Abstract
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.
We evaluated the burden of Shigella spp from children 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 study from 2015 to 2018.
The burden of early-onset disease caused by group B Streptococcus (GBS) has decreased dramatically in the United States over the past 20 years. Universal culture-based screening at 35 to 37 weeks ...gestational age and use of intrapartum antibiotic prophylaxis are the cornerstones of prevention measures that have led to this decline. GBS, however, remains the leading cause of early-onset neonatal sepsis in the United States. Revised guidelines for prevention of perinatal GBS are planned for issuance in 2010. This article discusses implementation challenges for clinicians caring for pregnant women and newborns and presents an updated algorithm for neonatal management.
Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted ...1–2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya.
We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November–December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1–4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung.
We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes.
Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Acute febrile illness (AFI) is a common reason for healthcare seeking and hospitalization in Sub-Saharan Africa and is often presumed to be malaria. However, a broad range of pathogens cause fever, ...and more comprehensive data on AFI etiology can improve clinical management, prevent unnecessary prescriptions, and guide public health interventions. We conducted surveillance for AFI (temperature greater than or equal to38.0°C <14 days duration) among hospitalized patients of all ages at four sites in Kenya (Nairobi, Mombasa, Kakamega, and Kakuma). For cases of undifferentiated fever (UF), defined as AFI without diarrhea (greater than or equal to3 loose stools in 24 hours) or lower respiratory tract symptoms (cough/difficulty breathing plus oxygen saturation <90% or in children <5 years chest indrawing), we tested venous blood with real-time PCR-based TaqMan array cards (TAC) for 17 viral, 8 bacterial, and 3 protozoal fever-causing pathogens. From June 2017 to March 2019, we enrolled 3,232 AFI cases; 2,529 (78.2%) were aged <5 years. Among 3,021 with outcome data, 131 (4.3%) cases died while in hospital, including 106/2,369 (4.5%) among those <5 years. Among 1,735 (53.7%) UF cases, blood was collected from 1,340 (77.2%) of which 1,314 (98.1%) were tested by TAC; 715 (54.4%) had no pathogens detected, including 147/196 (75.0%) of those aged <12 months. The most common pathogen detected was Plasmodium, as a single pathogen in 471 (35.8%) cases and in combination with other pathogens in 38 (2.9%). HIV was detected in 51 (3.8%) UF cases tested by TAC and was most common in adults (25/236 10.6% ages 18-49, 4/40 10.0% ages greater than or equal to50 years). Chikungunya virus was found in 30 (2.3%) UF cases, detected only in the Mombasa site. Malaria prevention and control efforts are critical for reducing the burden of AFI, and improved diagnostic testing is needed to provide better insight into non-malarial causes of fever. The high case fatality of AFI underscores the need to optimize diagnosis and appropriate management of AFI to the local epidemiology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A U.S. case-control study (2010–2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive ...pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes.
We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC’s Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010–2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %).
Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4–96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7–93.3 %), 50.2 % (28.4–80.5 %), and 93.8 % (69.8–98.8 %) against serotypes 19A, 3, and 19F, respectively.
At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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.
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.
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.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
The impact of human immunodeficiency virus (HIV) on pregnancy outcomes for women on antiretroviral therapy (ART) in sub-Saharan Africa remains unclear.
Methods
Pregnant women in ...Kenya were enrolled in the second trimester and followed up to delivery. We estimated effects of treated HIV with 3 pregnancy outcomes: loss, premature birth, and low birth weight and factors associated with HIV-positive status.
Results
Of 2113 participants, 311 (15%) were HIV infected and on ART. Ninety-one of 1762 (5%) experienced a pregnancy loss, 169/1725 (10%) a premature birth (<37 weeks), and 74/1317 (6%) had a low-birth-weight newborn (<2500 g). There was no evidence of associations between treated HIV infection and pregnancy loss (adjusted relative risk aRR, 1.19; 95% confidence interval CI, .65–2.16; P = .57), prematurity (aRR, 1.09; 95% CI, .70–1.70; P = .69), and low birth weight (aRR, 1.36; 95% CI, .77–2.40; P = .27). Factors associated with an HIV-positive status included older age, food insecurity, lower education level, higher parity, lower gestation at first antenatal clinic, anemia, and syphilis. Women who were overweight or underweight were less likely to be HIV infected compared to those with normal weight.
Conclusions
Currently treated HIV was not significantly associated with adverse pregnancy outcomes. HIV-infected women, however, had a higher prevalence of other factors associated with adverse pregnancy outcomes.
We estimated the effect of currently treated HIV on pregnancy loss, prematurity, and low birth weight. We found no differences in the risk of the 3 adverse pregnancy outcomes between pregnant HIV-uninfected women and HIV-infected women on antiretroviral treatment.
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.
Residents of long-term care facilities (LTCFs), particularly those in skilled nursing facilities (SNFs), have experienced disproportionately high levels of COVID-19-associated morbidity and mortality ...and were prioritized for early COVID-19 vaccination (1,2). However, this group was not included in COVID-19 vaccine clinical trials, and limited postauthorization vaccine effectiveness (VE) data are available for this critical population (3). It is not known how well COVID-19 vaccines protect SNF residents, who typically are more medically frail, are older, and have more underlying medical conditions than the general population (1). In addition, immunogenicity of the Pfizer-BioNTech vaccine was found to be lower in adults aged 65-85 years than in younger adults (4). Through the CDC Pharmacy Partnership for Long-Term Care Program, SNF residents and staff members in Connecticut began receiving the Pfizer-BioNTech COVID-19 vaccine on December 18, 2020 (5). Administration of the vaccine was conducted during several on-site pharmacy clinics. In late January 2021, the Connecticut Department of Public Health (CT DPH) identified two SNFs experiencing COVID-19 outbreaks among residents and staff members that occurred after each facility's first vaccination clinic. CT DPH, in partnership with CDC, performed electronic chart review in these facilities to obtain information on resident vaccination status and infection with SARS-CoV-2, the virus that causes COVID-19. Partial vaccination, defined as the period from >14 days after the first dose through 7 days after the second dose, had an estimated effectiveness of 63% (95% confidence interval CI = 33%-79%) against SARS-CoV-2 infection (regardless of symptoms) among residents within these SNFs. This is similar to estimated effectiveness for a single dose of the Pfizer-BioNTech COVID-19 vaccine in adults across a range of age groups in noncongregate settings (6) and suggests that to optimize vaccine impact among this population, high coverage with the complete 2-dose series should be recommended for SNF residents and staff members.
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DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine ...performance under ‘real world’ conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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