Paroxysmal Kinesigenic Dyskinesia: First Molecularly Confirmed Case from Africa

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder, with an excellent response to carbamazepine treatment. It has been described in various populations, but not yet in an African population. Case report: In a patient who reported to clinic with side effects of carbamazepine, PRRT2 gene screening was performed based on a clinical history compatible with PKD. A common PRRT2 mutation was identified in this patient, hereby the first genetically confirmed PRRT2-associated PKD in Africa. Discussion: Reporting genetic confirmation of an unusual movement disorder from an equally unusual location shows the wide geographical distribution of PRRT2-associated disease. It also illustrates recognizability of this treatable disorder where the easiest accessible diagnostic tool is neurological history and examination

Diagnosis and Interim Treatment Outcomes from the First Cohort of Multidrug-Resistant Tuberculosis Patients in Tanzania.

Kibong'oto National Tuberculosis Hospital (KNTH), Kilimanjaro, Tanzania. Characterize the diagnostic process and interim treatment outcomes from patients treated for multidrug-resistant tuberculosis (MDR-TB) in Tanzania. A retrospective cohort study was performed among all patients treated at KNTH for pulmonary MDR-TB between November 2009 and September 2011. Sixty-one culture-positive MDR-TB patients initiated therapy, 60 (98%) with a prior history of TB treatment. Forty-one (67%) were male and 9 (14%) were HIV infected with a mean CD4 count of 424 (±106) cells/µl. The median time from specimen collection to MDR-TB diagnosis and from diagnosis to initiation of MDR-TB treatment was 138 days (IQR 101-159) and 131 days (IQR 32-233), respectively. Following treatment initiation four (7%) patients died (all HIV negative), 3 (5%) defaulted, and the remaining 54 (89%) completed the intensive phase. Most adverse drug reactions were mild to moderate and did not require discontinuation of treatment. Median time to culture conversion was 2 months (IQR 1-3) and did not vary by HIV status. In 28 isolates available for additional second-line drug susceptibility testing, fluoroquinolone, aminoglycoside and para-aminosalicylic acid resistance was rare yet ethionamide resistance was present in 9 (32%). The majority of MDR-TB patients from this cohort had survived a prolonged referral process, had multiple episodes of prior TB treatment, but did not have advanced AIDS and converted to culture negative early while completing an intensive inpatient regimen without serious adverse event. Further study is required to determine the clinical impact of second-line drug susceptibility testing and the feasibility of alternatives to prolonged hospitalization

Hospital Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Tertiary Care Hospital in Moshi, Tanzania, as Determined by Whole Genome Sequencing

Objective. To determine molecular epidemiology of methicillin-resistant S. aureus in Tanzania using whole genome sequencing. Methods. DNA from 33 Staphylococcus species was recovered from subcultured archived Staphylococcus isolates. Whole genome sequencing was performed on IlluminaMiseq using paired-end 2x250 bp protocol. Raw sequence data were analyzed using online tools. Results. Full susceptibility to vancomycin and chloramphenicol was observed. Thirteen isolates (43.3%) resisted cefoxitin and other antimicrobials tested. Multilocus sequence typing revealed 13 different sequence types among the 30 S. aureus isolates, with ST-8 (n = seven, 23%) being the most common. Gene detection in S. aureus stains were as follows: mecA, 10 (33.3%); pvl, 5 (16.7%); tst, 2 (6.7%). The SNP difference among the six Tanzanian ST-8MRSA isolates ranged from 24 to 196 SNPs and from 16 to 446 SNPs when using the USA300_FPR3757 or the USA500 2395 as a reference, respectively. The mutation rate was 1.38 x 10(-11) SNPs/site/year or 1.4 x 10(-6) SNPs/site/year as estimated by USA300 FPR3757 or the USA500 2395, respectively. Conclusion. S. aureus isolates causing infections in hospitalized patients in Moshi are highly diverse and epidemiologically unrelated. Temporal phylogenetic analysis provided better resolution on transmission and introduction of MRSA and it may be important to include this in future routines

Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, Northern Tanzania. A case-control study was conducted at Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford University's HIV drug resistance database and REGA subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios (OR) with 95% confidence interval (95% CI) investigated predictors of VF. P-value < 5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF, 61 (49.2%) had VS and 82 (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty-five out of 26 selected samples from cases were successfully sequenced. Twenty-four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside analogue reverse transcriptase inhibitor (NNRTI)-resistance associated mutations as the majority (92%). Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated mutations were M184V (n = 17), K70R (n = 7) and D67N (n = 6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-resistance associated mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Two samples (8%) had at least one mutation associated with protease inhibitor resistance. Age [aOR = 0.94, 95% CI (0.90-0.97), p < 0.001] and occupation [aOR = 0.35, 95% CI (0.12-1.04), p = 0.059] associated with VF. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy. Resistance testing will help to guide switching of HIV drugs

Prevalence, determinants and knowledge of antibacterial self-medication: A cross sectional study in North-eastern Tanzania.

Self-medication is very common especially in developing countries and is documented to be associated with many health risks including antibiotic resistance. This study investigated the prevalence, determinants and knowledge of self-medication among residents of Siha District in Tanzania. A cross-sectional study was conducted among 300 residents in a rural District of Kilimanjaro region, North-eastern Tanzania from 1st to 28th April 2017. A semi-structured questionnaire was used to collect information regarding drugs used, knowledge, history and reasons for antibiotic self-medication. Log-binomial regression analysis was done using STATA 13 to examine factors associated with self-medication. A slightly majority of the respondents (58%) admitted to self-medication. Antibiotics most commonly utilized were amoxycillin (43%) and an antiprotozoal drug metronidazole (10%). The most common symptoms that led to self-medication were cough (51.17%), headache/ fever/ malaria (25.57%) and diarrhoea (21.59%). The most common reasons for self-medication were emergency illness (24.00%), health facility charges (20.33%), proximity of pharmacy to home (17.00%) and no reason (16.66%). Almost all reported that self-medication is not better than seeking medical consultation, 98% can result into harmful effects and 96% can result to drug resistance. The level of self-medication in this study is comparable with findings from other studies in developing countries. Pharmacies were commonly used as the first point of medical care. There is therefore a need for educative antibiotic legislative intervention to mitigate the adverse effects of antibiotic self-medication in Siha district in Tanzania

Enteric Pathogens Detected in Children under Five Years Old Admitted with Diarrhea in Moshi, Kilimanjaro, Tanzania

Despite the availability and wide coverage of rotavirus vaccinations in Tanzania, there is still a significant number of diarrhea cases being reported, with some patients requiring hospital admission. We investigated diarrhea-causing pathogens and determined the effect of co-infection on clinical symptoms. Total nucleic acid was extracted from archived stool samples (N = 146) collected from children (0–59 months) admitted with diarrhea in health facilities in Moshi, Kilimanjaro. Pathogen detection was performed using the quantitative polymerase chain reaction with custom TaqMan Array cards. The Poisson model was used to determine the effect of co-infection on clinical presentation during admission. Of all the participants, 56.85% were from rural Moshi with a median age of 11.74 months (IQR: 7.41–19.09). Vomiting (88.36%) and a fever (60.27%) were the most frequent clinical manifestations. At least one diarrhea-associated pathogen was detected in 80.14% (n = 117) of the study population. The most prevalent pathogens were rotavirus 38.36% (n = 56), adenovirus 40/41 19.86% (n = 29), Shigella/EIEC 12.33% (n = 18), norovirus GII 11.44% (n = 17) and Cryptosporidium 9.59% (n = 14). Co-infections were detected in 26.03% of the study population (n = 38). The presence of multiple pathogens in the stool samples of children with diarrhea indicates poor sanitation and may have significant implications for disease management and patient outcomes

Ceftriaxone use in a tertiary care hospital in Kilimanjaro, Tanzania:A need for a hospital antibiotic stewardship programme

Excessive use of antibiotics, especially watch group antibiotics such as ceftriaxone leads to emergence and spread of antimicrobial resistance (AMR). In low and middle-income countries (LMICs), antibiotics are overused but data on consumption is scarcely available. We aimed at determining the extent and predictors of ceftriaxone use in a tertiary care university teaching hospital in Kilimanjaro, Tanzania. A hospital-based cross-sectional study was conducted from August 2013 through August 2015. Patients admitted in the medical, surgical wards and their respective intensive care units, receiving antimicrobials and other medications for various ailments were enrolled. Socio-demographic and clinical data were recorded in a structured questionnaire from patients' files and logistic regression was performed to determine the predictors for ceftriaxone use. Out of the 630 patients included in this study, 322 (51.1%) patients were on ceftriaxone during their time of hospitalization. Twenty-two patients out of 320 (6.9%) had been on ceftriaxone treatment without evidence of infection. Ceftriaxone use for surgical prophylaxis was 44 (40.7%), of which 32 (72.7%) and 9 (20.5%) received ceftriaxone prophylaxis before and after surgery, respectively. Three (6.8%) received ceftriaxone prophylaxis during surgery. Predicting factors for that the health facility administered ceftriaxone were identified as history of any medication use before referral to hospital [OR = 3.4, 95% CI (1.0-11.4), p = 0.047], bacterial infection [OR = 18.0, 95% CI (1.4-225.7, p = 0.025)], surgical ward [OR = 2.9, 95% CI (0.9-9.4), p = 0.078] and medical wards [OR = 5.0, 95% CI (0.9-28.3), p = 0.070]. Overall, a high ceftriaxone use at KCMC hospital was observed. Antimicrobial stewardship programs are highly needed to monitor and regulate hospital antimicrobial consumption, which in turn could help in halting the rising crisis of antimicrobial resistance

Nanopore sequencing technology for clinical diagnosis of infectious diseases where laboratory capacity is meager: A case report

In resource-limited settings, patients are often first presented to clinical settings when seriously ill and access to proper clinical microbial diagnostics is often very limited or non-existing. On February 16th, 2022 we were on a field trip to test a completely field-deployable metagenomics sequencing set-up, that includes DNA purification, sequencing, and bioinformatics analyses using bioinformatics tools installed on a laptop for water samples, just outside Moshi, Tanzania. On our way to the test site, we were contacted by the nearby Machame hospital regarding a child seriously ill with diarrhea and not responding to treatment. Within the same day, we conducted an onsite metagenomics examination of a fecal sample from the child, and Campylobacter jejuni was identified as the causative agent. The treatment was subsequently changed, with almost immediate improvement, and the child was discharged on February 21st

Comparison of patients that completed intensive phase of MDR-TB therapy to those that died.

*<p>Excludes 3 patients that defaulted.</p>†<p>Excludes 8 patients for whom follow-up sputum culture results unavailable.</p><p>N/a =  not applicable.</p