Search

Background: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations. Methods: Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies. Results: Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles. Conclusion: This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among P. falciparum malaria patients.

Karol J Marwa,1 Anthony Kapesa,2 Erasmus Kamugisha,3 Göte Swedberg4 1Department of Pharmacology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 2Department of Community Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 3Department of Biochemistry, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 4Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, SwedenCorrespondence: Karol J Marwa, Department of Pharmacology, Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania, Tel +255769861421, Email carol_maro@yahoo.com; karoljuliusmarwa@gmail.comBackground: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations.Methods: Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies.Results: Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles.Conclusion: This review reports lack of influence of

Background Sub-Saharan Africa has the highest burden of malaria in the world. Artemisinin-based combination therapies (ACTs) have been the cornerstone in the efforts to reduce the global burden of malaria. In the effort to facilitate early detection of resistance for artemisinin derivatives and partner drugs, WHO recommends monitoring of ACT's efficacy in the malaria endemic countries. The present systematic meta-analysis study summarises the evidence of therapeutic efficacy of the commonly used artemisinin-based combinations for the treatment of uncomplicated P. falciparum malaria in Sub-Saharan Africa after more than a decade since the introduction of the drugs. Methods Fifty two studies carried out from 2010 to 2020 on the efficacy of artemether-lumefantrine or dihydro-artemisinin piperaquine or artesunate amodiaquine in patients with uncomplicated P. falciparum malaria in Sub-Saharan Africa were searched for using the Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. Data was extracted by two independent reviewers. Random analysis effect was performed in STATA 13. Heterogeneity was established using I-2 statistics. Results Based on per protocol analysis, unadjusted cure rates in malaria infected patients treated with artemether-lumefantrine (ALU), artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DHP) were 89%, 94% and 91% respectively. However, the cure rates after PCR correction were 98% for ALU, 99% for ASAQ and 99% for DHP. Conclusion The present meta-analysis reports the overall high malaria treatment success for artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine above the WHO threshold value in Sub-Saharan Africa.

Background. The severity of malaria infection depends on the host, parasite and environmental factors. Merozoite surface protein (msp) diversity determines transmission dynamics, P. falciparum immunity evasion, and pathogenesis or virulence. There is limited updated information on P. falciparum msp polymorphisms and their impact on artemether-lumefantrine treatment outcomes in Tanzania. Therefore, this study is aimed at examining msp genetic diversity and multiplicity of infection (MOI) among P. falciparum malaria patients. The influence of MOI on peripheral parasite clearance and adequate clinical and parasitological response (ACPR) was also assessed. Methods. Parasite DNA was extracted from dried blood spots according to the manufacture's protocol. Primary and nested PCR were performed. The PCR products for both the block 2 region of msp1 and the block 3 regions of msp2 genes and their specific allelic families were visualized on a 2.5% agarose gel. Results. The majority of the isolates, 58/102 (58.8%) for msp1 and 69/115 (60.1%) for msp2, harboured more than one parasite genotypes. For the msp1 gene, K1 was the predominant allele observed (75.64%), whereas R033 occurred at the lowest frequency (43.6%). For the msp2 gene, the 3D7 allele was observed at a higher frequency (81.7%) than the FC27 allele (76.9%). The MOIs were 2.44 for msp1 and 2.27 for msp2 (p = 0.669). A significant correlation between age and multiplicity of infection (MOI) for msp1 or MOI for msp2 was not established in this study (rho = 0.074, p = 0.521 and rho = -0.129, p = 0.261, respectively). Similarly, there was no positive correlation between parasite density at day 1 and MOI for both msp1 (rho = 0.113, p = 0.244) and msp2 (rho = 0.043, p = 0.712). The association between MOI and ACPR was not observed for either msp1 or mps2 (p = 0.776 and 0.296, respectively). Conclusions. This study reports high polyclonal infections, MOI and allelic frequencies for both msp1 and msp2. There was a lack of

Background: Artemisinin based combination therapies (ACTs) have been a cornerstone in the treatment of malaria in the world. A rapid decline in dihydroartemisinin piperaquine (DHP) and artemether lumefantrine (ALU) efficacies has been reported in some parts of South East Asia, the historical epicenter for the antimalarial drug resistance. Prolonged drug use is associated with selection of resistant parasites due to exposure to inadequate drug levels hence effects on treatment outcomes in malaria. ALU and DHP are used as first line and alternative first line, respectively, in Tanzania. This study was carried in lgombe, Tanzania to assess the efficacies of ALU and DHP in routine treatment of uncomplicated malaria among children. Methods: This was a prospective study involving children up to 10 years and followed up for 28 and 35 days as per the WHO protocol, 2015 for monitoring antimalarial drug efficacy. The primary end points were crude and adjusted Adequate Clinical and Parasitological Response (ACPR), parasite clearance rate and reported adverse events. Results: A total of 205 children with uncomplicated malaria were enrolled. One hundred and sixteen participants were treated with ALU, while 89 participants were treated with DHP. Two participants in the ALU group were lost within the 24 h of follow-up. The PCR unadjusted ACPR was 108 (94.7%) for ALU and 88 (98.9%) for DHP, while the PCR adjusted ACPR was 109(95.6%) and 88(98.9%) for ALU and DHP, respectively, at 28 day follow-up. No treatment failure was observed in both groups. Cumulative risk of recurrent parasitemia was similar in both groups (p = 0.32). Age and parasite density were strong predictors for persistent day 1 parasitemia (p = 0.034 and 0.026, respectively). Nausea and vomiting, abdominal pain and headache were the most clinical adverse events reported in both groups of patients. Conclusion: The present study shows that ALU and DHP are still efficacious after more than a decade of use with PCR corre

Anthony Kapesa,1 Namanya Basinda,1 Elias C Nyanza,2 Joshua Monge3,†, Sospatro E Ngallaba,4 Joseph R Mwanga,4 Eliningaya J Kweka5,6 1Department of Community Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 2Department of Environmental and Occupational Health and GIS, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 3Department of Health, Ukerewe District Council, Mwanza, Tanzania; 4Department of Epidemiology, Biostatisticsand Behavioural Sciences, School of Public Health, Catholic University of Health Sciences and Allied Sciences, Mwanza, Tanzania; 5Department of Parasitology and Medical Entomology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 6Division of Livestock and Human Disease Vector Control, Tropical Pesticides Research Institute, Arusha, Tanzania†Deceased — died on June 16, 2019Correspondence: Eliningaya J Kweka Email eliningaya.kweka@tpri.go.tzBackground: Surveillance of the clinical morbidity of malaria remains key for disease monitoring for subsequent development of appropriate interventions. This case study presents the current status of malaria morbidities following a second round of mass distribution of long-lasting insecticidal nets (LLINs) on Ukerewe Island, northwestern Tanzania.Methods: A retrospective review of health-facility registers to determine causes of inpatient morbidities for every admitted child aged < 5 years was conducted to ascertain the contribution of malaria before and after distribution of LLINs. This review was conducted from August 2016 to July 2018 in three selected health facilities. To determine the trend of malaria admissions in the selected facilities, additional retrospective collection of all malaria and other causes of admission was conducted for both < 5- and > 5-year-old patients from July 2014 to June 2018. For comparison purposes, monthly admissions of malaria and other causes from all health

Background: Male involvement in reproductive health (RH) services in Africa has been associated with improved maternal and child health outcomes. The objective of this study was to determine the prevalence and factors affecting male partner attendance to available reproductive health services in Shinyanga district, north-western Tanzania. Methods: A house to house survey using a structured questionnaire was conducted among randomly selected married men. Additional in-depth interviews were conducted among married men found attending RH services. Factors that motivates the uptake of locally available RH services together with their partners were explored. Results: A total of 204 men participated in the study, 94.4 % (193/204) of them reported to have ever attended the RH service with their female partners at least once whereas 50.6% (103/204) of them attended at least thrice. Three quarters (154/204) attended HIV counselling and testing (VCT) and 63% (129/204) attended antenatal services (ANC). Reported attendance to sexually transmitted infections (STIs/STDs), prevention of HIV transmission from mother to child (PMTCT), and reproductive health cancer services were all less than 13%. The male partners age group (25-34 years; χ2=9.347, df =3 p-value < 0.001), female partner invitation to HR services (χ2= 29.901, df=1, p-value <0.001) and having less than 2 children (χ2= 6.201, df= 2, p-value < 0.05) were associated with higher RH service attendance. Only 20% (4/20) of married men attended RH because they expected better health outcomes in their presence whilst majority attended because they were summoned or just happen to be at the clinic for other purposes. Conclusion: The male attendance to RH services together with their female partners’ in rural Shinyanga was mainly focused ANC and VCT. Most of men attended because were verbally invited by their partners. Education on couple communication empowerment among women attending RH clinics could sustainably impro

Background: Benign breast diseases are a neglected entity in developing countries despite the fact that they constitute the majority of breast complaints. There is a paucity of published information regarding benign breast diseases in Tanzania. This study describes our experience in the management of benign breast diseases outlining the clinicopathological pattern and treatment modalities of these diseases in our local setting. Methods: This prospective descriptive study was conducted between November 2009 and March 2013 at Bugando Medical Centre in Tanzania on female patients aged 10 years and above presenting with benign breast diseases. Results: A total of 346 female patients with benign breast diseases were studied. The majority of patients, 255 (73.7%) were younger than 30 years. Breast lump was the most frequent presentation in 67.6% of patients. Fibroadenoma 95 (60.0%) was the most frequently diagnosed benign breast disease followed by fibrocystic changes (19.0%). Out of 295 patients who had histopathological examination, 64 (21.7%) had proliferative lesions. Of these, 18 (28.1%) had proliferative lesions with atypia while 46(71.9%) had proliferative lesions without atypia. Eight (2.6%) patients were HIV positive with the median CD 4+ count of 258 cells/μl. The majority of patients, 295(85.2%) underwent surgical treatment of which lumpectomy was the most common procedure performed. Conclusion: Benign breast diseases are more common than malignancies in our environment and occur mainly in young women less than 30 years of age and were mostly fibroadenoma and fibrocystic change. Though premalignant lesions of proliferative lesions with atypia were less common in this study, it is advisable that all cases of breast lesions should be carefully evaluated to exclude possibility of breast cancer.

Background: Despite the growing recognition of domestic violence as a public health and human rights concern, it remains rampant in developing countries and has a negative impact on the victim’s health. This study describes the injury characteristics and treatment outcome of trauma associated with domestic violence in north-western Tanzania. Methods: This was a descriptive prospective study of patients who were managed for domestic violence related trauma at Bugando Medical Centre in Mwanza, Tanzania from April 2009 to March 2014. Results: A total of 324 patients (M: F = 1: 10.6) were studied. Majority of the patients were in the second and third decades of life. The perpetrators were mainly husbands and ex-partners (55.5%). Suspecting sexual partner being unfaithful was the most common reason given by victims for domestic violence in 63.4% of cases. Blunt and sharp objects (56.8%) were the most common weapons used. Gunshot injuries were recorded in 0.6% of cases. The head/neck was commonly affected in 68.5%. Soft tissue injuries (77.8%) were the most frequent type of injuries. The majority of patients (65.4%) sustained mild injuries. Twentythree (7.1%) patients were HIV positive. Surgical treatment was performed in only 34.6% of cases. Complication rate was 26.8%. The median hospital stay was 12 days. Mortality rate was 6.5%. The main predictors of mortality were advanced age (> 60 years), late presentation, severity of injury, severe head injury, HIV seropositivity, low CD 4 count (<200 cells), surgical site infection (p<0.001). More than twothirds of patients were lost to follow up. Conclusion: Domestic violence related trauma remains rampant in northwestern Tanzania and contributes significantly to high morbidity and mortality. Urgent preventive measures targeting at reducing the occurrence of domestic physical violence is necessary to reduce the morbidity and mortality resulting from these injuries.

Background: Breast cancer and its treatment constitute a great challenge in resource limited countries as found in Africa. This study was conducted to assess the quality of operable breast cancer in our setting and compare with the international standards. Methods: This was a retrospective study of histologically confirmed breast cancer patients seen at the department of Surgery of Bugando Medical Centre from January 2004 to December 2013. The details of patients were obtained using data derived prospectively from and also from patients’ files kept in the Medical Record Department, the surgical wards, operating theatre and histopathology laboratory. The study variables included demographic data, menopausal status, duration of illness, preoperative diagnosis, tumor size, pathological nodal status, clinical stage, histopathological type and grade, and treatment modalities. This information was collected using a pre-formed questionnaire. Results: A total of 374 patients were studied. The median age at diagnosis was 48 years (range 18- 84 years). Pre-operative bilateral mammography was performed in 56 (14.9%) and fine needle aspiration cytology in 221 (59.0%) patients. Triple assessment before definitive surgery was performed in only 42 (11.2%) patients. Excisional biopsy was performed in 214 (57.2%) patients. Complete pre-operative staging according to AJCC was performed in 289 (77.3%) patients. Definitive surgical procedure was performed in 372 (99.5%) patients, of which 366 (98.4%) patients had mastectomy. Axillary dissection was performed in 224 (65.5%) patients. None of our patients had sentinel node biopsy performed. The tumor size, histopathological grade, margins of excision, and the total number of nodes removed were recorded in 158 (42.5%), 308 (82.4%), 69(18.5%) and 198 (53.2%) patients respectively. Histopathological type was reported in all patients (100%). Estrogen receptor and progesterone receptor status was not reported in all patients. Adjuvant chemoth

Motorcycle helmets have been reported to reduce the risk of death and head injuries following motorcycle accidents. The aim of this descriptive prospective study was to determine the injury outcome among helmeted and non-helmeted motorcyclists and passengers at a tertiary hospital in north-western Tanzania. A total of 654 patients involved in the motorcycle accident were studied. Of these, 468 (71.6%) were motorcyclists (riders) and the remaining 186 (28.4%) were passengers. The median age of patients at presentation was 26 years. Male outnumbered females by a ratio of 4.5: 1. Helmet use was reported in 312 (47.7%) patients. Non-helmeted patients were young compared with helmeted patients and this was statistically significant (p=0.021). The rate of helmet use was significantly higher among motorcyclists than among passengers (p=0.004). History of alcohol consumption prior to the accident was reported in 212 (32.4%) patients. The rate of helmet use was significantly low among alcohol consumers compared with non-alcohol consumers (p=0.011). Lack of helmet use was significantly associated with abnormal head Computed Tomography scans, admission to the Intensive care unit, severe trauma, and worse traumatic brain injury severity (p<0.001). Helmet use was significantly associated with shorter period of hospitalization and reduced mortality rate (p<0.001). Motorcycle helmet use is still low in this part of Tanzania and this poses a great impact on injury outcome among motorcycle injury patients. This observation calls for action to implement more widespread injury prevention and helmet safety education and advocacy.