Comparison of Real-Q 2019-nCoV and DaAn Gene 2019-nCoV polymerase chain reaction assays for the detection of SARS-CoV-2.

BACKGROUND: Various nucleic acid amplification assays for the diagnosis of SARS-CoV-2 infection have been developed, and there is a need to assess their test performance relative to one another. The aim of this study was to compare the performance characteristics of the Biosewoom Real-Q 2019-nCoV assay targeting the E and RdRP genes to DaAn Gene 2019-nCoV kit targeting the N gene and ORF1ab in the diagnosis of SARS-CoV-2. METHODS: We performed a diagnostic comparison study by testing nasopharyngeal samples for SARS-CoV-2 using the two reverse transcription polymerase chain reaction (RT-PCR) assays. Assay agreement was assessed by overall percent agreement, negative percent agreement, positive percent agreement, and Cohen's kappa coefficient. RESULTS: A total of 48 nasopharyngeal samples were tested using the two assays. One sample was invalid, and three showed inconclusive results with Real-Q; hence, 44 were included for the comparative analysis. Overall, percent agreement between the assays was 93.2% (95% CI 81.3%-98.6%), Positive percent agreement (PPA) was 86.4% (95% CI 65.1%-97.1%) and negative percent agreement (NPA) was 100% (95% CI 84.6%-100%). The kappa coefficient was 0.86 (95% CI 0.72-1.01). Three samples (6.8%) were positive with DaAn gene kit and negative with Real-Q. The fluorescence intensity for Real-Q reporter dyes was low. CONCLUSION: The two kits showed high levels of concordance in their detection of SARS-CoV-2 despite having different gene targets. The Biosewoom kit can be improved through addressing the fluorescence intensity of the target dyes, and feedback was given to the manufacturer.

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.).

Salmonella enterica serovar Typhi H58 clone has been endemic in Zimbabwe from 2012 to 2019.

BACKGROUND: Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control. OBJECTIVES: To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics. METHODS: A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis. RESULTS: A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, ß-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs. CONCLUSIONS: This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.

Evaluation of the InTray and Compact Dry culture systems for the diagnosis of urinary tract infections in patients presenting to primary health clinics in Harare, Zimbabwe.

Antimicrobial resistance surveillance data is lacking from many resource-limited settings mainly due to limited laboratory testing. Novel culture systems may address some of the limitations of conventional culture media and expand the availability of microbiology services. The aims of this study were to evaluate the performance of InTray COLOREX Screen/ESBL and Compact Dry for the detection of uropathogens and of extended-spectrum beta-lactamase (ESBL)-producing organisms from urine samples. Urines samples were collected from patients presenting with symptoms of urinary tract infection to primary care clinics in Harare. Performance of the InTray COLOREX Screen, ESBL and Compact Dry chromogenic media were compared to the reference of culture using Brilliance UTI agar and conventional antimicrobial susceptibility testing. A total of 414 samples were included in the analysis. Of the included samples, 98 were positive on Brilliance UTI agar and 83 grew Enterobacterales. The sensitivities and specificities for Enterobacterales were 89.2% (95% CI 80.4-94.9) and 98.2% (95% CI 96.1-99.3) for InTray Screen and 95.2% (95% CI 88.1-98.7) and 99.7% (95% CI 98.3-100) for Compact Dry. Extended-spectrum beta-lactamases were present in 22 isolates from the Brilliance UTI agar. The sensitivity of the InTray COLOREX ESBL culture plates for the detection of ESBL-producing organisms was 95.5% (95% CI 77.2-99.9) and specificity was 99.5% (95% CI 98.2-99.9%). Our findings show good performance of the novel culture systems for the detection of uropathogens and ESBL-producing organisms. Both systems have several advantages over conventional media and have the potential to expand and decentralize laboratory testing.

Pneumococcal Conjugate Vaccine Impact on Meningitis and Pneumonia Among Children Aged <5 Years-Zimbabwe, 2010-2016.

BACKGROUND: Streptococcus pneumoniae is a leading cause of pneumonia and meningitis in children aged <5 years. Zimbabwe introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2012 using a 3-dose infant schedule with no booster dose or catch-up campaign. We evaluated the impact of PCV13 on pediatric pneumonia and meningitis. METHODS: We examined annual changes in the proportion of hospitalizations due to pneumonia and meningitis among children aged <5 years at Harare Central Hospital (HCH) pre-PCV13 (January 2010-June 2012) and post-PCV13 (July 2013-December 2016) using a negative binomial regression model, adjusting for seasonality. We also evaluated post-PCV13 changes in serotype distribution among children with confirmed pneumococcal meningitis at HCH and acute respiratory infection (ARI) trends using Ministry of Health outpatient data. RESULTS: Pneumonia hospitalizations among children aged <5 years steadily declined pre-PCV13; no significant change in annual decline was observed post-PCV13. Post-PCV13 introduction, meningitis hospitalization decreased 30% annually (95% confidence interval [CI], -42, -14) among children aged 12-59 months, and no change was observed among children aged 0-11 months. Pneumococcal meningitis caused by PCV13 serotypes decreased from 100% in 2011 to 50% in 2016. Annual severe and moderate outpatient ARI decreased by 30% (95% CI, -33, -26) and 7% (95% CI, -11, -2), respectively, post-PCV13 introduction. CONCLUSIONS: We observed declines in pediatric meningitis hospitalizations, PCV13-type pneumococcal meningitis, and severe and moderate ARI outpatient visits post-PCV13 introduction. Low specificity of discharge codes, changes in referral patterns, and improvements in human immunodeficiency virus care may have contributed to the lack of additional declines in pneumonia hospitalizations post-PCV13 introduction.

Monovalent Rotavirus Vaccine Effectiveness Against Rotavirus Hospitalizations Among Children in Zimbabwe.

BACKGROUND: Rotavirus is a leading cause of mortality among children <5 years old. We evaluated monovalent rotavirus vaccine effectiveness (VE) under conditions of routine use at 2 surveillance sites in Harare, Zimbabwe, after vaccine introduction in May 2014. METHODS: Children aged <5 years hospitalized or treated in the accident and emergency department (A&E) for acute watery diarrhea were enrolled for routine surveillance. Copies of vaccination cards were collected to document vaccination status. Among children age-eligible to receive rotavirus vaccine, we estimated VE, calculated as 1 - odds ratio, using a test-negative case-control design. RESULTS: We included 903 rotavirus-positive cases and 2685 rotavirus-negative controls in the analysis; 99% had verified vaccination status. Rotavirus-positive children had more severe diarrhea than rotavirus-negative children; 61% of cases and 46% of controls had a Vesikari score ≥11 (P < .01). Among cases and controls, 31% and 37%, respectively, were stunted for their age (P < .01). Among children 6-11 months old, adjusted 2-dose VE against hospitalization or treatment in A&E due to rotavirus of any severity was 61% (95% confidence interval [CI], 21%-81%) and 68% (95% CI, 13%-88%) against severe rotavirus disease. Stratified by nutritional status, adjusted VE was 45% (95% CI, -148% to 88%) among stunted infants and 71% (95% CI, 29%-88%) among infants with a normal height for age. CONCLUSIONS: Monovalent rotavirus vaccine is effective in preventing hospitalizations due to severe rotavirus diarrhea among infants in Zimbabwe, providing additional evidence for countries considering rotavirus vaccine introduction that live, oral rotavirus vaccines are effective in high-child-mortality settings.

Cost of a human papillomavirus vaccination project, Zimbabwe.

OBJECTIVE: To determine the cost of Zimbabwe's human papillomavirus (HPV) vaccination demonstration project. METHODS: The government of Zimbabwe conducted the project from 2014-2015, delivering two doses of HPV vaccine to 10-year-old girls in two districts. School delivery was the primary vaccination strategy, with health facilities and outreach as secondary strategies. A retrospective cost analysis was conducted from the provider perspective. Financial costs (government expenditure) and economic costs (financial plus the value of existing or donated resources including vaccines) were calculated by activity, per dose and per fully immunized girl. RESULTS: The project delivered 11 599 vaccine doses, resulting in 5724 fully immunized girls (5540 at schools, 168 at health facilities and 16 at outreach points). The financial cost for service delivery per fully immunized girl was United States dollars (US$) 5.34 in schools, US$ 34.90 at health facilities and US$ 288.63 at outreach; the economic costs were US$ 17.39, US$ 41.25 and US$ 635.84, respectively. The mean financial cost per dose was US$ 19.76 and per fully immunized girl was US$ 40.03 (economic costs were US$ 45.00 and US$ 91.19, respectively). The largest number of doses delivered (5788) occurred during the second vaccination round (the second group's first dose concurrently delivered with the first group's second dose), resulting in the lowest financial and economic service delivery costs per dose: US$ 1.97 and US$ 6.79, respectively. CONCLUSION: The mean service delivery cost was lower in schools (primary strategy) and when more girls were vaccinated in each round, demonstrating scale efficiency.

Trends of rubella incidence during a 5-year period of case based surveillance in Zimbabwe.

BACKGROUND: Rubella is a disease of public health significance owing to its adverse effects during pregnancy and on pregnancy outcomes. Women who contract rubella virus during pregnancy may experience complications such as foetal death or give birth to babies born with congenital rubella syndrome. Vaccination against rubella is the most effective and economical approach to control the disease, and to avoid the long term effects and high costs of care for children with congenital rubella syndrome as well as to prevent death from complications. Zimbabwe commenced rubella surveillance in 1999, despite lacking a rubella vaccine in the national Expanded Programme on Immunization, as per the World Health Organization recommendation to establish a surveillance system to estimate the disease burden before introduction of a rubella vaccine. The purpose of this analysis is to describe the disease trends and population demographics of rubella cases that were identified through the Zimbabwe national measles and rubella case-based surveillance system during a 5-year period between 2007 and 2011. METHODS: Data from the Zimbabwe National Measles Laboratory for the 5-year study period were analysed for age, sex, district of origin, seasonality, and rubella IgM serostatus. RESULTS: A total of 3428 serum samples from cases of suspected measles in all administrative districts of the country were received by the laboratory during this period. Cases included 51% males and 49% females. Of these, 2999 were tested for measles IgM of which 697 (23.2%) were positive. Of the 2302 measles IgM-negative samples, 865 (37.6%) were rubella IgM-positive. Ninety-eight percent of confirmed rubella cases were children younger than 15 years of age. Most infections occurred during the dry season. CONCLUSIONS: The national case-based surveillance revealed the disease burden and trends of rubella in Zimbabwe. These data add to the evidence for introducing rubella-containing vaccine into the national immunization programme.

Factors affecting diagnosis and management of hypertension in Mazowe District of Mashonaland Central Province in Zimbabwe: 2012.

BACKGROUND: From 2005 to 2011 Mazowe District recorded a gradual decline in prevalence of hypertension in the face of rising incidence of complications like stroke. This raised questions on whether diagnosis and management of hypertensive patients is being done properly. METHODS: We conducted an analytic cross sectional study at three hospitals in Mazowe District where we randomly selected 201 of 222 patients from out patients departments and interviewed a convenience sample of 23 healthcare workers. Structured interviewer administered questionnaires were used to collect data on demographic characteristics and knowledge from patients, as well as knowledge and practices from health workers. Physical measurements were done on all patients. Frequencies; proportions, odds ratios, Chi square test and stratified & logistic regression analysis were done using Epi info version 3.5.4 while graphs were generated using Microsoft excel®. Calculations were done at 95% confidence interval. RESULTS: Prevalence, awareness, control, compliance, and complication rate of hypertension were: 69.7%, 56.2%, 22.0%, 59.8% and 20.7% respectively. Independent risk factors for hypertension were age (POR 3.09; 95% CI: 1.27-7.5), obesity (POR 4.37; 95% CI: 1.83-10.4), and previous high blood pressure reading (POR 19.86; 95% CI: 8.61-45.8). Complications included cardiac failure (8.6%), visual defects (4.3%) and stroke (3.6%). Co-morbid human immunodeficiency virus (10.7%) and diabetes mellitus (12.1%) were identified among respondents. Knowledge was poor in 47.7% of health workers. CONCLUSIONS: Risk factors found in this study are consistent with other studies. Health service factors are the main reasons for poor diagnosis and management of hypertension. Health workers need training on diagnosis and management of hypertension. Guidelines, digital sphygmomanometers and adequate drug supply are needed. District has since purchased digital BP machines and requested assistance with training on clinical features of hypertension, use of digital machines, and how to properly measure BP. A policy document on non-communicable diseases including hypertension was subsequently developed by the Ministry of Health and Child Care and currently awaiting endorsement by parliament.

Cost of human papillomavirus vaccine delivery at district and health facility levels in Zimbabwe: A school-based vaccination program targeting multiple cohorts.

BACKGROUND: After a pilot project in 2014-15 Zimbabwe introduced the human papillomavirus (HPV) vaccine nationally in 2018 for girls aged 10-14 years through a primarily school-based vaccination campaign with two doses administered at 12-month intervals. In 2019, a first dose was delivered to a new cohort of girls in grade 5 of girls age 10 years if out-of-school (OOS), along with a second dose to the 2018 multiple cohorts. Additional effort was made to identify and mobilize OOS girls by Village Health Workers (VHWs) in the community. Zimbabwe reported 1,569,905 doses of HPV vaccine administered during the 2018 and 2019 campaigns. This analysis evaluated the cost of Zimbabwe's national HPV vaccine introduction. METHODS: A retrospective, incremental, ingredients-based cost analysis from the provider perspective was conducted in 2018 and 2019. Financial and economic cost data were collected at district and health facility levels using a two-stage cluster sampling approach and four cost dimensions: program activity, resource input, payer, and administrative level. Costs are presented in 2020 US$ in total and per dose. RESULTS: The total weighted costs for combined district and health facility administrative levels were US$ 828,731 (financial) and US$ 2,060,943 (economic). For service delivery, the total weighted cost per dose was US$ 0.16 (financial) and US$ 0.59 (economic). The program activities with the largest share of total weighted financial cost were training (37% of total) and service delivery (30%), while the largest shares of total weighted economic costs were service delivery (45%) and training (19%). Efforts by VHWs to reach OOS girls resulted in an additional US$ 2.99 in financial cost per dose and US$ 7.79 in economic cost per dose. CONCLUSION: The service delivery cost per dose was lower than that documented in the pilot program cost analysis in Zimbabwe and studies elsewhere, reflecting a campaign delivery approach that spread fixed costs over a large vaccination cohort. The additional cost of reaching OOS girls with the HPV vaccine was documented for the first time in low- and middle-income countries, which may provide information on potential costs for other countries.

Nationwide introduction of HPV vaccine in Zimbabwe 2018-2019: Experiences with multiple cohort vaccination delivery.

The World Health Organization (WHO) recommends the human papillomavirus (HPV) vaccine for girls aged 9-14 years for cervical cancer prevention and encourages vaccinating multiple cohorts in the first year to maximize impact. The HPV vaccine was introduced nationwide in Zimbabwe in 2018 through a 1-week school-based campaign to multiple cohorts (all girls 10-14 years old), followed by a single cohort (grade 5 girls in school and age 10 girls out-of-school) in 2019. During the 2019 campaign, the multiple cohort's second dose was concurrently delivered with the single cohort's first dose. We interviewed national-level key informants, reviewed written materials, and observed vaccination sessions to document HPV vaccine introduction in Zimbabwe and identify best practices and challenges. Key informants included focal persons from government health and education ministries, in-country immunization partners, and HPV Vaccine Strategic Advisory Group members. We conducted a desk review of policy/strategy documents, introduction plans, readiness reports, presentations, and implementation tools. Vaccination sessions were observed in three provinces during the 2019 campaign. Key informants (n = 8) identified high cervical cancer burden, political will, vaccine availability, donor financing, and a successful pilot program as factors driving the decision to introduce the HPV vaccine nationally. The school-based delivery strategy was well accepted, with strong collaboration between health and education sectors and high community demand for vaccine identified as key contributors to this success. Challenges with transitioning from a multiple age-based to single grade- and age-based target population as well as funding shortages for operational costs were reported. Zimbabwe's first multiple cohort, school-based HPV vaccination campaign was considered successful-primarily due to strong collaboration between health and education sectors and political commitment; however, challenges vaccinating overlapping cohorts in the 2019 campaign were observed. Integration with existing health and vaccination activities and continued resource mobilization will ensure sustainability of Zimbabwe's HPV vaccination program in the future.

Multiple cohort HPV vaccination in Zimbabwe: 2018-2019 program feasibility, awareness, and acceptability among health, education, and community stakeholders.

INTRODUCTION: Zimbabwe introduced human papillomavirus (HPV) vaccine nationally in May 2018, targeting multiple cohorts (girls aged 10-14 years) through a school-based vaccination campaign. One year later, the second dose was administered to the multiple cohorts concurrently with the first dose given to a new single cohort of girls in grade 5. We conducted cross-sectional surveys among health workers, school personnel, and community members to assess feasibility of implementation, training, social mobilization, and community acceptability. METHODS: Thirty districts were selected proportional to the volume of the HPV vaccine doses delivered in 2018; two health facilities were randomly selected within each district. One health worker, school health coordinator, village health worker, and community leader were surveyed at each selected health facility and surrounding area during January-February 2020, using standard questionnaires. Descriptive analysis was completed across groups. RESULTS: There were 221 interviews completed. Over 60% of health workers reported having enough staff to carry out vaccination sessions in schools while maintaining routine vaccination services in health facilities. All school health coordinators felt the HPV vaccine should be delivered in schools in the future. Knowledge of the correct target cohort eligibility decreased from 91% in 2018 to 50% in 2020 among health workers. Understanding of HPV infection and use of HPV vaccine for cervical cancer prevention was above 90% for all respondents. Forty-two percent of respondents reported hearing rumors about the HPV vaccine, primarily regarding infertility and safety. CONCLUSIONS: Findings demonstrate the presence of highly knowledgeable staff at health facilities and schools, strong community acceptance, and a school-based HPV program considered feasible to implement in Zimbabwe. However, misunderstandings regarding target eligibility and rumors persist, which can impact vaccine uptake and coverage. Continued social mobilization efforts to maintain community demand and training on eligibility were recommended. Integration, partnerships, and resource mobilization are also needed to ensure program sustainability.

HPV vaccination coverage in three districts in Zimbabwe following national introduction of 0,12 month schedule among 10 to 14 year old girls.

BACKGROUND: Zimbabwe has one of the highest incidence rates of cervical cancer in the world - 61.7 per 100,000 women. The government of Zimbabwe introduced bivalent HPV vaccine with a 0,12 month schedule to all 10-14 year old girls using a pulsed-campaign approach in May 2018 (dose 1) and May 2019 (dose 2). METHODS: In August 2019, we conducted a population-based, two-stage cluster survey of households with girls who were eligible for the national HPV vaccination program to determine two-dose HPV vaccination coverage in three districts of Zimbabwe. All households with girls currently aged 11 to 15 years were line-listed through a census conducted in the pre-selected clusters from each district prior to survey administration. A simple random sample of eligible households was selected from these lists to estimate HPV vaccine coverage at sufficient power with a margin of error of +/- 5%. Criteria for district selection included estimated vaccine uptake (low, medium, high), rural/urban/peri-urban, geographic area, estimated number of girls not in school, and recent natural disasters or disease outbreaks. We oversampled households with girls aged 13 or 14 years at the time of dose 1. RESULTS: On-time dose 1 uptake ranged from 88 to 94% and two-dose HPV vaccine coverage ranged from 75 to 86% across the three districts. Nearly all vaccinations occurred in schools, and less than 2% of girls did not attend school. There were challenges assessing ages of girls at schools prior to vaccination - 9% of girls vaccinated were less than 10 years old at time of dose 1. DISCUSSION: Zimbabwe has demonstrated that high uptake and successful completion of 2-dose HPV vaccination can be achieved with an annual dosing schedule. Efforts going forward will need to focus on minimizing dropout between doses and routinizing annual vaccinations in schools for every subsequent new cohort of eligible girls in the country.

Effectiveness of typhoid conjugate vaccine in Zimbabwe used in response to an outbreak among children and young adults: A matched case control study.

BACKGROUND: Zimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare. METHODS: A matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls. FINDINGS: Of 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls. The adjusted VE against confirmed TF was 75% (95%CI: 1-94, p = 0.049) compared to facility controls, and 84% (95%CI: 57-94, p < 0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26-77, p = 0.153) compared to facility controls, and 67% (95%CI: 35-83, p = 0.002) compared to community controls six months to 45 years old. INTERPRETATION: This study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.