Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

Our study describes neonates from low- and middle-income countries with neonatal invasive candidiasis (NIC). Most of them were outside the groups considered at high risk for NIC described in high-income countries. Candida spp. epidemiology was also different. The mortality was high (22%). Further research in these settings is required.

Spectrum of antibiotic resistance in UTI caused by Escherichia coli among HIV-infected patients in Uganda: a cross-sectional study.

BACKGROUND: Antimicrobial drug resistance is one of the top ten threats to global health according to the World Health Organization. Urinary tract infections (UTIs) are among the most common bacterial infections and main reason for antibiotic prescription. The incidence of UTIs appears to be high among people living with HIV. We sought to determine the most common UTI pathogens among HIV infected patients and evaluate their susceptibility towards antibiotics. METHODS: We performed a cross-sectional study among HIV-infected patients aged ≥ 18 years presenting at an HIV care specialized clinic with symptoms suggestive of a urethritis. Urine cultures were subjected to antibiotic susceptibility testing according to Clinical Laboratory Standards Institute. The data was analyzed using STATA, we performed Pearson's Chi-square and Fisher's exact tests to compare differences between proportions. RESULTS: Out of the 200 patients, 123 (62%) were female. The median age was 41.9 years (IQR 34.7-49.3). Only 32 (16%) urine cultures showed bacterial growth. Escherichia coli was the most commonly isolated uropathogen (72%), followed by Klebsiella pneumoniae (9%). E. coli was completely resistant to cotrimoxazole and ampicillin; resistance to ciprofloxacin and ceftriaxone was 44% and 35% respectively; 9% to gentamicin; no resistance detected to nitrofurantoin and imipenem. CONCLUSIONS: Our findings are congruent with the Uganda national clinical guidelines which recommends nitrofurantoin as the first line antibiotic for uncomplicated UTI. Significant ciprofloxacin and ceftriaxone resistance was detected. In the era of emerging antibiotic resistance, understanding the local susceptibilities among sub-populations such as HIV infected patients is crucial. Further investigation is needed to address reasons for the low bacterial growth rate observed in the urine cultures.

Giardia duodenalis in Ugandan Children Aged 9-36 Months in Kampala, Uganda: Prevalence and Associated Factors.

Giardia duodenalis is a common gastrointestinal pathogen globally that has been associated with growth failure in children. Most of the studies have been done in school-age children, and there is a paucity of data in pre-school children. We determined the prevalence and factors associated with G. duodenalis infection in children aged 9-36 months presenting to Mulago Hospital with diarrhea or cough. Demographic and socio-economic characteristics, animal ownership, medical history, and physical examination findings were recorded. Stool was tested for G. duodenalis using real-time quantitative polymerase chain reaction (qPCR), and additional tests included stool microscopy and qPCR for Cryptosporidium. The overall prevalence of G. duodenalis infection was 6.7% (214/3,173). In children with diarrhea the prevalence was 6.9% (133/1,923), whereas it was 6.5% (81/1,250) in those with cough as the main symptom. Of 214 children with G. duodenalis infection, 19 (8.9%) were co-infected with Cryptosporidium. Older children (25-36 months) were more likely to have G. duodenalis infection (adjusted odds ratio [aOR]: 2.93, 95% CI: 1.93-4.43). Use of an unimproved toilet (aOR: 1.38, 95% CI: 1.04-1.83) and the wet season (aOR: 1.33, 95% CI: 1.00-1.77) were associated with increased infection. Other factors associated with infection were recurrent diarrhea (aOR: 2.46, 95% CI: 1.64-3.70) and passing of mucoid stool (aOR: 2.25, 95% CI: 1.08-4.66). Having a ruminant at the homestead was also associated with infection (aOR: 1.83, 95% CI: 1.20-2.79). Giardia duodenalis infection occurred in 1 of 15 children aged 9-36 months with diarrhea or cough in Kampala, Uganda. Further studies are needed to clarify the zoonotic significance of G. duodenalis infection in this setting.

Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS.

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.

A Cross-Cutting Approach to Surveillance and Laboratory Capacity as a Platform to Improve Health Security in Uganda.

Global health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda.