Population structure of Salmonella enterica Typhi in Harare, Zimbabwe (2012-19) before typhoid conjugate vaccine roll-out: a genomic epidemiology study.

BACKGROUND: The continued emergence of Salmonella enterica serovar Typhi, with ever increasing antimicrobial resistance, necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe, in 2018 from a multidrug resistant S Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine programme. We aimed to investigate the emergence and evolution of antimicrobial resistance of endemic S Typhi in Zimbabwe and to determine the population structure, gene flux, and sequence polymorphisms of strains isolated before a typhoid conjugate vaccine programme to provide a baseline for future evaluation of the effect of the vaccination programme. METHODS: In this genomic epidemiology study, we used short-read whole-genome sequencing of S Typhi isolated from clinical cases of typhoid fever in Harare, Zimbabwe, between Jan 1, 2012, and Feb 9, 2019, to determine the S Typhi population structure, gene flux, and sequence polymorphisms and reconstructed the evolution of antimicrobial resistance. Maximum likelihood time-scaled phylogenetic trees of Zimbabwe isolates in the context of global isolates obtained from the National Center for Biotechnology Information were constructed to infer spread and emergence of antimicrobial resistance. FINDINGS: The population structure of S Typhi in Harare, Zimbabwe, from 2012 to 2019 was dominated by multidrug resistant genotype 4.3.1.1.EA1 (H58) that spread to Zimbabwe from neighbouring countries in around 2009 (95% credible interval 2008·5-2010·0). Acquisition of an IncN plasmid carrying antimicrobial resistance genes including a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene contributed to non-susceptibility and resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S Typhi genotype 3.3.1 strains were present throughout. INTERPRETATION: The currently dominant S Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional antimicrobial resistance though acquisition of a plasmid and mutation in the gyrA gene. This study provides a baseline population structure for future evaluation of the effect of the typhoid conjugate vaccine programme in Harare. FUNDING: Bill & Melinda Gates Foundation and the Biotechnology and Biological Sciences Research Council Institute Strategic Programme.

Lessons learnt from implementing the Good Governance for Medicines Programme in Zimbabwe.

WHO launched the Good Governance for Medicines (GGM) programme in 2004 with the aim of fighting the problem of corruption in the pharmaceutical sector. Zimbabwe adopted the GGM programme in 2015 and developed its own implementation framework (GGM-IF) in 2017 based on the WHO global guidelines and recommendations. Zimbabwe's GGM-IF emerged from; (1) home-based expertise, (2) extensive local consultations and (3) effective incorporation into existing institutions. The GGM-IF committed to implementing a focused programme over a 5-year period from 2017 to 2022 with the expressed goal of improving transparency and accountability in the pharmaceutical sector as a key enabler to improve access to medicines. Midway through its projected lifespan, some notable achievements materialised attributed to key success drivers, including mutual collaboration with the Ministry of Health and Child Care's existing Global Fund supported Quality Assurance Programme. Key challenges faced include limited funding for the programme, a shifting policy environment driven by a political transition and reorientation of priorities in the wake of the COVID-19 pandemic. This manuscript articulates 3-year operationalisation of Zimbabwe's GGM-IF highlighting the success drivers, implementation challenges and lessons learnt.

Faecal carriage of ESBL producing and colistin resistant Escherichia coli in avian species over a 2-year period (2017-2019) in Zimbabwe.

Introduction: Extended spectrum beta-lactamase (ESBL) producing Escherichia coli have become widespread among food producing animals. These strains serve as a reservoir of antibiotic resistance genes (ARGs) and act as a possible source of infection to humans as transmission can occur by direct or indirect contact. Methods: This study investigated the faecal carriage of ESBL producing and colistin resistant E. coli in poultry over a 2-year period (2017-2019) from Zimbabwe. A total of 21 ESBL positive isolates from poultry cloacal specimens were selected for whole genome sequencing from animal E. coli isolates bio-banked at the National Microbiology Reference laboratory using phenotypic susceptibility testing results from the National Escherichia coli Surveillance Program to provide representation of different geographical regions and year of isolation. Cloacal swabs were collected from 3000 broiler live birds from farm 1 and from farm 2, 40 backyard chickens and 10 ducks were sampled. Antimicrobial susceptibility and ESBL testing were performed as per Clinical Laboratory Standards Institute guidelines. Whole genome sequencing of ESBL producing isolates was used to determine sequence types (STs), ARGs, and phylogroups. Results: Twenty-one of the included E. coli isolates were confirmed as ESBL producers. Three defined sequence type clonal complexes (CCs) were identified (ST10CC, ST155CC and ST23CC), with ST10CC associated with the most antibiotic resistant profile. The ESBL phenotype was linked to the presence of either cefotaximase-Munich-14 (CTX-M-14) or CTX-M-79. Plasmid mediated quinolone resistant determinants identified were qnrB19 and qnrS1 and one ST10CC isolate from farm 1 broiler chickens harbored a mobile colistin resistance gene (mcr-1). Phylogenetic groups most identified were B1, A and unknown. Discussions: The avian ESBL producing E. coli belonged to a diverse group of strains. The detection of several ARGs highlights the importance of implementing enhanced control measures to limit the spread in animals, environment, and humans. This is the first report of mcr-1 in Zimbabwe, which further underscores the importance of the One Health approach to control the spread and development of AMR.

Molecular epidemiology of extended-spectrum beta-lactamase-producing extra-intestinal pathogenic Escherichia coli strains over a 2-year period (2017-2019) from Zimbabwe.

This study was designed to characterize extended-spectrum beta-lactamase (ESBL)-producing extra-intestinal pathogenic Escherichia coli (E.coli) (ExPEC) associated with urinary tract infections in nine different geographic regions of Zimbabwe over a 2-year period (2017-2019). A total of 48 ESBL-positive isolates from urine specimen were selected for whole-genome sequencing from 1246 Escherichia coli isolates biobanked at the National Microbiology Reference laboratory using phenotypic susceptibility testing results from the National Escherichia coli Surveillance Programme to provide representation of different geographical regions and year of isolation. The majority of ESBL E. coli isolates produced cefotaximase-Munich (CTX-M)-15, CTX-M-27, and CTX-M-14. In this study, sequence types (ST) 131 and ST410 were the most predominant antimicrobial-resistant clones and responsible for the increase in ESBL-producing E. coli strains since 2017. Novel ST131 complex strains were recorded during the period 2017 to 2018, thus showing the establishment and evolution of this antimicrobial-resistant ESBL clone in Zimbabwe posing an important public health threat. Incompatibility group F plasmids were predominant among ST131 and ST410 isolates with the following replicons recorded most frequently: F1:A2:B20 (9/19, 47%), F2:A1: B (5/19, 26%), and F1:A1:B49 (8/13, 62%). The results indicate the need for continuous tracking of different ESBL ExPEC clones on a global scale, while targeting specific STs (e.g. ST131 and ST410) through control programs will substantially decrease the spread of ESBLs among ExPEC.

Distribution of schistosomiasis and soil transmitted helminthiasis in Zimbabwe: towards a national plan of action for control and elimination.

BACKGROUND: Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009-2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted. METHODOLOGY: A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques. MAIN FINDINGS: Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p<0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened. CONCLUSION AND RECOMMENDATIONS: This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe.

Factors associated with HIV infection among children born to mothers on the prevention of mother to child transmission programme at Chitungwiza Hospital, Zimbabwe, 2008.

BACKGROUND: Zimbabwe is one of the five countries worst affected by the HIV/AIDS pandemic with HIV infection contributing increasingly to childhood morbidity and mortality. Among the children born to HIV positive mothers participating in the PMTCT programme, 25% tested positive to HIV. We investigated factors associated with HIV infection among children born to mothers on the PMTCT programme. METHODS: A 1:1 unmatched case-control study was conducted at Chitungwiza Hospital, Zimbabwe, 2008. A case was defined as a child who tested HIV positive, born to a mother who had been on PMTCT programme. A control was a HIV negative child born to a mother who had been on PMTCT programme. An interviewer-administered questionnaire was used to collect data on demographic characteristics, risk factors associated with HIV infection and immunization status. RESULTS: A total of 120 mothers were interviewed. Independent risk factors associated with HIV infection among children included maternal CD4 count of less than 200 during pregnancy [aOR = 7.1, 95% CI (2.6-17)], mixed feeding [aOR = 29, 95% CI (4.2-208)], being hospitalized since birth [aOR = 2.9, 95% CI (1.2-4.8)] whilst being exclusively breast fed for less than 6 months [aOR = 0.1 (95% CI 0.03-0.4)] was protective. CONCLUSIONS: HIV infection among children increased if the mother's CD4 count was ≤200 cells/µL and if the child was exposed to mixed feeding. Breastfeeding exclusively for less than six months was protective. We recommended exclusive breast feeding period for the first six months and stop breast feeding after 6 months if affordable, sustainable and safe.

Community mortality from cholera: urban and rural districts in Zimbabwe.

In 2008-2009, Zimbabwe experienced an unprecedented cholera outbreak with more than 4,000 deaths. More than 60% of deaths occurred at the community level. We conducted descriptive and case-control studies to describe community deaths. Cases were in cholera patients who died outside health facilities. Two surviving cholera patients were matched by age, time of symptom onset, and location to each case-patient. Proxies completed questionnaires regarding mortality risk factors. Cholera awareness and importance of rehydration was high but availability of oral rehydration salts was low. A total of 55 case-patients were matched to 110 controls. The odds of death were higher among males (adjusted odd ratio [AOR] = 5.00, 95% confidence interval [CI] = 1.54-14.30) and persons with larger household sizes (AOR = 1.21, 95% CI = 1.00-1.46). Receiving home-based rehydration (AOR = 0.21, 95% CI = 0.06-0.71) and visiting cholera treatment centers (CTCs) (AOR = 0.07, 95% CI = 0.02-0.23) were protective. Receiving cholera information was associated with home-based rehydration and visiting CTCs. When we compared cases and controls who did not go to CTCs, males were still at increased odds of death (AOR = 5.00, 95% CI = 1.56-16.10) and receiving home-based rehydration (AOR = 0.14, 95% CI = 0.04-0.53) and being married (AOR = 0.26, 95% CI = 0.08-0.83) were protective. Inability to receive home-based rehydration or visit CTCs was associated with mortality. Community education must reinforce the importance of prompt rehydration and CTC referral.

Trends in performance of the national measles case-based surveillance system, Ministry of Health and Child Welfare, Zimbabwe (1999 - 2008).

INTRODUCTION: Since adoption of the measles case-based surveillance system in Zimbabwe in 1998, data has been routinely collected at all levels of the health delivery system and sent to national level with little or no documented evidence of use to identify risky populations, monitor impact of interventions and measure progress towards achieving measles elimination. We analysed this data to determine trends in the national measles case-based surveillance system (NMCBSS). METHODS: A retrospective record review of the NMCBSS dataset for period 1999 -2008 was conducted, assessing trends in proportions of investigated cases; timeliness and nature of specimens received at laboratory; timeliness of feedback of serology results, proportion of cases confirmed as measles and national annualized rates of investigation. Comparisons with WHO performance indicators were done. The secondary data analysis was done in Excel and Epi-Info statistical software. RESULTS: Cumulatively 4994 suspected cases were reported and investigated between 1999 and 2008. Reported suspected and confirmed measles cases declined from 24, 5% and 5.9% respectively in 2000 to 3.9% and 1.0% respectively in 2008. Proportion of cases with blood specimens collected and proportion reaching laboratory timely increased from 83% and 65% respectively in 1999, to 100% and 82% respectively in 2008. Proportion of specimens arriving at laboratory in good condition improved from 65% in 2004 to 94% in 2008 while timeliness of feedback of serology results improved from 4% in 2004 to 65% in 2008. Sensitivity of the NMCBSS however has been weakening, declining from 9.04 cases investigated per 100,000 population per year in 2000 to 1.58 cases/100,000/year in 2008. CONCLUSION: The NMCBSS improved in quality, timeliness and feedback of laboratory results of specimens sent for investigation, but its sensitivity declined mainly due to reduced capacity to detect and confirm measles cases. We recommend training staff on active surveillance of cases and more support and supervisory visits to strengthen EPI surveillance.

Trends in Performance of the National Measles Case-Based Surveillance System; Ministry of Health and Child Welfare; Zimbabwe (1999 - 2008)

Introduction: Since adoption of the measles case-based surveillance system in Zimbabwe in 1998; data has been routinely collected at all levels of the health delivery system and sent to national level with little or no documented evidence of use to identify risky populations; monitor impact of interventions and measure progress towards achieving measles elimination. We analysed this data to determine trends in the national measles case-based surveillance system (NMCBSS). Methods: A retrospective record review of the NMCBSS dataset for period 1999 -2008 was conducted; assessing trends in proportions of investigated cases; timeliness and nature of specimens received at laboratory; timeliness of feedback of serology results; proportion of cases confirmed as measles and national annualized rates of investigation. Comparisons with WHO performance indicators were done. The secondary data analysis was done in Excel and Epi-Info statistical software. Results: Cumulatively 4994 suspected cases were reported and investigated between 1999 and 2008. Reported suspected and confirmed measles cases declined from 24; 5 and 5.9 respectively in 2000 to 3.9and 1.0 respectively in 2008. Proportion of cases with blood specimens collected and proportion reaching laboratory timely increased from 83 and 65 respectively in 1999; to 100 and 82 respectively in 2008. Proportion of specimens arriving at laboratory in good condition improved from 65 in 2004 to 94 in 2008 while timeliness of feedback of serology results improved from 4 in 2004 to 65in 2008. Sensitivity of the NMCBSS however has been weakening; declining from 9.04 cases investigated per 100 000 population per year in 2000 to 1.58 cases/100 000/year in 2008. Conclusion: The NMCBSS improved in quality; timeliness and feedback of laboratory results of specimens sent for investigation; but its sensitivity declined mainly due to reduced capacity to detect and confirm measles cases. We recommend training staff on active surveillance of cases and more support and supervisory visits to strengthen EPI surveillance

Phenotypic, genotypic, and antibiotic sensitivity patterns of strains isolated from the cholera epidemic in Zimbabwe.

This paper details the phenotypic, genotypic, and antibiotic sensitivity patterns of 88 Vibrio cholerae strains from Zimbabwe. Of the 88 strains, 83 were classified as "altered El Tor" and 5 as "hybrid El Tor" strains. All of the strains were susceptible to tetracycline, doxycycline, ciprofloxacin, and azithromycin by disc diffusion, but susceptibility to tetracycline and azithromycin diminished when observed using the MIC method.

Postnatal depression by HIV status among women in Zimbabwe.

BACKGROUND: Postnatal depression (PND) is a serious public health problem in resource-limited countries. Research is limited on PND affecting HIV-infected women in sub-Saharan Africa. Zimbabwe has one of the highest antenatal HIV infection rates in the world. We determined the prevalence and risk factors of PND among women attending urban primary care clinics in Zimbabwe. METHODS: Using trained peer counselors, a simple random sample of postpartum women (n = 210) attending the 6-week postnatal visit at two urban primary care clinics were screened for PND using the Shona version of the Edinburgh Postnatal Depression Scale (EPDS). All women were subsequently subjected to mental status examination using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depression by two psychiatrists who had no knowledge of the EPDS test results. RESULTS: Of the 210 mothers (31 HIV positive, 148 HIV negative, 31 unknown status) enrolled during the postpartum period, 64 (33%) met DSM-IV criteria for depression. The HIV prevalence was 14.8%. Of the 31 HIV-infected mothers, 17(54%) met DSM-IV criteria for depression. Univariate analysis showed that multiparity (prevalent odds ratio [OR] 2.22, 95% confidence intervals [CI] 1.15-4.31), both parents deceased (OR 2.35, 95% CI 1.01-5.45), and having experienced a recent adverse life event (OR 8.34, CI 3.77-19.07) were significantly associated with PND. Multivariate analysis showed that PND was significantly associated with adverse life event (OR 7.04, 95% CI 3.15-15.76), being unemployed (OR 3.12, 95% CI 1.23-7.88), and multiparity (OR 2.50, 95% CI 1.00-6.24). CONCLUSIONS: Our data indicate a high burden of PND among women in Zimbabwe. It is feasible to screen for PND in primary care clinics using peer counselors. Screening for PND and access to mental health interventions should be part of routine antenatal care for all women in Zimbabwe.

Validation of the Edinburgh Postnatal Depression Scale among women in a high HIV prevalence area in urban Zimbabwe.

UNLABELLED: Despite the significant burden of common mental disorders (CMD) among women in sub Saharan Africa, data on postnatal depression (PND) is very limited, especially in settings with a high HIV prevalence. The Edinburgh Postnatal Depression Scale (EPDS), a widely used screening test for PND has been validated in many countries, but not in Zimbabwe. We assessed the validity of the EPDS scale among postpartum women compared with Diagnostic Manual of Mental Disorders (DSM-IV) criteria for major depression. Six trained community counselors administered the Shona version of the EPDS to a random sample of 210 postpartum HIV-infected and uninfected women attending two primary care clinics in Chitungwiza. All women were subsequently subjected to mental status examination using DSM IV criteria for major depression by 2 psychiatrists, who were blinded to the subject's EPDS scores. Data were analyzed using receiver operating characteristic (ROC) curve analysis. Of the 210 postpartum mothers enrolled, 64 (33%) met DSM IV criteria for depression. Using a cut-off score of 11/12 on the Shona version of the EPDS for depression, the sensitivity was 88%, and specificity was 87%, with a positive predictive value of 74%, a negative predictive value of 94%, and an area under the curve of 0.82. Cronbach's alpha coefficient for the whole scale was 0.87. CONCLUSION: The Shona version of the EPDS is a reliable and valid tool to screen for PND among HIV-infected and un-infected women in Zimbabwe. Screening for PND should be integrated into routine antenatal and postnatal care in areas with high HIV prevalence.