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.

Low IL-6, IL-10, and TNF-α and High IL-13 Cytokine Levels Are Associated with Severe Hepatic Fibrosis in Schistosoma mansoni Chronically Exposed Individuals.

Several studies have attributed the etiopathogenesis of chronic Schistosoma mansoni related hepatic fibrosis to unregulated immune responses against trapped parasite ova in the host. However, there is limited data on immune profiles associated with varying degrees of the disease in a population under chronic exposure to the parasite. We therefore investigated the role of selected T-helper (Th)1, Th2, and Th17 cytokines in relation to hepatic fibrosis severity among individuals resident in a hyper-Schistosoma mansoni endemic region of Western Zambia. Two hundred and forty-four S. mansoni infected individuals with and without fibrosis were analysed for cytokine profiles. Based on hepatic fibrosis stage as determined by ultrasound, participants were categorized into Group 0, Group I, Group II, and Group III. Cytokines were measured in S. mansoni egg stimulated whole blood culture supernatants using the BD Cytometric Bead Array kits. Compared to the nonfibrotic group, participants in the severe hepatic fibrotic group produced less interleukin- (IL-) 6, IL-10, and tumour necrosis factor-alpha (TNF-α). On the other hand, IL-13 was significantly elevated in this group compared to the nonfibrotic group (p < 0.001). Our results suggest that low IL-6, IL-10, and TNF-α and high IL-13 levels may influence S. mansoni disease progression.

Genomic signature of multidrug-resistant Salmonella enterica serovar typhi isolates related to a massive outbreak in Zambia between 2010 and 2012.

Retrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole-genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the multilocus sequence type (MLST), haplotype, plasmid replicon, antimicrobial resistance genes, and genetic relatedness by single nucleotide polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients, with a fatality rate of 0.5%. Most (83.0%) isolates were multidrug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype, H58B. Most isolates contained a chromosomally translocated region containing seven antimicrobial resistance genes, catA1, blaTEM-1, dfrA7, sul1, sul2, strA, and strB, and fragments of the incompatibility group Q1 (IncQ1) plasmid replicon, the class 1 integron, and the mer operon. The genomic analysis revealed 415 SNP differences overall and 35 deletions among 33 of the isolates subjected to whole-genome sequencing. In comparison with other genomes of H58, the Zambian isolates separated from genomes from Central Africa and India by 34 and 52 SNPs, respectively. The phylogenetic analysis indicates that 32 of the 33 isolates sequenced belonged to a tight clonal group distinct from other H58 genomes included in the study. The small numbers of SNPs identified within this group are consistent with the short-term transmission that can be expected over a period of 2 years. The phylogenetic analysis and deletions suggest that a single MDR clone was responsible for the outbreak, during which occasional other S. Typhi lineages, including sensitive ones, continued to cocirculate. The common view is that the emerging global S. Typhi haplotype, H58B, containing the MDR IncHI1 plasmid is responsible for the majority of typhoid infections in Asia and sub-Saharan Africa; we found that a new variant of the haplotype harboring a chromosomally translocated region containing the MDR islands of IncHI1 plasmid has emerged in Zambia. This could change the perception of the term "classical MDR typhoid" currently being solely associated with the IncHI1 plasmid. It might be more common than presently thought that S. Typhi haplotype H58B harbors the IncHI1 plasmid or a chromosomally translocated MDR region or both.

High Schistosoma mansoni disease burden in a rural district of western Zambia.

Schistosoma mansoni disease is endemic in most parts of rural Zambia, and associated complications are common. We conducted a cross-sectional study among 754 people in rural communities of Kaoma District, western Zambia to determine the burden of S. mansoni infection and associated morbidity. Parasitology and ultrasonography assessments were conducted on consenting participants. The overall prevalence of S. mansoni infection and geometric mean egg count (GMEC) were 42.4% (304) and 86.6 eggs per gram (95% confidence interval = 75.6-99.6), respectively. Prevalence was highest in the age group of 15-19 years old (adjusted prevalence ratio = 1.70, P = 0.017). S. mansoni-related portal fibrosis was detected in 26% of the participants screened. Participants above 39 years old were 2.93 times more likely to have fibrosis than the 7-9 years old age group (P = 0.004). The study highlights the high burden of S. mansoni disease in this area and calls for immediate interventions to avert complications associated with the disease.

Diagnosis of Schistosoma mansoni without the stool: comparison of three diagnostic tests to detect Schistosoma [corrected] mansoni infection from filtered urine in Zambia.

Diagnosis for intestinal Schistosoma mansoni lacks sensitivity and is arduous to conduct. The standard diagnostic tests, Kato-Katz (KK) and circulating cathodic antigen (CCA) both lack sensitivity and with KK, require obtaining, transporting, and examining fresh stool. We compared diagnostic efficacy of KK, CCA, and polymerase chain reaction (PCR) to detect S. mansoni infection (species-specific DNA) from 89 filtered urine samples collected in Zambia. The PCR was the strongest indicator of positive cases with sensitivity and specificity of 100% in comparison to CCA (67% and 60%) and KK (50% and 100%). High positive and negative predictive values (100%) were also indicative of robustness of PCR. The same pattern was observed when stratified for sex and age group-specific analysis. Diagnosis of S. mansoni from filtered urine samples by PCR is an effective means to detect low intensity infection and would enhance the effectiveness of surveillance and control programs of schistosomiasis.

Extremely drug-resistant Salmonella enterica serovar Senftenberg infections in patients in Zambia.

Two cases of extremely drug-resistant Salmonella enterica serovar Senftenberg isolated from patients in Zambia were investigated by utilizing MIC determinations and whole-genome sequencing. The isolates were resistant to, and harbored genes toward, nine drug classes, including fluoroquinolones and extended-spectrum cephalosporins, contained two plasmid replicons, and differed by 93 single-nucleotide polymorphisms.

Human-animal anthrax outbreak in the Luangwa valley of Zambia in 2011.

There has been a reduction of incidences of anthrax in the developed countries but it is still a public health problem in the developing countries where communities live in interface areas with wildlife. An outbreak of anthrax in Hippopotamus amphibious was observed in Zambia. Following the death of hippopotamuses, suspected human cases were reported. The objective of this study was to isolate and confirm Bacillus anthracis and to determine the antimicrobial susceptibility for the management of the disease. Of the specimens collected, 29.4% (95% confidence interval [CI], 11.4-56.0) were from humans, 42.1% (95% CI, 21.1-66.0) were from hippopotamuses and 20.0% (95% CI, 6.61-44.3) from the soil were found to be positive were for B. anthracis. An antimicrobial susceptibility test revealed that all the isolates were found to be sensitive to the recommended antibiotics. The disease control was achieved by case management and by explaining to the communities that they should avoid contact with animals that die from unknown causes.

Impact of cotrimoxazole on carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae in HIV-infected children in Zambia.

This is a substudy of a larger randomized controlled trial on HIV-infected Zambian children, which revealed that cotrimoxazole prophylaxis reduced morbidity and mortality despite a background of high cotrimoxazole resistance. The impact of cotrimoxazole on the carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae as major causes of childhood mortality in HIV-infected children was investigated since these are unclear. Representative nasopharyngeal swabs were taken prior to randomization for 181 of 534 children (92 on cotrimoxazole and 89 on placebo). Bacterial identification and antibiotic susceptibility were performed by routine methods. Due to reduced mortality, prophylactic cotrimoxazole increased the median time from randomization to the last specimen from 48 to 56 months (P = 0.001). The carriage of H. influenzae was unaltered by cotrimoxazole. Carriage of S. pneumoniae increased slightly in both arms but was not statistically significant in the placebo arm. In S. pneumoniae switching between carriage and no carriage in consecutive pairs of samples was unaffected by cotrimoxazole (P = 0.18) with a suggestion that the probability of remaining carriage free was lower (P = 0.10). In H. influenzae cotrimoxazole decreased switching from carriage to no carriage (P = 0.02). Cotrimoxazole resistance levels were higher in postbaseline samples in the cotrimoxazole arm than in the placebo arm (S. pneumoniae, P < 0.0001; H. influenzae, P = 0.005). Cotrimoxazole decreased switching from cotrimoxazole resistance to cotrimoxazole sensitivity in S. pneumoniae (P = 0.002) and reduced the chance of H. influenzae remaining cotrimoxazole sensitive (P = 0.05). No associations were observed between the percentage of CD4 (CD4%), the change in CD4% from baseline, child age at date of specimen, child gender, or sampling month with carriage of either pathogen.