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Background: Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania. Methods: Plasmodium falciparum samples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-α, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites. Results: Overall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for ≥ 50.0% of the markers), and > 50.0% of the samples (range = 47.6–59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (RS = 7.48, range = 7.27–8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (He = 0.83, range = 0.80–0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (FST) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-α was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic. Conclusion: Microsatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-α, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-α alone or with any of the other three markers could be adopted for use in TES in Tanzania. [ABSTRACT FROM AUTHOR]

Background: Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. Methods: A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). Results: Sequencing success was ≥ 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. Conclusion: This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT. [ABSTRACT FROM AUTHOR]

High‐throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up‐to‐date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high‐burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania countrywide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome‐wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, approximately separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from nearby districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts (including two infections carrying pfk13‐R561H), and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region‐level complexity‐of‐infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared. [ABSTRACT FROM AUTHOR]

Objectives: Tanzania has the third highest birth rate of sickle cell anaemia (SCA) in Africa, but few studies describe severity of complications or available treatments, especially in Northwest Tanzania around Lake Victoria where the sickle gene is most prevalent. This is a report of the spectrum of clinical disease and range of interventions available at Bugando Medical Centre (Bugando) in Northwest Tanzania in Africa. Methods: A cross-sectional study was carried out in Bugando between 1 August 2012 and 30 September 2012. Children (<15 years old) with SCA attending Bugando were sequentially enrolled. A trained research assistant completed a Swahili questionnaire with the parent or guardian of each participant concerning demographic information, clinical features of disease, and treatments received. Results: Among the 124 participants enrolled, the median age was 6 years (interquartile range [IQR] 4–8.5), and only 13 (10.5%) were < 3 years old. Almost all participants (97.6%) had a prior history of a vaso-occlusive episode, 83 (66.9%) had prior acute chest syndrome, and 21 (16.9%) had prior stroke. In the preceding 12 months, 120 (96.8%) had been hospitalized, and a vaso-occlusive episode was the most common reason for hospitalization (35.5%). Prescriptions for folic acid (92.7%) and malaria prophylaxis (84.7%) were common, but only one had received a pneumococcal vaccine, and none had received hydroxyurea or prophylactic penicillin. Conclusion: Children with SCA receiving care in Tanzania are diagnosed late, hospitalized frequently, and have severe complications. Opportunities exist to improve care through wider access to screening and diagnosis as well as better coordination of comprehensive care. [ABSTRACT FROM PUBLISHER]

Background: Strong health laboratory systems and networks capable of providing high quality services are critical components of the health system and play a key role in routine diagnosis, care, treatment and disease surveillance. This study aimed to assess the readiness of the national health laboratory system (NHLS) and its capacity to support care and treatment of HIV/AIDS in Tanzania. Methods: A documentary review was performed to assess the structure of the health system with reference to the status and capacity of the NHLS to support HIV diagnosis. Key informant interviews were also held with laboratory staff in all levels of the health care delivery system in four regions with different levels of HIV prevalence. Information sought included availability and utilization of laboratory guidelines, quality and the capacity of laboratories for diagnosis of HIV. Results: The findings indicate that a well-established NHLS was in place. However, the coordination of HIV laboratory services was found to be weak. Forty six respondents were interviewed. In most laboratories, guidelines for HIV diagnosis were available but health care providers were not aware of their availability. Utilization of the guidelines for HIV diagnosis was higher at national level than at the lower levels. The low level of awareness and utilization of guidelines was associated with inadequate training and supervision. There was a shortage of human resource, mostly affecting the primary health care level of the system and this was associated with inequity in employment and training opportunities. Laboratories in public health facilities were better staffed and had more qualified personnel than private-owned laboratories. Conclusion: Tanzania has a well established national health laboratory network sufficient to support HIV care and treatment services. However, laboratories at the primary health care level are constrained by inadequate resources and operate within a limited capacity. Improving the laboratory capacity in terms of number of qualified personnel, staff training on the national guidelines, laboratory diagnostic tools and coordination should be given a higher priority. [ABSTRACT FROM AUTHOR]

Highlights: [•] Malaria is commonly misdiagnosed in Tanzania. [•] More than 80% of adults with suspected malaria did not have malaria. [•] The agreement between routine malaria BS and RDT was only fair. [•] Malaria PCR generally agreed with rapid malaria diagnostic tests. [•] HIV infection was associated with delayed malaria parasite clearance. [Copyright &y& Elsevier]

Introduction: Rotavirus infections frequently cause acute gastroenteritis in humans and are the most important cause of severe dehydrating diarrhea in young children in both developed and developing countries. Methodology: This was a prospective cross-sectional, hospital-based study on 300 children ≤ 5 years with acute watery diarrhea who attended Bugando Medical Centre (BMC) and Nyamagana District hospital between May and November 2009. Stool specimens were tested for rotavirus infection using latex agglutination test. Data were cleaned and analyzed using SPSS 11.0. Results: Of 300 children with acute watery diarrhea, 136 (45.3%) were female and the mean age was 12.63 months (SD = 10.4). Sixty-two (20.7%) children were found to have rotavirus infection. Of children with severe malnutrition three (37.5%) were infected with rotavirus. Fifty-two (84%) of children with rotavirus infection were below two years of age. Severe dehydration was present in 48 (16%) children of whom 12 (25%) were infected with rotavirus compared to 18 (16.6%) of 109 children with no dehydration. Living next door to a child with diarrhea was highly associated with rotavirus infection (43% versus 19%; p = 0.036). The mean hospital stay among children with rotavirus infection was 3.66 days versus 2.5 days for those without rotavirus (p = 0.005). Conclusion: Rotavirus infection is prevalent in Mwanza region and contributes to prolonged hospital stay. Proper education on hygiene to control diarrheal diseases among children should be emphasized. Extensive studies to determine the serotypes of rotavirus are warranted in the region before rotavirus vaccine is introduced. [ABSTRACT FROM AUTHOR]

Background: Skin cancers are a major risk associated with albinism and are thought to be a major cause of death in African albinos. The challenges associated with the care of these patients are numerous and need to be addressed. The aim of this study was to outline the pattern and treatment outcome of skin cancers among albinos treated at our centre and to highlight challenges associated with the care of these patients and proffer solutions for improved outcome. Methods: This was a retrospective study of all albinos with a histopathological diagnosis of skin cancer seen at Bugando Medical Centre from March 2001 to February 2010. Data collected were analyzed using descriptive statistics. Results: A total of 64 patients were studied. The male to female ratio was 1.5:1. The median age of patients was 30 years. The median duration of illness at presentation was 24 months. The commonest reason for late presentation was financial problem. Head and the neck was the most frequent site afflicted in 46(71.8%) patients. Squamous cell carcinoma was the most common histopathological type in 75% of cases. Surgical operation was the commonest modality of treatment in 60 (93.8%) patients. Radiotherapy was given in 24(37.5%) patients. Twenty-seven (42.2%) of the patients did not complete their treatment due to lack of funds. Local recurrence following surgical treatment was recorded in 6 (30.0%) patients. Only thirty-seven (61.7%) patients were available for follow-up at 6-12 months and the remaining patients were lost to follow-up. Conclusions: Skin cancers are the most common cancers among albinos in our environment. Albinism and exposure to ultraviolet light appears to be the most important risk factor in the development of these cancers. Late presentation and failure to complete treatment due to financial difficulties and lack of radiotherapy services at our centre are major challenges in the care of these patients. Early institution of preventive measures, early presentation and treatment, and follow-up should be encouraged in this population for better outcome. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance. Methods: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440–600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively. Results: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene. Conclusion: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631 [ABSTRACT FROM AUTHOR]

Introduction: Although there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. Methodology: In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. Results: Despite considerable genetic diversity, the spa types t690 (29.1%) and t7231 (41.6%), as well as the sequence types (ST) 88 (54.2%) and 1797 (29.1%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8%, 62.5%, 41.6%, 45.8% and 50% of the strains, respectively. Conclusion: We present the first thorough typing of MRSA at a Tanzanian hospital. Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures. [ABSTRACT FROM AUTHOR]