Unravelling patient pathways in the context of antibacterial resistance in East Africa.

BACKGROUND: A key factor driving the development and maintenance of antibacterial resistance (ABR) is individuals' use of antibiotics (ABs) to treat illness. To better understand motivations and context for antibiotic use we use the concept of a patient treatment-seeking pathway: a treatment journey encompassing where patients go when they are unwell, what motivates their choices, and how they obtain antibiotics. This paper investigates patterns and determinants of patient treatment-seeking pathways, and how they intersect with AB use in East Africa, a region where ABR-attributable deaths are exceptionally high. METHODS: The Holistic Approach to Unravelling Antibacterial Resistance (HATUA) Consortium collected quantitative data from 6,827 adult outpatients presenting with urinary tract infection (UTI) symptoms in Kenya, Tanzania, and Uganda between February 2019- September 2020, and conducted qualitative in-depth patient interviews with a subset (n = 116). We described patterns of treatment-seeking visually using Sankey plots and explored explanations and motivations using mixed-methods. Using Bayesian hierarchical regression modelling, we investigated the associations between socio-demographic, economic, healthcare, and attitudinal factors and three factors related to ABR: self-treatment as a first step, having a multi-step treatment pathway, and consuming ABs. RESULTS: Although most patients (86%) sought help from medical facilities in the first instance, many (56%) described multi-step, repetitive treatment-seeking pathways, which further increased the likelihood of consuming ABs. Higher socio-economic status patients were more likely to consume ABs and have multi-step pathways. Reasons for choosing providers (e.g., cost, location, time) were conditioned by wider structural factors such as hybrid healthcare systems and AB availability. CONCLUSION: There is likely to be a reinforcing cycle between complex, repetitive treatment pathways, AB consumption and ABR. A focus on individual antibiotic use as the key intervention point in this cycle ignores the contextual challenges patients face when treatment seeking, which include inadequate access to diagnostics, perceived inefficient public healthcare and ease of purchasing antibiotics without prescription. Pluralistic healthcare landscapes may promote more complex treatment seeking and therefore inappropriate AB use. We recommend further attention to healthcare system factors, focussing on medical facilities (e.g., accessible diagnostics, patient-doctor interactions, information flows), and community AB access points (e.g., drug sellers).

Prevalence, antifungal susceptibility and etiology of vulvovaginal candidiasis in sub-Saharan Africa: a systematic review with meta-analysis and meta-regression.

Vulvovaginal candidiasis (VVC) is a commonly occurring form of mucocutaneous candidiasis in women. The aim of this study was to comprehensively investigate the prevalence, antifungal susceptibility, and etiology of VVC in sub-Saharan Africa (SSA). A search of studies was conducted in seven online databases and the reference lists of selected studies. Observational studies published between January 2000, to July 2021, that met the eligibility criteria were included. Meta-analyses with random and fixed-effects model, and subgroup analyses were performed using STATA 16.0. A total of 41 studies including 15 723 participants were included in the meta-analyses. The pooled prevalence of VVC was 33% (95% Confidence Interval (CI): 28-38%, I2 = 98%, P < 0.001). Pregnant women had 6% higher odds of having VVC compared to non-pregnant women Odds Ratio (OR): 1.06, 95% CI: 0.99-1.13, P = 0.107). The odds of diagnosing VVC were 40% higher in symptomatic patients than general study population (OR: 1.4, 95% CI: 1.3-1.5, P < 0.0001). In 17 studies, a total of 2112 isolates of Candida species were reported: 1514 (71.7%) Candida albicans, 510 (24.1%) non-albicans Candida (NAC) species and 88 (4.2%) unidentified Candida spp. Of the NAC species detected, Candida glabrata (40.9%, n = 209), Candida krusei (21.2%, n = 108), and Candida tropicalis (22.7%, n = 116) were the most common. Resistance to fluconazole in Candida albicans using disc diffusion methods ranged from 6.8% in Cameroon to 53.7% in Ethiopia. One-third of women in SSA have VVC, mainly caused by C. albicans. Data on the susceptibility of the Candida isolates to commonly used antifungal agents is limited and warrants further research. LAY SUMMARY: The overarching aim of this study was to comprehensively investigate the prevalence, antifungal susceptibility, and causative species of vulvovaginal candidiasis (VVC) in sub-Saharan Africa (SSA). A detailed search of studies was conducted to retrieve eligible observational studies published 'between' January 1, 2000, to July 31, 2021. From the 41 selected studies including 15 723 participants, VVC was found in 33% of the participants. The chances of diagnosing VVC was 40% higher in symptomatic patients compared to the general study population. In 71.7% of the cases, C. albicans was the causative species of VVC. We conclude that about one-third of women in SSA have VVC, mainly caused by C. albicans.

High diversity of Candida glabrata in a tertiary hospital-Mwanza, Tanzania.

Candida glabrata is a genetically diverse human pathogenic yeast, whose subpopulations have been documented to vary geographically. Here, we report MLST genotypes and antifungal drug susceptibility of C. glabrata isolates from Africa. Among 47 mostly urogenital isolates, we found 13 sequence types, amounting to a 27% genetic population difference. More than half of the isolates were of novel sequence types. ST18 was most predominant and had reduced susceptibility to fluconazole. There was clear segregation of STs between urine and vaginal specimen. In Tanzania, the C. glabrata population is genetically diverse, and divergent from those seen in other countries.

Virulence and susceptibility patterns of clinical Candida spp. isolates from a tertiary hospital, Tanzania.

Despite the increased burden of human immunodeficiency virus (HIV) and other comobidities in developing countries, information regarding antifungal susceptibility patterns of Candida spp. and their virulence potential are still limited. Here, we report the virulence and antifungal susceptibility patterns of Candida spp. from varieties spectrum of candidiasis in a tertiary hospital, Tanzania. The study was conducted from March to December 2017. Candida spp. from clinical samples were characterized. Antifungal susceptibility patterns based on EUCAST guidelines and virulence activities (phospholipase, protease, hemolysin, and coagulase activity) were determined. A total of 399 Candida spp. isolates were obtained, of these, 278, 51 and 47 were C. albicans, C. tropicalis, and C. glabrata, respectively. Phospholipase 193/268, protease 32/51 and coagulase 25/47 were the most frequently detected virulence activities in C. albicans, C. tropicalis, and C. glabrata, respectively. Protease and phospholipase were frequently detected virulence activities from C. albicans from blood and esophageal brushes. The median zone diameter of protease activities was significantly larger among C. tropicalis than C. albicans. C. albicans, and C. tropicalis isolates were 100% sensitive to caspofungin. The proportions of C. albicans isolate resistant to fluconazole, voriconazole and posaconazole were 3.1, 3.6%, and 1.8%, respectively. In conclusion, the majority of Candida spp. isolates were sensitive to fluconazole. There are different phenotypes of C. albicans, C. glabrata and C. tropicalis based on susceptibility and virulence activities patterns, necessitating further molecular characterizations to place them in global perspective. Routine antifungal susceptibility testing to guide clinical therapy should be encouraged in developing countries.

Predictors of the extended-spectrum-beta lactamases producing Enterobacteriaceae neonatal sepsis at a tertiary hospital, Tanzania.

The study was conducted to establish predictors of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) neonatal sepsis and mortality in a tertiary hospital, Tanzania. Between July and December 2016, blood culture was performed in neonates with clinical features of sepsis and neonates/mothers/guardians were screened for ESBL colonization. Selected isolates underwent whole genome sequencing to investigate relatedness. Logistic regression analysis was performed to determine predictors for ESBL-PE associated neonatal sepsis and mortality. Neonatal ESBL-PE sepsis was detected in 32(10.5%) of the 304 neonates investigated. Neonatal ESBL-PE sepsis was independently predicted by admission at the Intensive care Unit and positive mother and neonate ESBL-PE colonization. Deaths occurred in 55(18.1%) of neonates. Neonates infected with ESBL-PE, admitted at ICU, increased age and those transferred from other centres had significantly high mortality rates. Gram-negative bacteria formed the majority (76%) of the isolates, of which 77% were ESBL-PE. Virulent Klebsiella pneumoniae ST45 carrying blaCTX-M-15 were commonly isolated from neonates. Klebsiella pneumoniae (ST45) were the predominant cause of ESBL-PE neonatal sepsis and mortality. Improved infection control and antibiotic stewardship are crucial in controlling the spread of resistant strains. Rapid diagnostic tests to detect ESBL-PE in low-income countries are needed to guide treatment and reduce ESBL-PE-associated mortality.

Rubella natural immunity among adolescent girls in Tanzania: the need to vaccinate child bearing aged women.

BACKGROUND: Rubella primary infection during early stages of pregnancy is associated with high risk of congenital Rubella syndrome (CRS). Prevention of CRS in the resource-limited countries requires multiple strategies. Here, we document the data on the magnitude of Rubella natural immunity among adolescent girls which is a crucial group in devising effective control strategies to prevent CRS. METHODS: A cross sectional study involving 397 adolescent girls was conducted in the city of Mwanza involving five secondary schools. Socio-demographic and other relevant information were collected using pre-tested data collection tool. Rubella IgG antibodies were determined using enzyme immunoassay. The presence of Rubella IgG titers of >10 IU/ml indicated natural immunity. RESULTS: The mean age of the study participants was 15.18 ± 1.48 years. Of 397 girls, 340 (85.6%) and 57 (14.4%) were from secondary schools representing peri-urban and rural areas, respectively. Out of 397 girls, 90.4% (95% CI: 87-93) were found to be naturally immune with median Rubella IgG antibodies titers of 56.7 IU/ml interquartile range (IQR): 40.8-137. The median Rubella IgG antibodies titers were significantly high in adolescent girls from families with high socio-economic status (63.96 vs. 47.13 IU/ml, P < 0.001) and in adolescent girls from peri-urban areas of the city (63.33 vs. 39.9 IU/ml, P < 0.001). CONCLUSION: The majority of adolescent girls in the city of Mwanza are naturally immune to Rubella virus. There is a need to compare the effectiveness of screening and vaccinating susceptible adolescent girls with the effectiveness of vaccinating all women of childbearing in controlling CRS in low-income countries.

Prevalence of HIV infection and uptake of HIV/AIDS services among fisherfolk in landing Islands of Lake Victoria, north western Tanzania.

BACKGROUND: New HIV infections in Tanzania have been decreasing, however some populations remain at higher risk. Despite of that, evidence on the magnitude of HIV infection and the associated factors and HIV/AIDS services uptake among fisherfolk in Tanzania are inadequately explored. This study therefore aimed at determining prevalence of HIV infection and utilization of HIV/AIDS services among fishfolk in selected Islands of Lake Victoria for evidence-based interventions. METHODS: Cross-sectional study determining status of HIV infection among fisherfolk (n = 456) and retrospective review of voluntary counselling and testing (VCT) registry (n = 1744) were done in Buchosa and Muleba districts. Structured questionnaire and HIV rapid test kits with the standard testing protocol were used as research tools. RESULTS: A total of 269 (58.9%) male and 187 (41.1%) female fisherfolk were recruited during the community survey. Prevalence of HIV infection was 14% in all surveyed landing sites with a site variation from as low as 7.2% to as high as 23.8%. Participants employed in fishing related employment had higher odds of being HIV infected (5.4 times) than those who practiced fishing and partly farming [OR = 5.40; 95%CI 1.88-15.61; p < 0.001]. Participants employed in fishing related employment had higher odds of being HIV infected (5.4 times) than those practiced fishing and farming [OR = 5.40; 95%CI 1.88-15.61; P < 0.001]. Lack of formal education [aOR = 3.37; 95%CI 1.64-6.92; p < 0.001], being older [aOR = 1.06; 95%CI 1.03-1.09] and using alcohol [aOR = 2.26; 95%CI 1.23-4.15] predicted the likelihood of contracting HIV infection. Approximately three quarters (76%) of respondents had ever tested for HIV infection within past 1 year. Moreover, about half of the study participants had used condom inconsistently and 5 out of 14 (37.5%) of participants who knew their status had never started treatment. Despite the low uptake of most HIV preventive services, majority (88%) of male fisherfolk were circumcised. CONCLUSION: The magnitude of HIV infection among fisherfolk was up to 3 times higher than that of the general populations in Muleba and Buchosa districts. Higher age, using alcohol and lack of formal education predicted increased likelihood of HIV infection. The uptake of key HIV/AIDS curative and preventive services was generally low.

The magnitude and correlates of Parvovirus B19 infection among pregnant women attending antenatal clinics in Mwanza, Tanzania.

BACKGROUND: Human parvovirus B19 (B19) infection has been associated with congenital infection which may result into a number of the adverse pregnancy outcomes. The epidemiology and the magnitude of B19 infections among pregnant women have been poorly studied in developing countries. This study was done to establish preliminary information about the magnitude of B19 among pregnant women attending antenatal clinics in the city of Mwanza, Tanzania. METHODS: A cross-sectional study was conducted between December 2014 and June 2015 among 258 pregnant women attending two antenatal clinics representing rural and urban areas in the city of Mwanza. Socio-demographic data were collected using structured data collection tool. Specific B19 IgM and IgG antibodies were determined using indirect enzyme linked immunosorbent assay kits (DRG Instruments GmbH, Germany). Data were analyzed using STATA version 11 software. RESULTS: The median age of study participants was 21 IQR (19-25) years. Of 253 pregnant women; 116(44.96%), 109(42.25%) and 33(12.79%) were in the first, second and third trimester respectively. The majority 168(66.4%) of women were from urban areas. Of 253 pregnant women, the overall prevalence of IgM was 83(32.8%) while that of IgG was 142(55.0%) among 258 women tested. A total of 50(19.4%) women were positive for both IgG and IgM indicating true IgM positive. History of baby with low birth weight (OR: 10, 95% CI: 1.82-58.05, P = 0.01) was independent predictor of B19 IgG seropositivity and being at the third trimester was protective (OR: 0.38, 95% CI: 0.16-0.92, P = 0.03). The IgG titers were found to decrease significantly as gestational age increases (Spearman's rho = -0.2939, p = 0.0004) CONCLUSION: More than a half of pregnant women in Mwanza city are B19 IgG sero-positive with about one third of these being B19 IgM seropositive. Further studies to determine the impact of B19 infections among pregnant women and their newborns are recommended in developing countries.

Aspergillus fumigatus carrying TR34/L98H resistance allele causing complicated suppurative otitis media in Tanzania: Call for improved diagnosis of fungi in sub-Saharan Africa.

BACKGROUND: Suppurative otitis media (SOM) is a major public health concern worldwide and is associated with increased morbidity. Cases of fungal suppurative otitis media were studied to establish the effect of fungi in otitis media. METHODS: Ear swabs from 410 patients were collected aseptically using sterile cotton swabs from discharging ear through perforated tympanic membrane. Swabs were subjected to microscopic and culture investigations. The species of fungal growing on Sabouraud's agar were identified using MALDI-TOF MS. For moulds broth micro dilution method following EUCAST guidelines was employed to determine susceptibility patterns against itraconazole, voriconazole and posaconazole. RESULTS: A total of 44 (10.74 %) cases with positive fungal culture growth were studied. The median age of patients with fungal infection was 29.5 (IQR 16-43) years. Of 44 patients; 35 (79.6 %) had pure growth of one type of fungal. Candida albicans was the most common fungus isolated (n = 13; 29.6 %) followed by Aspergillus versicolor (n = 8; 18.2 %). A total of 7 (15.9 %) patients had disease complication at time of enrollment; of them 6 (13.6 %) had hearing loss. On follow up 7 (15.9 %) had poor treatment outcome. All five Aspergillus fumigatus strains resistant itraconazole with reduced susceptibility to voriconazole and posaconazole carried carrying TR34/L98H resistance allele. In addition, all Penicillium citrinum isolates were resistant to voriconazole while all Penicillium sumatrense were resistant to both itraconazole and voriconazole. There were non-significant association of poor treatment outcome and female gender, being HIV positive and being infected with moulds. CONCLUSION: Fungal infections play a significant role in SOM pathology in our setting. Diagnosis of fungal infections in developing countries should be improved so that appropriate management can be initiated on time to prevent associated complications.

Predictors of blaCTX-M-15 in varieties of Escherichia coli genotypes from humans in community settings in Mwanza, Tanzania.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae commonly cause infections worldwide. Bla CTX-M-15 has been commonly detected in hospital isolates in Mwanza, Tanzania. Little is known regarding the faecal carriage of ESBL isolates and bla CTX-M-15 allele among humans in the community in developing countries. METHODS: A cross-sectional study involving 334 humans from the community settings in Mwanza City was conducted between June and September 2014. Stool specimens were collected and processed to detect ESBL producing enterobacteriaceae. ESBL isolates were confirmed using disc approximation method, commercial ESBL plates and VITEK-2 system. A polymerase chain reaction and sequencing based allele typing for CTX-M ESBL genes was performed to 42 confirmed ESBL isolates followed by whole genome sequence of 25 randomly selected isolates to detect phylogenetic groups, sequence types plasmid replicon types. RESULTS: Of 334 humans investigated, 55 (16.5 %) were found to carry ESBL-producing bacteria. Age, history of antibiotic use and history of admission were independent factors found to predict ESBL-carriage. The carriage rate of ESBL-producing Escherichia coli was significantly higher than that of Klebsiella pneumoniae (15.1 % vs. 3.8 %, p = 0.026). Of 42 ESBL isolates, 37 (88.1 %) were found to carry the bla CTX-M-15 allele. Other transferrable resistance genes were aac(6')Ib-cr, aac(3)-IIa, aac(3)-IId, aadA1, aadA5, strA, strB and qnrS1. Eight multi-locus sequence types (ST) were detected in 25 E. coli isolates subjected to genome sequencing. ST-131 was detected in 6 (24 %), ST-38 in 5 (20 %) and 5 (20 %) clonal complex - 10(ST-617, ST-44) of isolates. The pathogenic phylogenetic groups D and B2 were detected in 8/25 (32 %) and 6/25 (24 %) of isolates respectively. BlaCTX-M-15 was found to be located in multiple IncY and IncF plasmids while in 13/25(52 %) of cases it was chromosomally located. CONCLUSION: The overlap of multi-drug resistant bacteria and diversity of the genotypes carrying CTX-M-15 in the community and hospitals requires an overall approach that addresses social behaviour and activity, rationalization of the antibiotic stewardship policy and a deeper understanding of the ecological factors that lead to persistence and spread of such alleles.

Predictors of disease complications and treatment outcome among patients with chronic suppurative otitis media attending a tertiary hospital, Mwanza Tanzania.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a major health problem in developing countries causing hearing loss and life threatening complications. Early and effective treatment based on the knowledge of causative micro-organisms and predictors of outcome are crucial in preventing these associated complications. This study was conducted to determine the predictors of CSOM complications, treatment outcome and antimicrobial susceptibility of pathogens, thus providing essential evidence to formulate a policy for management of CSOM. METHODS: This was a prospective hospital based cross sectional study involving 301 patients attending Ear Nose and Throat (ENT) clinics at Bugando Medical Centre (BMC) between October 2013 and March 2014. A standardized data collection tool was used to collect demographics and clinical characteristics of patients with CSOM. Ear swabs were collected using sterile cotton swabs and transported to the laboratory for culture and antibiotic susceptibility testing. RESULTS: Out of 301 patients with CSOM; 187 (62.1 %) had positive aerobic culture within 48 h of incubation. Disease complications and poor treatment outcome were observed in 114 (37.8 %, 95 % CI; 32.2-43.3) and 46 (15.3 %, 95 % CI; 11.2-19.3) respectively. On multivariate logistic regression analysis factors found independently to predict both disease complications and poor treatment outcome were otalgia, being infected by multi drug resistant bacteria and being HIV positive. Prolonged illness duration before seeking medical attention was also found to be associated with disease complications (OR 1.029, 95 % CI 1.007-1.05, p = 0.01). A total of 116 (61 %) of gram negative bacteria were isolated. Of 34 Staphylococcus aureus, 14 (41 %) were found to be methicillin resistant Staphylococcus aureus (MRSA) while of 116 g negative enteric bacteria, 49 (42 %) were extended spectrum beta lactamases producers (ESBL). CONCLUSIONS: Findings of this study suggest that positive HIV status, infection due to multidrug resistant pathogens and otalgia are significantly associated with disease complications and poor treatment outcome. Of great importance this study confirms that prolonged illness duration without seeking medical attention significantly predicts disease complications. Urgent preventive measures and laboratory guided early treatment are necessary to reduce complications associated with CSOM.

Sero-conversion rate of Syphilis and HIV among pregnant women attending antenatal clinic in Tanzania: a need for re-screening at delivery.

BACKGROUND: Despite the available cost effective antenatal testing and treatment, syphilis and human immunodeficiency virus (HIV) are still among common infections affecting pregnant women especially in developing countries. In Tanzania, pregnant women are tested only once for syphilis and HIV during antenatal clinic (ANC) visits. Therefore, there are missed opportunities for syphilis and HIV screening among those who were not tested during ANC visits and those acquiring infections during the course of pregnancy. This study was designed to determine the syphilis and HIV seroprevalence at delivery and seroconversion rate among pregnant women delivering at Bugando Medical Centre (BMC). METHODS: A cross sectional, hospital-based study involving pregnant women attending Bugando Medical Centre (BMC) antenatal clinic was done from January to March 2012. Serum samples were collected and tested for HIV and syphilis using HIV and syphilis rapid tests. Demographic and clinical data were collected using a standardized data collection tool and analysed using STATA version 11. RESULTS: A total of 331 and 408 women were screened for syphilis and HIV during antenatal respectively. Of 331 women who screened negative for syphilis at ANC, nine (2.7%) were seropositive at delivery while of 391who tested negative for HIV during ANC eight (2%) were found to be positive at delivery. Six (1.8%) and 23 (9%) of women who did not screen for syphilis and HIV at ANC were seropositive for syphilis and HIV at delivery respectively. There was significant difference of seroprevalence for HIV, among women who tested negative at ANC and those who did not test at ANC (2% vs.9%, P,<0.001). The overall prevalence of syphilis and HIV at delivery was 15 (2.3%) and 48 (7.2%) respectively. Syphilis seropositivity at delivery was significantly associated with HIV co-infection (p < 0.001), male partner circumcision (p = 0.011) and alcohol use among women (p < 0.001). CONCLUSIONS: The current protocol of screening for syphilis and HIV only once during pregnancy as practiced in Tanzania may miss women who get re-infected and seroconvert during pregnancy. Re-screening for syphilis and HIV during the course of pregnancy and at delivery is recommended in Tanzania as it can help to identify such women and institute appropriate treatment.

Utility of qualitative C- reactive protein assay and white blood cells counts in the diagnosis of neonatal septicaemia at Bugando Medical Centre, Tanzania.

BACKGROUND: Neonatal septicaemia diagnosis based on clinical features alone is non-specific leading to the initiation of unnecessary antibiotic treatment posing a danger of increased antibiotic resistance. In the present study the utility of serial qualitative C-reactive protein (CRP) assay and white blood cells count (WBC) in the diagnosis of neonatal septicaemia was investigated using blood culture as gold standard. METHODS: A total of 305 neonates admitted at Bugando Medical Centre (BMC) neonatal units between September 2013 and April 2014 were enrolled. Demographic and clinical data were collected using standardized data collection tool. Blood specimens were collected for blood culture, WBC count and qualitative CRP assay. RESULTS: Of 305 neonates; 224 (73.4%) were ≤ 72 hrs of age and 91(29.8%) had low birth weight. The positive CRP assay was observed in 67 (22.0%), 80 (26.2%) and 88 (28.9%) of neonates on day 1, 2 and 3 respectively; with any CRP positive occurred in 104 (34.1%) of neonates. The sensitivities of CRP assay in the diagnosis of septicaemia using culture as gold standard on day 1, 2, 3 and any positive were 40.4%, 53.2%, 54.8% and 62.9% respectively. While specificities were 82.7%, 80.7%, 77.8% and 73.3% respectively. Higher sensitivity of 75% was observed when CRP was used to diagnose gram negative septicaemia compared to 50% that was observed in the diagnosis of gram positive septicaemia. WBC count of ≥13 × 109 /L had sensitivity and specificity of 64.5% and 66.7% respectively with area under the curve of 0.694. When the any positive CRP and WBC of ≥13 × 109 /L were used the sensitivity increased to 90.3% with specificity of 50%. Neonates with septicaemia due to gram negative bacteria were significantly found to have higher rates of positive CRP than neonates with gram positive septicaemia and with negative culture (p < 0.001, OR 8.2, 95 CI; 2.9-26). CONCLUSION: In place where blood culture is limited neonates having clinical features of neonatal sepsis with positive qualitative CRP assay and increased WBC should urgently be initiated on appropriate sepsis management in order to reduce morbidity and mortality associated with neonatal sepsis.

Treatment seeking and antibiotic use for urinary tract infection symptoms in the time of COVID-19 in Tanzania and Uganda.

Background: There is still little empirical evidence on how the outbreak of coronavirus disease 2019 (COVID-19) and associated regulations may have disrupted care-seeking for non-COVID-19 conditions or affected antibiotic behaviours in low- and middle-income countries (LMICs). We aimed to investigate the differences in treatment-seeking behaviours and antibiotic use for urinary tract infection (UTI)-like symptoms before and during the pandemic at recruitment sites in two East African countries with different COVID-19 control policies: Mbarara, Uganda and Mwanza, Tanzania. Methods: In this repeated cross-sectional study, we used data from outpatients (pregnant adolescents aged >14 and adults aged >18) with UTI-like symptoms who visited health facilities in Mwanza, Tanzania and Mbarara, Uganda. We assessed the prevalence of self-reported behaviours (delays in care-seeking, providers visited, antibiotics taken) at three different time points, labelled as 'pre-COVID-19 phase' (February 2019 to February 2020), 'COVID-19 phase 1' (March 2020 to April 2020), and 'COVID-19 phase 2' (July 2021 to February 2022). Results: In both study sites, delays in care-seeking were less common during the pandemic than they were in the pre-COVID phase. Patients in Mwanza, Tanzania had shorter care-seeking pathways during the pandemic compared to before it, but this difference was not observed in Mbarara, Uganda. Health centres were the dominant sources of antibiotics in both settings. Over time, reported antibiotic use for UTI-like symptoms became more common in both settings. During the COVID-19 phases, there was a significant increase in self-reported use of antibiotics like metronidazole (<30% in the pre-COVID-19 phase to 40% in COVID phase 2) and doxycycline (30% in the pre-COVID-19 phase to 55% in COVID phase 2) that were not recommended for treating UTI-like symptoms in the National Treatment Guidelines in Mbarara, Uganda. Conclusions: There was no clear evidence that patients with UTI-like symptoms attending health care facilities had longer or more complex treatment pathways despite strict government-led interventions related to COVID-19. However, antibiotic use increased over time, including some antibiotics not recommended for treating UTI, which has implications for future antimicrobial resistance.

Predominance of multidrug-resistant bacteria causing urinary tract infections among symptomatic patients in East Africa: a call for action.

Background: In low- and middle-income countries, antibiotics are often prescribed for patients with symptoms of urinary tract infections (UTIs) without microbiological confirmation. Inappropriate antibiotic use can contribute to antimicrobial resistance (AMR) and the selection of MDR bacteria. Data on antibiotic susceptibility of cultured bacteria are important in drafting empirical treatment guidelines and monitoring resistance trends, which can prevent the spread of AMR. In East Africa, antibiotic susceptibility data are sparse. To fill the gap, this study reports common microorganisms and their susceptibility patterns isolated from patients with UTI-like symptoms in Kenya, Tanzania and Uganda. Within each country, patients were recruited from three sites that were sociodemographically distinct and representative of different populations. Methods: UTI was defined by the presence of >104 cfu/mL of one or two uropathogens in mid-stream urine samples. Identification of microorganisms was done using biochemical methods. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion assay. MDR bacteria were defined as isolates resistant to at least one agent in three or more classes of antimicrobial agents. Results: Microbiologically confirmed UTI was observed in 2653 (35.0%) of the 7583 patients studied. The predominant bacteria were Escherichia coli (37.0%), Staphylococcus spp. (26.3%), Klebsiella spp. (5.8%) and Enterococcus spp. (5.5%). E. coli contributed 982 of the isolates, with an MDR proportion of 52.2%. Staphylococcus spp. contributed 697 of the isolates, with an MDR rate of 60.3%. The overall proportion of MDR bacteria (n = 1153) was 50.9%. Conclusions: MDR bacteria are common causes of UTI in patients attending healthcare centres in East African countries, which emphasizes the need for investment in laboratory culture capacity and diagnostic algorithms to improve accuracy of diagnosis that will lead to appropriate antibiotic use to prevent and control AMR.

Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda.

Antibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviour, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce. The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Using data from 6,388 patients, we analysed patterns of self-reported treatment seeking behaviours ('patient pathways') using process mining and single-channel sequence analysis. Among those with microbiologically confirmed UTI (n = 1,946), we used logistic regression to assess the relationship between treatment seeking behaviour, AB use, and the likelihood of having a multi-drug resistant (MDR) UTI. The most common treatment pathway for UTI-like symptoms in this sample involved attending health facilities, rather than other providers like drug sellers. Patients from sites in Tanzania and Uganda, where over 50% of patients had an MDR UTI, were more likely to report treatment failures, and have repeat visits to providers than those from Kenyan sites, where MDR UTI proportions were lower (33%). There was no strong or consistent relationship between individual AB use and likelihood of MDR UTI, after accounting for country context. The results highlight the hurdles East African patients face in accessing effective UTI care. These challenges are exacerbated by high rates of MDR UTI, suggesting a vicious cycle of failed treatment attempts and sustained selection for drug resistance. Whilst individual AB use may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of variations in ABR.

Comparison of Horizontal blaCTX-M Gene Transfer via Conjugation among Extended Spectrum ß-Lactamases Producing Escherichia coli Isolates from Patients with Urinary Tract Infection, Their Animals, and Environment.

Background: The dissemination of the extended spectrum ß-lactamases (ESBL) producing E. coli poses a significant public health problem. Understanding the efficiency and frequency of horizontal gene transfer via conjugation of ESBL producing E. coli is imperative towards devising prevention and control measures. This study compared the frequencies and efficiencies of horizontal blaCTX-M gene transfer via conjugation among Escherichia coli isolates from urine and gastrointestinal tract (GIT) of patients with urinary tract infection (UTI), their animals and environment. Methods: Horizontal blaCTX-M gene transfer via conjugation by a broth mating experiment was performed using 50 confirmed ESBL producing E. coli isolates as donors and Escherichia coli J53 (F-, met, pro, Azr), as the recipient. The transconjugants were detected and their frequencies and efficiencies of conjugation were measured and compared between ESBL producing E. coli isolates multi-sourced from urine, GIT, animals and environment. Antimicrobial susceptibility testing of all resulting transconjugants was performed. DNA was extracted from all transconjugants to confirm the presence and the acquisition of blaCTX-M gene. Results: Out of 50 ESBL producing E. coli isolates harboring blaCTX-M gene, 37 (74.0%) successfully exercised horizontal gene transfer through conjugation. All transconjugants were confirmed phenotypically and genotypically by PCR. Of note, all of the isolates from environment 100.0% (7/7) performed conjugation, exhibiting the highest transfer efficiency, followed by isolates from urine and animals, with the conjugation transfer efficiency of 77.8% (14/18) and 76.1% (10/13), respectively. The isolates from the environment conjugated with a significant more efficiency than those from the GIT [Two-sample test of proportions; p-value = 0.0119]. The overall conjugation transfer frequencies ranged from 0.4 × 10-14 - 5.5 × 10-11 per donor cells with the highest median conjugation transfer frequency observed among isolates from animal (3.23 × 10-12 [IQR: 0.70 × 10-12 - 7.22 × 10-12]) followed by that of isolates from the environment (1.60 × 10-12 [IQR: 0.30 × 10-12 - 5.0 × 10-12]). Conclusion: ESBL producing E. coli from human, animals and environment exercises horizontal blaCTX-M gene transfer efficiently with the highest occurrence among isolates from the environment and animals. The antimicrobial resistance control and prevention strategies should be widened up to explore strategies to prevent horizontal AMR gene transfer.

Neonatal infection in Sub-Saharan Africa: a cross-sectional pilot study on bacterial pathogens and maternal risk factors.

Introduction: Although child morbidity and mortality could be reduced in Sub-Saharan Africa during the last years both remain high. Since neonatal infections play a major role, we conducted a cross-sectional pilot study in the lake region of Western Tanzania in order to analyze not only the prevalence of neonatal infection with its bacterial etiology including antimicrobial resistance pattern but also to detect potential maternal risk factors. Methods: We screened 156 women for potential risk factors and examined their neonates for clinical signs of an infection including microbiological verification. All women were interviewed for medical history and their socio-economic background. High-vaginal swabs (HVS) of pregnant women and blood cultures of sick infants were investigated for bacterial pathogens using culture followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) or polymerase-chain-reaction (PCR)-based assays. Antimicrobial resistances were determined using a disk diffusion test and verified by VITEK 2. Maternal malaria, blood glucose, and hemoglobin levels were determined by rapid tests and helminth infections by stool microscopy. Results and discussion: Our results showed a prevalence of 22% for neonatal infections. In total, 57% of them had culture-positive bloodstream infections with Gram-negative bacteria being the most prevalent. All these expressed resistance against ampicillin. The prevalence of maternal infection with helminths or Plasmodium was low, indicating that anti-worming strategies and intermittent preventive treatment of malaria for pregnant women (IPTp) are effective. The study identified maternal urinary tract infection (UTI) and an elevated blood glucose level as potential maternal risk factors for early neonatal infection, an elevated blood glucose level, and maternal anemia for a late-onset infection. Conclusion: Our study, therefore, indicates that monitoring maternal UTI in the last trimester as well as levels of maternal hemoglobin and blood glucose might be important to predict and eventually manage neonatal infections. As Gram-negative bacteria with resistance to ampicillin were most prevalent in culture-proven neonatal sepsis, WHO recommendations for calculated antibiosis in the sick young infant should be discussed.

A Point Prevalence Survey of Antimicrobial Use at Geita Regional Referral Hospital in North-Western Tanzania.

We conducted a point prevalence survey (PPS) to determine the prevalence of antibiotic use at Geita Regional Referral Hospital (GRRH) located along the shores of Lake Victoria in north-western Tanzania. This has led to the identification of gaps for improvement. This PPS study was conducted on 9-10 March 2023. Patient-related information, including sociodemographic and clinical data, was collected from medical records. STATA software version 15.0 was used to perform descriptive data analysis. About 94.8% (55/58) patients were on antibiotics with a mean (±SD) prescription of 2 (±0.5) antibiotic agents ranging from 1 to 4 different agents. The commonest indications of the antibiotic prescription were medical prophylaxis 47.3% (26/55) followed by empiric treatment 41.8% (23/55). In total, 110 prescriptions were made, of which metronidazole (25.5%; n = 28), ceftriaxone (23.6%; n = 26), and ampicillin-cloxacillin (23.6%; n = 26) were frequently observed. Only 67.3% (n = 74) of prescriptions complied with Tanzania Standard Treatment Guidelines. Moreover, according to the WHO-AWaRe classification, 50.9%, 23.6%, and 25.5% were under the Access category, Watch category, and Not Recommended category, respectively. The prevalence of antibiotic use among patients admitted to GRRH was high, whereby medical prophylaxis and empiric treatment were the commonest indications for antibiotic prescription. To support rational therapy and antimicrobial stewardship initiatives, we recommend that laboratories in regional hospitals be equipped to conduct sustained routine culture and antimicrobial susceptibility testing.

Efficacy of disinfectants on control and clinical bacteria strains at a zonal referral hospital in Mwanza, Tanzania: a cross sectional hospital-based study.

Contaminated-hospital surfaces are an important source of pathogenic bacteria causing health-care associated infection (HCAIs). Monitoring the performance of disinfectants that are routinely used to clean hospital surfaces is critical for prevention and control of HCAIs. Nevertheless, the evaluation of the performance of disinfectants and their efficacy are not routinely practiced in most resource-limited countries. This study was designed to determine the efficacy of sodium dichloroisocyanurate (NaDCC) and chloroxylenol against American Type Culture Collection (ATCC) and their respective multidrug resistant (MDR) strains causing neonatal sepsis at a zonal referral hospital in Mwanza, Tanzania. Four ATCC (n = 4) and their respective MDR strains of Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were used. The suspension test was used with contact time of 1, 5 and 10 min with starting concentration of 105 bacterial colony forming unit per milliliters (CFU/mL). The log10 reduction value at specified bacteria-disinfectant contact time was used to assess the efficacy of 0.5%NaDCC and 4.8% chloroxylenol in-use and freshly prepared solutions. In-use 0.5%NaDCC demonstrated poor log reduction (˂ 5log) against MDR-clinical isolates. Freshly laboratory prepared 0.5% NaDCC had 100% microbial reduction at 1, 5 and 10 min of both ATCC and MDR strains up to 48 h after preparation when compared with freshly prepared 4.8% chloroxylenol (˂ 5log). Freshly, prepared 0.5% NaDCC should be used in health-care facilities for effective disinfection practices.