Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa.

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.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.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.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.)

Symmetrical Peripheral Gangrene as a Rare Complication of Malaria: A Case Report from the Arthur Davison Children's Hospital in Ndola, Zambia

Malaria is a common parasitic disease with very high mortality in tropical&nbsp; countries including Zambia. Symmetrical Peripheral Gangrene (SPG) is a rare complication of malaria, associated with Plasmodium falciparum infection. Reported here is a case of SPG in a 2 year3-month-oldZambian toddler and highlight the need for awareness and prompt diagnosis and treatment. Key words: Symmetrical Peripheral Gangrene, Plasmodium Falciparum Malaria, Toddler, Zambi

Rotavirus breakthrough infections responsible for gastroenteritis in vaccinated infants who presented with acute diarrhoea at University Teaching Hospitals, Children's Hospital in 2016, in Lusaka Zambia.

BackgroundIn Zambia, before rotavirus vaccine introduction, the virus accounted for about 10 million episodes of diarrhoea, 63 000 hospitalisations and 15 000 deaths in 2015, making diarrhoea the third leading cause of death after pneumonia and malaria. In Zambia, despite the introduction of the vaccine acute diarrhoea due to rotaviruses has continued to affect children aged five years and below. This study aimed to characterise the rotavirus genotypes which were responsible for diarrhoeal infections in vaccinated infants aged 2 to 12 months and to determine the relationship between rotavirus strains and the severity of diarrhoea in 2016.MethodsStool samples from infants aged 2 to 12 months who presented to the hospital with acute diarrhoea of three or more episodes in 24 hours were tested for group A rotavirus. All positive specimens that had enough sample were genotyped using reverse transcriptase Polymerase Chain Reaction (RT-PCR). A 20-point Vesikari clinical score between 1-5 was considered as mild, 6-10 as moderate and greater or equal to 11 as severe.ResultsA total of 424 stool specimens were tested of which 153 (36%, 95% CI 31.5% to 40.9%) were positive for VP6 rotavirus antigen. The age-specific rotavirus infections decreased significantly (p = 0.041) from 2-4 months, 32.0% (49/118) followed by a 38.8% (70/181) infection rate in the 5-8 months' category and subsequently dropped in the infants aged 9-12 months with a positivity rate of 27.2%. 38.5% of infants who received a single dose, 34.5% of those who received a complete dose and 45.2% (19/42) of the unvaccinated tested positive for rotavirus. The predominant rotavirus genotypes included G2P[6] 36%, G1P[8] 32%, mixed infections 19%, G2P[4] 6%, G1P[6] 4% and G9P[6] 3%.Discussion and conclusionResults suggest breakthrough infection of heterotypic strains (G2P[6] (36%), homotypic, G1P[8] (32%) and mixed infections (19%) raises concerns about the effects of the vaccination on the rotavirus diversity, considering the selective pressure that rotavirus vaccines could exert on viral populations. This data indicates that the rotavirus vaccine has generally reduced the severity of diarrhoea despite the detection of the virus strains

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

Feasibility of Implementing an Early Intervention Program in an Urban Low-Income Setting to Improve Neurodevelopmental Outcome in Survivors Following Birth Asphyxia

Birth asphyxia is a leading cause of neonatal mortality, accounting for 23% of neonatal deaths. An early intervention program (EIP) could improve neuro-developmental outcomes in survivors of birth asphyxia, but its feasibility in low-income countries has not been tested.  In this pilot study in Zambia, eighty live-born infants &#62; 1500 g of weight who had birth asphyxia and received resuscitation with bag and mask were enrolled for a study of standard care or EIP. Mothers/babies pairs were randomized into control (standard care) and intervention (EIP) groups and were followed up at home on a bi-weekly basis from 8 weeks to 8 months of age. Forty two mothers/babies (52.5%) completed the study at 8 months. Reasons for not completing the study were: 19 (50.1%) were lost to follow up, 16 (42.1%) withdrew, and 3 (7.8%) died. Follow-up to 8 months of age was not feasible for the majority in a large urban city with a low income population. Thus, interventions for children who have suffered birth asphyxia that require additional health care visits may not be currently feasible in the setting tested. There is a need to conduct further EIP studies to determine ways to improve follow up rates of children surviving birth asphyxia. Integrating early intervention programs with other successful health programs, such as the existing immunization programs, may improve follow up rates

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

Molecular Characterisation of a Rare Reassortant Porcine-Like G5P[6] Rotavirus Strain Detected in an Unvaccinated Child in Kasama, Zambia

A human-porcine reassortant strain, RVA/Human-wt/ZMB/UFS-NGS-MRC-DPRU4723/2014/G5P[6], was identified in a sample collected in 2014 from an unvaccinated 12 month old male hospitalised for gastroenteritis in Zambia. We sequenced and characterised the complete genome of this strain which presented the constellation: G5-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The genotype A8 is often observed in porcine strains. Phylogenetic analyses showed that VP6, VP7, NSP2, NSP4, and NSP5 genes were closely related to cognate gene sequences of porcine strains (e.g., RVA/Pig-wt/CHN/DZ-2/2013/G5P[X] for VP7) from the NCBI database, while VP1, VP3, VP4, and NSP3 were closely related to porcine-like human strains (e.g., RVA/Human-wt/CHN/E931/2008/G4P[6] for VP1, and VP3). On the other hand, the origin of the VP2 was not clear from our analyses, as it was not only close to both porcine (e.g., RVA/Pig-tc/CHN/SWU-1C/2018/G9P[13]) and porcine-like human strains (e.g., RVA/Human-wt/LKA/R1207/2009/G4P[6]) but also to three human strains (e.g., RVA/Human-wt/USA/1476/1974/G1P[8]). The VP7 gene was located in lineage II that comprised only porcine strains, which suggests the occurrence of independent porcine-to-human reassortment events. The study strain may have collectively been derived through interspecies transmission, or through reassortment event(s) involving strains of porcine and porcine-like human origin. The results of this study underline the importance of whole-genome characterisation of rotavirus strains and provide insights into interspecies transmissions from porcine to humans

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