The Burden of Invasive Bacterial Disease and the Impact of 10-Valent Pneumococcal Conjugate Vaccine in Children <5 years hospitalized for Meningitis in Lusaka, Zambia, 2010-2019.

BACKGROUND: Despite the availability of vaccines, invasive bacterial diseases remain a public health concern and cause childhood morbidity and mortality. We investigated the characteristics of etiological agents causing bacterial meningitis in children <5 years in the years pre- (2010-2012) and post- (2014-2019) 10-valent pneumococcal conjugate vaccine (PCV10) introduction in Zambia. METHODS: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hi), and Neisseria meningitidis (Nm) from cerebrospinal fluid (CSF) were identified by microbiological culture and/or real-time polymerase chain reaction. RESULTS: During the surveillance period, a total of 3811 children were admitted with suspected meningitis, 16% (598 of 3811) of which were probable cases. Bacterial meningitis was confirmed in 37% (221 of 598) of the probable cases. Spn pneumoniae, Hi, and Nm accounted for 67% (148 of 221), 14% (31 of 221), and 19% (42 of 221) of confirmed cases, respectively. Thirty-six percent of pneumococcal meningitis was caused by 10-valent pneumococcal conjugate vaccine (PCV10) serotypes, 16% 13-valent pneumococcal conjugate vaccine and 39% by nonvaccine serotype (NVS). There was an association between the introduction of PCV10 vaccination and a decrease in both Spn meningitis and the proportion of PVC10 serotypes in the postvaccination period. Antimicrobial susceptibility of 47 Spn isolates revealed 34% (16 of 47) penicillin resistance. The 31 serotyped Hi accounted for 74% type b (Hib) and 10% type a (Hia). All 42 serogrouped Nm belonged to serogroup W. CONCLUSIONS: There was a decline in pneumococcal meningitis and proportion of PCV10 serotypes in the postvaccination period. However, the serotype replacement with non-PCV10 serotypes and penicillin resistance warrant continued surveillance to inform policy.

Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa.

BACKGROUND: Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries. METHODS: Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method. RESULTS: Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence [i.e., the incidence during the risk window vs. all other times], 0.25; 95% confidence interval [CI], <0.001 to 1.16); findings were similar for the 1 to 7 days after dose 2 (relative incidence, 0.76; 95% CI, 0.16 to 1.87). In addition, the risk of intussusception in the 8 to 21 days or 1 to 21 days after either dose was not found to be higher than the background risk. CONCLUSIONS: The risk of intussusception after administration of monovalent human rotavirus vaccine was not higher than the background risk of intussusception in seven lower-income sub-Saharan African countries. (Funded by the GAVI Alliance through the CDC Foundation.).

Risk Factors Associated With Increased Mortality From Intussusception in African Infants.

OBJECTIVES: Morbidity and mortality from intussusception, the leading cause of bowel obstruction in infants, is higher in Africa than in other regions of the world, but the reasons have not been well examined. We sought to identify risk and protective factors associated with death or intestinal resection following intussusception. METHODS: Infants with intussusception from 7 sub-Saharan African countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) were enrolled through active, hospital-based surveillance from February 2012 to December 2016. We examined demographic, clinical, and socioeconomic factors associated with death or intestinal resection following intussusception, using multivariable logistic regression. RESULTS: A total of 1017 infants <1 year of age with intussusception were enrolled. Overall, 13% of children (133/1017) died during the hospitalization, and 48% (467/966) required intestinal resection. In multivariable analyses, female sex [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2-3.3], longer duration of symptoms before presentation (OR 1.1; 95% CI 1.0-1.2), and undergoing intestinal resection (OR 3.4; 95% CI 1.9-6.1) were associated with death after intussusception. Diagnosis by ultrasound or enema (OR 0.4; 95% CI 0.3-0.7), and employment of a household member (OR 0.7; 95% CI 0.4-1.0) were protective against intestinal resection. CONCLUSIONS: Delays in hospital presentation and female sex were significantly associated with death, whereas higher socioeconomic status and availability of radiologic diagnosis reduced likelihood of undergoing resection. Efforts should be intensified to improve the awareness, diagnosis, and management of intussusception in sub-Saharan African countries to reduce morbidity and mortality from intussusception in these resource-limited settings.

Declines in Pneumonia and Meningitis Hospitalizations in Children Under 5 Years of Age After Introduction of 10-Valent Pneumococcal Conjugate Vaccine in Zambia, 2010-2016.

BACKGROUND: Pneumococcus is a leading cause of pneumonia and meningitis. Zambia introduced a 10-valent pneumococcal conjugate vaccine (PCV10) in July 2013 using a 3-dose primary series at ages 6, 10, and 14 weeks with no booster. We evaluated the impact of PCV10 on meningitis and pneumonia hospitalizations. METHODS: Using hospitalization data from first-level care hospitals, available at the Ministry of Health, and from the largest pediatric referral hospital in Lusaka, we identified children aged <5 years who were hospitalized with pneumonia or meningitis from January 2010-December 2016. We used time-series analyses to measure the effect of PCV10 on monthly case counts by outcome and age group (<1 year, 1-4 years), accounting for seasonality. We defined the pre- and post-PCV10 periods as January 2010-June 2013 and July 2014-December 2016, respectively. RESULTS: At first-level care hospitals, pneumonia and meningitis hospitalizations among children aged <5 years accounted for 108 884 and 1742 admissions in the 42 months pre-PCV10, respectively, and 44 715 and 646 admissions in the 30 months post-PCV10, respectively. Pneumonia hospitalizations declined by 37.8% (95% confidence interval [CI] 21.4-50.3%) and 28.8% (95% CI 17.7-38.7%) among children aged <1 year and 1-4 years, respectively, while meningitis hospitalizations declined by 72.1% (95% CI 63.2-79.0%) and 61.6% (95% CI 50.4-70.8%), respectively, in these age groups. In contrast, at the referral hospital, pneumonia hospitalizations remained stable and a smaller but significant decline in meningitis was observed among children aged 1-4 years (39.3%, 95% CI 16.2-57.5%). CONCLUSIONS: PCV10 introduction was associated with declines in meningitis and pneumonia hospitalizations in Zambia, especially in first-level care hospitals.

Multicountry Analysis of Spectrum of Clinical Manifestations of Children <5 Years of Age Hospitalized with Diarrhea.

After introduction of rotavirus vaccine, other pathogens might become leading causes of hospitalizations for severe diarrhea among children <5 years of age. Our study in 33 hospitals in 7 countries found acute gastroenteritis accounted for most (84%) reported hospitalizations of children with diarrhea. Bloody and persistent diarrhea each accounted for <1%.

Children infected by human herpesvirus 6B with febrile seizures are more likely to develop febrile status epilepticus: A case-control study in a referral hospital in Zambia.

BACKGROUND: Human herpesvirus 6B (HHV-6B) is the causative agent of Roseola infantum, and has also been suggested to play a role in the pathogenesis of febrile seizures in young children, a percentage of whom go on to develop febrile status epilepticus (FSE), but the existing data is conflicting and inconclusive. HHV-6A is a distinct species, rarely detected in most parts of the world, but prior studies suggest a higher prevalence in febrile African children. We describe a case-control study comparing the frequency of HHV-6A and/or HHV-6B infections in children with febrile seizures (including FSE) and a control group of febrile children without seizures. METHODS: We recruited children aged 6 to 60 months admitted with a febrile illness with (cases) or without (controls) seizures presenting within 48 hours of commencement of fever. Three milliliters of whole blood was centrifuged and plasma stored at -80°C for pooled screening for HHV-6B and HHV-6A by Taqman real-time polymerase chain reaction. RESULTS: 102 cases and 95 controls were recruited. The prevalence of HHV-6B DNA detection did not differ significantly between cases (5.8% (6/102)) and controls (10.5% (10/95)) but HHV-6B infection was associated with FSE (OR, 15; 95% CI, [1.99-120]; P= 0.009). HHV-6A was not detected. CONCLUSION: Prevalence of HHV-6B was similar among cases and controls. Within the FS group, HHV-6B infection was associated with FSE, suggesting HHV-6B infections could play a role in the pathogenesis of FSE.

Review of Naturally Occurring Intussusception in Young Children in the WHO African Region prior to the Era of Rotavirus Vaccine Utilization in the Expanded Programme of Immunization.

Rotavirus vaccines, Rotarix and RotaTeq, are increasingly being introduced in national immunization programmes in Africa to prevent severe dehydrating acute gastroenteritis. A low-level risk of intussusception has been associated with rotavirus vaccines. We reviewed published data on intussusception in children <2 years of age in Africa. PubMed electronic database search was used to retrieve papers published on intussusception. The search was further refined to identify surveillance reports and case series conducted from 1980 to 2014, with at least 25 cases. The initial search identified 34 studies, and the refined search yielded 16. Intussusception occurred naturally in infants 2-4 months and peaked around 5-8 months of age. Delayed presentation was common and required surgical intervention in 87% (1008 of 1158) of cases with a high CFR, 10-33.7%. In African children, intussusception has been reported infrequently at a young age when the first dose of rotavirus vaccine is administered.

Impact of Rotavirus Vaccination on Diarrheal Hospitalizations in Children Aged <5 Years in Lusaka, Zambia.

BACKGROUND: Monovalent rotavirus vaccine was introduced in the routine public health immunization program in Lusaka, Zambia, in January 2012 and was rolled out countrywide in November 2013. We examined the effect of rotavirus vaccination on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE at a large referral hospital in Lusaka. METHODS: Data were derived from ongoing hospital-based AGE surveillance from January 2009 to December 2014. Pre-rotavirus vaccine introduction (2009-2011) and post-rotavirus vaccine introduction (2013-2014) periods were compared for annual changes in hospitalizations for AGE and rotavirus; 2012 was excluded as a transition year. Hospital administrative discharge data were used to compare trends in all-cause diarrhea discharges and in-hospital diarrhea deaths captured by HIMS pre- and post-rotavirus vaccine introduction. RESULTS: Between January 2009 and December 2014, 5937 children <5 years of age presenting with AGE had their stools collected and tested for rotavirus by enzyme immunoassay. The rotavirus positivity rate declined from 40.1% (449/1121) in prevaccine years to 30.2% (250/828;P< .001) in 2013 and 24.7% (157/635;P< .001) in 2014. The greatest reduction was noted in infants, with the rotavirus positivity rate in this age group declining from 40.9% in prevaccine years to 34.0% (P= .009) in 2013 and 26.2% (P< .001) in 2014. Following rotavirus vaccine introduction, seasonal peaks of rotavirus and all-cause AGE were dwarfed. From HIMS data, compared to the prevaccine era, reductions of 18%-29% in all-cause diarrhea hospitalizations and 27%-33% in-hospital diarrhea deaths among children <1 year of age were observed in 2013 and 2014. CONCLUSIONS: We observed a significant reduction in AGE-associated in-hospital morbidity and mortality following rotavirus vaccine introduction. The greatest reduction was seen in infants <1 year who accounted for 84.4% of rotavirus hospitalizations prior to vaccine introduction.

Zinc absorption from biofortified maize meets the requirements of young rural Zambian children.

BACKGROUND: The zinc content of maize, a major global food staple, is generally insufficient alone to meet the requirements of young children. OBJECTIVES: The primary objective of this study was to determine whether substitution of biofortified maize (34 µg zinc/g grain) for control maize (21 µg zinc/g) was adequate to meet zinc physiologic requirements in young children for whom maize was the major food staple. A secondary objective was to compare total daily zinc absorption when maize flour was fortified with zinc oxide to a total concentration of 60 µg zinc/g. METHODS: Participants included 60 rural Zambian children with a mean age of 29 mo who were randomly assigned to receive 1 of 3 maize types (control, biofortified, or fortified) all of which were readily consumed (>100 g on 1 d). Total daily zinc intake (from maize and low-zinc relish) was determined from duplicate diet collections. Multiplication by fractional absorption of zinc, measured by a dual isotope ratio technique, determined the total daily zinc absorption on the day the test meals were given. RESULTS: The mean ± SD total daily zinc intake (milligrams per day) from the biofortified maize (5.0 ± 2.2) was higher (P < 0.0001) than for the control maize (2.3 ± 0.9). Intake of zinc from the fortified maize (6.3 ± 2.6) did not differ from the biofortified maize. Fractional absorption of zinc from control maize (0.28 ± 0.10) did not differ from the biofortified maize (0.22 ± 0.06). Total daily absorption of zinc (milligrams per day) from the biofortified maize (1.1 ± 0.5) was higher (P = 0.0001) than for the control maize (0.6 ± 0.2), but did not differ from the fortified maize (1.2 ± 0.4). CONCLUSIONS: These results indicate that feeding biofortified maize can meet zinc requirements and provide an effective dietary alternative to regular maize for this vulnerable population. This trial was registered at clinicaltrials.gov as NCT02208635.

Characterization of human respiratory syncytial virus in children with severe acute respiratory infection before and during the COVID-19 pandemic.

Objectives: Annual outbreaks of human respiratory syncytial virus (HRSV) are caused by newly introduced and locally persistent strains. During the COVID-19 pandemic, global and local circulation of HRSV significantly decreased. This study was conducted to characterize HRSV in 2018-2022 and to analyze the impact of COVID-19 on the evolution of HRSV. Design/methods: Combined oropharyngeal and nasopharyngeal swabs were collected from children hospitalized with severe acute respiratory infection at two hospitals in Zambia. The second hypervariable region of the attachment gene G was targeted for phylogenetic analysis. Results: Of 3113 specimens, 504 (16.2%) were positive for HRSV, of which 131 (26.0%) and 66 (13.1%) were identified as HRSVA and HRSVB, respectively. In early 2021, an increase in HRSV was detected, caused by multiple distinct clades of HRSVA and HRSVB. Some were newly introduced, whereas others resulted from local persistence. Conclusions: This study provides insights into the evolution of HRSV, driven by global and local circulation. The COVID-19 pandemic had a temporal impact on the evolution pattern of HRSV. Understanding the evolution of HRSV is vital for developing strategies for its control.

Antibiotic prescribing patterns and carriage of antibiotic-resistant Escherichia coli and Enterococcus species in healthy individuals from selected communities in Lusaka and Ndola districts, Zambia.

Objectives: This study assessed antibiotic prescribing patterns in primary healthcare facilities and antimicrobial resistance (AMR) profiles of commensal Escherichia coli and enterococci isolated from pregnant women and children under 5 years of age. Materials and methods: This cross-sectional study was conducted in Lusaka and Ndola districts of Zambia. Prescription pattern data were obtained from hospital pharmacies. Identification and antimicrobial susceptibility profiles of E. coli and enterococci were determined by conventional methods, while confirmation of both pathogens and AMR genes were determined by PCR. Data were analysed using WHONET and SPSS version 25.0. Results: Most prescribed antibiotics at the primary healthcare facilities belonged to the Access group of the WHO Access, Watch and Reserve (AWaRe) classification. All the primary healthcare facilities adhered to the AWaRe framework of ≥60% prescribed antibiotics belonging to the Access group. However, resistance was highest in the Access group of antibiotics. E. coli resistance to ampicillin ranged from 71% to 77% and to co-trimoxazole from 74% to 80%, while enterococcal resistance to tetracycline was 59%-64%. MDR was highest in E. coli (75%) isolates, while XDR was highest in enterococcal isolates (97%). The identified AMR genes in E. coli included blaCTX-M, sul2 and qnrA, while those of enterococci included erm(B), erm(C) and erm(A). Conclusions: Resistance was highest in the prescribed WHO Access group of antibiotics. These findings highlight the need to use local susceptibility data to formulate country-specific treatment guidelines in line with WHO AWaRe classification and enforce regulations that prohibit easy access to antibiotics.

Perspectives on development and advancement of new tuberculosis vaccines.

Tuberculosis (TB) remains a leading cause of death worldwide and is estimated to have caused 1.3 million deaths worldwide in 2022. Approximately one quarter of the world's population are infected with Mycobacterium tuberculosis, of whom up to 10% will progress to developing active TB disease. Achieving the World Health Organization End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence worldwide by 2035 remains a daunting task. The continuing spread of multidrug-resistant TB adds another obstacle to achieving global TB control. Larger funding pledges coupled with technological advances have recently enabled the enhancement of TB vaccine development efforts. These are yielding a pipeline of over 17 products currently in different stages of clinical trials. Emerging promising phase I and II trial results and advancement to phase III trials have necessitated "vaccine preparedness" in parallel so that a smooth transition from any positive clinical trial result to phase IV evaluation and implementation into policy and practice can follow. Promotion of a human rights-based approach, which recognizes and upholds the fundamental rights of all affected by the disease, is essential to ensure universal access to quality TB vaccines, regardless of their background or personal circumstances.

Malaria is the leading cause of acute kidney injury among a Zambian paediatric renal service cohort retrospectively evaluated for aetiologies, predictors of the need for dialysis, and outcomes.

BACKGROUND: Whilst malaria is a prominent aetiology associated with acute kidney injury (AKI) in many parts of Africa, a shift in the traditional AKI aetiologies has been witnessed in sections of the continent. Additionally, limited access to dialysis worsens patient outcomes in these low-resource settings. This retrospective cross-sectional study aimed to determine the associated aetiologies, predictors of need for dialysis and malaria-associated AKI (MAKI), and outcomes of AKI and dialysis among children evaluated by the renal service in Lusaka, Zambia. METHODS: The study sampled all children aged 16 years or below, diagnosed with AKI between 2017 and 2021, by the renal unit at the University Teaching Hospitals- Children's Hospital (UTH-CH), and retrospectively abstracted their records for exposures and outcomes. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. Frequency and percentage distributions were used to describe the occurrence of AKI aetiologies and treatment outcomes. Predictors of the need for dialysis, MAKI, and poor treatment outcome were identified by using multivariable logistic regression models. RESULTS: A total of 126 children diagnosed with AKI were included in this study. Malaria was the most frequent aetiology of AKI(61.1% (77/126, 95% Confidence Interval (CI): 52.0%-69.7%)). Of the 126 children with AKI, 74.6% (94) underwent dialysis. Predictors of the need for dialysis were oliguria (p = 0.0024; Odds ratio (OR) = 7.5, 95% CI: 2.1-27.7) and anuria (p = 0.0211; OR = 6.4, 95% CI = 1.3, 30.7). A fifth (18.3%, 23/126) of the children developed chronic kidney disease (CKD), 5.6% (7/126) died and, a year later, 77% (97/126) were lost to follow-up. CONCLUSION: At UTH-CH, malaria is the most frequent aetiology among children with AKI undergoing dialysis and children from low-medium malaria incidence areas are at risk; a considerable proportion of children with AKI need dialysis and Tenchoff catheter use in AKI is advocated.

Genomic Analysis of G2P[4] Group A Rotaviruses in Zambia Reveals Positive Selection in Amino Acid Site 7 of Viral Protein 3.

The G2P[4] genotype is among the rotavirus strains that circulate commonly in humans. Several countries have reported its immediate upsurge after the introduction of rotavirus vaccination, raising concern about sub-optimal vaccine effectiveness against this genotype in the long term. This study aimed to gain insight into the evolution of post-vaccine Zambian G2P[4] group A rotavirus (RVA) strains and their overall genetic make-up by analysis of sequence alignments at the amino acid (AA) level. Twenty-nine Zambian G2P[4] rotavirus strains were subjected to whole-genome sequencing using the Illumina MiSeq® platform. All the strains exhibited the typical DS-1-like genotype constellation, and the nucleotide sequences of the 11 genome segments showed high nucleotide similarities (>97%). Phylogenetic analyses together with representative global G2P[4] RVA showed that Zambian strains clustered into human lineages IV (for VP2, VP4, VP7, NSP1, and NSP5), V (for VP1, VP3, VP6, NSP2, and NSP3), and XXIII (for NSP4). The AA differences between the lineages where the study strains clustered and lineages of global reference strains were identified and analyzed. Selection pressure analysis revealed that AA site seven in the Viral Protein 3 (VP3) genome segment was under positive selection. This site occurs in the region of intrinsic disorder in the VP3 protein, and Zambian G2P[4] strains could potentially be utilizing this intrinsically disordered region to survive immune pressure. The Zambian G2P[4] strains from 2012 to 2016 comprised the G2P[4] strains that have been circulating globally since the early 2000s, highlighting the epidemiological fitness of these contemporary G2P[4] strains. Continuous whole-genome surveillance of G2P[4] strains remains imperative to understand their evolution during the post-vaccination period.

Lymphatic Filariasis Elimination Status: Wuchereria bancrofti Infections in Human Populations after Five Effective Rounds of Mass Drug Administration in Zambia.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2011 determined LF as being endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. In order to determine whether LF prevalence has been sufficiently reduced to levels less than 2% antigenemia and less than 1% microfilaremia, a pre-transmission assessment survey (pre-TAS) was conducted. Therefore, post-MDA pre-TAS was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence. We conducted a cross-sectional seroprevalence study involving 600 participants in each evaluation unit (EU) or each district. The study sites (sentinel and spot-check sites) were from districts that were the implementation units (IUs) of the LF MDA. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052, of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic districts a prevalence of Wb antigens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2% for antigenaemia, except for Chibombo district. The majority of participants that tested positive for Wuchereria bancrofti (Wb) Antigens (Ag) were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts, except for Chibombo, passed pre-TAS. This further implies that there is a need to conduct transmission assessment surveys (TASs) in these districts.

Phenotypic and genotypic antibiotic susceptibility profiles of Gram-negative bacteria isolated from bloodstream infections at a referral hospital, Lusaka, Zambia.

Bloodstream infections (BSI) caused by antimicrobial-resistant (AMR) Gram-negative bacteria (GNB) are a significant cause of morbidity and mortality. Third-generation cephalosporins (3GCs) have been used as empiric treatment for BSI and other invasive infections for years; however, their overuse could promote the emergence of extended-spectrum beta-lactamases (ESBLs). Thus, this study aimed to determine the epidemiological, clinical and microbiological features and the effects of antimicrobial resistance on the outcomes of BSIs at a referral hospital in Lusaka, Zambia. This was a six-month prospective facility-based study undertaken at a referral hospital in Lusaka, Zambia. As part of the routine diagnosis and patient care, blood samples for bacteriological culture were collected from patients presenting with fever and processed for pathogen identification and antimicrobial susceptibility testing using the VITEK 2 Compact instrument. ESBLs and plasmid-mediated quinolone resistance (PMQR) associated genes were determined using the polymerase chain reaction method. Patient information was collected using a structured data collection sheet and entered in CSpro 7.6. Data were analysed in WHOnet and STATA version 14. A total of 88 GNB were isolated, of which 76% were Enterobacterales, 14% Acinetobacter baumannii and 8% Pseudomonas aeruginosa. Resistance to third and fourth-generation cephalosporins was 75% and 32%, respectively. Noteworthy was the high prevalence (68%) of inappropriate empirical treatment, carbapenem resistance (7%), multi-drug resistance (83%) and ESBL-producers (76%). In comparison to E. coli as a causative agent of BSI, the odds of death were significantly higher among patients infected with Acinetobacter baumannii (OR = 3.8). The odds of death were also higher in patients that received 3GCs as empiric treatment than in those that received 4GCs or other (none cephalosporin) treatment options. Structured surveillance, yearly antibiogram updates, improved infection control and a well functional antimicrobial stewardship (AMS) program, are of utmost importance in improving appropriate antimicrobial treatment selection and favourable patient outcomes.

Exploring the feasibility of integration of surveillance for intussusception into the routine monitoring of adverse events following immunization by countries of the WHO African Region for Africa.

Surveillance for intussusception (IS) post-rotavirus vaccine introduction in World Health Organization Africa Region (WHO/AFRO) has been restricted mainly to the large referral teaching hospitals. The choice of these facilities for surveillance was made to utilize the abundant expertise of specialists in paediatrics and surgery in these hospitals who can diagnose and manage such patients with IS. The surveillance has been well coordinated by the African Intussusception Surveillance Network established in 2012. This network has supported surveillance across the African region and has accumulated a huge database of IS cases in children < 1 year with findings that have demonstrated safety of the monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline). However, safety data on the pentavalent and RotaTeq (Merck Vaccine) is not yet available from the African region. Although, this network has provided much needed data, there is an inherent bias in monitoring and reporting of IS cases in only large tertiary hospitals. This time limited special project does not capture suspected intussusception cases with no access to hospital facilities used for monitoring IS. Additionally, the design requires extensive resources to support collection of high-quality data for monitoring IS, which is unsustainable. For these reasons suitable linkages between IS monitoring and routine Adverse Event Following Immunization (AEFI) should be established for continuity of monitoring of this condition. We propose alignment of the two systems that offers opportunity for high profile recognition and to enhance a sustainable system for diagnosis, treatment and continuous assessment of intussusception occurring in infancy.

Organophosphate insecticide poisoning with monocrotophos-induced fabricated illness in a 7-year-old girl with refractory seizures over a 4-year period.

Munchausen syndrome by proxy is a form of abuse in which an adult, usually the mother, deceives health workers by exaggerating, falsifying or directly inducing psychological or physical symptoms in the child victim for psychological gratification. In 2013, the American Academy of Pediatrics coined the term 'caregiver-fabricated illness in a child' to describe this form of child abuse. A 7-year-old girl had many encounters with health workers over a period of 4 years and presented with evolving clinical features including refractory seizures and red urine for which she was followed up as a case of acute intermittent porphyria. She was later discovered to be the victim of chronic monocrotophos organophosphate poisoning by her mother. If all medical staff who manage children are to avoid becoming inadvertent participants in medical child abuse, this case report is an important reminder that a high index of suspicion is warranted in cases which present a diagnostic dilemma and who respond unexpectedly to treatment.Abbreviations AIP: Acute intermittent porphyria; APSAC: American Professional Society on the Abuse of Children; ASM: anti-seizure medication; CFIC: caregiver-fabricated illness in a child; CT: computed tomography: DVT: deep vein thrombosis; EEG: electroencephalogram: ESR: erythrocyte sedimentation rate; HDW: high-dependency ward; ICU: intensive care unit; LFT: liver function test; MBP: Munchausen syndrome by proxy; NICU: neonatal intensive care unit; RFT: renal function test; TB: Tuberculosis; UTH-CH: University Teaching Hospitals Children's Hospital.

Antimicrobial susceptibility and genomic profiling of Salmonella enterica from bloodstream infections at a tertiary referral hospital in Lusaka, Zambia, 2018-2019.

Objectives: This study investigated antimicrobial susceptibility and genomic profiling of S. enterica isolated from bloodstream infections at a tertiary referral hospital in Lusaka, Zambia, 2018-2019. Method: This was a prospective hospital-based study involving routine blood culture samples submitted to the microbiology laboratory at the University Teaching Hospital. Identification of S. enterica and determination of antimicrobial susceptibility profiles was achieved through conventional and automated methods. Whole-genome sequencing (WGS) was conducted, and the sequence data outputs were processed for species identification, serotype determination, multilocus sequence typing (MLST) profile determination, identification of antimicrobial resistance determinants, and phylogeny. Results: Seventy-six Salmonella enterica were isolated and 64 isolates underwent WGS. Salmonella Typhi (72%) was the most prevalent serotype. Notable was the occurrence of invasive non-typhoidal Salmonella Typhimurium ST313 (3%), resistance to cephalosporins (4%) and ciprofloxacin (5%), multidrug resistance (46%), and reduced susceptibility to ciprofloxacin (30%) and imipenem (3%). Phylogenetic cluster analysis showed multiple Salmonella serovars with a wide range of genetic diversity. Conclusion: The genetic diversity of Salmonella Typhi, high prevalence of multidrug resistance, and the emergence of ciprofloxacin and cephalosporin resistance warrants improved hygiene and water and sanitation provision, continued surveillance to apprise antibiograms and inform policy, and the introduction of the typhoid conjugate vaccine.

Burden and epidemiology of rotavirus diarrhea in selected African countries: preliminary results from the African Rotavirus Surveillance Network.

Severe rotavirus diarrhea in children <5 years of age is a major public health problem; however, limited regional and country specific data on rotavirus disease burden are available from sub-Saharan Africa. In June 2006, the World Health Organization Regional Office for Africa initiated rotavirus surveillance in selected African countries. With use of standardized methodology developed by the World Health Organization, children <5 years of age who were hospitalized with severe diarrhea were enrolled, and stool specimens were collected for detection of rotavirus strains with use of a commercial enzyme immunoassay. Rotavirus strains were further characterized for G and P types with use of a reverse-transcriptase polymerase chain reaction. From June 2006 through December 2008, rotavirus surveillance was established at 14 sites in 11 African countries. Of 5461 stool samples collected from children enrolled in 8 countries with 1 or 2 complete years of data, 2200 (40%) were positive for rotavirus. Ninety percent of all rotavirus hospitalizations occurred among children aged 3-12 months. Predominant types included G1P[8] (21%), G2P[4] (7%), and P [8] (29%); however, unusual types were also detected, including G8P[6] (5%), G8P[8] (1%), G12P[6] (1%), and G12P[6] (1%). A high percentage of mixed rotavirus infections was also detected. These preliminary results indicate that rotavirus is a major cause of severe diarrheal disease in African children.