98% (73% to 100%) beyond 150 days; during Omicron, hospitalizations were too infrequent to precisely estimate VE. CONCLUSIONS: BNT162b2 protected children and adolescents against mild to moderate and severe COVID-19. VE was lower during Omicron predominance including BA.4/BA.5, waned after dose 2 but increased after a monovalent booster. Children and adolescents should receive all recommended COVID-19 vaccinations. |
Effectiveness of COVID-19 mRNA vaccines in preventing COVID-19-associated outpatient visits and hospitalizations among American indian and Alaska native persons, January-November 2021: A test-negative case-control analysis using surveillance data
Lutz CS , Hartman RM , Vigil DE , Britton A , Burrage AB , Campbell AP , Close RM , Desnoyers C , Dobson J , Garcia S , Halasa N , Honie E , Kobayashi M , McMorrow M , Mostafa HH , Parker D , Pohl K , Prill MM , Richards J , Roessler KC , Sutcliffe CG , Taylor K , Swango-Wilson A , Va P , Verani JR , Singleton RJ , Hammitt LL . Open Forum Infect Dis 2023 10 (4) ofad172 BACKGROUND: Despite the disproportionate morbidity and mortality expeHealth Equity and Health Disparitiesrienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. METHODS: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. RESULTS: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. CONCLUSIONS: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population. |
Prevalence of Salmonella in stool during the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018
Kasumba IN , Powell H , Omore R , Hossain MJ , Sow SO , Ochieng JB , Badji H , Verani JR , Widdowson MA , Sen S , Nasrin S , Permala-Booth J , Jones JA , Roose A , Nasrin D , Sugerman CE , Juma J , Awuor A , Jones JCM , Doh S , Okoi C , Zaman SMA , Antonio M , Hunsperger E , Onyango C , Platts-Mills J , Liu J , Houpt E , Neuzil KM , Kotloff KL , Tennant SM . Clin Infect Dis 2023 76 S87-s96 BACKGROUND: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa. METHODS: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods. RESULTS: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P < .001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P = .04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P = .001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P = .002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%); NTS isolates were susceptible to ciprofloxacin at all sites. CONCLUSIONS: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa. |
Histo-Blood Group Antigen Null Phenotypes Associated With a Decreased Risk of Clinical Rotavirus Vaccine Failure Among Children <2 Years of Age Participating in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in Kenya, Mali, and the Gambia
Schwartz LM , Oshinsky J , Reymann M , Esona MD , Bowen MD , Jahangir Hossain M , Zaman SMA , Jones JCM , Antonio M , Badji H , Sarwar G , Sow SO , Sanogo D , Keita AM , Tamboura B , Traoré A , Onwuchekwa U , Omore R , Verani JR , Awuor AO , Ochieng JB , Juma J , Ogwel B , Parashar UD , Tate JE , Kasumba IN , Tennant SM , Neuzil KM , Rowhani-Rahbar A , Elizabeth Halloran M , Atmar RL , Pasetti MF , Kotloff KL . Clin Infect Dis 2023 76 S153-s161 BACKGROUND: Previously studied risk factors for rotavirus vaccine failure have not fully explained reduced rotavirus vaccine effectiveness in low-income settings. We assessed the relationship between histo-blood group antigen (HBGA) phenotypes and clinical rotavirus vaccine failure among children <2 years of age participating in the Vaccine Impact on Diarrhea in Africa Study in 3 sub-Saharan African countries. METHODS: Saliva was collected and tested for HBGA phenotype in children who received rotavirus vaccine. The association between secretor and Lewis phenotypes and rotavirus vaccine failure was examined overall and by infecting rotavirus genotype using conditional logistic regression in 218 rotavirus-positive cases with moderate-to-severe diarrhea and 297 matched healthy controls. RESULTS: Both nonsecretor and Lewis-negative phenotypes (null phenotypes) were associated with decreased rotavirus vaccine failure across all sites (matched odds ratio, 0.30 [95% confidence interval: 0.16-0.56] or 0.39 [0.25-0.62], respectively]. A similar decrease in risk against rotavirus vaccine failure among null HBGA phenotypes was observed for cases with P[8] and P[4] infection and their matched controls. While we found no statistically significant association between null HBGA phenotypes and vaccine failure among P[6] infections, the matched odds ratio point estimate for Lewis-negative individuals was >4. CONCLUSIONS: Our study demonstrated a significant relationship between null HBGA phenotypes and decreased rotavirus vaccine failure in a population with P[8] as the most common infecting genotype. Further studies are needed in populations with a large burden of P[6] rotavirus diarrhea to understand the role of host genetics in reduced rotavirus vaccine effectiveness. |
Antibiotic-prescribing practices for management of childhood diarrhea in 3 Sub-Saharan African countries: Findings from the vaccine impact on diarrhea in Africa (vida) study, 2015-2018
Awuor AO , Ogwel B , Powell H , Verani JR , Sow SO , Hossain MJ , Ochieng JB , Juma J , Jamka LP , Roose A , Doh S , Deichsel EL , Onwuchekwa U , Keita AM , Antonio M , Jones JCM , Zaman SMA , Badji H , Kasumba IN , Nasrin D , Platts-Mills JA , Houpt ER , Berendes DM , Sugerman CE , Widdowson MA , Tennant SM , Mintz ED , Omore R , Kotloff KL . Clin Infect Dis 2023 76 S32-s40 BACKGROUND: Despite antibiotic prescription being recommended for dysentery and suspected cholera only, diarrhea still triggers unwarranted antibiotic prescription. We evaluated antibiotic-prescribing practices and their predictors among children aged 2-59 months in the Vaccine Impact on Diarrhea in Africa (VIDA) Study performed in The Gambia, Mali, and Kenya. METHODS: VIDA was a prospective case-control study (May 2015-July 2018) among children presenting for care with moderate-to-severe diarrhea (MSD). We defined inappropriate antibiotic use as prescription or use of antibiotics when not indicated by World Health Organization (WHO) guidelines. We used logistic regression to assess factors associated with antibiotic prescription for MSD cases who had no indication for an antibiotic, at each site. RESULTS: VIDA enrolled 4840 cases. Among 1757 (36.3%) who had no apparent indication for antibiotic treatment, 1358 (77.3%) were prescribed antibiotics. In The Gambia, children who presented with a cough (adjusted odds ratio [aOR]: 2.05; 95% confidence interval [95% CI]: 1.21-3.48) were more likely to be prescribed an antibiotic. In Mali, those who presented with dry mouth (aOR: 3.16; 95% CI: 1.02-9.73) were more likely to be prescribed antibiotics. In Kenya, those who presented with a cough (aOR: 2.18; 95% CI: 1.01-4.70), decreased skin turgor (aOR: 2.06; 95% CI: 1.02-4.16), and were very thirsty (aOR: 4.15; 95% CI: 1.78-9.68) were more likely to be prescribed antibiotics. CONCLUSIONS: Antibiotic prescription was associated with signs and symptoms inconsistent with WHO guidelines, suggesting the need for antibiotic stewardship and clinician awareness of diarrhea case-management recommendations in these settings. |
Survey-based assessment of water, sanitation, and animal-associated risk factors for moderate-to-severe diarrhea in the Vaccine Impact On Diarrhea in Africa (VIDA) Study: The Gambia, Mali, and Kenya, 2015-2018
Berendes DM , Fagerli K , Kim S , Nasrin D , Powell H , Kasumba IN , Tennant SM , Roose A , Jahangir Hossain M , Jones JCM , Zaman SMA , Omore R , Ochieng JB , Verani JR , Widdowson MA , Sow SO , Doh S , Sugerman CE , Mintz ED , Kotloff KL . Clin Infect Dis 2023 76 S132-s139 BACKGROUND: Pediatric exposures to unsafe sources of water, unsafely managed sanitation, and animals are prevalent in low- and middle-income countries. In the Vaccine Impact on Diarrhea in Africa case-control study, we examined associations between these risk factors and moderate-to-severe diarrhea (MSD) in children <5 years old in The Gambia, Kenya, and Mali. METHODS: We enrolled children <5 years old seeking care for MSD at health centers; age-, sex-, and community-matched controls were enrolled at home. Conditional logistic regression models, adjusted for a priori confounders, were used to evaluate associations between MSD and survey-based assessments of water, sanitation, and animals living in the compound. RESULTS: From 2015 to 2018, 4840 cases and 6213 controls were enrolled. In pan-site analyses, children with drinking water sources below "safely managed" (onsite, continuously accessible sources of good water quality) had 1.5-2.0-fold higher odds of MSD (95% confidence intervals [CIs] ranging from 1.0 to 2.5), driven by rural site results (The Gambia and Kenya). In the urban site (Mali), children whose drinking water source was less available (several hours/day vs all the time) had higher odds of MSD (matched odds ratio [mOR]: 1.4, 95% CI: 1.1, 1.7). Associations between MSD and sanitation were site-specific. Goats were associated with slightly increased odds of MSD in pan-site analyses, whereas associations with cows and fowl varied by site. CONCLUSIONS: Poorer types and availability of drinking water sources were consistently associated with MSD, whereas the impacts of sanitation and household animals were context-specific. The association between MSD and access to safely managed drinking water sources post-rotavirus introduction calls for transformational changes in drinking water services to prevent acute child morbidity from MSD. |
Exploring survey-based water, sanitation, and animal associations with enteric pathogen carriage: Comparing results in a cohort of cases with moderate-to-severe diarrhea to those in controls in the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018
Berendes DM , Omore R , Prentice-Mott G , Fagerli K , Kim S , Nasrin D , Powell H , Jahangir Hossain M , Sow SO , Doh S , Jones JCM , Ochieng JB , Juma J , Awuor AO , Ogwel B , Verani JR , Widdowson MA , Kasumba IN , Tennant SM , Roose A , Zaman SMA , Liu J , Sugerman CE , Platts-Mills JA , Houpt ER , Kotloff KL , Mintz ED . Clin Infect Dis 2023 76 S140-s152 BACKGROUND: The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. METHODS: In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics. RESULTS: Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12-2.17), as well as cows (RR, 1.61; 95% CI, 1.16-2.24) and sheep (RR, 1.48; 95% CI, 1.11-1.96) living in the compound, were associated with Shiga toxin-producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15-1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp. CONCLUSIONS: Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children. |
Etiology, presentation, and risk factors for diarrheal syndromes in 3 Sub-Saharan African countries after the introduction of rotavirus vaccines from the Vaccine Impact on Diarrhea in Africa (VIDA) Study
Buchwald AG , Verani JR , Keita AM , Jahangir Hossain M , Roose A , Sow SO , Omore R , Doh S , Jones JCM , Nasrin D , Zaman SMA , Okoi C , Antonio M , Ochieng JB , Juma J , Onwuchekwa U , Powell H , Platts-Mills JA , Tennant SM , Kotloff KL . Clin Infect Dis 2023 76 S12-s22 BACKGROUND: Diarrheal disease is heterogeneous, including watery diarrhea (WD) and dysentery, some cases of which become persistent diarrhea (PD). Changes in risk over time necessitate updated knowledge of these syndromes in sub-Saharan Africa. METHODS: The Vaccine Impact on Diarrhea in Africa (VIDA) study was an age-stratified, case-control study of moderate-to-severe diarrhea among children <5 years old in The Gambia, Mali, and Kenya (2015-2018). We analyzed cases with follow-up of about 60 days after enrollment to detect PD (lasting ≥14 days), examined the features of WD and dysentery, and examined determinants for progression to and sequelae from PD. Data were compared with those from the Global Enteric Multicenter Study (GEMS) to detect temporal changes. Etiology was assessed from stool samples using pathogen attributable fractions (AFs), and predictors were assessed using χ2 tests or multivariate regression, where appropriate. RESULTS: Among 4606 children with moderate-to-severe diarrhea, 3895 (84.6%) had WD and 711 (15.4%) had dysentery. PD was more frequent among infants (11.3%) than in children 12-23 months (9.9%) or 24-59 months (7.3%), P = .001 and higher in Kenya (15.5%) than in The Gambia (9.3%) or Mali (4.3%), P < .001; the frequencies were similar among children with WD (9.7%) and those with dysentery (9.4%). Compared to children not treated with antibiotics, those who received antibiotics had a lower frequency of PD overall (7.4% vs 10.1%, P = .01), and particularly among those with WD (6.3% vs 10.0%; P = .01) but not among children with dysentery (8.5% vs 11.0%; P = .27). For those with watery PD, Cryptosporidium and norovirus had the highest AFs among infants (0.16 and 0.12, respectively), while Shigella had the highest AF (0.25) in older children. The odds of PD decreased significantly over time in Mali and Kenya while increasing significantly in The Gambia. CONCLUSIONS: The burden of PD endures in sub-Saharan Africa, with nearly 10% of episodes of WD and dysentery becoming persistent. |
Management of diarrhea in young children in Sub-Saharan Africa: Adherence to world health organization recommendations during the Global Enteric Multisite Study (2007-2011) and the Vaccine Impact of Diarrhea in Africa (VIDA) Study (2015-2018)
Deichsel EL , Keita AM , Verani JR , Powell H , Jamka LP , Hossain MJ , Jones JCM , Omore R , Awuor AO , Sow SO , Sanogo D , Tapia MD , Neuzil KM , Kotloff KL . Clin Infect Dis 2023 76 S23-s31 BACKGROUND: Reducing diarrhea-related morbidity and mortality is a global priority, particularly in low-resource settings. We assessed adherence to diarrhea case management indicators in the Global Enteric Multisite Study (GEMS) and Vaccine Impact of Diarrhea in Africa (VIDA) study. METHODS: GEMS (2007-2010) and VIDA (2015-2018) were age-stratified case-control studies of moderate-to-severe diarrhea (MSD) in children aged <5 years. In this case-only analysis, we included children enrolled in The Gambia, Kenya, and Mali. A case with no dehydration received adherent care at home if they were offered more than usual fluids and at least the same as usual to eat. Children with diarrhea and some dehydration are to receive oral rehydration salts (ORS) in the facility. The recommendation for severe dehydration is to receive ORS and intravenous fluids in the facility. Adherent care in the facility included a zinc prescription independent of dehydration severity. RESULTS: For home-based management of children with MSD and no signs of dehydration, 16.6% in GEMS and 15.6% in VIDA were adherent to guidelines. Adherence to guidelines in the facility was likewise low during GEMS (some dehydration, 18.5%; severe dehydration, 5.5%). The adherence to facility-based rehydration and zinc guidelines improved during VIDA to 37.9% of those with some dehydration and 8.0% of children with severe dehydration. CONCLUSIONS: At research sites in The Gambia, Kenya, and Mali, suboptimal adherence to diarrhea case management guidelines for children aged <5 years was observed. Opportunities exist for improvement in case management for children with diarrhea in low-resource settings. |
Clinical and epidemiologic features of cryptosporidium-associated diarrheal disease among young children living in Sub-Saharan Africa: The Vaccine Impact on Diarrhea in Africa (VIDA) Study
Hossain MJ , Powell H , Sow SO , Omore R , Roose A , Jones JCM , Zaman SMA , Badji H , Sarwar G , Kasumba IN , Onwuchekwa U , Doh S , Awuor AO , Ochieng JB , Verani JR , Liu J , Tennant SM , Nasrin D , Jamka LP , Liang Y , Howie SRC , Antonio M , Houpt ER , Kotloff KL . Clin Infect Dis 2023 76 S97-s105 BACKGROUND: As part of the Vaccine Impact on Diarrhea in Africa (VIDA) Study, we examined the prevalence, clinical presentation, and seasonality of Cryptosporidium in children to understand its relative burden after the introduction of rotavirus vaccine. METHODS: VIDA was a 3-year, age-stratified, matched case-control study of medically attended acute moderate-to-severe diarrhea (MSD) in children aged 0-59 months residing in censused populations at sites in Kenya, Mali, and The Gambia. Clinical and epidemiologic data were collected at enrollment, and a stool sample was tested for enteropathogens by quantitative PCR. An algorithm was created based on the organism's cycle threshold (Ct) and association with MSD to identify the subset of Cryptosporidium PCR-positive (Ct <35) cases most likely to be attributed to MSD. Clinical outcomes were assessed at 2-3 months after enrollment. RESULTS: One thousand one hundred six (22.9%) cases of MSD and 873 controls (18.1%) were PCR positive for Cryptosporidium; 465 cases (42.0%) were considered attributable to Cryptosporidium, mostly among children 6-23 months. Cryptosporidium infections peaked in The Gambia and Mali during the rainy season, while in Kenya they did not have clear seasonality. Compared with cases with watery MSD who had a negative PCR for Cryptosporidium, cases with watery MSD attributed to Cryptosporidium were less frequently dehydrated but appeared more severely ill using a modified Vesikari scale (38.1% vs 27.0%; P < 0.001), likely due to higher rates of hospitalization and intravenous fluid administration, higher prevalence of being wasted or very thin very thin (23.4% vs 14.7%; P < 0.001), and having severe acute malnutrition (midupper arm circumference <115 mm, 7.7% vs 2.5%; P < 0.001). On follow-up, Cryptosporidium-attributed cases had more prolonged and persistent episodes (43.2% vs 32.7%; P <0 .001) and linear growth faltering (change in height-for-age z score between enrollment and follow-up: -0.29 vs -0.17; P < 0.001). CONCLUSIONS: The burden of Cryptosporidium remains high among young children in sub-Saharan Africa. Its propensity to cause illness and further impact children longer term by compromising nutritional status early in life calls for special attention to enable appropriate management of clinical and nutritional consequences. |
Shigella in Africa: New insights from the Vaccine Impact on Diarrhea in Africa (VIDA) Study
Kasumba IN , Badji H , Powell H , Hossain MJ , Omore R , Sow SO , Verani JR , Platts-Mills JA , Widdowson MA , Zaman SMA , Jones J , Sen S , Permala-Booth J , Nasrin S , Roose A , Nasrin D , Ochieng JB , Juma J , Doh S , Jones JCM , Antonio M , Awuor AO , Sugerman CE , Watson N , Focht C , Liu J , Houpt E , Kotloff KL , Tennant SM . Clin Infect Dis 2023 76 S66-s76 BACKGROUND: We evaluated the burden of Shigella spp from children aged 0-59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018. METHODS: Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis. RESULTS: The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%). CONCLUSIONS: A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin. |
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