Low Immune Activation in Early Pregnancy Is Associated With Preterm But Not Small-for-gestational-age Delivery in Women Infected With Human Immunodeficiency Virus Initiating Antiretroviral Therapy in Pregnancy: A Prematurity Immunology in HIV-infected Mothers and their Infants Study (PIMS) Case-control Study in Cape Town, South Africa.

BACKGROUND: Mechanisms underlying an association between human immunodeficiency virus (HIV) or antiretroviral therapy (ART) during pregnancy with risk of preterm delivery (PTD) and small-for-gestational-age (SGA) remain unclear. We explored the association between cellular immune activation and PTD or SGA in women with HIV initiating ART during or before pregnancy. METHODS: Women with HIV enrolled at median 15 weeks' gestation, were analyzed for immune markers, and matched on ART initiation timing (15 women initiated pre- and 15 during pregnancy). There were 30 PTD (delivery 25th percentile) as outcomes. Lymphocytes, monocytes, and dendritic cell populations and their activation status or functionality were enumerated by flow cytometry. RESULTS: PTD cases initiating ART in pregnancy showed decreased CD8+ T cell, monocyte, and dendritic cell activation; increased classical (CD14+CD16-) and intermediate (CD14+CD16+) monocyte frequencies; and decreased inflammatory monocytes (CD14dimCD16+) compared with SGA cases and term controls (all P < .05). Allowing for baseline viral load, the immune markers remained significantly associated with PTD but only in women initiating ART in pregnancy. Lower monocyte activation was predictive of PTD. TLR ligand-induced interferon-α and macrophage inflammatory protein-1β levels in monocytes were significantly lower in PTD women initiating ART in pregnancy. CONCLUSION: Low immune activation, skewing toward anti-inflammatory monocytes, and lower monocyte cytokine production in response to TLR ligand stimulation were associated with PTD but not SGA among women initiating ART in, but not before, pregnancy, suggesting immune anergy to microbial stimulation as a possible underlying mechanism for PTD in women initiating ART in pregnancy

Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya.

There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37-4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12-8.56) and 0.27 (95% CI 0.14-0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study

The global burden and epidemiology of invasive non-typhoidal Salmonella infections

Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas

The global burden and epidemiology of invasive non-typhoidal Salmonella infections

Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas

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

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

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

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

Unprogrammed Deworming in the Kibera Slum, Nairobi: Implications for Control of Soil-Transmitted Helminthiases

<div><p>Background</p><p>Programs for control of soil-transmitted helminth (STH) infections are increasingly evaluating national mass drug administration (MDA) interventions. However, “unprogrammed deworming” (receipt of deworming drugs outside of nationally-run STH control programs) occurs frequently. Failure to account for these activities may compromise evaluations of MDA effectiveness.</p><p>Methods</p><p>We used a cross-sectional study design to evaluate STH infection and unprogrammed deworming among infants (aged 6–11 months), preschool-aged children (PSAC, aged 1–4 years), and school-aged children (SAC, aged 5–14 years) in Kibera, Kenya, an informal settlement not currently receiving nationally-run MDA for STH. STH infection was assessed by triplicate Kato-Katz. We asked heads of households with randomly-selected children about past-year receipt and source(s) of deworming drugs. Local non-governmental organizations (NGOs) and school staff participating in school-based deworming were interviewed to collect information on drug coverage.</p><p>Results</p><p>Of 679 children (18 infants, 184 PSAC, and 477 SAC) evaluated, 377 (55%) reported receiving at least one unprogrammed deworming treatment during the past year. PSAC primarily received treatments from chemists (48.3%) or healthcare centers (37.7%); SAC most commonly received treatments at school (55.0%). Four NGOs reported past-year deworming activities at 47 of >150 schools attended by children in our study area. Past-year deworming was negatively associated with any-STH infection (34.8% vs 45.4%, p = 0.005). SAC whose most recent deworming medication was sourced from a chemist were more often infected with <i>Trichuris</i> (38.0%) than those who received their most recent treatment from a health center (17.3%) or school (23.1%) (p = 0.05).</p><p>Conclusion</p><p>Unprogrammed deworming was received by more than half of children in our study area, from multiple sources. Both individual-level treatment and unprogrammed preventive chemotherapy may serve an important public health function, particularly in the absence of programmed deworming; however, they may also lead to an overestimation of programmed MDA effectiveness. A standardized, validated tool is needed to assess unprogrammed deworming.</p></div

How can the typhoid fever surveillance in Africa and the severe typhoid fever in Africa programs contribute to the introduction of typhoid conjugate vaccines?

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