First name
Andrew
Middle name
P
Last name
Steenhoff

Title

Kinetics of pneumococcal antibodies among HIV-exposed, uninfected infants in Botswana.

Year of Publication

2022

Number of Pages

4764-4771

Date Published

06/2022

ISSN Number

1873-2518

Abstract

BACKGROUND: Streptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants.

METHODS: We conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes.

RESULTS: At birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55-93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age.

CONCLUSIONS: Both HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.

DOI

10.1016/j.vaccine.2022.06.059

Alternate Title

Vaccine

PMID

35773120

Title

Skin conditions among pediatric dermatology outpatients in Botswana.

Year of Publication

2022

Date Published

06/2022

ISSN Number

1525-1470

Abstract

BACKGROUND: An understanding of the prevalence patterns of skin diseases in children in Botswana is needed to guide national dermatological policy development, training, and resource allocation to improve patient care.

OBJECTIVE: To describe local skin disease patterns in children aged 0-18 years presenting for dermatologic care in Botswana.

METHODS: A retrospective review of records from 1st January 2011 to 31st December 2016 was conducted at the outpatient dermatology clinic of Princess Marina Hospital (PMH) in Gaborone, Botswana and outreach clinic sites.

RESULTS: There were 4413 pediatric visits constituting 18.6% of all dermatology visits. There was a slight male predominance of 1.2:1. The majority of disorders were noninfectious 80.1% (3537/4413) versus infectious 14.6% (645/4413), with 5.2% (231/4413) unclassified. In the noninfectious category, two-thirds were inflammatory, followed by disorders of nails, skin appendages, and pigmentary disorders. Atopic dermatitis was the most common inflammatory disorder. Over half of infectious skin diseases were viral, followed by fungal and bacterial disorders. In the HIV-related disorders, the majority were verrucae 94% (108/115) followed by Kaposi sarcoma. The nine most common skin diagnoses accounted for close to 70% of all skin diseases seen at the clinic, and these included atopic dermatitis (almost half of all cases), followed by verruca, acne, and vitiligo.

CONCLUSION: There is a high burden of skin disorders in children in Botswana. In our cohort, a small number of skin conditions made up the vast majority of pediatric diagnoses. This information can be used to guide dermatology training and resource allocation to better manage these common diseases.

DOI

10.1111/pde.15066

Alternate Title

Pediatr Dermatol

PMID

35761771

Title

'That's when I struggle' … Exploring challenges faced by care givers of children with tuberculosis in Botswana.

Year of Publication

2016

Number of Pages

1314-1319

Date Published

2016 Oct

ISSN Number

1815-7920

Abstract

SETTING: Government-funded public health clinics in and around Gaborone, Botswana.

OBJECTIVE: To explore the challenges faced by care givers of children on treatment for tuberculosis (TB) to inform a more child-friendly approach to Botswana's National TB Programme (NTP) strategy.

DESIGN: Qualitative study using 28 in-depth interviews with care givers of children receiving anti-tuberculosis treatment.

RESULTS: Care givers identified five main challenges: long delays in their child's diagnosis, difficulty attending clinic for daily treatment, difficulty administering TB medications, stock-outs of TB medications leading to treatment interruptions, and inadequate TB education. Care givers prioritized these same five areas to improve the overall management of their child's TB.

CONCLUSION: Our findings suggest that despite accessing care through an NTP that adheres to World Health Organization guidelines, care givers for children on treatment in Botswana continue to encounter significant challenges. While each of these represents a potential threat to successful treatment, they can be addressed with relatively small systematic and programmatic adjustments. These results will inform the next version of the Botswana NTP guidelines towards a more child- and care giver-centered approach.

DOI

10.5588/ijtld.15.0989

Alternate Title

Int. J. Tuberc. Lung Dis.

PMID

27725041

Title

Evaluation of Anatomically Designed Flocked Rectal Swabs for Use with the Biofire FilmArray™ Gastrointestinal Panel for Detection of Enteric Pathogens in Children Admitted to Hospital with Severe Gastroenteritis.

Year of Publication

2019

Date Published

2019 Sep 11

ISSN Number

1098-660X

Abstract

Diagnosing diarrheal disease is difficult in part due to challenges in obtaining and transporting a bulk stool specimen, particularly in resource-limited settings. We compared the performance of flocked rectal swabs to that of traditional bulk stool samples for enteric pathogen detection using the BioFire™ FilmArray Gastrointestinal panel in children admitted to 4 hospitals in Botswana with community onset severe gastroenteritis. Of the 117-matched flocked rectal swab/stool pairs, we found no significant difference in pathogen detection rates between the flocked rectal swab samples and traditional bulk stool sampling methods for any bacterial (168 versus 167, respectively), viral (94 versus 92, respectively), or protozoan (18 versus 18, respectively) targets. The combination of flocked rectal swab samples with FilmArray testing allows for the rapid diagnosis of infectious gastroenteritis, facilitating a test and treat approach for infections that are life-threatening in many resource-limited settings. Culture recovery rates for bacterial pathogens utilizing this approach need to be assessed.

DOI

10.1128/JCM.00962-19

Alternate Title

J. Clin. Microbiol.

PMID

31511336

Title

Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: a multicentre, randomised, controlled, factorial trial in Botswana.

Year of Publication

2022

Date Published

2022 Apr

ISSN Number

2059-7908

Abstract

<p><strong>INTRODUCTION: </strong>The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy ('test-and-treat') and/or&nbsp;<em>Lactobacillus reuteri</em> DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis.</p>

<p><strong>METHODS: </strong>This was a multicentre, randomised, factorial, controlled, trial. Children aged 2-60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to <em>L. reuteri</em>/placebo assignment; this was dosed as 1×10<sup>8</sup> cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov.</p>

<p><strong>RESULTS: </strong>Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus <em>L. reuteri&nbsp;</em>group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus <em>L. reuteri&nbsp;</em>group and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI -0.14 to 0.16 SD) or the&nbsp;<em>L. reuteri</em> intervention (mean decrease of 0.07 SD, 95% CI -0.22 to 0.08 SD) on adjusted HAZ at 60 days.</p>

<p><strong>CONCLUSIONS: </strong>In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of <em>L. reuteri&nbsp;</em>DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as <em>Shigella</em>) in their stool.</p>

<p><strong>TRIAL REGISTRATION NUMBER: </strong>NCT02803827.</p>

DOI

10.1136/bmjgh-2021-007826

Alternate Title

BMJ Glob Health

PMID

35418412

Title

The perceptions and practices of parents and children on acute pain management among hospitalized children in two Botswana referral hospitals.

Year of Publication

2022

Date Published

2022 Feb 18

ISSN Number

1532-8449

Abstract

<p><strong>BACKGROUND: </strong>Perceptions and practices of parties in pediatric pain are critical in children's access to adequate acute pain management. The personal factors of the child and parents have been shown to be central to pediatric pain management by the Symptom Management Theory.</p>

<p><strong>AIM: </strong>To describe children and parents/guardians' perceptions (knowledge, attitudes and beliefs) and practices regarding pediatric acute pain management and explain the influence of socio-cultural and environmental factors on those perceptions and practices.</p>

<p><strong>METHODS: </strong>Descriptive cross-sectional survey using modified versions of the American Pain Society Patient Outcome Questionnaire-Revised among parents/guardians and children.</p>

<p><strong>RESULTS: </strong>A convenience sample of 275 parents/guardians and 42 children aged 8 to 13 years admitted between date November 2018 and February 2019 to two Botswana tertiary hospitals completed the surveys. Forty-seven percent (n = 129) of parents/guardians reported the child to be in moderate-severe pain, while 38% (n = 16) of children reported pain as moderate-severe at the time of the survey. The children mean scores for cm-APS-POQ-R were 113(33) while parents/guardian's guardians for m-APS-POQ-R were 123(26). The subscales except for the parents/'guardians' pain interference (p = .96) were statistically significant (p = .000), showing adequate knowledge, positive attitudes and high pain intensity for both parents/guardians and children.</p>

<p><strong>CONCLUSION: </strong>Parent/guardians and children reported a high incidence of acute pain, were content with pain management services, and showed adequate knowledge of pediatric pain and its management. The incongruence between the intensity of pain, satisfaction on the adequacy of pain management and knowledge and attitudes demonstrated in this study need further inquiry.</p>

DOI

10.1016/j.pedn.2022.02.004

Alternate Title

J Pediatr Nurs

PMID

35190237

Title

The Prevalence, Intensity, Assessment, and Management of Acute Pain in Hospitalized Children in Botswana.

Year of Publication

2022

Date Published

2022 Jan 02

ISSN Number

1532-8635

Abstract

<p><strong>BACKGROUND: </strong>There is very limited clinical and observational data on acute pain experienced by children in sub-Saharan Africa.</p>

<p><strong>AIMS: </strong>To report the prevalence and intensity of acute pain, pain management practices, and describe associations between acute pain outcomes, children's and parents or guardian's demographics in hospitalized children aged 2 months to 13 years in Botswana.</p>

<p><strong>DESIGN: </strong>A descriptive correlational prospective observational study using five repeated cross-sectional samples.</p>

<p><strong>SETTINGS: </strong>Two referral hospitals in Botswana.</p>

<p><strong>PARTICIPANTS: </strong>The sample size included 308 children and 226 parents or guardians. Data were collected between November 2018 and February 2019 from children, their parents or guardians (&lt;7 years child), and the health record for pain documentation and treatment.</p>

<p><strong>MEASURES: </strong>Pain was measured using Faces Pain Scale-Revised for children ≥7 years, revised Face, Legs, Activity, Cry, Consolability scale for children &lt;7 years and numeric rating scale for parents or guardians.</p>

<p><strong>RESULTS: </strong>There are 1,290 data points for children of which 1,000 were children &lt;7 years and 999 data points for parents or guardians of children &lt;7 years were used in analysis. Fifty percent of children &lt;7 years were in pain using the revised Face, Legs, Activity, Cry, Consolability scale, whereas parents indicated 46% to be in pain. The pain prevalence for children ≥7 years was estimated at 54%. Pain was documentated at a rate of 54 % on the health records. Acetaminophen was most common analgesic across all age groups. Univariate associations of child &lt;7 years pain intensity was statistically significant (p ≤ .05) for weight, diagnosis, residence, and parent relationship. Parents reported pain intensity was statistically significant (p ≤ .05) for child sex, weight, diagnosis, residence, surgery, parent or guardian age and education. Only age and surgery were significant for children ≥7 years.</p>

<p><strong>CONCLUSIONS: </strong>Acute pain prevalence and intensity among hospitalized children in Botswana is low.</p>

DOI

10.1016/j.pmn.2021.11.012

Alternate Title

Pain Manag Nurs

PMID

34987004

Title

Characterizing the bioburden of ESBL-producing organisms in a neonatal unit using chromogenic culture media: a feasible and efficient environmental sampling method.

Year of Publication

2022

Number of Pages

14

Date Published

2022 01 24

ISSN Number

2047-2994

Abstract

<p><strong>INTRODUCTION: </strong>Infections due to extended spectrum beta-lactamase producing organisms (ESBL) have emerged as the leading cause of sepsis among hospitalized neonates in Botswana and much of sub-Saharan Africa and south Asia. Yet, ESBL reservoirs and transmission dynamics within the neonatal intensive care unit (NICU) environment are not well-understood. This study aimed to assess the efficiency and feasibility of a chromogenic-culture-media-based environmental sampling approach to characterize the ESBL bioburden within a NICU.</p>

<p><strong>METHODS: </strong>A series of four point-prevalence surveys were conducted at a 36-bed NICU at a public tertiary referral hospital in Botswana from January-June 2021. Samples were collected on 4 occasions under semi-sterile technique using 1) flocked swabs &amp; templates (flat surfaces); 2) sterile syringe &amp; tubing (water aspiration); and 3) structured swabbing techniques (hands &amp; equipment). Swabs were transported in physiological saline-containing tubes, vortexed, and 10 µL was inoculated onto chromogenic-agar that was selective and differential for ESBL (CHROMagar™ ESBL, Paris, France), and streaking plates to isolate individual colonies. Bacterial colonies were quantified and phenotypically characterized using biochemical identification tests.</p>

<p><strong>RESULTS: </strong>In total, 567 samples were collected, 248 (44%) of which grew ESBL. Dense and consistent ESBL contamination was detected in and around sinks and certain high-touch surfaces, while transient contamination was demonstrated on medical equipment, caregivers/healthcare worker hands, insects, and feeding stations (including formula powder). Results were available within 24-72&nbsp;h of collection. To collect, plate, and analyse 50 samples, we estimated a total expenditure of $269.40 USD for materials and 13.5 cumulative work hours among all personnel.</p>

<p><strong>CONCLUSIONS: </strong>Using basic environmental sampling and laboratory techniques aided by chromogenic culture media, we identified ESBL reservoirs (sinks) and plausible transmission vehicles (medical equipment, infant formula, hands of caregivers/healthcare workers, &amp; insects) in this NICU environment. This strategy was a simple and cost-efficient method to assess ESBL bioburden and may be feasible for use in other settings to support ongoing infection control assessments and outbreak investigations.</p>

DOI

10.1186/s13756-021-01042-2

Alternate Title

Antimicrob Resist Infect Control

PMID

35074019

Title

Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine.

Year of Publication

2022

Number of Pages

e0262225

Date Published

2022

ISSN Number

1932-6203

Abstract

<p>Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.</p>

DOI

10.1371/journal.pone.0262225

Alternate Title

PLoS One

PMID

34986196

Title

Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy.

Year of Publication

2021

Date Published

2021 Sep 11

ISSN Number

1751-7370

Abstract

<p>Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0-6 months of age) or bimonthly (6-12 months of age) from 179 mother-infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.</p>

DOI

10.1038/s41396-021-01108-4

Alternate Title

ISME J

PMID

34511605

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