Evaluating empiric antibiotic prescribing for hospitalized children in Mozambique through the introduction of a quarterly syndromic antibiogram: An implementation science protocol.

Antimicrobials are the most frequently prescribed drug in pediatrics, with an estimated 37% of infants and 61% of hospitalized children having received them. Approximately 20-50% of prescriptions have been shown to be potentially unnecessary or inappropriate. The World Health Organization (WHO) estimates that the continued increase in antimicrobial resistance by the year 2050 will lead to the death of 10 million people per year. This paper describes a protocol to be used in a future study to evaluate the implementation of a quarterly syndromic antibiogram, aimed to improve the use of antibiotics for the treatment of pediatric bacterial infections at the Maputo Central Hospital, Mozambique. This study uses implementation science methods framed by the Dynamic Adaption Process (DAP) and RE-AIM conceptual frameworks to develop a multi-phase, mixed-methods evaluation utilizing qualitative and quantitative approaches. The pediatric inpatient services at HCM consist of approximately 18 physicians and 60 nurses. Additionally, the microbiology laboratory consists of eight laboratory technicians. We anticipate analyzing approximately 9,000 medical records. Qualitative methods include in-depth interviews with clinicians, laboratory technicians, and administrators to explore current knowledge and practices around antibiotic decision making, facilitators and barriers to intervention implementation, as well as acceptability and satisfaction with the intervention roll-out. Qualitative analysis will be performed with NVivo 12 software. Quantitative methods include extracting data from existing records from the pediatric ward of Hospital Central de Maputo (HCM) guided by the RE-AIM framework to explore intervention utilization and other factors influencing its implementation. Quantitative descriptive and inferential statistical analysis will be performed using R Studio statistical software. The findings from this evaluation will be shared with hospital administrators and relevant national policymakers and may be used by the Ministry of Health in deciding to expand this approach to other hospitals. The expected results of this research include the development of standard operating guidelines for the creation, distribution, and use of a quarterly syndromic antibiogram for antibiotic decision making that is informed by local epidemiology. Findings from this study will be used to develop a larger multi-site trial in Mozambique.

Prevalence of sexually transmitted infections (STIs), associations with sociodemographic and behavioural factors, and assessment of the syndromic management of vaginal discharge in women with urogenital complaints in Mozambique.

In Mozambique, sexually transmitted infections (STIs) are estimated to be prevalent, but diagnosis and treatment of curable STIs rely only on syndromic management. We examined the prevalence of four non-viral STIs and HIV-1/2, based on etiological diagnosis, associations with sociodemographic and behavioural factors, and the STI diagnostic accuracy of the vaginal discharge syndromic management in women with urogenital complaints in Maputo, Mozambique. A cross-sectional study was performed in Maputo, Mozambique, February 2018-January 2019, enrolling 924 women of reproductive age with urogenital complaints. Endocervical/vaginal swabs were sampled and chlamydia, gonorrhoea, trichomoniasis and Mycoplasma genitalium infections were diagnosed using a multiplex real-time PCR (AmpliSens; InterLabServices). Serological testing was performed for HIV-1/2. A structured questionnaire collected metadata. All data were analyzed in STATA/IC 12.1 using descriptive statistics, chi-square tests and logistic regression model. About 40% of the women were less than 24 years old, 50.8% were single, 62.1% had their sexual debut between 12 and 17 years of age, and the main complaint was vaginal discharge syndrome (85%). The prevalence of chlamydia was 15.5%, trichomoniasis 12.1%, gonorrhoea 4.0%, M. genitalium 2.1%, and HIV-1/2 22.3%. The vaginal discharge syndrome flowchart had a sensitivity of 73.0%-82.5% and a specificity of 14%-15% for the detection of any individual non-viral STI in women with urogenital complaints. In total, 19.2% of the symptomatic women with chlamydia, trichomoniasis or gonorrhoea would not be detected and accordingly treated using the vaginal discharge syndromic management (missed treatment) and 70.0% of the women would be treated despite not being infected with any of these three STIs (overtreatment). In conclusion, a high prevalence of especially chlamydia, trichomoniasis, and HIV-1/2 was found in women of childbearing age with urogenital complaints in Maputo, Mozambique. Syndromic management of vaginal discharge revealed low accuracy in the detection of STIs in symptomatic women, especially low specificity, which resulted in under-treatment of STI-positive cases and incorrect or over-treatment of women with urogenital complaints, many of whom were negative for all the non-viral STIs. Etiological diagnosis is imperative for effective management of STIs in symptomatic and asymptomatic women.

Community-acquired bacteremia among HIV-infected and HIV-exposed uninfected children hospitalized with fever in Mozambique

Background: Bacteremia is a major cause of morbidity and mortality worldwide. Children infected with HIV present with patterns of bacteremia generally associated with poor prognosis. In Mozambique, data on bacteremia are sparce. Methods: We conducted an observational study of HIV-infected and HIV-exposed uninfected children, aged 0-59 months, hospitalized with fever between April 1, 2016 and February 28, 2019. A single bacterial culture was collected at admission. Descriptive statistics were used to summarize microorganisms detected and antibiotic susceptibility testing. Results: A total of 808 HIV-infected (90%) and HIV-exposed uninfected (10%) children were enrolled. Blood culture positivity was 12% (95% CI: 9.9%-14.4%). Five organisms accounted for most cases: Staphylococcus Aureus (37%), Klebsiella spp (11%), Salmonella spp (11%), Escherichia Coli (9%) and Micrococcus (7%). Antibiotic resistance was common. Nearly 70% of Staphylococcus Aureus were methicillin-resistant and roughly 50% of Klebsiella had ESBL production. Conclusion: Community-acquired bacteremia was common in HIV-infected and HIV-exposed uninfected children hospitalized in Mozambique with a febrile illness. High rates of MRSA and ESBL producing organisms has implications for empiric antibiotics utilized in Mozambique. Longitudinal data on the prevalence and antimicrobial resistance patterns of important pathogens are badly needed to guide policy for drug formulary expansion and antibiotic prescription guidelines.

Altered Mental Status Among Febrile Hospitalized HIV-Infected Children Aged 0-59 Months in Mozambique

Altered mental status (AMS) is a priority presenting sign that must be assessed in HIV-infected, febrile children, yet diagnosis is difficult in areas with limited diagnostic capacity. Malaria and bacterial meningitis have been reported as the most common causes of AMS in febrile children presenting to the hospital in sub-Saharan Africa. However, in an HIV-infected child, central nervous system manifestations are diverse. Methods: We conducted a clinical observational study of HIV-infected febrile children, aged 0-59 months, hospitalized in Mozambique and prospectively followed. Within this cohort, a nested study was designed to characterize children admitted with AMS and to assess factors associated with mortality. Univariate and multivariable analysis were performed comparing characteristics of the cohort by AMS status and evaluated demographic and clinical factors by in-hospital mortality outcome. Results: In total, 727 children were enrolled between April 2016 and February 2019, 16% had AMS at admission. HIV-infected, febrile children, who presented with AMS and who had a diagnosis of bacteremia, had a 4-fold increased relative odds of in-hospital mortality, and children who presented with neurologic symptoms on admission had a roughly 8-fold higher odds of in-hospital mortality relative to children without presenting neurologic findings. Conclusions: Mozambique has a pressing need to expand local diagnostic capacity. Our results highlight the critical need for clinicians to incorporate a broader differential into their potential causes of AMS, and to develop a Ministry of Health approved diagnostic and management algorithm, which is standardly used, to manage patients for whom reliable and relevant diagnostic services are not available.

Community-acquired bacteremia among HIV-infected and HIV-exposed uninfected children hospitalized with fever in Mozambique.

BACKGROUND: Bacteremia is a major cause of morbidity and mortality worldwide. Children infected with HIV present with patterns of bacteremia generally associated with poor prognosis. In Mozambique, data on bacteremia are sparce. METHODS: We conducted an observational study of HIV-infected and HIV-exposed uninfected children, aged 0-59 months, hospitalized with fever between April 1, 2016 and February 28, 2019. A single bacterial culture was collected at admission. Descriptive statistics were used to summarize microorganisms detected and antibiotic susceptibility testing. RESULTS: A total of 808 HIV-infected (90%) and HIV-exposed uninfected (10%) children were enrolled. Blood culture positivity was 12% (95% CI: 9.9%-14.4%). Five organisms accounted for most cases: Staphylococcus Aureus (37%), Klebsiella spp (11%), Salmonella spp (11%), Escherichia Coli (9%) and Micrococcus (7%). Antibiotic resistance was common. Nearly 70% of Staphylococcus Aureus were methicillin-resistant and roughly 50% of Klebsiella had ESBL production. CONCLUSION: Community-acquired bacteremia was common in HIV-infected and HIV-exposed uninfected children hospitalized in Mozambique with a febrile illness. High rates of MRSA and ESBL producing organisms has implications for empiric antibiotics utilized in Mozambique. Longitudinal data on the prevalence and antimicrobial resistance patterns of important pathogens are badly needed to guide policy for drug formulary expansion and antibiotic prescription guidelines.

Altered Mental Status Among Febrile Hospitalized HIV-Infected Children Aged 0-59 Months in Mozambique.

BACKGROUND: Altered mental status (AMS) is a priority presenting sign that must be assessed in HIV-infected, febrile children, yet diagnosis is difficult in areas with limited diagnostic capacity. Malaria and bacterial meningitis have been reported as the most common causes of AMS in febrile children presenting to the hospital in sub-Saharan Africa. However, in an HIV-infected child, central nervous system manifestations are diverse. METHODS: We conducted a clinical observational study of HIV-infected febrile children, aged 0-59 months, hospitalized in Mozambique and prospectively followed. Within this cohort, a nested study was designed to characterize children admitted with AMS and to assess factors associated with mortality. Univariate and multivariable analysis were performed comparing characteristics of the cohort by AMS status and evaluated demographic and clinical factors by in-hospital mortality outcome. RESULTS: In total, 727 children were enrolled between April 2016 and February 2019, 16% had AMS at admission. HIV-infected, febrile children, who presented with AMS and who had a diagnosis of bacteremia, had a 4-fold increased relative odds of in-hospital mortality, and children who presented with neurologic symptoms on admission had a roughly 8-fold higher odds of in-hospital mortality relative to children without presenting neurologic findings. CONCLUSIONS: Mozambique has a pressing need to expand local diagnostic capacity. Our results highlight the critical need for clinicians to incorporate a broader differential into their potential causes of AMS, and to develop a Ministry of Health approved diagnostic and management algorithm, which is standardly used, to manage patients for whom reliable and relevant diagnostic services are not available.

Multiple Concurrent Illnesses Associated with Anemia in HIV-Infected and HIV-Exposed Uninfected Children Aged 6-59 Months, Hospitalized in Mozambique.

Anemia is an increasingly recognized problem in sub-Saharan Africa. To determine the magnitude, severity, and associated factors of anemia among hospitalized children aged 6-59 months, HIV-infected and HIV-exposed uninfected children (a child born to a known HIV-infected mother) with a documented fever or history of fever within the prior 24 hours of hospital admission (N = 413) were included in this analysis. Of 413 children enrolled, 364 (88%) were anemic, with 53% classified as mild anemia (hemoglobin [Hb] 7-9.9 g/dL). The most common diagnoses associated with hospital admission included acute respiratory illness (51%), malnutrition (47%), gastroenteritis/diarrhea (25%), malaria (17%), and bacteremia (13%). A diagnosis of malaria was associated with a decrease in Hb by 1.54 g/dL (P < 0.001). In HIV-infected patients, malaria was associated with a similar decrease in Hb (1.47 g/dL), whereas a dual diagnosis of bacteremia and malaria was associated with a decrease in Hb of 4.12 g/dL (P < 0.001). No difference was seen in Hb for patients on antiretroviral therapy versus those who were not. A diagnosis of bacteremia had a roughly 4-fold increased relative odds of death during hospitalization (adjusted odds ratio = 3.97; 95% CI: 1.61, 9.78; P = 0.003). The etiology of anemia in high-burden malaria, HIV, tuberculosis, and poor nutrition countries is multifactorial, and multiple etiologies may be contributing to one's anemia at any given time. Algorithms used by physician and nonphysician clinicians in Mozambique should incorporate integrated and non-disease specific approaches to pediatric anemia management and should include improved access to blood culture.